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25 Cards in this Set
- Front
- Back
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Important elements of patient hx when venous thromboembolism (VTE) is suspect?
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1. Previous thrombotic events? Objectively documented?
2. Family hx of thrombotic events? 3. Age at presentation of first thrombotic event? 4. Presence or absence of known genetic or acquired risk factors? 5. Unusual location (hepatic/portal/mesenteric vein/cerebral sinus) or frequency of thrombosis? |
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Possible PE findings with VTE?
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DVT:
- localized pain, tenderness, swelling - discoloration of affected limp PE: - asymptomatic - may exhibit DOE, pleuritic chest pain, rarely hemoptysis - CXR is usually normal - Massive PE -- syncope, hypotension, marked hypoxemia, right ventricular dysfxn |
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How do we test for DVT?
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1. duplex doppler ultrasonography
-- test of choice for screening -- not sensitive for thrombi below the knee 2. contrast venography -- sensitive to both calf and thigh DVT -- useful in recurrent DVT w/ persistent abnormalities of the deep venous system |
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How do we test for PE?
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1. spiral CT
-- relative sensitivity compared to V/Q may depend on the size of vessel involved -- imporved specificity over V/Q and thus useful in pts w/ abnormal CXR prior to pursuing pulmonary angiography 2. Ventilation-perfusion scan (V/Q scan) -- normal scan essentially rules out PE -- mismatch defects (ventilation w/o perfusion) suggest PE -- pts w/ matched defects and abnormal CSR are difficult to interpret and frequently read as intermediate probability or indeterminate 3. Pulmonary angiography -- GOLD standard -- avoid in pts w/ evidence of pulm HTN |
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VTE Lab assessment?
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1. D-dimer
2. Eval for hypercoag state |
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Explain D-dimer values and VTEs.
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sensitive D-Dimer assays have a very high predictive value of a negative test when used to eval suspected VTE
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What do we look for when evaluating for hypercoag state?
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1. activated protein C resistance (clotting assay)
2. factor V leiden mutation (PCR) 3. prothrombin G20210A (PCR) 4. Antithrombin fxnal assay 5. protein C fxnal assay 6. protein S fxnal assay 7. lupus anticoag -- screening w/ PTT, dilute Russel viper venom time (dRVVT) -- 1:1 mix to demonstrate inhibitor pattern -- confirmatory test in presence of excess lipid (neutralized inhibitor) 8. serologic tests for antiphospholipid antibodies (i.e. cardiolipin) 9. plasma homocysteine |
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Caveats in testing for hypercoag states.
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Due to presence of an inflamm state and consumption by the thrombus, measurement of protein fxn and Ag levels is NOT reliable during an acute episode of thrombus
-- testing not recommended during acute event Antithrombic therapy can affect these measurements In general, testing for thrombophilia should be done 4-6wks after the pt has completed their course of oral anticoags |
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Anticoagulant agents?
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1. unfractionated heparin (UH)
2. Low molecular weight heparin (LMWH) 3. Warfarin 4. Hirudin (Refludan) 5. Argatroban 6. Fondaparinux 7. other novel agents |
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Unfractionated heparin
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Primary drug for treatment of acute thrombosis, both arterial and venous
Chemically: heterogenous mix of highy sulfated CHO polymers which BIND ANTITHROMBIN WITH HIGH AFFINITY Action: accelerates inhibition of coagulaton proteases-- factor Xa and thrombin-- by antithrombin -- May have antithrombin independent effects Admin IV and effective w/in minutes Half-life: Approx 1 1/2 hours Target: prolong PTT to 1.5-2.0 times control values Major complications: bleeding, HIT, and accelerated osteoporosis |
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Low molecular weight heparin
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Heparin prep depleted of high molec wt polymers
-- predom anti-factor Xa activity Dosed by weight (w/o monitoring coag times) and causes minimal or no PTT prolongation Antithrombotic effects equivalent to UH for prophylaxis/trtmt of DVT/PE More predictable pharmacodynamics making wt-based dosing w/o monitoring Lower incidence of HIT, possibly less incidenc of osteoporosis |
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Warfarin
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PRIMARY ORAL DRUG for anticoag
Mech: interferes w/ VitK dependent γ-carboxylation of coag proteases -- gradual decline of factors VII, IX, X, and prothrombin) in order of their respective half lives PT prolings w/in 2 days but pt not considered therapeutic until several more days (all factors reach steady state) Adjust to INR of 2.0-3.0 Complications: bleeding, warfarin-induced skin necrosis (rare), drug interactions INR needs to be carefully monitored following any med changes |
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Hirudan
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Recombinant version of leach anticoag protein
Low molecular weight DIRECT thrombin inhibitor Admin IV and monitored by PTT w/ target of 1.5 to 2.5 FDA approved drug for TREATMENT OF HIT Complications: increased risk of bleeding relative to haparin Cleared: kidneys |
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Argatroban
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Synthetic compound containing arginine
Binds serine active site in thrombin, competitively inhibiting its fxn FDA approved drug for TREATMENT of HIT Complications: increased risk of bleeding relative to heparin Cleared: liver |
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Foldaparinux
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Pentasaccharide that binds to ATIII caysing inhibition of factor Xa
Given s.q. |
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List antiplatelet agents.
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1. ASA
2. Clopidogrel 3. GpIIb/IIIa inhibitors (ReoPro) |
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ASA
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irreversibly inhibits platelet cyclooxygenase, blocking production of thromboxane A2, an important mediator of platelet activation
Cheap, effective tx for number of clinical syndromes: - asymptomatic males and females 50yo - silent MI - stable/unstable angina - acute MI - aortocoronary bypass surgery - acute occlusion following coronary angioplasty - peripheral vascular disease - transient cerebral ischemia - placental insufficiency - atrial fib - prosthetic heart valves |
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Clopidogrel
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thienopyridine derivative
Inhib ADP-dep platelet aggregation Requires hepatic metabolism; relatively long half-life **More effective than ASA in preventing ischemic stroke, MI or vascular death in pts at high risk Can be used in combo w/ ASA |
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GpIIb/IIIa inhibitors (ReoPro)
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Fab fragment of monoclonal Ab directed against the fibrin(ogen) receptor on platelets (GpIIb/IIIa)
Major risks: hemorrhage, thrombocytopenia Reduced risk of death, MI or urgent CABG following coronay angioplasty |
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Fibrinolytic agents?
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1. TPA
2. Urokinase 3. Streptokinase |
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MOA of fibrinolytic agents?
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Activate plasminogen to PLASMIN which degrades the fibrin thrombus
Systemic fibrinolytic state often seen w/ decreased fibrinogen, factor V, and factor VIII levels Broader use of fibrinolytics is primarily limited by ~0.5-1% incidence of cerebral hemorrhage noted in large MI trials |
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Indications for fibrinolysis?
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1. most commonly used in setting of acute MI
2. acute periph arterial obstruction (limb salvage) 3. recent use in ischemic stroke; tradeoff is relatively high since incidence of intracerebral bleed is 6-22% 4. massive PE with hemodynamic compromise |
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Standard treatment of VTE?
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1. Uncomplicated DVT/PE
- at least 5 days of heparin (UH or LMWH) overlapping w/ warfarin to achieve target INR 2-3 Duration: 3-6 mos for first event 2. "Idiopathic DVT" occurring in absence of precip clinical factors -- duration of tx should be longer Vena caval filters -- used to prevent PE in pts w/ absolute contraindications to anticoag, or for recurrent events on therapeutic anticoag |
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Anticoag for mechanical and prosthetic heart valves?
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Mechanical valves
-- lifelong risk -- target INR 2.5-3.5 Tissue (porcine) valves -- increased risk 1st 3 months -- target INR 2-3 |
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Anticoag for atrial fib?
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Chronic Afib is assoc w/ signif increased risk of thromboembolic stroke
-- warfarin superior to ASA for prevention -- may do equally well on ASA if no valvular heart disease or left ventric dysfxn |
