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Anti-M, a frequently encountered antibody of the MNS blood group system, is commonly regarded as a naturally occurring saline agglutinin that can occasionally exhibit clinically significant behaviour. Particularly when reactive at 37°C or during the antiglobulin phase, it can complicate pretransfusion testing and patient management in the blood bank. Three distinct cases (2 males. 1 female) in varying clinical scenarios, ranging from surgery to acute coronary syndrome, are described. The present cases presented discrepancies in blood grouping and compatibility testing, highlighting the challenges posed by the presence of Anti-M antibodies that react at or above room temperature and during the antiglobulin phase, thus defying the usual expectations. It is imperative to provide antigen-negative red cells and those that are compatible by an Indirect Antiglobulin Test (IAT) when Anti-M is reactive at 37°C to ensure safe transfusion. Hence, there is a need to underscore the potential clinical implications in transfusion medicine, as well as the nuances of detecting, identifying, and managing the presence of Anti-M antibodies in patients requiring transfusion.

A 48-year-old female presented to the emergency department with severe fatigue. Admission laboratory test results were hemoglobin 6.6 g/dL, platelet count 287,000/μL, and white blood cell count 25,200/μL. Lactate dehydrogenase was elevated at 898 U/L, haptoglobin was markedly decreased (< 31 mg/dL), indirect bilirubin was elevated (5.3 mg/dL), and the absolute reticulocyte count was low at 0.0050/μL. A sample was sent to the immunohematology reference laboratory. The direct antiglobulin test immunoglobulin G was negative; C3 was 1+. All cells were reactive at immediate spin phase, indirect antiglobulin testing (IAT) with polyethylene glycol, with low ionic strength saline, neat, prewarm, and in the solid phase. All cells were nonreactive at IAT-ficin. Additional testing included a cold antibody titer that was 1:4096 and thermal amplitude studies demonstrating reactivity of 2+ at 37°C. These results were consistent with a clinically significant anti-Pr and cold agglutinin disease (CAD). Although rituximab is effective in autoimmune hemolytic anemia, this may take weeks. The patient was treated with pegcetacoplan, a pegylated peptide that targets C3 inhibiting hemolysis. The patient was discharged on day 29 with a hemoglobin of 8 g/dL. This is a report of one of the first patients successfully treated with pegcetacoplan for CAD. [ABSTRACT FROM AUTHOR]

Background: Cold agglutinins (CAs) in blood samples can cause a reversible agglutination of red blood cell (RBC) which result in an incorrect complete blood count (CBC). So, it is important to explore new simple and feasible treatment conditions for clinical work. Methods: The CAs group included 32 samples with CAs. The parameters of CBC at room temperature or after prewarming at 37°C or 41°C for different time periods were compared. The consistency and correlation of those parameters were analyzed. The morphology of erythrocytes in the CAs group was observed manually. The control group included 45 samples without CAs and prewarmed at 37°C or 41°C for different time periods. The differences were also analyzed. Results: CAs have a significant effect on CBC. After prewarming at 37°C or 41°C the interferences are all corrected. Consider prewarming at 37°C for 120 minutes as the standard procedure. The consistency and correlation analysis showed there was no statistical difference between the results of each subgroup and standard group, except the MCHC of group 41°C 10 minutes. The correlation of parameters between all subgroups and the standard group is satisfied. Microscopic examination showed no RBC aggregation or fragmentation after prewarming at 41°C or 37°C. According to the maximum bias requirements for expert performance in Validation, Verification, and Quality Assurance of Automated Hematology Analyzers, 2nd Edition (CLSI H26-A2), the differences in over-all results in control group are negligible. Conclusions: The 41°C 2 minutes prewarming method is a rapid and effective way for treating samples with CAs. It is an efficient way to obtain more reliable CBC results, without specific instruments. [ABSTRACT FROM AUTHOR]

Overview: The use of extra-corporeal membrane oxygenation (ECMO) therapy to treat severe COVID-19 patients with acute respiratory failure is increasing worldwide. We reported herein the use of veno-venous ECMO in a patient with cold agglutinin haemolytic anaemia (CAHA) who suffered from severe COVID-19 infection. Description: A 64-year-old man presented to the emergency department (ED) with incremental complaints of dyspnoea and cough since one week. His history consisted of CAHA, which responded well to corticosteroid treatment. Because of severe hypoxemia, urgent intubation and mechanical ventilation were necessary. Despite deep sedation, muscle paralysis and prone ventilation, P/F ratio remained low. Though his history of CAHA, he still was considered for VV-ECMO. As lab results pointed to recurrence of CAHA, corticosteroids and rituximab were started. The VV-ECMO run was short and rather uncomplicated. Although, despite treatment, CAHA persisted and caused important complications of intestinal ischemia, which needed multiple surgical interventions. Finally, the patient suffered from progressive liver failure, thought to be secondary to ischemic cholangitis. One month after admission, therapy was stopped and patient passed away. Conclusion: Our case report shows that CAHA is no contraindication for VV-ECMO, even when both titre and thermal amplitude are high. Although, the aetiology of CAHA and its response to therapy will determine the final outcome of those patients. [ABSTRACT FROM AUTHOR]

The term "cold agglutinin (CA)" refers to a group of disorders caused by anti-erythrocyte autoantibodies that preferentially bind RBCs at cold temperatures (4°C-18°C). CAs contribute to 10 to 15% of autoimmune hemolytic anemia. We report a case of CAs diagnosed intraoperatively during emergency mitral valve replacement. [ABSTRACT FROM AUTHOR]

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive IgM antibodies leading to complement-mediated hemolysis. While CAD-associated venous thromboembolism is recognized, its role in arterial thromboembolic events, particularly ischemic stroke, is poorly defined. We report an 84-year-old woman who developed acute onset upper left extremity weakness following exposure to sub-zero temperatures. She had a history of similar transient episodes during cold seasons and recurrent anemia. Physical examination revealed decreased muscle strength in the upper left extremity (Grade 4+ out of 5) and scleral icterus. Laboratory findings showed normocytic anemia, elevated reticulocytes, high lactate dehydrogenase, indirect hyperbilirubinemia, and undetectable haptoglobin levels. Peripheral smear showed erythrocyte agglutination. Direct antiglobulin test was positive for C3d and IgM, confirming CAD. Vascular imaging showed significant atherosclerotic disease with near-occlusive (>80%) stenosis of the right internal carotid artery. The patient's transient ischemic attacks were attributed to compromised cerebral perfusion due to severe carotid artery stenosis, exacerbated by anemia from cold-induced hemolysis in CAD. Cold exposure precipitated hemolysis, leading to acute anemia and increased blood viscosity, further reducing cerebral blood flow and oxygen delivery. Spontaneous resolution of symptoms upon rewarming supported the role of CAD in her neurological deficits. This case underscores the potential for CAD to induce neurological deficits in patients with significant carotid artery stenosis. Clinicians should consider CAD as a contributory factor in patients presenting with transient neurological deficits precipitated by cold exposure, especially when significant arterial stenosis is present., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gonçalves et al.)

Introduction: Autoimmune hemolytic anemia (AIHA) is considered a chronic disease, with an overall good prognosis. However, recent reports indicate pre‐mature mortality. Causes of death have not been evaluated previously. Methods: In a nationwide setting, we identified all patients with warm type AIHA or cold agglutinin disease (CAD), and age–sex‐matched comparators from Denmark, 1980–2016. We estimated overall survival and cause‐specific mortality from anemia, infection, cardiovascular causes, hematological or solid cancer, bleeding, or other causes, using cumulative incidence proportions. Results: We identified 1460 patients with primary AIHA, 1078 with secondary AIHA, 112 with CAD, and 130 801 comparators. One‐year survival and median survival were, 82.7% and 9.8 years for primary AIHA, 69.1% and 3.3 years for secondary AIHA, and 85.5% and 8.8 years for CAD. Prognosis was comparable to the general population only in patients with primary AIHA below 30 years. In all other age and subgroups, the difference was considerable. Cumulated cause‐specific mortality at 1 year was increased among patients versus comparators. Discussion: All groups of autoimmune hemolytic anemia are associated with increased overall and cause‐specific mortality compared to the general population. This probably reflects unmet needs in both treatment and follow‐up programs. [ABSTRACT FROM AUTHOR]

Autoimmune hemolytic anemia (AIHA) may be the first manifestation of systematic lupus erythematosus (SLE). Antierythrocyte antibodies in SLE are mainly warm-type Immunoglobulin G (IgG), but mixed-type AIHA is also reported. Cold antibody-mediated hemolytic anemia is extremely rare in SLE. Only a few cases have been reported in the literature. A 37-year-old pregnant woman presented with features of hemolytic anemia and was later diagnosed as an SLE case. Although rare, a new case report highlights that cold-type autoimmune hemolytic anemia may be an early manifestation of SLE.

Objectives: The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41 °C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC) 370 g/L, in the presence of cold agglutinins. Methods: In this study, 60 blood samples (group 1) with the MCHC 370 g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). Results: The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. Conclusions: The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370 g/L.

Infection by SARS-CoV-2 virus is not solely limited to the common clinical presentation of acute respiratory distress syndrome, mainly because a wide spectrum of clinical manifestation has been observed. These presentations include, but are not limited to, neurological, cardiovascular, thromboembolic, hematologic, and autoimmune presentations. Within this wide spectrum, cases of autoimmune hemolytic anemia due to SARS-CoV-2 infection are rising. This is why primary care physicians should be ready to identify this clinical entity appropriately. [ABSTRACT FROM AUTHOR]

Roth spots can occur as ophthalmological manifestations of systemic pathologies that compromise the retinal capillary endothelium. A case report of retinopathy due to hemolytic anemia secondary to Epstein–Barr virus is presented. Given the clinical picture, several differential diagnoses were initially considered causing Roth spots that is why a brief review of the literature is carried out to raise awareness of the diverse pathologies that can be associated with the presence of Roth spots to provide timely referrals.

Cold agglutinins are autoantibodies that can cause primary hemolytic anemia and RBC agglutination syndrome. Secondary agglutination of RBCs may be found in hypothermia, as well as in cancers, infections, and traumatic injuries. This report presents the case of a 37-year-old man who suffered multiple injuries in a motorcycle accident. On admission, the patient's laboratory tests showed a high concentration of cold agglutinins associated with low RBC count, hemoglobin, and hematocrit, and elevated mean corpuscular hemoglobin and mean corpuscular volume. Intravenous immunoglobulin treatment was effective at reversing the abnormal blood parameters to normal. Unlike acute blood loss, which typically manifests with normal hemoglobin and hematocrit levels initially due to proportional loss of plasma and red cells, the presence of cold agglutinins can lead to abnormal agglutination and sequestration of RBCs, with low hemoglobin and hematocrit. The findings of this case report highlight the importance of recognizing cold agglutinins in trauma patients to avoid misdiagnosis and misinterpretation of laboratory results., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patel et al.)

IntroductionCryoproteins, such as cryoglobulins, cryofibrinogens and cold agglutinins, precipitate at low temperatures or agglutinate erythrocytes and dissolve again when warmed. Their pathogenetic and diagnostic importance in cold urticaria (ColdU) is unclear. In this study, we aimed to characterize the prevalence of cryoproteins in patients with ColdU.MethodsWe conducted 3 analyses: i) a systematic review and meta-analysis of published data using an adapted version of the Joanna Briggs Institute’s critical appraisal tool for case series, ii) a retrospective analysis of 293 ColdU patients treated at our Urticaria Center of Reference and Excellence (UCARE) from 2014 to 2019, and iii) a prospective observational study, from July 2019 to July 2020, with 49 ColdU patients as defined by the EAACI/GA2LEN/EDF/UNEV consensus recommendations.ResultsOur systematic review identified 14 relevant studies with a total of 1151 ColdU patients. The meta-analyses showed that 3.0% (19/628), 1.1% (4/357) and 0.7% (2/283) of patients had elevated levels of cryoglobulins, cryofibrinogens and cold agglutinins, respectively. Our retrospective analyses showed that cryoproteins were assessed in 4.1% (12/293) of ColdU patients. None of 9 ColdU patients had cryoglobulins, and one of 5 had cold agglutinins. In our prospective study, none of our patients had detectable cryoglobulins (0/48) or cryofibrinogens (0/48), but 4.3% (2/46) of patients had cold agglutinins (without any known underlying autoimmune or hematological disorder).ConclusionOur investigation suggests that only very few ColdU patients exhibit cryoproteins and that the pathogenesis of ColdU is driven by other mechanisms, which remain to be identified and characterized in detail.

Introduction: Cryoproteins, such as cryoglobulins, cryofibrinogens and cold agglutinins, precipitate at low temperatures or agglutinate erythrocytes and dissolve again when warmed. Their pathogenetic and diagnostic importance in cold urticaria (ColdU) is unclear. In this study, we aimed to characterize the prevalence of cryoproteins in patients with ColdU. Methods: We conducted 3 analyses: i) a systematic review and meta-analysis of published data using an adapted version of the Joanna Briggs Institute's critical appraisal tool for case series, ii) a retrospective analysis of 293 ColdU patients treated at our Urticaria Center of Reference and Excellence (UCARE) from 2014 to 2019, and iii) a prospective observational study, from July 2019 to July 2020, with 49 ColdU patients as defined by the EAACI/GA2LEN/EDF/UNEV consensus recommendations. Results: Our systematic review identified 14 relevant studies with a total of 1151 ColdU patients. The meta-analyses showed that 3.0% (19/628), 1.1% (4/357) and 0.7% (2/283) of patients had elevated levels of cryoglobulins, cryofibrinogens and cold agglutinins, respectively. Our retrospective analyses showed that cryoproteins were assessed in 4.1% (12/293) of ColdU patients. None of 9 ColdU patients had cryoglobulins, and one of 5 had cold agglutinins. In our prospective study, none of our patients had detectable cryoglobulins (0/48) or cryofibrinogens (0/48), but 4.3% (2/46) of patients had cold agglutinins (without any known underlying autoimmune or hematological disorder). Conclusion: Our investigation suggests that only very few ColdU patients exhibit cryoproteins and that the pathogenesis of ColdU is driven by other mechanisms, which remain to be identified and characterized in detail. [ABSTRACT FROM AUTHOR]

Secondary cold agglutinin autoimmune hemolytic anemia (AIHA) occurs most commonly due to infectious causes like Mycoplasma pneumonia and, more rarely, Epstein-Barr virus(EBV). Here we present a case of a 69-year-old female presenting with generalized weakness, who was found to have cold agglutinin hemolytic anemia. She unfortunately experienced some of the most severe complications of the disease including encephalopathy, hypoxia, and dry necrosis of peripheral extremities. Further investigation revealed an EBV infection, the rarest infectious cause of cold AIHA. She was started on steroids, the mainstay of treatment, but continued to worsen over the course of her extensive stay in the intensive care unit (ICU). Given the severity of the disease, the decision was made to use plasmapheresis and rituximab, the monoclonal antibody directed against CD20, as an experimental therapy. After adjunctive therapy was initiated, the patient began to clinically improve and ultimately made a full recovery. Rituximab is historically only effective in primary cold AIHA, but it appeared to elicit significant clinical improvement with our use in secondary cold AIHA. While there have been a handful of studies demonstrating its successful use in secondary cold AIHA, we propose that this medication be further studied to prevent the significant morbidity and mortality associated with the disease., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thomas et al.)

Background: Cold agglutinins are autoantibodies against RBC antigens, leading to hemolysis at less-than-physiological temperatures through complement fixation. Production can be triggered by infections, resulting in secondary cold agglutinin syndrome (CAS). This syndrome has been classically described in the setting of Mycoplasma pneumoniae infection, as well as with several viral pathogens. Cases: Here, we present two cases of cold agglutinins identified in the context of Covid-19 in critically ill patients treated at our institution. Each case was characterized by little in-vivo hemolysis, but these antibodies complicated laboratory assessment and renal replacement therapy. Management included anticoagulation and warming of dialysis circuit. Conclusions: Despite minimal in-vivo hemolysis, these antibodies are of clinical significance given their implications for laboratory assessment and renal replacement therapy, particularly with the frequency of multi-organ system dysfunction associated with severe Covid-19.

Cold agglutinin disease (CAD) is an uncommon form of cold autoimmune hemolytic anemia (AIHA). It should be considered in the differential diagnosis of elderly patients with unexplained chronic anemia presenting with or without cold-induced symptoms in the extremities, such as the fingers, ears, and nose. CAD is a complement-mediated process which leads to intravascular and extravascular hemolysis. A stepwise approach to laboratory testing can help confirm the diagnosis. Nearly all cold agglutinins are positive for the C3d direct antiglobulin test (DAT). A negative C3d DAT should prompt investigation of a possible warm AIHA. Ninety percent of cold agglutinins are of the IgM immunoglobulin class and should have a titer of 1:64 or higher at 4°C. Distinction from a warm AIHA is important, as therapy differs for the two entities. Corticosteroids are not effective at treating CAD and should not be used as therapy in these patients. Approximately 45–60% of patients with CAD respond to rituximab monotherapy. Combination therapy of rituximab and fludarabine has been shown to be effective in up to 76% of patients; however, patients experience more mild side effects with this treatment. New anti-complement drugs, such as eculizumab and sutimlimab, are currently in phase-3 trials to determine their efficacy and safety in patients with CAD.

Cold haemagglutination is a primary or acquired autoimmune disease involving antibodies that lead to agglutination of red blood cells at low temperature followed by complement fixation and haemolysis on rewarming. This disease can lead to adverse consequences in patients undergoing cardiothoracic surgery, especially when hypothermic cardiopulmonary bypass is applied. The authors discuss the management of two patients who underwent mitral valve replacement surgery while cold agglutinins were detected in the perioperative period. In the first patient, the diagnosis was made preoperatively followed by administration of glucocorticoids to achieve acceptable level of antibody titers. The second patient experienced haemoglobinuria during her intensive care unit stay. The case report describes the pathophysiology of cold agglutination, relevant laboratory investigations such as antibody titers and thermal amplitude, identification of at-risk patients, and management strategies to avoid serious complications.

Cold agglutinins (CA) in blood may cause false reduction in red blood cell (RBC) count and false increases of RBC indices, such as mean corpuscular haemoglobin concentration (MCHC). Preheating at 37 °C for 2 h is used to overcome this problem. We previously proposed the integration in a total laboratory automation (TLA) setting of a customized reflex test in the presence of MCHC >385 g/L for identifying spurious elevations due to CA. Here, we prospectively evaluate this approach after its introduction in our clinical practice. We evaluated 73 consecutive blood samples from 34 adult patients. Short heating (<1 min) at 41 °C using the reticulocyte channel of Sysmex XN-9000 platform was followed by calculation of optical parameters by the instrument software to ensure quick solution of the CA-dependent problems. After the reflex test in the reticulocyte channel, MCHC dropped below 385 g/L in 50 samples. The reflex markedly corrected the RBC number in eight samples obtained from three patients with CA condition. Two samples from markedly anaemic patients had low blood haemoglobin and RBC count before and after reflex. The remaining 13 samples were obtained from 12 patients, most of whom were on antiretroviral therapy or suffered severe electrolyte disorders, known conditions associated to increased MCHC. The implementation of the proposed automatic reflex by reticulocyte channel on the Sysmex XN-9000 platform in a TLA setting may solve the problem of spuriously high MCHC due to RBC agglutination for CA in a few minutes instead of waiting hours for sample preheating. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease eventually caused or reactivated by a viral infection, which can also lead to the production of cold agglutinins (CA). The nature of these autoantibodies is usually an IgM, less frequently an IgA or IgG, they agglutinate red blood cells at low temperatures. They can interfere with hematological parameters causing interpretation difficulties. We report a case of a 4-year-old boy who developed an IgG CA during recurrent HLH reactivated by EBV infection. The purpose of this observation is to underline HLH criteria and to analyze CA interference as well as its biological and clinical characteristics. [ABSTRACT FROM AUTHOR]

The presence of cold agglutinins (CAs) in samples intended for complete blood count (CBC) using automated haematology analysers might cause serious preanalytical errors. In this report we describe the case of a 90-year old female patient admitted to the Emergency department following trauma injuries. A blood testing on admission revealed surprisingly low red blood cell count (0.99 x 1012/L), low haematocrit (0.102 L/L) which did not correlate with haemoglobin concentration (100 g/L), and high erythrocytes indices (mean corpuscular haemoglobin, 101 pg; mean corpuscular haemoglobin concentration, 980 g/L). In the second sample, after repeated collection, almost equal results were observed. Blood smear examination under the microscope revealed clusters of erythrocytes. Cold agglutinins presence was suspected and, in order to get valid results, sample was warmed to 37 °C. Correction of CBC was observed. Furthermore, we performed some additional analysis to confirm the presence of CAs in this patient. The aim of this report was to present the laboratory findings in a case of CAs and propose a laboratory procedure for whole blood samples with suspected CAs. [ABSTRACT FROM AUTHOR]

Cold haemagglutination is a primary or acquired autoimmune disease involving antibodies that lead to agglutination of red blood cells at low temperature followed by complement fixation and haemolysis on rewarming. This disease can lead to adverse consequences in patients undergoing cardiothoracic surgery, especially when hypothermic cardiopulmonary bypass is applied. The authors discuss the management of two patients who underwent mitral valve replacement surgery while cold agglutinins were detected in the perioperative period. In the first patient, the diagnosis was made preoperatively followed by administration of glucocorticoids to achieve acceptable level of antibody titers. The second patient experienced haemoglobinuria during her intensive care unit stay. The case report describes the pathophysiology of cold agglutination, relevant laboratory investigations such as antibody titers and thermal amplitude, identification of at-risk patients, and management strategies to avoid serious complications. [ABSTRACT FROM AUTHOR]

Cold agglutinins are of unique relevance in cardiac surgerybecause of the use of hypothermic cardiopulmonary bypass (CPB). Cold autoimmune diseases are defined by the presence of abnormal circulating proteins (usually IgM or IgA antibodies) that agglutinate in response to a decrease in body temperature. These disorders include cryoglobulinemia and cold hemagglutinin disease.Immunoglobulin M autoantibodies to red blood cells, which activateat varying levels of hypothermia, can cause catastrophic hemagglutination,microvascular thrombosis, or hemolysis. Management of anesthesia in these patients includes strict maintenance of normothermia. Patients scheduled for the surgery requiring cardiopulmonary bypass present significant challenges. Use of systemic hypothermia may be contraindicated, and cold cardioplegia solutions may precipitate intracoronary hemagglutination with consequent thrombosis, ischemia, or infarction. Management of CPB andmyocardial protection requires individualized planning. We describea case of MV repair and CABG in a patient with high titercold agglutinins and high thermal amplitude for antibody activation.Normothermic CPB and continuous warm blood cardioplegia weresuccessfully used.

Pseudoneutropenia or low leucocyte count secondary to leucoagglutination is caused by ethylene diamine tetra acetic acid (EDTA) or cold agglutinins and is seen in benign and malignant disorders. We report a 34-year-old lady who was admitted with fever, vomiting, respiratory distress and productive cough. Complete blood count (CBC) at initial presentation revealed low haemoglobin (11.6 g/dL), total leucocyte count (TLC) (5900/mm3 ) with 50% polymorphs. Peripheral blood smear showed leucocytes in clusters. Another sample was asked for in citrate anticoagulant which showed a TLC of 5900/mm3 with 50% polymorphs and evidence of auto agglutination. Another collected in a prewarmed ethylene diamine tetra acetic acid (EDTA) tube, CBC showed a TLC of 9800/mm3 with 39% neutrophils suggestive of pseudoneutropenia due to cold agglutinins.

Clinically, in young immunocompetent adults, Epstein-Barr virus (EBV) usually manifests as infectious mononucleosis (IM). Typical clinical findings of EBV IM include fever, profound fatigue, pharyngitis, bilateral posterior cervical adenopathy, and splenomegaly. Respiratory involvement with EBV IM may occur, but is distinctly rare. We present a case of a 20 year old female who with classic EBV IM, but was inexplicably dyspneic and hypoxemic. Further diagnostic testing confirmed co-infection with Mycoplasma pneumoniae. As a non-zoonotic atypical community-acquired pneumonia (CAP), M. pneumoniae may rarely be accompanied by severe hypoxemia and even acute respiratory distress syndrome. She represented a diagnostic dilemma regarding the cause of her hypoxemia, i.e., due to EBV IM with pulmonary involvement or severe M. pneumoniae CAP. The patient slowly recovered with respiratory quinolone therapy. [ABSTRACT FROM AUTHOR]

Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.

Mycoplasma pneumoniae is one of the most common etiological agents producing the atypical pneumonia syndrome, especially in young adults. The case is reported here of a 30-year-old female with mycoplasmal pneumonia which presented with fever, cough, headache, leukopenia and thrombocytopenia. Cold agglutinins were developed during the illness. The patient was treated with ceftriaxone and azithromycin and was discharged in good clinical condition. In the following days she developed diarrhea and abdominal pain. C. difficile toxin was detected in the stool, and she was treated with metronidazole and made complete clinical recovery. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune hemolytic anemia can be classified depending on presence of warm, cold or mixed type of autoantibodies that are directed against antigens on the red blood cell surface. Here we report a case of pathological cold agglutinin disease which was eventually detected due to blood group discrepancy. Case details: A request was sent to the blood bank for two units of packed red cells in a diagnosed case of CLL which showed type IV discrepancy during blood grouping.The discrepancy was subsequently resolved after warm saline washing of red cells along with repetition of reverse grouping with pre-warmed serum. The direct antiglobulin test was positive and revealed autoanibodies against C3b/C3d only. Indirect antiglobulin test was performed with 3-cell panel in a polyspecific gel card (IgG+C3d) showed a pan-reactive pattern along with a positive autocontrol. Subsequently a cold agglutinin titration was performed and titers of 1024 at 4 °C; titer of 2 at room temperature were detected. Dithiothreitol (DTT) treatment of serum was undertaken and IgM type of autoantibody was detected in this case confirming a case of secondary cold agglutinin disease in this patient. Two units of red cells were transfused to this patient after successfully performing cross-match with pre-warmed serum. It was advised from the blood bank that the blood should be transfused slowly through a blood-warmer and patient should be kept in warm condition to avoid in-vivo hemolysis due to high titer of cold agglutinin. The transfusion was uneventful and patient is on regular follow-up till now. Conclusion: Thus we concluded that serological discrepancies observed in blood bank can successfully guide the bedside transfusion protocol in case of cold agglutinin disease. [ABSTRACT FROM AUTHOR]

Background: It is unclear why haemolysis may somewhat persist in patients with cold autoimmune haemolytic anaemia (cAIHA) at 37 °C (core temperature). Methods: Seven patients with cAIHA were included in this study. Serological testing was performed using standard techniques. Bound autoantibodies (aab) on patients' RBCs were analysed by the direct antiglobulin test (DAT), dual antiglobulin test (DDAT) and flow cytometry (FC) using pre-warmed RBCs (37 °C). Temperature-dependent complement binding was determined by incubation of patients' serum samples with group O RBCs and fresh serum complement. Results: The DAT was strongly positive with anti-C3d in all cases, independent of season and outside temperature. Haemolysis usually improved during warm periods of time, but decompensated following febrile infections, and persisted throughout the year, though exposure to the cold was strictly avoided. In addition, trace amounts of IgM aab were infrequently detectable on patients' RBCs even at 37 °C, and complement activation was demonstrated following incubation of RBCs with the causative aab at 37 °C. Conclusions: Binding of trace amounts of IgM aab at 37 °C may provide an explanation for the durable C3d-positive DAT and haemolysis in patients with cAIHA. [ABSTRACT FROM AUTHOR]

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Critical events during cardiopulmonary bypass (CPB) can challenge the most experienced perfusionists, anesthesiologists, and surgeons and can potentially lead to devastating outcomes. Much of the challenge of troubleshooting these events requires a key understanding of these situations and a well-defined strategy for early recognition and treatment. Adverse situations may be anticipated prior to going on CPB. Atherosclerosis is pervasive, and a high plaque burden may have implications in surgical technique modification and planning of CPB. Hematologic abnormalities such as cold agglutinins, antithrombin III deficiency, and hemoglobin S have been discussed with emphasis on managing complications arising from their altered pathophysiology. Jehovah’s witness patients require appropriate techniques for cell salvage to minimize blood loss. During initiation of CPB, devastating situations leading to acute hypoperfusion and multiorgan failure may be encountered in patients undergoing surgery for aortic dissection. Massive air emboli during CPB, though rare, necessitate an urgent diagnosis to detect the source and prompt management to contain catastrophic outcomes. Gaseous microemboli remain ubiquitous and continue to be a major concern for neurocognitive impairment despite our best efforts to improve techniques and refine the CPB circuit. During maintenance of CPB, adverse events reflect inability to provide optimal perfusion and can be ascribed to CPB machine malfunction or physiological aberrations. We also discuss critical events that can occur during perfusion and the need to monitor for organ perfusion in altered physiologic states emanating from hemodilution, hypothermia, and acid–base alterations. [ABSTRACT FROM PUBLISHER]

Background and Objectives The unexpected alloantibodies are usually found in the sera of those patients who have a history of blood transfusion and pregnancy. These alloantibodies cause many complications in patients with post-transfusion delayed hemolytic transfusion reactions. Case A 24-year-old man with melana, blood vomiting, and the history of discopathy and consumption of moleksicam was observed. In laboratory tests, incompatibility of the crossmatch test and discrepancy of blood grouping were observed. In the analysis of the antibody screening, positive reactions were observed with all of the cells in different phases of panels 3 and 11. On the next visit, similar results were obtained after 6 months. Conclusions If indicated for blood transfusion, only autologous blood is recommended to be administered to prevent hemolytic transfusion reactions. [ABSTRACT FROM AUTHOR]

Cryoproteins still remain largely undiagnosed despite their clinical relevance. Cryoglobulins, cryofibrinogen and cold agglutinins respectively show a significant association with autoimmune diseases and non-Hodgkin's lymphoma. The analytical part is relatively straightforward; however, the preanalytical phase is a challenge. This article briefly summarizes the relevant aspects to improve this situation. [ABSTRACT FROM AUTHOR]

Cold agglutinins are of unique relevance in cardiac surgery because of the use of hypothermic cardiopulmonary bypass (CPB). Cold autoimmune diseases are defined by the presence of abnormal circulating proteins (usually IgM or IgA antibodies) that agglutinate in response to a decrease in body temperature. These disorders include cryoglobulinemia and cold hemagglutinin disease. Immunoglobulin M autoantibodies to red blood cells, which activate at varying levels of hypothermia, can cause catastrophic hemagglutination, microvascular thrombosis, or hemolysis. Management of anesthesia in these patients includes strict maintenance of normothermia. Patients scheduled for the surgery requiring cardiopulmonary bypass present significant challenges. Use of systemic hypothermia may be contraindicated, and cold cardioplegia solutions may precipitate intracoronary hemagglutination with consequent thrombosis, ischemia, or infarction. Management of CPB and myocardial protection requires individualized planning. We describe a case of MV repair and CABG in a patient with high titer cold agglutinins and high thermal amplitude for antibody activation. Normothermic CPB and continuous warm blood cardioplegia were successfully used. [ABSTRACT FROM AUTHOR]

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Objectives. Cold agglutinin (CA) titers are one among the first pathological indicators for diagnosing Mycoplasma pneumoniae disease. We prospectively studied the prevalence of CAs in 300 HIV-positive and 75 HIV-negative individuals with respiratory disease in Chennai, India. Methods. The cold agglutination test was used and retrospectively compared with the results of a particle agglutination test. Results. While CAs were positive in 51 HIV cases, particle agglutination test detected anti-M pneumoniae antibodies from 43 cases with HIV disease (P = .001). The seroprevalence of CAs was 2.6% (n = 2) among HIV-negative participants. The mean CD4 count in CA-positive and -negative HIV cases was 107.4 ± 121.2 and 259.2 ± 247.2 cells/µL (P = .001), respectively. Conclusion. Our report suggests a basis for the existence of CAs in HIV-positive cases. Definitive diagnosis may be done only when CA detection is used in conjunction with a specific test. [ABSTRACT FROM AUTHOR]

Cross-reactivities of monoclonal reagents for red blood cell (RBC) typing are seen very rarely, e.g. in some reagents for testing of ABO or Lewis antigens. We report on two patients in whom we observed weak reactions using a monoclonal anti-c reagent containing clone MS35, but no reactions with anti-c reagents containing other monoclonal or polyclonal antibodies. To resolve this discrepancy, we studied RHCE exon 1 (Ex1) and 2 from genomic DNA of one patient and performed quality controls of the false-positive reacting anti-c reagent. RHCE Ex1 showed no abnormalities as well as RH Ex2 examined with primers specific for Ex2 D/C. No amplification product of RH Ex2 was received with primers specific for c. A titration study with untreated, papain-treated and sialidase-treated adult and newborn RBCs showed anti-i reactivity of the false-positive reacting reagent. This reactivity could not be removed by absorption with c-negative newborn RBCs without reducing the anti-c titre in the same way, indicating a cross-reactivity. Some manufacturers give a remark on a possible cold agglutinin activity of their monoclonal anti-c reagents in the instruction leaflet, but in order to avoid such irritation, we recommend to remove this cross-reactivity by dilution during the manufacturing process. [ABSTRACT FROM AUTHOR]

In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr1–3 subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated. The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database. Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid. Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding. [ABSTRACT FROM AUTHOR]

Variable domains (VH) of all known anti i/I cold agglutinin (CA) heavy chains are codified by the VH4-21 gene. While anti-i CAs are the expression of gene rearrangement without mutations represented by amino acid changes, anti-I CAs present, among others, a frequent somatic mutation of Gly by Asp at position 31. The hydropathy profile calculated for the CDR1H (position 30 to position 35), as well as some adjacent positions of the heavy chain belonging to anti-i and anti-I antibodies, showed the conformational changes accompanying the replacement of Gly by Asp. A MoAb (LP91), which had been obtained in BALB/c mice immunized with a Fabμ fragment from a monoclonal IgMκIIIb anti-I CA (protein KAU), proved capable of inhibiting human adult erythrocyte cryoagglutination by anti-I CAs but not that of fetal erythrocytes by anti-i CAs. Western blot analysis disclosed that such MoAbs recognized a sequential epitope located in the Fd fragment of all anti-I CAs employed in this study. With the purpose of checking whether Asp31 was involved in the epitope recognized by the MoAb, two peptides, D and G, were synthesized which mimicked the CDR1H structure of anti-I and anti-i, respectively; the MoAb only reacted with peptide D by FLISA. Subsequent experimental results indicate that the Gly/Asp mutation could be associated with the diverse specificity presented by these autoantibodies, a change determining a characteristic epitope/idiotope, recognized by LP91 in the CDR1H. [ABSTRACT FROM AUTHOR]