Search

[Objective] To identify the ABO blood group of a patient with rare B antigen-specific autoantibody with cold agglutinin, and evaluate the effect of blood transfusion. [Methods] Red blood cells of patient were washed with 37℃ physiological saline and treated with sulfhydryl reagent. ABO blood group antigen was detected by tube method and microcolumn gel method. After the cold agglutinin was removed by EDTA anticoagulant plasma absorbed by type O red blood cells at 4℃, the related blood group antibodies were detected by type B red blood cells absorbing and releasing liquid at 4℃. The blood transfusion effect of patients was evaluated by the changes of hemoglobin before and after transfusion, and their ABO blood group was continuously monitored. [Results] B antigen was detected in the positive setting of serological experiment, cold agglutinin was detected by absorption and elution of type O red blood cells, and anti-B antibody was detected by absorption and elution of type B red blood cells. That is, there was specific autoantibody against B antigen, and the antibody property was IgM. No adverse reactions occurred during the infusion of 3 U type O washed red blood cells and the infusion was effective. The patient was continuously followed for two months, and the forward and reverse blood group identification were consistent, both of which were type B. [Conclusion] According to the previous blood group identification results, serological identification and follow-up comprehensive analysis, the ABO blood group of the patient is type B, but there are transient high titer cold agglutinin and B antigen-specific autoantibodies.

Cold agglutinins are commonly identified in transfusion laboratories and are defined by their ability to agglutinate erythrocytes at 3–4°C, with most demonstrating a titer >64. Similarly, cryoglobulins can precipitate from plasma when temperatures drop below central body temperature, resulting in erythrocyte agglutination. Thankfully, disease associated from these autoantibodies is rare, but unfortunately, such temperature ranges are routinely encountered outside of the body's circulation, as in an extracorporeal circuit during hematopoietic progenitor cell (HPC) collection or human cell therapy laboratory processing. When agglutination occurs ex vivo , complications with the collection and product may be encountered, resulting in adverse events or product loss. Here, we endeavor to share our experience in preventing and responding to known cases at risk of or spontaneous HPC agglutination in our human cell therapy laboratory. Four cases of HPC products at risk for, or spontaneously, agglutinating were seen at our institution from 2018 to 2020. Planned modifications occurred, including ambient room temperature increases, tandem draw and return blood warmers, warm product transport and extended post-thaw warming occurred. In addition, unplanned modifications were undertaken, including warm HPC product processing and plasma replacement of the product when spontaneous agglutination of the product was identified. All recipients successfully engrafted after infusion. While uncommon, cold agglutination of HPC products can disrupt standard processes of collection and processing. Protocol modifications can circumvent adverse events for the donor and minimize product loss. Such process modifications should be considered in individuals with known risks for agglutination going to HPC donation/collection. [ABSTRACT FROM AUTHOR]

Cold agglutinin disease is a type of autoimmune haemolytic anaemia caused by autoantibodies that bind to red blood cell antigens at a cold temperature and causes extravascular haemolysis and sometimes thrombosis also. Due to exposure to a lower temperature during open-heart surgery, the activation of haemolysis may occur in the presence of cold agglutinin antibodies. We present the management of a cyanotic child who has undergone open-heart surgery after the detection of high cold agglutinin titres during routine pre-transfusion screening.

Antibodies to red blood cells (RBCs) may hemolyze erythrocytes via Fc-mediated phagocytosis or complement-dependent. Complement activation on RBCs can be detected by C3d-direct antiglobulin test (DAT), which is the only test in immune hematology that directly targets complement. However, a positive DAT with anti-C3d cannot distinguish between C3b-mediated extravascular hemolysis, C5b-C9-mediated intravascular hemolysis and C5b-C8-mediated eryptosis. Furthermore, DAT is not suitable to estimate the strength of hemolysis. Autoimmune hemolytic anemia (AIHA) is a rare disease that is caused by autoantibodies to red blood cells that is divided in warm AIHA and in cold agglutinin disease (CAD). The causative antibodies in CAD and sometimes in warm AIHA are from the IgM class. Depending on strength of complement activation they can induce extravascular hemolysis, intravascular hemolysis and eryptosis. We studied the three types of hemolysis by use of sera from patients with CAD under various conditions. We found that additionally to the routinely applied C3d-DAT, indirect tests for complement activity (free hemoglobin and Annexin V-binding to phosphatidylserine-exposing RBCs) should be used to determine the portion of extravascular, intravascular and eryptotic hemolysis. Eryptotic hemolysis may have a significant share in clinical relevant CAD or IgM warm AIHA, which should be considered for successful treatment. [ABSTRACT FROM AUTHOR]

Background Hand arm vibration syndrome (HAVS) is a condition caused by hand transmitted vibration from the use of hand-held vibrating tools or workpieces. The disease affects the vascular, neurological and musculoskeletal systems. The vascular component of HAVS is a form of secondary Raynaud's phenomenon. Other causes of disease must be excluded before attributing the cause to hand transmitted vibration. Aims To evaluate the prevalence, and utility of testing for, cryoglobulins and cold agglutinins in patients with HAVS symptoms. Methods A retrospective cohort study of 1183 patients referred for HAVS clinical assessment at St. Michael's Hospital, Toronto, Canada, between 2014 and 2020. The standard operating procedure at the clinic includes a detailed clinical and exposure history, physical examination, objective investigations and blood tests. Data were retrieved from patient chart review and laboratory investigation results for all cases with cryoglobulin and cold agglutinin testing. Results A total of 1183 patients had a serum cryoglobulin measurement. Eleven patients (1%) were positive. Seven positive results were 'low titre' (1% positive) and the other four results were 2%, 6%, 9% and 18%. The patient with a 9% positive cryoglobulin titre had previously diagnosed Sjögren's syndrome. There were no positive cold agglutinin tests in the 795 patients tested. Conclusions Routine testing for cryoglobulins and cold agglutinins in patients with HAVS symptoms is not recommended because test positivity rates are negligible. Testing may be considered if the clinical history or routine blood investigations suggest evidence of underlying cryoglobulinaemia or cold agglutinin disease. [ABSTRACT FROM AUTHOR]

Anti-IH is a common cold agglutinin that is typically clinically insignificant. We present a case that resulted in hemolysis. A 32-year-old male patient with transfusion-independent beta-thalassemia intermedia presented with symptomatic anemia. His blood sample typed as group B, D+ and demonstrated multiple alloantibodies and cold autoantibodies. He was transfused uneventfully, but re-presented 10 days later with recurrent, worsening anemia. At this time, transfusion of group O, phenotype-matched red blood cells (RBCs) resulted in an acute hemolytic reaction. While anemia was initially attributed to drug-mediated bone marrow toxicit y and subsequently to a delayed hemolytic reaction, further evaluation revealed Mycoplasma pneumoniae infection and a cold agglutinin (anti-IH specificity), indicating a likely autoimmune-mediated anemia due to an infectious etiology. Subsequent transfusion of 2 group B, phenotype-matched RBC units using a blood warmer was uneventful. Anti-IH is only rarely associated with hemolytic transfusion reactions, which may be exacerbated when transfusing group O RBC units to group B patients. M. pneumoniae infection likely led to cold agglutinin-mediated hemolysis of endogenous and transfused RBCs. The patient was successfully managed with intravenous immunoglobulin, steroids, rituximab, erythropoietin, hydroxyurea, and amoxicillin clavulanate/azithromycin. This case illustrates the importance of infectious disease evaluation in patients with unexplained anemia, the potential clinical significance of autoanti-IH, and the value of providing type-specific RBC units in these circumstances., (© 2024 Jennifer N. Chousal et al., published by Sciendo.)

We report a case of coexisting cold agglutinin and cryoglobulin in a patient with severe anemia following COVID-19 infection, in whom direct antiglobulin testing revealed C3d positivity and immunoglobulin G negativity. There was no evident hemolytic anemia, thrombosis, or clinically significant IgM monoclonal gammopathy. The anemia improved with folic acid supplementation alone accompanied by a decrease of the cold agglutination titer, and the direct antiglobulin test became negative. Despite continuous positivity for cryoglobulinemia, the patient exhibited no clinical symptoms such as thrombosis. Immunosuppressive therapy for cold-related hematologic disorders after COVID-19 infection should be considered carefully., 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, Kaneko et al.)

Cold agglutinin disease (CAD) is a distinct clinicopathologic entity characterized by clonal B-cell lymphoproliferative disorder in the bone marrow. B-cell gene mutations affect NF-ΚB as well as chromatin modification and remodeling pathways. Clonal immunoglobulins produced by B cells bind to red cells (RBCs) at cold temperatures causing RBC aggregation, complement cascade activation and cold-autoantibody autoimmune hemolytic anemia (cAIHA). The clinical picture shows cold-induced symptoms and cAIHA. Therapeutic options include “wait and watch”, rituximab-based regimens, and complement-directed therapies. Steroids must not be used for treating CAD. New targeted therapies are possibly identified after recent molecular studies.

Antibodies to red blood cells (RBCs) may hemolyze erythrocytes via Fc-mediated phagocytosis or complement-dependent. Complement activation on RBCs can be detected by C3d-direct antiglobulin test (DAT), which is the only test in immune hematology that directly targets complement. However, a positive DAT with anti-C3d cannot distinguish between C3b-mediated extravascular hemolysis, C5b-C9-mediated intravascular hemolysis and C5b-C8-mediated eryptosis. Furthermore, DAT is not suitable to estimate the strength of hemolysis. Autoimmune hemolytic anemia (AIHA) is a rare disease that is caused by autoantibodies to red blood cells that is divided in warm AIHA and in cold agglutinin disease (CAD). The causative antibodies in CAD and sometimes in warm AIHA are from the IgM class. Depending on strength of complement activation they can induce extravascular hemolysis, intravascular hemolysis and eryptosis. We studied the three types of hemolysis by use of sera from patients with CAD under various conditions. We found that additionally to the routinely applied C3d-DAT, indirect tests for complement activity (free hemoglobin and Annexin V-binding to phosphatidylserine-exposing RBCs) should be used to determine the portion of extravascular, intravascular and eryptotic hemolysis. Eryptotic hemolysis may have a significant share in clinical relevant CAD or IgM warm AIHA, which should be considered for successful treatment.

Abstract This case emphasizes the importance of prompt comprehensive investigation of anemia and myositis in patients infected with SARS‐CoV‐2 and early recognition of uncommon complications that can be associated with SARS‐CoV‐2 infection.

This case report concerns a 71 year old female patient who had a very low glycosylated hemoglobin (HbA1c) despite having a high level of fasting blood glucose. The patient had a decreased erythrocyte count, elevated red blood cell indices, and a reticulocyte count with no evidence of hemoglobinopathy. She reported receiving hydroxychloroquine treatment for systemic lupus erythematosus. Subsequent laboratory investigations revealed hemolysis with formation of cold agglutinin. Because cold agglutinins can interfere with HbA1c assays, the specimens were reanalyzed after warming. The complete blood count results improved, but the HbA1c result did not change. In patients in whom medications and/or medical conditions may interfere with HbA1c levels, alternative measures of glycemic control, such as fructosamine, could be beneficial. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are 2 distinct immune-mediated hematologic disorders. While no clear association exists between these 2 entities, complement activation is known to occur in both of them. Herein, we report a unique case of cold agglutinin hemolytic anemia in a patient with a known primary antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (n = 16) of 35 tested patients had a positive cold agglutinin test and 27% (n = 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (P = 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (P = 0.009) or immersion in cold water (P = 0.041), and aggravated by increased summer humidity (P = 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (P = 0.043), and lower disease control based on Urticaria Control Test (P = 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = −0.372, P = 0.028) and monocyte counts (r = −0.425, P = 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733, P = 0.025) and cold urticaria duration (r = 0.683, P = 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease.

Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (n = 16) of 35 tested patients had a positive cold agglutinin test and 27% (n = 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (P = 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (P = 0.009) or immersion in cold water (P = 0.041), and aggravated by increased summer humidity (P = 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (P = 0.043), and lower disease control based on Urticaria Control Test (P = 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = −0.372, P = 0.028) and monocyte counts (r = −0.425, P = 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733, P = 0.025) and cold urticaria duration (r = 0.683, P = 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease. [ABSTRACT FROM AUTHOR]

We report the case of an 82‐year old male patient admitted in our medical intensive care unit for diffuse skin lesions, 3 days after the onset of ceftriaxone for bilateral pneumonia without microbiological documentation. The patient concomitantly exhibited diffuse skin lesions compatible with livedo and neurological and haemodynamic failure. Biological analysis revealed acute haemolytic anaemia. Warming of patient, red blood‐cells transfusion and high‐doses corticosteroids were initiated and ceftriaxone was stopped. Despite these therapeutics, the patient exhibited multiple organ failure and died. The main suspected triggering factor of this acute and fatal haemolytic anaemia was ceftriaxone administration considering: (i) the delay between cephalosporin administration and symptoms; (ii) the worsening of livedo and acrocyanosis a few hours after meningeal ceftriaxone doses; and (iii) fatal evolution. Cephalosporin‐induced autoimmune haemolytic anaemia is a rare and serious cause of livedo that should be suspected in patients exhibiting livedo and acute haemolytic anaemia within hours/days following cephalosporin administration. [ABSTRACT FROM AUTHOR]

This case emphasizes the importance of prompt comprehensive investigation of anemia and myositis in patients infected with SARS‐CoV‐2 and early recognition of uncommon complications that can be associated with SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

The cold agglutinins (CAs) associated with Mycoplasma infection may give rise to autoimmune hemolytic anemia (AIHA), and in rare cases, results in severe crises requiring hospitalization. The present case was this kind with severe hemolytic crises due to clinically significant CA that had caused the life-threatening AIHA in association with the infection by Mycoplasma pneumoniae. The blood specimens were collected in the warm environment to obviate spontaneous autoagglutination. Autoimmune nature of the CA involved was established by the direct antiglobulin test (DAT) using reagents obtained from commercial sources. The serological specificity of the CA was ascertained by titration by saline tube test against the red blood cells (RBCs) from the adults and the newborn infants as well as the hemagglutination inhibition study using human milk as a source of the soluble I antigen. The patient's clinical and other details were obtained from the hospital records. A 20-year-old male admitted to the hospital with a severe hemolytic crisis that required blood transfusion. DAT on his RBCs was positive due to the presence of C3d complement fraction, in concurrence with a high-titer CAs with anti-I specificity and positive serological test for M. pneumoniae. A severe hemolytic crisis was evident by sudden drop in hemoglobin, presence of reticulocytes and erythroblasts in circulation. The patient was conservatively treated with antibiotics, steroid, and blood transfusions with improvement in condition and was discharged after 7 days of hospitalization. He was followed up for the next 3 months through which he continued to be in good condition. The investigations showed a rare case of the CA, with anti-I specificity, causing severe hemolytic crisis in association with M. pneumoniae infection that required hospitalization.

Skin involvement is not common as the first manifestation of Multiple Myeloma (MM). Although extremely rare, leucocytoclastic vasculitis, plasmasytoma, autoimmune bullous disease, livedo reticularis and Raynaud’s phenomenon may be the initial presentationof MM. Raynaud’s phenomenon and livedo reticularis related to cold exposure can be due to Cold Agglutinin Disease (CAD) or cryoglobulinemia and can be seen as the first manifestation of MM. In this case study, we described a 55-year-old man complaining of limbs livedo reticularis and Raynaud’s phenomenon during cold weather. Further evaluations revealed anemia and elevated ESR. Skull X-ray showed multiple punched-out lesions. Finally, serum protein electrophoresis and bone marrow aspiration confirmed the diagnosis of non-secretory MM as the underlying disease of CAD. The patient was referred to the hematologist for the treatment of MM.

Introduction: Immune checkpoint inhibitors are drugs that are included in the guidelines of hematological and solid cancer treatments, give highly effective results and increase T cell functionality. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. Case report: A 50-year-old male patient was admitted to an external center with complaints of chest pain and dyspnea. Thoracic CT revealed a 97 × 58 mm mass in the left lung, and a diagnosis of Small Cell Lung Cancer (SCLC) was made by biopsy. The PET/CT performed for staging was also evaluated as extensive stage small cell lung cancer. It was decided to give a combination of atezolizumab and carboplatin-etoposide to the patient. Management and outcome: The patient completed 3 cycles without any problem. Discordance was detected in the hemogram of the patient who came to the control for the assessment of response and had a regression in the imaging. Hemoglobin 9.6 g/dl (N: 14–17.5) hematocrit 14.8% (N: 41–51) were detected in the hemogram. Agglutinins were seen in the peripheral smear performed. Cold agglutinin (+4 positive) and indirect coombs (+3 positive) were found positive. Atezolizumab was stopped and methylprednisolone was started. After 10 days of treatment, discordance improved and methylprednisolone was discontinued by decreasing to half dose every 5 days. Discussion: With the increasing use of immune checkpoint inhibitors, the variety of side effects has increased and case reports have increased. After detection of cold agglutinin, IgG, cryoglobulin, mycoplasma pneumonia, hepatitis B, hepatitis C and HIV were found negative in the differential diagnosis, Our case appears to be immune checkpoint inhibitor-related Cold Agglutinin Disease (CAD). It should not be forgotten that immune checkpoint inhibitors, which are widely used, may cause CAD, and hemoglobin-hematocrit discordance should be paid attention to in routine controls. [ABSTRACT FROM AUTHOR]

Cold agglutinins (CA) are auto-antibodies that adhere to erythrocytes in cold temperatures, and can result in agglutination of red blood cells. This process can cause complementmediated intravascular hemolysis, which can be catastrophic. We describe a patient who developed CA during initiation of deep hypothermic circulatory arrest for emergent repair of Type A aortic dissection. The patient was found to have anti-I and anti-C antibodies and a positive direct Coombs test. CA resolved with re-warming, and resulted in no adverse events. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) can trigger autoimmune phenomena, with immune thrombocytopenia (ITP) the most common presentation. Upon cessation of CLL therapy, including ibrutinib, autoimmune flares can occur. In a 68-year-old man with CLL, ibrutinib was held for 2 weeks prior to elective shoulder surgery. Eleven days after stopping therapy, he presented with a purpuric rash on his right hip, buttock, and lower extremities. He experienced two episodes of seizure activity while hospitalized. MRI brain demonstrated patchy areas of altered signal involving deep white matter and sub-cortical white matter structures concerning for cerebral vasculitis. Although there was no evidence of hemolysis, serum cold agglutinin titer was elevated at > 1:512 and cryoglobulin levels were positive at 36%. He was diagnosed with type I cryoglobulinemia and treated with rituximab, plasmapheresis, methylprednisolone, and ibrutinib was restarted. This regimen resolved his symptoms. A rare complication of CLL is the production of cryoglobulins, which can present at initial diagnosis or in relapsed disease. Our case demonstrates that the cessation of ibrutinib therapy, even for a short time, can precipitate complications. To our knowledge, we report the first case of a patient with well-controlled CLL who rapidly developed cryoglobulinemic vasculitis after stopping ibrutinib therapy. [ABSTRACT FROM AUTHOR]

A 14-year-old female patient presented with a 3-day history of high fever and cough. It was learnt that she had started to use oseltamivir after her complaints started. Physical examination revealed decreased breath sounds in the lower and middle zones of the left lung and crepitant rales in the right lung. Some laboratory examination test results were as follows: hemoglobin 10.6 g/dL, hematocrit 33.5%, MCV 76.5 fL, white blood cell count 5.97x103 / uL, platelet count 180x103/uL, CRP 205.6 mg/L, procalcitonin 1.28 ng/mL. Posteroanterior (PA) chest X-ray showed consolidation in the middle and lower zones of the left lung and infiltration in the lower zone of the right lung. Treatment with ceftriaxone, clarithromycin and teicoplanin was started. On the third day of treatment, their body temperatures fell and her general condition improved. On the 10th day of clinical follow-up, chest X-ray findings improved significantly, In control tests hemoglobin (10.8 g/dL), hematocrit (20.6%), platelet count (519x103/uL), and reticulocyte count (2.14%), were also evaluated. Direct and indirect Coomb's tests yielded positive results. The results of some tests perfomed were as follows: Cold agglutinin titration test (1/2016), Cryoglobulin negative, Cryofibrinogen negative. Mycoplasma pneumoniae (M. pneumoniae) IgM 1.33 (positive), M. pneumoniae IgG 0.38 (negative), EBV - VCA IgM: 0.62 (negative), EBV - VCA IgG: 196 (positive). She was discharged with levofloxacin treatment without any additional treatment. Hemolysis crisis was not observed during the follow-up. Cold agglutination disease should be considered when hemoglobin - hematocrit incompatibility is detected in patients with lung infection. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a well-known disease characterized by autoimmune chronic inflammation and autoantibodies. Autoimmune hemolytic anemia (AHA) may develop in <10% of SLE patients due to these autoantibodies. SLE-related AHAs usually develop through warm-type antibodies. Cold antibodymediated haemolytic anemia in SLE is extremely rare and generally unresponsive to glucocorticoid therapy. In this article, a SLE case with cold agglutinin hemolytic anemia, who responded well to steroid treatment, is presented. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

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.

Cold agglutinin-induced hemolytic anemia as the primary presentation in systemic lupus erythematosus (SLE) is extremely rare. Only few cases have been reported in literature so far. Here, we report a 17-year-old girl who presented with features of hemolytic anemia and later diagnosed as a case of SLE.

Chronic agglutinin disease (CAD) is a rare form of adult autoimmune hemolytic anemia due to the presence of an IgM autoantibody that is active at low temperature and leads to the accelerated destruction of red blood cells throughout complement activation. It is now well admitted that CAD is actually, in most of the cases, a B cell monoclonal disease as proven by the presence of a monoclonal IgM with cold agglutinin activity and the presence of a bone marrow infiltrate which immunophenotypic characteristics can be distinguished from those of lymphoplasmacytic lymphoma. The management of CAD, which has long been empirical and mostly symptomatic, has improved with the use of rituximab alone or combined with chemotherapy in order to target the underlying B-cell clone. Moreover, the ongoing development of new complement inhibitors opens a promising era for the management of patients with severe and transfusion-dependent hemolysis. [ABSTRACT FROM AUTHOR]