Unusual Cause of Thrombocytopenia and Renal Failure in a 14-Year-Old Boy (MYH9-Associated Disorders).

MYH9-associated disorders represent rare group of autosomal dominant diseases and are caused by pathogenic mutations in the MYH9 gene. Clinically, they are represented by macro-platelet-thrombocytopenia, various degrees of renal dysfunction, hearing loss, and early onset cataracts. We describe the case of 14-year-old boy in medical follow-up from birth for thrombocytopenia. Systolic hypertension and nephrotic proteinuria were detected at preventive health check. Renal biopsy revealed sing of segmental glomerulosclerosis. Dialysis treatment was needed. Before transplantation due to the finding of chronic tonsillitis with positive bacterial capture in the culture examination, tonsillectomy was indicated. Postoperative period was complicated with arterial post-tonsillectomy hemorrhage. Six months after tonsillectomy, the patient underwent primary deceased-donor kidney transplantation without complication. Blood platelets showed fluctuating character in the zone of severe thrombocytopenia. However, no signs of bleeding were present. Three months after successful transplantation gene sequencing of whole exon was performed. The presence of the variant c.2105G>A [p.(Arg702HIS)] in exon 17 of the MYH9 gene has been detected. The variant c.2105G>A may be clinically manifested by progressive proteinuria with rapid deterioration of renal function. This case is an example of the delayed diagnosis of rare disease and highlights the usefulness of genetic testing.

Multimer Analysis of Von Willebrand Factor in Von Willebrand Disease with a Hydrasys Semi-Automatic Analyzer-Single-Center Experience.

von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder. This disorder develops as a result of defects and/or deficiency of the plasma protein von Willebrand factor (VWF). Laboratory testing for VWF-related disorders requires the assessment of both VWF level and VWF activity, the latter requiring multiple assays. As an additional step, an evaluation of VWF structural features by multimer analysis is useful in selective investigations. Multimer analysis is also important for the selection of a suitable VWF therapy preparation (desmopressin, VWF/FVIII concentrate, recombinant VWF) and the determination of the correct dose for the patient. Based on clinical and laboratory findings, including the analysis of VWF multimers, we classified our patients into individual types of VWD. Our study group included 58 patients. The study group consisted of 66% (38 patients) with VWD type 1, 5% (3 patients) with VWD type 2, 7% (4 patients) with VWD type 3, 5% (3 patients) with mixed type 1/2A VWD, and 17% (10 patients) comprising an unclassified group. In this article, we provide an overview of our practical experience using a new complementary method-the analysis of von Willebrand factor multimers with a semi-automatic analyzer Hydrasys 2 scan. We explain the principle, procedure, advantages, and pitfalls associated with the introduction of the VWF multimer analysis methodology into standard VWD diagnostics.

Rituximab-associated progressive multifocal leukoencephalopathy.

The definition "Progressive Multifocal Leukoencephalopathy" (PML) was first used in 1958 to describe a fatal demyelinating central nervous system (CNS) disease in patients with lymphoproliferative disorders. In 1971, the virus responsible for the disease was isolated and named John Cunningham virus (JCV). We present a rare case of a 62-year-old male with chronic lymphocytic leukemia and PML. In our work, we discuss the diagnostic and therapeutic challenges and offer suggestions for preventing PML development. The main learning points are: 1. Regularly check the level of immunoglobulins and the CD4+ : CD8+ T-cell ratio, intravenous administration of immunoglobulins should be considered when recording their reduction. 2. In checking the CD4+ : CD8+ T-cell ratio and verifying the impossibility of raising the level of immunoglobulins, we must weigh the possible benefits of continuing treatment with monoclonal antibody against the risks. 3. Physicians should maintain a high index of suspicion for the development of PML in patients under treatment with monoclonal antibodies, especially when there is a new development of neurological signs or symptoms.Key words: JC virus - progressive multifocal leukoencephalopathy - recommendation - rituximab.

Prothrombin gene 20210A mutation in Slovak population.

INTRODUCTION: Factor V Leiden (FVL) and prothrombin G20210A mutation (PTM) are the two most common genetic polymorphisms known to predispose to a first episode of venous thromboembolism (VTE). PTM is present in 2 % Caucasian population. The main aim of this study was to identify the PTM in the patients with positive history of thrombotic events vs. control subjects. MATERIALS AND METHODS: The assessment of PTM was performed by the PCR analysis of the chromosomal DNA, which was isolated from the peripheral blood leukocytes. RESULTS: Of the 2 274 patients included, 157 (6.9 %) were carriers of the PTM. The mutation was present only in 2.6 % (n = 8) of the 303 controls. The following clinical manifestations of PTM were analysed. We observed 123 venous thrombotic events, 46 arterial thrombosis and 14 spontaneous abortions. In this article we analyse other possible risk factors for thromboembolic events in patients with carriage of PTM. CONCLUSIONS: To our knowledge, this is the largest epidemiological study of PTM in Central Europe. Employing statistical analysis, we found relatively high prevalence of the PTM in both, the patients with positive thrombosis history (6.9 %), as well as in the control group (2.6 %). The risk of thrombosis by carriage of PTM is independent of age and gender. Study has shown relatively frequent presence of double carriership of PTM and factor V Leiden mutation (FVL).

The use of intravenous immunoglobulin in immune tolerance induction in inherited haemophilia A: a single-centre experience and a review of literature.

The immune tolerance induction is the treatment of choice for the eradication of factor VIII inhibitors, a serious complication of inherited haemophilia A. Despite the preferred treatment of patients with good prognosis and testing of different regimens, the immune tolerance is achieved in 70-80%. Several modifications of regimens including the addition of immunomodulatory agents were proposed in order to improve immune tolerance induction (ITI) outcome. Intravenous immunoglobulin has complex immunomodulatory properties and has been used in immune tolerance induction since the introduction of Malmö regimen in the 1980s. The aim of the work is to evaluate the published evidence of its use in ITI in haemophilia A. In addition, the authors' own experience with a high-dose regimen using human plasma-derived factor VIII containing von Willebrand factor and pulsed IVIg is reported. The course of three patients with severe inherited haemophilia A and inhibitor (all high responders, two with poor prognosis, one with rescue treatment) is described. At least partial success was achieved in all patients and no adverse events attributable to intravenous immunoglobulin were observed. Despite the limited evidence, the addition of intravenous immunoglobulin appears to be a promising treatment modification for patients with poor prognosis or previous failure of immune tolerance induction.

Wiskott-Aldrich syndrome caused by a new mutation associated with multifocal dermal juvenile xanthogranulomas.

Wiskott-Aldrich syndrome is a rare X-linked primary immunodeficiency clinically characterized by the triad of microthrombocytopenia, immunodeficiency, and eczema. Juvenile xanthogranuloma is a well-recognized benign disorder of infancy and early childhood from the group of non-Langerhans cell histiocytoses, with a good prognosis and spontaneous involution. We report a boy with Wiskott-Aldrich syndrome caused by a new, not previously described mutation associated with multifocal juvenile xanthogranuloma.

Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report.

INTRODUCTION: The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. CASE PRESENTATION: A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin) is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. CONCLUSION: Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

Successful immune tolerance induction with high-dose coagulation factor VIII and intravenous immunoglobulins in a patient with congenital hemophilia and high-titer inhibitor of coagulation factor VIII despite unfavorable prognosis for the therapy.

BACKGROUND: The production of factor VIII (FVIII) inhibitors is a serious problem of replacement therapy with FVIII concentrates in hemophiliacs. It affects 10-20% patients and leads to an increased risk of severe bleeding and its complications. Immune tolerance induction (ITI) is considered the appropriate treatment in such cases, despite different regimens without clearly defined effectiveness. ITI eradicates FVIII inhibitors and allows retreatment with FVIII concentrates in 70% of patients. CASE REPORT: The case of a patient with congenital hemophilia A in whom allo-antibodies against FVIII were identified in a high titer at the age of 5 after 70 exposures to human plasma FVIII concentrates is presented. A spontaneous decrease in inhibitor titer to 14 BU/ml within 6 months after the termination of FVIII administration allowed ITI, consisting of FVIII in high doses and intravenous immunoglobulins. Cessation of bleeding during the treatment was achieved with recombinant activated FVII (rFVIIa). ITI lasted for 22 months and, despite the high inhibitor titer at the start of ITI suggesting poor outcome, it led to eradication of the inhibitor. The prophylactic replacement therapy with FVIII was restarted and since then no signs of FVIII inhibitor have been observed. CONCLUSIONS: ITI with high-dose FVIII, intravenous immunoglobulins, and rFVIIa is a beneficial treatment option for hemophiliac A patients with high-titer FVIII inhibitor.