原發(fā)免疫性血小板減少癥合并血栓形成的臨床研究
發(fā)布時間：2018-10-09 15:09
【摘要】：研究背景與目的原發(fā)免疫性血小板減少癥(primary immune thrombocytopenia,ITP)是臨床最常見的出血性疾病。目前治療手段以減少血小板破壞及促血小板生成為主,以期達到提升血小板計數,預防或減輕出血的目的。但在臨床實踐中,我們觀察到少數ITP患者在治療中或治療結束后并發(fā)了動靜脈血栓,而且發(fā)生血栓時血小板計數多低于正常范圍。血栓的發(fā)生不僅平添了患者的病痛,延長了住院時間,增加了治療花費,也提高了我們對后續(xù)治療方案選擇的難度,陷入該如何兼顧血栓形成需要抗凝治療和血小板減少導致出血風險增加的兩難境地。近年來,部分國外研究報道ITP患者血栓發(fā)生率高于普通人群,但國內尚未見相關報道。為此,我們采用回顧性隊列研究分析了山東大學齊魯醫(yī)院收治的669例ITP患者發(fā)生動靜脈血栓的情況,探討影響血栓發(fā)生的危險因素,以早期發(fā)現伴有易栓傾向的ITP患者,做到及時監(jiān)測、提前干預并調整治療方案和治療目標,預防或減少血栓形成,降低病殘和病死率。研究對象與方法收集山東大學齊魯醫(yī)院于2007年1月1日至2016年7月30日收治的成人ITP患者共758例,排除失訪41例,未接受ITP治療48例,共669例患者納入研究。其中男性252例,女性417例,中位診斷年齡為40歲。包括新診斷ITP 166例,持續(xù)性ITP 191例,慢性ITP 312例。診斷標準依據2016年ITP中國專家共識。所有納入患者在隨訪期間至少接受過1次ITP治療。通過我院病案檢索系統(tǒng)搜集納入隊列研究的ITP患者的個人基本資料,依次對患者進行電話隨訪,記錄隨訪期間所有的血栓事件,并對患者信息進行基線調查,收集初診時患者的個人信息、實驗室數據及治療情況。根據隨訪期間內是否發(fā)生血栓分為血栓組和無血栓組。兩組之間各指標的比較采用單因素方差分析(連續(xù)性變量)和卡方檢驗(分類變量),計算ITP患者的發(fā)病密度和5年累積發(fā)病率,隊列資料用COX比例風險回歸模型來評估不同危險因素對血栓發(fā)生的影響。研究結果1、ITP患者血栓的發(fā)病密度為1.28/100人年(95%CI:0.83-1.94),動脈血栓和靜脈血栓則分別為 0.93/100 人年(95%CI:0.60-1.43)、0.42/100 人年(95%CI:0.15-1.12)。60 歲的 ITP 患者動脈血栓的發(fā)生率(IR=2.49,95%CI:1.52-3.89)比40歲的人群(IR=0.13,95%CI:0.05-0.34)高出18倍,靜脈血栓的發(fā)生率高出11倍,總血栓的發(fā)生率高出5倍。2、調整了混雜因素前后,年齡40歲(P0.01)、合并2個及以上心血管危險因素(P0.01)、既往血栓史1(P0.01)、3次及以上治療次數(P0.05)與血栓的發(fā)生始終存在顯著的關聯性。3、應用利妥西單抗,在調整模型前與血栓的發(fā)生無統(tǒng)計學意義(HR=0.48,95%CI:0.2-1.2,P0.05),在調整模型后存在顯著的統(tǒng)計學意義(HR=0.21,95%CI:0.1-0.5,P=0.001)。調整混雜因素前后,脾切除術、激素發(fā)生血栓的危險度略有變化,但P值始終大于0.05,結果無統(tǒng)計學意義。研究結論1、隨著年齡增加,ITP患者發(fā)生血栓的風險增高。2、合并多個心血管危險因素、既往血栓史及多次治療是ITP患者發(fā)生血栓的獨立危險因素。3、應用利妥昔單抗可以降低ITP患者的總血栓發(fā)生率,提示該藥可以作為一個預防血栓發(fā)生的保護性因素。
[Abstract]:Background and Objective Primary immune thrombocytopenia (ITP) is the most common hemorrhagic disease in clinic. Current treatment means to reduce platelet destruction and platelet production, with a view to achieving the goal of improving platelet count, preventing or reducing bleeding. In clinical practice, however, we observed that a few ITP patients complicated the venous thrombosis after or after the end of the treatment, and platelet counts were much lower in patients with thrombosis than in the normal range. The occurrence of the thrombus not only increases the pain of the patient, prolongs the hospitalization time, increases the treatment cost, but also improves the difficulty of selecting the subsequent treatment scheme, and falls into the dilemma of how to balance the thrombosis and reduce the risk of bleeding caused by coagulation therapy and thrombocytopenia. In recent years, some foreign studies reported that the incidence of thrombosis in ITP patients was higher than that of the general population, but there were no relevant reports in China. To this end, we analyzed 669 patients with ITP from Qilu Hospital of Shandong University using retrospective cohort study, and discussed the risk factors of influencing the occurrence of thrombus. Early intervention and adjustment of therapeutic regimen and treatment objectives to prevent or reduce thrombosis, reduce morbidity and mortality. Methods A total of 758 adults with ITP from Jan. 1, 2007 to July 30, 2016 were collected from Qilu Hospital of Shandong University from Jan. 1, 2007 to Jul. 30, 2016. Forty-four patients with ITP were excluded, and the total of 669 patients were included in the study. Among them 252 males and 417 females, the median age was 40 years. Including 166 cases of newly diagnosed ITP, 191 cases of persistent ITP and 312 cases of chronic ITP. Diagnostic criteria are based on the 2016 ITP China Expert Consensus. All patients included at least 1 ITP treatment during follow-up. Collect individual basic data of ITP patients included in cohort study through our medical record retrieval system, conduct telephone follow-up in sequence, record all thrombus events during follow-up period, conduct baseline survey on patient information, collect personal information of patients at the time of follow-up, Laboratory data and treatment. The thrombus was divided into thrombus group and no thrombus group according to whether there was thrombus in the follow-up period. A single-factor analysis of variance (continuity variable) and a card square test (categorical variable) were used to evaluate the incidence and cumulative incidence of ITP patients, and the Cox proportional risk regression model for cohort data was used to assess the effect of different risk factors on the occurrence of thrombus. Results 1. The incidence density of thrombus in ITP patients was 1. 28/ 100 (95% CI: 0. 83-1. 94), and arterial thrombosis and venous thrombosis were 0. 93/ 100 (95% CI: 0. 60-1. 43), 0. 42/ 100 person years (95% CI: 0. 15-1. 12). The incidence of arterial thrombosis in ITP patients (IR = 2.49, 95% CI: 1.52-3.89) was 18 times higher than that of 40-year-old (IR = 0. 13, 95% CI: 0. 05-0. 34), respectively. The incidence of venous thrombosis was 11 times higher, and the incidence of total thrombosis was 5 times higher. There was no significant correlation between the previous thrombus history 1 (P 0.01), 3 times and the number of treatments (P0.05) and the occurrence of thrombosis. There was a slight change in the risk of splenectomy and hormone thrombosis before and after the confounding factors, but the P value was always greater than 0.05. The results showed no statistical significance. Study conclusion 1: As age increases, there is an increased risk of thrombosis in ITP patients. 2. Multiple cardiovascular risk factors, past thrombus history and multiple treatments are independent risk factors for thrombosis in patients with ITP. It is suggested that the drug can be used as a protective factor for preventing thrombosis.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R558.2
本文編號：2259793
[Abstract]:Background and Objective Primary immune thrombocytopenia (ITP) is the most common hemorrhagic disease in clinic. Current treatment means to reduce platelet destruction and platelet production, with a view to achieving the goal of improving platelet count, preventing or reducing bleeding. In clinical practice, however, we observed that a few ITP patients complicated the venous thrombosis after or after the end of the treatment, and platelet counts were much lower in patients with thrombosis than in the normal range. The occurrence of the thrombus not only increases the pain of the patient, prolongs the hospitalization time, increases the treatment cost, but also improves the difficulty of selecting the subsequent treatment scheme, and falls into the dilemma of how to balance the thrombosis and reduce the risk of bleeding caused by coagulation therapy and thrombocytopenia. In recent years, some foreign studies reported that the incidence of thrombosis in ITP patients was higher than that of the general population, but there were no relevant reports in China. To this end, we analyzed 669 patients with ITP from Qilu Hospital of Shandong University using retrospective cohort study, and discussed the risk factors of influencing the occurrence of thrombus. Early intervention and adjustment of therapeutic regimen and treatment objectives to prevent or reduce thrombosis, reduce morbidity and mortality. Methods A total of 758 adults with ITP from Jan. 1, 2007 to July 30, 2016 were collected from Qilu Hospital of Shandong University from Jan. 1, 2007 to Jul. 30, 2016. Forty-four patients with ITP were excluded, and the total of 669 patients were included in the study. Among them 252 males and 417 females, the median age was 40 years. Including 166 cases of newly diagnosed ITP, 191 cases of persistent ITP and 312 cases of chronic ITP. Diagnostic criteria are based on the 2016 ITP China Expert Consensus. All patients included at least 1 ITP treatment during follow-up. Collect individual basic data of ITP patients included in cohort study through our medical record retrieval system, conduct telephone follow-up in sequence, record all thrombus events during follow-up period, conduct baseline survey on patient information, collect personal information of patients at the time of follow-up, Laboratory data and treatment. The thrombus was divided into thrombus group and no thrombus group according to whether there was thrombus in the follow-up period. A single-factor analysis of variance (continuity variable) and a card square test (categorical variable) were used to evaluate the incidence and cumulative incidence of ITP patients, and the Cox proportional risk regression model for cohort data was used to assess the effect of different risk factors on the occurrence of thrombus. Results 1. The incidence density of thrombus in ITP patients was 1. 28/ 100 (95% CI: 0. 83-1. 94), and arterial thrombosis and venous thrombosis were 0. 93/ 100 (95% CI: 0. 60-1. 43), 0. 42/ 100 person years (95% CI: 0. 15-1. 12). The incidence of arterial thrombosis in ITP patients (IR = 2.49, 95% CI: 1.52-3.89) was 18 times higher than that of 40-year-old (IR = 0. 13, 95% CI: 0. 05-0. 34), respectively. The incidence of venous thrombosis was 11 times higher, and the incidence of total thrombosis was 5 times higher. There was no significant correlation between the previous thrombus history 1 (P 0.01), 3 times and the number of treatments (P0.05) and the occurrence of thrombosis. There was a slight change in the risk of splenectomy and hormone thrombosis before and after the confounding factors, but the P value was always greater than 0.05. The results showed no statistical significance. Study conclusion 1: As age increases, there is an increased risk of thrombosis in ITP patients. 2. Multiple cardiovascular risk factors, past thrombus history and multiple treatments are independent risk factors for thrombosis in patients with ITP. It is suggested that the drug can be used as a protective factor for preventing thrombosis.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R558.2
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