Levofloxacin-Induced Autoimmune Hemolytic Anemia

2003 ◽  
Vol 37 (7-8) ◽  
pp. 1010-1013 ◽  
Author(s):  
Young R Oh ◽  
Sian M Carr-Lopez ◽  
James M Probasco ◽  
Peter G Crawley
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Case Reports ◽  
Stable Condition ◽  
Drug Event ◽  
Packed Red Blood Cells ◽  
Case Summary ◽  
Immune Mediated ◽  
Severe Jaundice

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 Temafloxacin was withdrawn from the market in 1992 due to this adverse effect.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.

scholarly journals Immune-Mediated Hematologic Complications of Checkpoint Inhibitors: A Review of the Literature

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5883-5883 ◽  
Author(s):  
Omar Sallam ◽  
Irbaz Bin Riaz ◽  
Ronald S. Go
Keyword(s):  
Clinical Trials ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Immune Mediated ◽  
Immune Neutropenia

Abstract Background: The incidence and types of hematologic complications from immune check point inhibitors are not well known. We conducted this review to describe immune-mediated hematologic complications reported in clinical trials, case series, and case reports. Methods: A pre-defined comprehensive search strategy was used to identify case reports, case series, and clinical trials using PubMed. Any study that reported hematologic complications was included. Data were extracted for demographic characteristics and occurrence of immune-mediated hematologic complications. We pooled the data to calculate the frequency of immune-mediated hematologic adverse effects. Results: A total of 689 of studies were retrieved using the search criteria and 75 were included in the analysis (31 case reports and case series and 44 clinical trials). There were 44 patients reported having immune-mediated hematologic complications, 4 of them in clinical trials. The complications included aplastic anemia, autoimmune hemolytic anemia, cryoglobulinemia, graft versus host disease, hemophilia A (acquired), immune neutropenia, immune thrombocytopenia, macrophage activation syndrome, myelodysplastic syndrome, pure red cell aplasia, and thrombotic thrombocytopenic purpura. However, the overall rates were very low, ranging from 1-2.2% in clinical trials. Immune thrombocytopenia was the most common (29.5%), followed by autoimmune hemolytic anemia (15.9%), and immune neutropenia (13.6%). Immune-mediated hematologic complications were reported in all classes of checkpoint inhibitors including anti-programmed cell death protein 1 (nivolumab and pembrolizumab), anti-programmed death ligand 1 (avelumab and durvalumab), and anti-cytotoxic T-lymphocyte-associated protein 4 inhibitors (ipilimumab and tremelimumab). Among patients reported in case reports and case series, the median age was 57 years (range, 29-85) and most were males (52.9%). The majority of the complications occurred in patients treated with ipilimumab (38.8%), nivolumab (27.7%) and pembrolizumab (16.0%). The onset was usually within the first week of receiving the first dose but could occur up to 17 months after drug initiation. Indefinite discontinuation of the immunotherapy was the mainstay of treatment resulting in resolution of complications in the majority (74.5%) of the patients. Two patients were re-challenged with the same checkpoint inhibitor and one experienced a relapse of immune cytopenia (autoimmune hemolytic anemia). Conclusion: Immune-mediated hematologic complications associated with checkpoint inhibitors are rare. They are usually reversible after discontinuation of such treatment. Relapses may occur with re-challenge. Disclosures No relevant conflicts of interest to declare.

scholarly journals Safe Start of Ibrutinib in Patients with Chronic Lymphocytic Leukemia and Uncontrolled Autoimmune Hemolytic Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5560-5560 ◽  
Author(s):  
Alejandro Garcia-Horton ◽  
Rosanne St. Bernard ◽  
Alejandro Lazo-Langner ◽  
Anargyros Xenocostas ◽  
Joy Mangel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Laboratory Data ◽  
Case Series ◽  
Lymphocytic Leukemia ◽  
Positive Direct

Abstract It is estimated that 4-10% of patients with chronic lymphocytic leukemia (CLL) will develop autoimmune hemolytic anemia (AIHA) over the course of their disease. Ibrutinib has proven to be effective in treatment of relapsed, refractory, 17p deleted, and treatment naïve CLL. The effect of ibrutinib on AIHA in the context of CLL has not been established since patients with active hemolysis were excluded from major trials. In this abstract, we present a case series of patients that were actively hemolyzing at the start of ibrutinib therapy and in which their AIHA achieved prolonged response. Patient characteristics and laboratory data are shown in Table. Five patients (3 women, 2 men), median age 61 years (range 57 to 78), with CLL and active, uncontrolled AIHA at the time of ibrutinib initiation were identified. Uncontrolled AIHA was defined as anemia with evidence of hemolysis (at least two of the following: increased reticulocyte count, elevated lactate dehydrogenase, elevated indirect bilirubin, and reduced haptoglobin and a positive direct antiglobulin test (DAT)). Patients had a median hemoglobin of 70 g/L (range 69-96) prior to start of ibrutinib and 3 of them required transfusion support for symptomatic anemia. All patients were receiving prednisone for management of AIHA at the time of ibrutinib initiation and had been on it for a median of 10 days (range 9 - 25) without AIHA resolution. 1 patient received intravenous immunoglobulin concurrently. All patients had received at least one line of therapy for CLL in the past and 3 had experienced previous AIHA responsive to steroids. AIHA in 2 patients was related to previous fludarabine exposure but had responded to a prednisone tapering schedule and were off steroids by the time of the new AIHA flare. Median hemoglobin of 130 g/L (range 113-149) was reached at time of AIHA response. All 5 patients tolerated 420mg oral daily of ibrutinib therapy and AIHA was controlled in a median of 6.5 weeks (range 6-10). Discontinuation of steroids was achieved in all patients at a median of 10 weeks (range 6-17) without evidence of further hemolysis. All patients except one are receiving ongoing follow up and have been followed up for a median of 130 weeks (range 15-150) since ibrutinib start. Patients have not shown evidence of AIHA relapse and continue off AIHA treatment (prednisone). One patient required discontinuation of ibrutinib 6 months after starting due to neutropenia but there was no evidence of AIHA relapse in follow up. The patient has passed away from unrelated GI bleed 2 years after the initial AIHA event. This is the largest case series to our knowledge on the safe start of ibrutinib in CLL complicated by active AIHA. Hemolysis in all patients responded to a short prednisone taper with ibrutinib concurrently and obtained a sustained response at follow up without any flare ups or further AIHA treatment use. These cases suggest that it is safe to start ibrutinib during uncontrolled, active hemolysis in contrast to 2 previous case reports that suggested causal relationship between ibrutinib and onset of severe CLL-associated AIHA (Rider et al, 2015; Hodskins et al, 2014). As previously reported, AIHA occurrence or relapse once ibrutinib has been started is rare (Rogers et al, 2016). Disclosures No relevant conflicts of interest to declare.

Autoimmune Hemolytic Anemia in HIV: A Case Series and Review of the Literature.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3858-3858 ◽  
Author(s):  
David P.H. Wu ◽  
Joseph Caperna ◽  
Erin Reid
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Case Reports ◽  
Clinical Manifestations ◽  
Case Series ◽  
High Dose ◽  
Hiv Patients ◽  
Latino Male ◽  
Positive Direct

Abstract Background: Patients infected with HIV are more likely to have positive direct antiglobulin tests (Toy, Am J of Hem 1985) but there have only been a few reports of HIV-related AIHA (autoimmune hemolytic anemia) in the literature. Here we report three new cases of AIHA in HIV infected patients diagnosed from July 2003 to September 2005 at UCSD. Methods: Patients were identified by clinical presentation to the HIV service. All cases were considered highly likely by hematologists to have AIHA (lab data table 1). Results: Patient #1 was a 43 yo Caucasian male with CD4 < 50 prior ITP and untreated recently diagnosed visceral KS. On presentation, he reported dyspnea and had hepatosplenomegaly. His Hb was 5.2, retic 14%, LDH 459, Ibili 0.7, haptoglobin <7; + microspherocytes on smear. He was started on high-dose glucocorticoids (GC) before PRBC transfusion, and tolerated it well other than one fever to 100F. He received prednisone (pred) 60mg daily with taper. 3 weeks later at follow-up he self-tapered pred to 20mg and Hb was 11.1. Once off pred, his Hb remained stable at 11 when he died from PML approximately 4 months after remission of AIHA. Patient #2 is a 43 yo Latino male presenting with syncope, dizziness, dyspnea and palpations. His Hb was 5.4, retic 8%, LDH 366, Ibili 1.2, haptoglobin < 7, with smears showing extensive microspherocytes. He was treated with high-dose GC and received PRBC with heparin prophylaxis. His Hb recovered to 12. He was tapered off GC over 8 months and remains in remission for the past 2 months with Hb 14. Patient #3 is a 38 yo Latino male with dyspnea. His Hb was 5.7, retic 8%. He symptomatically improved with PRBC, and subsequently had a rapid response to GC. Hb peaked at 13.5 through tapering of pred by 10 mg weekly to 30 mg daily. The patient missed follow-up and continued the rapid taper, hemolysis recurred 1 month after pred cessation. Pred 60mg qd was restarted with resolution of hemolysis; this recurred even with slow taper (2mg/week) below 20mg daily. Pred again increased to 60 mg daily and danazol 600mg bid added with resolution of hemolysis. Pred taper to 20 mg was tolerated. Conclusions: AIHA in HIV patients has been described mainly in single case reports and abstracts (Koduri, Am Jo Hematology 2002). Only a few reports include long-term follow-up and fewer have included precipitants for AIHA. Within 2 years, we have three HIV patients with documented AIHA under different clinical manifestations and responses to treatment. One patient had a recent diagnosis of KS, the 2nd had received penicillin for syphilis and the 3rd had no recent medical complications. All 3 patients tolerated transfusion which resulted in symptomatic improvement and responded successfully to pred. Patient #3 who had a high CD4, was the only one with recurrence of hemolysis upon pred taper; perhaps a higher CD4 count may be associated with more persistent AIHA. In the literature, there are 14 other cases of idiopathic AIHA in adults with HIV (summary table to be presented at meeting). Of the 6 cases with reported CD4 counts, all were less than 200. 4/14 cases had inadequate reticulocyte response demonstrating existence of additional factors contributing to anemia. Most cases (10/14) responded to standard AIHA treatments including GC, IVIG and splenectomy. Overall 5/14 had died at the time of the reports; 2 of these deaths were related to PCP after remission of AIHA. 2/8 cases receiving PRBC died of DIC that occurred after transfusion. Table 1 Case Hb gm/dl Retic % LDH IU/L Hapto mg/dl IBili mg/dl CD4 #/ml 1 5.2 13.9 459 <7 0.9 82 2 5.4 8.1 366 <7 1.2 86 3 5.7 8.1 317 <7 2.1 424

scholarly journals Autoimmune Hemolytic Anemia as a Complication of Congenital Anemias. A Case Series and Review of the Literature

2021 ◽  
Vol 10 (15) ◽  
pp. 3439
Author(s):  
Irene Motta ◽  
Juri Giannotta ◽  
Marta Ferraresi ◽  
Kordelia Barbullushi ◽  
Nicoletta Revelli ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Case Series ◽  
Intravenous Immunoglobulins ◽  
Point Of View ◽  
First Line ◽  
Human Erythropoietin ◽  
Immune Mediated ◽  
Hemolytic Crisis ◽  
Life Threatening

Congenital anemias may be complicated by immune-mediated hemolytic crisis. Alloantibodies are usually seen in chronically transfused patients, and autoantibodies have also been described, although they are rarely associated with overt autoimmune hemolytic anemia (AIHA), a serious and potentially life-threatening complication. Given the lack of data on the AIHA diagnosis and management in congenital anemias, we retrospectively evaluated all clinically relevant AIHA cases occurring at a referral center for AIHA, hemoglobinopathies, and chronic hemolytic anemias, focusing on clinical management and outcome. In our cohort, AIHA had a prevalence of 1% (14/1410 patients). The majority were warm AIHA. Possible triggers were recent transfusion, infection, pregnancy, and surgery. All the patients received steroid therapy as the first line, and about 25% required further treatment, including rituximab, azathioprine, intravenous immunoglobulins, and cyclophosphamide. Transfusion support was required in 57% of the patients with non-transfusion-dependent anemia, and recombinant human erythropoietin was safely administered in one third of the patients. AIHA in congenital anemias may be challenging both from a diagnostic and a therapeutic point of view. A proper evaluation of hemolytic markers, bone marrow compensation, and assessment of the direct antiglobulin test is mandatory.

scholarly journals Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia in Association with Antiphospholipid Syndrome

2021 ◽  
pp. 1-4
Author(s):  
Ram Gelman ◽  
Fadi Kharouf ◽  
Yuval Ishay ◽  
Alexander Gural
Keyword(s):  
Hemolytic Anemia ◽  
Antiphospholipid Syndrome ◽  
Complement Activation ◽  
Autoimmune Hemolytic Anemia ◽  
Cold Agglutinin ◽  
Primary Antiphospholipid Syndrome ◽  
Unique Case ◽  
Hematologic Disorders ◽  
Clear Association ◽  
Immune Mediated

Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are 2 distinct immune-mediated hematologic disorders. While no clear association exists between these 2 entities, complement activation is known to occur in both of them. Herein, we report a unique case of cold agglutinin hemolytic anemia in a patient with a known primary antiphospholipid syndrome.

scholarly journals ‘Failure’ of laser prophylaxis in an eye with stickler syndrome

2021 ◽  
Vol 11 (4) ◽  
pp. 110-111
Author(s):  
Michael P Blair
Keyword(s):  
Vision Loss ◽  
Clinical Course ◽  
Case Reports ◽  
Visual Outcome ◽  
Stickler Syndrome ◽  
Connective Tissue Disorders ◽  
Macular Function ◽  
Giant Retinal Tear ◽  
Case Summary

Background: Stickler syndrome is one of the most common inherited connective tissue disorders and is an important cause of pediatric vision loss due to a high risk of retinal detachment in these patients. Methods: Case report. Case summary: This case reports describes the clinical course of a 10 year old boy with Sticklers Syndrome who underwent bilateral peripheral laser prophylaxis. During routine follow up, he was found to have an asymptomatic giant retinal tear (GRT) with limited sub-retinal fluid expansion due to prior prophylactic laser. He underwent surgery with vitrectomy and scleral buckle with vision remaining at 20/25 at 6 month follow up. Conclusion: Although the utility of laser prophylaxis in Stickler patients is debated, this case demonstrates that after laser prophylaxis, even if GRT develops, expansion can be limited. Laser prophylaxis along with frequent examinations, can prevent development of PVR and complex detachments and preserve macular function with excellent visual outcome.

A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia

2019 ◽  
Vol 143 (3) ◽  
pp. 244-249 ◽  
Author(s):  
Caroline I. Piatek ◽  
Hillel Bocian ◽  
Sandra Algaze ◽  
Ilene C. Weitz ◽  
Casey O'Connell ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Immune Modulation ◽  
Complete Response ◽  
Primary Objective ◽  
Additional Treatment ◽  
Lymphocytic Leukemia ◽  
Immunocompromised Patients ◽  
Treatment Changes

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy. Complete response (CR) was defined as a hemoglobin (Hgb) ≥12 g/dL. Partial response (PR) was defined as Hgb 10–11.9 g/dL or ≥2 g/dL increase in Hgb. Sustained response was defined as Hgb ≥10 g/dL with no treatment changes. A total of 16 patients with relapsed/refractory WAIHA received RCD (7 primary WAIHA, 9 secondary WAIHA) for a median of 4 cycles (range: 2–6). The median pretreatment Hgb was 10.0 g/dL (range: 4.3–12.2). The median best Hgb achieved was 12.5 g/dL (range: 10.6–15.1) with a median of 2 cycles until best Hgb response. The OR was 94% (11 CR, 4 PR). Two immunocompromised patients were admitted for infections during RCD treatment. There were no deaths during the treatment or follow-up period. Following a response to RCD, 4 patients received noncorticosteroid immune modulation therapy and 4 patients continued on corticosteroid therapy. Seven patients received no additional treatment.

Interleukin-10–mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4529-4536 ◽  
Author(s):  
Andrew M. Hall ◽  
Frank J. Ward ◽  
Mark A. Vickers ◽  
Lisa-Marie Stott ◽  
Stanislaw J. Urbaniak ◽  
...  
Keyword(s):  
T Cell ◽  
Blood Cell ◽  
Hemolytic Anemia ◽  
Red Blood Cell ◽  
Regulatory T Cell ◽  
Autoimmune Hemolytic Anemia ◽  
T Cell Responses ◽  
Interleukin 10 ◽  
Cell Responses ◽  
Immune Mediated

Regulatory T cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-γ or to secrete the regulatory cytokine interleukin 10 when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4+phenotype. Serial results from individual patients demonstrated that this bias toward proliferative or interleukin-10 responses was unstable over time and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin 10 and dependent on cytotonic T lymphocyte–associated antigen (CTLA-4) costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease.

A Rare Cause of Anemia in Inflammatory Bowel Diseases: A Case Report and Review of Literature

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5385-5385
Author(s):  
Waqas Ahmed ◽  
Kevin Monroe ◽  
James Essell ◽  
E. Randolph Broun
Keyword(s):  
Case Report ◽  
Hemolytic Anemia ◽  
Inflammatory Bowel Diseases ◽  
Autoimmune Hemolytic Anemia ◽  
Blood Smear ◽  
Rare Complication ◽  
Peripheral Blood Smear ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Introduction: Anemia is a common problem in patients with inflammatory bowel diseases (IBD), and its etiology is usually multifactorial. It can be produced by chronic blood loss, nutritional deficiencies, and drugs such as salazopyrine; however it can also due to auto immune hemolysis, which is a rare complication of IBD. We report a case of coombs positive autoimmune hemolytic anemia associated with ulcerative colitis both diagnosed at the same presentation. Case Report: A 32 year old man with no significant past medical history presented with complaint of dark colored urine, jaundiced skin and fatigue for 4 weeks. He also reported diarrhea mixed intermittently with blood for last few months. Physical exam was consistent with jaundice and anemia (pallor and icterus) with slightly palpable spleen. Initial lab work up showed Hb of 3.8 with normal platelet and WBC count, high reticulocytes count of 7% .LFT showed serum bilirubin of 3.6 (direct 0.4) with normal serum ALT and AST levels .Serum LDH was high (1032 U/l) while serum haptoglobin was low (0.11 mg/dl). Peripheral smear showed anisopoikilocytosis & spherocytosis. (See Figure 1) Further investigations revealed a positive direct Coombs test consistent with diagnosis of autoimmune hemolytic anemia. CT abdomen and pelvis showed mild splenomegaly & non-specific enlarged mesenteric lymph nodes. Colonoscopy revealed ulcerative pancolitis confirmed by histological findings of biopsies taken. Patient received PRBC transfusions and was started on steroids and mesalamine and was discharged on maintenance dose. His symptoms resolved in 4 weeks and Hb remained stable with no evidence of further hemolysis at 4 month follow up .Repeated CT abdomen & pelvis showed resolution of the lymphadenopathy. Figure 1: Peripheral Blood smear showing anisopoikilocytosis & spherocytosis. Figure 1:. Peripheral Blood smear showing anisopoikilocytosis & spherocytosis. Discussion: Autoimmune hemolytic anemia (AIHA) is a rare complication of IBD. The exact underlying pathogenesis of this association remains obscure; however it has been attributed to the production of cross reacting anti erythrocyte antibodies. In AIHA associated with IBD, corticosteroids are considered to be first line therapy and often cause remission of hemolysis along with treatment for IBD Immunomodulators and splenectomy has been used for patients with refractory AIHA. Colectomy done for fulminant colitis has also been reported to induce remission of AIHA. Further studies for long term follow up and pathogenesis of this association are warranted.

Clinical Heterogeneity Of Autoimmune Hemolytic Anemia: A 35-Years Retrospective Study Of 157 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3428-3428
Author(s):  
Wilma Barcellini ◽  
Bruno Fattizzo ◽  
Tommaso Radice ◽  
Anna Zaninoni ◽  
Nicoletta Revelli ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Acute Infection ◽  
Thermal Characteristics ◽  
Response Rates ◽  
Cytotoxic Drugs ◽  
Clinical Heterogeneity ◽  
Life Threatening

Abstract The clinical presentation of autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening forms. The aim of this study was to correlate the clinical and serological characteristics of the disease, usually classified as warm (WAIHA), cold (CHD), and mixed, based on the thermal and isotype characteristics of the anti-RBC antibody (IgG, IgM or both, respectively). One-hundred fifty seven AIHA patients (61 M and 96 F, median age 57, range 5-95) referred to our institution from 1978 to September 2012 were investigated. They had been followed-up for a median of 26 months (range 12-271), and 50% were still in follow-up. As regards the thermal characteristics 40% of cases were WAIHA, 32% CHD, 19% mixed forms and 9% atypical (12 DAT negative and 1 DAT positive for IgA only). Considering the severity of anemia at onset 33% of cases had Hb levels<6 g/dl, 34% Hb 6-8 g/dL, 18% Hb 8-10 g/dL, and 15% Hb>10 g/dL. The most severe AIHA cases were mainly mixed (18/30, 60% p=0.001) and atypical (6/13, 46%) forms, whereas only a small fraction of CHD was characterized by a severe onset (8/51, 16% p=0.002). Reticulocytopenia (<100.000 mmc) was more frequently observed in cases with severe onset (14/52, 27%), possibly contributing to the clinical picture. Eleven patients experienced an acute event at the onset of hemolysis and the majority of them (7/11, 63% ) were WAIHA; we recorded 4 deep venous thrombosis (with 2 subsequent pulmonary embolisms), 1 disseminated intravascular coagulation, 3 cardiac ischemic events, 2 acute renal failure and 4 acute infection (3 pneumonias and 1 sepsis); 18 patients died because of AIHA during the follow up. As regard therapy, we considered steroids, splenectomy, cytotoxic drugs and rituximab: 45% of cases (mostly WAIHA) were treated with steroids only, 23% with 2 lines, 10% with 3, and 6% with 4 or more lines; splenectomy was performed in 20 cases, mostly mixed and severe forms (p=0.001); 23 patients were treated with various cytotoxic drugs, and 33 with rituximab (the latter was more frequently administered in clinically severe cases, and in mixed and atypical forms, p=0.009). On the whole, the most severe patients were those who underwent 3 or more lines of therapy, compared with the other cases (14/52 versus 11/105, p=0.015). Finally, 16% of cases have never been treated, mostly CHD with mild anemia. Transfusions were performed in 65 cases, plasma-exchange in 3 (all with Hb<6 g/dL), and erythropoietin administered in 6 cases. Of note, the presence of an Hb value lower than 6 g/dL at onset was a risk factor for the requirement of 3 or more lines of therapy (odds ratio 3.148, CI 95% 1.312-7.552). Response rates to steroid therapy were similar in warm, cold, mixed and atypical AIHAs (on average 70%). Responses to rituximab were similar in cold and other AIHA forms (70-80%). Splenectomy, was ineffective in the 2 CHD who underwent surgery, whereas response rates were 63% in WAIHA and 80% in mixed and atypical cases. In conclusion, AIHAs showed a marked clinical heterogeneity, 1/3 of cases with a severe onset and with life threatening complications. These cases are frequently mixed or atypical forms and refractory to different therapies. Disclosures: No relevant conflicts of interest to declare.

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