Mixed Warm and Cold Autoimmune Hemolytic Anemia With Concomitant Immune Thrombocytopenia Following Recent SARS-CoV-2 Infection and Ongoing Rhinovirus Infection.

Mixed-type autoimmune hemolytic anemia (AIHA) is a term used to describe hemolysis occurring in the context of both warm and cold reactive autoantibodies to red blood cells. Immune thrombocytopenia (ITP) is an acquired form of thrombocytopenia potentially complicated by hemorrhage due to autoantibodies reactive with platelets and megakaryocytes. Diagnosis of ITP requires exclusion of other known causes of thrombocytopenia. AIHA and ITP may be primary disorders or associated with lymphoproliferative, autoimmune, or viral infections. Here, we report a rare case of simultaneous mixed-type autoimmune hemolytic anemia with immune thrombocytopenia following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection treated with Paxlovid followed by Rhinovirus infection.

COVID-19 Vaccines and Autoimmune Hematologic Disorders.

Worldwide vaccination against SARS-CoV-2 has allowed the detection of hematologic autoimmune complications. Adverse events (AEs) of this nature had been previously observed in association with other vaccines. The underlying mechanisms are not totally understood, although mimicry between viral and self-antigens plays a relevant role. It is important to remark that, although the incidence of these AEs is extremely low, their evolution may lead to life-threatening scenarios if treatment is not readily initiated. Hematologic autoimmune AEs have been associated with both mRNA and adenoviral vector-based SARS-CoV-2 vaccines. The main reported entities are secondary immune thrombocytopenia, immune thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and a newly described disorder, so-called vaccine-induced immune thrombotic thrombocytopenia (VITT). The hallmark of VITT is the presence of anti-platelet factor 4 autoantibodies able to trigger platelet activation. Patients with VITT present with thrombocytopenia and may develop thrombosis in unusual locations such as cerebral beds. The management of hematologic autoimmune AEs does not differ significantly from that of these disorders in a non-vaccine context, thus addressing autoantibody production and bleeding/thromboembolic risk. This means that clinicians must be aware of their distinctive signs in order to diagnose them and initiate treatment as soon as possible.

A Rare Case of COVID-19 Associated With Autoimmune Hemolytic Anemia, Thrombocytopenia and Acute Kidney Injury.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has numerous effects on different systemic organs other than the lungs. In this case report, we look at the presentation of a young female who was diagnosed with autoimmune hemolytic anemia (AIHA), kidney injury and thrombocytopenia during coronavirus disease 2019 (COVID-19) infection. She recovered well without the need for steroids. As demonstrated by this case, COVID-19 infection can be associated with the development of AIHA. The purpose of this report is to indicate that COVID-19 can present unusually with different clinical manifestations enough to require hospitalization.

Cytomegalovirus-Induced Coombs-Positive Hemolysis or Drug-Induced Hemolysis in an Immunocompetent Young Adult.

Coombs-positive hemolytic anemia induced by cytomegalovirus (CMV) infection is a rare phenomenon, often not life-threatening in immunocompetent young adults. To date, the pathogenesis of CMV-induced severe hemolysis is still unknown. Here, we discuss a case of a 22-year-old male without significant past medical history who presented with severe hemolytic anemia that required four units of packed red blood cells. Urinalysis showed microscopic hematuria but urine culture and drug screen reported normal findings. Hemoccult result at the bedside was negative. Abdominal ultrasound and computed tomography (CT) imaging all resulted in normal findings except for splenomegaly measured 18 cm. Hematology was consulted which showed a positive direct Coombs antibody test with 3+ IgG and 3+ complement. Peripheral blood smear showed no evidence of schistocytes or occasional teardrop cells but showed toxic granulations and neutrophils indicating an underlying infection. The patient had a bone marrow biopsy which showed erythroid hyperplasia with a slight increase in sideroblast cells; but revealed no evidence of lymphoma, leukemia, or dysplasia. Infectious workup reported negative findings for HIV and hepatitis panel. However, Epstein-Barr virus (EBV) IgM antibodies to viral capsid antigen (VCA) was reported with a value of greater than 160 U/mL. Polymerase chain reaction (PCR) testing for cytomegalovirus (CMV) DNA detected high titers with 481269 IU/mL. The patient initially received intravenous immunoglobulin (IVIG) therapy for five days, antiviral medication for seven days, and high dose therapeutic corticosteroids resulting in stabilization of his blood hemoglobin (Hb) level. Infections commonly underlie secondary autoimmune hemolytic anemia (AIHA), or it can also be a result of therapy that further exacerbates the course of AIHA. Possible CMV manifestations inducing severe hemolytic anemia in immunocompetent individuals have received inadequate attention. CMV serology studies are not collected regularly in patients with hemolysis, so the incidence of this disorder might be under-reported. Thus, clinicians should take initiative to consider an underlying infection in the differential diagnosis of hemolytic anemia before opting for invasive procedures such as bone marrow biopsy. Randomized control trials are needed for a conclusive treatment specific to hemolytic anemia induced by CMV.

Hyperhemolysis in a patient with sickle cell disease and recent SARS-CoV-2 infection, with complex auto- and alloantibody work-up, successfully treated with tocilizumab.

BACKGROUND: Hyperhemolysis syndrome (HHS) is a severe delayed hemolytic transfusion reaction seen in sickle cell disease (SCD) patients, characterized by destruction of donor and recipient RBCs. It results in a drop in hemoglobin to below pretransfusion levels and frequently reticulocytopenia. CASE REPORT: We report a case of a man in his thirties with SCD with a recent hospitalization 2 weeks prior for COVID-19. His red cell antibody history included anti-Fy(a) and warm autoantibody. At that time, he was given 2 units of RBC and discharged with a hemoglobin of 10.2 g/dl. He returned to the hospital approximately 1.5 weeks later with hemoglobin 6.0 g/dl and symptoms concerning for acute chest syndrome. Pretransfusion testing now showed 4+ pan-agglutinin in both gel-based and tube-based testing. Alloadsorption identified an anti-N and a strong cold agglutinin. Three least incompatible units were transfused to this patient over several days, with evidence of hemolysis. Further reference lab work revealed anti-Fya , anti-Fyb , anti-Lea , anti-Leb , and an anti-KN system antibody. The patient's hemoglobin nadired at 4.4 g/dl. The patient was treated with a single dose of tocilizumab, his hemoglobin stabilized, and he was discharged. DISCUSSION: We present a case of HHS proximate to recent SARS-CoV-2 infection with multiple allo and autoantibodies identified. Information on the relationship between SARS-CoV-2 infection and HHS is limited; however, it is possible that inflammation related to COVID-19 could predispose to HHS. Tocilizumab is an approved treatment for COVID-19. Additionally, tocilizumab appears to be a promising treatment option for patients with HHS.

Autoimmune Hemolytic Anemia Exacerbation Associated With COVID-19 Infection and Markedly Elevated Inflammatory Markers.

The association between previously diagnosed autoimmune hemolytic anemia and exacerbations due to coronavirus disease 2019 (COVID-19) infection is a rare phenomenon that is not well understood. In this case, we present a 68-year-old female with a past medical history significant for systemic lupus erythematosus (SLE), splenectomy, and autoimmune hemolytic anemia (AIHA) since childhood that had been very well controlled with only one previous exacerbation. This patient's chief complaint and clinical symptoms at admission were related to hemolytic anemia and not active COVID-19 infection. This case report reveals a possible association between the hyperinflammatory syndrome caused by COVID-19 and the exacerbation of previously well-controlled autoimmune diseases.

Hyperhemolysis in the Setting of Mixed-Autoimmune Hemolytic Anemia: A Rare Complication of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human pathogen known for its predilection on the respiratory system. Herein, we present a unique case in which a patient developed hyperhemolysis in the setting of mixed autoimmune hemolytic anemia (AIHA) secondary to SARS-CoV-2. A 33-years-old male with a past medical history of resolved immune thrombocytopenic purpura (ITP) presented to the hospital with symptoms of jaundice after being infected with SARS-CoV-2. On admission, his Hgb was 12.5 g/dL. Lab results showed indirect bilirubin of 13 mg/dL, LDH at 759 U/L, haptoglobin <10, and the percent reticulocyte count was 2.33%. A direct antiglobulin test (DAT) was also positive for C3, IgG, anti-E, in addition to both warm and cold autoantibodies. PCR was positive for COVID-19. Within two days of admission, his Hgb dropped to 5.9 g/dL. A total of seven units of packed red blood cell (pRBC) was required to achieve a Hgb of 6 g/dL in 48 hours. Patients with preexisting hematological abnormalities have a propensity to develop AIHA in the setting of the virus. The majority of the cases described in the literature were associated with warm AIHA. Our patient tested positive for both warm and cold antibodies, which may partially explain the mechanism behind hyperhemolysis in our patient.

Exacerbation of Secondary Cold Agglutinin Syndrome in the Setting of SARS-CoV-2.

In this report, we present a case of exacerbation of cold agglutinin syndrome (CAS) potentially due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. An 83-year-old female with a history of cold agglutinin hemolytic anemia presented with shortness of breath, productive cough, worsening orthopnea, darkening fingers and urine, and jaundice. Laboratory investigations found elevated white blood cells (WBC) and total bilirubin, severely low hemoglobin, and positive direct Coombs test. Moreover, SARS-CoV-2 RNA was also found to be positive in a sample from the nasal swab by reverse transcription-polymerase chain reaction (RT-PCR), indicating exacerbation of CAS secondary to viral coronavirus 2019 (COVID-19) infection. A treatment regime for SARS-CoV-2 consisting of five days of remdesivir and seven days of dexamethasone 6 mg IV was initiated, resulting in significant improvement in the patient's condition.

[Development of autoimmune hemolytic anemia after BNT162b2 mRNA COVID-19 vaccination].

A 75-year-old woman with a history of postoperative chemotherapy for lung adenocarcinoma and a history of Helicobacter pylori eradication for idiopathic thrombocytopenic purpura (ITP) was admitted to the department of hematology and oncology for the treatment of anemia 2 weeks after BNT162b2 mRNA COVID-19 vaccination. Her blood examination revealed direct and indirect Coombs test-positive hemolytic anemia and elevation of serum LDH and indirect bilirubin levels. No obvious trigger other than BNT162b2 mRNA COVID-19 vaccination was found. She was diagnosed with autoimmune hemolytic anemia (AIHA), and oral prednisolone therapy was administered. The anemia improved soon after the administration of prednisolone. Although vaccination is considered to be very important for suppressing the spread of COVID-19, there have been reports of increasing risk of ITP development and deterioration caused by BNT162b2 mRNA COVID-19 vaccination. Because the number of vaccinated people is increasing rapidly, hematologists must be vigilant to the development of AIHA after BNT162b2 mRNA COVID-19 vaccination although case reports of this phenomenon have been very rare thus far.

New-onset Evans syndrome associated with systemic lupus erythematosus after BNT162b2 mRNA COVID-19 vaccination.

Evans syndrome presents as concurrent autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Systemic lupus erythematosus (SLE) is the most frequent autoimmune disorder associated with Evans syndrome. We herein report a case of new-onset Evans syndrome associated with SLE after BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccination in a 53-year-old woman. Blood examination at diagnosis showed hemolytic anemia with a positive Coombs test and thrombocytopenia. Hypocomplementemia and the presence of lupus anticoagulant indicated a strong association with SLE. Prednisolone administration rapidly restored hemoglobin level and platelet count. This case suggests that mRNA COVID-19 vaccination may cause an autoimmune disorder. Physicians should be aware of this adverse reaction by mRNA COVID-19 vaccination and should consider the benefits and risks of vaccination for each recipient.

A Case of COVID-19-Associated Autoimmune Hemolytic Anemia With Hyperferritinemia in an Immunocompetent Host.

We report an interesting case of a middle-aged gentleman who presented with diabetic ketoacidosis (DKA) and tested polymerase chain reaction (PCR) positive for COVID-19 infection. His hospital stay was complicated by acute kidney injury, hematuria, and normocytic anemia. Initial chest x-ray demonstrated bibasilar opacities. D-dimer and C-reactive protein were elevated. During his hospital stay, his hemoglobin decreased from 13.4 g/dL to 9 g/dL, and further workup demonstrated ferritin of 49,081 ng/mL with lactate dehydrogenase of 1665 U/L. He was treated with prednisone and folic acid for autoimmune hemolytic anemia (AIHA). Ferritin was downtrended, and hemoglobin stabilized. As demonstrated by this case report and prior literature review, COVID-19 infection can be associated with AIHA.

Late-onset myocardial infarction and autoimmune haemolytic anaemia in a COVID-19 patient without respiratory symptoms, concomitant with a paradoxical increase in inflammatory markers: a case report.

BACKGROUND: In December 2019, a new coronavirus (named severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) spread from China, causing a pandemic in a very short time. The main clinical presentation of SARS-CoV-2 infection (COVID-19, coronavirus disease-2019) is pneumonia, but several cardiovascular complications may also occur (e.g., acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure and cardiogenic shock). Direct or indirect mechanisms induced by SARS-CoV-2 could be implicated in the pathogenesis of these events. CASE PRESENTATION: We report herein the third case of COVID-19 autoimmune haemolytic anaemia (AIHA) reported so far, which occurredwithout any other possible explanations in a Caucasian patient. The patient also suffered from ST-elevation myocardial injury. CONCLUSIONS: Both complications occurred quite late after COVID-19 diagnosis and were probably precipitated by systemic inflammation, as indicated by a significant delayed increase in inflammatory markers, including interleukin-6 (IL-6).

Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection.

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.