肝硬化門靜脈高壓性外周血細(xì)胞減少與手術(shù)預(yù)后

呂云福 韓曉玉 吳鴻飛 常順伍 邱慶安

·論 著·(門靜脈高壓癥外科專題)

肝硬化門靜脈高壓性外周血細(xì)胞減少與手術(shù)預(yù)后

呂云福 韓曉玉 吳鴻飛 常順伍 邱慶安

目的 探討肝炎后肝硬化門靜脈高壓性脾腫大病人外周血細(xì)胞減少的構(gòu)成比及對(duì)手術(shù)預(yù)后的影響。方法 研究1991年1月至2015年6月筆者醫(yī)院收治肝炎后肝硬化門靜脈高壓性脾腫大病人并發(fā)外周血細(xì)胞減少376例的臨床資料，并將外周血細(xì)胞減少進(jìn)行分度，比較它們的預(yù)后。結(jié)果 并發(fā)單種血細(xì)胞減少者占30.1%(113/376)，兩種血細(xì)胞減少者占35.9%(135/376)，三種血細(xì)胞均減少者占34.0%(128/376)。全組均行脾臟切除+門奇斷流術(shù)，行分流術(shù)58例(15.4%)。單種血細(xì)胞減少與多種血細(xì)胞減少的手術(shù)預(yù)后比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，在376例血細(xì)胞減少中，血小板計(jì)數(shù)(PLT)減少與白細(xì)胞計(jì)數(shù)減少、紅細(xì)胞計(jì)數(shù)減少的手術(shù)預(yù)后比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。以PLT減少為主，將血細(xì)胞減少分為輕、中、重三度，分別給予<2分、2～3分和>3分進(jìn)行病例統(tǒng)計(jì)分析，其預(yù)后差異也有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論 外周血細(xì)胞減少對(duì)手術(shù)預(yù)后有一定影響，單種血細(xì)胞減少的手術(shù)預(yù)后明顯優(yōu)于多種血細(xì)胞減少，輕度血細(xì)胞減少的預(yù)后明顯優(yōu)于重度血細(xì)胞減少，血細(xì)胞減少越多越嚴(yán)重、預(yù)后越差。

肝硬化門靜脈高壓癥；外周血細(xì)胞減少；分度；手術(shù)預(yù)后

肝炎后肝硬化門靜脈高壓性脾腫大病人并發(fā)嚴(yán)重消化道出血，嚴(yán)重脾功能亢進(jìn)和肝癌時(shí)，通常需要手術(shù)治療，影響手術(shù)預(yù)后的因素盡管有多種[1]，但外周血細(xì)胞減少是一種不可忽視的因素。外周血細(xì)胞減少是指入院后第一次從外周靜脈血中抽出的血液，細(xì)胞計(jì)數(shù)低于正常檢測(cè)值，即白細(xì)胞計(jì)數(shù)(WBC)<4.0×109/L、紅細(xì)胞計(jì)數(shù)(RBC)<3.5×1012/L和血小板計(jì)數(shù)(PLT)<100×109/L稱為血細(xì)胞減少。本文研究了1991年1月至2015年6月筆者醫(yī)院收治肝炎后肝硬化門靜脈高壓性脾腫大病人376例的臨床資料，就其對(duì)手術(shù)預(yù)后的影響進(jìn)行分析，現(xiàn)報(bào)告如下。

資料與方法

一、臨床資料

在376例中，男性257例，女性119例，男女之比為2.2∶1。年齡5～79歲，中位年齡43歲。全組均為肝炎后肝硬化、脾臟普遍增大，B超或CT測(cè)量脾臟大小平均為224 mm×159 mm×95 mm。上消化道造影或胃鏡檢查均顯示，食管下段和胃底均有中、重度靜脈曲張，76例(20.2%)因消化道出血而入院，179例(47.6%)既往有出血史。全組經(jīng)輸血，補(bǔ)充已缺少的血液有形成分后，行脾切除術(shù)，同時(shí)行賁門周圍血管離斷術(shù)376例(附加脾腎靜脈分流58例)。

二、手術(shù)預(yù)后定義

手術(shù)預(yù)后主要有痊愈、好轉(zhuǎn)和死亡三種。痊愈是指腹水、腹脹及出血癥狀消失，減少的血細(xì)胞開始上升并接近正常值，肝臟功能改善，術(shù)后無(wú)嚴(yán)重并發(fā)癥，能安全出院；死亡是指術(shù)后住院期間死亡，包括病情危重，病人家屬要求出院后1周內(nèi)的死亡；否則為好轉(zhuǎn)。

三、統(tǒng)計(jì)學(xué)分析

運(yùn)用SPSS(18.0版)統(tǒng)計(jì)軟件，單因素分析采用卡方檢驗(yàn)，多單因素分析采用多元線性回歸處理，P<0.05表示差異有統(tǒng)計(jì)學(xué)意義。

結(jié) 果

本文376例中，單種血細(xì)胞減少占30.1%(113/376)，兩種血細(xì)胞減少占35.9%(135/376)，三種血細(xì)胞均減少占34.0%(128/376)。單種血細(xì)胞減少構(gòu)成比及治療結(jié)果比較見表1，結(jié)果顯示僅RBC減少組組間比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；其余各組組間比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。

單種血細(xì)胞減少與兩種血細(xì)胞減少的療效比較，差異有統(tǒng)計(jì)學(xué)意義(χ2=7.446，P=0.024)，見表2。單種血細(xì)胞減少與多種血細(xì)胞減少的療效比較，差異也有統(tǒng)計(jì)學(xué)意義(χ2=7.819，P=0.02)，見表3。

表2 單種血細(xì)胞與兩種血細(xì)胞減少療效比較[例(%)]

表3 單種血細(xì)胞減少與多種血細(xì)胞減少療效比較[例(%)]

注：*指兩種以上血細(xì)胞減少

表1 113例單種血細(xì)胞減少治療結(jié)果組內(nèi)比較[例(%)]

表4 376例血細(xì)胞的多元線性回歸分析

于是，以PLT減少為主，同時(shí)結(jié)合單種血細(xì)胞減少療效比較中有顯著差異的RBC減少和臨床經(jīng)驗(yàn)(WBC減少)，將376例血細(xì)胞減少病例進(jìn)行分權(quán)、打分。PLT>50×109/L打1分，(30～50)×109/L打2分，<30×109/L打3分；RBC(3～4)×1012/L打0分，<3×1012/L打1分；WBC (2～4)×109/L打0分，<2×109/L打1分。將外周血細(xì)胞減少總分分為輕(<2分)、中(2～3分)、重(>3分)三度(表5)。

表5 外周血細(xì)胞減少(脾功能亢進(jìn))分級(jí)

不同分值對(duì)手術(shù)預(yù)后的影響見表6，三組療效比較差異有統(tǒng)計(jì)學(xué)意義(χ2=10.163，P=0.034)。

表6 不同分值對(duì)治療結(jié)果影響的比較[例(%)]

討 論

肝炎后肝硬化門靜脈高壓性脾臟腫大病人并發(fā)外周血細(xì)胞減少約70%表現(xiàn)為多種血細(xì)胞減少，30%表現(xiàn)為單種血細(xì)胞減少。

從表1看，單種血細(xì)胞減少，只有RBC組內(nèi)比較療效差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。從表2、3可知，單種血細(xì)胞減少與兩種和多種血細(xì)胞減少的療效比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，表明血細(xì)胞減少越多術(shù)后療效越差。

在多種血細(xì)胞減少中，采用多元線性回歸分析，發(fā)現(xiàn)PLT減少是影響手術(shù)療效的主要因素(P<0.05)，而RBC減少、WBC減少和Hb下降均無(wú)統(tǒng)計(jì)學(xué)意義，被列為非主要因素。RBC減少在單種血細(xì)胞減少組內(nèi)療效比較中有顯著性差異，但在多因素中比較差異無(wú)統(tǒng)計(jì)學(xué)意義，可能與單種血細(xì)胞減少組樣本比較小、有一定的局限性有關(guān)。WBC減少無(wú)論是單因素分析還是多因素分析，對(duì)手術(shù)預(yù)后的影響均不大，我們有2例病人WBC在1×109/L以下,術(shù)后也能順利康復(fù)出院，這可能與術(shù)后沒(méi)有遭遇嚴(yán)重感染有關(guān)。從理論上講，貧血應(yīng)與預(yù)后有關(guān)，而本研究無(wú)論從單因素分析還是多因素分析，差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，可能是術(shù)前、術(shù)中注意輸血，貧血得到糾正之故。PLT減少雖在單因素比較中差異無(wú)統(tǒng)計(jì)學(xué)意義，但隨著病例數(shù)的加大，在多因素線性回歸分析中卻顯示唯一有顯著意義的主要因素。

1907年，Chauffard使用脾功能亢進(jìn)這一名稱[13]。1949年Doan[14]做了進(jìn)一步研究，提出脾功能亢進(jìn)的必備條件：①脾臟腫大；②血中有一種或數(shù)種血細(xì)胞成分減少；③骨髓正?；虺试錾鸂顟B(tài)；④脾切除術(shù)后血液成分的病理性改變消失。這4點(diǎn)必備條件是對(duì)診斷脾功能亢進(jìn)總體而言，然而肝硬化門靜脈高壓癥病人因脾腫大本身就是門靜脈高壓癥應(yīng)具備的條件、故評(píng)價(jià)肝硬化門靜脈高壓癥病人的脾功能亢進(jìn)主要依據(jù)外周血細(xì)胞的減少和脾切除術(shù)后原減少的血細(xì)胞恢復(fù)至正?；蚪咏?。

合理的分度有利于評(píng)估疾病的程度；有利于表述和學(xué)術(shù)交流；有利于與病人及其家屬溝通病情，減少醫(yī)療糾紛；有利于選擇治療，如系重度血細(xì)胞減少或脾功能亢進(jìn)，手術(shù)切除腫大的脾臟是理想的選擇；有利于術(shù)前采取措施[16]，預(yù)先防范，提高治愈率。

2 Karasu Z,Gurakar A, Kerwin B,et al. Effect of transjuqular intrahepatic portosystemic shunt on thrombocytopenia associated with cirrhosis.Dig Dis Sci,2000,45:1971-1976.

3 Fadi NB，J Carlos T，Kevin D，et al.Prevalence of Peripheral Blood Cytopenias Hypersplenism)in Patients With Nonalcoholic Liver Disease. Am Coll of Gastroeterology，2000，95：2937-2939.

4 Yan F，Li W，Gao J，et al. cDN Amicoarray-based screening of differentially expressed genes in macrophages in the spleen of patients with portal Hypertension and hypersplenism. Nan Fang Yi Ke Da Xue Xue Bao,2006,26:1548-1551.

5 李路豪,黨曉衛(wèi),李林,等.門靜脈高壓病人部分脾栓塞術(shù)后并發(fā)脾膿腫的危險(xiǎn)因素及治療.腹部外科,2015,28:394-398.DOI: 10.3969/j.issn.1003-5591.2015.06.005.

7 Zhang JY, Wang Y, Zhang J, et al.Risk factors associated with failure from endoscopic therapy in acute non-variceal upper gastrointestinal bleeding.Beijing Da Xue Xue Bao,2010,42:703-707.

8 Cui Y, Hei F, Long C, et al. Perioperative monitoring of thromboelastograph on hemostasis and therapy for cyanotic infants undergoing complex cardiac surgery. Artif Organs,2009,33:909-914.

9 呂云福,李新秋,黃偉煒,等.門靜脈高壓性脾功能亢進(jìn)病人的外周血細(xì)胞變化.中華普通外科雜志,2007,22:702.

10 Matsuura T, Hayashida M, Saeki I, Taguchi T.The risk factors of persistent thrombocytopenia and splenomegaly after liver transplantation.Pediatr Surg Int,2010,26:1007-1010.

11 Johansson PI, Stensballe J.Hemostatic resuscitation for massive bleeding: the paradigm of plasma and platelets--a review of the current literature.Transfusion,2010,50:701-710.DOI:10.1111/j.1537-2995.2009.02458.x.

12 Shontz R, Karuparthy V, Temple R,et al.Prevalence and risk factors predisposing to coagulopathy in patients receiving epidural analgesia for hepatic surgery. Reg Anesth Pain Med,2009,34:308-311.DOI: 10.1097/AAP.0b013e3181ac7d00.

13 Bashour FN, Teran JC, Mullen KD. Prevalence of peripheral blood cytopenias(hypersplenism)in patients with nonalcoholic liver disease. Am J Gastroeterol,2000,95:2937-2939.

14 Doan CA.Hypersplenism. Bull N Y Acad Med,1949,25:625-650.

15 Lv Y,Han X,Gong X,et al.Grading of peripheral cytopenias caused by nonalcoholic cirrhotic portal hypertension and its clinical significance. Cell Biochem Biophys,2015,71:1141-1145.DOI: 10.1007/s12013-014-0321-x.

16 Shaz BH, Dente CJ, Nicholas J, et al.Increased number of coagulation products in relationship to red blood cell products transfused improves mortality in trauma patients.Transfusion,2010,50:493-500.DOI:10.1111/j.1537-2995.2009.02414.x.

Liver cirrhosis portal hypertension decreased peripheral blood cells and surgical outcomes

LyuYunfu,HanXiaoyu,WuHongfei,ChangShunwu,QiuQingan.

DepartmentofGeneralSurgery,HainanProvincialPeople'sHospital,Haikou570311,China

LyuYunfu,Email:yunfu_lv@126.com

Objective To investigate the constituent ratio of peripheral cytopenias in patients with splenomegaly caused by post-hepatitic cirrhotic portal hypertension and potential influence of peripheral cytopenias on prognosis. Methods Between January 1991 and June 2015, 376 cases of post-hepatitic cirrhotic portal hypertension induced splenomegaly patients associated with peripheral cytopenias, undertook surgery in our hospital, and their clinical data was reviewed. Furthermore, peripheral cytopenias and prognosis in them was graded and compared. Results Patients associated with mono-lineage, bi-lineage, and tri-lineage cytopenias, respectively accounted for 30.1% (113/376), 35.9% (135/376), and 34.0% (128/376). Significant statistical differences (P<0.05) in post-operative prognostic could be noted in patients in contrast of mono-lineage cytopenias and multi-linage cytopenias. In all patients, postoperative prognosis demonstrated significant correlation with thrombocytopenia, leukopenia and erythropenia (P<0.05). According to the severity of thrombocytopenia, cytopenia was graded as mild, medium and severe, referring to <2 grade，2-3 grade and >3 grade respectively. The prognosis revealed significant differences among three groups (P<0.05). Conclusions Peripheral cytopenias can influence postoperative prognosis in patients with splenomegaly caused by post-hepatitic cirrhotic portal hypertension. The prognosis in patients associated with mono-linage peripheral cytopenias is better than those associated with multi-linage cytopenias, and prognosis in patients associated with mild peripheral cytopenias is obviously better than those associated with severe cytopenias. Our study demonstrates the more severe the peripheral cytopenias is, the worse the prognosis is.

Liver cirrhosis portal hypertension; Peripheral cytopenias; Grading; Postoperative prognosis

海南省科技合作專項(xiàng)資金項(xiàng)目(KJHZ2015-28)

570311 海口，海南省人民醫(yī)院普外中心

呂云福， Email:yunfu_lv@126.com

R657.3+4；R657.3+1

A [DOI] 10.3969/j.issn.1003-5591.2016.03.002

楊鎮(zhèn)，裘法祖.關(guān)于門靜脈高壓癥預(yù)后結(jié)局的研究. 腹部外科，2003，16:68-70.

10.3969/j.issn.1003-5591.2003.02.001.

2016-03-16)