🧬 Chapter 527 · Hereditary Predisposition to Thrombosis (Thrombophilia)

Nelson Textbook of Pediatrics 22nd Edition | Inherited thrombophilias: Factor V Leiden (most common, APC resistance), prothrombin G20210A, antithrombin deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia (MTHFR polymorphism — not a risk factor alone). Clinical presentation: neonatal purpura fulminans (homozygous protein C/S deficiency), DVT, PE, cerebral sinovenous thrombosis. Testing: functional assays (protein C, S, antithrombin) and DNA analysis (FVL, prothrombin). Management: anticoagulation (heparin, LMWH, warfarin, DOACs).

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📋 30 Clinical Scenarios — Hereditary Thrombophilia

📇 High‑Yield Review Cards (Thrombophilia)

🩺 Clinical Recognition: Hereditary Thrombophilia

Select a presentation for diagnostic clues and management.

📋 Stepwise Management of Hereditary Thrombophilia

🔑 Key Principles — Nelson Chapter 527
• Factor V Leiden (FVL): Most common (3-7% of Caucasians). APC resistance. Heterozygous: 5-7x risk, homozygous: 50-80x risk. No routine testing; test if unprovoked VTE, family history, or recurrent VTE.
• Prothrombin G20210A: 2-3x risk. Test with FVL.
• Antithrombin (AT), protein C (PC), protein S (PS) deficiencies: Strong risk factors. Homozygous PC/PS deficiency → neonatal purpura fulminans. Do NOT test during acute thrombosis (false low levels). Retest after anticoagulation stopped or off warfarin (PC/PS are vitamin K-dependent).
• Hyperhomocysteinemia: MTHFR C677T polymorphism alone is NOT a risk factor. Test homocysteine level.
• Indications for testing: Unprovoked VTE in child/adolescent, recurrent VTE, unusual site thrombosis (cerebral, portal, mesenteric), strong family history of VTE, neonatal purpura fulminans.

    ⚡ Reflex Prompts — Clinical Decisions in Thrombophilia

    📖 Summary: Hereditary Thrombophilia — Nelson Chapter 527