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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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