Thrombophilia/hypercoagulable states

Suspect in Pts with venous or arterial thrombosis at a young age or unusual locations, recurrent thrombi, miscarriages, and positive family history.

Inherited Hypercoagulable States

Hypercoagulable states: DIC, tumors (adenocarcinoma), pancreatitis, vasculitis (temporal arteritis, primary CNS vasculitis, SLE, PAN, Wegener's granulomatosis), OCP, smoking, DM, nephrotic syndrome, APA syndromes, surgery, trauma, childbirth, homocystinuria, dehydration, thrombocytosis, leukostasis, infection, sickle cell disease, PCV, leukemia, cyroglobulinemia. Deficiency of protein C, protein S, or ATIII.

Elevated PT and PTT: very high levels of warfarin, common pathway defect, some lupus anticoagulant.

Elevated PT: Warfarin, Vit K deficiency, liver disease, DIC, extrinsic pathway defect.

Coagulopathy Tests: CBC, Plt, PTT, PT/INR, fibrinogen, D-dimer, protein C and S (cannot be tested if pt on warfarin), antithrombin III (cannot be tested if pt on heparin), anticardiolopin Ab, lupus anticoagulant, ESR, RF, ANA, HBEP.

Elevated PTT: heparin, anticardiolopin Ab, lupus anticoagulant, intrinsic pathway defect, hemophilia, DIC.

ATIII def. Check levels. Use direct thrombin inhibitor followed by warfarin.

    • Acquired thrombophilias:

      • APA synd: Anticardiolipin ab, Lupus anticoag, d-dimer: Venous and arterial thrombosis.

      • PNH: RBC or WBC flow cytometry for CD55, CD59, CD24: Venous and arterial thrombosis.

      • Stasis: immobilization due to surgery, CHF. Venous thrombosis

      • Malignancy, OCPs, HRT, tamoxifen, pregnancy, nephrotic syndrome: Venous thrombosis

      • Myeloproliferative d/o, HIT, PCV, Walenstrom's macroglobulinemia, sickle cell, acute leukemia: Venous and arterial thrombosis

      • Vasculitis, trauma, FB, IBD: Venous and arterial thrombosis

Tx:

    • Asx with inherited d/o consider prophylactic anticoag, if addition of acquired risk factor seen in patient.

    • Thrombosis with inherited d/o: lifelong anticoag.

Antiphospholipid syndrome (APA):

    • Definition: 1 or more clinical and 1 or more laboratory criteria

      • Clinical: arterial or venous thrombosis in any tissue or organ and

      • complications of pregnancy:

        • 3 or more consecutive spontaneous abortions before 10 wks or 1 or more fetal loss after 10 wks or premature birth complicated by eclampsia, preeclampsia, or placental insufficiency, before 34 wks.

      • Lab: +ve mod-high titer of anticardiolipin IgG or IgM antibodies, or lupus anticoagulant abs, and beta2-glycoprotein-1 antibodies that react with negatively charged phospholipid on 2 or more occasions at least 12 wks apart.

    • Clinical manifestations: DVT, PE, CVA, recurrent fetal loss, VHD, thrombocytopenia, hemolytic anemia, livedo reticularis, and nephropathy.

      • Arterial vs. venous clots: Pt. who have had one or the other trend to continue to have that kind. Most common thrombosis is DVT, but most common arterial-side clot is stroke.

      • Catastrophic APS: widespread acute thrombotic microangiopathy with MOD and mortality.

    • Etiologies: idiopathic, secondary due to autoimmune synd (SLE), malignancy, infections, drug reactions.

    • Dx: antiphospholipid antibodies classified by method of detection.

      • ACL-ab: anticardiolipin antibody, a mitochondrial phospholipid. IgG is more specific than IgM.

      • Lupus anticoagulant (LA)-ab prolongs phospholipid-dependent coagulation reactions

        • ▲ PTT that does not correct with mixing study but does correct with excess phospholipids or platelets

        • PT is not affected because the reaction contains much more phospholipid

      • False positive VDRL: nontreponemal test for syphilis in which cardiolipin is part of antigen complex

    • Tx: lifelong warfarin after a thrombotic event; goal INR (2 - 3). Because these Abs can falsely raise PTT, heparinoids should be measured using anti-factor Xa levels. ASA prophylaxis for high risk asx Pts.