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Heparin Resistance Research Paper

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Heparin resistance (HR) is a common event in cardiac operations and it refers to the need for administration of unusually high doses of heparin to achieve therapeutic levels of activated clotting time (ACT > 400 seconds). CHEST guidelines defined HR as the use of >35,000 units of heparin per 24 hours (excluding initial bolus doses). It has been observed in many disease states, such as cancer. HR can worsen the progression of acute coronary syndrome, venous thromboembolism (VTE), and other conditions requiring anticoagulation therapy. In a series of five hundred consecutive patients undergoing coronary revascularization, HR was observed in 104 patients (21%). In another series, two hundred consecutive patients undergoing coronary revascularization…show more content…
This was based on the findings of a randomized controlled trial that randomly assigned 131 patients with HR to have their heparin therapy monitored by either anti-factor Xa or aPTT. Although the risks of recurrent VTE and bleeding were similar in both arms, heparin doses were significantly lower in patients being monitored by anti-factor Xa. Since heparin potentiates the action of AT III cofactor, a deficiency of this enzyme can lead to inadequate heparinization. As clinicians, we should be mindful of the effect of heparin therapy on AT III and interpret its level carefully. Therefore, AT III levels should be assessed preoperatively. HR can also occur as a result of heparin clearance, increased level of heparin-binding proteins, and elevated levels of fibrinogen and factor VIII. In known cases of AT III deficiency, administration of AT III concentrate can help achieving the target aPTT levels and reduce heparin use. 1000 international units of AT III concentrate is usually given if ACT is less than 400 seconds despite administration of total dose of 750 units/kg of heparin. Due to AT III high cost, administration of 2-4 units of fresh frozen plasma is another approach in these cases. However, the latter has its own drawback of increased risks associated with blood products…show more content…
This was a 50 years old Caucasian man with VTE and lung cancer who required more than 66,000 units of UFH daily. Patient was transitioned to OLHDE and anti-Xa was measured on day 4 of therapy (after 4 hours of dose administration). It was within therapeutic range at 0.87 units/mL (local reference range is 0.5 – 1.0 units/mL). The authors reported that the dose was chosen strictly because it made academic sense; it was not based on any clinical trials. Patient was maintained on the same dose and has been transferred to medical floor with no thrombotic or bleeding
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