Pocket Medicine

HEMATOLOGY-ONCOLOGY

HYPERCOAGULABLE STATES

Suspect in Pts with venous or arterial thrombosis at young age or unusual locationsrecurrent thromboses or pregnancy loss or  FHx

Diagnostic evaluation (not routinely required for initial VTE)

•  APC resistance screen; prothrombin PCR test; functional assays for proteins C and S, ATIII; homocysteine level; factor VIII levels; anticardiolipin and lupus anticoagulant Ab.  Also consider nephrotic syndrome, PNH (esp. if mesenteric thrombus).

•  Consider JAK2 mutation testing if suspect MPN or splanchnic thrombosis.

•  Proteins C & S and ATIII levels are affected by acute thrombosis and anticoagulation ∴ levels best assessed ≥2 wk after completing anticoagulation course

•  Age-appropriate malignancy screening ( in 7–10% in “idiopathic” DVT; Annals 2008;149:323)

Treatment

•  Asx w/ inherited risk factor: consider prophylactic anticoag. if develops acquired risk factor

•  Thrombosis w/ inherited risk factor: see “Venous Thromboembolism”

Antiphospholipid syndrome (APS) ( J Thromb Haemost 2006;4:295; NEJM 2013;368:1033)

•  Definition: dx requires ≥1 clinical & ≥1 laboratory criteria

Clinical: thrombosis (any) or complication of pregnancy (≥3 spont. abortions before 10 wk or ≥1 fetal loss after 10 wk or premature birth before 34 wk)

Laboratory:  moderate–high titer anticardiolipin (ACL),  lupus anticoagulant (LA) or β2-glycoprotein-I (β2-GP-I) Ab on ≥2 occasions at least 12 wk apart

•  Clinical: DVT/PE/CVArecurrent fetal lossthrombocytopenia, hemolytic anemia, livedo reticularis; “catastrophic APS” = ≥3 organ systems in <1 wk w/  APLA & tissue microthrombi (Lupus2003;12:530) → 44% mortality (Arth Rheum 2006;54:2568)

•  Antiphospholipid antibodies (APLA) ✓ if: SLE, age <40 y & arterial thromb, recurrent venous thromb, spontaneous abortion

ACL: Ab against cardiolipin, a mitochondrial phospholipid; IgG more specific than IgM

LA: Ab that prolongs phospholipid-dependent coagulation reactions; ∴ ↑ PTT that does not correct with mixing study but does correct with excess phospholipids or platelets; PT not affected b/c the reaction contains much more phospholipid

β2-GP-I:  Ab against β2-glycoprotein-I, IgG or IgM

False  VDRL: nontreponemal test for syphilis in which cardiolipin is part of Ag complex

Clinical significance of different Abs in pathogenesis uncertain

Risk of thromboembolic phenomena may increase with titer of APLs

•  Etiologies: primary (idiopathic) or secondary due to autoimmune syndromes (eg, SLE), malignancyinfections, drug reactions

•  Treatment: UFH/LMWH → warfarin after thromboembolic event (lifelong for most Pts)

Intensity of anticoagulation controversial (Arthritis Rheum 2007;57:1487)

Initial venous thrombosis: INR 2–3 (NEJM 2003;349:1133;   J Thromb Haemost 2005;3:848)

Initial arterial thrombosis: typically INR 2–3 + ASA 81, although some treat to INR 3–4

Recurrent thrombosis on warfarin: INR 3–4 vs. LMWH (Arth Rheum 2007;57:1487)

Consider ASA prophylaxis for high-risk asx Pt (eg, SLE)