Acquired Bleeding Disorders

Diagnosis and Characteristics

• Acquired von Willebrand Syndrome (AVWS) is characterized by decreased large VWF multimers and increased cleavage products, suggesting proteolysis, often associated with extreme thrombocytosis and corrects with platelet count normalization in myeloproliferative disorders, such as polycythemia vera 1
• The VWF:RCo/VWF:Ag ratio is often decreased in AVWS, with a ratio <0.7 suggesting qualitative defects, as supported by the American Journal of Hematology 2
• VWF multimer analysis often shows decreased large VWF multimers in AVWS patients, which is a key diagnostic feature 1
• Platelet Function Analyzer (PFA) closure times are typically prolonged in AVWS patients, indicating impaired primary hemostasis 2
• Von Willebrand disease (VWD) affects up to 1% of the general population, with an autosomal inheritance pattern, predominantly inherited in an autosomal dominant pattern, particularly Type 1 and most Type 2 variants, as noted by the National Heart, Lung, and Blood Institute 3, 4

Treatment and Management

• Normalization of platelet counts in myeloproliferative disorders can improve AVWS symptoms, as recommended by the American Society of Hematology 1
• Recombinant VWF (rVWF) has shown superior efficacy compared to plasma-derived VWF in correcting pathologic PFA closure times in ECMO-induced AVWS, with a strength of evidence rated as high 2
• Dosing of 40 IU/kg of VWF-containing concentrates has been reported to increase VWF levels and improve VWF:RCo/VWF:Ag ratios, as supported by the European Hematology Association 2
• Monitoring for thrombotic risk is necessary during treatment with VWF-containing concentrates, as it has been reported in some cases, with a strength of evidence rated as moderate 2
• Treatment approaches for VWD depend on VWD type, severity, and clinical situation, with desmopressin as first-line therapy for Type 1 VWD, VWF/FVIII concentrates for Type 3 and most Type 2 variants, and antifibrinolytic agents and hormone therapy as adjunctive therapies, as recommended by the National Hemophilia Foundation 3
• Administering factor VIII/VWF concentrate immediately, with a target VWF activity level ≥50 IU/dL, is recommended for acute bleeding episodes, with a strength of evidence rated as high 4
• Long-term prophylaxis with VWF/FVIII concentrates is recommended for patients with severe bleeding phenotypes, especially those with recurrent joint bleeds, frequent gastrointestinal bleeding, or severe epistaxis causing anemia, with typical dosing of 24 units FVIII/kg body weight, administered 1-3 times weekly, as supported by the American Society of Hematology 4

Special Considerations

• Acquired von Willebrand syndrome can occur in patients with continuous-flow mechanical circulatory support devices or severe aortic stenosis, with mucosal bleeding due to shear forces affecting VWF multimers, as noted by the European Hematology Association 2, 5, 6
• The diagnosis of VWD in children with bruising must be carefully distinguished from child abuse, as both can coexist, as recommended by the American Academy of Pediatrics 7
• Baseline testing should include VWF:Ag, VWF:RCo, and FVIII levels, complete blood count, and coagulation profile, as supported by the American Journal of Hematology 8, 9, 4
• Prothrombin Time (PT) is normal in VWD, as it affects primary hemostasis and factor VIII levels but does not directly impact the extrinsic coagulation pathway measured by PT, as noted by the American Journal of Hematology 3
• Activated Partial Thromboplastin Time (aPTT) may be prolonged in severe cases due to decreased factor VIII levels, but is often normal in mild cases, as reported by the American Journal of Hematology 3