They are talking to us with high probability of a mesangial IgA glomerulonephritis or Berger's disease. Therefore, we are going to discard options one by one: 1: True. Serum IgA elevation is found in up to 50% of cases. 2: True. Mesangial IgA deposits are present in almost 100% of cases. 3: This option is false, because this glomerulonephritis is classically manifested with nephritic and not nephrotic syndrome (although in some rare cases proteinuria in nephrotic range does appear, but in the MIR they do not ask about these rare cases). 4: At the beginning this option generated doubts in me, but looking in the literature, it is true that the evolution to renal failure (according to last series) occurs in about 25% of the cases, so this option is true. 5: Skin biopsy, because it is easier to perform than renal biopsy, is the diagnostic technique of choice (the skin lesions that constitute Schonlein-Henoch purpura, so frequently associated with this entity and which the patient in the case presents, are biopsied).

They are talking to us with high probability of a mesangial IgA glomerulonephritis or Berger's disease. Therefore, we are going to discard options one by one: 1: True. Serum IgA elevation is found in up to 50% of cases. 2: True. Mesangial IgA deposits are present in almost 100% of cases. 3: [HIDDEN], because this glomerulonephritis is classically manifested with nephritic and not nephrotic syndrome (although in some rare cases proteinuria in nephrotic range does appear, but in the MIR they do not ask about these rare cases). 4: At the beginning this option generated doubts in me, but looking in the literature, it is true that the evolution to renal failure (according to last series) occurs in about 25% of the cases, [HIDDEN]. 5: Skin biopsy, because it is easier to perform than renal biopsy, is the [HIDDEN] (the skin lesions that constitute Schonlein-Henoch purpura, so frequently associated with this entity and which the patient in the case presents, are biopsied).

30-year-old man with no past history of interest. He comes for consultation due to the presence of small erythematous-violaceous lesions that on palpation appear to be raised in the pretibial region. The analytical study shows a complete blood count and coagulation study without alterations, and in the biochemistry, creatinine and ions are also within the normal range. The urinary sediment study shows hematuria, for which the patient had already been studied on other occasions, without obtaining a definitive diagnosis. Regarding the entity you suspect in this case, it is FALSE that:

In 20 to 50% of cases there is elevation of serum IgA concentration.

In the renal biopsy the mesangial deposits of IgA are characteristic.

It is frequent the existence of proteinuria in nephrotic range.

It is considered a benign entity since less than 1/3 of patients progress to renal failure.

The cutaneous biopsy allows to establish the diagnosis in up to half of the cases.

Evolution of immunoglobulin A nephropathy into Henoch-Schönlein purpura in an adult patient.

We report the first case of the evolution of immunoglobulin A (IgA) nephropathy into Henoch-Schönlein purpura in an adult patient. A 28-year-old man presented with an episode of gross hematuria and acute renal failure. The serum IgA level was increased and renal biopsy findings were diagnostic of IgA nephropathy. In addition, many renal tubuli were filled by red blood cell casts and presented a marked tubular necrosis. Coincidental with the disappearance of gross hematuria, renal function progressively improved. The patient continued to have microhematuria, normal renal function, and isolated bouts of macroscopic hematuria. Ten years later, the patient developed arthralgias, a purpuric rash in the legs, gross hematuria, and an elevated serum creatinine level. A skin biopsy showed leukocytoclastic vasculitis with IgA deposits. The renal biopsy showed histologic lesions very similar to those observed in the first biopsy 10 years before: mesangial proliferation with mesangial deposition of IgA and tubular necrosis with obstruction of renal tubuli by red blood cell casts. The serum creatinine level returned to normal. Recurrent episodes of purpura associated with macroscopic hematuria persisted during the follow-up, but without worsening of renal function. An interesting feature of our patient was the development of reversible renal failure associated with macroscopic hematuria on two different occasions. Although this complication has been described in IgA nephropathy, it has been rarely reported in Henoch-Schönlein purpura. It is possible that IgA nephropathy and Henoch-Schönlein purpura are different clinical manifestations of the same disease and probably share a common pathogenesis. Our case is a demonstrative example of this hypothesis.

Crescentic IgA nephropathy.

We report five cases of crescentic IgA nephropathy. All are males, 16-60 years of age. One case each came to medical attention with uremia, nephrotic syndrome, and gross hematuria; two cases presented with microhematuria and proteinuria on routine urinalysis. All had hypertension, azotemia (serum creatinine 1.6-9.4 mg/dl), proteinuria (greater than 6 g/24 hr in four cases), hypoalbuminemia (less than 3 g/dl), and hematuria (gross in two cases). All progressed to end-stage renal failure renal failure ending in dialysis (three cases) or death from unrelated causes (two cases). Prednisone, 60 mg/day for 1 month in two patients (with two 1-g doses of iv methylprednisolone in 1 case) did not improve the serum creatinine level, but one patient subsequently experienced a less rapid fall in renal function. A crescentic glomerulonephritis was present in all biopsies (crescents in 31-80% of glomeruli; mean, 50%). The size and stage of the crescents were variable. Numerous glomeruli had focal or diffuse sclerosis. In all cases, there was a 3 or 4+ deposition of IgA. Low-intensity staining for IgG and IgM was noted in four and three patients, respectively. On electron microscopy, dense granular mesangial deposits were noted in all cases and in four patients capillary subepithelial deposits were also observed. This form of IgA nephropathy is not common, but some studies indicate that it may occur in about 5% of patients with IgA nephropathy.

IgA nephropathy

For an adult patient with isolated hematuria, tests such as ultrasound of the kidney and cystoscopy are usually done first to pinpoint the source of the bleeding. These tests would rule out kidney stones and bladder cancer, two other common urological causes of hematuria. In children and younger adults, the history and association with respiratory infection can raise the suspicion of IgA nephropathy. A kidney biopsy is necessary to confirm the diagnosis. The biopsy specimen shows proliferation of the mesangium, with IgA deposits on immunofluorescence and electron microscopy. However, patients with isolated microscopic hematuria (i.e. without associated proteinuria and with normal kidney function) are not usually biopsied since this is associated with an excellent prognosis. A urinalysis will show red blood cells, usually as red cell urinary casts. Proteinuria, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement

[Clinical studies of the prognosis in cases of chance proteinuria and/or hematuria].

A total of 174 cases that consulted due to chance proteinuria and/or hematuria (CPH) were studied as to its clinical course, in particular patients' prognosis. They were selected from 311 patients on whom renal biopsy was performed from December, 1975 to December, 1985 in our institute. Furthermore, IgA nephropathy which occupied the major part of the CPH group was also studied as a prognostic factor. The CPH group showed 81% of disease stabilizing rate in 10 years' follow-up. In various data such as chemical analysis of blood and urine, immunoglobulin levels, and renal function at the time of biopsy, daily urinary protein excretion (greater than 1 g/day) statistically showed a significant correlation to deterioration of the renal function during the follow up. However, hematuria was not found correlated. Of CPH group, 48% was diagnosed to be with IgA nephropathy. The patients with IgA nephropathy with CPH, comparing with the cases without CPH, were younger and had better renal function and milder change of renal mesangial proliferation. The 10 years-disease stabilizing rates of the disease were 81% in CPH and 63% in non CHP group. In conclusion, prognostic factors affecting renal function in the CPH group was found to be daily urinary protein excretion and, if diagnosed as IgA nephropathy by biopsy, pathological changes were also shown to be prognostic factors. Therefore, CPH patients having proteinuria over 1 g/day must be examined by renal biopsy and when IgA nephropathy is diagnosed, long time follow-up is necessary and re-biopsy for examination of pathological change during the interval is recommended.

[Membranous glomerulonephritis in children: 20 cases].

Twenty cases of membranous glomerulonephritis have been diagnosed between 1978 and 1988 in children (13 girls, 7 boys) aged 4 to 15 years, observed for a 5.1 +/- 2.9 year period. The conditions of the diagnosis were: routine urinalysis in 10 cases, edema in eight, and the surveyance of a D-penicillamine treatment in two. All the patients had proteinuria (0.3 to 15 g/24 h) ranging to nephrotic syndrome in nine children. Microscopic hematuria was found in 16 children (80%). Elevated blood pressure was recorded in two cases at the time of diagnosis, and developed in two other cases during the follow-up. One child experienced renal failure at the onset of the disease. Most histological lesions consisted in stage II membranous glomerulonephritis. Immunofluorescence study (18 biopsies/20) always showed granulosus and intensive IgC deposits, associated with IgM and IgA deposits which were less marked; intensive extra-membranous C3 deposits were noted in 11 cases. As to the etiology, D-penicillamine was responsible for two cases (10%) and HBs antigen in one (5%); the nephropathy was considered as idiopathic in the 17 remaining cases (85%). Regarding the evolution: in eight cases (38%) proteinuria disappeared by 54 +/- 28 months; in 10 cases (55%), proteinuria persisted after 41 +/- 31 months; hematuria, which was present at onset, disappeared in most cases (13/17); in one case (5%), end-stage renal failure occurred within 3 years. The patient with initial renal failure has been last sight off.(ABSTRACT TRUNCATED AT 250 WORDS)

[Borderline indications for renal biopsy].

The Authors report 3 cases with clinical renal manifestations where the indication to perform a renal biopsy was defined as borderline. The uncertain indication was related to the clinical presentation, with a pattern of urinary abnormalities, such as isolated microscopic hematuria, microscopic hematuria associated with mild proteinuria, and isolated proteinuria. In addition, similar questions on biopsy are raised for chronic renal failure and elderly patients. In the literature, microscopic hematuria without significant proteinuria shows that 25% of adult patients have no histological abnormalities. A higher percentage is found among children. The other cases exhibit a pattern of IgA nephropathy, Alport's syndrome, thin BM nephropathy and arteriolar C3 deposition. The percentage of an abnormal histological picture increases if the patients have a family history of hematuria, and if there are concomitant episodes of macroscopic hematuria, because of an increase in IgA nephropathy and Alport's syndrome, respectively. In the last cases, therefore the indication to perform a renal biopsy increases. For those patients without these characteristics, a renal biopsy can be delayed whereas in cases of microscopic hematuria with proteinuria or isolated proteinuria the indication for a renal biopsy is stronger, because the spectrum of glomerulopathies is wider, and the possible evolution to renal failure after 10 years is higher (10-14% of cases). In patients with chronic renal failure the biopsy is contraindicated for cases where the thickness of the cortical section of the kidney is lower than 8-10 mm, because of possible technical difficulties, lower diagnostic information due to sclerosis and higher risk of complications. The prolonged bleeding time and the consequent risk of bleeding can be avoided by i.v. infusion of vasopressin 2 hours prior to biopsy. The higher indications are for those patients who may be susceptible to a medical treatment, capable to slowing down the progression of nephropathy. Finally, in elderly patients the biopsy is indicated in almost all cases because of the recently confirmed high incidence of glomerulopathies. In the aged there is a higher frequency of membranous GN, crescentic-ANCA associated GN, amyloidosis and, according to some Authors, post-infectious GN. In all cases a precise histological diagnosis can correct an erroneous diagnosis made according to clinical data alone. In the elderly the indication for biopsy aims at making an exact diagnosis of nephropathy, especially for acute renal failure: for this purpose age itself should not become an obstacle.

[Asymptomatic microhematuria].

Microscopic haematuria is an urinary finding more and more frequently observed in routine analysis in childhood; the diagnostic problems, most of which unresolved, are yet the principal questions of concern. We have studied 123 patients during five years from 1975 to 1980, and followed them for 1-8 years (mean 4 years). Our experience allowed us to consider "normal" or without remarkable pathologic significance a urinary finding less than or equal to 5.000 RBC/m' at the Addis count. Such findings were pointed out in 55 cases (44%); 27 patients (22%) had 5-10.000 RBC/m', 34 cases (27,6%) presented 10-50.000 RBC/m' and 7 cases (5,7%) had more then 50.000 RBC/m'. The familiar background, the clinical, biological and immunological data, the roentgenographic investigations and the renal biopsy carried out in the 4 groups of patients, led us to the following conclusions: 1) 26% of the 123 cases had a "unexplained;; microscopic haematuria with complete lack of anamnestic data, symptomatology and with normal biological findings. 2) in 65,8% of the cases it was possible to discover frequent upper respiratory tract infections (and allergy in 5,6% of them). 3) in 26% of the patients we discovered a previous or actual genito-urinary (10,5% and 15,5% respectively) infection: 9,4% of 96 urography demonstrated a variable degree of nephro-urological abnormalities. 4) 23 children (18,7%) was selected for renal biopsy, primarily by the hypocomplementemia and positive anti-DNA ab. test, and secondly by elevated degree of microhematuria. The histological and immunohistochemical studies demonstrated the presence of mesangial proliferation glomerulonephritis with IgG-IgA-C3 deposits in 7 cases (30% of the cases biopsied and 5,6% of the total), 69,6% of the cases had only minimal charges with negative immunofluorescence. 5) A mean follow-up of 4 years in two groups of patients (less than or greater than 6 years of age) has demonstrated that microscopic haematuria remains unchanged in 18-19% of both groups. A more marked improvement or normalization has been documented in the children more than 6 years aged (p less than 0,001) while a worsening has been observed in the children less than 6 years aged (p less than 0,005), with a statistically significant difference between the two groups considered.

Renal biopsy

The following are examples of the most common reasons for native kidney biopsy: Haematuria (or blood in the urine) can occur with a number of conditions that affect the kidneys and urinary tract. While renal biopsy is not indicated in all cases of haematuria, it may be performed in those with glomerular haematuria (blood that is thought to come from damage to the glomerulus) or when combined with features of progressive renal disease (e.g. increasing proteinuria, elevated blood pressure and kidney failure). One example is the nephritic syndrome. Proteinuria (or protein in the urine) occurs in many renal conditions. Renal biopsy is usually reserved for patients with high or increasing levels of proteinuria, or for patients who have proteinuria along with other signs of renal dysfunction. One example is the nephrotic syndrome.

[Primary IgA mesangial nephropathy (Berger's disease): clinico-pathological study].

From 1976 to December 1984 IgA nephropathy (IgAN) was diagnosed in 40 patients at the Nephrology Division of the Hospital das Clínicas, São Paulo University. In order to estimate the incidence of the disease in our city, we reviewed the kidney biopsies of the year 1984: IgAN constituted 6.5% of all biopsies of primary glomerular nephropathies. Of the 40 patients 67.5% were males and 32.5% females. Their age varied between 4 and 49 years and 72.5% were in the 2nd and 3rd decades of life at the beginning of the disease. From the racial standpoint, 82.5% of the patients were white, 10% were yellow and 7.5% black. The most frequent clinical manifestation, presented by 62.5% of patients, was macroscopic hematuria in close association with an acute infectious process. In the remaining 37.5% of cases the clinical picture of the disease was very variable, and did not evoke the diagnosis of IgAN. The initial laboratory investigation showed proteinuria in 92.5% of patients; it was under 1g/24h in 40%, it ranged from 1 to 3g/day in 37.5% and was over 3.5g/24h in 15% of them. Hematuria was present in all 40 cases and the red cells displayed moderate dismorphism. Glomerular filtration rate, evaluated by creatinine clearance in 39 patients, was over 90 ml/min/1.73m2 in 70%, ranged between 50 and 89 ml/min/1.73m2 in 7.5% and was under 25 ml/min/1.73m2 in 20% of them. Total complement CH50 was found normal in 79.4% and was slightly reduced in 20.6%. The C3 fraction showed slight reduction in 9.5% and C4 was found normal in all instances. Serum IgA was increased in 21% of the cases. All patients were submitted to percutaneous renal biopsy. Proliferative mesangial lesions were found in 82.5% of cases; they were focal in 42.5% and diffuse in 40%. In 15% of the patients, the glomeruli were entirely normal on light microscopy. In one case they were crescent-shaped, exhibiting 82% of the glomeruli this form. The immunofluorescence findings were quite uniform, with granular deposits occupying only the mesangium, with a global and diffuse distribution in all glomeruli. IgA was the dominant immunoglobulin deposited in the 40 cases and C3 was also found in the same localization and distribution in all biopsies, generally with a lesser intensity than IgA. IgG was present in 85% of cases and IgM in 32.5% of the biopsies, in the majority of them with the intensity of traces.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-term outcome of adult patients with minimal urinary abnormalities and normal renal function.

To define the long-term outcome of patients with minimal urinary abnormalities (defined by the presence of microscopic hematuria with no or less than 1 gm/day proteinuria), and normal renal function (defined by a serum creatinine < 1.3 mg/dl), we retrospectively studied patients who fulfilled the above criteria and had a kidney biopsy done before the year of 1992 (i.e. at least followed up for 5 years), with a definite pathological diagnosis. A total of 41 cases among 719 cases of primary glomerulonephritis (5.7%) were enrolled into the study. There were 19 males and 22 females with a mean age of 35.4+/-14.7 years at biopsy. The duration of renal disease was 116.0+/-60.5 months and the duration of follow-up post biopsy was 100.2+/-38.1 months. The pathological diagnosis was: IgA nephropathy (21 cases), focal glomerulosclerosis (9 cases), mesangial proliferative glomerulonephritis (8 cases), membranous glomerulonephritis (2 cases) and acute glomerulonephritis (1 case). At the end of follow-up, 8 cases (19.5%) had a certain degree of renal insufficiency including 2 (4.9%) in end-stage renal disease. The other cases were either in complete remission (6 cases) or stable condition (27 cases) with persistent microscopic hematuria and normal renal function. The long-term outcome was not correlated with any of the following parameters: age, sex, disease duration, serum creatinine at presentation, daily protein loss at presentation, degree of glomerular change and degree of interstitial inflammatory cell infiltration. However, a poor long-term outcome was correlated with tubular atrophy (p < 0.05) and interstitial fibrosis (p < 0.05). We conclude that a minimal urinary abnormality with normal renal function at presentation does not necessarily imply a favorable long-term outcome in certain patients. Tubular atrophy and interstitial fibrosis but not glomerular change correlates with a worse prognosis. This further emphasizes the importance of renal biopsy in such cases.

Diabetic nephropathy

It is recommended that diabetics have their albumin levels checked annually, beginning immediately after a diagnosis of type 2 diabetes and five years after a diagnosis of type 1 diabetes. Medical imaging of the kidneys, generally by ultrasonography, is recommended as part of a differential diagnosis if there is suspicion of urinary tract obstruction, urinary tract infection, kidney stones or polycystic kidney disease. Conformation kidney biopsy should only be performed if non-diabetic kidney disease is suspected. Urine analysis in patients with diabetic kidney disease is often bland. In cases of severely increased microalbuminuria, hematuria might be present. fat bodies might be present in patients who develop nephrotic-range proteinuria. Staging To stage the degree of damage in this (and any) kidney disease, the serum creatinine is determined and used to calculate the estimated glomerular filtration rate (eGFR). Normal eGFR is equal to or greater than 90ml/min/1.73 m2.

Thin basement membrane disease

A kidney biopsy is the only way to diagnose thin basement membrane disease. It reveals thinning of the glomerular basement membrane from the normal 300 to 400 nanometers (nm) to 150 to 250 nm. However, a biopsy is rarely done in cases where the patient has isolated microscopic hematuria, normal kidney function, and no proteinuria. The prognosis is excellent in this setting unless the clinical manifestations progress, as occurs in most males and some females with Alport syndrome and many patients with IgA nephropathy. Treatment Most patients with thin basement membrane disease need only reassurance. Indeed, this disease was previously referred to as "benign familial hematuria" because of its usually benign course. Angiotensin converting enzyme inhibitors have been suggested to reduce the episodes of hematuria, though controlled studies are lacking. Treating co-existing hypercalciuria and hyperuricosuria will also be helpful in reducing hematuria.

Renal biopsy findings and clinical indicators of patients with hematuria without overt proteinuria.

Whether to perform a renal biopsy for isolated hematuria remains a matter of controversy. We performed renal biopsy in hematuria without overt proteinuria patients and reported the proportion of glomerulonephritis, pathological activities, and statistical analysis of indicators associated with glomerulonephritis. Among 203 patients who underwent renal biopsy in Okubo Hospital, Japan, between January 2008 and October 2013, we identified 56 patients who fulfilled the criteria: (1) urine dipstick examination shows equal to or greater than ± blood on three or more visits, (2) proteinuria <0.3 g/day (g/g Cr), (3) eGFR ≧60 ml/min/1.73 m(2), and (4) no current medication for renal disease. We investigated biopsy findings and compared the clinical indicators in the IgA nephropathy (IgAN) and non-IgAN group. The pathological diagnosis was IgAN in 35 cases (62 %), thin basement membrane disease (TBMD) in 7 (13 %), minor glomerular abnormality (MGA) in 6 (11 %), glomerular basement membrane (GBM) abnormality in 5 (9 %), and others in 3 (5 %). The histological grade of IgAN was I in 90 % and II in 10; 31 % of patients had some crescentic lesions. Comparisons between the IgAN and non-IgAN group revealed significant differences in age of onset (26 ± 13 vs. 34 ± 17 years, p = 0.04), serum IgA (340 ± 114 vs. 220 ± 101 mg/dl, p < 0.01), proteinuria (0.08 [0-0.25] vs. 0 [0-0.23] g/day [g/gCr], p < 0.01), and the presence of poikilocytes (40 vs. 10 %, p = 0.02). The proportion of IgAN in hematuria without overt proteinuria was high and the pathological activities were variable. Patients with hematuria without overt proteinuria should continue their medical follow-up and the best timing of biopsy may be controversial for these patients who have multiple risk factors of IgAN.

Cyclosporine therapy could be considered for membranoproliferative glomerulonephritis with immunoglobulin A deposits: a case report.

Membranoproliferative glomerulonephritis (MPGN), a rare glomerulonephritis that causes nephrotic syndrome in children, is often difficult to treat. Typical immunofluorescence findings include strong C3 staining in a granular pattern along the glomerular capillary wall and negative IgA staining. IgA-dominant MPGN without hypocomplementemia has been reported. Herein, we report a rare case of MPGN with hypocomplementemia and predominant IgA subclass 2 deposits. An 11-year-old girl showed proteinuria on a school urinalysis screening and presented with upper eyelid edema. The urinalysis showed elevated urinary protein levels and hematuria. Laboratory examinations revealed the following: serum albumin, 1.3 g/dL; serum creatinine, 0.54 mg/dL; and C3c, 67 mg/dL (normal range: 73-138 mg/dL). The physical and laboratory findings did not suggest autoimmune diseases. A renal biopsy was then performed. Specimen examination under a light microscope showed mesangial cell proliferation, increased mesangial matrix with lobulation, and some double contours of the glomerular basement membrane in almost all glomeruli, which are characteristic findings of MPGN. Immunofluorescent studies showed IgA deposits not only in the mesangial regions but also along the capillary walls, which were more strongly stained than C3. IgA subclass staining showed a stronger immunoreactivity for IgA2 than IgA1. Electron microscopic studies showed electron-dense deposits in the subendothelial, subepithelial, and paramesangial regions. Based on these findings, the patient was diagnosed with IgA-dominant MPGN. Accordingly, she was treated with three courses of methylprednisolone pulse therapy (MPT), followed by prednisolone, mizoribine, and lisinopril. Although hypocomplementemia improved after three courses of MPT, nephrotic-range proteinuria and hypoalbuminemia remained; therefore, two courses of MPT were additionally administered, and the immunosuppressant was changed from mizoribine to cyclosporine (CsA). Finally, the urinary protein level decreased, and a subsequent renal biopsy, two years later, showed improvement in the lesions. We report an atypical case of MPGN with IgA2 dominant deposits along the glomerular capillary wall and in the mesangial region. The case was refractory to standard therapy but sensitive to CsA, which resulted in remission. Our findings suggest that CsA may be useful as an immunosuppressant to treat refractory MPGN.

[Histopathological assessment of renal biopsy specimens of subjects with urine abnormality].

Between April 1985 and April 1992, 25,672 men (age 47 +/- 9 years, mean +/- SD) and 9,791 women (48 +/- 9 years) underwent mass urinalysis in the Center for Adult Complete Physical Examination in our hospital. The results revealed proteinuria in 6.3% of the men and 4.4% of the women and hematuria in 17.4% of the men and 37.8% of the women. Thirty-five subjects with asymptomatic persistent proteinuria and/or hematuria identified as a result of follow-up testing by the nephrologists at our hospital underwent renal biopsy. All of the biopsy specimens obtained were examined by light microscopy, fluorescence microscopy and electron microscopy. Histopathological findings in the biopsy specimens from these 35 subjects were as follows: One case (3%) of chronic pyelonephritis, 11 cases (31%) of IgA nephropathy, 4 cases (11%) of IgA nephropathy (severe type), 5 cases (14%) of membranous nephropathy, 4 cases (11%) of thin basement membrane disease (TMD), 7 cases (28%) of benign nephrosclerosis and 3 cases (9%) of minor glomerular abnormality. Light microscopy, fluorescence microscopy and electron microscopy for histopathological assessment of renal specimens, especially for the diagnosis of TDM, which was not uncommon, were indispensable tools in our study. Moreover, it is essential for proteinuria and hematuria to be tested simultaneously using the same standard method in all the urine specimens collected.

[Glomerulonephritis with mesangial IgA deposit (IgA mesangiopathy?)].

Clinical correlations and evolution were studied in 34 biopsies from patients with the following diagnosis: Henoch-Schönlein purpura in 17, monosymptomatic hematuria in 11, idiopathic nephrotic syndrome in 3, and Fanconi Syndrome, Systemic lupus erythematosus and tubulointerstitial nephritis, one for each diagnosis respectively. All these biopsies showed anti-IgA mesangial deposits, by immunofluorescence techniques with variable morphology by light microscopy. Endo and extracapillary proliferation was the most frequent lesions. Twenty cases had follow-up observation for over 2 years: 7 cases were in remission, hematuria and/or proteinuria persisted in 10 and 3 cases progressed to chronic renal failure. In conclusion, mesangial IgA deposits are not an infrequent finding in renal biopsies performed in the Hospital Infantil de México. Although the predominant clinical diagnosis was either Henoch-Schönlein purpura or monosymptomatic hematuria, other diagnosis were also found. Some cases with this mesangiopathy presented as idiopathic nephrotic syndrome or post-streptococcal glomerulonephritis, but with serum complement within normal levels. Long-term prognosis was related to glomerular morphology as in other glomerulopathies.

Military nephrology: a review of cases 1985-2011.

Evidence of the prevalence of renal pathology in military populations is rare, probably as a result of a traditionally cautious military medical attitude that limits applicants with evidence of renal disease joining the Armed Forces and the continued service of military personnel who develop this later. The aim of this paper is to provide the first comprehensive review of renal diseases in a British military population. An archive of out-patient consultations, discharge summaries and renal biopsies between 1985 and 2011 was reviewed. Cases were classified according to diagnosis providing a frequency distribution over this 26-year period. Serum creatinine concentration and demographic data permitted retrospective calculation of estimated glomerular filtration rate (eGFR) at presentation and follow-up. Calculation of an annualised rate of deterioration of eGFR (ml/min/1.73 m2/y) was undertaken when there were at least four follow-up values. In those cases where there was a statistically significant negative correlation with time, the probability of deterioration of renal function according to diagnosis was calculated. Where numbers of patients with a given diagnosis were sufficient for statistical purposes, correlations were also attempted between initial eGFR and both initial mean arterial pressure (MAP) and initial proteinuria. The most frequent condition was IgA nephropathy, present in 115/346 (33%) of cases. Follow-up data permitted analysis of change in eGFR in 50 of these and 11 (22%) deteriorated. In this condition, there were statistically significant negative correlations between initial eGFR and MAP (r = -0.35, p = 0.0008) and proteinuria (r = -0.4, p = 0.0006). Other conditions showing deterioration despite therapeutic interventions included adult polycystic kidney disease (15/2 2 = 68%) and membranous nephropathy (4/ 7 = 57%). Altogether, 8/13 (61%) conditions included cases where eGFR deteriorated and this was present in 40/161 (25%) individual cases. Cases of renal disease are discovered de novo in serving military personnel and, despite interventions to maintain renal function, a significant proportion deteriorate supporting the traditionally restrictive policy concerning applicants with evidence of renal disease.

Henoch-Schönlein purpura and IgA nephropathy in father and son.

Considerable controversy exists as to whether Henoch-Schönlein purpura and Iga nephropathy are different clinical manifestations of the same disease or if, on the contrary, they are separate entities. We report on the development of Henoch-Schönlein purpura and IgA nephropathy in 2 members of the same family. Patient 1, a 63-year-old man, presented with purpura in the legs, abdominal pain, hematuria, renal failure and proteinuria. A biopsy of a purpuric skin lesion showed small-vessel vasculitis, and a renal biopsy showed diffuse proliferative glomerulonephritis with prominent IgA deposits, thus making the diagnosis of Henoch-Schönlein purpura. Serum IgA was increased. Patient 2, the 30-year-old son of patient 1, underwent renal biopsy for the investigation of microscopic hematuria and proteinuria. There was no history of skin rash, and serum creatinine was normal. A renal biopsy showed expansion of the mesangial matrix and marked IgA deposition. HLA typing confirmed that they shared a haplotype. HLA B35 or DR4 were absent. These results demonstrate that Henoch-Schönlein purpura and IgA nephropathy can possibly be genetically related and therefore support the notion that these two diseases probably share a common pathogenesis.

[Minimal change nephrotic syndrome with predominant mesangial IgA deposits: clinicopathological study].

It has been reported that minimal change nephrotic syndrome (MCNS) shows no deposit of immunoglobulins or complement components in the glomeruli. We found 6 patients with IgA deposits in the glomeruli among 101 patients with MCNS, and examined the clinicopathological features of these cases. In all cases, light microscopy showed minor glomerular abnormalities. However, immunohistochemical study demonstrated marked IgA deposits in the glomerular mesangium. IgM was detected in 5 cases, IgG in 2, C3 in 2, and Clq in 1. On electron microscopy, small mesangial deposits were found in all cases and foot process effacement was partially demonstrated. There were no abnormalities in the glomerular basement membrane. The renal functions were within normal ranges in all 6 cases. In three cases, biopsies were performed within a month after the initiation of profuse proteinuria. In the other three cases, frequent relapses had been observed for 6 to 15 years before the biopsies. However, all patients ultimately revealed complete remission with corticosteroid treatment. Serum IgA levels were within normal range in examined 4 cases. Hematuria was negative in all of them. The clinical findings seem to be identical to MCNS rather than IgA nephropathy, and IgA deposits may have no pathogenetic significance, although the pattern of deposition looks quite similar to that of IgA nephropathy. These results indicate that the renal lesions in the 6 patients may belong to the subtype of MCNS, rather than IgA nephropathy.

Asymptomatic microscopic haematuria in young males.

The study involved 120 young males (aged 20.5 +/- 2.5 years) having undergone successful kidney biopsy because of asymptomatic haematuria with the aims to assess the prevalence of histological diagnosis and the natural history of the disease. The patients were selected from the population of conscripts who were referred to our clinic as a result of asymptomatic microhaematuria. All patients had a negative history of kidney disease, normal creatinine clearance (Ccr), while extrarenal causes of microhaematuria were excluded. The patients were divided into a group of 62 patients with isolated microhaematuria (IMH; proteinuria < 0.3 g/day) and a group of 58 patients with asymptomatic microhaematuria and proteinuria (AMHP; proteinuria > 0.3 g/day). After kidney biopsy patients were monitored for 3-9 years. Normal biopsies and minor abnormalities were more frequent in IMH than in AMHP patients, who had IgA nephritis more frequently and significantly higher total pathohistological score. Based on the clinical and histological features, recommendations on patients' ability for military service were made. During the follow-up period, normal Ccr maintained in all patients. Macrohaematuria appeared in 42 patients and proteinuria worsened in eight patients (seven with AMHP). Urinary abnormalities disappeared in 20 patients with IMH and in eight with AMHP (p = 0.04). Minimal histological changes and disappearance of urinary abnormalities were more frequent in IMH than in AMHP patients. Kidney biopsy is useful only in patients with AMHP but it is not necessary in IMH patients.

IgA nephropathy

Natural history Since IgA nephropathy commonly presents without symptoms through abnormal findings on urinalysis, there is considerable possibility for variation in any population studied depending upon the screening policy. Similarly, the local policy for performing kidney biopsy assumes a critical role; if it is a policy to simply observe patients with isolated bloody urine, a group with a generally favourable prognosis will be excluded. If, in contrast, all such patients are biopsied, then the group with isolated microscopic hematuria and isolated mesangial IgA will be included and improve the prognosis of that particular series.

[Variations in histologic and ultrastructural findings in renal glomerular biopsies].

On the basis of 506 renal biopsies performed within a six-year period (237 of which were evaluated electron-microscopically) the authors discovered that in 11 cases the diagnosis based on electron microscopic examination had to be corrected or supplemented by the diagnostic statement of membranous glomerulonephritis. These cases included 1 boy (HBsAg positive), 2 men and 8 women were middle aged. 5 women were treated due to polyarthritis. All cases when examined light-microscopically yielded a pattern evaluated as normal, or as minute abnormalities of glomeruli. Half-thick sections were not sufficient for the diagnosis. 3 cases of biopsies yielded a variously developed chronic tubulointerstitial nephritis, two cases were accompanied with polyarthritis. On the basis of the latter the authors consider the electron microscopic examination as indicated: 1. in cases when the diagnosis statement is not achieved by other examinations, 2. findings are in the range of the so-called variable norm, 3. in all cases of minute abnormalities in glomeruli detected without electron microscopy, 4. the impact of any of effective drugs cannot be excluded, 5. the diagnostic conclusion based on renal biopsy and the clinical-laboratory pattern of the disease are inconsistent. The authors assume that especially the fourth and fifth groups are going to be gradually supplemented and made more precise. (Fig. 1, Ref. 5.).

Factors predicting progression of IgA nephropathies.

The difficulties in defining the natural history of primary IgA nephropathy (IgAN) depend upon the pre-selection of patients for renal biopsy, a true individual variability - ranging from asymptomatic to rapidly progressive forms - as well as the use of different classifications of the renal lesions and statistical analyses sometimes carrying incorrect modalities. Long-term natural history studies have demonstrated that the rate of progression has an extremely wide range, from 5 to 25% after 10 years and 25-50% at 20 years, and complete remission is reported as well in 5 to 30% of cases. A geographic variability has been confirmed in a tri-continental study, explainable only partly by the earlier referral. Among the factors predicting progression, the more frequent in cohorts showing worse actuarial survival at 10 years are those associated with the advanced phases of renal damage, as increased creatinine level, arterial hypertension and nephrotic range proteinuria. A multivariate statistical approach showed the relevance of proteinuria during follow-up (percent duration of massive proteinuria or proteinuria at 1 year) more than proteinuria at the onset. Mean blood pressure value (MAP) and proteinuria during follow-up were independent predictors of end-stage CKD. Note the predictive value of severe microscopic hematuria in several studies. As far as histological features are concerned, strong independent predictors of progression at Cox multivariate analysis are the severity of glomerular sclerosis and interstitial fibrosis. The presence of crescents was a risk factor in almost all studies at univariate analysis, but did not maintain a significant predictor value at multivariate analysis. Conversely the association between crescents and tuft adhesions, possibly resulting from previous segmental necrosis, was found to be a significant risk factor. The extent of mesangial proliferation and parietal expansion of deposits was not significantly associated to unfavourable prognosis at multivariate analysis. The analysis of risk factors for progression of IgAN related to Henoch-Schoenlein purpura (HSP) failed to demonstrate any prognostic value for the presence and severity of extra-renal signs of vasculitis or presence of triggering factors. At multivariate Cox analysis, age and mean proteinuria during follow-up were powerful independent prognostic predictors. Proteinuria at baseline was not significantly related to renal progression, nor were hypertension or impaired renal function at onset. It is of interest that data at onset and at renal biopsy (renal function impairment, hypertension, nephrotic-range proteinuira) were not significantly related with renal detrimental progression. Neither had prognostic value the finding of crescents involving up to 75% of glomeruli.

[Severe proteinuria in IgA nephropathy. Clinicopathological study of 8 cases with 100 serial sections].

Using 100 serial sections for light microscopy, we studied the clinicopathologic characteristics of IgA nephropathy with severe proteinuria. Eight out of 128 cases with IgA nephropathy exhibited severe proteinuria of 3.0g/day or more. These cases consisted of 5 males and 3 females with an age range from 15 to 73 years. Daily proteinuria ranged from 3.3 to 7.1 g. At the time of biopsy, the serum creatinine level was 1.2 mg/dl or more in 6 cases; two of these developed end-stage renal failure during the follow-up period. In most of the cases, routine sections for light microscopy revealed moderate to severe mesangial proliferation and tubulointerstitial damage. In 7 cases, variable percentages of glomeruli, ranging from 20% to 95%, were involved by chronic lesion represented by sclerosis and fibrous crescents/adhesion, while only 2 cases exhibited active lesion characterized by segmental glomerular necrosis and/or cellular/fibrocellular crescents. In contrast, thorough observation of 100 additional serial sections disclosed the focal presence of active lesion in all except one case with features of endstage kidney. In addition, the highest percentage of glomeruli with active lesion in the serial sections correlated well with the severity of proteinuria. The results suggested that severe proteinuria in IgA nephropathy depends on, at least in part, focal outbreak of active lesion characterized by segmental glomerular necrosis and cellular/fibrocellular crescents.

[Histopathologic changes in the kidneys in patients with asymtomatic pathologic findings in urine].

The authors had analyzed histopathologic changes in the kidneys of patients with asymptomatic abnormalities of urine analyzing if they were correlated with the type of pathologic finding in urine. Retrospective study comprised a total of 76 patients with asymptomatic urine abnormalities. In all three groups of patients, formed upon the type of pathologic finding in urine, were determined heterogeneous histopathologic changes, and different types of glomerulonephritis, respectively. The most frequent histopathologic finding was IgA nephropathy, observed in 16.7% patients with isolated proteinuria, in 50% patients with isolated microscopic hematuria and in 55.9% patients with associated urine abnormalities. In distinction from the other two groups of patients, in the group of patients with isolated proteinuria normal histologic finding was very frequently found (25% patients), and in group of patients with associated urine abnormalities were observed more severe histopathologic forms of glomerulonephritis, such as membranoproliferative glomerulonephritis. It was concluded that different types of glomerulonephritis most frequently caused asymptomatic abnormalities of urine in younger patients.

IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature.

To clarify the natural history of IgA nephropathy and to determine important factors in the progressive loss of renal function in affected patients, 121 patients with IgA nephropathy were followed for a median of 92 months. The cumulative probability of not progressing to end-stage renal failure (that is, of renal survival) was 0.87 at 15 years after the onset of 1st symptoms and 0.86 at 10 years after presentation and biopsy. Eight percent of patients progressed to end-stage renal failure, and 12% had a greater than 20% decline in renal function. A complete remission of disease activity was seen in 12% of patients, and the remaining 68% maintained stable renal function. When the final serum creatinine was expressed as a percentage of the initial serum creatinine for each patient and compared with all other variables, a number of factors were found to affect renal outcome. Of the presenting features, increased age, family history of nephritis, longer duration of symptoms, and presence of either nephrotic-range proteinuria or hypertension were all associated, by univariate analysis, with an adverse outcome, while a history of recurrent macroscopic hematuria and infection-associated exacerbations of disease activity were associated with a favorable outcome. Multivariate analysis showed that nephrotic-range proteinuria had an independent adverse effect. Of the initial laboratory findings, by univariate analysis, the number of hyaline casts, the degree of impairment of renal function, the degree of proteinuria, raised beta globulins on serum protein electrophoresis, and serum C4 concentrations were all associated with an adverse outcome, while the severity of initial hematuria and pyuria were associated with a favorable outcome. Renal biopsy findings associated with an adverse outcome by univariate analysis include, on light microscopy, the percentage of glomeruli with global sclerosis or segmental sclerosis or adhesions, the degrees of tubular atrophy or interstitial fibrosis, interstitial inflammation and blood-vessel thickening, and, on immunofluorescence, the intensity of IgA deposition. Multivariate analysis showed independent adverse effects on renal outcome of global glomerulosclerosis, segmental glomerulosclerosis or adhesions, and a combined mesangial and capillary wall deposition of IgM. Features at final assessment or during follow-up associated with an adverse outcome include, by univariate analysis, the number of hyaline casts, the degree of impairment of renal function, the degree of proteinuria, reduced serum IgG and IGM concentrations, reduced final IgA expressed as a percentage of the initial IgA concentration, transient decreases of creatinine clearance during follow-up of > 10% or > 20%, and persistence or development of hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)

[The value of urine sediment cytomorphology in the ambulatory differential diagnosis of hematuria].

In order to improve early diagnosis of urotheliale neoplasms (UN) in nephrology outpatient clinic, 274 patients (221 male and 53 female, mean age 54 yrs), with recurrent hematuria (> 5 E/hpf) were investigated in years 1994-1998. The following examinations of fresh urine sediment were performed: in 114pts (group 1) erythrocytes of urine sediment examined with phase-contrast microscopy (PCM); in 129pts (group II) urine sediment examined with classical oncological cytology; in the III-rd group of 31pts (29M and 2F, aged 61-72), both methods were used because of high suspicion on UN on the ground of initial result of PCM, precisely clinical anamnesis as well as predominance of men in advanced age. Results were as follows. In the I-st group, in 6 from 42pts with urological hematuria in PCM, what means 5.2% of the whole group and 14% of the subgroup with urological hematuria, in further standard urological examination bladder carcinoma was found. In the II-nd group, positive result of urinary cytology (GI to GIII) was found in 7pts, what means 5.4% of the whole group. Results of urine cytology were confirmed later in the standard urological examination, which detected bladder carcinoma in all these patients. In the III-rd group, bladder carcinoma was found in all 22pts with urological hematuria in PCM. In 19 patients from this subgroup, urinary cytology was positive for UN (GI to GIII). In the remaining 3pts results of urinary cytology were false negative. False positive result of urinary cytology occurred in one from 9pts with glomerular hematuria and clinical or morphological (in renal biopsy) evidence of glomerulonephritis. On the results of the study, we propose--as an obligatory--in every case of recurrent hematuria of urological origin in PCM, examination of fresh urinary sediment with classical oncological cytology, especially if the patient belongs to the high risk group for urotheliale neoplasms.

[Clinicopathological correlation of young onset chronic glomerulonephritis].

In a retrospective analytical study involving 98 children with primary glomerulonephritis who were seen by us at our hospital during a 2-year period from 1984 through 1985 and who had renal biopsy performed previously, attempts were made to correlate pathological findings with both clinical findings and prognosis. The results are summarized as follows: 1) Of 87 patients with asymptomatic chronic glomerulonephritis, glomerular findings were those of minimal change lesion, mesangial proliferative nephritis, MPGN, membranous nephropathy and FGS or sclerosing nephritis in 29.9%, 51.7%, 13.8%, 1.1% and 3.5%, respectively. Among the other 11 patients in whom the diagnosis was made after manifesting the nephritic symptoms, minimal change was noted less frequently and MPGN was detected more frequently than in the aforementioned asymptomatic group. IgA nephropathy was estimated to account for 44.2% of cases of asymptomatic chronic nephritis. 2) Mild mesangial proliferation was observed relatively frequently and severe mesangial proliferation or MPGN rather infrequently in hematuria cases without proteinuria while in those with severe proteinuria minimal change lesion was uncommon and severe mesangial proliferative changes, MPGN or FGS were relatively frequent. 3) In 22 patients with IgA nephropathy and 11 with non-IgA nephritis the severity of glomerular changes was related to the intensity of proteinuria at the time of renal biopsy. 4) A 3 to 5 years' follow-up study of patients with mesangial proliferative nephritis inclusive of IgA nephropathy disclosed that 26-28% of patients became free from urinary abnormalities, 27-37% had persistent hematuria without proteinuria and 24-32% still had proteinuria of 2 plus or above. Patients with milder glomerular changes had a definitely better prognosis than those with severe glomerular lesions.

[Clinicopathological study on IgA nephritis].

Clinicopathological study on IgA nephritis was carried out in order to clarify the factors to promote the progression of the disease. Total 118 cases of IgA nephritis confirmed with renal histology of the biopsied tissue were followed up in our kidney center at least two years following the biopsy. As a result, histological changes tended to be more severe in elder group at the time of biopsy and longer history of the disease. Renal function tended to be decreased in the cases with more proteinuria. Nephrotic syndrome seems to be one of the processes in which the disease is exacerbated. In addition, 21 cases with rather progressive courses following the biopsy revealed poor control of blood pressure, frequent upper respiratory infection, and more physical activities on their lives, which appear to be the risk factors. Clinical symptoms such as hematuria and proteinuria and histological changes were significantly more severe in the cases with IgA depositions spreading into the glomerular basement membrane, as compared to the ordinary cases with IgA depositions, limited in the mesangium. These results suggested that IgA depositions in glomerular basement membrane might be also one of the poor prognostic factors.

[A case of childhood IgA nephropathy who developed rapidly progressive glomerulonephritis in one-year clinical course].

A 10-year-old girl who presented with microscopic hematuria, proteinuria and normal renal function has been followed up for the past two years. At the first examination, renal biopsy revealed focal/segmental lesions accompanying by occaisional necrosis and small crescents. Diagnosis of IgA nephropathy was given by light, electron and immunofluorescent microscopic findings. She started on the treatment with dipyridamol and was followed up for one year without any serious complications. Thereafter, she suddenly developed severe deterioration of renal function (serum creatinine 2.7 mg/dl) with nephrotic syndrome and hypertension. The second renal biopsy done at this time indicated the presence of typical crescentic glomerulonephritis with mesangial proliferation. No vasculitis was noted. She was intensively treated with steroids, anticoagulants and other medication and responded fairly well clinically. The third renal biopsy performed 5 months afterwards demonstrated marked histological improvement, but there was still present mesangial proliferation and varied degrees of sclerotic changes with fibrocellular crescents. Focal interstitial fibrosis and collapsed tubules were also seen. At present, 5 months after the last renal biopsy, she has improved much better and her serum creatinine decreased to 1.9 mg/dl, although proteinuria of 3 g/day still persists. It is suggested that only a small segmental necrosis with crescent formation in IgA nephropathy should be considered as an important indicator of disease activity in the evaluation of prognosis.

[Asymptomatic haematuria (author's transl)].

Mesangioproliferative glomerulonephritis of varying severity was found by renal biopsy in 86.2% among 130 patients with asymptomatic haematuria. 3.2% had benign nephrosclerosis, 3.2% had benign nephrosclerosis, 1.6% had interstitial nephritis and one patient showed a previously undiagnosed perimembranous glomerulonephritis. Normal renal parenchyma was observed in only 6.9% of cases. Iummunohistological findings were positive in 25.7% of investigated cases. The majority were IgA deposits combined with IgG and C3 complement. The intensity of haematuria is not correlated with the type and severity of histological changes. "Physiological" haematuria (erythrocytes less than 7/ml) which is usually considered normal must be re-evaluated as a consequence of these histological findings. After exclusion of urological or extrarenal disease only histological investigation of the kidneys will bring the final diagnosis. Repeated radiographical or urological investigations can thus be avoided. The risks of percutaneous renal biopsy under fluoroscopic or sonographic control are decidedly less than the information gained from histological evaluation. The different histological findings indicate that isolated haematuria should be considered only as a symptom and not as a uniform disease indicating focal nephritis.

IgA nephropathy

In December 2021, budesonide (Tarpeyo) was approved for medical use in the US to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression. Prognosis Male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidemia, older age, familial disease and elevated creatinine concentrations are markers of a poor outcome. Frank hematuria has shown discordant results with most studies showing a better prognosis, perhaps related to the early diagnosis, except for one group which reported a poorer prognosis. Proteinuria and hypertension are the most powerful prognostic factors in this group. There are certain other features on kidney biopsy such as interstitial scarring which are associated with a poor prognosis. ACE gene polymorphism has been recently shown to have an impact with the DD genotype associated more commonly with progression to kidney failure.


If they wanted us to answer that it is a TTP (answer 1) they would probably associate anemia and in the smear they would surely tell us about schistocytes. Not to say that the patient's symptoms would probably be much more than epistaxis. The other two answers, you do not have to hesitate with them. Nothing points to that.

If they wanted us to answer that it is a TTP (answer 1) they would probably associate anemia and in the smear they would surely tell us about schistocytes. Not to say that the patient's symptoms would probably be much more than epistaxis. [HIDDEN]. Nothing points to that.

An 18-year-old patient comes to the emergency department with epistaxis of several days' evolution, with no personal or family history of interest. On examination he is afebrile, multiple ecchymoses are observed, no splenomegaly is palpable. Laboratory tests: leukocytes 7.2 x103/μL, Hb 12.3 g/dL, platelets 6.0 x103/μL. Thrombocytopenia is confirmed in the smear, where platelets of increased size are observed. Coagulation and biochemistry studies are normal. What do you consider the most probable diagnosis?

Immune thrombocytopenic purpura

Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is discouraged by the American Society of Hematology practice guidelines and a normal bleeding time does not exclude a platelet disorder. Bone marrow examination may be performed on patients over the age of 60 and those who do not respond to treatment, or when the diagnosis is in doubt. On examination of the marrow, an increase in the production of megakaryocytes may be observed and may help in establishing a diagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinician's preference, as there is disagreement on whether the 80 percent specificity of this test is sufficient to be clinically useful.

Thrombocytopenia.

Thrombocytopenia is defined as a platelet count of less than 150 × 10(3) per µL. It is often discovered incidentally when obtaining a complete blood count during an office visit. The etiology usually is not obvious, and additional investigation is required. Patients with platelet counts greater than 50 × 10(3) per µL rarely have symptoms. A platelet count from 30 to 50 × 10(3) per µL rarely manifests as purpura. A count from 10 to 30 × 10(3) per µL may cause bleeding with minimal trauma. A platelet count less than 5 × 10(3) per µL may cause spontaneous bleeding and constitutes a hematologic emergency. Patients who present with thrombocytopenia as part of a multisystem disorder usually are ill and require urgent evaluation and treatment. These patients most likely have an acute infection, heparin-induced thrombocytopenia, liver disease, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation, or a hematologic disorder. During pregnancy, preeclampsia and the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are associated with thrombocytopenia. Patients with isolated thrombocytopenia commonly have drug-induced thrombocytopenia, immune thrombocytopenic purpura, pseudothrombocytopenia, or if pregnant, gestational thrombocytopenia. A history, physical examination, and laboratory studies can differentiate patients who require immediate intervention from those who can be treated in the outpatient setting. Treatment is based on the etiology and, in some cases, treating the secondary cause results in normalization of platelet counts. Consultation with a hematologist should be considered if patients require hospitalization, if there is evidence of systemic disease, or if thrombocytopenia worsens despite initial treatment.

Teetering on a liver's edge: a case report highlighting clinical decision-making in thrombocytopenia.

This report illustrates the importance of a detailed history and physical exam and careful analysis of hematologic parameters when diagnosing ITP. This case demonstrates that even with subtle deviations from typical ITP findings one must promptly reevaluate the diagnosis. This case also highlights the importance of peripheral smear review by an expert in pediatric hematopathology. A previously healthy 10 year-old Asian boy presented with 2 months of easy bruising. Review of systems was negative for any constitutional symptoms. On examination, he appeared well but had numerous large ecchymoses. He had no appreciable lymphadenopathy or splenomegaly. The liver was palpable 1.5 cm below the costal margin. A complete blood count (CBC) showed: platelets = 17 × 109/L, hemoglobin = 128 g/L, white blood cell count = 5.43 × 109/L, and neutrophils = 1.63 × 109/L. A blood smear was reported as normal. Urate was 370 umol/L and lactate dehydrogenase (LDH) was 803 U/L. The child was admitted with a presumptive diagnosis of immune thrombocytopenic purpura (ITP) and treated with intravenous immunoglobulin. The following day, the blood smear was reviewed by a hematopathologist who identified blasts. A bone marrow aspiration (BMA) confirmed the diagnosis of precursor B-cell acute lymphoblastic leukemia. In children presenting with suspected ITP, leukemia should always be considered. A BMA was historically performed on all patients with presumed ITP to rule out leukemia. In 2011, the American Society of Hematology (ASH) stopped recommending routine BMA in patients suspected of having ITP. ASH advises in cases with unusual findings on history, physical examination or CBC, it is reasonable to perform a BMA. Our patient had mild hepatomegaly, which may have qualified him for a BMA. He also had an elevated LDH and urate, which are not listed as criteria for BMA by ASH but were considered atypical for ITP by the clinical team. A literature search did not reveal any primary data assessing these markers. While corticosteroids are a first line treatment in ITP, they must be reserved for when clinicians are confident that the patient does not have leukemia. Steroid administration prior to diagnosing leukemia results in delayed diagnosis and may increase the risk of complications and decrease survival.

Thrombocytopenia

Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in 20% of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000 per microliter. Thrombocytopenia can be contrasted with the conditions associated with an abnormally high level of platelets in the blood: thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known). Signs and symptoms

Blood cell

The normal range (99% of population analyzed) for platelets is 150,000 to 450,000 per cubic millimeter. If the number of platelets is too low, excessive bleeding can occur. However, if the number of platelets is too high, blood clots can form thrombosis, which may obstruct blood vessels and result in such events as a stroke, myocardial infarction, pulmonary embolism, or blockage of blood vessels to other parts of the body, such as the extremities of the arms or legs. An abnormality or disease of the platelets is called a thrombocytopathy, which can be either a low number of platelets (thrombocytopenia), a decrease in function of platelets (thrombasthenia), or an increase in the number of platelets (thrombocytosis). There are disorders that reduce the number of platelets, such as heparin-induced thrombocytopenia (HIT) or thrombotic thrombocytopenic purpura (TTP), that typically cause thromboses, or clots, instead of bleeding.

Gestational thrombocytopenia

Diagnosis Gestational thrombocytopenia will become evident during the mid-second trimester through the third trimester of pregnancy and it is diagnosed based on exclusion. For example, women with a history of immune thrombocytopenia or thrombocytopenia, prior to pregnancy, will not be diagnosed with gestational thrombocytopenia. Patients with low platelet counts, lower than 70,000 / μL, will be difficult to diagnose. The reason is because low platelet counts maybe due to gestational thrombocytopenia or immune thrombocytopenia. In such cases, a treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin) will be instructed. If there is an improvement in the platelet levels, the patient will be diagnosed with immune thrombocytopenia, and if not the patient will be diagnosed with severe gestational thrombocytopenia In order for the physician to determine the underlying cause of the gestational thrombocytopenia, the following tests are conducted -

Thrombocytopenia

Signs and symptoms Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individuals with thrombocytopenia may experience external bleeding such as nosebleeds, or bleeding gums. Some women may have heavier or longer periods or breakthrough bleeding. Bruising, particularly purpura in the forearms and petechiae in the feet, legs, and mucous membranes, may be caused by spontaneous bleeding under the skin. Eliciting a full medical history is vital to ensure the low platelet count is not secondary to another disorder. Ensuring that the other blood cell types, such as red blood cells and white blood cells are not also suppressed, is also important. Painless, round, and pinpoint (1 to 3 mm in diameter) petechiae usually appear and fade, and sometimes group to form ecchymoses. Larger than petechiae, ecchymoses are purple, blue, or yellow-green areas of skin that vary in size and shape. They can occur anywhere on the body.

Idiopathic thrombocytopenic purpura associated with splenic tuberculosis: case report.

Tuberculosis is still one of the most prevalent and fatal infectious diseases in spite of considerable improvements in medical science. Splenic tuberculosis is a rare form of extrapulmonary tuberculosis. There are limited numbers of cases in which immune thrombocytopenia is associated with splenic tuberculosis. We report a case of immune thrombocytopenic purpura due to splenic tuberculosis. Our case was a 58-year-old female with headache, gum bleeding, redness in legs, and ecchymoses on the arms for 10 days. On admission to hospital, laboratory tests were as follows: platelet count 6.000/mmc (150 000-450 000), haemoglobin: 12 g/dl, WBC: 8000/mm3, erythrocyte sedimentation rate: 58 mm/h and C-reactive protein was in normal ranges. After standard laboratory tests, the patient was diagnosed with idiopathic thrombocytopenic purpura. The patient presented abdominal lymphadenopathies and spleen in normal size in radiological examinations. Diagnostic laparotomy and splenectomy and lymph node excision was performed and splenic tuberculosis was detected in pathologic and microbiologic examination. The patient was successfully treated with apheresis platelets suspension, intravenous immunoglobulin and antituberculous therapy. In conclusion, splenic tuberculosis should be suspected in patients who have fever, abdominal lymphadenopathies and immune thrombocytopenic purpura. Histopathological examination is still an ideal method to confirm the diagnosis, suitably aided by microbiological examination.

InternalMed_Harrison

The history and physical examination, results of the CBC, and review of the peripheral blood smear are all critical components in the initial evaluation of thrombocytopenic patients (Fig. 140-2). The overall health of the patient and whether he or she is receiving drug treatment will influence the differential diagnosis. A healthy young adult with thrombocytopenia will have a much more limited differential diagnosis than an ill hospitalized patient who is receiving multiple medications. Except in unusual inherited disorders, decreased platelet production usually results from bone marrow disorders that also affect red blood cell (RBC) and/or white blood cell (WBC) production. Because myelodysplasia can present with isolated thrombocytopenia, the bone marrow should be examined in patients presenting with isolated thrombocytopenia who are older than 60 years of age. While inherited thrombocytopenia is rare, any prior platelet counts should be retrieved and a family history regarding

Schistocyte

Schistocyte count A normal schistocyte count for a healthy individual is <0.5% although usual values are found to be <0.2%. A schistocyte count of >1% is most often found in thrombotic thrombocytopenic purpura, although they are more often seen within the range of 3–10% for this condition. A schistocyte count of <1% but greater than the normal value is suggestive of disseminated intravascular coagulation, but is not an absolute diagnosis. The standard for a schistocyte count is a microscopic examination of a peripheral blood smear.

Thrombocytopenia

Immune thrombocytopenic purpura Many cases of immune thrombocytopenic purpura (ITP) also known as idiopathic thrombocytopenic purpura, can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts under 50,000 are usually monitored with regular blood tests, and those with counts under 10,000 are usually treated, as the risk of serious spontaneous bleeding is high with such low platelet counts. Any patient experiencing severe bleeding symptoms is also usually treated. The threshold for treating ITP has decreased since the 1990s; hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000, although exceptions to this observation have been documented.

InternalMed_Harrison

The mortality ranges from 30 to >80% depending on the underlying disease, the severity of the DIC, and the age of the patient. The diagnosis of clinically significant DIC is based on the presence of clinical and/or laboratory abnormalities of coagulation or thrombocytopenia. The laboratory diagnosis of DIC should prompt a search for the underlying disease if it is not already apparent. There is no single test that establishes the diagnosis of DIC. The laboratory investigation should include coagulation tests (aPTT, PT, thrombin time [TT]) and markers of fibrin degradation products (FDPs), in addition to platelet and red cell count and analysis of the blood smear. These tests should be repeated over a period of 6–8 h because an initially mild abnormality can change dramatically in patients with severe DIC.

Gestational thrombocytopenia

Gestational (incidental) thrombocytopenia is a condition that commonly affects pregnant women. Thrombocytopenia is defined as the drop in platelet count from the normal range of 150,000 –400,000 / μL to a count lower than 150,000 / μL. There is still ongoing research to determine the reason for the lowering of platelet count in women with a normal pregnancy. Some researchers speculate the cause to be dependent on dilution, decreased production of platelets, or an increased turnover event. Although women with normal pregnancy experience a low platelet count, women experiencing a continuous drop in platelet will be diagnosed with thrombocytopenia and women with levels greater than 70,000 / μL will be diagnosed with gestational thrombocytopenia. Thrombocytopenia affects approximately 7-10% of pregnant women and of the 7-10%, within that population; approximately 70-80% have gestational thrombocytopenia

Thrombocytopenic purpura

Thrombocytopenic purpura are purpura associated with a reduction in circulating blood platelets which can result from a variety of causes, such as kaposi sarcoma. Types By tradition, the term idiopathic thrombocytopenic purpura is used when the cause is idiopathic. However, most cases are now considered to be immune-mediated. Another form is thrombotic thrombocytopenic purpura. Diagnosis Diagnosis is done by the help of symptoms and only blood count abnormality is thrombocytopenia. Treatment See also Aspirin Hematopoietic ulcer Thrombocyte References External links Vascular-related cutaneous conditions Coagulopathies

Thrombocytopenia in Pregnancy -- History and Physical

A physical exam provides clues towards determining the etiology of thrombocytopenia. Patients with gestational thrombocytopenia are often healthy, asymptomatic women who are found to have low platelets on lab investigations. [6] [5] [4] On the contrary, a pregnant woman with TMA is usually a gravely-ill patient often presenting to the emergency room or admitted to high-risk obstetric units. Patients with low platelet count usually present with mucocutaneous bleeding. However, joint bleed or severe bleeding should prompt a workup towards severe coagulopathies like DIC. Physical exam should also evaluate for hepatomegaly and/or splenomegaly (cirrhosis, lymphoproliferative disorders, etc.), skeletal deformities (like absent radius, humeral abnormality and sometimes phocomelia seen in thrombocytopenia absent radii syndrome) and skin exam (like petechiae or purpura seen commonly with ITP, or, eczema seen in Wiskott-Aldrich Syndrome). [7] [29]

Thrombocytopenia

Increased destruction Abnormally high rates of platelet destruction may be due to immune or nonimmune conditions, including: Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Hemolytic–uremic syndrome Disseminated intravascular coagulation Paroxysmal nocturnal hemoglobinuria Antiphospholipid syndrome Systemic lupus erythematosus Post-transfusion purpura Neonatal alloimmune thrombocytopenia Hypersplenism Dengue fever Gaucher's disease Zika virus Medication-induced These medications can induce thrombocytopenia through direct myelosuppression: Valproic acid Methotrexate Carboplatin Interferon Isotretinoin Panobinostat H2 blockers and proton-pump inhibitors Other causes Lab error, possibly due to the anticoagulant EDTA in CBC specimen tubes; a citrated platelet count is a useful follow-up study Snakebite Niacin toxicity Lyme disease Thrombocytapheresis (also called plateletpheresis) Niemann–Pick disease Diagnosis

Efficient diagnosis of thrombocytopenia.

Thrombocytopenia may be a benign, incidental finding in an asymptomatic patient or the sign of a potentially life-threatening disorder. The history, physical examination and peripheral blood smear can assist the physician in determining the diagnosis and treatment. After the initial blood count is repeated to help eliminate the possibility of laboratory error, a thorough history, complete physical examination, complete blood cell count and appropriate laboratory tests are required. The history may reveal related illnesses, risk factors such as infection or drug use, or a family history suggestive of congenital thrombocytopenia. The physical examination should concentrate on the lymphatic and hepatosplenic systems, with the physician looking for jaundice, fever or petechiae. With the review of a complete blood cell count and a peripheral smear examination, the initial work-up is completed and may prevent additional, unnecessary testing. Etiology-specific tests follow if needed. Serious spontaneous bleeding is usually a risk only in patients with platelet levels under 20,000 per mm3.

Coagulation

Decreased platelet numbers (thrombocytopenia) is due to insufficient production (e.g., myelodysplastic syndrome or other bone marrow disorders), destruction by the immune system (immune thrombocytopenic purpura/ITP), or consumption (e.g., thrombotic thrombocytopenic purpura/TTP, hemolytic-uremic syndrome/HUS, paroxysmal nocturnal hemoglobinuria/PNH, disseminated intravascular coagulation/DIC, heparin-induced thrombocytopenia/HIT). Most consumptive conditions lead to platelet activation, and some are associated with thrombosis. Coagulation factor disorders The best-known coagulation factor disorders are the hemophilias. The three main forms are hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency or "Christmas disease") and hemophilia C (factor XI deficiency, mild bleeding tendency).

Thrombocytopenia -- History and Physical

History. Obtaining a thorough history helps to identify the etiology of thrombocytopenia. Patients with platelets greater than 50000/mL, rarely have symptoms. Patients with platelets under 20000/mL most likely have spontaneous bleeding.

Lemierre's syndrome

Production of bacterial toxins such as lipopolysaccharide leads to secretion of cytokines by white blood cells which then both lead to symptoms of sepsis. F. necrophorum produces hemagglutinin which causes platelet aggregation that can lead to diffuse intravascular coagulation and thrombocytopenia. Diagnosis Diagnosis and the imaging (and laboratory) studies to be ordered largely depend on the patient history, signs and symptoms. If a persistent sore throat with signs of sepsis are found, physicians are cautioned to screen for Lemierre's syndrome. Laboratory investigations reveal signs of a bacterial infection with elevated C-reactive protein, erythrocyte sedimentation rate and white blood cells (notably neutrophils). Platelet count can be low or high. Liver and kidney function tests are often abnormal.

Platelet

Disorders Adapted from: The three broad categories of platelet disorders are "not enough"; "dysfunctional"; and "too many". Thrombocytopenia Immune thrombocytopenias (ITP) – formerly known as immune thrombocytopenic purpura and idiopathic thrombocytopenic purpura Splenomegaly Gaucher's disease Familial thrombocytopenia Chemotherapy Babesiosis Dengue fever Onyalai Thrombotic thrombocytopenic purpura HELLP syndrome Hemolytic–uremic syndrome Drug-induced thrombocytopenic purpura (five known drugs – most problematic is heparin-induced thrombocytopenia (HIT) Pregnancy-associated Neonatal alloimmune associated Aplastic anemia Transfusion-associated Pseudothrombocytopenia idiopathic thrombocytopenic purpura Vaccine induced immune thrombocytopenia Gilbert's syndrome

Check for a family history of thrombocytopenia or bleeding disorders.

Neonatal alloimmune thrombocytopenia

Related conditions Immune thrombocytopenic purpura (), sometimes called idiopathic thrombocytopenic purpura is a condition in which autoantibodies are directed against a patient's own platelets, causing platelet destruction and thrombocytopenia. Anti-platelet autoantibodies in a pregnant woman with immune thrombocytopenic purpura will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by will have platelet counts <50,000 μL−1 and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with .

[The analysis of national examination for the license of medical practice in Japan (reference to the hematological clinical laboratory data)].

It seems to us an important task to analyze the problems appeared in the national examinations of the license of medical practice in respect of clinical laboratory data. The national examination of medical license in Japan begun from 1946, about 45 years ago. In those days, clinical examination is not so developed, a pastoral era, so clinical pathology was not clearly distinguished from internal medicine. Recently it is widely emphasized that national examination for the practical medical practice should be focused on the primary care medicine, so on, which has evidently influenced the appearance rate and number of miscellaneous kinds of clinical laboratory data in the examination problems. On the other hand, We have studied the tendency and mode of appearance of clinical laboratory data in the question of above mentioned examination for several years, in general, and especially in the areas of hematology. The cardinal questions of hematological field were blood cell count (RBC, hematocrit, hemoglobin, WBC, white cell differential, PLATELET), blood sedimentation rate, coagulation and fibrinolysis factor, bone marrow findings in miscellaneous diseases, classification and staging of malignant lymphomas, so on. In conclusion, the rate of appearance and significance of clinical laboratory data in the examination mentioned is more and more increased. However, comprehensive education of clinical pathology now is improved but not accomplished, which reflects tendency and styles of the problems of the examination. So more efforts will be needed to those who continuously study clinical pathology and educate them to the medical students.

Plateletpheresis

Platelet transfusion Platelet transfusions are traditionally given to those undergoing chemotherapy for leukemia, multiple myeloma, those with aplastic anemia, AIDS, hypersplenism, idiopathic thrombocytopenic purpura (ITP), sepsis, bone marrow transplant, radiation treatment, organ transplant or surgeries such as cardiopulmonary bypass. Platelet transfusions should be avoided in those with thrombotic thrombocytopenic purpura (TTP) because it can worsen neurologic symptoms and acute renal failure, presumably due to creation of new thrombi as the platelets are consumed. It should also be avoided in those with heparin-induced thrombocytopenia (HIT) or disseminated intravascular coagulation (DIC). In adults, platelets are recommended in those who have levels less than 10,000/µL, or less than 20,000/µL if a central venous catheter is being placed, or less than 50,000/µL if a lumbar puncture or major surgery is required. Whole blood platelets

[The diagnosis of ITP].

Idiopathic thrombocytopenic purpura(ITP) is a hematologic disorder which causes thrombocytopenia. The diagnosis of ITP is based on the history, physical examination and, complete blood count, and examination of the peripheral smear. The diagnostic criteria of ITP established by the Ministry of Health, Welfare, and Labor in Japan requires the bone marrow examination and the measurement of platelet associated IgG, but those tests are not always necessary according to the guidelines developed by the American Society of Hematology. The appropriate strategies for the diagnosis of ITP need to be established. In this paper, some new examinations which may help the diagnosis of ITP are also demonstrated.

InternalMed_Harrison

The physical examination can document an enlarged spleen, evidence of chronic liver disease, and other underlying disorders. Mild to moderate splenomegaly may be difficult to appreciate in many individuals due to body habitus and/or obesity but can be easily assessed by abdominal ultrasound. A platelet count of approxi- FIGURE 140-2 Algorithm for evaluating the thrombocytopenic mately 5000–10,000 is required to maintain vascular integrity in the patient. DIC, disseminated intravascular coagulation; RBC, red blood microcirculation. When the count is markedly decreased, petechiae cell; TTP, thrombotic thrombocytopenic purpura.

Neonatal alloimmune thrombocytopenia

Mothers with thrombocytopenia or a previous diagnosis of should be tested for serum anti-platelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable anti-platelet antibody should be started on therapy for their which may include steroids or . Fetal blood analysis to determine the platelet count is not generally performed as -induced thrombocytopenia in the fetus is generally less severe than . Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. Other conditions causing a low platelet count Other conditions that can cause a low platelet count in the neonate include bacterial and viral infection, disseminated intravascular coagulation and other rare congenital conditions associated with a low platelet count.

[Management of thrombocytopenia].

Thrombocytopenia is defined by a platelet level below 150 G/l. However, the limit of 100 G/l seems more appropriate to determine which thrombocytopenia will require further investigation. Initially, a thorough medical history should be performed as well as screening for any signs of bleeding. After having excluded the presence of platelet aggregates, it should be determined whether thrombocytopenia is isolated or associated with other abnormalities (cytopenias, coagulation disorder, abnormal renal or liver tests). Causes of thrombocytopenia along with the biological tests to achieve diagnosis, will be detailed in this article. We will then determine the medical emergencies that will need to be addressed to a reference center : active bleeding, biological signs of disseminated intravascular coagulation, acute renal failure, platelet count < 30 G/l (or < 50 G/l if the patient is on anticoagulation or antiplatelet therapy), significant and/or brutal onset pancytopenia. Outside these situations where vital prognosis is engaged, the patient should be rapidly addressed in case of platelet count between 30 and 50 G/l without any concomitant anticoagulation or antiplatelet therapy. Platelet levels between 50 and 100 G/l will require investigation, without any urgency, in outpatient haematology clinic.

Gestational thrombocytopenia

Women who have platelet levels lower than 70,000 / μL, during pregnancy, maybe experiencing severe gestational thrombocytopenia or immune thrombocytopenia. In such cases, if the treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin) does not improve the platelet count, the patient will be diagnosed with severe gestational thrombocytopenia. Severe gestational thrombocytopenia may pose a risk for complications with the use of epidural or general anesthesia during delivery. Prognosis Those who have no previous history of thrombocytopenia, besides the occurrence in previous pregnancies (gestational thrombocytopenia), the platelet levels will go back to a normal range 1–2 months after the delivery. Post delivery, approximately 1–3 months later, women with gestational thrombocytopenia should have a complete blood test conducted. Lastly, gestational thrombocytopenia is a disorder that may reoccur in future pregnancies

Disseminated Intravascular Coagulation -- Evaluation

No single history, physical exam, or laboratory component can lead to a diagnosis of or rule out DIC; therefore, a combination of both subjective, objective, and laboratory findings should be utilized to make a diagnosis of DIC. Laboratory findings suggestive of DIC include both an increased prothrombin time (PT) and an increased partial thromboplastin time (PTT), as well as a decreased fibrinogen level as widespread activation and consumption of the clotting cascade occurs. The overall platelet count and hematocrit level may be reduced as well. Schistocytes or fragmented erythrocytes are also commonly seen on a peripheral blood smear. The presence of fibrin split products additionally has a high sensitivity but low specificity for the presence of DIC. A specific scoring system to assess for the presence of DIC was established in 2007. This score includes platelet count, fibrin markers such as D-dimer, prolonged PT, and fibrinogen level, with a score over five indicating a high likelihood for overt DIC. [18] [19] [20] [21]

[Idiopathic thrombocytopenic purpura in children].

Idiopathic (immune) thrombocytopenic purpura (ITP) is the most frequent hemorrhagic disease in children. It represents the acquired megakaryocytic thrombocytopenia with the shortened life of platelets because of immunologic damage (antibodies absorbed by platelets). In the case of this acquired hemorrhagic disorder, in spite of compensatory increased function of the bone marrow, there is a reduced number of platelets because of their increased destruction by the reticuloendothelial system (destructive thrombocytopenia). There are three forms of ITP: acute, chronic and intermittent. The acute form occurs in 80-90% of cases with bleeding episodes lasting a few days or weeks, but no longer than 6 months. The chronic form occurs in 10-15% of children, while the rarest-intermittent form is characterized by periods of normalization in regard to the number of platelets but also with relapse in intervals of 1-3 months. The disease is caused by an immunological disorder in the sense of an imbalanced immune response. Immunologic damages of platelets cause shortening of the opsonized platelets life span. The most frequent platelet opsonins are the immumoglobulin G (IgG) antibodies directed at the platelet membrane in the form of autoantibodies, alloantibodies or possibly absorbed antigen caused by microorganism infection or drug intake. It is typical for the phenomenon of bleeding that it starts suddenly and without any other sign of illness. The most frequent acute form appears between the second and fourth year, and is characterized by seasonal occurrence usually after acute viral infections. Children older than 10 years of age, like adults, often have the chronic form associated with other immunologic disorders. The disease affects girls more often than boys (about three times more often) with moderate and constant increase of antiplatelet antibodies. Hemorrhagic manifestations include: petechiae, purpura, epistaxis, gastrointestinal and genitourinary bleeding. They depend on the grade of thrombocytopenia, although there is no strict correlation between the number of platelets and volume of bleeding. Low mortality of the acute ITP is almost exclusively due to intracranial hemorrhage. LABORATORY STUDIES: Thrombocytopenia represents a decrease in the number of blood platelets being a basic abnormality of the blood count. The half-life of platelets in ITP is shortened. Detection of antiplatelet antibodies is connected with technical difficulties, so they are established in about 30% of cases. Bleeding time is prolonged and so is the coagulum retraction which may be completely missed. The Rumpel-Leede test is positive. Clinical differentiation of drug-induced thrombocytopenia is not possible. However, other differential diagnostic possibilities are thrombotic-thrombocytopenic purpura and hemolytic-uremic syndrome. A child with aplastic anemia or acute leukemia, beside thrombocytopenia, has a characteristic finding of white and red blood cell count. Thrombocytopenia with absent radii syndrome is associated with skeletal system abnormalities. New knowledge about the role of the immune system in ITP determines the modern therapeutic modalities. In cases of acute ITP in children, there are two therapeutic options or therapies of choice: corticosteroids and high doses of intravenous immunoglobulin. Immunosupressive therapy means anti Rh(D) immunoglobulin, cyclosporine, cytostatics, danazol, loaded platelets. In cases of distinctive hemorrhagic syndrome there are also indications for platelet transfusion. Nowadays splenectomy is more restricted, because one third of cases is unsuccessful, whereas plasmapheresis is rarely used in children because of possible complications. ITP is the most frequent hemorrhagic disease in children. The disease is basically caused by an immunologic disorder with platelet destruction due to increased immunoglobulin on their membrane. (ABSTRACT TRUNCATED)