Coagulation-fibrinolysis changes during off-pump bypass: effect of two heparin doses.
BACKGROUND
To date, no study has tested the effect of different heparin dosages on the hemostatic changes during off-pump coronary artery bypass graft (OPCABG) surgery, and a wide variety of empirical anticoagulation protocols are being applied. We tested the effect of two different heparin dosages on the activation of the hemostatic system in patients undergoing OPCABG procedures.


METHODS
Forty-two patients eligible for OPCABG procedures were assigned in a randomized fashion to low-dose heparin (150 IU/kg) or high-dose heparin (300 IU/kg). Prothrombin fragment 1+2, plasmin/alpha(2)-plasmin inhibitor complex, D-dimer, soluble tissue factor, tissue factor pathway inhibitor, total thrombin activatable fibrinolysis inhibitor (TAFI), and activated TAFIa were assayed by specific enzyme-linked immunosorbent assays at six different timepoints, before, during, and after surgery. Platelet function was evaluated by means of an in vitro bleeding time test, platelet function analyzer-100.


RESULTS
The OPCABG surgery was accompanied by significant changes of all plasma biomarkers, indicative of systemic activation of coagulation and fibrinolysis. A significant increase in circulating TAFIa was detected perioperatively and postoperatively, and multiple regression analysis indicated that prothrombin F1+2 but not plasmin/alpha(2)-antiplasmin complex was independently associated with TAFIa level. Platelet function analyzer-100 values did not change significantly after OPCABG. All hemostatic changes were similar in the two heparin groups, even perioperatively, when the difference in anticoagulation was maximal.


CONCLUSIONS
Both early and late hemostatic changes, including TAFI activation, are similarly affected in the low-dose and high-dose heparin groups, suggesting that the increase in heparin dosage is not accompanied by a better control of clotting activation during OPCABG surgery.
Paparella
Domenico
D
Department of Emergency and Organ Transplant, Division of Cardiac Surgery, University of Bari, Bari, Italy. dpaparella@cardiochir.uniba.it
Semeraro
Fabrizio
F
Scrascia
Giuseppe
G
Galeone
Antonella
A
Ammollo
Concetta T
CT
Kounakis
Giorgios
G
de Luca Tupputi Schinosa
Luigi
L
Semeraro
Nicola
N
Colucci
Mario
M
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001760:Bleeding Time; D025901:Carboxypeptidase B2; D047549:Coronary Artery Bypass, Off-Pump; D003327:Coronary Disease / Q000097:blood* / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006488:Hemostasis, Surgical; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011183:Postoperative Complications / Q000097:blood; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D013925:Thromboplastin / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D008074:Lipoproteins; D010446:Peptide Fragments; D011498:Protein Precursors; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; C051928:lipoprotein-associated coagulation inhibitor; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D006493:Heparin; D013925:Thromboplastin; D025901:Carboxypeptidase B2; D005341:Fibrinolysin