Wendel H P, Schulze H J, Heller W, Hoffmeister H M
Department of Surgery, University of Tuebingen, Germany.
J Cardiothorac Vasc Anesth. 1999 Aug;13(4):388-92. doi: 10.1016/s1053-0770(99)90208-2.
To examine the extent of platelet activation during extracorporeal circulation by using the combination of heparin-coated oxygenation systems and high-dose aprotinin therapy, and to examine the affinity and thereby the protective capacity of aprotinin to the glycoprotein (GP) receptors of the platelet membrane.
Experimental in vitro study.
Research laboratory of a university hospital.
Thirty-two volunteers (blood donors).
Thirty-two oxygenation circuits of the same construction series (16 heparin-coated and 16 noncoated) were investigated in a closed system of a heart-lung machine model with fresh human whole blood. In each of these two groups, eight circuits with and eight without a high-dose aprotinin application (250 kallikrein inhibitory units [KIU]/mL) were investigated. In all four groups, the number of platelets declined continuously during the 90-minute recirculation period. Group I (no heparin coating, no aprotinin) showed the greatest reduction; group IV (heparin coating, aprotinin) had a significantly smaller decrease in platelet number (p < 0.01). Platelet factor 4 (PF-4) levels, released from the alpha-granule, were in inverse proportion to the platelet loss. After 90 minutes of recirculation, the PF-4 values increased to 615.8% +/- 559.5% and 237.2% +/- 179.0% of the initial value for groups I and IV, respectively (p < 0.01). Affinity chromatography and immunoblotting techniques were used to evaluate the affinity of aprotinin for the GP receptors of the platelet membrane. The affinity appeared in the following order: GPIIb < GPIIIa < GPIb.
Heparin-coated oxygenation systems and additional aprotinin caused significantly less platelet damage in an in vitro cardiopulmonary bypass model. Chromatographic and immunologic methods could prove aprotinin's affinity for the platelet receptor proteins GPIb and GPIIb-IIIa and therefore its probable role in diminishing the triggering of the platelet activation cascade.
