A 28-year-old man with a known bleeding disorder presents with acute hemarthrosis of the right knee. On examination, he has multiple bruises at various stages of healing on his arms and legs. His mother and maternal uncle both have a similar bleeding tendency. What is the most common cause of this inherited bleeding disorder?

Explanation

## Hemophilia A: The Most Common Coagulation Factor Deficiency ### Clinical Clues in This Case **Key Point:** Hemophilia A (Factor VIII deficiency) is the most common inherited coagulation factor deficiency, accounting for ~80% of all hemophilias. 1. **Hemarthrosis** — hallmark of severe Factor VIII deficiency - Spontaneous or post-trauma joint bleeding - Knees, elbows, ankles most commonly affected - Leads to chronic arthropathy if untreated 2. **Deep tissue and muscle hematomas** — indicated by bruises at various stages - Characteristic of Factor VIII deficiency - Absent in platelet disorders or vWD 3. **X-linked inheritance pattern** - Mother and maternal uncle affected → X-linked recessive inheritance - Maternal uncle (hemizygous) affected confirms X-linked pattern - Patient is hemizygous male (affected) ### Comparison: Coagulation Factor Deficiencies | Feature | Factor VIII (Hemophilia A) | Factor V | Prothrombin (Factor II) | Factor VII | | --- | --- | --- | --- | --- | | Prevalence | Most common (~1 in 5,000–10,000) | Extremely rare (1 in 1 million) | Extremely rare | Rare (1 in 500,000) | | Inheritance | X-linked recessive | Autosomal recessive | Autosomal recessive | Autosomal recessive | | PT | Normal | Prolonged | Prolonged | Prolonged | | aPTT | Prolonged | Prolonged | Prolonged | Normal | | Bleeding pattern | Joint, muscle, deep tissue | Mucosal + joint | Mucosal + deep tissue | Mucosal | | Family history | Mother/maternal relatives | Both parents affected | Both parents affected | Both parents affected | **High-Yield:** Hemophilia A accounts for ~80% of hemophilias; Hemophilia B (Factor IX deficiency) accounts for ~20%. Together they are the most common inherited bleeding disorders after vWD. ### Pathophysiology - Factor VIII is a cofactor for Factor IXa in the intrinsic tenase complex - Deficiency → impaired thrombin generation → delayed clot formation - Particularly affects secondary hemostasis in high-shear environments (joints, muscles) **Clinical Pearl:** Spontaneous hemarthrosis is virtually pathognomonic for severe Factor VIII deficiency (activity <1%) and indicates need for immediate replacement therapy to prevent joint destruction. **Mnemonic:** **JOINT** — Joint bleeds, Oral mucosa (less common), INTramuscular hematomas, and deep Tissue bleeding are the hallmarks of Factor VIII deficiency. [cite:Harrison 21e Ch 179; Robbins 10e Ch 4]