scholarly journals Efficacy of eculizumab in refractory life‐threatening warm autoimmune hemolytic anemia associated with chronic myelomonocytic leukemia

2020 ◽  
Vol 8 (12) ◽  
pp. 2641-2644
Author(s):  
Anne‐Cécile Gauchy ◽  
Maxime Hentzien ◽  
Alain Wynckel ◽  
Victoire de Marcellus ◽  
Cyrielle Rodier ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Chronic Myelomonocytic Leukemia ◽  
Refractory Life ◽  
Life Threatening ◽  
Myelomonocytic Leukemia

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 NUDT15 polymorphism explains serious toxicity to azathioprine in Indian patients with chronic immune thrombocytopenia and autoimmune hemolytic anemia: a case series

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anup J. Devasia ◽  
Raveen Stephen Stallon Illangeswaran ◽  
Infencia Xavier Raj ◽  
Biju George ◽  
Poonkuzhali Balasubramanian
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Immune Thrombocytopenia ◽  
Case Series ◽  
Severe Toxicity ◽  
Toxic Side Effect ◽  
Case Presentation ◽  
Oral Ulcers ◽  
Asian Patients ◽  
Life Threatening

AbstractObjectivesAzathioprine (AZA) is a commonly used immunosuppressant in patients with autoimmune diseases. The toxic side effect to AZA (myelosuppression, hair loss, and oral ulcers) are highly unpredictable which can be life threatening if not identified earlier and dose adjustments made or the drug is withdrawn.Case presentationHere we report a case series of five patients with severe toxicity while on treatment with AZA for autoimmune hemolytic anemia (n=1) and Immune thrombocytopenia (n=4). The common thiopurine methyltransferase (TPMT) variants (TPMT*2, *3A, *3B) were not present in these patients. However, all these patients had the NUDT15 415C>T variant that has been reported to explain serious toxicity to thioguanine in Asian patients.ConclusionsOur report suggests pre-emptive genotype-based dosing of AZA could reduce adverse toxicity and hence better outcome.

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.

Expression of CD47, CD35, CD55 and CD59 on Red Cells from Patients with Warm Autoimmune Hemolytic Anemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3738-3738
Author(s):  
Melca O. Barros ◽  
Mihoko Yamamoto ◽  
Maria S. Figueiredo ◽  
Elisa Y. Kimura ◽  
Jose Orlando Bordin
Keyword(s):  
Hemolytic Anemia ◽  
Lupus Erythematosus ◽  
Autoimmune Hemolytic Anemia ◽  
Experimental Studies ◽  
Red Cells ◽  
High Dose ◽  
Healthy Controls ◽  
Life Threatening ◽  
Positive Direct ◽  
Cd59 Expression

Abstract Autoimmune hemolytic anemia (AIHA) is defined as an increased destruction of red cells (RBC) in the presence of anti-RBC autoantibodies. CD47 is an integrin-associated protein expressed on all cells including RBCs. Animal models show that CD47 deficiency contributes to accelerated development of AIHA, while CD35 (CR1- complement receptor 1), CD55 (decay accelerating factor), and CD59 (membrane inhibitor of reactive lysis) are complement inhibitory proteins. Using flow cytometry analysis, in this study we evaluated the expression of CD47, CD35, CD55, and CD59 on RBCs of patients with warm AIHA before any treatment had been initiated. The study population consisted of 12 patients with active AIHA [M:F = 6:6, median age: 32 yrs (3 – 73)], and 20 healthy controls [M:F = 9:11, median age: 36 yrs (25 – 71)]. Ten patients presented idiopathic AIHA while 2 subjects had secondary AIHA (systemic lupus erythematosus and non-Hodgkin’s lymphoma). At presentation the median Hb level was 6.6 mg/dL (range: 2.9 to 10 mg/dL), and the median absolute reticulocyte count was 324 × 109/L (range: 215 to 756 × 109/L). At the time of the analyses, all 12 patients had a positive direct antiglobulin test (DAT), 12 (100%) had IgG on their RBCs, 5 (41.7%) had IgG plus C3, and none had C3 alone. The strength of agglutination of all positive DATs showed a strong reaction. The RBC eluates prepared by a dichloromethane technique from the cell samples were positive in all 12 patients, but the retrieved autoantibodies were pan-reactive showing no specific reactivity. The mean fluorescence intensity (MFI) of the expression of CD47, CD35 and CD55 on RBCs of AIHA patients and healthy individuals were not statistically different (CD47 = 464.4 and 464.4; CD35 = 186.8 and 194.3; CD55 = 396.9 and 381.1, respectively). Four patients with life-threatening AIHA were treated with high dose of steroids and RBC transfusions, but 3 patients evolved to death. Two patients who died presented low CD55 expression on their RBCs at diagnosis. AIHA patients showed significant lower CD59 expression on RBCs than healthy controls (MFI = 512.3 ± 28.0 and 553.7 ± 36.6, P = .03). Although CD59 expression in patients that evolved to remission was not significantly different from healthy controls (MFI = 538.5 ± 14.4 and 553.7 ± 36.6), the expression of CD59 on RBCs of 3 AHAI patients who died were significantly lower than that seen on RBCs of healthy controls (MFI = 433.6 ± 69.6 and 553.7 ± 36.6, P = .0001). Although experimental studies have suggested that CD47 has a profound influence on the severity of AIHA in mice, our preliminary data on 12 patients with AIHA did not demonstrate difference on the expression of CD47 on RBCs of patients with warm AIHA or healthy indibiduals. On the other hand, complement regulatory proteins (CD35, CD55, and CD59) may play an important role in protecting RBC destruction through the activation of complement. Our results suggest that patients with life-threatening warm AIHA may present significant CD59 deficiency on their RBCs that may increase the susceptibility of cells to complement-mediated lysis resulting in severe clinical hemolysis.

scholarly journals Myeloid Disease with the CSF3R T618I Mutation after CLL

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Maria Eduarda Couto ◽  
Susana Bizarro ◽  
Domingos Sousa ◽  
Nelson Domingues ◽  
Isabel Oliveira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hemolytic Anemia ◽  
Bone Marrow Aspirate ◽  
Chronic Myelomonocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Myeloproliferative Disease ◽  
Increased Risk ◽  
Long Time ◽  
Chronic Myeloproliferative Disease ◽  
Myelomonocytic Leukemia

Chronic lymphocytic leukemia (CLL) is frequently an indolent diagnosis, with most of the patients being under surveillance for long time. There is an increased risk of a second neoplasia in CLL, rarely hematological (in the myeloid lineage is even rarer). A 58-year-old male was diagnosed with CLL in 2012, remaining in regular surveillance until 2014. Then, the CLL progressed, and 6 cycles of rituximab, fludarabine, and cyclophosphamide were prescribed with partial response. He remained in surveillance and suffered 2 episodes of autoimmune hemolytic anemia until 2019. Then, the hemolytic anemia relapsed and a neutrophilia became evident (progressing slowly), as well as a thrombocytopenia and splenomegaly without adenopathy were found. The bone marrow aspirate showed a chronic myeloproliferative disease without dysplasia. A peripheral blood search for the CSF3R mutation (T618I) was positive, also suggesting Chronic Neutrophilic Leukemia (CNL). For a discrete monocytosis, a chronic myelomonocytic leukemia (CMML) was also considered. Hydroxyurea was then prescribed. The T618I CSF3R mutation is highly suggestive of CNL (being diagnostic criteria for CNL); however, this case may also suggest CMML as a possible diagnosis (there are other mutations in the CSF3R gene described for CMML, but not the T618I, which is highly exclusive of CNL according to the literature). To our knowledge, this is the first report of a possible CNL in a CLL patient (the opposite was already described in 1998).

scholarly journals Autoimmune Hemolytic Anemia and Red Blood Cell Autoantibodies

2015 ◽  
Vol 139 (11) ◽  
pp. 1455-1458 ◽  
Author(s):  
Erin Quist ◽  
Scott Koepsell
Keyword(s):  
Blood Cell ◽  
Clinical Significance ◽  
Hemolytic Anemia ◽  
Red Blood Cell ◽  
Autoimmune Hemolytic Anemia ◽  
Underlying Disease ◽  
Laboratory Findings ◽  
Life Threatening ◽  
The Common ◽  
Ancillary Studies

Autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell (RBC) antibodies that destroy RBCs. Although autoimmune hemolytic anemia is rare, RBC autoantibodies are encountered frequently and can complicate transfusion workups, impede RBC alloantibody identification, delay distribution of compatible units, have variable clinical significance that ranges from benign to life-threatening, and may signal an underlying disease or disorder. In this review, we discuss the common presenting features of RBC autoantibodies, laboratory findings, ancillary studies that help the pathologist investigate the clinical significance of autoantibodies, and how to provide appropriate patient care and consultation for clinical colleagues. Pathologists must be mindful of, and knowledgeable about, this entity because it not only allows for direct clinical management but also can afford an opportunity to preemptively treat an otherwise silent malignancy or disorder.

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