Clotting and fibrinolytic disturbance during lung transplantation: effect of low-dose aprotinin. Groningen Lung Transplant Group.
Patients undergoing lung transplantation are often confronted with a bleeding problem that may be due in part to the use of cardiopulmonary bypass and its activation of blood clotting and fibrinolysis.


OBJECTIVE
We performed a prospective study to determine whether and to what extent the clotting and fibrinolytic systems are being activated and whether low-dose aprotinin is effective in inhibiting blood activation during lung transplantation.


METHODS
Thirty lung transplantations performed on 29 patients were divided into a group with cardiopulmonary bypass alone (n = 12), a group with cardiopulmonary bypass and 2 x 10(6) KIU aprotinin administered at the beginning of bypass in the pump prime (n = 12), and a group without cardiopulmonary bypass (n = 6). Serial blood samples were taken from the recipient before anesthesia, seven times during the operation, and 4 and 24 hours thereafter.


RESULTS
Results show that in the group having cardiopulmonary bypass alone, the concentration of the clotting marker thrombin/antithrombin III complex increased significantly during the early phase of the operation (p < 0.01) and remained high until the end of the operation. Levels of tissue-type plasminogen activator, a trigger of fibrinolysis released by injured endothelium, also increased sharply in the early phase of the operation in the cardiopulmonary bypass group (p < 0.01), followed by a significant increase in fibrin degradation products (p < 0.01). In the aprotinin group, a significant reduction of thrombin/antithrombin III complex (p < 0.05), tissue-type plasminogen activator (p < 0.05), and fibrin degradation products (p < 0.05) was observed in the early phase of the operation compared with levels in the bypass group, but these markers increased late during bypass associated with a significant drop (p < 0.05) of plasma aprotinin level monitored by plasmin inhibiting capacity. In the nonbypass group, concentrations of thrombin/antithrombin III complex and tissue-type plasminogen activator also rose significantly (p < 0.05) in the early phase of the operation, but the levels were significantly lower than those of the bypass group (p < 0.05). Blood loss during the operation was 2521 +/- 550 ml in the bypass group, 1991 +/- 408 ml in the aprotinin/bypass group, and 875 +/- 248 ml in the nonbypass group.


CONCLUSIONS
These results suggest that clotting and fibrinolysis are activated during lung transplantation, especially in patients undergoing cardiopulmonary bypass. Aprotinin in a low dose significantly reduced activation of clotting and fibrinolysis in the early phase of the operation but not during the late phase of lung transplantation.
Gu
Y J
YJ
University Hospital Groningen, The Netherlands.
de Haan
J
J
Brenken
U P
UP
de Boer
W J
WJ
Prop
J
J
Van Oeveren
W
W
D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D007611:Aprotinin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D016063:Blood Loss, Surgical; D002315:Cardiopulmonary Bypass; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D005342:Fibrinolysis / Q000187:drug effects*; D006490:Hemostatics / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007430:Intraoperative Care; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D011446:Prospective Studies; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D006490:Hemostatics; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D007611:Aprotinin; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin