RECOMBINANT HUMAN MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR ATTENUATES POSTBYPASS THROMBOCYTOPENIA

Background. Cardiopulmonary bypass contributes to platelet loss and dy sfunction by exposure to shear stresses, foreign surfaces, and hypothe rmia. This study tested the hypothesis that pegylated recombinant huma n megakaryocyte growth and development factor (PEG-rHuMGDF) accelerate s recovery of the platelet population after hypothermic extracorporeal circulation (HEC). Methods. In a blinded study, subcutaneous injectio ns of drug or placebo were given to dogs daily for 3 days preoperative ly (day 0, 1, and 2) with no drug on day 3. On day 4, the animal was p repared for arteriovenous HEC. After heparinization, HEC was initiated at 30 to 40 mt kg-l min-l. Hypothermic extracorporeal circulation (25 degrees C) was continued for 90 minutes. Results. Preoperative platel et count (x10(3) platelets/mu L) did not differ from predrug count in placebo (256 +/- 27 versus 255 +/- 20) or PEG-rHuMGDF (271 +/- 30 vers us 291 +/- 38). During 60 minutes of HEC, the platelet count decreased to similar to 10% of baseline in placebo (29 +/- 5) and PEG-rHuMGDF ( 46 +/- 8), and recovered to similar to 70% of baseline after rewarming (90 minutes of HEC: placebo, 185 +/- 17, versus PEG-rHuMGDF, 169 +/- 22). After HEC, platelet count was greater in PEG-rHuMGDF-treated anim als (p < 0.05) without altering function (aggregation responses). With in the first 6 hours after HEC, platelet count in PEG-rHuMGDF-treated animals was rising and increased to 260 +/- 29 (p < 0.01), but was unc hanged in placebo animals (186 +/- 21). Thereafter, platelet count in placebo animals declined to a nadir of 124 +/- 15 (72 hours after HEC) , whereas platelet count in PEG-rHuMGDF animals approximated the preop erative value (>200) at all times. Conclusions. Appropriately timed pr esurgical administration of PEG-rHuMGDF counteracts post-HEC relative thrombocytopenia without increasing platelet population and enhancing aggregation preoperatively or during extracorporeal circulation. (Ann Thorac Surg 1998;66:1216-23) (C) 1998 by The Society of Thoracic Surge ons.