Technical-Induced Hemolysis in Patients with Respiratory Failure Supported with Veno-Venous ECMO – Prevalence and Risk Factors

The aim of the study was to explore the prevalence and risk factors for technical-induced hemolysis in adults supported with veno-venous extracorporeal membrane oxygenation (vvECMO) and to analyze the effect of hemolytic episodes on outcome. This was a retrospective, single-center study that included 318 adult patients (Regensburg ECMO Registry, 2009–2014) with acute respiratory failure treated with different modern miniaturized ECMO systems. Free plasma hemoglobin (fHb) was used as indicator for hemolysis. Throughout a cumulative support duration of 4,142 days on ECMO only 1.7% of the fHb levels were above a critical value of 500 mg/l. A grave rise in fHb indicated pumphead thrombosis (n = 8), while acute oxygenator thrombosis (n = 15) did not affect fHb. Replacement of the pumphead normalized fHb within two days. Neither pump or cannula type nor duration on the first system was associated with hemolysis. Multiple trauma, need for kidney replacement therapy, increased daily red blood cell transfusion requirements, and high blood flow (3.0–4.5 L/min) through small-sized cannulas significantly resulted in augmented blood cell trauma. Survivors were characterized by lower peak levels of fHb [90 (60, 142) mg/l] in comparison to non-survivors [148 (91, 256) mg/l, p≤0.001]. In conclusion, marked hemolysis is not common in vvECMO with modern devices. Clinically obvious hemolysis often is caused by pumphead thrombosis. High flow velocity through small cannulas may also cause technical-induced hemolysis. In patients who developed lung failure due to trauma, fHb was elevated independantly of ECMO. In our cohort, the occurance of hemolysis was associated with increased mortality.     

Acute immune hemolysis induced by a degradation product of amphotericin B

We report here on an eight-year-old boy who first developed acute intravascular hemolysis following therapy with amphotericin B (AmB) and subsequently a delayed hemolytic transfusion reaction due to alloantibodies. Although there is as yet no evidence for metabolism of AmB in vivo, the hemolysis appeared to be the result of sensitization against a degradation product of the drug. The patient's serum contained a hemagglutinating IgM antibody that reacted with all red blood cells (RBC) tested in the presence of plasma obtained from patients receiving AmB (ex vivo antigen), but not in the presence of their urine, AmB itself, or with AmB-pretreated RBC. These findings indicate that the antibody was directed against a degradation product of AmB, presumably a trace metabolite, that has not yet been identified.     

Association of sex, age and ABO-Rh(D) type with unexpected antibodies among multitransfused thalassemia patients in Bikaner, Rajasthan, India

The thalassemia has become a sensitive issue for clinical and public health owing to the morbidity and mortality caused and potential risks associated with multiple transfusions. Here, a blood bank based cross sectional analytical study was carried out during the period of three months from January 2017 to March 2017, among transfusion dependent beta thalassemia major patients. ABO-Rh(D) blood grouping and screening for unexpected red cell antibodies (other than anti-A and anti-B antibodies) were performed on a Immucor Galileo Neo System (fully automated immunohematology analyzer). Out of 56 patients, 37 (66%) were males and 19 (34%) were females with a male to female ratio of 1.95:1. Two cases (3.6%) were detected positive by antibody screening. Alloimmunization was statistically analyzed on the basis of age, sex and subjects'' ABO-Rh blood group. This study underlines the need for unexpected antibody screening among thalassemic patients receiving blood transfusion therapy.     

Fatal hemolytic anemia associated with metformin: A case report

Introduction

Metformin is a widely prescribed biguanide antidiabetic drug that has been implicated as a cause of hemolytic anemia in three previous case reports. We report a case of rapidly fatal hemolysis that was temporally associated with the initiation of metformin treatment for diabetes. Clinicians need to be aware of this rare but potentially serious side effect of metformin.

Case presentation

A 56-year-old Caucasian man with type 2 diabetes mellitus was started on metformin to improve glycemic control. Shortly afterwards, he developed progressive fatigue, exertional dyspnea, cranberry-colored urine and jaundice. Laboratory studies showed severe hemolysis, with a drop in hemoglobin from 14.7 to 6.6 g/dl over 4 days, markedly elevated lactate dehydrogenase, bilirubin and reticulocyte counts, and a low haptoglobin level. A peripheral blood smear showed no schistocytes, and a direct Coombs test was positive for anti-IgG and negative for anti-C3. Despite corticosteroid treatment and transfusion of packed red blood cells, the patient developed increasing dyspnea, hypotension, further decline in hemoglobin to 3.3 g/dl, and fatal cardiorespiratory arrest 12 hours after admission.

Conclusion

The serologic findings in this case suggest an autoimmune hemolytic anemia, caused either by a drug-induced autoantibody or a warm autoantibody. Based on the temporal association with metformin and the lack of other clear precipitating causes, we propose that metformin-induced hemolysis with a drug-induced autoantibody is a strong possibility. This mechanism differs from a previously described case with a possible antibody to the erythrocyte-drug complex. It has been shown, however, that hemolysis may occur via multiple mechanisms from the same drug. Clinicians should consider the possibility of metformin-associated immune hemolytic anemia in patients with otherwise unexplained hemolysis.

     

An unusual sample of irregular anti-A1, probably causing an early delayed transfusion reaction

An unusual case of a 37 degrees C-active irregular anti-A1 is reported. Apparently consisting mainly of IgG, the antibody appeared in an A2B recipient only two days after massive transfusion of A1-cells in absence of previous transfusion. It was associated with severe hemolysis and renal failure which was reversed after exchange transfusion.     

Quality determinants of erythrocyte destined for transfusion.

An overview is given of a series of standard assays to evaluate the quality of red cell concentrates for transfusion. These are visual inspection, assessment of hemolysis, quantitation of 2,3-DPG and nucleotide levels (especially ATP) and evaluation of morphology. These parameters, relatively easy to measure, are main determinants of in vivo recovery after transfusion. In addition, some other assays are described, which should give more information about the function of red blood cells after transfusion. These assays include plasma-induced hemolysis, binding of annexin-V, deformability measurements and a rat model to judge oxygen delivery by human red blood cells (RBC). Especially in judging new protocols for the preparation of red cell products, involving e.g. improved additive solutions or pathogen inactivation methods, these quality parameters should not be compromised.     

The Prevalence of unexpected antibodies in Saudi's plasma prior blood transfusion and their association with clinical conditions: A cross-sectional study

Unexpected antibodies, also called irregular antibodies, are not known to exist in a person's serum before testing. This research aims to assess the prevalence of unexpected antibodies and their correlation with several clinical conditions. This cross-sectional prospective study, undertaken from June 2019 to June 2020, included ABO, Rh grouping, cross-matching, and antibody screening. Antibody identification was performed only on patients who tested positive in the screening test. From a total of 9764 participants who were screened for unexpected antibodies, 107 (1.1%) tested positive. The Rh blood group system antibodies were the most frequent, particularly anti-D. There was also a significant correlation between the unexpected antibodies and history of transfusion, pregnancy, and autoimmune diseases as P ≤ 0.05. The most prominent unexpected antibodies in the study belong to the Rh system (Anti-D). Moreover, as a result of the strong correlation between the unexpected antibodies as well as the history of transfusion, pregnancy, and autoimmune diseases, the highest safety criteria must be followed during the transfusion of blood to patients with these clinical conditions.     

The use of recombinant erythropoietin in the reduction of blood transfusion rates in craniosynostosis repair in infants and children

The vast majority of infants and children undergoing craniosynostosis correction receive a blood transfusion. The risks of blood transfusion include, but are not limited to, acute hemolytic reactions (approximately 1 of 250,000), human immunodeficiency virus (approximately 1 of 200,000), hepatitis B and C (approximately 1 of 30,000 each), and transfusion-related lung injuries (approximately 1 of 5000). This prospective, single-blinded, randomized study was undertaken to examine the safety and efficacy of preoperative single weekly dosing with erythropoietin (epoetin alfa) in reducing the rate of transfusion in infants and small children undergoing craniosynostosis repair. A total of 29 patients (<8 years) undergoing craniosynostosis repair were randomized into two groups: one received preoperative erythropoietin (600 U/kg) weekly for 3 weeks, and the other served as a control. All caregivers responsible for blood transfusions were blinded, and strict criteria for transfusion were established. A pediatric hematologist monitored both groups, and all patients received supplemental iron (4 mg/kg). Fourteen patients were randomized to receive erythropoietin, and eight of these 14 patients (57 percent) required transfusion (mean age, 17 months; mean weight, 10.1 kg). Of the six patients not requiring transfusion, three were younger than 12 months old (mean, 6 months). Fourteen of 15 patients (93 percent) in the control group (mean age, 13 months; mean weight, 9.3 kg) required a blood transfusion during the study. The only control patient not requiring transfusion was the eldest (5 years old). The difference between the two groups was statistically significant (Fisher's exact test = 0.03). The control group showed no change in hemoglobin levels from baseline to preoperative levels, but the erythropoietin group increased their average hemoglobin levels from 12.1 to 13.1 g/dl. There were no adverse effects noted among children receiving erythropoietin, nor were there any surgical complications. The authors conclude that the preoperative administration of erythropoietin significantly raised hemoglobin levels and reduced the need for a blood transfusion with craniosynostosis correction. More suggestions are made that may further reduce the need for blood transfusions, and a cost-benefit analysis is discussed.     

A case of hemolytic disease in a newborn associated with anti-Wra (WRIGHT) antibodies

A french woman delivered a third full-term male baby who had a strongly positive direct antiglobulin test. During the pregnancy and after the delivery, the woman had a negative irregular antibody screening test using standard red blood cell panels. The compatibility testing between the mother's serum and the father's red blood cells was strongly positive and the antibody was identified as an anti-Wra. The baby developed a mild hyperbilirubinemia and recovered without treatment. This child was probably responsible for his mother's immunization since the two previous children were Wra negative and the mother had no history of blood transfusion or abortion.     

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。     

55例自身血回收的临床应用探讨

总结和分析在心脏手术中进行自身血回收的经验。1999年1月－2000年3月,上海市胸科医院共进行自身血回收55例,其中男性27例,女性25例。年龄范围19－71岁,体表面积1．3－2．2m^2。本院应用的是意大利dideco公司生产的自身血回收机及其管道,不仅回收手术野血,而且回收体外循环管道内的残余血液。结果：55例患者均康复。自身血回收组患者的术后用血量和ICU时间与对照组相比,均显著降低（P＜0．05）。讨论：自身血回收技术除可减少患者术后用血量和ICU时间与对照组相比,均显著降低（P＜0．05）。讨论：自身回收技术除要减少患者术后用血、缓解血源紧张、避免血源性疾病外,还可提供以下有利条件：①为稀有血型患者提供手术保障;②可提供手术中发生意义大出血时的应急处理手段;③为外地患者就医和手术提供方便,并能减轻经济负担。     

Trauma to erythrocytes induced by long term in vitro pumping using a roller pump

The objective of this study is to investigate the impact of trauma on erythrocyte caused by long term in vitro pumping using roller pump. Ten bags of human blood (400 ml each) were provided by a local blood bank and they were divided into two groups with five bags in each group. Each blood bag was subject to pumping in a closed circuit, which was composed of silica gel tubes and a roller pump. Polystan and COBE pumps were used for the two groups, respectively. The blood was pumped for 16 h in vitro. Free hemoglobin (FHb), platelets (PLT), erythrocyte fragility (EF), and morphological analysis of erythrocytes observed under scanning electron microscope were measured to evaluate the impact of trauma on erythrocytes. A small amount of blood was collected for analysis before pumping, at the end of the 4th hour and then every 2 h till the end of the 16th hour. Some blood samples were also collected for electron microscope scanning before pumping and every 4 h during pumping. It was found that FHb and PLT linearly increased with the pumping time. There was a significant correlation between the two parameters (r=0.7745, p<0.001). The hemolysis indexes of the two groups were 0.296 and 0.3993 mg/L/h, respectively, with no significant difference. During the pumping process, EF changed slightly. The observation of scanning electron microscopy showed various deformed erythrocytes after pumping, including the distortion of cell membrane and the appearance of echinocytes, which increased with pumping time. This study demonstrated that long term pumping using roller pump not only caused the immediate rupture of red blood cells, i.e. the immediate hemolysis, but also caused sub-trauma to a large number of erythrocytes, which led to the delayed hemolysis. The change of erythrocyte morphology was the basis of the delayed hemolysis.     

Biophysical responses of red cell-membrane systems to very low concentrations of inorganic mercury

Changes in red blood cell size, deformability, and osmotic fragility are indicators of altered condition and/or altered regulatory processes at the whole cell and membrane levels. An agent, such as HgCl2, that brings about specific changes of this kind can therefore serve as a selective probe of such cell condition and regulatory state. Conversely, for a health-threatening agent "active" in this way, the cell-membrane responses serve to clarify the more fundamental bases of its toxicity, as well as to permit identification and characterization of its early and low-level actions on living systems. Taking advantage of recent advances in the technique of "resistive pulse spectroscopy," we present a coordinated study of these three interrelated biophysical properties for the interactions of HgCl2 with human red cells. We thereby are able to extend previous studies of this kind into domains of shorter time (instantaneous exposures), lower level exposures (down to 10(-9) M, well below the level of acute human toxicity), as well as to additional kinds of responses (e.g., "dynamic osmotic hemolysis"). For conditions ranging from 10(-4) to 10(-9) M in HgCl2, for instantaneous to 90-min-incubated exposures, for medium osmolarities from 120 to 300, the matrix of observed cell responses includes relative swelling as well as shrinkage, changes in deformability, and both enhancement of and protection against osmotic hemolysis. Some unexpected short-term effects of time and temperature of storage of blood cell stock samples, with respect to increasing and decreasing osmotic fragility, are also reported. These apparently disparate results are interpreted in terms of mercury interactions with cell and membrane SH groups, and a reasonable rationale is presented for most of the responses in terms of disruption of passive and active Na+-K+, gradient controls, plus interactions with cellular proteins.     

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。     

Incidence of unexpected red blood cell antibodies in the north of China

This study aimed to investigate the frequency of unexpected antibodies and evaluate the cumulative incidence of additional unexpected antibodies in Beijing. From January 1, 2011 to December 31, 2014, blood samples from 2,095 patients from 98 medical institutes in Beijing were sent to the Beijing Red Cross Blood Center for antibody identification. Of the unexpected antibodies, 29.5% were autoantibodies and 70.5% were alloantibodies. Anti-E was the most prevalent form of allo-antibodies (n = 445), accounting for 52.9% of the Rh system, followed by anti-M (76.6% of the MNS system) and then 142 cases of anti-C,e, 128 cases of anti-E,c, and 113 cases of anti-Lea. The cumulative incidences of additional antibodies were 0.55% (after the first transfusion), 1.82% (second time), 2.33% (fourth time), 3.07% (firth time), and 4.24% (seventh time). Antibody against the Rh system was the most prevalent, followed by antibodies against MNS, Lewis, Kidd, P1, and Duffy.     

Potential role of serum magnesium measurement as a biomarker of acute Falciparum malaria infection in adult patients

Serum magnesium concentration was measured in 80 adult patients (age range: 18–40 yr) presenting with acute, uncomplicated falciparum malaria infection and a control group of 20 age-matched, healthy individuals. The mean serum magnesium concentration in the patients was 1950.0 ±10.0 μg/dL. The control serum magnesium was 640.0±40.0 μg/dL. This represents an over threefold increase in serum magnesium levels above normal value, p<0.01. The key pathogenic event in acute falciparum malaria infection is the hemolysis of both infected and uninfected red blood cells. Therefore, the increased serum magnesium concentration might occur because of the hemolysis arising from erythrocytic merogony because red blood cells contain high amounts of magnesium. In conclusion, the increased serum magnesium has potential application as a biomarker of acute falciparum malaria infection in adults.     

Systematic review of role of polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus.

OBJECTIVE: To assess the role of polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus. DESIGN: Published studies of hepatitis C transmission were examined. Twenty nine studies with identified sources of hepatitis C infection who were tested for presence of hepatitis C RNA by polymerase chain reaction were reviewed, including studies of vertical transmission (n = 21), transmission after transplantation (n = 3), transfusion of blood components (n = 3), and needlestick exposure (n = 2). SUBJECTS: All patients identified in studies. RESULTS: A total of 2022 people who had been exposed to sources positive for antibody to hepatitis C were identified. Among 1148 people exposed to sources positive by polymerase chain reaction 148 cases of transmission occurred compared with no definite case among 874 people exposed to negative sources. Rates of transmission from positive sources were 6.2% for perinatal exposure, 6.1% after needlestick exposure, 78% after solid organ or bone marrow transplantation, and 83% after transfusion of blood components. Other factors influencing risk of vertical transmission were coinfection with HIV and level of hepatitis C viraemia. CONCLUSIONS: Negative results by polymerase chain reaction indicate an extremely low probability of transmission of hepatitis C from a person with antibody to hepatitis C.     

Effects of citrated whole blood transfusion in response to hemorrhage.

BACKGROUND AND PURPOSE: Standard treatment for massive hemorrhage in dogs is infusion of whole blood or of packed red blood cells with fresh frozen plasma if whole blood is not available. Although most whole blood is collected using a citrate-based anticoagulant, knowledge of citrate's relevant non-anticoagulant effects is not widespread. Citrate's anticoagulant activity is achieved through chelation of divalent metal cations (e.g., magnesium, calcium), which may exacerbate cardiovascular and metabolic insults attributable to hemorrhage. METHODS: Blood pressures, gas tensions, metabolites, and electrolytes; myocardial metabolites, pressures, and contractility; cardiac output; and left cranial descending and circumflex coronary artery flows were measured in 21 anesthetized dogs after hemorrhage was induced by collection of blood into a citrated reservoir to mean arterial pressure of 45 mm Hg for approximately 60 min (until arterial lactate concentration was 7.0 mmol/L), followed by a 1-h transfusion and 2 h of maintenance. RESULTS: Arterial ionized calcium concentration, total peripheral resistance, and myocardial function decreased significantly during hemorrhage. All aforementioned responses but myocardial function continued to decrease during the initial 20 min of transfusion, then began to recover. Total peripheral resistance and end-systolic elastance were the only factors significantly related to calcium concentration. CONCLUSION: Transfusion with citrated whole blood may significantly alter calcium concentration, negatively affecting myocardial and vascular function.