RBC autoantibodies in autoimmune lymphoproliferative syndrome

BACKGROUND: Patients with autoimmune lymphoproliferative syndrome (ALPS) have an autosomal dominant genetic defect that affects lymphocyte apoptosis and is associated with chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity, particularly affecting RBCs, WBCs, and platelets. STUDY DESIGN AND METHODS: DATs were performed on 34 consecutive patients with ALPS and 37 of their clinically unaffected relatives. The effects of age, sex, race, and immunoglobulin levels on the incidence of autoantibodies and clinical hemolysis were assessed. RESULTS: The DAT was positive in 21 (62%) of ALPS patients but in only 1 (3%) of their relatives (p = 0.001). The DAT reacted because of IgG alone in 43 percent, complement alone in 5 percent, and IgG plus complement in 19 percent; 33 percent of the patients' cells had a positive reaction with polyspecific reagent only. All 10 ALPS patients with a history of hemolytic anemia had a positive DAT. Sixty percent of them had only IgG on their cells, 30 percent had IgG and complement, and 10 percent reacted only with polyspecific reagent. Of the 11 patients with a positive DAT and no history of hemolytic anemia, IgG alone was present in 27 percent, complement alone in 9%, and IgG plus complement in 9 percent; 55 percent had positive DATs only with polyspecific reagent. Among ALPS patients, those with a positive DAT had greater quantities of cells with increased alpha and ss T-cell receptors that phenotyped as CD4-CD8- and higher IgG levels. CONCLUSIONS: The DAT results in ALPS patients are most similar to those found in warm autoimmune hemolytic anemia. The DAT is useful to distinguish affected and unaffected persons within an ALPS family.     

Vaccination-associated immune hemolytic anemia in two children

BACKGROUND: Two children in whom acute autoimmune hemolytic anemia (AIHA) developed after vaccination were studied. CASE REPORTS: The children were a 20-month-old girl and a 21-month-old boy. The diagnosis of AIHA was made in accordance with established criteria (hemolysis, positive DAT, and lack of other reasons for the hemolysis). Serologic tests were performed according to standard technique. RESULTS: The girl experienced two attacks of hemolysis. The first episode occurred 2 weeks after oral polio vaccination, and the second episode was observed 7 months later, when she received a simultaneous vaccination against mumps, rubella, and measles. The DAT was strongly positive with anti-C3d. No autoantibodies were detectable in either episode. The boy experienced acute hemolysis a few days after a simultaneous revaccination against diphtheria-pertussis-tetanus, Haemophilus influenzae, hepatitis B, and polio. The DAT using anti-IgG was strongly positive, and the DAT performed with anti-C3d was weakly positive. CONCLUSION: Vaccination-induced AIHA resembles those forms of AIHA related to infectious diseases, and it may occur more frequently than has been reported.     

Aquired immune hemolytic anemias

Aquired immune hemolytic anemias are classified in autoimmune hemolytic anemia (AIHA) of warm type, cold agglutinine disease, paroxysmal cold hemoglobinuria, drug-induced immune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria. The autoantibodies in AIHA of warm type react most strongly at 37 degrees C (warm autoantibodies). They are of the IgG, less commonly of the IgM and IgA classes. The cause of autoimmunization remains obscure in 50% of the patients (idiopathic AIHA). In the remaining cases, the AIHA is associated with other diseases. Corticosteroids are the mainstay of therapy, but most patients with AIHA of warm type require additional treatment with azathioprine or other drugs. Cold agglutinins are the cause of hemolysis in about 10% of patients with AIHA. Paroxysmal cold hemoglobinuria (Donath-Landsteiner) is less common and occur in children following infections. Drugs are the cause of hemolysis in about 10% of all cases with AIHA. The true incidence of alloimmune hemolytic anemias including neonatal immune hemolytic anemias is unknown. The paroxysmal nocturnal hemoglobinuria is rare. It is caused by complement activation due to aquired membrane defects.     

84例自身免疫性溶血性贫血IgG抗体亚型与临床意义的分析

目的　研究温抗体型自身免疫性溶血性贫血ＩｇＧ亚型及其临床意义。方法　回顾性分析８４ 例患者ＩｇＧ亚型与临床特点的关系。结果　８４ 例患者中ＩｇＧ１ ＋ＩｇＧ３ ＋ Ｃ３ｄ 型占４５．０％ ,ＩｇＧ１ ＋ＩｇＧ３型占１５ ．５％ ,ＩｇＧ１ ＋ Ｃ３ｄ型占１１．０％ ,Ｃ３ｄ型占１０ ．７％ ,ＩｇＧ１ 型占９．５％ ,ＩｇＧ３ ＋ Ｃ３ｄ占８．３ ％ 。各型中均以女性为主,合计占６９ ．５％ 。ＩｇＧ３ 阳性各型的临床表现相似,各项临床指标异常最严重;ＩｇＧ１ 阳性的各型次之;Ｃ３ｄ 型最轻。Ｈｂ＜６０ ｇ／Ｌ、总胆红素＞ ４０ μｍｏｌ／Ｌ、ＦＨｂ＞ ６０ ｍｇ／Ｌ的患者百分率三组间比较,差异有显著性（Ｐ＜０ ．０５） 。ＩｇＧ１ 型与ＩｇＧ３ 型都随Ｃｏｏｍｂｓ 试验积分增高,其临床表现及溶血程度加重。ＩｇＧ３ 阳性的患者治疗有效率为６８ ．２％ ,ＩｇＧ１ 阳性患者有效率为１００％ 。结论　ＩｇＧ 亚型中以ＩｇＧ１ ＋ＩｇＧ３ 为主。ＩｇＧ３ 阳性的患者临床表现及溶血程度严重,治疗效果差     

自身免疫性溶血性贫血的免疫分型及临床分析

目的 对64例自身免疫性溶血性贫血(AIHA)患者血液中红细胞上结合的抗体进行免疫分型,进一步指导临床治疗.方法 采用免疫分型技术及相关溶血性贫血系列检测法.结果 发病较多的是青壮年,女性多于男性,类型分布以IgG C3型多见,且贫血、溶血程度重,余依次为C3型、IgG型.结论 AIHA免疫分型可判定疾病的严重程度以及为临床治疗提供依据.     

Evaluation of the manual hexadimethrine bromide (Polybrene) technique in the investigation of autoimmune hemolytic anemia

The use of the direct manual hexadimethrine bromide (Polybrene) test (DPT) in the investigation of patients for autoimmune hemolytic anemia (AIHA) was evaluated. Seventy-nine blood samples from 68 patients were tested. A direct antiglobulin test (DAT) using monospecific reagents and the DPT were performed, and a concentrated ether eluate was tested. The DAT was positive in 62 (78%) of 79 patients and negative in 17 (22%). There is a good correlation among DAT, eluate, and DPT in demonstrating the presence of immunoglobulin on the red cell surface. In contrast, the DPT does not detect C3d and is often negative in cases of AIHA in which C3d alone is demonstrated by the DAT. In DAT-negative cases, DPT results correlated with reactive eluates. However, in four cases of steroid-responsive, DAT-negative hemolytic anemia, the DPT supported the diagnosis of AIHA when the eluate did not react. The DPT is a useful additional screening test for the investigation of AIHA, but it is not recommended as a replacement for either eluate testing or the DAT.     

Serologic findings in autoimmune hemolytic anemia associated with immunoglobulin M warm autoantibodies

BACKGROUND: Autoimmune hemolytic anemia (AIHA) associated with immunoglobulin M (IgM) warm autoantibodies is unusual but often severe, with more fatalities than other types of AIHA. Diagnosing this type of AIHA can be difficult because routine serologic data are not always informative.
STUDY DESIGN AND METHODS: Forty-nine cases of IgM warm AIHA in 25 years were studied by serologic methods.
RESULTS: Routine direct antiglobulin tests (DATs) detected red blood cell (RBC)-bound C3 in 90 percent of cases (65% had C3 but no immunoglobulin G [IgG] on their RBCs) and IgG in 24 percent. IgM was detected on 29 of 47 (62%) patients' RBCs; RBC-bound IgM was detected in 14 of 47 cases by a tube DAT method and in an additional 15 of 21 (71%) cases using fluorescein isothiocyanate anti-IgM and flow cytometry. Eighty-one percent of eluates from patients' RBCs reacted. Warm autoagglutinins were present in 94 percent of serum samples; untreated and enzyme-treated RBCs were hemolyzed at 37°C by 13 and 65 percent of serum samples, respectively. Most agglutinins were optimally reactive at 30 to 37°C. Patients' RBCs were spontaneously agglutinated in 78 percent of cases; washing with 37°C saline or treating RBCs with dithiothreitol resolved this problem. Clear specificity of autoantibody was defined in 35 percent of serum samples.
CONCLUSION: IgM warm AIHA can be confused with cold agglutinin syndrome and "mixed/combined"-type AIHA; a serologic workup by a specialist reference laboratory can help with the diagnosis.     

A dual antiglobulin test for the detection of weak or nonagglutinating immunoglobulin M warm autoantibodies

BACKGROUND: Immunoglobulin (Ig)M warm autoantibodies (AABs) usually cause severe autoimmune hemolytic anemia (AIHA) and, in some cases, red blood cell (RBC)‐bound IgM cannot be detected. We describe a simple dual antiglobulin test (DDAT) for diagnosing such cases. STUDY DESIGN AND METHODS: A patient with erroneously suspected cold agglutinin syndrome was investigated. The direct antiglobulin test (DAT) was performed using standard techniques and dual (two stages) antiglobulin reagents (IgG rabbit anti‐human IgM, IgG goat anti‐rabbit IgG). RESULTS: A cold agglutinin syndrome was diagnosed initially, as the patient's serum was reactive with RBCs at a temperature of 28°C or less, and the DAT was strongly positive with anti‐C₃d. Six months later, the patient was reexamined at this hospital due to progressive hemolysis. His RBCs were found to be coated with IgM warm AABs that only became detectable using a DDAT, and his serum contained only a weak cold agglutinin. The hemolysis remained refractory to treatment with prednisolone and also prednisolone plus azathioprine, but gradually improved after treatment with prednisolone plus cyclophosphamide. CONCLUSION: Weak or nonagglutinating RBC‐bound IgM warm antibodies can be identified by the presented DDAT.     

IgA-mediated autoimmune hemolytic anemia in an infant

Autoimmune Hemolytic anemia (AIHA) a relatively uncommon form of hemolytic anemia in children, occurs due to the premature destruction of red blood cells caused by presence of autoantibodies directed against antigens on RBCs. Warm reactive AIHA is the most common form due to IgG isotype of immunoglobulin class binding to autologous RBCs at 37⁰C and confirmed with a positive DAT screening. We present a case of DAT-negative primary warm AIHA in an infant due to IgA antibody. A 10 month old male infant presented with dark colored urine and irritability for past two months, with associated history of fever, diarrhea and vomiting. He had received one red cell transfusion 10 days prior. On physical examination he had pallor with tachycardia without splenomegaly. On investigation his hemoglobin was 5.8 g/dl, WBC 25.9 × 10³/mm³ and normal platelets counts. Peripheral blood smear had spherocytes and biochemical values showed high bilirubin and LDH. Immunohematological work up revelaed polyspecific DAT was negative but monospecific DAT screening showed strong (4+) positivity for IgA and a weak IgG positivity. The patient was diagnosed as IgA-mediated Warm AIHA and was started on prednisolone at 2 mg/kg/day following which hemoglobin improved over the next 2 months. After 2 weeks, prednisolone was tapered and stopped by the end of 3 months. Patients with clinical and laboratory evidence of acute hemolysis, an additional screening for IgA antibody may be done even in cases where poly-specific DAT is negative. Early detection helps in avoiding further investigations and provide efficient management.     

Cisplatin-induced nonimmunologic adsorption of immunoglobulin by red cells

Antibodies to cisplatin, an extensively used anticancer chemotherapeutic agent, have been implicated previously as a cause of immune hemolytic anemia. Investigation of a suspected case of cisplatin-induced hemolytic anemia in a 40-year-old man demonstrated that IgG could be adsorbed nonimmunologically by reagent red cells in vitro. This phenomenon was found to be a source of possible error in the interpretation of studies identifying specific cisplatin antibodies. Furthermore, cisplatin was found to be capable of producing a positive direct antiglobulin test (DAT), owing to the nonspecific adsorption of immunoglobulin and complement in vivo. Although this finding did not result in acute hemolysis, it may cause confusion in the investigation of DAT-positive hemolytic anemias. We question whether previous reports of cisplatin-induced hemolytic anemia are accurate in their assessment that such hemolysis was mediated immunologically. Future studies of suspected cases of hemolysis induced by this drug should include serologic investigation adequate to demonstrate the presence of specific cisplatin antibodies. A positive DAT in such patients should not be considered proof of drug-induced immune hemolytic anemia.     

Posttransplant immune-mediated hemolysis

BACKGROUND: Immune-mediated hemolysis is a well-recognized complication of transplantation, but few reports have drawn together the different mechanisms that could be involved. STUDY DESIGN AND METHODS: The clinical and laboratory records of three patients are used to illustrate different types and complexities of posttransplant immune-mediated RBC destruction. RESULTS: Patient 1 received bone marrow from an HLA-matched, unrelated donor. At 7 months after transplant, his Hb level fell to 50 g per L. The serum contained warm autoantibodies, and the DAT was strongly positive for IgG, IgM, and C3d; an eluate yielded IgG and IgM autoantibodies. Autoimmune hemolytic anemia was diagnosed. Patient 2, blood group A, experienced severe hemolysis 14 days after receiving a lung from a group O donor. The DAT was positive for IgG. Serum and RBC eluate contained anti-A produced by immunocompetent B cells in the transplanted lung-this was the passenger lymphocyte syndrome. Patient 3 experienced posttransplant hemolysis caused by two different immune mechanisms. Originally group A, D- with anti-C, -D, -E, she received a peripheral blood progenitor cell (PBPC) transplant from her HLA-identical group A, D+ son. Six months later, chimerism was evident; the remaining recipient marrow was still producing antibodies that destroyed D+ RBCs made by the transplant. Later, autoimmune hemolytic anemia also developed; the DAT became positive for IgG, and warm autoantibodies were eluted from D- RBCs. CONCLUSION: An understanding of the causes and circumstances under which posttransplant immune hemolysis arises is required for proper management. As more patients become long-term survivors of unrelated bone marrow and/or PBPC transplants, chimerism and complex serologic problems will become more common.     

Association of positive direct antiglobulin test (DAT) with nonreactive eluate and drug-induced immune hemolytic anemia (DIHA)

Background and Objectives: Drug-induced immune hemolytic anemia is a rare condition that occurs primarily because of drug-induced antibodies, either dependent or independent and positive direct antiglobulin test. Our aim was to evaluate the association of positive DAT with nonreactive eluate and DIHA. Materials and Methods: From 2014–2018, we evaluated 159 patients who presented positive DAT with a nonreactive eluate. Laboratory and clinical analyses were performed including HIV, HBV and HCV testing. All patients were exposed to the following drugs: Dipyrone in 63.5 %, Furosemide in 28.9 %, Metoclopramide in 34.6 % and Ondansetron in 41.5 %. Results: Results of DAT showed IgG in 125 (78.4 %) patients and C3d in 24 (15.1 %) with reactions varying from 1+ to 4+. HIV test was positive in 10 (16.1 %) patients, HBV was positive in 3 (4.7 %) and HCV was positive in, 1 (1.5 %). There was no clinical significance when the parameters of hemoglobin, hematocrit, reticulocytes and LDH were evaluated, only a slight increase in bilirubin, especially, in patients with positive DAT reacting 3+/4+ due to IgG and C3d sensitization. Clinical evaluations showed that all patients were asymptomatic. Conclusions: The association of drugs with positive DAT can be a challenge to transfusion services and immunohematology reference laboratories. There was no evidence of any case of severe hemolysis with clinical repercussion through the clinical and laboratory findings analyzed with the drugs associated with positive DAT. Dipyrone and Furosemide have already been associated with DIHA but there are no studies reporting the association of Metoclopramide and Ondansetron with DIHA.     

Comparison of DATs using traditional tube agglutination to gel column and affinity column procedures

BACKGROUND: Detection of immunoglobulin or complement bound to RBCs by using the DAT is valuable in the diagnosis of immune-mediated hemolytic anemia. Traditionally, the DAT has been performed by tube agglutination using anti-IgG or anti-C3d. The purpose of this study was to compare the tube agglutination DAT to gel microcolumn, affinity microcolumn, and flow cytometric DATs on RBCs coated in vitro and on patient RBC samples. STUDY DESIGN AND METHODS: RBCs from 84 patients were assessed by tube agglutination DAT, one gel microcolumn DAT, and two affinity microcolumn DATs. One affinity microcolumn assay was unmodified and one was modified by the addition of polyspecific antiglobulin or anti-IgG as a secondary antibody. RBCs from 15 of the 84 patients underwent analysis by flow cytometry with fluorescence-labeled anti-IgG. The assays were also compared by using D+ RBCs sensitized with serially adjusted concentrations of anti-D. RESULTS: Both tube agglutination and gel microcolumn DATs were positive in 49 patient samples; both assays were negative in 20 samples, and the results were discordant in 15. Gel microcolumn DATs were more likely than were tube agglutination DATs to detect IgG on RBCs. Affinity microcolumn DATs were less likely than gel microcolumn or tube agglutination DATs to detect IgG on RBCs. Flow cytometry results were the same as gel microcolumn results in 12 of 15 patient samples and the same as tube agglutination results in 13 of 15. Tube agglutination and both affinity microcolumn assays reacted with RBCs coated with anti-D that was diluted 1-in-100. The gel microcolumn and flow cytometry assays reacted with RBCs coated with anti-D diluted 1-in-400. There was no correlation between tube agglutination and gel microcolumn DATs in detecting bound C3d. CONCLUSION: Detection of IgG bound to RBCs was not consistent with the methods described. Gel microcolumn DATs were more sensitive than tube agglutination and affinity microcolumn DATs. Given the varied results of these assays, reference laboratories should not rely on a single method for DATs. More comprehensive testing should be performed when the tube agglutination DAT is negative in a patient with suspected immune-mediated hemolytic anemia. Further comparisons are necessary to determine the proficiency of flow cytometric assays.     

酸化甘油溶解试验阳性的自身免疫性溶血性贫血实验指标分析

目的:评价酸化甘油溶解试验阳性的自身免疫性溶血性贫血的实验室特点。方法:对2001年1月-2003年11月我院酸化甘油溶解试验阳性的临床病例进行回顾性分析。结果:108例酸化甘油溶解试验阳性的患者中，有12例为自身免疫性溶血性贫血，其中IgG5例，IgG C3型3例，C3型2例；骨髓Coombs试验阳性1例(IgG、C3、IgM、IgA四种抗体均为阳性)；Coombs亚型1例IgG1阳性。结论:部分自身免疫性溶血性贫血患者酸化甘油溶解试验阳性。     

Delayed hemolytic transfusion reactions. Evidence for complement activation involving allogeneic and autologous red cells

Twenty-six patients with delayed hemolytic transfusion reactions ( DHTR ) were investigated. The reaction of hemolysis often was concealed by other disorders that were usually associated with signs of hemolysis or blood loss. Coating of red cells was analyzed with regard to IgG and/or complement bound in vivo. Although many of the alloantibodies involved (K [8]; E [5]; Fya [2]; Fyb [2]; D [1]; c [1]; multiple [7]) are usually thought to be incapable of complement activation, a strongly positive direct antiglobulin test (DAT) due to C3d was found in all cases. On first examination after transfusion, C3d was present on circulating red cells in large amounts and remained discernible for weeks and even months. IgG on red cells was detected by the DAT in only 10 out of 26 cases. By means of a sensitive radioimmunoassay, IgG was demonstrated in 16 out of 17 cases, but usually in small quantities. Despite the low IgG concentrations, the causative alloantibodies could be eluted in 25 of 26 cases, and, as shown by sequential investigations, in six cases were recoverable from circulating red cells for over 100 days posttransfusion. Since the antiglobulin reactions due to anti-complement were usually strong, not of the "mixed- field" type, and in some cases remained detectable on circulating red cells for months, we conclude that complement is regularly activated in DHTR and binds not only to donated but probably also to autologous red cells.     

Influence of immunohematological markers on severity of in vivo hemolysis in human warm autoimmune haemolytic anemia

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.     

Clinical significance of serologic markers related to red blood cell autoantibodies production after red blood cell transfusion—severe autoimmune hemolytic anemia occurring after transfusion and alloimmunization: successful treatment with rituximab

BACKGROUND: The association of autoantibody formation with blood transfusion was previously noted. Severe autoimmune hemolytic anemia (AIHA) diagnosed after red blood cell (RBC) transfusion determined us to undertake this study and investigate the incidence and clinical significance of autoantibodies occurring after transfusion by a retrospective review of blood bank and medical records.
STUDY DESIGN AND METHODS: We report a lymphoma patient who developed severe autohemolysis after blood transfusion and alloantibody production. The hemolysis was refractory to steroids and chemotherapy and ceased after rituximab. We also retrospectively assessed the blood bank records for a 2-year period to identify the patients who developed autoantibodies after blood transfusion and examined laboratory, clinical features, and outcome.
RESULTS: From January 2005 through December 2006, 375 direct antiglobulin tests (DATs) and 3409 indirect antiglobulin tests (IATs) were found to be positive. Thirty-eight patients with positive DATs and IATs had demonstrable RBC warm-type autoantibodies occurring after blood transfusion; 27 of them had also one or more alloantibodies. Clinical and laboratory signs of hemolysis were absent in all patients (except the case reported). In another 5 patients alloantibodies were retrieved from RBC eluate and serum without evidence of autoantibodies; therefore, a delayed serologic transfusion reaction was diagnosed.
CONCLUSION: RBC autoantibodies are quite commonly found after blood transfusion. Nevertheless, clinically significant AIHA is a rare but at times a life-threatening phenomenon. We describe a first case of successful treatment with rituximab of refractory posttransfusion AIHA. Rituximab must be further evaluated for this indication.     

One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is an uncommon finding characterized by a sudden decrease in hemoglobin after treatment with the putative drug. The full range of drugs causing DIIHA and the initial serologic presentation are not fully appreciated. This work identifies additional drugs associated with DIIHA and offers additional insights about diagnosis. STUDY DESIGN AND METHODS: A 20-year retrospective review of testing in one laboratory was performed. Patient sex, age, medication history, initial direct antiglobulin test (DAT) and indirect antiglobulin test, method of drug-dependent antibody (DDA) detection, and specificity were reviewed. RESULTS: Seventy-one patients with 73 DDAs to 23 different drugs were identified. The following DDA specificities were identified: cephalosporins (37), penicillin and/or penicillin derivatives (12), nonsteroidal anti-inflammatory drugs (NSAIDs) (11), quinine and/or quinidine (7), and others (6). Fifty-two percent (37) were due to cephalosporins with 27 cefotetan-dependent antibodies detected. Four NSAIDs required urinary metabolite for detection. DAT was strongly positive, at least 2+, in 75 percent (51/68) of patients with a positive DAT. Initial eluate was negative in 52 patients, weak positive (<2+) in 14 patients, and strong positive (>or=2+) in 2 patients. Serologic results showed characteristics of warm autoimmune hemolytic anemia (AIHA) in 22 or 31 percent of all cases and cold-reactive AIHA in 2 cases. CONCLUSIONS: It is important to consider DIIHA when a patient serologically presents as either warm- or cold-type AIHA to avoid erroneous diagnosis. Based on these findings, the strength of the initial DAT is much stronger than previously reported for all types of drug-induced immune hemolysis. This report is also unique in the number of NSAIDs reported. A new classification of categorizing DDA is proposed.     

Mixed-type autoimmune hemolytic anemia: differential diagnosis and a critical review of reported cases

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is usually classified as either warm or cold type. During the past few decades, mixed types (Mxs) have also been described in a number of cases (6%‐8% of AIHA), often without serologic data to support the diagnosis. In this study, we demonstrate that the incidence of Mx AIHA in our institution is extremely rare. STUDY DESIGN AND METHODS: Between August 1998 and August 2007, all in‐ and outpatients with detectable warm autoantibodies (WABs) were included in this study. Serologic testing was performed using standard techniques for the detection of red blood cell antibodies. RESULTS: From a total of 2194 patients with detectable WABs, only 2 patients (<0.1%) developed both WABs and cold agglutinins (CAs), which in the presence of clinical evidence of hemolytic anemia, satisfies the criteria for Mx AIHA. Only 1 of these patients, however, showed cold and warm hemolysis. Insignificant CAs at temperatures of not more than 24°C were found in 242 patients. CONCLUSION: There is evidence that the presence of CAs with high thermal amplitude and WABs may lead to confusion and misdiagnosis in some patients with AIHA. This study demonstrates that Mx AIHA is less common than previously reported.     

直接抗人球蛋白试验阳性的类型鉴别及临床意义

目的　通过直接抗人球蛋白试验 (DAT)阳性的类型鉴别 ,有助于临床对自身免疫性溶血性贫血 (AIHA)的正确诊断 ;对血库交叉配血不合的处理有指导意义。方法　DAT阳性标本分AIHA组和非AIHA组 ,进行免疫分型 ,然后把IgG或IgG C3的标本进行放散试验 ,利用放散液与标准抗体筛查细胞进行间接抗人球蛋白试验 (IAT)。结果　AIHA组患者的放散液均同标准抗体筛查细胞反应 ,非AIHA组除了 1例SLE患者外均为阴性反应。结论　DAT阳性患者可以分为两类 :自身抗体引起和免疫复合物引起