Is there a phase of hypercoagulability when aprotinin is used in cardiac surgery?
To determine a possible phase of hypercoagulability after the use of high-dose aprotinin, a prospective randomized double-blind study was performed. Twenty patients undergoing aortocoronary bypass surgery were investigated, a placebo group P (n = 10) was compared to an aprotinin group A (n = 10). Examining parameters of thrombin activation and fibrinolysis, we found during extracorporeal circulation--under continuous aprotinin infusion--a significant inhibition of thrombin activation and fibrinolysis in the aprotinin group (thrombin-antithrombin-III-complexes: 95 +/- 23 micrograms/l, d-dimers: 448 +/- 60 ng/ml, plasminogen activity: 33 +/- 3%, plasminogen activator inhibitor: 98 +/- 14 U/ml) compared to the placebo group (thrombin-antithrombin-III-complexes: 143 +/- 13 micrograms/l, d-dimers: 2755 +/- 430 ng/ml, plasminogen activity: 125 +/- 15%, plasminogen activator inhibitor: 10 +/- 4 U/ml). In contrast, after stopping the aprotinin infusion--from the end of extracorporeal circulation until the morning of the first postoperative day--strong thrombin activation took place in the aprotinin group (d-dimers increased from 472 +/- 90 to 1607 +/- 140 ng/ml), while in the placebo group a decrease could be registered. At this time, the fibrinolysis was still reduced in the aprotinin group (plasminogen activity: 48 +/- 6% vs 85 +/- 16% in the placebo group). In conclusion, interference with the thrombohemorrhagic balance induces hypercoagulability after the use of high-dose aprotinin, with elevated levels of thrombin-antithrombin-III-complexes, d-dimers, and plasminogen and a decreased level of plasminogen activator inhibitor. In our opinion, it is necessary to prevent this counter-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Feindt
P
P
Department of Thoracic and Cardiovascular Surgery, Homburg University Hospital, Germany.
Seyfert
U
U
Volkmer
I
I
Huwer
H
H
Kalweit
G
G
Gams
E
E
D000368:Aged; D000990:Antithrombin III / Q000032:analysis; D007611:Aprotinin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001778:Blood Coagulation Disorders / Q000139:chemically induced*; D001780:Blood Coagulation Tests; D006348:Cardiac Surgical Procedures; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis; D006801:Humans; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D010958:Plasminogen / Q000032:analysis; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011446:Prospective Studies
D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D010958:Plasminogen; D007611:Aprotinin; D010447:Peptide Hydrolases; D010960:Plasminogen Activators