Plasma exchange in autoimmune hemolytic anemia (AIHA)

Plasma exchange therapy in autoimmune hemolytic anemia (AIHA) was used in four patients (two with warm hemolytic anemia and two with cold hemolytic anemia). The size of each plasma exchange approximated 1 plasma volume; three consecutive daily exchanges removed 80–90% of the immunoglobulins—immunoglobulin G (IgG) and immunoglobulin M (IgM)—. complement (C₃, C₄), and reduced antibody titers. Transfusion requirements dramatically decreased after plasma exchange in each case. In two patients, red blood cell (RBC) survival studies were performed to more accurately assess the effect of plasma exchange therapy, since steroid and/or immunosuppressive therapy was given concomitantly. In one case of cold AIHA, homologous ⁵¹Cr-RBC were injected 4 days prior to plasma exchange and repeat injection (same donor) following completion of plasma exchange. The survival curve prior to plasma exchange therapy had a T 1/2 = 7.8 days (r = ?0.988) and after plasma exchange therapy had a T 1/2 = 20.4 days (r = ?0.925). RBC survival studies using homologous ⁵¹Cr-RBC were also performed in a patient with warm AIHA. The survival curve before plasma exchange had a T 1/2 = 2 days (r = ?0.95), and postplasma exchange a T 1/2 = 1.8 days (r = ?0.91). Plasma exchange therapy seems to have a beneficial effect in cold rather than warm autoimmune hemolytic anemia.     

Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.     

Iguratimod in treatment of primary Sjögren’s syndrome concomitant with autoimmune hemolytic anemia: A case report

BACKGROUNDPrimary Sjögren''s syndrome (pSS) concomitant with autoimmune hemolytic anemia (AIHA) but without eye and mouth dryness is exceedingly rare. Iguratimod (IGU) has been widely used in the treatment of pSS. However, there are few reports about the application of IGU in pSS concomitant with AIHA. CASE SUMMARYHere, we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness. The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed, and was finally diagnosed with pSS concomitant with AIHA. The patient was treated with IGU along with prednisone and hydroxychloroquine, and her hemoglobin, reticulocytes and IgG returned to normal levels.CONCLUSIONIGU was effective for and well tolerated by our patient with pSS concomitant with AIHA, and may be a promising therapy for the treatment of this disease.     

抗CD20单克隆抗体治疗难治性自身免疫性溶血性贫血

本研究初步观察抗CD20单克隆抗体利妥昔（rituximab）用于治疗难治性自身免疫性溶血性贫血（AIHA）的疗效和安全性。对1例用糖皮质激素、脾切除治疗无效的AIHA患者,采用利妥昔单克隆抗体,375mg/m2,每周1次,共4次,观察溶血症状的改变并监测血红蛋白（Hb）水平及其它检验指标,同时观察有无不良反应发生。结果表明,首次治疗后11天乳酸脱氢酶（LDH）、总胆红素（TBIL）、直接胆红素（IBIL）逐渐下降,第45天降至正常范围;首剂治疗25天后Hb水平比治疗之前升高到95-100g/L以上。治疗后已4月余,患者仍处于缓解状态。治疗过程中未发生明显不良反应。结论：抗CD20单克隆抗体利妥昔用于治疗难治性自身免疫性溶血性贫血是有效而且安全的。     

Refractory autoimmune hemolytic anemia in a systemic lupus erythematosus patient: A clinical case report

Warm autoimmune hemolytic anemia (AIHA) is a hematologic disorder with an incidence of 1–3 per 10⁵ individuals/year. Patients with systemic lupus erythematosus (SLE) develop AIHA in 3% of adult cases and 14% of pediatric cases. We report a case of AIHA refractory to multiple lines of treatment in a patient with SLE, who eventually responded to a proteasome inhibitor‐based combination. A patient with systemic lupus erythematous was diagnosed with symptomatic autoimmune hemolytic anemia. The patient was refractory to multiple lines of treatment including prednisone, intravenous immune globulin, methylprednisolone, rituximab, cyclophosphamide, mycophenolate mofetil, and splenectomy. She eventually had a beneficial response to a proteasome inhibitor‐based combination with bortezomib plus mycophenolate mofetil. The treatment of refractory autoimmune hemolytic anemia can be challenging. Patients with AIHA refractory to primary or secondary treatments must resort to receiving novel therapeutic modalities including combinations targeting plasma cell, T‐ and B‐cell proliferation.     

Direct antiglobulin test-negative autoimmune hemolytic anemia in a patient with β-thalassemia minor during pregnancy: A case report

BACKGROUNDSevere refractory anemia during pregnancy can cause serious maternal and fetal complications. If the cause cannot be identified in time and accurately, blind symptomatic support treatment may cause serious economic burden. Thalassemia minor pregnancy is commonly considered uneventful, and the condition of anemia rarely progresses during pregnancy. Autoimmune hemolytic anemia (AIHA) is rare during pregnancy with no exact incidence available. CASE SUMMARYWe report the case of a 30-year-old β-thalassemia minor multiparous patient experiencing severe refractory anemia throughout pregnancy. We monitored the patient closely, carried out a full differential diagnosis, made a diagnosis of direct antiglobulin test-negative AIHA, and treated her with prednisone and intravenous immunoglobulin. The patient gave birth to a healthy full-term baby.CONCLUSIONCoombs-negative AIHA should be suspected in cases of severe hemolytic anemia in pregnant patients with and without other hematological diseases.     

Transfusion support with RBCs from an Mk homozygote in a case of autoimmune hemolytic anemia following diphtheria-pertussis-tetanus vaccination

BACKGROUND: Autoimmune hemolytic anemia (AIHA) in children, although unusual, is often associated with recent infection. Several reports have identified the diphtheria-pertussis-tetanus (DPT) vaccination as a possible trigger for AIHA. STUDY DESIGN AND METHODS: Life-threatening AIHA was diagnosed in a 6-week-old infant 5 days after receiving a DPT vaccination. The patient required daily transfusion and/or exchange transfusion for 3 weeks. RBCs from an Mk homozygote were found compatible with the patient's autoantibody. Transfusion of RBCs from an Mk homozygote and later RBCs from an individual (K.T.) with a variant glycophorin, Mi.VII, were required to sustain the patient's Hb level until autoantibody production ceased, as evidenced by a fall in antibody titer and the patient's Hct returning to normal. RESULTS: The DAT was positive (3+) with only anti-C3 on presentation. An IgM cold reactive autoantibody with probable anti-Pr specificity and high thermal amplitude (37 degrees C) was identified in the serum. The DAT was no longer positive after transfusion with compatible blood. CONCLUSION: This case represents life-threatening AIHA in an infant, temporally related to a DPT injection and responsive to a combination of immunosuppression and transfusion of rare compatible blood.     

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.     

首发症状Coombs试验阴性自身免疫性溶血性贫血的非何杰金淋巴瘤(英文)

非何杰金淋巴瘤(NHL)伴发自身免疫性溶血性贫血(AIHA)或AIHA发生在NHL诊断之前或治疗过程中已有不少报道,但以Coombs试验阴性AIHA为首发症状的NHL鲜有报道。在此,本文报道1例1.5年反复溶血发作的Coombs试验阴性AIHA后合并NHL的患者。患者女性,69岁,根据病史和实验室检查诊断为Coombs试验阴性AIHA,给予强的松治疗后血红蛋白恢复正常,停药后溶血反复复发2次,强的松治疗仍有效。第3次复发时强的松治疗无效,并出现颈部淋巴结肿大,病理检查确诊为NHL。给予6个疗程的CHOP方案化疗,NHL治愈,但溶血仍不能控制,给予小剂量利妥昔单克隆抗体(rituximab,RTX)治疗后,溶血很快停止,此后给予3次小剂量RTX进行维持治疗,NHL和AIHA呈持续缓解状态。结论:本文报告了一例十分罕见的非何杰金淋巴瘤,其发病时的主要临床症状为Coombs阴性自身免疫性溶血性贫血。     

Fatal disseminated intravascular coagulation and pulmonary thrombosis following blood transfusion in a patient with severe autoimmune hemolytic anemia and human immunodeficiency virus infection

BACKGROUND: Autoimmune hemolytic anemia (AIHA) has rarely been reported in association with human immunodeficiency (HIV) infection and never as a presenting manifestation. Similarly, disseminated intravascular coagulation (DIC) is a very infrequent complication of HIV infection. CASE REPORT: An unusual patient is described who at the time of presentation with severe AIHA was found to be HIV positive. Shortly thereafter, he developed DIC, pulmonary thrombi, and right heart failure that proved fatal, in spite of intensive supportive measures. CONCLUSION: Although the etiology of the DIC and pulmonary thrombi could not be established, they are most likely related to aggressive transfusion therapy, with associated intravascular hemolysis.     

Thyroid storm and warm autoimmune hemolytic anemia

Graves’ disease is often associated with other autoimmune disorders, including rare associations with autoimmune hemolytic anemia (AIHA). We describe a unique presentation of thyroid storm and warm AIHA diagnosed concurrently in a young female with hyperthyroidism. The patient presented with nausea, vomiting, diarrhea and altered mental status. Laboratory studies revealed hemoglobin 3.9 g/dL, platelets 171 × 10⁹ L^?1, haptoglobin <5 mg/dL, reticulocytosis, and positive direct antiglobulin test (IgG, C3d, warm). Additional workup revealed serum thyroid stimulating hormone (TSH) <0.01 μIU/mL and serum free-T4 (FT4) level 7.8 ng/dL. Our patient was diagnosed with concurrent thyroid storm and warm AIHA. She was started on glucocorticoids to treat both warm AIHA and thyroid storm, as well as antithyroid medications, propranolol and folic acid. Due to profound anemia and hemodynamic instability, the patient was transfused two units of uncrossmatched packed red blood cells slowly and tolerated this well. She was discharged on methimazole as well as a prolonged prednisone taper, and achieved complete resolution of the thyrotoxicosis and anemia at one month. Hyperthyroidism can affect all three blood cell lineages of the hematopoietic system. Anemia can be seen in 10–20% of patients with thyrotoxicosis. Several autoimmune processes can lead to anemia in Graves’ disease, including pernicious anemia, celiac disease, and warm AIHA. This case illustrates a rarely described presentation of a patient with Graves’ disease presenting with concurrent thyroid storm and warm AIHA.     

Rituximab as successful therapy in a patient with refractory paroxysmal cold hemoglobinuria

BACKGROUND: Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) attributed to a biphasic hemolysin known as the Donath-Landsteiner (DL) antibody. It is most commonly encountered as an acute transient AIHA after a viral infection in children; the disease resolves after cessation of the infection. The rarest form of PCH is a chronic form in adults that is not (nowadays) associated with infection and is not responsive to conventional therapies. Rituximab has been found to be effective therapy in other forms of AIHA, such as cold agglutinin syndrome, that are refractory to conventional therapies. We describe a case of PCH refractory to steroids that responded to rituximab therapy on two separate occasions. CASE REPORT: A 64-year-old woman with fatigue was found to be profoundly anemic with laboratory findings consistent with AIHA. She was admitted for the workup and management of her disease after she failed to respond to a course of oral steroids. Laboratory evaluation demonstrated a positive DL test suggesting PCH. She was given a course of rituximab that resulted in normalization of her hemoglobin concentration. She presented 9 months later with recurrent hemolysis. She was given another course of rituximab that again resulted in termination of hemolysis. The patient remained in remission since her last dose of rituximab 19 months previously. CONCLUSION: To our knowledge, this is the first report of an adult case of refractory PCH successfully treated with rituximab.     

164例Coombs试验阳性的自身免疫性溶血性贫血的临床研究

目的:研究自身免疫性溶血性贫血(AIHA)的临床特征,进一步指导治疗。方法:采用回顾性分析患者资料,率的比较采用精确概率法,均值比较采用t检验。结果:AIHA多发生在女性,继发性占49％,以胶原系统疾病为主,Coombs分型以IgG C_3型为主IgG IgM阳性的患者临床表现最严重,环孢霉素A(CsA)联用皮质激素组有效率为90.9％。结论:皮质激素仍为治疗AIHA的首选药物,合用CsA可提高疗效,缩短疗程。     

Autoimmune hemolytic anemia

Diagnosis of autoimmune hemolytic anemia (AIHA) requires both serologic evidence of an autoantibody and hemolysis. Based on the characteristic temperature reactivity of the autoantibody to red cell membranes, AIHA is classified into warm AIHA or cold AIHA (cold agglutinin disease and paroxysmal cold hemoglobinuria). Sensitized RBCs are destructed by intravascular and/or extravascular hemolysis. On the basis of etiology, AIHA are classified as idiopathic or secondary. The common cause of secondary AIHA is lymphoproliferative disorders, autoimmune diseases, and infections. The first line therapy of patients with warm AIHA is glucocorticoids and primary treatment for cold AIHA is avoiding cold exposure. The other standard treatments include splenectomy and immunosuppressive drugs. Recently, rituximab, a monoclonal anti-CD20 antibody, has been used in refractory AIHA with excellent responses.     

QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine

OBJECTIVE: To report QTc interval prolongation associated with combination therapy including levofloxacin, imipramine, and fluoxetine. CASE SUMMARY: A 49-year-old white female presented to the emergency department with fever, aches, and pains for the past 3 days. She was diagnosed and treated for pyelonephritis in the hospital. Therapy included intravenous levofloxacin 500 mg every 24 hours and ceftriaxone 2 g every 24 hours, along with her medications upon admission, including imipramine 50 mg at bedtime and fluoxetine 10 mg/day. She was discharged after 5 days and returned the next day with chest tightness and shortness of breath. Upon the second admission, a 12-lead electrocardiogram showed a QTc interval of 509 msec. Levofloxacin was discontinued and the QTc interval fell to 403 msec. The patient was discharged 3 days later and instructed to consult with her primary care physician about discontinuing imipramine. DISCUSSION: This adverse drug reaction is thought to be a pharmacodynamic additive effect among fluoxetine, imipramine, and levofloxacin. Fluoxetine is a potent inhibitor of CYP2D6, and imipramine is metabolized by CYP2D6. Therefore, fluoxetine is able to increase the plasma concentrations of imipramine, leading to QT interval prolongation. Taken with imipramine, levofloxacin can lead to even greater prolongation of the QT interval. Based on the Naranjo probability scale, levofloxacin was possibly associated with cardiac arrhythmias in our patient. CONCLUSIONS: The use of levofloxacin alone, or more often in concomitant therapy with other medications that are known to prolong the QT interval, may cause QT interval prolongation; however, additional studies/case reports are needed to validate this conclusion.     

Autoimmune hemolytic anemia in childhood: serologic features in 100 cases

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Plasma exchange and rituximab treatment for lenalidomide‐associated cold agglutinin disease

BACKGROUND: Lenalidomide is an amino‐substituted analog of thalidomide with potent immunomodulatory properties. The drug has been widely used for treatment of multiple myeloma and myelodysplastic syndrome (MDS) associated with 5q‐abnormality. The most common side effects are cytopenias, infections, and deep venous thrombosis. CASE STUDY: We report a clinical observation of severe autoimmune hemolytic anemia (AIHA) due to cold agglutinin disease (CAD) that developed 11 days after initiation of lenalidomide treatment in a patient with MDS who relapsed after allogeneic bone marrow transplantation. RESULTS: CAD was diagnosed by the presence of hemolytic variables and cold agglutinin detected in patient's plasma. The antibody screen, which was performed at 37°C, was negative throughout. The direct antiglobulin test was positive only for complement (C3d). These findings supported the diagnosis of CAD associated with lenalidomide administration. Other causes of hemolysis including ABO incompatibility and infectious etiologies were ruled out. Rituximab therapy in conjunction with daily plasma exchange decreased the rate of hemolysis and transfusion requirement in our case. CONCLUSION: In addition to warm AIHA, lenalidomide use can also be associated with development of CAD. Rituximab given in conjunction with plasma exchange can be effective in treating CAD in this setting.     

Autoimmune hemolytic anemia associated with anti-Sc1

A case of autoimmune hemolytic anemia (AIHA) in a young child is described. The hemolysis was resistant to steroid therapy but responded to splenectomy and intravenous immunoglobulin. The autoantibody was shown to be anti-Sc1 by both serologic and immunoblotting techniques. This seems to be the first report of an autoanti-Sc1 detected by immunoblotting and the first example of AIHA in a child caused by autoanti-Sc1.     

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.     

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.