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肝移植受者的血小板减少症:预测因素、对真菌感染的影响及内源性血小板生成素的作用

Thrombocytopenia in liver transplant recipients: predictors, impact on fungal infections, and role of endogenous thrombopoietin.

作者信息

Chang F Y, Singh N, Gayowski T, Wagener M M, Mietzner S M, Stout J E, Marino I R

机构信息

Veterans Affairs Medical Center and University of Pittsburgh, Thomas E. Starzl Transplantation Institute, Pennsylvania 15240, USA.

出版信息

Transplantation. 2000 Jan 15;69(1):70-5. doi: 10.1097/00007890-200001150-00014.

Abstract

BACKGROUND

Thrombocytopenia is a frequent and potentially serious complication in liver transplant recipients. The role of endogenous thrombopoietin level in posttransplant thrombocytopenia, has not been fully defined in liver transplant recipients. Additionally, there is accumulating evidence to suggest that platelets play a important role in antimicrobial host defense.

METHODS

There were 50 consecutive liver transplant recipients studied. Variables predictive of thrombocytopenia, its impact on infectious morbidity and outcome, and serial thrombopoietin (TPO) serum concentration were assessed.

RESULTS

The median pretransplant platelet count was 67 x 10(3)/cmm. After the liver transplantation, the median nadir platelet count was 33 x 10(3)/cmm and was reached a mean of 6 days after the transplant. A lower pretransplant platelet count (r= +.068, P=.0001), lower serum albumin before the transplants (r=+0.39, P=.014), longer operation time (r=0.27, P=.05), higher intraoperative packed red cells (r=0.28, P=.049) and fresh frozen plasma transfusions (r=0.42, P=.004), higher bilirubin at Day 7 (r=-.386, P=.005), and higher serum creatinine at Day 7 after the transplants (r=-.031, P=.025) correlated significantly with a lower nadir in platelets after the transplant. Nadir in platelet count was significantly lower in nonsurvivors compared with survivors (16 vs. 36 x 10(3)/cmm, P=.0001). Forty-three percent (9 of 21) of the patients with nadir platelet counts of < or =30 x 10(3)/cmm had a major infection within 30 days of the transplant compared with 17% (5 of 29) with nadir platelet counts > 30 x 10(3)/cmm (P=.04). Fungal infections occurred in 14% of the patients with nadir platelet counts of < or =30 x 10(3)/cmm versus 0% in those with nadir platelet counts of > 30 x 10(3)/cmm (P=.06); all patients with fungal infections had nadir platelet counts of < or =30 x 10(3)/cmm before fungal infection. Nadir in platelet count preceded the first major infection by a median of 7 days. Pretransplant TPO level did not differ between survivors (mean 103 pg/ml) or nonsurvivors (mean 144 pg/ml). After the transplantation, TPO levels increased in both groups. TPO level peaked at Day 7 and subsequently declined in survivors. Nonsurvivors had persistent thrombocytopenia despite a progressive rise in TPO level; TPO level was significantly higher at Day 7 (P=.02), Day 9 (P=.0019), and Day 14 (P=.04) in nonsurvivors compared with survivors.

CONCLUSION

Persistent thrombocytopenia portended a poor outcome in liver transplant recipients and was not related to low TPO levels. Thrombocytopenia preceded infections and identified a subgroup of liver transplant patients susceptible to early major infections; its precise role in fungal infections warrants validation in larger studies.

摘要

背景

血小板减少症是肝移植受者常见且可能严重的并发症。内源性血小板生成素水平在肝移植受者移植后血小板减少症中的作用尚未完全明确。此外,越来越多的证据表明血小板在抗菌宿主防御中起重要作用。

方法

连续研究了50例肝移植受者。评估了预测血小板减少症的变量、其对感染性发病率和结局的影响以及血小板生成素(TPO)血清浓度的变化情况。

结果

移植前血小板计数中位数为67×10³/cmm。肝移植后,血小板计数最低点中位数为33×10³/cmm,平均在移植后6天达到。移植前血小板计数较低(r = +0.68,P = 0.0001)、移植前血清白蛋白较低(r = +0.39,P = 0.014)、手术时间较长(r = 0.27,P = 0.05)、术中输注浓缩红细胞较多(r = 0.28,P = 0.049)和新鲜冰冻血浆较多(r = 0.42,P = 0.004)、术后第7天胆红素较高(r = -0.386,P = 0.005)以及术后第7天血清肌酐较高(r = -0.31,P = 0.025)与移植后血小板最低点较低显著相关。非存活者的血小板计数最低点显著低于存活者(16 vs. 36×10³/cmm,P = 0.0001)。血小板计数最低点≤30×10³/cmm的患者中有43%(21例中的9例)在移植后30天内发生了严重感染,而血小板计数最低点>30×10³/cmm的患者中这一比例为17%(29例中的5例)(P = 0.04)。血小板计数最低点≤30×10³/cmm的患者中有14%发生真菌感染,而血小板计数最低点>30×10³/cmm的患者中这一比例为0%(P = 0.06);所有真菌感染患者在真菌感染前血小板计数最低点均≤30×10³/cmm。血小板计数最低点比首次严重感染提前出现的中位数为7天。移植前存活者(平均103 pg/ml)和非存活者(平均144 pg/ml)的TPO水平无差异。移植后,两组TPO水平均升高。TPO水平在第7天达到峰值,随后存活者中TPO水平下降。尽管TPO水平逐渐升高,非存活者仍持续存在血小板减少症;与存活者相比,非存活者在第7天(P = 0.02)、第9天(P = 0.0019)和第14天(P = 0.04)的TPO水平显著更高。

结论

持续性血小板减少症预示肝移植受者预后不良,且与低TPO水平无关。血小板减少症先于感染出现,并确定了一组易发生早期严重感染的肝移植患者亚组;其在真菌感染中的确切作用有待在更大规模研究中验证。

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