title: Is there evidence that fresh frozen plasma is superior to antithrombin administration to treat heparin resistance in cardiac surgery?
abstract: A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, 'in [patients with heparin resistance] is [treatment with FFP] superior [to antithrombin administration] in [achieving adequate anticoagulation to facilitate safe cardiopulmonary bypass]?' More than 29 papers were found using the reported search, of which six represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Antithrombin (AT) binds to heparin and increases the rate at which it binds to thrombin. The levels of antithrombin in the blood are an important aspect of the heparin dose-response curve. When the activated clotting time (ACT) fails to reach a target >480, this is commonly defined as heparin resistance (HR). Heparin resistance is usually treated with a combination of supplementary heparin, fresh frozen plasma (FFP) or antithrombin III concentrate. There is a paucity of evidence on the treatment of heparin resistance with FFP, with only five studies identified, including one retrospective study, one in vitro trial and three case reports. AT has been studied more extensively with multiple studies, including a crossover trial comparing AT to supplemental heparin and a multicentre, randomized, double blind, placebo-controlled trial. Antithrombin (AT) concentrate is a safe and efficient treatment for heparin resistance to elevate the activated clotting time (ACT). It avoids the risk of transfusion-related acute lung injury (TRALI), volume overload, intraoperative time delay and viral or vCJD transmission. Antithrombin concentrates are more expensive than fresh frozen plasma and may put patients at risk of heparin rebound in the early postoperative period. Patients treated with AT have a lower risk of further FFP transfusions during their stay in hospital. We conclude that the treatment of HR with FFP may not restore the ACT to therapeutic levels with adequate heparinization, but AT is efficient with benefits including lower volume administration, less risk of TRALI and lower risk of transfusion-related infections.
authors.affiliation: Department of Cardiothoracic Surgery, Aberdeen Royal Infirmary, Aberdeen, UK.
authors.forename: Gwyn W
authors.initials: GW
authors.lastname: Beattie
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jeffrey
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D019985:Benchmarking; D001777:Blood Coagulation / Q000187:drug effects; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004351:Drug Resistance; D019317:Evidence-Based Medicine; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006493:Heparin
keywords: Antithrombin; Cardiopulmonary bypass; Heparin resistance; Plasma; Review