Background Autoimmune hemolytic anemia (AIHA) has many known disease associations, including autoimmune, lymphoproliferative, and certain infectious diseases, as well as various medications. Studies have found that severe cases of coronavirus disease 2019 (COVID‐19) may be associated with coagulopathies; however, the potential association with AIHA is not clear. Case Report A patient with no known risk factors or underlying predisposition for developing AIHA presented to a hospital with vague symptoms and profound anemia with a complicated blood bank evaluation. She was found to have COVID‐19 and AIHA, for which extensive laboratory testing was performed, including direct antiglobulin tests, elution studies, and cold agglutinin titers, to identify the causative autoantibody. She required multiple blood transfusions and therapeutic interventions before clinical stabilization. Discussion AIHA is a complex disease with a spectrum of presentations and clinical severity. Many diseases have been associated with a propensity for developing AIHA; however, there are few cases in the literature of patients with COVID‐19 and AIHA. Most of the reports involve patients with other underlying conditions that are known to be associated with the development of AIHA. The presentation, clinical findings, and therapeutic interventions in a patient with severe AIHA, without other underlying conditions, in the setting of COVID‐19 are discussed. Conclusions There are few reports of patients with concurrent COVID‐19 and AIHA, and the association is not clear. Although COVID‐19 has been shown to be associated with coagulopathies, more research is required to determine whether AIHA may also be a potential complication.

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.

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis, and is challenging to diagnose due to the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL (IQR 4.8-9.0 g/dL) and nadir of 5.5 g/dL (IQR 4.4-7.2 g/dL). The most common direct antiglobulin test (DAT) result was the presence of complement and absence of IgG bound to red blood cells, though other findings were observed in one-third of cases. Seventy-one patients had DL antibody class and specificity reported, of which 83.1% were IgG anti-P. The use of corticosteroids is common, though we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Amongst patients with follow-up, 99% (213/216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.

The COVID-19 pandemic has resulted in severe ongoing blood shortages across the US, despite employment of numerous blood-conservation measures. Massive transfusion protocols (MTP) are one resourceintensive practice that utilize significant amounts of blood products. Alterations to the composition of MTP parameters to conserve scarce biologic resources have hitherto not been examined during the pandemic. Methods: An anonymous 18-question survey was administered to 115 hospitals with valid email contact information. Survey questions addressed whether institutions have altered their MTPs due to the COVID-19 pandemic and blood shortages, and if so, what adjustments they have made. Additional details concerning potential differences in the number and cycles of MTPs and blood product wastage during the COVID-19 pandemic compared to the year prior were assessed. Results: 50 responses were received (43 % response rate). 10 % (5/50) of institutions altered their MTPs utilizing a variety of approaches in attempt to conserve blood during the COVID-19 pandemic. Four additional institutions intend to alter them if it becomes necessary. Following onset of the COVID-19 pandemic, 24 % of institutions (12/50) reported an increase in monthly MTP activations, while 16 % (8/50) reported decreased activations compared to prior to the pandemic. 22 % (11/50) of institutions experienced increased blood wastage, whereas 16 % (8/50) reported decreased waste compared to pre-pandemic. Discussion: The results of this survey highlight a variety of mechanisms by which institutions have attempted to conserve blood via altering MTPs. Whether an institution adjusted their MTP does not correlate with changes in blood product wastage compared to pre-pandemic.

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