title: Hemostatic activation and inflammatory response during cardiopulmonary bypass: impact of heparin management.
abstract: BACKGROUND
  Cardiac surgery involving cardiopulmonary bypass (CPB) leads to fulminant activation of the hemostatic-inflammatory system. The authors hypothesized that heparin concentration-based anticoagulation management compared with activated clotting time-based heparin management during CPB leads to more effective attenuation of hemostatic activation and inflammatory response. In a randomized prospective study, the authors compared the influence of anticoagulation with a heparin concentration-based system (Hepcon HMS; Medtronic, Minneapolis, MN) to that of activated clotting time-based management on the activation of the hemostatic-inflammatory system during CPB.
  
  
  METHODS
  Two hundred elective patients (100 in each group) undergoing standard cardiac surgery in normothermia were enrolled. No antifibrinolytic agents or aprotinin and no heparin-coated CPB systems were used. Samples were collected after administration of the heparin bolus before initiation of CPB and after conclusion of CPB before protamine infusion.
  
  
  RESULTS
  There were no differences in the pre-CPB values between both groups. After CPB there were significantly higher concentrations ( < 0.05) for heparin and a significant reduction in thrombin generation (25.2 +/- 21.0 SD vs. 34.6 +/- 25.1), d-dimers (1.94 +/- 1.74 SD vs. 2.58 +/- 2.1 SD), and neutrophil elastase (715.5 +/- 412 SD vs. 856.8 +/- 428 SD), and a trend toward lower beta-thromboglobulin, C5b-9, and soluble P-selectin in the Hepcon HMS group. There were no differences in the post-CPB values for platelet count, adenosine diphosphate-stimulated platelet aggregation, antithrombin III, soluble fibrin, Factor XIIa, or postoperative blood loss.
  
  
  CONCLUSIONS
  Compared with heparin management with the activated clotting time, heparin concentration-based anticoagulation management during CPB leads to a significant reduction of thrombin generation, fibrinolysis, and neutrophil activation, whereas there is no difference in the effect on platelet activation. The generation of fibrin even in the presence of high heparin concentrations most likely has to be attributed to the reduced antithrombin III concentrations or reduced inhibition of clot-bound thrombin. Therefore, in addition to maintenance of higher heparin concentrations, monitoring and substitution of antithrombin III should be considered to ensure more efficient antithrombin activity during CPB.
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000758:Anesthesia; D000925:Anticoagulants / Q000627:therapeutic use*; D015415:Biomarkers; D001772:Blood Cell Count; D016063:Blood Loss, Surgical; D001803:Blood Transfusion; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D016896:Treatment Outcome; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D006493:Heparin