Lecture on Von Willebrand Disease and Qualitative Platelet Disorders

Introduction

• Speaker: Eric from Strong Medicine
• Main Topics: Pathogenesis, clinical manifestations, diagnosis, and treatment of von Willebrand disease and qualitative platelet disorders

Platelet Function Overview

• Adhesion: Platelets bind to exposed collagen or von Willebrand factor (vWF) via GP1B9-5 complex
• Activation: Release of compounds (vWF, fibrinogen, clotting factor V, ADP, thromboxane A2)
  • Conformational changes in receptors (GP2B3A)
  • Change in platelet shape
• Aggregation: vWF and fibrinogen bridge between platelets, forming a plug

Von Willebrand Factor (vWF)

• Large glycoprotein produced in platelets and endothelial cells
• Carrier protein for clotting factor VIII
• Mixture of multimers linked by disulfide bridges

Von Willebrand Disease (vWD)

• Pathogenesis: Decreased/dysfunctional vWF
• Prevalence: Most common inherited bleeding disorder
• Classification:
  • Type 1: Quantitative defect, autosomal dominant, mild to severe bleeding
  • Type 2: Qualitative defect, autosomal dominant/recessive, moderate to severe bleeding
  • Type 3: Total/near-total absence of vWF, autosomal recessive, severe bleeding

Clinical Manifestations

• Common bleeding forms: Epistaxis, oral cavity bleeding, menorrhagia, postpartum hemorrhage
• Type 3: Muscle hematomas, hemarthrosis
• Intracranial hemorrhage uncommon

Diagnosis

• Normal platelet count, possibly prolonged PTT
• Specific tests: Ristocetin cofactor activity, vWF antigen, Factor VIII activity
• Additional: Multimer distribution, ristocetin-induced platelet aggregation

Treatment

• For active bleeding/surgery: Desmopressin (DDAVP), vWF concentrate, antifibrinolytics
• Acquired vWD: Autoantibodies, adsorption, shear stress-induced proteolysis

Qualitative Platelet Disorders

• Acquired Disorders: More common than inherited
  • Causes: Medications, uremia, alcohol, liver failure
• Treatment: Desmopressin, RBC transfusion, cryoprecipitate, avoid platelet transfusion

Inherited Platelet Disorders

• Bernard-Soulier Syndrome: Defect in GP1B95 complex, giant platelets
• Glansman Thrombocytopenia: Defect in GP2B3A, aggregation issue
• MYH9-related Disorder: MYH9 gene defect, giant platelets, other symptoms (hearing loss, cataracts)
• Gray Platelet Syndrome: Absence of alpha granules, macrothrombocytopenia, gray platelets

Conclusion

• Next topic: Coagulation deficiencies such as hemophilia

These notes summarize the key points from Eric's video on von Willebrand disease and qualitative platelet disorders, focusing on understanding the pathogenesis, clinical features, diagnosis, and treatment options for these conditions.