Document Detail


Recombinant human megakaryocyte growth and development factor attenuates postbypass thrombocytopenia.
MedLine Citation:
PMID:  9800809     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Nakamura; C F Toombs; I G Duarte; R S Ronson; L S Schmarkey; S L Katzmark; J Robinson; D L Dillehay; J Vinten-Johansen; R A Guyton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  66     ISSN:  0003-4975     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-12-02     Completed Date:  1998-12-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1216-23     Citation Subset:  AIM; IM    
Affiliation:
Department of Surgery, Carlyle Fraser Heart Center of Emory University, Atlanta, Georgia, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation / drug effects
Blood Platelets / drug effects
Cardiopulmonary Bypass / adverse effects*
Dogs
Humans
Hypothermia, Induced
Injections, Subcutaneous
Platelet Aggregation / drug effects
Platelet Count / drug effects
Polyethylene Glycols / administration & dosage,  pharmacology*
Preoperative Care
Recombinant Proteins / administration & dosage,  pharmacology
Thrombocytopenia / etiology,  prevention & control*
Thrombopoietin / administration & dosage,  pharmacology*
Time Factors
Chemical
Reg. No./Substance:
0/Polyethylene Glycols; 0/Recombinant Proteins; 0/polyethylene glycol-recombinant human megakaryocyte growth and development factor; 9014-42-0/Thrombopoietin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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