-
Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection.Annals of Hematology Jan 2021Higher levels of D-dimer, LDH, and ferritin, all have been associated with the poor prognosis of COVID-19. In a disease where there are acute inflammation and... (Comparative Study)
Comparative Study
Higher levels of D-dimer, LDH, and ferritin, all have been associated with the poor prognosis of COVID-19. In a disease where there are acute inflammation and compromised oxygenation, we investigated the impact of initial hemoglobin (Hgb) levels at Emergency Department (ED) triage on the severity and the clinical course of COVID-19. We conducted a cross-sectional study on 601 COVID-19 patients in a COVID-19 national referral center between 13 and 27 June 2020. All adult patients presented at our hospital that required admission or hotel isolation were included in this study. Patients admitted to the intensive care unit (ICU) had a lower initial Hgb than those admitted outside the ICU (12.84 g/dL vs. 13.31 g/dL, p = 0.026) and over the course of admission; the prevalence of anemia (Hgb < 12.5 g/dL) was 65% in patients admitted to ICU, whereas it was only 43% in non-ICU patients (odds ratio of 2.464, 95% CI 1.71-3.52). Anemic ICU patients had a higher mortality compared with non-anemic ICU patients (hazard ratio = 1.88, log-rank p = 0.0104). A direct agglutination test (DAT) for all anemic patients showed that 14.7% of ICU patients and 9% of non-ICU patients had autoimmune hemolytic anemia (AIHA). AIHA patients had significantly longer length of hospital stay compared with anemic patients without AIHA (17.1 days vs. 14.08 days, p = 0.034). Lower Hgb level at hospital presentation could be a potential surrogate for COVID-19 severity.
Topics: Adult; Aged; Anemia, Hemolytic, Autoimmune; COVID-19; Cross-Sectional Studies; Disease-Free Survival; Female; Hemoglobins; Humans; Intensive Care Units; Male; Middle Aged; SARS-CoV-2; Survival Rate
PubMed: 32918594
DOI: 10.1007/s00277-020-04256-3 -
Current Opinion in Hematology Nov 2018Pathogenic autoantibodies directed against red blood cells (RBCs) may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Much of what is... (Review)
Review
PURPOSE OF REVIEW
Pathogenic autoantibodies directed against red blood cells (RBCs) may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Much of what is known about the etiology and pathogenesis of AIHA has been learned from observations made in human patients and murine models, but many questions remain; importantly, it is still unclear why some people generate RBC-specific autoantibodies. The combination of technological advancements applied to existing models and the development of new AIHA murine models will continue to provide considerable insight into the initiation of AIHA and provide a platform for the design of more effective therapies.
RECENT FINDINGS
Advancements in well described murine models of AIHA show that reticulocytes are preferentially targeted by anti-RBC autoantibodies and an increase in oxidative stress may trigger autoantibody production. Additionally, a new murine model of erythrocyte autoreactivity demonstrates that T cell tolerance is the stopgap for autoimmunity. Moreover, unlike many self-antigens, data suggest that RBC self-antigens are not presented in the thymus thereby escaping the scrutiny of T cell central tolerance mechanisms and placing emphasis on peripheral tolerance instead. Information gained from this new model provide novel insight into how the immune system responds to RBC autoantigens and provides a tractable platform to discover new therapies for AIHA.
SUMMARY
Murine models of AIHA have provided significant understanding into the risk factors for AIHA. The application of new technologies and models of erythrocyte autoreactivity is a pathway with the potential to elucidate how tolerance to RBC autoantigens is established, maintained, and broken down.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Disease Models, Animal; Erythrocytes; T-Lymphocytes
PubMed: 30169458
DOI: 10.1097/MOH.0000000000000459 -
Journal of Infection and Chemotherapy :... Sep 2023
Topics: Humans; Anemia, Hemolytic, Autoimmune; COVID-19
PubMed: 37271340
DOI: 10.1016/j.jiac.2023.06.001 -
American Journal of Hematology May 2019Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause... (Clinical Trial)
Clinical Trial
Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi-AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22-110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2-12.9 g/dL) and 6.3 g/dL (IQR, 6.1-8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were rechallenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi-AIHA were similar in DAT positive and negative patients. ICPi-AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi-AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first-line treatment in the majority of patients with ICPi-AIHA, and most patients who are rechallenged with an ICPi do not appear to develop recurrence of AIHA.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Female; Glucocorticoids; Hemoglobins; Humans; Immunosuppression Therapy; Male; Middle Aged
PubMed: 30790338
DOI: 10.1002/ajh.25448 -
Indian Pediatrics Aug 2021To analyze clinical and laboratory parameters, and treatment outcomes of children with autoimmune hemolytic anemia (AIHA).
OBJECTIVE
To analyze clinical and laboratory parameters, and treatment outcomes of children with autoimmune hemolytic anemia (AIHA).
METHODS
Retrospective analysis of 50 children aged 0-18 years. Monospecific direct antiglobulin test (DAT) and investigations for secondary causes were performed. Disease status was categorized based on Cerevance criteria.
RESULTS
Median (range) age at diagnosis was 36 (1.5-204) months. AIHA was categorized as cold (IgM+,C3+/cold agglutinin+) (35%), warm (IgG+ with/without C3+) (28%), mixed (IgG+, IgM+, C3+) (15%) and paroxysmal cold hemoglobinuria (4%). Primary AIHA accounted for 64% cases. Treatment modalities included steroid (66%), intravenous immunoglobulin (IVIg) (4%), steroid+IVIg (4%), and steroid+rituximab (4%). Treatment duration was longer for secondary AIHA than primary (11 vs 6.6 months, P<0.02) and in patients needing polytherapy than steroids only (13.3 vs 7.5 months, P<0.006). During median (range) follow-up period of 73 (1-150) months, 29 (58%) remained in continuous complete remission, 16 (32%) remained in complete remission.
CONCLUSIONS
Infants with AIHA have a more severe presentation. Monospecific DAT and a thorough search for an underlying cause help optimize therapy in most patients of AIHA.
Topics: Anemia, Hemolytic, Autoimmune; Child; Coombs Test; Hemoglobinuria, Paroxysmal; Humans; Infant; Retrospective Studies; Rituximab
PubMed: 33634793
DOI: 10.1007/s13312-021-2282-7 -
Tidsskrift For Den Norske Laegeforening... Nov 2009Knowledge of autoimmune hemolytic anemia is rapidly increasing, especially on pathogenesis, associated disorders and aspects of transfusion immunology. New treatment... (Review)
Review
BACKGROUND
Knowledge of autoimmune hemolytic anemia is rapidly increasing, especially on pathogenesis, associated disorders and aspects of transfusion immunology. New treatment options have emerged.
MATERIAL AND METHOD
This review is based on selected publications, a non-systematic search in PubMed and the authors' own research.
RESULTS
Autoimmune hemolytic anemia is a heterogeneous group of diseases. The warm-antibody type is frequently associated with chronic lymphocytic leukemia or autoimmune systemic disease. Corticosteroids are still the first-line therapy and splenectomy is second-line, while rituximab has become an option in refractory disease. Blood transfusions require specific precautions such as restrictive use, extensive phenotyping of antigens and testing for alloantibodies and biological compatibility. Primary chronic cold agglutinin disease, a subgroup of cold-antibody autoimmune hemolytic anemia, is a clonal lymphoproliferative bone marrow disease. This subgroup is usually refractory to corticosteroids and patients with few clinical symptoms and slight anemia may not require drug therapy. However, in a majority, effective drugs are needed. The best documented therapy is infusions with rituximab, but new options are being tested. Immune hemolytic anemia associated with drugs occurs less frequently now than before.
INTERPRETATION
Subgroups and associated or underlying disease should be identified in patients with autoimmune hemolytic anemia. The therapeutic implications of subclassification are important. Patients who have cold agglutinin disease and need therapy should be included in prospective trials.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Autoantibodies; Blood Transfusion; Child; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Prednisolone; Rituximab
PubMed: 19898570
DOI: 10.4045/tidsskr.09.0161 -
Saudi Medical Journal Apr 2019Ovarian teratoma is a rare cause of autoimmune hemolytic anemia (AIHA) by warm antibodies, resistant to corticosteroid therapy. This also implies that ovarian teratoma...
Ovarian teratoma is a rare cause of autoimmune hemolytic anemia (AIHA) by warm antibodies, resistant to corticosteroid therapy. This also implies that ovarian teratoma should be included in the differential diagnosis of AIHA, whether or not associated with pregnancy. We present a case of a primigravida who presented with ovarian dermoid cysts and AIHA at 24 weeks of gestation. The patient received corticosteroids, intravenous immunoglobulin, rituximab, and multiple blood transfusions, with no significant improvement. Hemoglobin levels returned to normal only after laparoscopic ovarian cystectomy. Autoimmune hemolytic anemia caused by dermoid cyst is a rare condition especially in pregnancy. However, in light of similar case reports and review of the existing literature, we conclude that surgical excision should be considered when AIHA and ovarian teratoma coexist.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Female; Humans; Ovarian Neoplasms; Ovariectomy; Ovary; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Teratoma; Treatment Outcome; Young Adult
PubMed: 30957135
DOI: 10.15537/smj.2019.4.24107 -
Journal of General Internal Medicine Mar 2020
Topics: Anemia, Hemolytic, Autoimmune; Babesiosis; Humans
PubMed: 31713032
DOI: 10.1007/s11606-019-05506-5 -
The American Journal of Case Reports Feb 2022BACKGROUND Autoimmune hemolytic anemia and immune thrombocytopenia are rare complications of brucellosis; only a few cases have been reported in the literature. While... (Review)
Review
BACKGROUND Autoimmune hemolytic anemia and immune thrombocytopenia are rare complications of brucellosis; only a few cases have been reported in the literature. While pancytopenia is common and was reported in Saudi Arabia, the description of autoimmune hemolytic anemia or immune thrombocytopenia has not yet been reported in the kingdom. Hematological complication usually requires supportive treatment, and it is expected to improve with the initiation of antimicrobial therapy for brucellosis. There are few reports on the treatment of patients that fail to improve with conventional therapy. CASE REPORT A 46-year-old previously healthy Saudi woman was admitted to our hospital after multiple visits to the emergency department with chief concerns of fever and fatigability for 30 days. The examination was remarkable only for fever of 38.4°C and tender hepatomegaly. Laboratory tests upon admission were significant of pancytopenia, with a white blood count of 3×10⁹/L, hemoglobin of 8.1 g/dL, platelet of 13×10⁹/L, moderate hyponatremia, hypokalemia, and metabolic acidosis. Tuberculosis was ruled out and pan-sensitive brucellosis was diagnosed. She was started on standard antimicrobial therapy without significant improvement. Further testing revealed Coomb's-positive hemolytic anemia and possible immune-mediated severe thrombocytopenia. She was treated with glucocorticoids and intravenous immunoglobulin, with dramatic response. CONCLUSIONS Autoimmune-mediated destruction of blood lines in brucellosis is rare. It should be sought as a potential diagnosis in case of persistent anemia and/or thrombocytopenia that is severe or fails to improve with proper antimicrobial coverage. Early involvement of hematologists and initiation of glucocorticoid with or without intravenous immunoglobulin is crucial.
Topics: Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Brucellosis; Female; Humans; Middle Aged; Saudi Arabia; Thrombocytopenia
PubMed: 35210389
DOI: 10.12659/AJCR.935187 -
International Journal of Molecular... Apr 2024Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown... (Review)
Review
Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath-Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.
Topics: Anemia, Hemolytic, Autoimmune; Humans; Autoantibodies; Disease Management; Coombs Test
PubMed: 38673882
DOI: 10.3390/ijms25084296