Anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II and renal impairment using heparin and the platelet glycoprotein IIb-IIIa antagonist tirofiban.
BACKGROUND
Patients with heparin-induced thrombocytopenia type II require an alternative to standard heparin anticoagulation. However, in patients with renal impairment, anticoagulation during cardiopulmonary bypass with agents such as danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation with unfractionated heparins combined with prostacyclin, a potent platelet aggregation inhibitor, is associated with severe hypotension. The authors investigated a new concept using unfractionated heparins after platelet inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist tirofiban.


METHODS
Ten patients with heparin-induced thrombocytopenia type II and renal impairment were enrolled in the investigation. All had heparin-induced thrombocytopenia type II antibodies present as proved by the heparin-induced platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked immunosorbent assay, or both. In all patients, preoperative anticoagulation to an activated partial thromboplastin time of 40-60 s was performed with r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10 microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1) x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional unfractionated heparins were only administered if activated clotting time decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer concentrations, as a marker of venous thromboembolism, were measured before and 12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started immediately with r-hirudin to anticoagulation to an activated partial thromboplastin time of 40-60 s.


RESULTS
The postoperative blood loss ranged from 110 to 520 ml. No patient needed reexploration. In no patient was there clinical evidence of thrombosis or embolism in the postoperative period or of a critical increase of the D-dimer concentrations, suggesting venous thromboembolism. Transfusion of platelets was necessary in only two patients.


CONCLUSIONS
The protocol is easy to perform and no increased postoperative bleeding and no thromboembolic complications occurred. The combination of unfractionated heparins and tirofiban may be an alternative to other anticoagulation strategies in patients with heparin-induced thrombocytopenia.
Koster
A
A
Department of Anesthesia, Deutsches Herzzentrum Berlin, Berlin Germany. koster@dhzb.de
Kukucka
M
M
Bach
F
F
Meyer
O
O
Fischer
T
T
Mertzlufft
F
F
Loebe
M
M
Hetzer
R
R
Kuppe
H
H
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D051437:Renal Insufficiency / Q000097:blood*; D013921:Thrombocytopenia / Q000139:chemically induced*; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C036309:fibrin fragment D; D014443:Tyrosine; D006493:Heparin; D000077466:Tirofiban