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BACKGROUND: Autoimmune haemolytic anaemia (AIHA) is a decompensated acquired haemolysis caused by the host's immune system acting against its own red cell antigens. The aim of this national survey is to capture real-world data of clinical practices in AIHA by collecting responses from clinical haematologists across India. METHODOLOGY: In this cross-sectional study, a structured, 26-question online survey was conducted in India by few members of the special interest group in immunohaematology between January and March, 2022. The final survey consisted of questions covering place of work, amount of AIHA cases being evaluated by the haematologist over preceding years, basic demographic, clinical and laboratory features of the patients being treated under them etc. Descriptive statistical analysis was performed during the assessment. RESULTS: The survey response rate was 48.2% (53/110), 69.8% (37/53) have diagnosed and managed more than 10 AIHA cases in the last 3 years with a female preponderance. There was considerable variability in response. While 56.6% (30/53) of respondents do have the access to the facilities to subtype AIHA cases; 32.1% (17/53) of clinicians would prefer administering high dose steroids for 6 weeks or more in non-responding patients, and only 45.3% (24/53) would assess the risks of thrombosis in AIHA. There is unanimous agreement among the participants that health-related quality of life should be taken into consideration in patients and the need for a national registry of patients with AIHA in India. CONCLUSION: The current national survey showed that some aspects of AIHA management were consistent; others were less so, but also significant variations were observed in certain clinical practices, where the evidence base is limited. A joint effort is needed to establish a national patient registry by including both clinical haematologists and transfusion medicine specialists which could potentially standardise AIHA management and future research in India.
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Anemia Hemolítica Autoinmune , Humanos , Femenino , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/etiología , Estudios Transversales , Calidad de Vida , Hemólisis , India/epidemiologíaRESUMEN
Thrombotic thrombocytopenic purpura (TTP) secondary to dengue fever is a very unusual occurrence. Both conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, we present a young lady who suffered dengue fever followed by microangiopathic anemia, thrombocytopenic purpura, and altered sensorium. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. As soon as, we diagnosed the patient as having TTP, we treated her with serial plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms and laboratory parameters also normalized. Hence, timely diagnosis and starting appropriate treatment immediately are key factors for successful outcomes.
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BACKGROUND: With shortages of blood globally in the COVID-19 pandemic, many hospitals and blood centers have successfully implemented blood conservation strategies and strategies to maintain blood donations and blood inventory. Here, we reported our experience of utilization of blood components for transfusion in the current COVID-19 pandemic and discussed the patient blood management (PBM) methods and importance of judicious blood usage in any pandemic. MATERIALS AND METHODS: The retrospective study of 8 months was divided into pre-COVID and COVID periods. Parameters that included number of blood requisitions, blood components reserved and transfused, clinical speciality wise blood usage in both the periods were analysed. Blood utilization indices were computed using recommended equations. RESULTS: We observed an unusual pattern of blood utilization with significant disruption on blood supply and demand chain in this pandemic. A mean drop of 50.7% blood requisitions was observed in the COVID period. The period observed transfusion of 3608 units of blood components with a mean drop of 49.7% when compared to pre-COVID period. Mean drop of 46.6%, 54.4%, 53.4% and 52.7% were observed in packed red blood cell, fresh frozen plasma, platelet concentrate and cryoprecipitate transfusions in the COVID period. Blood component utilization was significantly reduced in most clinical specialities. The mean cross match to transfusion ratio in the COVID period was 1.28 with a mean increase in transfusion probability and transfusion index by 18.2% and 22.2% respectively. CONCLUSION: Although a constant transfusion support was needed in few clinical specialities throughout the pandemic, strict adherence to PBM protocols and practice of first in, first out method of blood dispensing helped the blood centre to support all patients needing blood transfusion.
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BACKGROUND: Few international studies have reported the prevalence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in healthy, asymptomatic blood donors. These findings have definitely raised queries regarding blood safety and transfusion-transmitted coronavirus disease (COVID)-19. We conducted this first anti-SARS-CoV-2 seroprevalence survey among the healthy blood donors in Eastern India. MATERIALS AND METHODS: The study included 611 healthy blood donors who donated whole blood (WB) in our blood center. For detailed analysis, social and demographic details of all donors like gender, age, weight, occupation, and place of residence were included. Donor eligibility criteria for WB donation were followed as per existing national guidelines. Residual serum samples leftover after screening the mandatory infectious markers were tested for the presence of anti-SARS-CoV-2 IgG directed against domain S1 and S2 of the SARS-CoV-2 spike protein using automated enhanced chemiluminescence technology following the manufacturer's instructions. RESULTS: The mean overall seroprevalence of anti-SARS-CoV-2 antibody in blood donors was observed to be 4.4% (95% confidence interval 3.8-4.9) with a monthly increasing trend. Seroprevalence adjusted for sensitivity and specificity of the assay was 4.1%. The mean S/Co values of reactive donor samples were observed to be 2.99 and 3.42 in June and July 2020, respectively (P = 0.013). No significant variation in seroprevalence rate was observed among donor variables like donor age, gender, profession, and educational qualification. A higher significant prevalence of antibody was observed among voluntary donors and donors residing in suburban areas (P < 0.05). Among the ABO blood groups, no statistical significance of seroprevalences was observed among the various ABO blood groups. CONCLUSION: We conclude that despite many limitations in the current study, we found 4.4% seroprevalence of anti-SARS-CoV-2 antibody in the asymptomatic, healthy, epidemiologically, and medically screened blood donors. These data are definitely the tip of an iceberg and signify much higher seroprevalence in the normal population and indicate that protective measures like masking and social distancing should remain implemented for a long term.
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Autoantibody production in autoimmune haemolytic anemia (AIHA) is the result of the loss of self-immunological tolerance of the host. Here we investigated the various immunohematological markers that may influence the severity of in vivo hemolysis in warm AIHA (WAIHA). Complete direct antiglobulin test (DAT) evaluation and immunohematological characterization were performed in 247 patients of WAIHA following departmental protocols. Clinical and laboratory details of patients were obtained from patient file. The median age of WAIHA patients was 47 years with a female preponderance. Lymphoproliferative diseases were the major underlying causes of secondary WAIHA. The mean haemoglobin (Hb) and reticulocyte count (Retic) were 6.43 gm/dL and 7.58% respectively. Single autoantibody bound to red cells was investigated in 151 patients. The main IgG subclass was IgG1. Multiple autoantibodies like IgG+ C, IgG+IgA and IgG+IgA+C were found in 87 (35.2%) patients. Free autoantibodies were observed in 112 patients with a median indirect antiglobulin test (IAT) reactivity of 2+. Derangement of haematological and biochemical values was statistically significant with increase in DAT reactivity, presence of multiple autoantibodies on red cells, coating of red cells by IgG3 or multiple IgG subclass, higher DAT dilution and increasing IAT reactivity. We conclude that several important but simple immunohematological parameters may influence the degree of in vivo hemolysis in WAIHA. Since a set of common haematological and biochemical test determines the severity of in vivo hemolysis therefore a comprehensive clinical and immunohematological evaluation is advisable for a correct diagnostic and therapeutic workup of WAIHA.
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Anemia Hemolítica Autoinmune , Hemólisis , Humanos , Femenino , Persona de Mediana Edad , Anemia Hemolítica Autoinmune/diagnóstico , Inmunoglobulina G , Autoanticuerpos , Inmunoglobulina ARESUMEN
Background Most individuals with Covid-19 infection develop antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the dynamics of these antibodies is variable and not well-studied. We aimed to determine the titres of naturally acquired antibodies over a 12-week follow-up. Methods We recruited healthcare workers who had tested positive on a specific quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for SARS-CoV-2, and then tested for the presence of immunoglobulin G (IgG) antibody against the same virus at baseline and again at 6 and 12 weeks. The antibody titre was determined by a semi-quantitative assay based on signal/cut-off ratio. Healthcare workers with antibody positivity were divided into those with high titre (ratio ≥12) and low titre (<12). Their demographic details and risk factors were surveyed through a Google form and analysed in relation to the antibody titres at three time-points. Results Of the 286 healthcare workers, 10.48% had high antibody titres. Healthcare workers who had tested positive by qRT-PCR and those who had received the Bacille Calmette-Guérin (BCG) vaccination or other immune-boosters had a higher frequency of high antibody titres. While there was a significant decline in antibody titres at 6 and 12 weeks, 87.46% of individuals positive for IgG antibody persisted to have the antibody even at 12 weeks. Conclusion Healthcare workers who tested positive for SARS-CoV-2 on qRT-PCR had a high positivity for the specific antibody, which continued to express in them even at 12 weeks. Further follow-up is likely to enhance our understanding of antibody kinetics following SARS-CoV-2 infection.
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COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios Longitudinales , SARS-CoV-2 , Personal de Salud , Factores de Riesgo , Anticuerpos AntiviralesRESUMEN
The application of flow cytometry (FC) is diverse and this powerful tool in used in multiple disciplines such as molecular biology, immunology, cancer biology, virology, and infectious disease screening. FC analyzes a single cell or a particle very rapidly as they flow past single or multiple lasers while suspended in buffered solution. FC has a great impact in the field of transfusion medicine (TM) due to its ability to analyze individual cell population and cell epitopes by sensitive, reproducible, and objective methodologies. The main uses of FC in TM are detection of fetomaternal hemorrhage, diagnosis of paroxysmal nocturnal hemoglobinuria, quantification of D antigen, detection of platelet antibody, quality control of blood components, for example, residual leukocyte counts and evaluation of CD34-positive hematopoietic progenitor cells in stem cell grafts. In recent years, FC has been implemented as an alternative method for the detection and characterization of red cell autoantibodies in autoimmune hemolytic anemia. Many workers considered FC as a very good complement when aberrant expression of various erythrocyte antigens needs to be elucidated. It has been extensively used in the resolution of ABO discrepancies and chimerism study. FC has also been used successfully in various platelet immunological studies. In the recent past, FC has been used in several studies to assess the platelet storage lesions and elucidate granulocyte/monocyte integrity and immunology. FC analysis of CD34+ stem cells is now the method of choice to determine the dosage of the collected progenitor cells. The technique is vastly used to evaluate residual leukocytes in leukodepleted blood components. We conclude that flow cytometers are becoming smaller, cheaper, and more user-friendly and are available in many routine laboratories. FC represents a highly innovative technique for many common diagnostic and scientific fields in TM. Finally, it is the tool of choice to develop and optimize new cellular and immunotherapeutic trials.
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BACKGROUND: With blood component therapy becoming the standard of care in transfusion medicine globally, the quality control (QC) of these components has become a routine and mandatory program in all blood centers. Extensive utilization of blood components has been observed in our multidisciplinary tertiary care hospital. We use quadruple bag systems and automated component extraction facilities for collection and processing of whole blood (WB). In this study, we analyzed our data relating to QC of all blood components which we prepare and issue for transfusion. MATERIALS AND METHODS: The retrospective 5-year study comprised 47,430 WB collections which were separated into blood components using quadruple bags and automated component extraction machine. A total of 90 units of WB were processed into blood components for the machine calibration and validation. Routine use of the system was started once the calibration and validation results were acceptable. At least 1% of each component prepared was subjected to QC as per departmental standard operating procedures. Statistical analysis was done using the SPSS statistical package. RESULTS: The mean volume, hematocrit (Hct), platelet (PLT), and white blood cell (WBC) in 350 and 450 mL WB units were 394.63 mL, 39.43%, 0.93 × 1011, and 3.12 × 109 and 507.75 mL, 40.72%, 1.13 × 1011, and 3.45 × 109, respectively, with mean recovery of PLT and WBC in buffy coat being 95.54% and 68.63% and 97.87% and 74.51%, respectively. As high as 89.91% RBC recovery was noted in the packed red blood cell units which were subjected to QC. QC of random donor platelets was performed in 979 (2.36%) units with acceptable results. The mean fibrinogen and FVIII values were estimated to be 469.17 mg and 217.34 IU (1.07 IU/mL) and 600.21 mg and 273.39 IU (1.11 IU/mL) in fresh frozen plasma units prepared from 350 and 450 mL WB, respectively. A total of 578 (1.62%) units of cryoprecipitate were investigated for QC with favorable results. CONCLUSION: We conclude that QC data generated in this study will provide invaluable information about the performance of the latest blood collection systems. QC of all blood components under study complied with both national and international standards. We opine that all blood centers should establish a complete QC program and adhere to departmental protocols and manufacturer's instructions for its execution and effective outcome.
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BACKGROUND: Significant blood loss and requirement of allogenic blood transfusion during or after total knee replacement (TKR) have been reported. Incidence of blood transfusion in TKR is highly variable and depends on several factors. We investigated the blood utilization in patients undergoing TKR in our hospital and depicted the important risk factors that determine the need of allogenic blood transfusion in primary unilateral TKR. MATERIALS AND METHODS: The study included 1241 consecutive patients undergoing primary unilateral total knee arthroplasty. All the surgeries were performed by a single surgical team of orthopedists following standard procedure. Patient and disease details were obtained from patient file and hospital information system. Compatibility test was performed in blood bank before blood reservation following mandatory guidelines. Details of test, blood issue, and blood transfusion were documented in the blood bank. RESULTS: Of 1241 enrolled patients, 1069 (86.2%) were female. The median age of patients was 66 years with mean preoperative hemoglobin of 9.9 g/dL. Allogenic blood transfused was needed in 223 (17.9%) patients. Diabetes mellitus, hypertension, thyroid disorders, and chronic heart diseases were the major comorbid conditions. Risk factors such as gender, American Society of Anesthesiologists score, preoperative hemoglobin, and intraoperative and postoperative blood losses were significantly associated with blood transfusion. CONCLUSION: The risk factors determining blood transfusion in TKR vary between studies, however, all centers should establish standard operating procedures describing the surgical procedure and transfusion support in TKR. In addition, each center may develop specific blood management strategy to rationalize blood transfusion in TKR and overall successful care in TKR.
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Antigen - antibody complexes on heavily coated red cells in Warm autoimmune haemolytic anemia (WAIHA) often activates the complement pathway and red cells bound C3 complement component are encountered in complement associated WAIHA (CWAIHA). Patients belonging to CWAIHA and non-complement associated WAIHA (NCWAIHA) may demographically, clinically and immunohematologically behave differently therefore we planned to study the clinical and immunohematological characteristics of CWAIHA and NCWAIHA with emphasis to various potential factors associated with CWAIHA. The prospective study included 229 patients of WAIHA. Complete DAT evaluation was performed in all these patients. Details of patients and their hematological and biochemical parameters were obtained from patient file and Hospital Information System. In vivo hemolysis was documented as per the criteria established by previous workers. Statistical analysis was done using SPSS statistical package. Of the total 229 patients of WAIHA, 83 (36.2%) belonged to the complement associated WAIHA group. A total of 146 (63.8%) patients were females of which 43 (29.4%) had CWAIHA. The median age of WAIHA patients was 37 years. A total of 46 (56.1%) patients above age 40 years suffered from CWAIHA. Where secondary WAIHA was found in 121 (52.8%) patients; more than half (61.4%) with CWAIHA had underlying aetiology. Over 95% of patients in both categories presented with weakness and pallor. Strong DAT (> 2 +) was observed in 86.7% of CWAIHA patients. Factors like gender, age, aetiology and DAT IgG dilution were independent risk factors for CWAIHA. DAT remained positive even at the end of 10 months of successful treatment. We conclude that detailed characterization of WAIHA with particular emphasis to complement and non-complement associated WAIHA is essential to evaluate the disease characters, immunological behaviours, prognosis and therapeutic management. Moreover an understanding of the risk factors of CWAIHA will help physicians / hematologists and immunohematologists to manage WAIHA more prudently and solicitously.
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"Auto-anti-A1" has been sparsely discussed in the literature. Only few workers in the past depicted such antibody in transfused and nontransfused patients. The current case is probably the first example of auto-anti-A1 in a healthy young blood donor who was typed as ABO Group "A1B." The cold reacting autoantibody in the donor was serologically characterized in details and was found to be nonhemolytic. ABO discrepancy was resolved and the donor was finally typed as "A1B Negative." Therefore, we concluded that auto-anti-A1 may be a rare cause of ABO discrepancy and its resolution is essential to confirm blood group and subsequent blood transfusion management.
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The increases in major surgeries, transplantations and speciality clinics have significantly increased the utilization of platelet concentrates including single donor platelets (SDP). The advantages of SDP or apheresis platelet have been discussed elaborately by previous authors as compared to random donor platelets. Here we share our experiences of plateletpheresis procedures using the modern apheresis machines with regards to product quality and donor safety. This study included 3016 procedures of plateletpheresis (1397 on Amicus and 1619 on Trima accel cell separators) on eligible donors using recommended apheresis kits. A target yield of 3 × 1011 was set as the end point of each procedure. Donor details, procedure details and donor adverse reactions if any were documented. Statistical analysis was done using the SPSS statistical package (version 13, USA). Of the total 6276 donors screened 2049 (32.6%) were deferred due to various reasons. Out of remaining 4227 eligible donors; 3016 (71.4%) underwent plateletphereis procedures based on the requirement of SDP by the patients. Mean pre-procedure platelet count and hematocrit in donors were 188.3 × 106/mL and 41.7% respectively. Mean procedure time in Amicus (76.6 min) was significantly more than the Trima accel (64.3 min) (p = 0.02). Platelet yield by Trima accel and Amicus was 2.96 × 1011 and 3.08 × 1011 respectively (p = 0.061). A total of 40 donors (1.33%) suffered adverse effect during or after apheresis procedures. While the modern plateletpheresis devices are both donor and user friendly at the same time they provide quality product consistently in lesser time.
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BACKGROUND: Transfusion of allogeneic blood in breast cancer surgery is variable, and differences of transfusion incidence have been observed in the literature. Most hospital guidelines including ours dictate group and reserve policy of blood before breast surgery. Here, we aimed to audit the blood utilization in patients undergoing elective breast surgery in our hospital and thereby optimize the blood ordering schedule, economic burden, and loss of clinical resources. MATERIALS AND METHODS: The study included 478 breast cancer surgeries over a period of 6 years. Patient and disease details were obtained from patient file and hospital information system. Blood samples sent to blood bank were subjected to compatibility test and reserved. All transfusions were documented, and statistical analysis was done. RESULTS: Of the total 478 patients, most underwent wide local excision of the breast and modified radical mastectomy. A total of 16 patients received 71 units of blood and blood components in all categories of surgeries. Only 103 were younger women (≤40 years), with a mean age of 31 years. Nontransfused patients were significantly more than transfused ones (P < 0.05). Frequency of blood transfusion was more in young patients (4.9%). Seven (22.6%) of the total 31 Stage IV patients received blood transfusions. Frequency of blood transfusion was more in patients undergoing surgery after chemotherapy (8.8%). A significant loss of time and loss of revenue was observed. CONCLUSION: We conclude that routine compatibility test is not justified for all patients undergoing breast surgery. A more targeted approach is needed to reduce blood demand and associated cost to patient and blood transfusion services.
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BACKGROUND: Seroprevalence studies for COVID-19 evaluate the extent of undetected transmission in a defined community, with special significance among health care workers (HCW) owing to their greater exposure and potential to transmit. METHODS: A total of 1122 HCW (approximately 25% of the employees) of a large tertiary care hospital in India were recruited for this cross-sectional study. COVID PCR-positive HCW were excluded. Based on their risk-assessment, participants were grouped into three categories. A questionnaire was administered and they were tested for SARS-CoV-2-IgG antibodies using the chemiluminescence. RESULTS: The overall seroprevalence among workers was 11.94%, which included 19.85% in COVID units, 11.09% in non-COVID units, and 8% in administrative workers (p=0.007). Antibody prevalence was highest in the department of gastroenterology (11.94%), followed by oncology (10.53%), pathology (10.26%), emergency medicine (7.84%) and critical care medicine (7%). Housekeeping staff, food and beverage staff, lab assistants and technicians had higher seroprevalence rate than doctors and nurses (p < 0.0001). HCW with a history of BCG vaccination in childhood and those who received an adequate prophylactic dose of hydroxychloroquine (HCQ) had a lower seroprevalence as compared to those who did not (7.31% vs. 16.8% and 1.30% vs. 11.25% respectively). CONCLUSION: BCG vaccination, HCQ prophylaxis, and the job profile influence the seroprevalence rate in HCW. Seroprevalence rate and follow-up evaluation of its durability may help hospitals to triage their staff at risk, rationalize their placement, prioritize the use of PPE, thereby potentially reducing the risk.
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Infecciones por Coronavirus , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , Niño , Estudios Transversales , Personal de Salud , Humanos , India/epidemiología , SARS-CoV-2 , Estudios Seroepidemiológicos , Centros de Atención TerciariaRESUMEN
Mismatched blood transfusion due to immunohematological discrepancy is relatively uncommon and in most instances occurs due to Type IV blood group discrepancy which is the discrepancies between forward and reverse groupings. Here, we present a case of a 15-year-old girl with preexisting autoimmune hemolytic anemia (AIHA) who inadvertently received 3 units of wrongly matched packed red blood cell (PRBC), followed by severe intravascular hemolysis. On detailed immunohematological investigation, the patient was found to be autoimmunized and diagnosed with "mixed AIHA" and the patient's blood group was confirmed as "A" positive. Three units of group-specific "best match" PRBC was transfused under close observation without any adverse effect. This highlights the importance of carrying out both forward and reverse blood groupings to avoid mismatched blood transfusion.
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BACKGROUND AND AIM: Patients with warm autoimmune hemolytic anemia (AIHA) may carry immunoglobulin (Ig) M antibodies that react at room temperature and are nonpathological, but few may have cold agglutinins that react at or above 30°C and are referred to as "mixed" AIHA (MAIHA). Here, we present our experience on characterizing MAIHA both clinically and serologically. MATERIALS AND METHODS: Out of 134 AIHA patients, 13 diagnosed as MAIHA were subjected to detailed immunohematological characterization. Most patients were severely anemic and required urgent transfusions. Resolution of blood group discrepancy, elution, Donath-Landsteiner test, and adsorption study were performed following established protocol. "Best match" blood units were selected and transfused to patients. RESULTS: Eight of the 13 patients had severe hemolysis. The median age of patient was 37 years with a female preponderance and secondary MAIHA was observed in 8 (61.5%) patients. Blood group discrepancy was encountered in 4 (30.8%) patients. Multiple red cell bound autoantibodies and high titer serum-free IgM autoantibodies were detected in all samples. Twenty-nine units of "best match" packed red blood cells were transfused to 12 patients without any adverse reaction. Improvement in hematological and biochemical values was observed in all follow-up patients. CONCLUSION: Patients with MAIHA often present with severe hemolysis necessitating blood transfusions. While red cells are coated with multiple autoantibodies, both warm reactive IgG and cold reactive IgM autoantibodies are present in the serum. These serological complexities not only render a crossmatch incompatibility but often lead to blood group discrepancy. "Best match" blood transfusion is always lifesaving.
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This case marks the beginning of issuing cross-matched platelet products in Eastern India. A known case of aplastic anemia, on regular transfusion support, now presented with obstructed ventral periumbilical hernia requiring urgent surgical intervention. Platelet count at presentation was 13,000/µL. Platelet cross-matching was done by solid phase method. Ten units of random donor platelets were crossmatched. Five units were compatible and transfused. Counts rose to 84,000/µL after 1 h. Surgery was completed successfully. Thus, 50% units were compatible. This indicates possible underlying alloimmunization. Rapid count rise enabled completion of this urgent surgery. This rapid rise of platelet count would not have been possible without cross matching. We conclude that platelet cross matching is a powerful tool for alloimmunized patients.
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BACKGROUND AND AIM: Cold agglutinin syndrome (CAS) primary or secondary represents approximately 16-32% of autoimmune hemolytic anemia cases. Most patients present with mild, chronic hemolytic anemia with exacerbation of the condition in the cold environment. Red cell transfusions are only indicated when there is a life-threatening anemia causing crisis. We studied the clinical and serological characterization of CAS with the aim that the information gained from this study would help in proper diagnosis and management of these patients. MATERIALS AND METHODS: The prospective study included nine patients who were admitted with severe anemia. Detailed work-up were conducted to establish the diagnosis, severity of in vivo hemolysis and transfusion management. RESULTS: All patients presented with pallor, weakness, fatigue and painful fingers and toes with exacerbation of symptoms in winter months. Secondary CAS was observed in three patients suffering from malignant lymphoma. Red cells of all patients were coated with complements (C3) more specifically C3d. In one patient suffering from malignant lymphoma, the cold autoagglutinin titer was as high as 4096. Autoantibody in seven patients was specific to "I" antigen and one to "i" antigen. CONCLUSIONS: We conclude that detailed clinical and serological characterization is needed to diagnose and manage CAS. Whereas avoidance of cold exposure is the primary therapy, but no critical patient should be denied blood transfusion due to serological complications. All transfusion services should follow the correct protocol to maximize blood safety in CAS.