Recombinant human megakaryocyte growth and development factor attenuates postbypass thrombocytopenia.
BACKGROUND
Cardiopulmonary bypass contributes to platelet loss and dysfunction by exposure to shear stresses, foreign surfaces, and hypothermia. This study tested the hypothesis that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) accelerates recovery of the platelet population after hypothermic extracorporeal circulation (HEC).


METHODS
In a blinded study, subcutaneous injections of drug or placebo were given to dogs daily for 3 days preoperatively (day 0, 1, and 2) with no drug on day 3. On day 4, the animal was prepared for arteriovenous HEC. After heparinization, HEC was initiated at 30 to 40 mL x kg(-1) x min(-1). Hypothermic extracorporeal circulation (25 degrees C) was continued for 90 minutes.


RESULTS
Preoperative platelet count (x10(3) platelets/microL) did not differ from predrug count in placebo (256+/-27 versus 255+/-20) or PEG-rHuMGDF (271+/-30 versus 291+/-38). During 60 minutes of HEC, the platelet count decreased to approximately 10% of baseline in placebo (29+/-5) and PEG-rHuMGDF (46+/-8), and recovered to approximately 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 animals (p < 0.05) without altering function (aggregation responses). Within 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 unchanged 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 preoperative value (>200) at all times.


CONCLUSIONS
Appropriately timed presurgical administration of PEG-rHuMGDF counteracts post-HEC relative thrombocytopenia without increasing platelet population and enhancing aggregation preoperatively or during extracorporeal circulation.
Nakamura
M
M
Department of Surgery, Carlyle Fraser Heart Center of Emory University, Atlanta, Georgia, USA.
Toombs
C F
CF
Duarte
I G
IG
Ronson
R S
RS
Schmarkey
L S
LS
Katzmark
S L
SL
Robinson
J
J
Dillehay
D L
DL
Vinten-Johansen
J
J
Guyton
R A
RA
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004285:Dogs; D006801:Humans; D007036:Hypothermia, Induced; D007279:Injections, Subcutaneous; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011300:Preoperative Care; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013921:Thrombocytopenia / Q000209:etiology / Q000517:prevention & control*; D013926:Thrombopoietin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin