OBJECTIVE: To analyze the clinical features and laboratory characteristics of patients with cold agglutinin disease (CAD)/cold agglutinin syndrome (CAS) who were positive for acidified-serum lysis test (Ham test), and to compare them with Ham test negative CAD/CAS patients and paroxysmal nocturnal hemoglobinuria (PNH) patients, in order to provide references for the differential diagnosis of these diseases. METHODS: 53 patients diagnosed with CAD/CAS and 67 patients diagnosed with classic PNH in our hospital from January 2015 to December 2020 were retrospectively analyzed. The patients were grouped according to clinical diagnosis and results of cold agglutinin test (CAT), direct antiglobulin test (DAT), Ham test and PNH clone detection. The clinical and laboratory characteristics of each group were compared. RESULTS: The patients were grouped as follows: Ham^- CAD/CAS group, CAD/CAS patients negative for Ham test (n=36); Ham⁺ CAD/CAS group, CAD/CAS patients positive for Ham test (n=17); classic PNH group (n=67). Compared with the classic PNH group, the Ham⁺ CAD/CAS group had a higher median age (P =0.024), weaker positivity of Ham test, higher positive rates of CAT and DAT, and lower positive rate of PNH clone detection (all P <0.001). The proportions of patients with splenomegaly and cyanosis in Ham⁺ CAD/CAS group were significantly higher than those in classic PNH group (P =0.002 and P <0.001). Ham⁺ CAD/CAS group displayed lower red blood cell count (RBC) and lactate dehydrogenase (LDH) level (P =0.007 and P <0.001), and higher mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and indirect bilirubin (IBIL) level (P =0.003, P =0.004 and P =0.006) than those in classic PNH group. The levels of serum complement C3 and C4 in Ham⁺ CAD/CAS group were lower than those in classic PNH group (P =0.001 and P <0.001). The positive rate of urinary occult blood in Ham⁺ CAD/CAS group was lower than that in classic PNH group (P =0.010). The clinical and laboratory characteristics of Ham⁺ CAD/CAS group were similar to those of Ham^- CAD/CAS group, except for median age, hemoglobin (Hb), MCHC, mean corpuscular volume (MCV), reticulocyte ratio (Ret), Ham test results, DAT positive types, and proportion of splenomegaly. CONCLUSION Some clinical features and laboratory indicators of CAD/CAS patients with positive results of Ham test are different from those of classic PNH patients, but relatively similar to those of CAD/CAS patients with negative results of Ham test. These results may provide a reference for differential diagnosis of related diseases.
Humans ; Anemia, Hemolytic, Autoimmune/blood* ; Retrospective Studies ; Hemoglobinuria, Paroxysmal/diagnosis* ; Female ; Male ; Coombs Test ; Diagnosis, Differential ; Middle Aged ; Adult

Objective To investigate the clinical characteristics,treatment responses,and prognosis of patients with idiopathic multicentric Castleman disease(iMCD)complicated by autoimmune hemolytic anemia(AIHA). Methods The patients diagnosed with iMCD in Peking Union Medical College Hospital from January 2010 to December 2023 and having complete baseline blood routine data were retrospectively enrolled in the study.The iMCD patients were further assigned into AIHA and non-AIHA groups based on baseline laboratory examinations,and the clinical characteristics and prognosis were compared between the two groups. Results A total of 341 patients with iMCD were enrolled in this study,including 277(81.2%)exhibiting anemia at baseline.Five(1.8%)patients were identified as having iMCD-AIHA,all of whom were iMCD-not otherwise specified type complicated by warm antibody-type AIHA,and two of them were simultaneously diagnosed with Evans syndrome.The timing relationship between the first onset of AIHA and iMCD diagnosis varied,with 2 patients experiencing their first hemolytic episode prior to the diagnosis of iMCD.In terms of treatment,the therapy targeting iMCD was effective in alleviating AIHA.The AIHA group had a poorer prognosis(HR=4.61,95% CI=1.08-19.80,P=0.040)and a lower 5-year survival rate(90% vs.60%,P=0.024)than the non-AIHA group.Conclusions iMCD-AIHA is clinically rare,and AIHA can occur at different stages of iMCD.Although the primary treatment principle remains targeting iMCD,great attention should be paid to the exacerbation of immune dysfunction caused by AIHA and the possible adverse prognosis it may bring.
Humans ; Anemia, Hemolytic, Autoimmune/diagnosis* ; Castleman Disease/diagnosis* ; Retrospective Studies ; Male ; Female ; Prognosis ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent

Thrombotic microangiopathy (TMA) is a group of highly heterogeneous, acute and severe clinicopathological syndromes, characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and ischemic injury of end organs. TMA has the characteristics of dangerous condition, multiple organ involvement and high mortality. Patients with severe TMA need to be admitted to intensive care unit (ICU) for organ function support therapy. Early and rapid evaluation, differential diagnosis, and timely and effective treatment are the key to improve the prognosis of TMA patients. Here, we review the pathophysiological changes, diagnosis differential diagnosis, and treatment of the severe TMA in adult.
Adult ; Humans ; Thrombotic Microangiopathies/therapy* ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Anemia, Hemolytic/therapy* ; Treatment Outcome ; Diagnosis, Differential

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.
Male ; Humans ; Aged ; Anemia, Hemolytic, Autoimmune/diagnosis* ; Sjogren's Syndrome/diagnosis* ; Anemia, Hemolytic/complications* ; Dry Eye Syndromes/complications* ; Autoantibodies

OBJECTIVE: To investigate the clinical features and laboratory characteristics of primary autoimmune hemolytic anemia (AIHA) patients with negative results of direct antiglobulin test (DAT) by tube test but positive results by microcolumn gel assay, in order to provide references for the diagnosis of these patients. METHODS: 59 patients diagnosed with primary AIHA in our hospital from January 2015 to December 2020 were retrospectively analyzed. According to the results of tube test and microcolumn gel assay, the cases were divided into 3 groups, and the clinical and laboratory characteristics of each group were compared. RESULTS: The cases were grouped as follows: Group I, cases with negative results by both methods of DAT (n=5); Group II, cases with negative results by tube test but positive results by microcolumn gel assay (n=26); Group III, cases with positive results by both methods of DAT (n=28). There was no significant difference in age and sex between Group II and other groups, whereas the positive rate of anti-IgG + anti-C3d of Group II was lower than that in Group III (P=0.015). The main clinical manifestations of Group II were chest tightness, shortness of breath, fatigue, as well as yellow skin and sclera or dark urine, but the incidence rate of these symptoms was not significantly different from other groups. Anemia related indexes in Group II such as red blood cell (RBC) count and hemoglobin (Hb) were lower than the reference intervals, but there was no significant difference compared with other groups. Hemolysis related indexes in Group II such as reticulocyte (Ret) ratio, indirect bilirubin (IBIL), lactate dehydrogenase (LDH) and free-hemoglobin (F-Hb) were higher than the reference intervals, and the latter two items were signficantly higher than those in Group I (P=0.031 and P=0.036). Serum complement C3 and C4 in Group II were higher than those in Group III (P=0.010 and P=0.037). CONCLUSION Anemia severity of primary AIHA patients who were negative of DAT by tube test but positive by microcolumn gel assay was similar to those with negative or positive results by both DAT methods, but the mechanism and degree of complement system involved in hemolysis might be different. Results above may be helpful for laboratory diagnosis of this kind of patients.
Anemia, Hemolytic, Autoimmune/diagnosis* ; Bilirubin ; Complement C3 ; Coombs Test/methods* ; Erythrocytes ; Hemolysis ; Humans ; Lactate Dehydrogenases ; Negative Results ; Retrospective Studies

OBJECTIVE: To analyze one case of multiple myeloma (MM) initially presenting cold agglutinin syndrome (CAS), so as to improve clinical understanding and screening of this disease. METHODS: The clinical data, laboratory examination, bone marrow result, diagnosis and treatment of the patient were analyzed and summarized to provide ideas and clinical experience for the early diagnosis and treatment of CAS secondary to MM. RESULTS: The clinical manifestations of asthenia, hemolysis, jaundice and scattered livedo reticularis were caused by CAS secondary to MM, which was different from the general Raynaud's phenomenon. IgMκ type MM was definitely diagnosed according to the morphological features of bone marrow cells and immunofixation electrophoresis. After 3 courses of chemotherapy with BAD regimen and enhanced thermal support, anemia was corrected, M protein was decreased and the cold agglutinin phenomenon was significantly reduced. The evaluation of efficacy reached very good partial response. CONCLUSION There are very few MM patients with CAS as the initial presentation, so it is easy to misdiagnose. Early diagnosis and individual therapy are particularly important, which requires clinicians to observe and gain experience further.
Anemia, Hemolytic, Autoimmune/diagnosis* ; Cryoglobulins ; Early Diagnosis ; Humans ; Multiple Myeloma/diagnosis*

IgG4-related disease (IgG4-RD) is a rare autoimmune fibrosis disease characterized by elevated serum IgG4 and tissues as well as organs infiltrated with IgG4-positive cells, resulting in swelling and damage.It is currently treated as first-line treatment with glucocorticoids. Autoimmune hemolytic anemia (AIHA) is also a relatively rare disease that caused by autoreactive erythrocyte antibodies. Although both are autoimmune-related diseases, they rarely overlap. The relationship between them is not clear. A case of IgG4-RD combined with AIHA is reported. The patient has shortness of breath, cough, and sputum after physical activity. Physical examination showed appearance of anemia, yellow staining of skin and sclera, palpable neck and multiple swollen lymph nodes. Laboratory examination, bone marrow biopsy, and lymph node biopsy confirmed the diagnosis. Therefore, clinicians should develop ideas and raise awareness of such diseases.
Anemia, Hemolytic, Autoimmune ; diagnosis ; drug therapy ; Autoimmune Diseases ; complications ; Biopsy ; Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease ; complications ; diagnosis

Diagnosis of thrombotic microangiopathy (TMA) is challenging due to its close association with other forms of microangiopathic hemolytic anemia, such as malignant hypertension and disseminated intravascular coagulation, and because other manifestations including cytopenia and acute kidney injury are manifestations of other medical comorbidities. Further challenges for accurate diagnosis include distinguishing between primary and secondary TMA, as well as between hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). TTP is typically differentiated from HUS by the presence of more severe thrombocytopenia, along with a higher frequency of altered mental status with relatively preserved renal function. However, the clinical course can vary among patients, requiring polymerase chain reaction testing of patient stools for enterohemorrhagic Escherichia coli and a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) assay. To reduce the mortality rate, prompt initiation of plasmapheresis is important in cases where TPP cannot be excluded. Future advances enabling more rapid testing for ADAMTS13 levels will reduce the need for unnecessary plasmapheresis, so that treatment strategy can be more optimized.
Acute Kidney Injury ; Anemia, Hemolytic ; Comorbidity ; Diagnosis ; Diagnosis, Differential ; Disseminated Intravascular Coagulation ; Enterohemorrhagic Escherichia coli ; Hemolytic-Uremic Syndrome ; Humans ; Hypertension, Malignant ; Mortality ; Plasma Exchange ; Plasmapheresis ; Polymerase Chain Reaction ; Purpura, Thrombotic Thrombocytopenic ; Thrombocytopenia ; Thrombospondins ; Thrombotic Microangiopathies

Anemia, Hemolytic ; chemically induced ; diagnosis ; Ceftriaxone ; adverse effects ; Child ; Cochlear Implantation ; adverse effects ; Hearing Loss, Sensorineural ; surgery ; Humans ; Male ; Vestibular Aqueduct

BACKGROUND: Warm autoimmune hemolytic anemia (w-AIHA) is an uncommon disease with heterogeneous response to treatment. Steroids are the standard treatment at diagnosis, whereas rituximab has recently been recommended as the second-line therapy of choice. Our main objective was to document the response to treatment in patients with newly diagnosed w-AIHA, including the effectiveness of low-dose rituximab as frontline treatment and for refractory disease. METHODS: Patients with w-AIHA from 2002 to 2017 were included. Relapse-free survival (RFS), probability of maintained response (MR), and time-to-response were analyzed using the Kaplan–Meier method. Response was classified as complete, partial, and no response. RESULTS: We included 64 adults with w-AIHA (39 women and 25 men). The median age was 37 (16–77) years. Response rates to steroids alone were 76.7%, rituximab plus steroids, 100%; and cyclophosphamide, 80%. RFS with steroids at 6, 36, and 72 months was 86.3%, 65.1%, and 59.7%, respectively. Eighteen patients received rituximab at 100 mg/wk for 4 weeks plus high-dose dexamethasone as first-line therapy, with RFS at 6, 36, and 72 months of 92.3%, 58.7% and 44.1%, respectively. Eight patients refractory to several lines of therapy were treated with low-dose rituximab, and all achieved a response (three complete response and five partial response) at a median 16 days (95% confidence interval, 14.1–17.8), with a 75% probability of MR at 103 months; the mean MR was 81.93±18 months. CONCLUSION: Outcomes of w-AIHA treatment were considerably heterogeneous. Low rituximab doses plus high dexamethasone doses were effective for refractory disease.
Adult ; Anemia, Hemolytic, Autoimmune ; Cyclophosphamide ; Dexamethasone ; Diagnosis ; Female ; Humans ; Methods ; Mexico ; Rituximab ; Splenectomy ; Steroids