Coagulation factor disorders

Coagulation Cascade - The Clotting Symphony

• Intrinsic Pathway: Activated by endothelial damage. Measured by aPTT.
  • Factors: XII, XI, IX, VIII.
  • 📌 Mnemonic: PITT (Partial thromboplastin time, Intrinsic).
• Extrinsic Pathway: Activated by tissue injury releasing Tissue Factor (TF). Measured by PT.
  • Factor: VII.
  • 📌 Mnemonic: PET (Prothrombin time, Extrinsic).
• Common Pathway: Begins at Factor X, leading to a fibrin clot.
  • Factors: X, V, II (Prothrombin), I (Fibrinogen).

⭐ Calcium (Factor IV) is a required cofactor for most activation steps. Citrate in blood collection tubes chelates calcium to prevent clotting before testing.

Hemophilia A & B - Royalty's Bleeding Curse

• Pathophysiology: X-linked recessive disorders leading to defective intrinsic coagulation cascade.
• Clinical Presentation: Recurrent hemarthrosis (painful, swollen joints), deep tissue hematomas, and prolonged bleeding after minor trauma or surgery. Severity correlates with factor activity level.

Von Willebrand Disease - The Commonest Bleeder

• Most common inherited bleeding disorder, usually Autosomal Dominant.
• Pathophysiology: Deficiency or defect in von Willebrand Factor (vWF) impairs platelet adhesion and decreases circulating Factor VIII (vWF is its carrier).
• Presentation: Mucocutaneous bleeding (epistaxis, gingival bleeding, menorrhagia), easy bruising. Unlike hemophilia, hemarthrosis is rare.
• Labs:
  • ↑ Bleeding time
  • ↑ PTT (due to low FVIII), but may be normal
  • Normal PT
• Treatment: Desmopressin (DDAVP) for minor bleeding; vWF-containing concentrates for severe cases.

⭐ The Ristocetin cofactor assay is the definitive diagnostic test. It measures vWF function; in vWD, ristocetin fails to induce normal platelet agglutination.

Acquired Disorders - DIC, Vitamin K, & Liver Disease

• Vitamin K Deficiency:

  • Required for factors II, VII, IX, X, and proteins C & S. 📌 1972 + C/S.
  • Causes: Warfarin, broad-spectrum antibiotics, malabsorption.
  • Labs: Initially ↑ PT, later ↑ PTT. Normal platelet count.

• Liver Disease:

  • ↓ Synthesis of all factors except Factor VIII.
  • ↓ Thrombopoietin → thrombocytopenia.
  • Labs: ↑ PT, ↑ PTT, ↑ Bleeding Time.

• Disseminated Intravascular Coagulation (DIC):

  • Widespread clotting activation consumes factors & platelets, leading to bleeding.
  • Labs: ↑ PT, ↑ PTT, ↑ BT; ↓ Platelets, ↓ Fibrinogen; ↑↑ D-dimer.

⭐ In DIC, schistocytes (fragmented RBCs) on a peripheral smear are a key finding, resulting from mechanical damage as red cells pass through microthrombi.

High‑Yield Points - ⚡ Biggest Takeaways

• Hemophilia A (Factor VIII) and B (Factor IX) are X-linked recessive disorders causing hemarthrosis and deep tissue bleeding; they show an isolated ↑ PTT.
• von Willebrand disease, the most common inherited bleeding disorder, presents with mucocutaneous bleeding, an ↑ bleeding time, and a normal or ↑ PTT.
• Vitamin K deficiency impairs factors II, VII, IX, X, C, and S, leading to an ↑ PT and PTT.
• DIC shows widespread factor consumption, causing ↑ PT, ↑ PTT, thrombocytopenia, and schistocytes.