重组人巨核细胞生长发育因子减轻体外循环后血小板减少症。

Recombinant human megakaryocyte growth and development factor attenuates postbypass thrombocytopenia.

作者信息

Nakamura M, Toombs C F, Duarte I G, Ronson R S, Schmarkey L S, Katzmark S L, Robinson J, Dillehay D L, Vinten-Johansen J, Guyton R A

机构信息

Department of Surgery, Carlyle Fraser Heart Center of Emory University, Atlanta, Georgia, USA.

出版信息

Ann Thorac Surg. 1998 Oct;66(4):1216-23. doi: 10.1016/s0003-4975(98)00807-8.

DOI:10.1016/s0003-4975(98)00807-8

PMID:9800809

Abstract

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.

摘要

背景

体外循环会因暴露于剪切应力、异物表面及低温环境而导致血小板丢失和功能障碍。本研究检验了聚乙二醇化重组人巨核细胞生长和发育因子（PEG-rHuMGDF）能加速低温体外循环（HEC）后血小板数量恢复的假说。

方法

在一项双盲研究中，术前3天（第0、1和2天）每天给犬皮下注射药物或安慰剂，第3天不注射药物。第4天，将动物准备好进行动静脉HEC。肝素化后，以30至40 mL×kg⁻¹×min⁻¹启动HEC。低温体外循环（25℃）持续90分钟。

结果

术前血小板计数（×10³个血小板/微升）在安慰剂组（256±27对255±20）或PEG-rHuMGDF组（271±30对291±38）与给药前计数无差异。在HEC的60分钟内，安慰剂组（29±5）和PEG-rHuMGDF组（46±8）的血小板计数降至基线的约10%，复温后（HEC 90分钟）恢复至基线的约70%（安慰剂组，185±17，对PEG-rHuMGDF组，169±22）。HEC后，PEG-rHuMGDF治疗的动物血小板计数更高（p<0.05），且功能未改变（聚集反应）。在HEC后的前6小时内，PEG-rHuMGDF治疗的动物血小板计数上升并增至260±29（p<0.01），而安慰剂组动物则无变化（186±21）。此后，安慰剂组动物的血小板计数降至最低点124±15（HEC后72小时），而PEG-rHuMGDF组动物的血小板计数在所有时间均接近术前值（>200）。