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1.
Rinsho Ketsueki ; 63(10): 1379-1385, 2022.
Article in Japanese | MEDLINE | ID: covidwho-2110946

ABSTRACT

There is currently no evidence that a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine might be associated with the development of autoimmune hemolytic anemia or disease progression in patients with mature B-cell neoplasm. Our patient was a 71-year-old man with indolent mature B-cell neoplasm who had been monitored for many years without treatment. After receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine, he developed severe warm autoimmune hemolytic anemia. Although steroid therapy improved his anemia, he continued to develop IgM-monoclonal gammopathy, renal insufficiency, and splenomegaly. He was diagnosed with splenic marginal zone lymphoma after undergoing splenectomy. The splenectomy improved the patient's symptoms. We assessed his SARS-CoV-2 specific antibody response, but the patient's serologic response to the vaccine was impaired. In patients with mature B-cell neoplasm, a non-specific immune response after vaccination might be associated with paraneoplastic syndromes.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 Vaccines , COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, B-Cell , Paraproteinemias , Splenic Neoplasms , Aged , Humans , Male , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/complications , BNT162 Vaccine , COVID-19/complications , COVID-19 Vaccines/adverse effects , Immunoglobulin M , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Lymphoma, B-Cell/drug therapy , Paraproteinemias/complications , SARS-CoV-2 , Splenic Neoplasms/complications
3.
Am J Clin Pathol ; 157(6): 844-851, 2022 06 07.
Article in English | MEDLINE | ID: covidwho-2051264

ABSTRACT

OBJECTIVES: To summarize the epidemiologic, clinical, and laboratory characteristics of autoimmune hemolytic anemia (AIHA) secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. METHODS: We conducted a systematic review using standardized keyword search to identify all reports of SARS-CoV-2 infection or vaccination and AIHA across PubMed, Web of Science, Scopus, and Google Scholar through September 24, 2021. RESULTS: Fifty patients (mean [SD] age, 50.8 [21.6] years) diagnosed with coronavirus disease 2019 (COVID-19) and AIHA were identified. AIHA subtypes and number of patients were as follows: cold AIHA (n = 18), warm AIHA (n = 14), mixed-type AIHA (n = 3), direct antiglobulin test (DAT)-negative AIHA (n = 1), DAT-negative Evans syndrome (n = 1), Evans syndrome (n = 3), and subtype not reported (n = 10). Mean (SD) hemoglobin at AIHA diagnosis was 6.5 [2.8] g/dL (95% confidence interval, 5.7-7.3 g/dL). Median time from COVID-19 symptom onset to AIHA diagnosis was 7 days. In total, 19% (8/42) of patients with COVID-19-associated AIHA with reported outcomes were deceased. Four patients (mean [SD] age, 73.5 [16.9] years) developed AIHA following SARS-CoV-2 vaccination: Pfizer-BioNTech BNT162b2 vaccine (n = 2); Moderna mRNA-1273 vaccine (n = 1); undisclosed mRNA vaccine (n = 1). AIHA occurred after 1 dose in 3 patients (median, 5 days). CONCLUSIONS: SARS-CoV-2 infection and vaccination are associated with multiple AIHA subtypes, beginning approximately 7 days after infectious symptoms and 5 days after vaccination.


Subject(s)
COVID-19 , Vaccines , 2019-nCoV Vaccine mRNA-1273 , Aged , Anemia, Hemolytic, Autoimmune , BNT162 Vaccine , COVID-19 Vaccines , Humans , Middle Aged , SARS-CoV-2 , Thrombocytopenia , Vaccines, Synthetic , mRNA Vaccines
5.
BMJ Case Rep ; 15(8)2022 Aug 31.
Article in English | MEDLINE | ID: covidwho-2019952

ABSTRACT

A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293 units/L and bilirubin of 228 µmol/L, refractory to standard treatment with corticosteroids and rituximab. An emergency splenectomy was performed that slowed haemolysis but did not completely ameliorate it. Eculizumab, a terminal complement pathway inhibitor, was initiated to arrest intravascular haemolysis and showed a favourable response. AIHA is rare but described after the SARS-CoV-2 Pfizer-BioNTech vaccine. This case highlights the rare complication of AIHA, the use of emergency splenectomy for disease control, and the use of eculizumab.


Subject(s)
Anemia, Hemolytic, Autoimmune , BNT162 Vaccine , COVID-19 , Adolescent , Anemia, Hemolytic, Autoimmune/complications , Antibodies, Monoclonal, Humanized , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/adverse effects , Bilirubin , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Complement Inactivating Agents/therapeutic use , Hemoglobins , Hemolysis , Humans , Immunologic Factors/therapeutic use , Lactate Dehydrogenases , Male , RNA, Messenger/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2 , Splenectomy/adverse effects
6.
J Clin Lab Anal ; 36(9): e24629, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1966051

ABSTRACT

BACKGROUND: Cold agglutinin syndrome (CAS) is associated with various diseases. Several studies of CAS associated with coronavirus disease 2019 (COVID-19) reported hemolytic anemia and thrombosis; however, the clinical significance of cold agglutinins (CA) in patients with COVID-19 is unclear. Here, we present two cases of CA identified in the context of COVID-19 without hemolytic anemia and clotting. CASE REPORT AND DISCUSSION: Two patients with no known risk factors for CA were diagnosed with COVID-19; peripheral blood smears reveal red blood cells (RBCs) agglutination. These patients showed a high CA titer. We confirmed retrospectively that the CA was an anti-I antibody. The two COVID-19 cases with a high CA titer showed no hemolysis or thrombosis. Mycoplasma pneumoniae is known to cause CAS, but not all patients who have a high CA titer show hemolysis. Coagulation abnormalities are documented in severe COVID-19 cases. Although CA increases the risk of thrombosis in those with lymphoproliferative diseases, the role of anti-I antibodies in COVID-19 is unclear. The impact of CAS on clinical presentations in COVID-19 remains a matter of verification. CONCLUSIONS: A high CA titer was identified in COVID-19 patients without hemolytic anemia and clotting. Anti-I antibodies were identified. Further studies are required to clarify the pathophysiology of CA in COVID-19.


Subject(s)
Anemia, Hemolytic, Autoimmune , Anemia, Hemolytic , COVID-19 , Antibodies , Cryoglobulins , Hemolysis , Humans , Retrospective Studies
7.
Intern Med ; 61(11): 1789-1793, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1951851

ABSTRACT

Secondary cold agglutinin syndrome (CAS) is autoimmune hemolytic anemia secondary to infections and lymphoid disorder. We here report the first Asian case of CAS secondary to novel coronavirus disease 2019 (COVID-19). A 72-year-old Japanese woman presented with a 2-week history of dyspnea and cough, and laboratory data revealed severe hemolytic anemia with a hemoglobin level of 4.7 g/dL. She was diagnosed with COVID-19, CAS, and monoclonal gammopathy of undetermined significance (MGUS). The anemia responded to corticosteroids administered for COVID-19 and required maintenance therapy. Although corticosteroids are not a standard therapy for CAS, they might be effective for CAS secondary to COVID-19 complicated with MGUS.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 , Monoclonal Gammopathy of Undetermined Significance , Adrenal Cortex Hormones/therapeutic use , Aged , Anemia, Hemolytic, Autoimmune/complications , Anemia, Hemolytic, Autoimmune/drug therapy , COVID-19/complications , Cryoglobulins , Female , Humans , Immunoglobulin M , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Monoclonal Gammopathy of Undetermined Significance/drug therapy
8.
Immunobiology ; 227(4): 152240, 2022 07.
Article in English | MEDLINE | ID: covidwho-1914499

ABSTRACT

Previous case reports have described patients with COVID-19-associated autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) which is characterized by a positive direct antiglobulin (DAT) or "Coombs" test, yet the mechanism is not well understood. To investigate the significance of Coombs test reactivity among COVID-19 patients, we conducted a retrospective study on hospitalized COVID-19 patients treated at NMC Royal Hospital between 15 April and 30 May 2020. There were 27 (20%) patients in the Coombs-positive group and 108 (80%) in the Coombs-negative group. The cold agglutinin titer was examined in 22 patients due to symptoms suggestive of cold agglutinin disease, and all tested negative. We demonstrated a significant association with reactive Coombs test results in univariate analysis through clinical findings such as ICU admission rate, the severity of COVID-19, and several laboratory findings such as CRP, D-dimer, and hemoglobin levels lactate dehydrogenase, and RDW-CV. However, only hemoglobin levels and disease severity had a statistically significant association in multivariate analysis. A possible explanation of COVID-19-associated positive Coombs is cytokine storm-induced hyperinflammation, complement system activation, alterations of RBCs, binding of SARS-CoV-2 proteins to hemoglobin or its metabolites, and autoantibody production. Coombs-positive patients were tested for hemolysis using indirect bilirubin, consumed haptoglobin, and/or peripheral smear that ruled out any evidence of hemolysis. Understanding this etiology sheds new light on RBC involvement as a pathophysiological target for SARS-CoV-2 by interfering with their function; consequently, therapies capable of restoring RBC function, such as erythrocytapheresis, could be repurposed for the treatment of worsening severe and critical COVID-19.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/drug therapy , Antibodies, Anti-Idiotypic/therapeutic use , Coombs Test/methods , Hemoglobins , Hemolysis , Humans , Retrospective Studies , SARS-CoV-2
9.
Hematol Oncol Clin North Am ; 36(2): 325-339, 2022 04.
Article in English | MEDLINE | ID: covidwho-1914449

ABSTRACT

Warm autoimmune hemolytic anemia (wAIHA) is an uncommon and heterogeneous disorder caused by autoantibodies to RBC antigens. Initial evaluation should involve the DAT, with wAIHA typically IgG positive with or without C3 positivity, and a search for underlying conditions associated with secondary wAIHA, which comprise 50% of cases. First-line therapy involves glucocorticoids, increasingly with rituximab, though a chronic relapsing course is typical. While splenectomy and a number of immunosuppressive therapies have been used in the setting of relapsed and refractory disease, the optimal choice and sequence of therapies is unknown, and clinical trials should be offered when available. Newer investigational targets include spleen tyrosine kinase inhibitors, monoclonal antibodies targeting CD38, Bruton's tyrosine kinase inhibitors, complement inhibitors, and antibodies against neonatal Fc receptors.


Subject(s)
Anemia, Hemolytic, Autoimmune , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/therapy , Autoantibodies/therapeutic use , Humans , Infant, Newborn , Protein Kinase Inhibitors/therapeutic use , Rituximab/therapeutic use , Splenectomy
10.
Expert Rev Clin Immunol ; 18(7): 731-745, 2022 07.
Article in English | MEDLINE | ID: covidwho-1890482

ABSTRACT

INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is classified according to the direct antiglobulin test (DAT) and thermal characteristics of the autoantibody into warm and cold forms, and in primary versus secondary depending on the presence of associated conditions. AREAS COVERED: AIHA displays a multifactorial pathogenesis, including genetic (association with congenital conditions and certain mutations), environmental (drugs, infections, including SARS-CoV-2, pollution, etc.), and miscellaneous factors (solid/hematologic neoplasms, systemic autoimmune diseases, etc.) contributing to tolerance breakdown. Several mechanisms, such as autoantibody production, complement activation, monocyte/macrophage phagocytosis, and bone marrow compensation are implicated in extra-/intravascular hemolysis. Treatment should be differentiated and sequenced according to AIHA type (i.e. steroids followed by rituximab for warm, rituximab alone or in association with bendamustine or fludarabine for cold forms). Several new drugs targeting B-cells/plasma cells, complement, and phagocytosis are in clinical trials. Finally, thrombosis and infections may complicate disease course burdening quality of life and increasing mortality. EXPERT OPINION: Beyond warm and cold AIHA, a gray-zone still exists including mixed and DAT negative forms representing an unmet need. AIHA management is rapidly changing through an increasing knowledge of the pathogenic mechanisms, the refinement of diagnostic tools, and the development of novel targeted and combination therapies.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/therapy , Humans , Quality of Life , Rituximab/therapeutic use , SARS-CoV-2
11.
J Assoc Physicians India ; 70(5): 11-12, 2022 May.
Article in English | MEDLINE | ID: covidwho-1857647

ABSTRACT

This report describes a case of Autoimmune Hemolytic Anemia that was possibly induced by COVID-19 in a patient with history of Chronic Liver Disease and Diabetes Mellitus. Autoimmune responses like hemolytic anemia are known to be triggered by viral infections. COVID-19 is reported to be inducing Autoimmune Hemolytic Anemia in susceptible individuals. This is a case report of a 65 year old male with history of chronic alcoholism, who tested positive for COVID-19 infection which was treated as per protocols and was uncomplicated at the time of discharge. After about three months he presented with complaints of breathlessness which on laboratory evaluation revealed Direct Coombs test positive hemolytic anemia. Anemia improved with blood transfusion and steroid administration but patient eventually developed hepatorenal syndrome and expired.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 , Hepatorenal Syndrome , Liver Diseases , Aged , Anemia, Hemolytic, Autoimmune/complications , Anemia, Hemolytic, Autoimmune/etiology , Autoimmunity , COVID-19/complications , Humans , Male
12.
BMJ Case Rep ; 15(4)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1832378

ABSTRACT

Impaired immune response with uncontrolled inflammation and various immunological disorders have been reported during SARS-CoV-2 infection. Here, we report a case of cold agglutinin disease occurring during a severe coronavirus disease 2019 (COVID-19) in a French intensive care unit. A patient was presented with acute respiratory distress syndrome, acute renal failure and haemolytic anaemia. Direct antiglobulin test was positive with a cold agglutinin titre of 1/512. No other cause than COVID-19 explained the occurrence of cold agglutinin disease; however, causality could not be formally established. Persistent anaemia despite transfusion therapy and the short-term life-threatening, prompted the infusion of a monoclonal anti-C5 antibody (eculizumab). Eculizumab therapy quasi-fully resolved haemolysis within a few days, but ultimately the patient died from his severe COVID-19 infection. Data regarding the specific treatment of cold agglutinin disease during COVID-19 are rare. Although additional studies are warranted, eculizumab may be considered in critical situations.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/etiology , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , Humans , SARS-CoV-2
14.
authorea preprints; 2022.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.164864429.97531353.v1

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) is a member of Beta coronaviruses that became pandemic by March of 2020. The hematological manifestations related to COVID-19 are mostly lymphopenia, thrombocytopenia, elevated D-dimer, and ferritin levels. Autoimmune hemolytic anemia (AIHA) associated with COVID-19 has been described rarely; however, to our knowledge, complement-mediated autoimmune hemolytic anemia (CM-AIHA) has not been reported in children. Here, we report a child with COVID-19 associated with CM-AIHA.


Subject(s)
Coronavirus Infections , COVID-19 , Anemia, Hemolytic, Autoimmune , Thrombocytopenia , Hemolysis
16.
Hematol Oncol Clin North Am ; 36(2): 353-363, 2022 04.
Article in English | MEDLINE | ID: covidwho-1734426

ABSTRACT

Autoimmune hemolytic anemia (AHIA) is the group of acquired autoimmune conditions resulting from the development of autologous antibodies directed against autologous red blood cell antigens resulting in red cell lysis. Beyond the presence, severity, and duration of hemolysis which can lead to symptomatic anemia, additional complications at presentation and during treatment require a high degree of clinical vigilance. These include among others cutaneous, thrombotic, renal disorders, and infectious disorders. Complications can be due to the presence of the pathologic antibody itself, the process of hemolysis, or attributed to treatment. Comprehensive management of AIHA requires awareness and assessment of complications at diagnosis, during, and following treatment.


Subject(s)
Anemia, Hemolytic, Autoimmune , Hematopoietic Stem Cell Transplantation , Thrombosis , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/therapy , Erythrocytes , Hematopoietic Stem Cell Transplantation/adverse effects , Hemolysis , Humans
17.
Am J Hematol ; 97(6): 691-699, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1704611

ABSTRACT

Patients with relapsed warm antibody autoimmune hemolytic anemia (wAIHA) have limited treatment options. Fostamatinib is a potent, orally administered spleen tyrosine kinase inhibitor approved in the United States and Europe for the treatment of adults with chronic immune thrombocytopenia (ITP). This phase 2 study evaluated the response to fostamatinib, administered at 150 mg BID orally with or without food in adults with wAIHA and active hemolysis with hemoglobin (Hgb) <10 g/dL who had failed at least one prior treatment. Hemoglobin levels and safety assessments were performed at visits every 2 weeks. The primary endpoint was Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by week 24 without rescue therapy or red blood cell transfusion. Eleven of 24 (46%) patients achieved the primary endpoint. Increases in median Hgb were detected at week 2 and sustained over time. Median lactate dehydrogenase levels and reticulocyte counts generally declined over time with little change in median haptoglobin levels. The most common adverse events (AEs) were diarrhea (42%), fatigue (42%), hypertension (27%), dizziness (27%), and insomnia (23%). AEs were manageable and consistent with the fostamatinib safety database of over 3900 patients across multiple diseases (rheumatoid arthritis, B-cell lymphoma, COVID-19, and ITP). No new safety signals were detected. Fostamatinib may be a promising therapeutic option for wAIHA. A randomized, double-blind, phase 3 study is nearing completion.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 , Adult , Aminopyridines , Anemia, Hemolytic, Autoimmune/drug therapy , Humans , Morpholines , Oxazines , Pyridines , Pyrimidines
18.
Int J Mol Sci ; 22(16)2021 Aug 21.
Article in English | MEDLINE | ID: covidwho-1662690

ABSTRACT

Infection with viruses, such as the lactate dehydrogenase-elevating virus (LDV), is known to trigger the onset of autoimmune anemia through the enhancement of the phagocytosis of autoantibody-opsonized erythrocytes by activated macrophages. Type I interferon receptor-deficient mice show enhanced anemia, which suggests a protective effect of these cytokines, partly through the control of type II interferon production. The development of anemia requires the expression of Fcγ receptors (FcγR) I, III, and IV. Whereas LDV infection decreases FcγR III expression, it enhances FcγR I and IV expression in wild-type animals. The LDV-associated increase in the expression of FcγR I and IV is largely reduced in type I interferon receptor-deficient mice, through both type II interferon-dependent and -independent mechanisms. Thus, the regulation of the expression of FcγR I and IV, but not III, by interferons may partly explain the exacerbating effect of LDV infection on anemia that results from the enhanced phagocytosis of IgG autoantibody-opsonized erythrocytes.


Subject(s)
Anemia, Hemolytic, Autoimmune/immunology , Arterivirus Infections/immunology , Interferons/metabolism , Lactate dehydrogenase-elevating virus/immunology , Receptors, IgG/metabolism , Anemia, Hemolytic, Autoimmune/virology , Animals , Arterivirus Infections/virology , Host-Pathogen Interactions , Mice, Inbred C57BL , Mice, Knockout , Phagocytosis
19.
J Investig Med High Impact Case Rep ; 10: 23247096211073258, 2022.
Article in English | MEDLINE | ID: covidwho-1632182

ABSTRACT

Discussion of the hematologic complications of vaccination for severe acute respiratory syndrome coronavirus-2 (COVID-19) has primarily focused on the development of vaccine-associated immune thrombosis with thrombocytopenia (VITT). Other hematologic complications are uncommon. We report the case of a patient who developed immunoglobulin G (IgG)-mediated autoimmune hemolytic anemia (AIHA) after the Moderna COVID-19 messenger ribonucleic acid (mRNA) vaccine.


Subject(s)
Anemia, Hemolytic, Autoimmune , COVID-19 , Vaccines , Anemia, Hemolytic, Autoimmune/chemically induced , COVID-19 Vaccines , Humans , RNA, Messenger/genetics , SARS-CoV-2
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