title: Low-dose protamine based on heparin-protamine titration method reduces platelet dysfunction after cardiopulmonary bypass.
abstract: OBJECTIVE
  The heparin-protamine titration method that uses the Hepcon hemostasis management system (Medtronic HemoTec Inc, Englewood, Colo) reduced blood loss in cardiac surgery in previous reports, but the mechanism is not fully understood. This study tests the hypothesis that reduced protamine administration preserves platelet function in human cardiac surgery.
  
  
  METHODS
  Platelet count, alpha-granule secretion, and aggregation to thrombin before and after cardiopulmonary bypass in human beings were evaluated. In the control group (n = 14), a fixed dose of protamine (3 mg/kg) was administered. In the titration group (n = 20), protamine doses were based on the heparin concentration measured by the Hepcon system.
  
  
  RESULTS
  Heparin concentrations before protamine administration were higher in the titration group (P =.0012), but protamine doses of patients in the titration group were markedly lower than those of the control group (P <.0001). During protamine infusion at a rate of 0.3 mg. kg(-1). min(-1), the percentage of granule membrane protein-140-positive platelets significantly increased in the control group compared with the titration group (18.8% +/- 8.6% vs 13.0% +/- 5.3%, P =.0188). After protamine administration, aggregation of washed platelets to thrombin recovered almost to the preoperative level in the titration group; however, it remained lower in the control group (20% +/- 20% vs 55% +/- 18%, P =.0009).
  
  
  CONCLUSIONS
  Low-dose administration of protamine, based on a heparin-protamine titration method, restores not only the blood coagulation but also the platelet responses to thrombin and attenuates platelet alpha-granule secretion during heparin neutralization. Overdose of protamine activates platelets and may predispose patients to excessive bleeding after cardiac surgery.
authors.affiliation: Division of Cardiovascular Surgery, Insitute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Shigeta
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: Y
authors.initials: Y
authors.lastname: Hiramatsu
authors.forename: T
authors.initials: T
authors.lastname: Jikuya
authors.forename: Y
authors.initials: Y
authors.lastname: Terada
authors.forename: N
authors.initials: N
authors.lastname: Atsumi
authors.forename: Y
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
authors.forename: T
authors.initials: T
authors.lastname: Mitsui
mesh_terms: D016063:Blood Loss, Surgical / Q000517:prevention & control; D001791:Blood Platelet Disorders / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003594:Cytoplasmic Granules / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage / Q000378:metabolism*; D006494:Heparin Antagonists / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011479:Protamines / Q000008:administration & dosage* / Q000378:metabolism; D012189:Retrospective Studies; D013917:Thrombin / Q000378:metabolism; D017186:Titrimetry
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin; D013917:Thrombin