title: Preoperative low molecular weight heparin reduces heparin responsiveness during cardiac surgery.
abstract: OBJECTIVE
  Cardiac surgery with cardiopulmonary bypass requires systemic anticoagulation, defined by an activated clotting time (ACT) of 400-480 sec. Patients with altered heparin responsiveness require disproportionately higher doses of heparin to achieve this target ACT. A common risk factor for heparin resistance is preoperative heparin therapy. Recently, therapy with low molecular weight heparin (LMWH) has become an acceptable substitute for prolonged heparin therapy. The current study examines the effect of preoperative LMWH therapy on subsequent heparin responsiveness during cardiac surgery.
  
  
  METHODS
  Records of patients undergoing cardiac surgery with cardiopulmonary bypass over a period of four months were reviewed. We identified patients who, during the week preceding surgery, had received prolonged (>24 hr) therapy with either sc LMWH (LMWH group) or continuous iv unfractionated heparin (Heparin group). A Control group consisted of patients who received neither heparin nor LMWH preoperatively. The heparin sensitivity index (calculated as the first change in ACT from baseline divided by the first intraoperative heparin dose, normalized to body weight), was compared among groups using ANOVA.
  
  
  RESULTS
  One hundred and thirty-nine patients were included in the analysis. The heparin sensitivity index was 33-45% higher in the Control group (1.6+/-0.7 sec.IU-1.kg-1; P<0.0001) compared to the LMWH (1.2+/-0.4 sec.IU-1.kg-1) and Heparin (1.1+/-0.5 sec.IU-1.kg-1) groups. In a multivariable model, the use of preoperative LMWH remained a significant predictor of reduced intraoperative heparin responsiveness (P=0.002).
  
  
  CONCLUSIONS
  Prolonged preoperative LMWH therapy, similar to the known effect of prolonged unfractionated heparin infusion, reduces subsequent intraoperative response to heparin.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710, USA. baryo001@mc.duke.edu
authors.forename: Shahar
authors.initials: S
authors.lastname: Bar-Yosef
authors.forename: Heidi B
authors.initials: HB
authors.lastname: Cozart
authors.forename: Barbara
authors.initials: B
authors.lastname: Phillips-Bute
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Grocott
mesh_terms: D000368:Aged; D000768:Anesthesia, General; D000925:Anticoagulants / Q000009:adverse effects* / Q000494:pharmacology; D020152:Antithrombin III Deficiency / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016022:Case-Control Studies; D004361:Drug Tolerance; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011300:Preoperative Care; D012044:Regression Analysis; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D014914:Whole Blood Coagulation Time / Q000379:methods
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin