Higher rates of bleeding and use of treatment products among young boys compared to girls with von Willebrand disease.

There are limited observational studies among children diagnosed with von Willebrand Disease (VWD). We analyzed differences in bleeding characteristics by sex and type of VWD using the largest reported surveillance database of children with VWD (n = 2712), ages 2 to 12 years old. We found that the mean ages of first bleed and diagnosis were lowest among children with type 3 VWD. It was even lower among boys than girls among all VWD types, with statistically significant difference among children with type 1 or type 3 VWD. Children with type 3 VWD also reported higher proportions of ever having a bleed compared to other VWD types, with statistically higher proportions of boys compared to girls reporting ever having a bleed with type 1 and type 2 VWD. A similar pattern was observed with the use of treatment product, showing higher usage among type 3 VWD, and among boys than girls with type 1 and type 2 VWD. While there were no differences in life quality or in well-being status by sex, children with type 3 VWD showed a greater need for mobility assistance compared to children with type 1 and type 2 VWD. In an adjusted analysis among children with type 1 VWD, boys showed a significant association of ever bleeding [hazard ratio 1.4; P-value <.001)] compared to girls. Understanding phenotypic bleeding characteristics, well-being status, treatment, and higher risk groups for bleeding among pre-adolescent children with VWD will aid physicians in efforts to educate families about bleeding symptoms.

How I treat low von Willebrand factor levels.

Partial quantitative deficiency of plasma von Willebrand factor (VWF) is responsible for the majority of cases of von Willebrand disease (VWD), the most common inherited human bleeding disorder. International consensus guidelines recommend that patients with reduced plasma VWF antigen (VWF:Ag) levels and bleeding phenotypes be considered in 2 distinct subsets. First, patients with marked reductions in plasma VWF levels (<30 IU/dL) usually have significant bleeding phenotypes and should be classified with "type 1 VWD." In contrast, patients with intermediate reduced plasma VWF levels (in the range of 30-50 IU/dL) should be considered in a separate category labeled "low VWF levels." These patients with low VWF commonly display variable bleeding phenotypes and often do not have VWF gene sequence variations. Because the pathophysiology underlying low VWF levels remains largely undefined, diagnosis and management of these patients continue to pose significant difficulties. In this article, we present a number of clinical case studies to highlight these common clinical challenges. In addition, we detail our approach to establishing a diagnosis in low VWF patients and discuss strategies for the management of these patients in the context of elective surgery and pregnancy.

Severe transfuse related acute lung injury (TRALI) syndrome in a 14 years old girl with a history of type I von Willebrand disease.

Von Willebrand disease (vWD) is the most common inherited bleeding disorder based on an autosomal abnormality of von Willebrand factor. Transfusion is a lifesaving medical intervention among patients with bleeding disorders. Patients with vWD are exposed to Transfuse Related Acute Lung Injury (TRALI) when they become recipients of multiple blood products and repeated transfusions. TRALI is a non-hemolytic transfusion reaction induced by infusions of intravenous immunoglobulin, platelets (suspended in plasma), whole blood, cryoprecipitates, and fresh frozen plasma (FFP). We report a 14 years old white girl, with a history of type 1 von Willebrand disease (vWd), recipient of 2 units' fresh-frozen plasma (FFP) and 1 unit whole blood transfusion who developed an acute respiratory distress with severe hypoxemia and bilateral pulmonary infiltrate on chest X-ray within 3 hours of the whole blood transfusion, completely reversible after mechanical ventilation. Concluding, patients with vWd who received recurrent transfusions have an increased risk of TRALI. Physicians must be familiar with it as a cause of white lung X-ray pattern.

Use of autologous platelet-rich clots for the prevention of local injury bleeding in patients with severe inherited mucocutaneous bleeding disorders.

Stopping or preventing local bleeding in patients with inherited bleeding disorders linked to abnormal platelet function is traditionally treated by transfusion of blood cell products or recombinant factor VIIa. We now report the use in such patients of autologous platelet-rich clots as an aid to preventing bleeding and to facilitating tissue regeneration at superficial sites. Two patients with von Willebrand's disease (VWD) type 2B and one patient with type I Glanzmann thrombasthenia were treated after tooth extraction and dental surgery. A fourth patient with platelet-type VWD underwent a skin biopsy. Whereas all four patients had a lifelong history of bleeding complications, the application of an autologous platelet-rich clot immediately after surgery combined with tranexamic acid intake to slow fibrinolysis prevented blood loss and resulted in rapid and normal healing. This new procedure is simple, safe and inexpensive; it provides extra security for patients with a bleeding risk undergoing dentistry or superficial surgery.

Advances in the diagnosis and management of type 1 von Willebrand disease.

Von Willebrand disease (VWD) is an autosomally inherited bleeding disorder caused by a deficiency and/or abnormality of von Willebrand factor (VWF). VWF is a multimeric adhesive protein that plays an important role in primary hemostasis by promoting platelet adhesion to the subendothelium at sites of vascular injury and platelet-platelet interactions at high-shear rate conditions. Furthermore, VWF is the carrier of factor VIII, thus indirectly contributing to the coagulation process. Most cases have a partial quantitative deficiency of VWF (type 1 VWD) with variable bleeding tendency, whereas qualitative variants (type 2 VWD), due to a dysfunctional VWF, are clinically more homogeneous and account for approximately 20-30% of cases. Type 3 VWD is rare and these patients have moderate-to-severe bleeding diathesis, display a recessive pattern of inheritance and virtual absence of VWF. The diagnosis of VWD may be difficult, especially in type 1 disease, since the laboratory phenotype of the disorder is very heterogeneous and confounded by the influence on VWF levels by factors outside the VWF gene (e.g., blood group). An array of tests are usually required to characterize the several types of the disorder in order to predict the best treatment modality. Desmopressin is the treatment of choice for most patients with type 1 VWD because it corrects the the dual defects of hemostasis, that is, abnormal coagulation expressed by low levels of factor VIII and abnormal platelet adhesion expressed by the reduction of VWF.