Cold Autoimmune Hemolytic Anemia Research Articles

Cold autoimmune hemolytic anemia resolved by rituximab

Sir, Cold-agglutinin-induced autoimmune hemolytic anemia (AIHA) may be a therapeutic challenge.[1] In this setting, rituximab has been used with favorable results.[2,3] We have recently observed and successfully treated with rituximab a 78-year woman who presented a 2-year history of active cold AIHA unresponsive to prednisone and cyclosporine. The patient reported a long history of hypertension, glaucoma, severe osteoporosis, and osteoarthrosis; she was found to have difficulty walking given the severe damages of ankles and lumbar (L1 to L3) vertebral bodies. At admission, the laboratory evaluation showed a normochromic and normocytic anemia (hemoglobin, Hb = 8.0 g/dL) with reticulocytosis and a typical hemolytic pattern. A comprehensive radiological examination, including a chest X-rays and a total body computed tomography scan, revealed no abnormalities. Gross agglutinants were seen on blood film. An erythroid hyperplasia besides a normal representation of myeloid and megakaryocytic precursors resulted from the examination of the bone marrow smears and by a trephine biopsy. Immunohaematological investigations revealed a strongly positive direct antiglobulin test (DAT) and anti-C3 antisera with the presence of a cold IgG (1:512) active from 3°C to 20°C. Therefore, a salvage therapy with rituximab as a 4-h intravenous infusion at the dose of 375 mg/m2 once weekly for a total of four doses was given. No adverse reactions were observed. To begin after the second dose of rituximab, Hb levels constantly increased and this finding was paralleled by the decrease of the reticulocyte count. Three months after the last dose of rituximab, the DAT became negative. To date, at the 13-months follow-up, the patient’s Hb level and serum markers of hemolysis are normal and the DAT is negative. AIHA due to cold agglutinins is a difficult to treat disease presenting a variable response to corticosteroids, immunosuppressive drugs, alkylating cytostatics, interferon, corticosteroids, and splenectomy.[1] Our patient lost the therapeutic response to prednisone and cyclosporine which had been administered for many years. The present report adds another case to the relatively sparse data on idiopathic cold AIHA treated with rituximab, for which favorable results have been reported[2,3] with a response rate of approximately 60% and an acceptable cost-effective profile.[4] In conclusion, in our experience, rituximab was safely administered and provided the means to obtain sustained remissions, representing an optimal tool in this setting even in order to spare bone loss, skeletal complications, and other steroid-related side effects, which may be particularly devastating and aggravating the frailty of the older patients.

Dramatic response to rituximab in a child with severe cold autoimmune hemolytic anemia arising after allogeneic hematopoietic SCT

Dramatic response to rituximab in a child with severe cold autoimmune hemolytic anemia arising after allogeneic hematopoietic SCT

Autoimmun hemolytisk anemi

Knowledge of autoimmune hemolytic anemia is rapidly increasing, especially on pathogenesis, associated disorders and aspects of transfusion immunology. New treatment options have emerged. This review is based on selected publications, a non-systematic search in PubMed and the authors' own research. Autoimmune hemolytic anemia is a heterogeneous group of diseases. The warm-antibody type is frequently associated with chronic lymphocytic leukemia or autoimmune systemic disease. Corticosteroids are still the first-line therapy and splenectomy is second-line, while rituximab has become an option in refractory disease. Blood transfusions require specific precautions such as restrictive use, extensive phenotyping of antigens and testing for alloantibodies and biological compatibility. Primary chronic cold agglutinin disease, a subgroup of cold-antibody autoimmune hemolytic anemia, is a clonal lymphoproliferative bone marrow disease. This subgroup is usually refractory to corticosteroids and patients with few clinical symptoms and slight anemia may not require drug therapy. However, in a majority, effective drugs are needed. The best documented therapy is infusions with rituximab, but new options are being tested. Immune hemolytic anemia associated with drugs occurs less frequently now than before. Subgroups and associated or underlying disease should be identified in patients with autoimmune hemolytic anemia. The therapeutic implications of subclassification are important. Patients who have cold agglutinin disease and need therapy should be included in prospective trials.

Rituximab Therapy for Treatment of Chronic Warm Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia (AIHA) is a disorder in which auto antibodies are directed against red blood cells resulting in severe anemia. It is a relatively uncommon disorder with an estimated incidence of 1–3 cases per 100,000 persons per year. These disorders are classified as either warm AIHA or cold AIHA depending on the temperature at which the auto antibodies show maximal binding. First line therapy for patients (pts) with warm AIHA is corticosteroids, 20% achieve complete remission most patients require maintenance treatment. Splenectomy is the usual second line treatment. Cytotoxic and immunosuppressive medications can be tried. Rituximab a monoclonal antibody against CD 20 has also shown efficacy in pt with chronic AIHA.In this study we retrospectively studied 2 cases of chronic warm AIHA. Case 1 was a female diagnosed with AIHA at the age of 15 years with a history of vasculitis. AIHA had a relapsing and a remitting course. She was treated with steroids, splenectomy, cytotoxic therapy with cyclophosphamide and immunosuppressive therapy with azathioprine with no long-term remission. At 36 yr of age she had a relapse, steroids induced a minimal response, cyclophosphamide induced a partial response. She developed hemorrhagic cystitis hence cyclophosphamide was discontinued. Rituximab was administered at 375mg/m2 weekly for 3 doses with minimal response. After 4 weeks she was given 3 more doses of weekly rituximab with minimal response. 2 weeks after the last Rituximab dose, pt developed pancytopenia, gram-negative sepsis and died.Case 2 was also a female who was diagnosed with AIHA at the age of 21 years, etiology was considered idiopathic. She had a relapsing remitting course as well. She had been treated with steroids, splenectomy, cytotoxic therapy and immunosuppressive therapy. At 41 years of age she relapsed, this episode was, not responsive to steroids, Rituximab 375mg/m2 was infused weekly for 3 weeks with minimal improvement, after 6 weeks, 3 more doses of Rituximab were infused. She had a gradual improvement of her hemoglobin over 4 months and pt has been in remission since. She has had a sustained response for over 24 months.There have been a few case series published about the effects of Rituximab in pt with warm AIHA, with an estimated complete response ranging from 40 – 100%. The toxicities of this therapy in this pt population has been not been well documented. We conclude that Rituximab must be used cautiously in pt with AIHA. Prospective Randomized clinical trails are needed to assess the efficacy of Rituximab in pt with warm AIHA.

Diagnosis and treatment of autoimmune haemolytic anaemias in adults: a clinical review

Autoimmune haemolytic anaemia (AIHA) is an immune disorder caused by antibodies directed against unmodified autologous red cells. The disorder may be a primary (idiopathic) or a secondary disease. The diagnosis is based on the presence of anaemia, signs of haemolysis with reticulocytosis, low haptoglobin, increased lactate dehydrogenase, elevated indirect bilirubin, and a positive direct antiglobulin test (Coombs test). Sometimes, not all of these typical features are present. Most AIHA are caused by warm antibodies, whereas cold antibodies are less commonly detected. While half of the warm antibody-based AIHA are idiopathic anaemias, almost all cold antibody AIHA are secondary anaemias. Underlying diseases are Non Hodgkin's lymphomas and systemic autoimmune disorders, and less frequently organ transplantation, infections, or solid tumors. Moreover, AIHA is an important complication of treatment with nucleoside analogs. Most patients with AIHA require therapy. In warm antibody AIHA, standard first line therapy are glucocorticosteroids with or without high dose immunoglobulins, whereas splenectomy is considered second-line therapy. Response rates of primary AIHA to corticosteroid therapy are high. After initial remission, the dose should be tapered down slowly and with caution, and in some cases, low-dose maintenance therapy is required. The efficacy of standard therapy is low in secondary AIHA that develops in lymphoma patients, posttransplant patients, or tumor patients. Among other immunosuppressive treatments, rituximab (anti-CD20) appears to be highly effective in patients with warm antibody AIHA refractory to standard therapy. Mycophenolate mofetil is quite effective in AIHA patients with an underlying autoimmune or lymphoproliferative disease. Patients with cold agglutinins are refractory to steroids and splenectomy. Half of these patients may respond to rituximab, although responses usually are short-lived. Sometimes, AIHA that is associated with malignant lymphomas or tumors, disappears after successful anti-lymphoma or anti-tumor therapy.

Severe Refractory Autoimmune Hemolytic Anemia with Both Warm and Cold Autoantibodies: Complete Response with Rituximab.

Mixed warm and cold autoimmune hemolytic anemia (AIHA) runs a chronic course with severe, intermittent exacerbations. Therapeutic options for treatment of hemolysis associated with mixed AIHA are limited. There have been only two reported cases of effective use of rituximab in the treatment of mixed AIHA. We report a case of severe mixed AIHA that did not respond to steroids and responded to one cycle of rituximab. A 62-year-old male presented with dyspnea, jaundice and splenomegaly. Blood work revealed severe anemia (hemoglobin 4.9 g/dl) with biochemical evidence of hemolysis. Exposure to cold led to worsening of hemolysis and hemoglobinuria. Direct antiglobulin test was positive for IgG and complement (C3d); and cold agglutinins were detected. Bone marrow revealed erythroid hyperplasia. Positron emission tomography scan showed no sites of pathologic uptake. There was no other evidence of a lymphoid or myeloid disorder. Initial therapy consisted of avoidance of cold, intravenous methylprednisolone and a trial of plasmapheresis; however, there was no clinically significant response and the patient continued to be transfusion dependent. He was then started on intravenous rituximab 375 mg/m2/week. After two treatments, hemoglobin stabilized and transfusion requirement diminished. [Display omitted] Rituximab, continued for a total of four weeks, led to complete resolution of hemolytic anemia and associated symptoms. At his last visit, about 8 months after initial rituximab treatment patient continues to be in complete remission. This is the first reported case of mixed type AIHA not responding to steroid therapy with complete response to only one cycle of rituximab. Previous two reports of rituximab use in mixed AIHA have described initial brief response to steroids and the use of rituximab at the time of relapse. In both the cases, response to one cycle of rituximab was short-lived requiring a second cycle of rituximab. Our case demonstrates that severe hemolysis associated with mixed AIHA can be unresponsive to steroid therapy and a single cycle of rituximab may lead to prompt and durable complete remission. Rituximab is an effective treatment for mixed AIHA, especially when immediate response is desired, and merits further evaluation in this setting.

Autoimmune hemolytic anemia in childhood: serologic features in 100 cases

Red blood cell (RBC) autoimmunization is a relatively uncommon cause of anemia in children and presents some differences from those of adults. Due to its frequency, autoimmune hemolytic anemia (AIHA) in childhood has prompted very few studies, and the literature consists mostly of sporadic case histories. The objective of this study was to stress the importance of an appropriate serologic diagnosis in suspected cases. This report describes the immunohematologic features of 100 patients with AIHA studied in the Immunohaematologic Unit of Blood Bank, "La Sapienza" University of Rome. The patients were diagnosed in the same department from 1983 to 2003. The peak incidence of AIHA was in the first 4 years of life. No sex predominance was noted. Warm AIHA was the most common type of acquired immune hemolytic anemia; it comprised 64 of the 100 patients, whereas 26 patients showed a cold AIHA. Associated AIHA showed a slightly more frequent incidence (54/100) compared to idiopathic forms of AIHA (46/100). In this study serologic records of 100 children with confirmed AIHA are reported. This series, much larger than any previously reported, is critically reviewed and analyzed to delineate the immunologic features of the disease in childhood.

Sirolimus rescue for tacrolimus‐associated post‐transplant autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) has been reported to occur after renal transplantation, and typically does so in the first few weeks post-transplant. We report on a 3-yr-old child who developed cold AIHA nearly 1 yr after an ABO identical, living donor renal transplant from his mother. Numerous transfusions, pulse steroids, repeat plasma exchange treatments, and IVIG were unsuccessful. Nearly 3 wk into his illness, tacrolimus was changed to cyclosporine, and then to sirolimus, and resulted in a prompt response. He currently has a normal renal function and a normal hemoglobin level on sirolimus monotherapy.

Treatment of Autoimmune Hemolytic Anemia

The appropriate therapy of autoimmune hemolytic anemia (AIHA) is dependent on the correct diagnosis and classification of this family of hemolytic disorders. Although the majority of cases are warm AIHA, there are several distinct types of cold AIHA and a number of drug-induced etiologies of AIHA, which must be investigated to determine if stopping a drug will induce a remission. In warm AIHA, corticosteroids are standard, followed by consideration of splenectomy in recalcitrant cases. If steroids and splenectomy are insufficient, other forms of immunosuppressive therapy are typically initiated. In cold AIHA, keeping the patient warm in often sufficient, but therapy directed at an underlying lympholiferative disorder may be helpful. Brisk hemolysis, inadequate responses to therapy, and worsening anemia require transfusion therapy. Although the pretransfusion workup is made difficult by the presence of the autoantibody, transfusion services can usually provide blood safe for transfusion by excluding underlying alloantibodies. When transfusion is urgently required and compatible blood cannot be located, incompatible blood may be provided as a life-saving measure. Communication between the transfusion service and the hematologist is critical to assess the risks in these settings. Hemoglobin-based oxygen carriers may provide an important bridging therapy in the future. Requests for "least incompatible" blood do not enhance transfusion safety and often result in unnecessary delays.

A Last Resort Modality Using Cryofiltration Apheresis for the Treatment of Cold Hemagglutinin Disease in a Veterans Administration Hospital

Cold hemagglutinin disease is a cold autoimmune hemolytic anemia (cAIHA) caused by an autoantibody, such as IgM, directed against the I-antigen present on the surface of erythrocytes. Cold exposure can activate this system causing hemolysis, hemagglutination, microvascular thrombosis, or acrocyanosis. Thus, surgical procedures requiring hypothermia, such as coronary artery bypass surgery, present a significant problem in patients with cAIHA. The purpose of this study was to evaluate the safety and effectiveness of cryofiltration apheresis (CFA), used as a last resort, for the treatment of cAIHA. Effectiveness was evaluated by clinical assessment and laboratory evaluations of cold agglutinin titer, immunoglobulins, and other plasma proteins. Safety was evaluated by vital signs, monitoring, and laboratory measurements of complements, hematology and blood chemistry. Five patients with cAIHA were treated by CFA using the cryoglobulin (CG) filter (Pall Medical, Ann Arbor, MI, USA). Four patients received only one CFA procedure, while one patient received four CFA treatments. The cold agglutinin titers were fairly low, ranging from 1 : 1 to 1 : 2048. However, a wide thermal amplitude(4-37 degrees C) was observed in most patients. Two out of five patients responded favorably with reduction in titer. The two responders had acute forms of cAIHA with serum positive for cryoglobulins. The three non-responders had chronic forms of cAIHA with negative cryoglobulins. CFA effectively removed cryoprotein precipitates while conserving other plasma components. The CG filter was biocompatible with no complement activation or observed complications due to CFA or CG filter. While the mechanism of action in treating this type of patient population with CFA is unknown, the plausible theories are discussed.

CHILDHOOD REFRACTORY AUTOIMMUNE HAEMOLYTIC ANAEMIA: IS THERE A ROLE FOR ANTI‐CD20 THERAPY (RITUXIMAB)?

CHILDHOOD REFRACTORY AUTOIMMUNE HAEMOLYTIC ANAEMIA: IS THERE A ROLE FOR ANTI‐CD20 THERAPY (RITUXIMAB)?

Mixed warm and cold antibody-type autoimmune hemolytic anemia in a healthy pregnant woman with primary cytomegalovirus infection

Mixed warm and cold antibody-type autoimmune hemolytic anemia in a healthy pregnant woman with primary cytomegalovirus infection

Plasmalymphacytapheresis in the treatment of cold autoimmune hemolytic anemia

Journal of Clinical ApheresisVolume 11, Issue 1 p. 50-50 Letter to the Editor Plasmalymphacytapheresis in the treatment of cold autoimmune hemolytic anemia A.P. Shpakova M.D., A.P. Shpakova M.D. Haematology Research Center, Laboratory of Clinical Immunologie, Laboratory of Apheresis, Moscow, RussiaSearch for more papers by this authorN.N. Kalinin M.D., N.N. Kalinin M.D. Haematology Research Center, Laboratory of Clinical Immunologie, Laboratory of Apheresis, Moscow, RussiaSearch for more papers by this author A.P. Shpakova M.D., A.P. Shpakova M.D. Haematology Research Center, Laboratory of Clinical Immunologie, Laboratory of Apheresis, Moscow, RussiaSearch for more papers by this authorN.N. Kalinin M.D., N.N. Kalinin M.D. Haematology Research Center, Laboratory of Clinical Immunologie, Laboratory of Apheresis, Moscow, RussiaSearch for more papers by this author First published: 1996 https://doi.org/10.1002/(SICI)1098-1101(1996)11:1<50::AID-JCA11>3.0.CO;2-0Citations: 1 Haematology Research Center, Laboratory of Clinical Immunologie, Laboratory of Apheresis, Moscow, Russia AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume11, Issue11996Pages 50-50 RelatedInformation

Fatal outcome in a patient with autoimmune hemolytic anemia associated with an IgM bithermic anti‐ITP

Several cold autoantibodies (usually IgG) with IT specificity have been reported previously, as have autoantibodies with joint I and P blood group specificities (IP1, ITP1, iP1, IP). A fatal outcome associated with an IgM cold autoantibody of ITP specificity is reported. A 54-year-old man suffered from progressively severe cold autoimmune hemolytic anemia for 9 months. Hemoglobin concentration ranged from 6 to 7 g per dL (60-70 g/L) and reticulocytes from 3 to 5 percent (0.030-0.050). The direct antiglobulin test was weakly positive for IgM and strongly positive for C3d. The serum contained a cold agglutinin that reacted strongest with cord i red cells (RBCs) > adult I RBCs > adult i RBCs, which is consistent with IT specificity. The Donath-Landsteiner test was positive; the reaction was neutralized by globoside. The serum reacted weakly or was negative with RBCs from five group p blood donors, which suggests anti-ITP specificity. Dithiothreitol treatment of the serum abolished the cold agglutinin reactivity, which suggests that the anti-IT was IgM. The patient received > 40 RBC transfusions and failed to respond to oral steroids, oral cytoxan, high-dose pulse intravenous steroids, and plasma exchange at room temperature and at 35 degrees C. He died of sepsis following an unsuccessful trial of chlorambucil. Autopsy revealed unsuspected disseminated non-Hodgkin's lymphoma. Serologic studies are consistent with our patient's having a single IgM cold autoantibody with IT and P specificities (anti-ITP) and requiring both specificities on the same RBC to permit maximal antibody expression.

Immune Hemolytic Anemia Associated with Biclonal Cold Autoagglutinins

A 65-year-old man with bladder outlet obstruction due to prostatic hypertrophy was incidentally discovered to have cold-antibody autoimmune hemolytic anemia (cold-aggluthinin syndrome; CAS) due to autoanti-I (titer 1,024 at 4 degrees C and 64 at 30 degrees C), and a biclonal gammopathy. Immunofixation electrophoresis of serum and a red blood cell eluate revealed the patient's autoantibody to be biclonal IgM kappa and IgA kappa. No underlying cause could be determined to explain the development of either the biclonal gammopathy or the CAS. To our knowledge, this is the first reported case of CAS associated with a biclonal gammopathy and biclonal cold autoagglutinins of the IgM kappa, IgA kappa type.

Inhibition of an anti‐Pr1d cold agglutinin by citrate present in commercial red cell preservative solutions

A patient with known cold autoimmune hemolyticanemia was admitted for surgery. Routine cold agglutinin evaluations, using commercial red cells (RBCs) in modified Alsever's preservative solution, revealed a cold agglutinin titer of 4 to 16. However, using RBCs washed four times with saline, a high-titer (greater than 2000 at 4 degrees C) cold autoagglutinin was demonstrated. The cold agglutinin was shown to be an IgM kappa paraprotein with anti-Pr1d specificity. The addition of Alsever's solution to washed RBCs inhibited the cold agglutinin. Each major component of Alsever's solution (neomycin, chloramphenicol, inosine, dextrose, and citrate) was tested individually; only citrate inhibited the patient's cold agglutinin. Various compounds structurally related to citrate were tested and found to cause various degrees of inhibition. The strongest inhibition correlated with the presence of either three carboxyl groups on molecules devoid of double-bonded carbon atoms or two carboxyl groups in cis configuration. A panel of 54 cold agglutinins, including 7 with anti-Pr specificity, was analyzed. None was significantly inhibited by Alsever's solution, although one with anti-Pr2 specificity was weakly inhibited. In summary, these studies describe an anti-Pr1d cold autoagglutinin that was inhibited by citrate in RBC preservative solutions. The failure to detect such a cold agglutinin can result from not washing RBCs free of citrate before testing.

Comparative biochemical and genetic characterization of clonally related human B-cell lines secreting pathogenic anti-Pr 2 cold agglutinins

To study the biology of cold autoimmune hemolytic anemia, Epstein-Barr virus (EBV)-transformed B-cell clones were established from a patient with splenic lymphoma associated with immune hemolysis due to an anti-Pr 2 cold autoantibody. Studies were performed comparing the cold autoantibody present in culture supernatants of these cell lines to the pathogenic cold autoantibodies present in the patient's plasma. Cytogenetic studies of splenic lymphocytes demonstrated an abnormal karyotype (51XX,+3,+9,+12,+13,+18). After EBV transformation, eight clones secreting IgM,κ anti-Pr were isolated; each clone had the same abnormal karyotype as above. DNA isolated from the clones and spleen was analyzed by Southern blot hybridization with J H, C μ, and C κ probes; identical gene rearrangements were seen in each case. Anti-Pr antibodies, isolated from culture supernatant and serum were compared by isoelectric focusing (IEF) and demonstrated similar banding patterns. Distinctive banding patterns, however, were observed in 2 8 clones, suggesting structural differences. Adsorption studies with red blood cells further showed that the observed IEF banding patterns were solely due to anti-Pr cold autoantibody. With a thin-layer chromatography method, the biochemical determinants recognized by the cold autoantibodies were defined as glycolipids containing Neu Acα2-3Galβ1-4Glc sequences. The data demonstrate that the autoantibodies of the EBV-transformed B-cell lines were similar to the pathogenic monoclonal serum autoantibody in both structure and specificity. These clonal cell lines may thus serve to further study the biology of human B-cell lymphomas with defined autoantibody specificity.

Serological and immunochemical assessment of anti-complement monoclonal antibodies

The antiglobulin test for the detection of red cell antibodies is included in almost all regimes for pretransfusion testing. The polyspecific reagents produced for this purpose usually contain anti-complement antibodies to enable the detection of certain complement-binding antibodies of clinical significance. In addition the diagnosis of Cold Auto-immune Haemolytic Anaemia (CHAD) is supported by a positive direct antiglobulin test (DAT) using a reagent containing anti-C3d. Anti-C3d is therefore a necessary component of a polyspecific reagent. Unfortunately, if the strength of anti-C3d from a polyclonal reagent is optimal, it tends to be associated with unwanted reactions with red cells that have been stored in serum or plasma [9]. Even when apparently pure antigen is used for immunization, animals may make large amounts of antibody against minor contaminants. The specificity and potency varies from one animal and even one breed to the next, making reagent production both time consuming and uncertain. In recent years several monoclonal antibodies have been produced with a specificity for complement components or for certain fragments. These include an antibody to C3 which reacts with a C3d epitope which appears to be exposed on all complement-coated red cells encountered in blood transfusion serology, NBTS-BRIC 8 ( Holt et al., 1985) [10] and an anti-C3c, WM1 [17]. Chaplin et al., 1980) [2, 3] has reported a comparative study of four monoclonal anti-C3d and a series of 32 antibodies to C3c and C3d have recently been described and detailed serological and immunochemical investigations reported [5]. Some antibodies react with fragments such as C3g ( Lachmann et al., 1980) [11] which are not always present or exposed on complement-coated red cells. In the present study the serological and immunochemical properties of antibodies 12 W 1, 12 W 2, 12 W 3, 12 W 4, 12 W 5 and 9 W 14 were investigated.

Autoantibodies to erythrocytes

Erythrocyte autoantibodies may be benign, present in the plasma of healthy individuals, or pathologic, causing autoimmune hemolysis. Autoimmune hemolytic anemia (AIHA) consists of two major clinical disorders: cold hemagglutinin disease (cold AIHA), due to an IgM antibody that preferentially agglutinates red blood cells (RBC) in the cold (4 °24°C), and the more common syndrome of warm reactive (37°C) IgG-induced autoimmune hemolytic anemia (warm AIHA). In cold AIHA, the IgM autoantibody induces clearance of red blood cells (RBC) in the liver through complement activation and deposition of C3 on erythrocytes (9). This complement-dependent hepatic clearance responds poorly to corticosteroids and splenectomy. In warm AIHA, the IgG-coated erythrocytes are cleared primarily via Fc receptors on reticuloendothelial cells in the spleen. This process usually responds to corticosteroids and splenectomy (Table 1). These autoimmune hemolytic disorders may be idiopathic or develop as a complication of a lymphoproliferative disorder, infection, or drug therapy. The diversity of RBC autoantibodies occurring in these different clinical settings has not yet been completely defined. In contrast, the diversity of autoantibodies involved in the pathogenesis of other autoimmune diseases, such as systemic lupus erythematosus and myasthenia gravis, has been explored in various ways by different laboratories (5, 10). From these studies it appears that distinctive clones of autoantibody-producing cells are associated with particular disease processes. Similar restrictions in antibody clonality may also be present in immune-mediated hemolytic disease. To date, the complexity of erythrocyte autoantibody expression has been approached by examination of the antigen-binding properties (specificities) of these immunoglobulins and by analysis of their heavy and light chain isotypes. The following will review the current knowledge of the specificity (function), isotype, and cellular origin of these antibodies.

Primary biliary cirrhosis and cold autoimmune hemolytic anemia: Effect of partial plasma exchange

The previously unreported occurrence of primary biliary cirrhosis with cold autoimmune hemolytic anemia is described. Red cell survival studies showed a t1/2 of 11.1 days. Partial plasma exchange increased red cell survival to 15.8 days. Concomitantly, alkaline phosphaiase, SGOT, SGPT, and bilirubin was reduced in predictable amounts but rebounded to prepheresis levels quickly. Although partial plasma exchange was effective in increasing red cell survival and in reducing the level of selected abnormal plasma components, the patient died 3 mo after initiation of plasma exchange therapy. Partial plasma exchange did not appear to have any long-term beneficial effects on either liver disease or the hemolytic process.