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.     

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。     

The diagnostic protocol for hereditary spherocytosis‐2021 update

BackgroundHereditary spherocytosis (HS), a commonly encountered hereditary hemolytic disease, is mostly inherited in an autosomal dominant manner. The clinical manifestations in patients with HS show obvious heterogeneity. Moreover, the sensitivity or specificity of some HS diagnostic tests are not ideal and may easily result in misdiagnosis or missed diagnosis in some patients. The objective of this study was to propose a simple and practical diagnostic protocol, which can contribute to the diagnosis of HS and its differential diagnosis with different types of hemolytic anemia such as thalassemia (THAL), autoimmune hemolytic anemia (AIHA), and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, thus, to provide an alternative simple and reliable method for better clinical diagnosis of HS.MethodsThrough combing our research with existing experimental technologies and studies, we propose a simple and practical protocol for HS diagnosis, which will help clinicians to improve HS diagnosis.ResultsCompared with the existing HS diagnostic protocols, the HS diagnostic protocol we proposed is simpler. In this new protocol, some experimental tests with ideal diagnostic efficiency are added, such as mean reticulocyte volume (MRV), mean sphered cell volume (MSCV), mean corpuscular volume (MCV), in combination with the observation of clinical manifestations, family investigation, routine tests for hemolytic anemia, genetic testing, and other screening tests.ConclusionThe HS diagnostic protocol we proposed could improve the clinical practice and efficiency of HS diagnosis.     

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.     

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.     

Sirolimus for Refractory Autoimmune Hemolytic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review of the Treatment of Post-Transplant Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia (AIHA) may occur after any type of allogeneic hematopoietic stem cell transplantation (HCT), even ABO-matched transplantation. It tends to be refractory to standard corticosteroid treatment and requires multiple transfusions. Though, there is no consensus regarding the optimal treatment for post-transplant severe AIHA. We present a pediatric patient with refractory AIHA after umbilical cord blood transplantation. She developed severe AIHA at 3 months after transplantation and was unresponsive to multiple treatment modalities, including corticosteroids, intravenous immunoglobulin, plasma exchange and rituximab, resulting in persistent transfusion dependency. Sirolimus, a mammalian target of rapamycin inhibitor, was started on day 67 after the onset of AIHA, and this patient was successfully rescued without any complications. Sirolimus induces apoptosis in autoreactive lymphocytes, increases regulatory T cells and has been reported to have a positive effect on AIHA following solid organ transplantation (SOT). We reviewed the literature regarding post-transplant AIHA in the PubMed database and evaluated the treatment outcome of sirolimus in AIHA after SOT.     

溶血性贫血治疗进展

自身免疫性溶血性贫血(AIHA)作为血液科和普内科的常见疾病,其本质为患者体内产生结合在红细胞表面的自身抗体,导致以红细胞破坏为核心环节的贫血.AIHA的诊断需要结合自身抗体的类型和溶血相关特点.AIHA的治疗以皮质激素、免疫抑制剂和脾脏切除术为主.近年来,由于抗CD20单抗等新药出现,AIHA的治疗有了更多的选择,尤其是对于常规一线治疗失败的患者.     

利妥昔单抗注射液治疗自身免疫性溶血性贫血患者的护理

目的探讨利妥昔单抗注射液治疗难治性自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)患者的护理方法。方法回顾性总结并分析2012年6月至2013年5月中国医学科学院血液病医院采用利妥昔单抗注射液治疗的6例复发/难治性AIHA患者的临床资料。结果经积极治疗,本组6例患者中,完全缓解3例、部分缓解3例、发生不良反应1例。结论利妥昔单抗注射液治疗难治性自身免疫性溶血性贫血具有一定的疗效,积极的护理干预可减少利妥昔单抗注射液引起的不良反应,有利于提高患者的生活质量。     

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.     

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.     

Levofloxacin-induced autoimmune hemolytic anemia

OBJECTIVE: To report a case of autoimmune hemolytic anemia (AIHA) secondary to levofloxacin. CASE SUMMARY: An 82-year-old white man was treated with levofloxacin 500 mg/d for cellulitis. Three days following completion of levofloxacin therapy, the patient presented to the emergency department with severe jaundice, dizziness, and loss of vision. He received packed red blood cells (PRBCs) and was discharged home. Two days later at the follow-up visit, he was diagnosed with AIHA secondary to levofloxacin. The patient was hospitalized and treated with a tapering dose of prednisone and additional PRBC infusion. He was discharged from the hospital in stable condition after 3 days. Repeated hematologic laboratory studies following discharge demonstrated that the hemolytic anemia had resolved. DISCUSSION: Hemolytic anemia due to levofloxacin is an extremely rare, but potentially fatal, adverse drug event. An objective causality assessment revealed that the adverse reaction was probable. To our knowledge, this is the first published case of levofloxacin-induced AIHA. However, there are published case reports of hemolytic anemia with other fluoroquinolones including ciprofloxacin (n = 12) and temafloxacin (n = 95). Temafloxacin was withdrawn from the market in 1992 due to this adverse effect. The mechanism by which levofloxacin triggers hemolytic anemia is unknown. We believe that an immune-mediated reaction is most likely. CONCLUSIONS: Levofloxacin-induced AIHA is a rare but serious complication of therapy. Immediate discontinuation of the offending medication and treatment of the hemolytic anemia are essential. Until more information is available, levofloxacin should not be prescribed for patients with previous reactions to any fluoroquinolone.     

Hemolytic anemia and plasma exchange

Hemolytic anemia is a disease caused by autoantibodies and resulting in various complaints and clinical symptoms. In about half of cases, the cause of autoimmune hemolytic anemia can not be determined. Corticosteroids are the first-line treatment option for warm autoantibody-related hemolytic anemia. In patients who develop steroid side effects or do not respond adequately, other immunosuppressives may be preferred. In case a rapid response is required or fulminant hemolysis occur, human immunoglobulins (IVIGs) may be added to treatment. Finally, plasma exchange (PE) may additionally be utilised. The essence of PE is based on the removal of immune complexes, protein-bound toxins, autoantibodies and high molecular weight solutes and protein-bound solutes. The main clinical aim of the removal of solutes is usually to gain a faster response than immunosuppressive therapy. Studies related to hemolytic anemia and PE are usually based on case reports. Our case report is about a patient with severe IgG subtype hemolytic anemia. The treatment was started with 1 mg/kg methylprednisolone; to which there was no response with weekly rituximab 375 mg/m² and IVIG administered. Because of unresponsiveness to all of the immunosuppresives, a total of 5 sessions of PE were added to the treatment procedure every other day. After these sessions, the requirement for transfusions has decreased and the patient underwent splenectomy. The patient is currently being followed up only on oral cyclosporine and the last hemoglobin level was 14.7 g /dl. In severe and refractory anemia, especially in the case of cardiovascular imbalance in fulminant hemolysis, PE may be preferred as a third series option after immunosuppressive treatments and play a role as a bridge to splenectomy.     

Microangiopathic hemolytic anemia in pregnancy

Microangipathic hemolytic anemia (MAHA) is a serious diagnosis and difficult to manage in pregnant patients as multiple life threatening conditions could present with MAHA. ADAMTS13 enzyme activity can be affected during pregnancy with multiple factors. A persistent extremely low ADAMTS13 enzyme activity levels, without an inhibitor, after the delivery was an important factor to establish the diagnosis. We present a case of likely congenital ADAMST13 deficiency that manifested for the first time in a pregnant woman at week 37 of pregnancy.     

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.     

美罗华治疗老年自身免疫性溶血性贫血的临床研究

目的 观察美罗华治疗老年自身免疫性溶血性贫血(AIHA)的作用.方法 采用常规方法和美罗华两种方法,对该科收治的老年AIHA患者进行治疗,观察美罗华的治疗效果.结果 美罗华治疗组血红蛋白水平较常规方法回升快(P<0.05),两种方法均未见严重的不良反应.结论 美罗华治疗老年AIHA患者安全、有效.     

A Rare Presentation of Epstein–Barr Virus Infection

BackgroundEpstein–Barr virus (EBV) is a herpesvirus spread by intimate contact. It is known to cause infectious mononucleosis. Complications, including hematologic pathology and splenic rupture, are uncommon. This report is a case of EBV-induced autoimmune hemolytic anemia and biliary stasis.Case ReportAn 18-year-old man presented to the emergency department with abdominal pain, nausea, vomiting, and jaundice. He did not have risk factors for liver injury or hepatitis. His vital signs were notable for a fever. On examination, he was obviously jaundiced, but not in distress. Laboratory evaluation showed hemolytic anemia and biliary stasis. Ultimately, his inpatient workup yielded positive EBV serology and a positive direct agglutinin test with cold agglutinins. He made a full recovery with supportive care.Why Should an Emergency Physician Be Aware of This?EBV is a widely disseminated herpesvirus. Infectious mononucleosis is a common presentation of acute infection, and treatment of EBV-related diseases are largely supportive. Complications, such as splenic rupture and hematologic pathology, are uncommon. Biliary stasis and autoimmune hemolytic anemia in the form of cold agglutinin disease secondary to EBV is rare, and typically resolves with supportive care and cold avoidance. More advanced treatment methods are available in the setting of severe hemolysis. Elevated transaminases, direct hyperbilirubinemia, or evidence of hemolytic anemia in the setting of a nonspecific viral syndrome should raise suspicion for EBV infection. Rapid recognition can lead to more prompt prevention and treatment of other EBV-related complications.     

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。     

Ham′s试验阳性的宽热幅异常冷凝集素型自身免疫性溶血性贫血

报告一例误诊为阵发性睡眠性血红蛋白尿症的宽热幅异常冷凝集素型自身免疫性溶血性贫血。患者冷凝素试验４℃效价＞４０９６，积分１０４；２５℃效价１２８，积分３８；３７℃效价６４，积分２２。讨论了两者在临床与溶血机制方面的鉴别诊断。     

Plasma exchanges do not increase red blood cell transfusion efficiency in severe autoimmune hemolytic anemia: a retrospective case-control study

Severe autoimmune hemolytic anemia (AIHA) can cause life-threatening hemolysis requiring red blood cell transfusions (RBT). The efficiency of RBT could be improved with the use of plasma exchanges (PEx) before RBT. The objective of this study was to assess the effectiveness of PEx in severe AIHA of adults. All adult patients with severe AIHA requiring RBT were included in this single center retrospective case-control study. The end point was change in hemoglobin (Hb) level after RBT, depending on whether PEx was done (experimental group) or not (control group). Thirty-one sessions of RBT following PEx were performed on the 5 patients of the experimental group and were compared with the 7 sessions of BT without PEx performed on the 4 patients of the control group. Despite a lower mean Hb value before the session of RBT (5.7 g/dl vs. 7.2 g/dl, P = 0.04) in the control group, the mean Hb value 5 (4-7) days following RBT (8.7 g/dl vs. 8.6 g/dl, P = 0.85) was not different in the experimental and in the control group, respectively. In a second analysis in which each patient was his own control (31 sessions of RBT following PEx vs. 51 sessions of RBT alone), the gain in Hb was not different (1.4 g/dl vs. 1.9 g/dl, P = 0.67). When RBT are required in severe AIHA of adults, the use of a single PEx before BT does not increase the efficiency of RBT based on day 5 evaluation.