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Pharmacotherapy of Venous Thromboembolism Prevention & Treatment

Marie Meyer, PharmD Candidate 2007

|Epidemiology |Incidence: 50,000-200,000 pulmonary embolism (PE) fatalities yearly |

| |250,000-600,000 symptomatic VTE cases yearly |

| |Causes: |

| |Abnormal blood flow: atrial fibrillation, left ventricular dysfunction, hemostasis, vessel obstruction, hyperviscosity, sickle cell anemia |

| | |

| |Abnormal surfaces in contact with blood: vessel injury, atherosclerosis, heart valve disease, heart valve replacement, indwelling catheters|

| | |

| |Abnormal coagulation proteins: protein C deficiency, protein S deficiency, antithrombin deficiency, activated protein C resistance, |

| |prothrombin mutation, elevated factor VIII and X, antiphospholipid antibodies, hyperhomocysteinemia, tumor cell procoagulants, high dose |

| |estrogen therapy/pregnancy |

|Disease State |Venous Thromboembolism (VTE) = thrombus (blood clot) formation in veins; clot may embolize (break off and travel through the circulation, |

|Definition |usually through the heart and into the lungs) |

| | |

| |Deep Venous Thrombosis (DVT) = blood clot in a deep vein (vein that accompanies an artery) |

| | |

| |Pulmonary Embolism (PE) = blockage of an artery in the lung, usually by a blood clot |

| |(rare: emboli may also be formed from fat cells, tumor cells, air bubbles, parasites, amniotic fluid) |

| | |

| |Thromboembolic stroke |

| |Ischemic stroke (85%) [symptoms last >24 hours (TIA if 40 |

| |pregnancy & postpartum, contraceptive or hormone replacement estrogen therapy |

| |selective estrogen receptor modulators |

| |malignancy, cancer therapy |

| |acute illness |

| |heart failure, respiratory failure |

| |obesity, smoking |

| |inflammatory bowel disease, nephrotic syndrome, myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, varicose veins, central|

| |venous catheterization, thrombophilia |

| | |

| |Thromboembolic stroke risk factors |

| |Valvular heart disease, prosthetic valve replacement |

| |Atrial fibrillation |

| |Dilated left atrium or left ventricle |

| |Hypertension |

| |Diabetes Mellitus |

| |Left ventricular dysfunction |

| |Anterior myocardial infarction |

| |History of previous stroke, TIA, VTE |

| | |

| | |

| | |

| | |

|Diagnosis |VTE laboratory tests |

| |D-dimer test – negative rules out VTE, positive requires confirmation by appropriate diagnostic test |

| |Hypercoaguable assessment |

| |protein C deficiency, protein S deficiency, anti-thrombin III deficiency, activated protein C resistance, antiphosphorlipid antibodies, |

| |anticardiolipin antibodies, lupus anticoagulant |

| | |

| |DVT diagnostic tests |

| |Venography/phlebography |

| |Ultrasound, Doppler, Duplex Doppler |

| |Impedance plethysmography |

| |I125 fibrinogen leg scan |

| | |

| |PE diagnostic tests |

| |Pulmonary angiography |

| |Lung scan – V/Q scan, ventilation/perfusion scan |

| | |

| |TIA/stroke diagnostic test |

| |Echocardiography |

|Desired Therapeutic |Prophylaxis |

|Outcomes* |Prevent VTE in hospitalized or surgical patients |

| | |

| |Treatment |

| |Prevent thrombus extension |

| |Prevent early and late VTE recurrences |

| |Prevent VTE mortality |

| | |

| |*The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126 |

|Treatment Options** | |

| |Non-phamacologic |

|(Non-drug and Drug | |

|Therapy – include all |Compression – elastic compression stockings, intermittent pneumatic compression |

|therapeutic |Thrombectomy, pulmonary embolectomy |

|classes/agents |Vena-cava filter |

|available and |Catheter extraction or fragmentation |

|preferences per |Ambulation |

|treatment guidelines) | |

| | |

|**See Treatment Options|Pharmacologic |

|Table | |

| |Heparins |

| |Unfractionated heparin (UFH) |

| |Low-molecular weigh heparins (LMWH) |

| |enoxaparin (Lovenox) |

| |dalteparin (Fragmin) |

| |tinzaparin (Innohep) |

| | |

| |Vitamin K antagonists (VKAs) |

| |Warfarin (Coumadin) |

| | |

| |Platelet inhibitors |

| |Aspirin |

| |Ticlopidine (Ticlid) |

| |Clopidogrel (Plavix) |

| |Note: Glycoprotein IIb/IIIa receptor antagonists are indicated for percutaneous coronary intervention, coronary stents, unstable angina, |

| |acute coronary syndrome (beyond the scope of this topic) |

| | |

| | |

| |Direct Thrombin Inhibitors |

| |Lepirudin (Refludan) |

| |Bivalirudin (Angiomax) |

| |argatroban |

| | |

| |Selective Anti-Xa Inhibitor |

| |Fondaparinux (Atrixa) |

| | |

| |Thrombolytics |

| |There is no evidence that supports the use of thrombolytic agents for the initial treatment of |

| |DVT in the large majority of patients. Furthermore, in patients with DVT, mortality from PE is very uncommon (approximately 1%) once |

| |anticoagulant therapy has been initiated*. |

| | |

| |For most patients with PE, we recommend clinicians not use systemic thrombolytic therapy* |

| | |

| |*The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126 |

| | |

|Monitoring |Platelets, hemoglobin, hematocrit, signs of bleeding, |

| |Activated partial thromboplastin time (aPTT) |

|(Efficacy and Toxicity |Prothrombin time (PT) |

|Parameters) |International normalized ratio (INR) = calculation |

| |INR = patient prothrombin time/mean normal prothrombin time |

| |ISI = international sensitivity index |

| |INR should be increased by 2-31/2 times depending upon indication. |

| | |

| |See treatment options table for complete monitoring per drug/class |

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