1 / 34

Hypercoagulable States

Hypercoagulable States. Hypercoagulable States. Acquired versus inherited “Provoked” vs idiopathic VTE Who should be tested for inherited thrombophilia ? What tests should be done & when? Anticoagulation recommendations Should family members be tested?. Virchow’s triad.

tavi
Download Presentation

Hypercoagulable States

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Hypercoagulable States

  2. Hypercoagulable States • Acquired versus inherited • “Provoked” vs idiopathic VTE • Who should be tested for inherited thrombophilia? • What tests should be done & when? • Anticoagulation recommendations • Should family members be tested?

  3. Virchow’s triad

  4. Was VTE “provoked”? • Medical and surgical history • Medications • Travel – air & ground • Review of systems • Cancer screening history

  5. Was VTE “provoked”? • Physical exam – including breast exam, rectal exam, pelvic exam for females, prostate exam for males • Age-appropriate cancer screening – MMG, Pap smear, colonoscopy, PSA • Do not recommend CT scans, etc. • Chest x-ray is reasonable

  6. Was VTE “provoked”? • CBC with diff • CMP • Urinalysis • Fecal occult blood test

  7. Inherited thrombophilia • Factor V Leiden (2.2) • Prothrombin gene mutation (2.8) • Protein C deficiency (7.3) • Protein S deficiency (8.5) • Antithrombin III deficiency (8.1) • Acquired – antiphospholipid antibody syndrome (APS)

  8. Who to test • <45 years old with unprovoked venous or arterial thromboembolic disease • >2 idiopathic thrombotic episodes • Thrombosis in unusual site • VTE & strong family history of VTE • History of recurrent fetal loss • ? VTE in reproductive age female

  9. Unusual sites • Cerebral veins • IVC, renal veins • Mesenteric veins • Portal and hepatic veins

  10. Recurrent fetal loss • Unexplained death at >10 weeks gestation–morphologically normal • Three or more 1st-trimester pregnancy losses without an intercurrent term pregnancy

  11. Who to test • What about a strong family history without personal history of VTE? • Test affected family member first • If history is very suggestive of inherited thrombophilia and there is no affected family member alive to be tested – needs appropriate counseling

  12. Hypercoagulable Work-up • “Hypercoag panel” -Protein C, protein S, AT III (functional) -Lupus anticoagulant -APC resistance • Factor V Leiden (if APC resistance low) • Prothrombin gene mutation • Anticardiolipin antibodies

  13. Timing of tests • Factor V Leiden and prothrombin mutation can be checked at any time • Wait at least 4-6 weeks after acute event to check lupus anticoagulant and cardiolipin antibodies (or later) • Most efficient to check all other tests >2 weeks after course of anticoagulation is completed

  14. Timing of Tests • In setting of acute VTE, proteins C & S and AT III may be decreased • Cardiolipin antibodies may be present as an acute phase reactant • Heparin interferes with AT III activity and lupus anticoagulant assays • Coumadin lowers proteins C & S

  15. Timing of Tests • In acute phase, if protein C or S is normal, that test does not need to be repeated • Some evidence that coumadin may increase AT III levels – if AT III is at low end of normal range, then test needs to be repeated off coumadin • Never need to repeat FVL or PTM test

  16. Antiphospholipid Antibody Syndrome (APS) • Clinical criteria: One or more episodes of venous, arterial, or small vessel thrombosis and/or morbidity with pregnancy • Laboratory criteria: Presence of anti-phospholipid antibodies on 2 or more occasions at least 12 weeks apart and <5y prior to clinical manifestations

  17. APS Clinical Criteria • Imaging or histologic evidence of thrombosis in any tissue or organ • Fetal death at >10 wks gestation • Premature birth before 34 weeks because of eclampsia, preeclampsia or placental insufficiency • >3 pregnancy losses <10 weeks

  18. APS Laboratory Criteria • Positive lupus anticoagulant • Moderate or high titer IgG and/or IgManticardiolipin antibodies • IgG or Ig M antibodies to beta2-glycoprotein-1 • On two or more occasions at least 12 weeks apart

  19. Antiphospholipid Antibody Syndrome • VTE • Stroke, white matter lesions • MI, nonbacterial endocarditis • Renal failure • Thrombocytopenia, TTP/HUS

  20. Livedoreticularis

  21. Catastrophic APS • Involvement of 3 or more organs, systems, or tissues • Develop simultaneously or in <1 week • Histopathologic evidence of small vessel occlusion • Presence of antiphospholipid antibodies Asherson et al., Lupus, 2003, 12:530

  22. Catastrophic APS • Treatment of underlying illness • Heparin acutely then warfarin • High dose steroids • Plasma exchange +/- IVIG if there is evidence of TTP/HUS • For survivors, lifelong warfarin

  23. Anticoagulation • Low molecular weight heparin acutely until INR therapeutic for 2 days • Warfarin for 3-6 months • INR 2.0-3.0 • For idiopathic DVT or inherited thrombophilia can discuss prolonged therapy – delays risk of recurrence

  24. What is this? Why does it happen?

  25. Warfarin skin necrosis • Protein C deficiency • Vitamin K dependent protein with relatively short half-life • Start warfarin after full heparinization documented by PTT or anti-Xa assay • Start at a low dose (2 mg a day) then gradually increase

  26. Warfarin skin necrosis • Stop warfarin • Give vitamin K • Heparinize • Consider protein C administration (FFP, protein C concentrate) • Can retreat with warfarin in setting of protein C administration

  27. AT III deficiency • Sometimes show resistance to heparin • May require larger doses • Consider antithrombin concentrate -Unusually severe thrombosis -Recurrent thrombosis in setting of adequate anticoagulation -Inability to adequately anticoagulate

  28. Discussion of lifelong anticoagulation • Recurrent idiopathic VTE • Idiopathic life-threatening VTE • Antiphospholipid antibody syndrome (with persistently elevated antibodies) • Antithrombin III deficiency • Homozygous or compound heterozygous defects

  29. Inherited thrombophilia & surgical prophylaxis • Consider as “high risk” group • Exception may be Factor V Leiden – prophylaxis based on risk of surgery • AT III deficiency – could consider antithrombin concentrate (retrospective & case reports only)

  30. Inherited thrombophilia and pregnancy • Anticoagulate during pregnancy and 6 weeks post-partum • AT III deficiency, homozygous FVL or PTM, compound heterozygotes • Personal history of VTE or strong family history of VTE use therapeutic dose, otherwise prophylactic dose

  31. Inherited thrombophilia and pregnancy • Heterozygous FVL or PTM, protein C or S deficiency • Prophylaxis if personal history of VTE • Consider if 1st degree relative with VTE at age <50 • If no prior history of VTE then only postpartum prophylaxis if C-section

  32. Should family members be tested? • Need to be counseled on how result will be used • Females of reproductive age • Protein C deficiency • If there is more than one inherited thrombophilia in the family • Usually we do

  33. When to refer to Hematology • Inherited thrombophilia with VTE • Recurrent idiopathic VTE without inherited thrombophilia • Contemplating lifelong anticoagulation • Patient request

  34. Questions?

More Related