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Thrombophilia

Thrombophilia. Definition Tendency to develop clots due to predisposing factors that may be genetically determined. Classification Inherited Acquired Inherited + acquired. Inherited Thrombophilia. Caused by defective gene Activated protein C resistance (factor V Leiden)- least severe

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Thrombophilia

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  1. Thrombophilia

  2. Definition • Tendency to develop clots due to predisposing factors that may be genetically determined

  3. Classification • Inherited • Acquired • Inherited + acquired

  4. Inherited Thrombophilia • Caused by defective gene • Activated protein C resistance (factor V Leiden)- least severe • Inhibitor deficiencies: protein S, proteinC, antithrombin (intermediate severity) • Prothrombin 20210A allele mutation hyperprothrombinaemia (v. severe) • Hyperhomocysteinaemia

  5. Inherited defects & thrombophilia

  6. Activated protein C resistance • Factor V Leiden • Gene mutation in chromosome 1 • Accounts for most but not all cases of APC resistance • Factor Va unresponsive to protein C • 15% of Causasians are carriers • Rare in Asians & Africans • heterozygotes 5-10x risk of clotting • homozygotes 50-100x risk

  7. Acquired thrombophilia • Antiphospholipid syndrome • lupus anticoagulant: anticoag in vitro, but pro-coag. in vivo • Suspect if : • a young person presents with MI, CVA, hepatic vein thrombosis (Budd- Chiari syndome) • Recurrent miscarriages • Incidental finding of prolonged APTT +platelets

  8. Drugs • Disease states: • Malignancy • connective tissue diseases • myeloproliferative disorders • pregnancy • surgery • trauma

  9. Mixed hereditary + acquired • Acquired conditions amplify the risk of clotting in those with underlying hereditary coagulatory defects • Examples: oral contraceptives, HRT, pregnancy, surgery

  10. When to suspect thrombophilia • +ve family history • occlusion at unusual sites e.g. brain, portal veins • recurrent thrombosis • unexpected VTE • unexpected occlusion of arterial tree e.g. young ppl with MI or CVA

  11. Arterial thrombosis • anticoagulation pathway anomalies rarely cause arterial events • Main differentials • Antiphospholipid syndrome • Hyperhomocysteinaemia • Dysfibroginaemia

  12. Evaluation • History • VTE or arterial occlusive disease in <50 • Recurrent VTEs • Family history- VTE in 1st degree relatives • Screen if >1 of the above is +ve

  13. Investigations • Screening of population is not justified because overall incidence of thrombosis is low • Screen people in whom an occlusive event has occurred and has unusual circumstances e.g. young age, recurrent episodes, family hx

  14. Acute Event • No need to investigate fully at this stage • Management the same regardless of cause • VTE • FBC, blood gas • D-dimer- good -ve predictive valuebut +ve test not specific • CXR • U/S • CTPA

  15. Investigations • FBC- platelets,  RBCs • APTT • good for picking up APC resistance • Patient’s plasma + Factor V deficient plasma: v. sensitive & specific for factor V Leiden • Thrombin time • Lupus anticoagulant, anticardiolipin & antiphospholipid antibodies

  16. Assays for Protein C/ protein S • Antigen level • Functional assay • Homocystein level • DNA analysis • factor V Leiden • Prothrombin 20210A

  17. Investigations • Results affected by: • acute thrombotic event • pregnancy • Disease states: liver, DIC, inflammation, surgery • Drugs: anticoagulants, OCPs

  18. Treatment- Acute Pulmonary Embolism • O2 • Inotrope support • Fluids • IV heparin- bolus followed by infusion, then oral warfarin after 24 hrs • Thrombolysis - consider in massive PE

  19. Treatment- Acute • DVT • below knee • TED stockings • Re- scan in 7-10 days • Anticoagulate if there is progression • above knee- anticoag x 3 months

  20. Treatment- Long term • +ve family hx but asymptomatic • Counselling • No action required • Anticoagulation (INR 2.0-3.0) • 1 episode of VTE in the presence of another triggering event - 3-6 months anticoagulation. Stop when triggering factor is gone • VTE without triggering factors- anticoagulant for 6 months, but indefinite if the episode was life-threatening

  21. Indefinite coagulation • > 2 spontaneous thrombotic events • Event AND > 1 hereditary defects • life-threatening thrombotic episode • ? Hereditary defect with 1st thrombotic episode- benefit unclear. But yes if patient is heterozygote for antithrombin deficiency ( risk of clotting compared to other herditary conditions). Maybe yes if there is protein C/S defect

  22. IVC filter • consider if patient still has recurrent VTEs despite adequate anticoagulation

  23. Prophylaxis • Pre-op LMWH • major op: give for 5-10 days • Aspirin not as effective as LMWH • Pregnancy -subcut. LMWH rather than warfarin

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