Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?

ABSTRACT

The recently reevaluated high prevalence of healthy carriers (1/2,000 in UK) of variant Creutzfeldt-Jakob Disease (v-CJD), whose blood might be infectious, suggests that the evolution of this prion disease might not be under full control as expected. After experimental transfusion of macaques and conventional mice with blood derived from v-CJD exposed (human and animal) individuals, we confirmed in these both models the transmissibility of v-CJD, but we also observed unexpected neurological syndromes transmissible by transfusion: despite their prion etiology confirmed through transmission experiments, these original cases would escape classical prion diagnosis, notably in the absence of detectable abnormal PrP with current techniques. It is noteworthy that macaques developed an original, yet undescribed myelopathic syndrome associating demyelination and pseudo-necrotic lesions of spinal cord, brainstem and optical tract without affecting encephalon, which is rather evocative of spinal cord disease than prion disease in human medicine. These observations strongly suggest that the spectrum of human prion diseases may extend the current field restricted to the phenotypes associated to protease-resistant PrP, and may notably include spinal cord diseases.     

Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. All components were capable of transmitting prion disease when donors were in the preclinical phase of infection, with the highest rates of infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<10⁶ WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post infection. However, in donor sheep (orally infected), the onset of detection of PrP^Sc in blood was much more variable, and generally later, compared to recipients (intravenous infection). This shows that the route and method of infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that blood transfusion can be a highly efficient route of transmission for prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.     

ABO血型正反定型及交叉配血实验在外科病人手术输血中应用

目的:探讨ABO血型正反定型及交叉配血实验在外科手术患者输血中的应用效果及影响因素。方法:选取我院自2017年2月-2019年2月收治的80例行ABO正反定型与交叉配血治疗的外科手术患者,记录ABO反定型与交叉配血不合的标本,使用2-Me处理被患者自身冷抗体凝集的红细胞,同时使用微柱凝胶法、凝聚胺法对血型不规则抗体以及特异性进行筛选和鉴定。分析ABO血型反定型不符合以及交叉配血不合的影响因素。结果:对正反定型完全无凝集反应的80例血清标本进行交叉配血实验,其中8例存在凝集反应,配血不合情况;导致外科手术患者输血中ABO血型反定型不符交叉配血不合的主要因素包括自身冷抗体、血型抗原性减弱、血型不规则抗体以及血型抗体效价减弱等。结论:ABO血型正反定型及交叉配血治疗中的患者中,大部分配血一致,少数的交叉配血不合,主要与自身冷抗体、血型抗原性减弱、血型不规则抗体以及血型抗体效价减弱等因素相关。     

White Blood Cell-Based Detection of Asymptomatic Scrapie Infection by Ex Vivo Assays

Prion transmission can occur by blood transfusion in human variant Creutzfeldt-Jakob disease and in experimental animal models, including sheep. Screening of blood and its derivatives for the presence of prions became therefore a major public health issue. As infectious titer in blood is reportedly low, highly sensitive and robust methods are required to detect prions in blood and blood derived products. The objectives of this study were to compare different methods - in vitro, ex vivo and in vivo assays - to detect prion infectivity in cells prepared from blood samples obtained from scrapie infected sheep at different time points of the disease. Protein misfolding cyclic amplification (PMCA) and bioassays in transgenic mice expressing the ovine prion protein were the most efficient methods to identify infected animals at any time of the disease (asymptomatic to terminally-ill stages). However scrapie cell and cerebellar organotypic slice culture assays designed to replicate ovine prions in culture also allowed detection of prion infectivity in blood cells from asymptomatic sheep. These findings confirm that white blood cells are appropriate targets for preclinical detection and introduce ex vivo tools to detect blood infectivity during the asymptomatic stage of the disease.     

输血内涵质量评价机制的建立与应用

目的 建立输血内涵质量评价机制,提高临床科学合理用血水平。方法 制定系统的评价方案,确定专项的评价标准,成立评审专家团队,依托数字化病案管理系统平台,分季度有重点地开展输血内涵质量评价。结果 输血评价平均成绩2014年143分,2013年139分,t小于0.01,差异有统计学意义;输血评价缺陷数,手术、非手术科室2014年比2013年分别下降了37.8%和14%;2012—2014年输血比例和人均用血量逐年下降;2013-2014年24小时大量用血人数和用血量分别下降40.9%、37.3%;二次手术用血人数持平,用血量下降14.1%。结论 建立输血内涵质量评价机制,实现全过程输血质量监控,提高了临床合理用血水平,保护稀缺血源,保障临床用血安全。

     

两种引流方式在单侧膝关节置换术后的前瞻性临床对比研究

目的:分析和比较单侧膝关节置换使用氨甲环酸术后两种不同引流方式(不夹管,夹管6小时后持续开放)对于手术的影响(出血量;并发症;康复锻炼等)。方法:根据纳入及排除标准,随机的将2015年6月-2017年6月在我院行单侧人工全膝关节置换的共计52例患者分为两组(不夹管组;夹管6小时后持续开放组)进行研究。每组各26例患者。分别观察和比较两组患者的各项术后资料:总引流量,总输血量,总失血量,小腿周径增幅,并发症等。同时对两组患者的膝关节功能进行评估和比较。结果:两组患者在年龄、性别组成、等一般临床资料的比较中未见显著差异(P0.05)。不夹管组的总失血量,总引流量,隐性失血量,输血量等指标显著高于夹管6小时组(P0.05)。术后两组患者在血栓,感染等并发症及小腿周径增幅等方面未见显著差异(P0.05)。结论:单侧膝关节置换术后早期进行夹管能够有效的减少总失血量、引流量等指标,更有利于患者术后的早期康复,而且不增加并发症的发生。     

No major change in vCJD agent strain after secondary transmission via blood transfusion

Background

The identification of transmission of variant Creutzfeldt-Jakob disease (vCJD) by blood transfusion has prompted investigation to establish whether there has been any alteration in the vCJD agent following this route of secondary transmission. Any increase in virulence or host adaptation would require a reassessment of the risk analyses relating to the possibility of a significant secondary outbreak of vCJD. Since there are likely to be carriers of the vCJD agent in the general population, there is a potential for further infection by routes such as blood transfusion or contaminated surgical instruments.

Methodology

We inoculated both wild-type and transgenic mice with material from the first case of transfusion associated vCJD infection.

Principal Findings

The strain transmission properties of blood transfusion associated vCJD infection show remarkable similarities to the strain of vCJD associated with transmission from bovine spongiform encephalopathy (BSE).

Conclusions

Although it has been hypothesized that adaptation of the BSE agent through secondary passage in humans may result in a greater risk of onward transmission due to an increased virulence of the agent for humans, our data presented here in two murine models suggest no significant alterations to transmission efficiency of the agent following human-to-human transmission of vCJD.     

不同比例新鲜冰冻血浆对大量输血患者凝血功能的影响

目的:探讨不同比例输注新鲜冰冻血浆对大量输血患者凝血功能的影响。方法:回顾性分析本院2018年1月至2018年12月收治的123例大量输血患者的临床资料,依据所输注新鲜冰冻血浆与红细胞比例不同,将其分为低比例组(1:3)、中比例组(1:2)、高比例组(1:1),比较三组患者输血前后凝血功能、血小板计数及电解质变化。结果:输血后,三组患者FIB较输血前明显降低,而PT、APTT较输血前显著升高(P0.05),高比例组PT和APTT明显低于中比例组和低比例组,FIB、血小板均高于中比例组和低比例组(P0.05),电解质水平优于低比例组和中比例组(P0.05)。结论:在大量输血时,提高血浆与红细胞比例有利于改善大量输血患者凝血功能障碍,减少电解质紊乱。     

血浆置换及血小板输注治疗特发性血小板减少性紫癜疗效观察

摘要 目的：探究血浆置换及血小板输注治疗特发性血小板减少性紫癜疗效。方法：选择2016年2月至2019年1月于我院接受治疗的60例特发性血小板减少性紫癜患者为研究对象,按照其选择治疗方式的差异将其分为血小板输注组（20例）及血浆置换（Plasma exchange,PE）组（40例）,对比两组患者治疗有效率、治疗前后血细胞计数变化情况以及治疗中各类不良反应发生情况。结果：血小板输注组患者治疗显效数10例,有效数6例,总有效率80.00 %,PE组患者治疗显效数27例,有效数12例,治疗总有效率97.50 %,PE组治疗总有效率高于血小板输注组（P<0.05）。与治疗前比较,PE组患者的PLT、RBC计数和Hb水平出现了明显的升高,WBC计数出现明显的下降（P<0.05）,血小板输注组PLT、RBC计数和Hb水平也出现明显升高,WBC计数水平出现下降（P<0.05）,但组间比较显示治疗后PE组患者上述指标均优于血小板输注组（P<0.05）。血小板输注组患者不良反应总发生人数为4人,不良反应总发生率为20.00 %,PE组总不良反应发生人数3人,不良反应总发生率为7.50 %,PE组不良反应总发生率明显低于血小板输注组（P<0.05）。结论：血血浆置换及血小板输注治疗均对特发性血小板减少性紫癜具有较好的治疗效果,能够显著改善患者血细胞计数异常情况,但血浆置换治疗安全性更高。     

自身免疫性溶血性贫血(AIHA)患者的不同输血方法与效果

目的:探讨不同输血方法治疗自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)的效果。方法:2017年1月-2018年12月选择在本院血液科诊治的64例自身免疫性溶血性贫血患儿,根据输血方法的不同分为观察组与对照组,各32例。观察组给予洗涤红细胞输注治疗,对照组给予非洗涤红细胞(悬浮红细胞)输注治疗,记录两组输血效果。结果:治疗后4 w观察组的总有效率显著高于对照组(100.0%vs.87.5%,P0.05)。两组治疗后4 w的红细胞计数与血红蛋白都显著高于治疗前,且观察组显著高于对照组(P0.05)。观察组的吸氧、机械通气、住院时间都显著少于对照组(P0.05)。观察组治疗过程的过敏反应、发热反应、紫癜等不良反应发生率显著低于对照组(3.1%vs. 21.9%,P0.05)。结论:洗涤红细胞输注治疗自身免疫性溶血性贫血患儿能促进机体红细胞计数与血红蛋白恢复正常,减少不良反应的发生,提高治疗效果与促进患儿康复。     

洗涤红细胞输注在早产儿贫血中的应用价值分析

目的:分析洗涤红细胞输注在早产儿贫血中的应用价值。方法:选取2015年10月~2017年11月我院需要输血治疗的贫血早产儿107例,均具有《早产儿管理指南》中的输血指征。采用随机数字表法将患儿分为两组,对照组53例输注红细胞悬浮液,观察组54例输注洗涤红细胞。比较两组患儿输血情况、治疗前后血液流变学相关指标、亚硝基硫醇(RSNO)、超氧化物歧化酶(SOD)和苯二醛(MDA)水平的变化及并发症的发生情况。结果:两组患儿输血量、输血次数、输血后血细胞压积和输血后血红蛋白水平比较均无统计学差异(P>0.05)。输血前,两组患儿全血高切黏度、全血低切黏度、血浆黏度、RSNO、SOD和MDA水平比较无统计学差异(P>0.05);输血后,两组全血高切黏度、全血低切黏度及血浆黏度均较输血前显著下降,且观察组以上指标均显著低于对照组(P<0.05);对照组患儿RSNO、SOD水平显著下降,MDA水平显著升高(P<0.05),观察组患儿以上指标均无显著变化(P>0.05)。观察组患儿呼吸暂停和院内感染的发生率显著低于对照组(P<0.05),两组脑白质损伤及颅内出血的发生率比较均无统计学差异(P>0.05)。结论:洗涤红细胞输注可显著改善贫血早产儿的血液流变学,降低应激反应及呼吸暂停和院内感染的发生率,且输血量、输血次数、输血后血细胞压积和输血后血红蛋白水平与输注红细胞悬浮液相当。     

Prospective investigation of transfusion transmitted infection in recipients of over 20 000 units of blood. TTI Study Group

ObjectivesTo follow up recipients of 20 000 units of blood to identify any transmissions of infections through blood transfusion.DesignFollow up study of recipients of transfusion.Setting 22 hospitals in north London.ParticipantAdult patients who had recently been transfused.Results9220 patients were recruited, and 5579 recipients of 21 923 units of blood were followed up. No transfusion transmitted infections were identified. The incidence of transfusion transmitted infections was 0 in 21 043 units (95% confidence interval for risk 0 to 1 in 5706 recipients) for hepatitis B; 0 in 21 800 units (0 to 1 in 5911 recipients) for hepatitis C; 0 in 21 923 units (0 to 1 in 5944 recipients) for HIV; and 0 in 21 902 units (0 to 1 in 5939 recipients) for human T cell leukaemia/lymphoma virus. Three patients acquired hepatitis B during or after hospital admission but not through transfusion; 176 (3%) had pre-existing hepatitis B infection. Sixteen (0.29%) patients had hepatitis C, and five (0.09%) had human T cell leukaemia/lymphoma virus.ConclusionsThe current risk of transfusion transmitted infections in the United Kingdom is very small, though hospital acquired infections may arise from sources other than transfusion. A considerable proportion of patients have pre-existing infections.     

神经外科手术中大量输血患者红细胞压积及凝血状态研究

摘要 目的：探讨神经外科手术中大量输血患者采用不同输血方法对红细胞压积及凝血状态的影响。方法：选择2017年2月至2019年12月在本院进行手术的神经外科患者104例,根据随机数字表法把患者分为观察组与对照组各52例。观察组给予自体输血治疗,对照组给予异体输血治疗,记录和比较患者红细胞压积及凝血状态变化情况。结果：所有患者都完成手术,两组的手术时间、术中输血量与补液量对比差异无统计学意义(P>0.05)。两组术后1 d的红细胞压积低于术前1 d(P<0.05),组间手术前后对比差异都无统计学意义(P>0.05)。两组术后1 d的凝血酶原时间(prothombin time,PT)与活化部分凝血活酶时间(activited partial thomboplastin time,APTT)值高于术前1 d(P<0.05),组间手术前后对比差异都无统计学意义(P>0.05)。观察组输血后7 d的感染发生率为1.9 %,显著低于对照组的15.4 %(P<0.05)。结论：神经外科手术中大量输血中采用自体输血并不会影响患者的红细胞压积与凝血状态,不会增加输血难度与输血量,但能有效减少感染等不良反应。     

基于探索性因子分析的输血科人员胜任力模型构建

??????? 目的 构建医院输血科室人员胜任力模型。方法 采用横断面问卷调查收集数据,采用探索性因子分析对胜任力模型内部结构进行分析。 结果 医院输血科室人员胜任力模型包含了6个公因子和24个特征指标,维度分别为：专业技能、个人特质、能力素质、防控差错、遵守规范和职业素养。结论 构建医院输血科室人员胜任力模型可以极大的丰富医院人力资源管理策略,在甄选、培训和绩效测评输血科室人员等方面具有积极的现实意义。     

限制性液体复苏对多发性骨折合并创伤失血性休克患者凝血功能、心肌损害指标及预后的影响

目的:探讨限制性液体复苏对多发性骨折合并创伤失血性休克患者凝血功能、心肌损害指标及预后的影响。方法:选取我院收治的多发性骨折合并创伤失血性休克患者77例,分为研究组(n=39)、对照组(n=38),对照组给予常规液体复苏,研究组给予限制性液体复苏,比较两组患者凝血功能、心肌损害指标、输液量、失血量、输血量、并发症发生率及病死率。结果:研究组的输液量、失血量、输血量均少于对照组(P0.05)。与复苏前相比,两组患者复苏1 h后凝血酶原时间(PT)、凝血活酶时间(APTT)、凝血酶时间(TT)均延长,且研究组长于对照组(P0.05);两组患者复苏1 h后肌酸激酶(CK)、肌酸激酶-同工酶(CK-MB)、肌钙蛋白T(CTnT)水平均下降,且研究组低于对照组(P0.05)。研究组复苏期间并发症发生率、病死率均低于对照组(P0.05)。结论:限制性液体复苏治疗多发性骨折合并创伤失血性休克患者,可改善患者凝血功能和预后,降低并发症发生率,同时还可减轻心肌损害。     

血栓弹力图指导食管癌患者临床输血的价值及其与常规凝血实验检测指标的相关性分析

目的:探讨血栓弹力图(TEG)指导食管癌患者临床输血的价值及其与常规凝血实验检测指标的相关性。方法:选取2017年1月-2019年3月在我院收治的食管癌手术治疗需输血的99例患者作为研究对象,将99例患者随机分为常规凝血功能检测组和TEG组,常规凝血功能检测组采用常规凝血实验检查结果指导输血,TEG组采用TEG检查结果指导输血,对比两组输血前后的常规凝血实验检测指标以及临床用血量,对比TEG组输血前后的TEG指标,分析TEG指标与常规凝血实验检测指标的相关性。结果:两组患者输血前凝血四项和血小板计数(PLT)差异无统计学意义(P>0.05),输血后两组活化凝血酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)均有不同程度的改善(P<0.05),TEG组PT、TT较常规凝血功能检测组低(P<0.05);输血后,TEG组患者凝血反应时间(R值)、血凝块形成时间(K值)较输血前降低,最大血凝块强度(MA值)、凝血综合指数(CI值)升高,凝血形成速率(Angle角)增大,差异有统计学意义(P<0.05);Pearson相关性分析结果显示,R值与APTT呈正相关(P<0.05),K值与PLT呈负相关,与FIB呈正相关(P<0.05),Angle角、MA值、CI值与FIB、PLT呈正相关(P<0.05);TEG组新鲜冰冻血浆、冷沉淀输注量少于常规凝血功能检测组,差异有统计学意义(P<0.05)。结论:TEG能更好地指导食管癌手术患者各种血液成分的合理输注,有效改善凝血异常情况,减少输血用量,TEG指标与常规凝血实验检测指标存在一定的相关性。     

Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal,population based study

Objective To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer''s disease in later life.Design Prospective, population based study.SettingPopulations of Kuopio and Joensuu, eastern Finland.ParticipantsParticipants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years'' follow up, a total of 1449 (73%) participants aged 65-79 took part in the re-examination in 1998.Results People with raised systolic blood pressure (⩾160 mm Hg) or high serum cholesterol concentration (⩾6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer''s disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer''s disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer''s disease.Conclusion Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer''s disease in later life.

What is already known on this topic

Vascular risk factors may play an important part as risk factors for Alzheimer''s diseaseNo population based studies have evaluated prospectively the impact of both midlife blood pressure and cholesterol concentration in both men and women on the subsequent development of Alzheimer''s disease

What this study adds

Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increased the risk of Alzheimer''s disease in later lifeRaised systolic blood pressure and hypercholesterolaemia may have a role in the pathogenesis of Alzheimer''s disease; more emphasis should be placed on identification and appropriate treatment of these conditions     

RhD正定型及不规则抗体筛查的临床意义分析

目的:探究RhD正定型及不规则抗体筛查在预防临床输血不良反应中的应用价值及临床意义。方法:回顾性分析2010年至2011年、2017年至2018年于首都医科大学附属北京同仁医院输血科实施输血治疗的1892例患者,将2010年至2011年未实施Rh D正定型及不规则抗体筛查时输血治疗的901例患者设为对照组,将2017年至2018年实施RhD正定型及不规则抗体筛查后输血治疗的991例患者设为观察组。对比两组输血不良反应发生率,分析不同血液成分、不同性别、不同年龄输血不良反应发生率,并就2017年、2018年受血者RhD正定型及不规则抗体特异性分布进行罗列。结果:(1)2010年输血不良反应发生率为3.49%,2011年为2.40%,2017年为1.33%,2018年为0.74%,对照组不良反应发生率明显高于观察组(P<0.05)。(2)观察组不同血液成分输血的不良反应发生率显著低于对照组(P<0.05)。(3)两组不同年龄和性别输血不良反应发生率对比差异无统计学意义(P>0.05)。(4)观察组共检出20例RhD正定型及不规则抗体阳性患者,其中抗-M型5例,抗-D型3例,抗-E型2例,抗-C型2例,抗-P型2例,抗-LEa型1例,抗-LEb型1例,抗-JKa型1例,抗-N型1例,抗-H型1例,非特异性抗体1例。结论:RhD正定型及不规则抗体筛查能够显著降低输血不良反应发生率,有助于提高配血的准确性,提高输血治疗的安全性。     

Clinical course of hepatitis C virus during the first decade of infection: cohort study

ObjectiveTo determine the clinical course of hepatitis C virus in the first decade of infection in a group of patients who acquired their infections on a known date.DesignCohort study.SettingClinical centres throughout the United Kingdom.Participants924 transfusion recipients infected with the hepatitis C virus (HCV) traced during the HCV lookback programme and 475 transfusion recipients who tested negative for antibodies to HCV (controls).ResultsAll cause mortality was not significantly different between patients and controls (Cox''s hazards ratio 1.41, 95% confidence interval 0.95 to 2.08). Patients were more likely to be certified with a death related to liver disease than were controls (12.84, 1.73 to 95.44), but although the risk of death directly from liver disease was higher in patients than controls this difference was not significant (5.78, 0.72 to 46.70). Forty per cent of the patients who died directly from liver disease were known to have consumed excess alcohol. Clinical follow up of 826 patients showed that liver function was abnormal in 307 (37.2%), and 115 (13.9%) reported physical signs or symptoms of liver disease. Factors associated with developing liver disease were testing positive for HCV ribonucleic acid (odds ratio 6.44, 2.67 to 15.48), having acquired infection when older (at age ⩾ 40 years; 1.80, 1.14 to 2.85), and years since transfusion (odds ratio 1.096 per year, 1.00 to 1.20). For patients with severe disease, sex was also significant (odds ratio for women 0.38, 0.17 to 0.88). Of the 362 patients who had undergone liver biopsy, 328 (91%) had abnormal histological results and 35 (10%) of these were cirrhotic.ConclusionsHepatitis C virus infection did not have a great impact on all cause mortality in the first decade of infection. Infected patients were at increased risk of dying directly from liver disease, particularly if they consumed excess alcohol, but this difference was not statistically significant.

What is already known on this topic

The clinical course of HCV infection is unclear because most information has come from studies of patients with established chronic liver diseaseStudies that follow patients from disease onset are rare because most HCV infections are asymptomatic

What this study adds

HCV infection does not have a great impact on all cause mortality in the first decade of infectionInfected patients have an increased risk of dying from a liver related cause, particularly if they consumed excess alcohol     

Improving Decision Making for Massive Transfusions in a Resource Poor Setting: A Preliminary Study in Kenya

BackgroundThe reality of finite resources has a real-world impact on a patient’s ability to receive life-saving care in resource-poor settings. Blood for transfusion is an example of a scarce resource. Very few studies have looked at predictors of survival in patients requiring massive transfusion. We used data from a rural hospital in Kenya to develop a prediction model of survival among patients receiving massive transfusion.MethodsPatients who received five or more units of whole blood within 48 hours between 2004 and 2010 were identified from a blood registry in a rural hospital in Kenya. Presenting characteristics and in-hospital survival were collected from charts. Using stepwise selection, a logistic model was developed to predict who would survive with massive transfusion versus those who would die despite transfusion. An ROC curve was created from this model to quantify its predictive power.ResultsNinety-five patients with data available met inclusion criteria, and 74% survived to discharge. The number of units transfused was not a predictor of mortality, and no threshold for futility could be identified. Preliminary results suggest that initial blood pressure, lack of comorbidities, and indication for transfusion are the most important predictors of survival. The ROC curve derived from our model demonstrates an area under the curve (AUC) equal to 0.757, with optimism of 0.023 based on a bootstrap validation.ConclusionsThis study provides a framework for making prioritization decisions for the use of whole blood in the setting of massive bleeding. Our analysis demonstrated an overall survival rate for patients receiving massive transfusion that was higher than clinical perception. Our analysis also produced a preliminary model to predict survival in patients with massive bleeding. Prediction analyses can contribute to more efficient prioritization decisions; these decisions must also include other considerations such as equity, acceptability, affordability and sustainability.