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Unfractionated heparin is the cornerstone for the treatment of acute venous thromboembolism. Although heparin is highly effective, it is always associated with some risk of hemorrhage. Published reports also have described failures of heparin therapy caused by subtherapeutic doses. When heparin is given by continuous IV infusion and the dose is regulated with an appropriate clotting time test, the incidence of serious hemorrhage is reduced and therapeutic efficacy is assured.
Few other medications with the toxicity of heparin that have been available for clinical use for so long have such a lack of uniformity in dosing and monitoring recommendations. Heparin has traditionally been dosed with an IV bolus dose of 5,000 to 10,000 units of heparin, followed by an infusion of 1,000 units per hour. Others have advocated that a more rational method of initiating therapy is to begin with a loading dose of 50-100 units/kg of heparin followed by a constant infusion of 15-25 units/kg/hr. Chenella, et al have described a method for determining initial heparin infusion rates based on the patient's individually determined volume of distribution (blood volume).
Several studies have provided evidence that, compared to standard care, weight-based dosing of heparin resulted in a shorter time to achieve therapeutic aPTT and fewer bleeding complications. Long-term follow-up has demonstrated a lower rate of recurrent thromboembolism for up to 3 months, giving added importance to accurate dosing in the early phases of treatment.
The optimal duration of heparin therapy for DVT is still uncertain. Traditionally, heparin is administered for 10 days with warfarin initiated on day 5. Studies in patients with acute DVT have established the safety and efficacy of a 4-5 day course of heparin therapy with warfarin started on day 1.
Unstable angina is a critical phase of coronary heart disease with high risk of myocardial infarction and death. One of the postulated mechanisms of UA is a cyclic formation, dissolution and reformation of clots. Therefore, full-dose heparin therapy is a primary intervention in unstable angina.
Studies have shown that steady-state heparin dose requirements are significantly less in patients with CAD compared with patients DVT, suggesting that different dosing nomograms are needed for each condition.
Acute myocardial infarction
The role of heparin in conjunction with thrombolytic therapy for the management of patients with acute MI continues to be controversial. Many issues, including the possible benefits and risks of this therapy, are unresolved. The rationale for administration of heparin following thrombolytic therapy is to maintain patency, this appears to be most important for the shorter-acting TPA. Based on the current evidence, it is reasonable to administer Intravenous heparin with either streptokinase or TPA.
Transient ischemic attack
Although platelet aggregation is thought to be the primary cause of TIA, there is some evidence that anticoagulants may reduce the rate of TIA's in patients receiving aspirin who remain symptomatic. Less intensive heparin therapy is recommended in treatment of TIA.
Cerebral ischemic infarction
The efficacy of heparin in the acute phase of ischemic cerebral vascular accident is unknown, given the studies performed so far. If heparin is to be used, it should only be initiated after a CAT scan has made certain that a cerebral hemorrhage has not occurred. As with TIA, less intensive heparin therapy is recommended in treatment of stroke.