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 Table of Contents  
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 288-291

Autoimmune hemolytic anemia complicating a non-severe SARS-COV2 pneumonia

1 Department of Anesthesia and Intensive Care, University Hospital in Tangier; Faculty of Medicine and Pharmacy of Tangier, Abdelmalek Essaadi University, Tangier, Morocco
2 Medical Biology Unit, Provincial Hospital Hassan 1er, Tiznit, Morocco

Date of Submission28-Aug-2022
Date of Acceptance23-Sep-2022
Date of Web Publication23-Dec-2022

Correspondence Address:
Dr. Youssef Dwassy
Medical Biology Unit, Provincial Hospital Hassan 1er, Tiznit
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amhs.amhs_199_22

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COVID-19 has been associated with a spectrum of hematological complications secondary to excessive activation of the immune system. In this article, we report the case of a 64-year-old patient who developed delayed autoimmune hemolytic anemia following a mild severe acute respiratory syndrome-coronavirus-2 infection. We will discuss its pathophysiological, clinical, and biological aspects as well as the clinical management of this complication.

Keywords: Autoimmune hemolytic anemia, autoimmunity, COVID-19

How to cite this article:
Motiaa Y, Dwassy Y. Autoimmune hemolytic anemia complicating a non-severe SARS-COV2 pneumonia. Arch Med Health Sci 2022;10:288-91

How to cite this URL:
Motiaa Y, Dwassy Y. Autoimmune hemolytic anemia complicating a non-severe SARS-COV2 pneumonia. Arch Med Health Sci [serial online] 2022 [cited 2023 Jan 31];10:288-91. Available from: https://www.amhsjournal.org/text.asp?2022/10/2/288/364958

  Introduction Top

COVID-19 infection appears to cause a strong activation of the immune system with cytokine storm and a severe pro-inflammatory state.[1],[2] This can result in a wide range of autoimmune disorders such as vasculitis, Guillain–Barré syndrome, antiphospholipid syndrome, and Evans syndrome.[1],[3],[4]

Various complement-mediated hemolytic anemias were reported.[5] These include paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA), particularly cold agglutinin disease (CAD), and hemolytic uremic syndrome (HUS).[5] COVID-19 vaccine was also reported to be a trigger event to complement activation.

In this article, we report a case of mild COVID-19 infection complicated with a delayed AIHA.

  Case Report Top

A 64-year-old woman with a history of diabetes mellitus on metformin, and a body mass index of 29 kg/m2, presented to the emergency department with a 5-day history of dry cough, fatigue, anosmia, and chest pain. She had a respiratory rate of 18 breaths/min, oxygen saturation was 95% on room air, she was apyrexial, her capillary blood glucose was 1.2 g/dL, and the electrocardiogram was normal. The reverse transcription-polymerase chain reaction was positive for severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) on nasopharyngeal swabs.

The patient did not have any complications related to her diabetes; she also did not have any history of asthma, hypertension, or a family history of autoimmune disease.

The patient was prescribed the treatment recommended by the Moroccan Committee of Experts at the Ministry of Health, which includes chloroquine 500 mg twice daily and azithromycin 500 mg the 1 day then 250 mg four times daily.

Laboratory studies were requested given her age and medical history. White blood cell count (WBC) was 5340/μL, lymphocyte count was 2403/μL, neutrophil count was 2189/μL, platelet count was 198,000/μL, hemoglobin was 13.4 g/dL, hematocrit was 40.2%, mean corpuscular volume (MCV) was 97.4 fI, mean corpuscular hemoglobin (MCH) was 32.2 pg, C-reactive protein (CRP) was 5.6 mg/L, and renal function was normal.

HbA1c was 6.5%, D-dimers were 4385 ng/l, and fibrinogen was 3.6 g/l. On contrast-enhanced computed tomography, there was no evidence of pulmonary embolism and lung parenchyma appeared normal. High-dose prophylactic anticoagulation was started with enoxaparin 1 mg/kg once daily for 4 weeks. The patient made a good recovery and was discharged from medical care.

Forty-five days later, the patient was readmitted for fatigue, dizziness, and chest pain. On examination, she had conjunctival jaundice, her heart rate was 95 bpm, and her blood pressure was 115/70 mmHg. She had no respiratory symptoms and denied any gastrointestinal or gynecological bleeding. She was apyrexial and there was no splenomegaly on examination.

Laboratory testing revealed a hemoglobin of 8.3 g/dL, hematocrit was 26%, WBC was 7560 g/μL (57.8% neutrophils), lymphocyte count was 2457/mm3, MCV was 103.6 fl, MCH was 35.5 pg, and platelet count was normal.

CRP was 5.6 mg/L, procalcitonin was 0.11 ng/ml, and renal function was normal with an estimated glomerular filtration rate of 94.5 mL/min/1.73 m2. D-dimers were 150 ng/l.

Additional tests showed high reticulocyte was 16.10% (352,950/mm3), haptoglobin was undetectable, lactate dehydrogenase (LDH) was 378 IU/L (normal is 250 IU/L), and direct Coombs test (direct antiglobulin test) was positive. Total bilirubin was 12 mg/dl (direct bilirubin 6 mg/dl) and ferritin was 905.5 ng/ml. Immune-mediated hemolysis was suspected based on these results and negative irregular antibody testing.

The peripheral blood smear revealed a spontaneous agglutination of red blood cells (RBCs), marked polychromasia, and a large number of nucleated RBCs with anisocytosis and macrocytosis [Figure 1].
Figure 1: Peripheral smear is done at anemic's diagnosis: (A) agglutination of RBCs, (B) polychromasia, and (C) a large number of nucleated RBCs with anisocytosis and macrocytosis. RBCs: Red blood cells

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Other laboratory tests were performed. Serum folate was 8.3 nmol/L, Vitamin B12 was 468 ng/L, and serologies for hepatitis B and C viruses and human immunodeficiency virus (HIV) were all negative. Other infections were ruled out such as Mycoplasma pneumonia, Legionella pneumophila, Chlamydia pneumonia, adenovirus, and influenza virus. Anti-double-stranded DNA antibodies and rheumatoid factor (10 IU/l) were negatives. However, extractable nuclear antigen (ENA) antibodies were detected and anticentromere B antibodies were positive.

The patient was treated for AIHA with prednisolone 1 mg/kg orally with good progress. A full blood count, repeated 4 weeks later, showed a marked improvement. [Table 1] and [Table 2] summarize the patient's blood results.
Table 1: Follow-up of blood count cells

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Table 2: Results of biological investigations

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  Discussion Top

Many studies have shown a relationship between COVID-19 infection and a variety of hematological autoimmune disorders, such as AIHA and regardless of the severity of lung damage. Increasing evidence suggests that SARS-COV-2 infection involves the activation of complement pathways implicated in the severity of the illness and the pathogenesis of various complications such as respiratory failure, disseminated intravascular coagulopathy, and hyperinflammatory state. Furthermore, the level of complement inflammatory mediators correlates with the severity of COVID-19 infection in terms of the need for oxygen therapy, ICU admission, and mortality.[6],[7] Eriksson et al. authors concluded that mannose-binding lectin, a marker of complement activation, correlated strongly with D-dimer levels, which are associated with mortality, regardless of the degree of systemic inflammation and organ dysfunction.[7] In other words, complement activation was present even in the absence of severe COVID-19 disease.

Several autoimmune disorders have been reported in patients with SARS-COV-2 infection

  • Hematologic autoimmune disorders: AIHA,[1],[8],[9],[10],[11],[12],[13],[14] idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, antiphospholipid syndrome, autoimmune neutropenia, Evans syndrome, PNH, CAD, and HUS[1],[4],[5],[14],[15],[16]
  • Other autoimmune disorders: GuillainBarré syndrome, Miller Fisher syndrome, and Kawasaki-like disease.[2]

AIHA is usually diagnosed close to or during the SARS-COV-2 Infection,[12] with various severity forms. In their study, Taherifard et al. found that the mean time to the onset of hematological autoimmune disorders (AIHA and others) from SARS-COV-2 infection was 11.8 ± 7.1 days.[1]

The origin of this autoimmune disorder is a hyperinflammatory state that initiates an innate immune response to SARS-COV-2 infection mediated particularly by complement.[6] The exact pathophysiology is still unknown, however.

In our patient, AIHA was suspected based on the presence of clinical characteristics of unexplained anemia, and laboratory evidence of hemolysis (elevated direct bilirubin, LDH, ferritin, reticulocyte with macrocytosis, and low haptoglobin level).

A positive direct antiglobulin test (Coombs test) was indicative of immune-mediated hemolysis. Anti-ENA antibodies were positive for centromere B. Other causes of hemolytic anemia such as viral infections (HBV, HCV, and HIV), bacterial infections (abdomen and chest), and drug overdose were excluded.

In our case, the time between the COVID-19 infection and the onset of hemolytic anemia symptoms was 45 days which is significantly longer than the average time reported in the literature.[1] Furthermore, our patient only suffered mild viral symptoms that did not require admission to the hospital.

Treatment of AIHA includes corticosteroids as the first line and rituximab for corticosteroid failure.[11] In other case reports, AIHA associated with COVID-19 infection was treated regardless of its cause. Intravenous immunoglobins were also used to treat AIHA associated with thrombocytopenia in Evans syndrome.[15] Our patient was treated with corticosteroids with a favorable outcome. The patient's follow-up showed a marked clinical and laboratory test improvement.

  Conclusion Top

AIHA is a recognized complication of COVID-19 infection, and it does not always correlate with the severity of the illness. This hematological complication can occur during the initial episode of SARS-COV-2 infection or few days following the diagnosis. Our case indicates that this complication can be delayed up to 6 weeks following the initial infection. The treatment of AIHA complicating COVID-19 infection is no different from that of AIHA of other causes. More studies are needed to determine the follow-up time required to monitor patients at risk of developing hematological and other autoimmune complications of COVID-19.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Taherifard E, Taherifard E, Movahed H, Mousavi MR. Hematologic autoimmune disorders in the course of COVID-19: A systematic review of reported cases. Hematology 2021;26:225-39.  Back to cited text no. 1
Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D, et al. Covid-19 and autoimmunity. Autoimmun Rev 2020;19:102597.  Back to cited text no. 2
Al-Saadi EA, Abdulnabi MA. Hematological changes associated with COVID-19 infection. J Clin Lab Anal 2022;36:e24064.  Back to cited text no. 3
Li M, Nguyen CB, Yeung Z, Sanchez K, Rosen D, Bushan S. Evans syndrome in a patient with COVID-19. Br J Haematol 2020;190:e59-61.  Back to cited text no. 4
Fattizzo B, Pasquale R, Bellani V, Barcellini W, Kulasekararaj AG. Complement mediated hemolytic anemias in the COVID-19 Era: Case series and review of the literature. Front Immunol 2021;12:791429.  Back to cited text no. 5
Defendi F, Leroy C, Epaulard O, Clavarino G, Vilotitch A, Le Marechal M, et al. Complement alternative and mannose-binding lectin pathway activation is associated with COVID-19 mortality. Front Immunol 2021;12:742446.  Back to cited text no. 6
Eriksson O, Hultström M, Persson B, Lipcsey M, Ekdahl KN, Nilsson B, et al. Mannose-binding lectin is associated with thrombosis and coagulopathy in critically Ill COVID-19 patients. Thromb Haemost 2020;120:1720-4.  Back to cited text no. 7
Capes A, Bailly S, Hantson P, Gerard L, Laterre PF. COVID-19 infection associated with autoimmune hemolytic anemia. Ann Hematol 2020;99:1679-80.  Back to cited text no. 8
Pelle MC, Tassone B, Ricchio M, Mazzitelli M, Davoli C, Procopio G, et al. 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. J Med Case Rep 2020;14:246.  Back to cited text no. 9
Jawed M, Hart E, Saeed M. Haemolytic anaemia: A consequence of COVID-19. BMJ Case Rep 2020;13:e238118.  Back to cited text no. 10
Lazarian G, Quinquenel A, Bellal M, Siavellis J, Jacquy C, Re D, et al. Autoimmune haemolytic anaemia associated with COVID-19 infection. Br J Haematol 2020;190:29-31.  Back to cited text no. 11
Lopez C, Kim J, Pandey A, Huang T, DeLoughery TG. Simultaneous onset of COVID-19 and autoimmune haemolytic anaemia. Br J Haematol 2020;190:31-2.  Back to cited text no. 12
Jacobs J, Eichbaum Q. COVID-19 associated with severe autoimmune hemolytic anemia. Transfusion 2021;61:635-40.  Back to cited text no. 13
Huscenot T, Galland J, Ouvrat M, Rossignol M, Mouly S, Sène D, et al. SARS-CoV-2-associated cold agglutinin disease: A report of two cases. Ann Hematol 2020;99:1943-4.  Back to cited text no. 14
Demir NA, Basturk A, Ural O, Sumer S, Erdogdu B, Kiratli HE, et al. A case of evans syndrome secondary to COVID-19. Blood Transfus 2021;19:85-8.  Back to cited text no. 15
Georgy JT, Jayakaran JA, Jacob AS, Gunasekaran K, Korula PJ, Devasia AJ, et al. Evans syndrome and immune thrombocytopenia in two patients with COVID-19. J Med Virol 2021;93:2642-4.  Back to cited text no. 16


  [Figure 1]

  [Table 1], [Table 2]


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