Bleeding and Coagulation Disorders

Overview

• Topics Covered:
  • Hemophilia A
  • Hemophilia B
  • Von Willebrand Disease
  • Factor V Leiden
  • Protein C and S Deficiency
• Aim: Simplify these disorders by understanding their pathophysiology.

Hemophilia A

• Type: Most common type of hemophilia; X-linked recessive disorder.
• Affected Individuals: Primarily affects males (one X chromosome).
• Mnemonic: Think of "Phil" as in "Dr. Phil", male association.
• Deficiency: Factor VIII (8) deficiency; intrinsic pathway disruption.
• Symptoms:
  • Hemarthrosis (bleeding into joint spaces).
  • Swelling out of proportion to injury.
• Diagnosis:
  • Normal PT, prolonged PTT (measures intrinsic pathway including Factor VIII).
  • Factor VIII assay (can be normal in mild cases).
• Treatment:
  • Factor VIII infusions.
  • Desmopressin (DDAVP) for mild cases (stimulates von Willebrand factor release).

Hemophilia B

• Type: Similar to Hemophilia A but less common.
• Deficiency: Factor IX deficiency; also X-linked recessive.
• Mnemonic: B9 - "benign tumor" association.
• Symptoms: Similar to Hemophilia A.
• Diagnosis:
  • Normal PT, prolonged PTT (measures intrinsic pathway including Factor IX).
  • Factor IX assay.
• Treatment:
  • Factor IX infusions.
  • Note: DDAVP not used (only effective for Factor VIII).

Von Willebrand Disease

• Type: Most common inherited bleeding disorder.
• Deficiency: Decrease in quantity/quality of von Willebrand factor.
• Symptoms:
  • Mucocutaneous bleeding, easy bruising.
• Diagnosis:
  • Normal PT, prolonged PTT (due to factor VIII degradation without von Willebrand factor).
  • Von Willebrand factor antigen/activity tests.
  • Ristocetin test (measures platelet aggregation).
• Treatment:
  • Desmopressin (DDAVP) for mild cases.
  • Von Willebrand factor concentrates for severe cases.

Factor V Leiden

• Type: Mutation leading to hypercoagulable state.
• Mutation: Factor V (resistant to inactivation by Protein C).
• Mnemonic: "Frequently Forming Lumps" (lumps = clots).
• Symptoms:
  • Venous thromboembolism (DVTs, PEs).
  • Miscarriages.
• Diagnosis:
  • Genetic testing for point mutation.
  • Initial protein C resistance test.
• Treatment:
  • Anticoagulation.

Protein C and S Deficiency

• Type: Decreased levels lead to hypercoagulable state.
• Function: Protein C and S inactivate Factors V and VIII (prevent excessive clotting).
• Symptoms:
  • Venous thromboembolism.
  • Warfarin-induced skin necrosis (due to transient hypercoagulable state from warfarin).
• Diagnosis:
  • Protein C and S assays (measure activity/levels).
• Treatment:
  • Anticoagulation.
  • Protein C concentrate for prophylaxis in surgeries or pregnancy.

Important Points

• Hemophilia A: Factor VIII deficiency, male patients, use DDAVP.
• Hemophilia B: Factor IX deficiency, similar treatment sans DDAVP.
• Von Willebrand Disease: Most common bleeding disorder, treat with DDAVP.
• Factor V Leiden: Most common inherited hypercoagulable state, treat with anticoagulation.
• Protein C and S Deficiency: Leads to hypercoagulability, manage with anticoagulation and protein C concentrates.