Factor VIII concentrate-responsive thrombocytopenia, hemolytic anemia, and nephropathy. Evidence that factor VIII:von Willebrand factor is involved in its pathogenesis

A 4-year-old Japanese girl had a congenital disorder that was characterized by recurrent thrombocytopenia, hemolytic anemia, hematuria, and proteinuria, which were repeatedly improved by the infusion of factor VIII concentrate. She developed the similar symptoms within 1 h after 1-desamino-8-D-arginine vasopressin (DDAVP) administration. Coagulation studies 30 and 60 min after DDAVP infusion showed a disappearance of large factor VIII:von Willebrand factor (VIII:vWF) multimers, which was the same abnormality that was observed at acute episodes. There were no significant changes in the plasma levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 before and after DDAVP infusion. These results provide further support that VIII:vWF is directly involved in the pathogenesis of this congenital disorder.     

Continuous infusion of von Willebrand factor and factor VIII after elective heart surgery in a 12-year-old girl with von Willebrand disease type 3

The continuous infusion of von Willebrand factor (VWF) in a 12-year-old girl with type 3 von Willebrand disease is described. The patient had elective heart surgery with cardiopulmonary bypass for closure of her atrial septum defect. The surgical procedure lasted 3 h. A presurgical bolus followed by a postoperative continuous infusion of factor VIII/VWF concentrates was administered. During the continuous infusion of clotting factors, stable plasma levels of hemostasis and avoidance of dangerously low levels of factor concentrates were achieved. No peri- or postsurgical complications occurred. Continuous infusion of clotting factors allows constant and hemostatic factor concentrations to be maintained with the possibility of dose titration and adjustment.     

Circumcision in a combined factor V and factor VIII deficiency using desmopressin (DDAVP)

Combined factor V and VIII deficiency is a rare inherited autosomal recessive single gene disorder commonly seen in the Middle East. Although the factor levels are between 5-30%, several authors have reported that these patients are more prone to bleeding compared to those having an isolated factor deficiency with the same levels. We report an eight-year-old boy with factor V and VIII deficiency who underwent a successful circumcision using desmopressin (DDAVP).     

Hydrops fetalis and fibrosarcoma: case report of an uncommon association

Fetal hydrops associated with neonatal tumours is an uncommon occurrence. The diagnosis can be established prenatally by ultrasound examination. The treatment of choice is surgery which may be curative. We report the case of a male born at 32 weeks gestation who presented with severe hydrops fetalis and a thoracic mass. The child could not be operated upon because of rapid clinical deterioration. The autopsy findings confirmed the diagnosis of congenital fibrosarcoma. This is, to our knowledge, the first case of hydrops fetalis associated with fibrosarcoma. Conclusion The association of hydrops fetalis and fibrosarcoma is an exceptional observation but can be added to the long list of differential diagnoses of non-immune hydrops.     

Hydrops fetalis and fibrosarcoma: case report of an uncommon association

Fetal hydrops associated with neonatal tumours is an uncommon occurrence. The diagnosis can be established prenatally by ultrasound examination. The treatment of choice is surgery which may be curative. We report the case of a male born at 32 weeks gestation who presented with severe hydrops fetalis and a thoracic mass. The child could not be operated upon because of rapid clinical deterioration. The autopsy findings confirmed the diagnosis of congenital fibrosarcoma. This is, to our knowledge, the first case of hydrops fetalis associated with fibrosarcoma. Conclusion The association of hydrops fetalis and fibrosarcoma is an exceptional observation but can be added to the long list of differential diagnoses of non-immune hydrops. Received: 28 November 1995 / Accepted: 31 May 1996     

Congenital microangiopathic hemolytic anemia and thrombocytopenia with unusually large von Willebrand factor multimers and von Willebrand factor-cleaving protease

Infantile or congenital cases of thrombotic microangiopathy have been reported that were familial and characterized by ongoing microangiopathic hemolysis and thrombocytopenia in the absence of regular fresh-frozen plasma transfusions. The authors describe a child with congenital microangiopathic hemolytic anemia and thrombocytopenia (CMHAT) who has received regular fresh-frozen plasma transfusions since infancy and has never had thrombotic complications. von Willebrand factor (vWF)-cleaving protease activity was studied in the patient's pretransfusion and posttransfusion plasma samples as well as in her parents' plasma. The effects of the patient's and a control subject's plasma on human microvascular endothelial cells were also investigated. Unusually large vWF multimers were present in the patient's plasma both before transfusion (thrombocytopenic) and after transfusion. Unlike cases of chronic relapsing thrombotic thrombocytopenic purpura, vWF-cleaving protease activity was present and treatment of cultured human endothelial cells with the patient's plasma did not induce apoptosis. These findings suggest that the patient with CMHAT may represent a different group in the broad spectrum of thrombotic microangiopathies.     

von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157:H7-associated hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) usually occurs after infection with Shiga toxin-producing bacteria. Thrombotic thrombocytopenic purpura, a disorder with similar clinical manifestations, is associated with deficient activity of a circulating metalloprotease that cleaves von Willebrand factor at the Tyr842-Met843 peptide bond in a shear stress-dependent manner. We analyzed von Willebrand factor-cleaving metalloprotease activity and the status of von Willebrand factor in 16 children who developed HUS after Escherichia coli O157:H7 infection and in 29 infected children who did not develop this complication. Von Willebrand factor-cleaving metalloprotease activity was normal in all subjects, but von Willebrand factor size was decreased in the plasma of each of 16 patients with HUS. The decrease in circulating von Willebrand factor size correlated with the severity of thrombocytopenia and was proportional to an increase in von Willebrand factor proteolytic fragments in plasma. Immunohistochemical studies of the kidneys in four additional patients who died of HUS demonstrated glomerular thrombi in three patients, and arterial and arteriolar thrombi in one patient. The glomerular thrombi contained fibrin but little or no von Willebrand factor. A decrease in large von Willebrand factor multimers, presumably caused by enhanced proteolysis from abnormal shear stress in the microcirculation, is common in HUS.     

Combination of von Willebrand disease type 1 and partial factor XII deficiency in children: clinical evidence for a diminished bleeding tendency

Factor XII deficiency can be associated with a thrombotic and VWF deficiency with a haemorrhagic clinical course. To study the potential influence of factor XII deficiency on bleeding tendency in patients suffering from VWD we retrospectively compared the clinical outcome of children with either an isolated factor XII deficiency, an isolated VWD, or a combination of both. Patients with the combined coagulation defect showed significantly fewer bleeding events when compared to patients with isolated VWD, although ristocetin cofactor activities were reduced to a comparable degree. As far as aPTT values are concerned, there were no significant differences among the three groups. Whether this combination of thrombophilic and haemorrhagic coagulation disorders is only coincidental or the result of an active modulation of one of the two counteracting coagulation factors is not known at present.     

新生儿窒息后早期血浆VWF D-二聚体及蛋白C水平的变化

目的：探讨新生儿窒息后早期血浆血管性假血友病因子(VWF)、D二聚体(D-D)以及蛋白C(PC)的变化规律观察新生儿窒息对凝血功能的影响及临床意义。方法：检测39例新生儿窒息后血浆VWF、D D及PC水平,并与25例正常新生儿比较。结果：新生儿重度窒息后血浆VWF、D D平均值分别为：(140.18±28.38)%,(3.92±1.50) mg/L,与对照组平均值(111.80±17.19)%,(0.42±0.21) mg/L比较均增高显著,差异有显著性意义(P＜0.01＝;PC平均值(2.85±0.55) μg/ml,与对照组(4.73±1.88) μg/ml比较明显降低,P<0.01;重度窒息组与轻度窒息组VWF、D D、PC平均值(128.99±11.18)%,(1.43±0.84) mg/L,(4.17±1.32) μg/ml比较变化明显(P＜0.01 或 0.05)。轻度窒息组血浆VWF、 DD平均值与对照组比较亦增高显著(P＜0.01 或 0.05),而血浆PC平均值降低不明显,与对照组比较差异无显著性意义(P＞0.05)。3组血小板计数均在正常范围,但重度窒息组血小板值较对照组低。结论：新生儿窒息后早期存在内皮细胞损伤及凝血功能异常,反映血液呈高凝状态,且各项指标异常程度与窒息分度有关。血管内皮损伤在窒息病理生理学中具有重要意义。     

Staphylococcal scalded skin syndrome: An uncommon symptomatology revealing an immune deficiency

Primary immune deficiencies associated with hyper-IgE syndrome are rare diseases with clinical features dominated by recurring cutaneous and visceral bacterial infections, particularly infections due to Staphylococcus species. Most of these infections are associated with milder inflammation compared to normal. We report a primary immune deficiency associated with a hyper-IgE syndrome revealed by a staphylococcal scalded skin syndrome in a 5-year-old girl. The patient presented with a severe staphylococcal infection with extensive skin lesions and disseminated intravascular coagulation. She received intravenous fluids to compensate for fluid losses and anti-staphylococcal antibiotics. Coagulopathy was also corrected. However, the progression was rapidly fatal.     

Decreased clearance of von Willebrand factor in a patient with type 2B von Willebrand disease following development of immune thrombocytopenia

We report a case of concurrent type 2B von Willebrand disease (VWD) and immune thrombocytopenia (ITP). The patient had characteristic loss of von Willebrand factor (VWF) high molecular weight multimers (HMWM) but a normal platelet count in the initial 8 years after diagnosis of type 2B VWD. When he developed severe thrombocytopenia, however, both his VWD indices and VWF HMWM normalized. As his platelet count increased, he again lost the HMWM and his VWD indices decreased. These results suggest that the severe thrombocytopenia led to decreased clearance of VWF, especially the HMWM.