Comparative study between traditional increasing heparin dose versus the use of fresh frozen plasma in management of heparin resistance

Abstract

Unfractionated heparin is indicated for the treatment or prevention of venous or arterial thromboembolism. Heparin therapy is effective in reducing morbidity and mortality associated with established thromboemboli (e.g., deep venous thrombosis, pulmonary embolism) and in reducing the risk of thrombus formation as in myocardial infarction, unstable angina or coronary angioplasty. Also heparin is used in interventional cardiology, cardiac surgery, and vascular surgery. Heparin can be used in combination with anti¬- thrombotic therapy in patients with unstable angina or non–ST-segment elevation/non–Q-wave myocardial infarction receiving platelet glycoprotein-receptor inhibitors. Heparin exerts its anticoagulant effect by activating antithrombin. The heparin-AT complex inactivates a number of coagulation enzymes, including thrombin factor (IIa) and factors Xa, IXa, XIa, and XIIa. Of these, thrombin and factor Xa are the most responsive to inhibition.

Because UFH has a narrow therapeutic window and may cause bleeding complications, aggressive monitoring is necessary to ensure efficacy and patient safety. Several tests are available to monitor UFH therapy including whole blood clotting time, aPTT, activated clotting time, anti–factor Xa activity, and plasma heparin concentrations. Heparin resistance is defined as the need for more than 35,000 units per day to prolong the aPTT into the therapeutic range. In contrast, during cardiac bypass procedure the definition of heparin resistance is based on activated clotting time with an ACT less than 400 seconds after receiving greater than 600 U/kg of heparin. Antithrombin (AT) deficiency is argued to be a primary cause of heparin resistance. In addition to AT deficiency, increased heparin clearance, elevations in heparin-binding proteins, and elevations in factor VIII and/or fibrinogen. Aprotinin and nitroglycerin may cause drug-induced heparin resistance. Treatment of heparin resistance includes administering fresh frozen plasma as a source of AT, or administering increasingly higher doses of heparin to bind all available AT. Commercially prepared purified lyophilized human AT concentrates are also available. This study compared the effect of traditional increasing heparin dose versus fresh frozen plasma administration in the management of heparin resistance on one hundred adult patients of both sexes. All Patients were assigned randomly by using computerized program to one of the two equal groups. Group A: fifty (50) patients received fresh frozen plasma for management of heparin resistance.by the following regimen: 2 units of fresh frozen plasma were given and were repeated every 12 hours with fixed heparin dose till therapeutic level was reached. Group B: fifty (50) patients received traditional increased dose of heparin for the management of heparin resistance by following the Weight based nomogram for continuous intra-vascular UFH infusion. All patients were assessed by aPTT and anti-Xa heparin assays together with platelets count for early detection of heparin induced thrombocytopenia.