Severe haemolytic anaemia in COVID 19- A rare manifestation.

Sir,

The novel severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) affects various organ systems including the cardiovascular, gastrointestinal and neurological systems.[1]

Autoimmune haemolytic anaemia (AIHA) is a rare immune disorder in which antibodies are produced against body's own red cells. Association of AIHA with coronavirus disease (COVID)-19 has been rarely reported.

A 42-year-old female patient presented with fatigue, headache and bleeding per rectum since 3 days; she had no history of fever or upper respiratory tract infection and normal oxygen saturation. On clinical examination, she was pale and icteric and had healing fissure in ano with no active bleeding. On day two, patient complained of severe breathlessness, peripheral oxygen saturation (SpO2) 85% with hypotension and patient was shifted to intensive care unit (ICU) for further management. The oxygen was administered with facemask at 10 l/min and norepinephrine infusion started at 0.5-1 μg/kg/min. The chest radiogram and echocardiogram did not show any abnormality. Computed tomography (CT) chest [Figure 1] revealed a CORADS score of 6 and the reverse transcription polymerase chain reaction (RT PCR) assay detected the presence of SARS-CoV-2 on day three of admission. On investigation, her haemoglobin level was 3 g% and peripheral blood smear showed predominantly macrocytic hypochromic cells with a few microcytes, anisocytosis, reticulocytosis and neutrophilia. Malignant diseases, such as leukaemia and lymphoma, were ruled out as the peripheral smear did not show abnormal cells of haematological origin. Autoimmune diseases, such as systemic lupus erythematosus, were also ruled out. There was no history of medication intake (non-steroidal anti-inflammatory drugs or cephalosporins) or blood transfusion in the past known to cause drug-induced AIHA. Arterial blood gas analysis was not required as hypoxaemia was anticipated due to severe anaemia. Considering the severe anaemia and increasing breathlessness, a decision to transfuse packed red cells was taken. Her cell grouping was AB Rh D positive, whereas her serum grouping was of O group with autocontrol positive drawing attention to the pathology (O Rh D positive per previous records). Cross-matching with both AB Rh D positive and O Rh D positive packed cells were incompatible, concomitantly direct antiglobulin and indirect antiglobulin tests were also positive. Her blood also showed autoagglutination (titres <1:64), which was reactive at 37°C and with antihuman globulin phase; hence a provisional diagnosis of mixed AIHA was established secondary to infection. Intravenous methylprednisolone 30 mg/kg for 3 days, 20 mg/kg for next 3 days, and 5 mg/kg for next 4 days was started till irradiated or compatible blood was arranged as per British Society of Haematology guidelines.[2] Oral prednisolone 1 mg/kg was continued for 2 weeks and gradually tapered. The patient showed marked improvement in the next 24 h [Table 1], could be managed without any blood transfusion and ionotropic supports could be discontinued. A diagnosis of secondary AIHA triggered by COVID-19 was ascertained by exclusion as the patient had no other suggestive history.

Figure 1

(a) Opacification in the right peripheral lung fields and (b) Opacifications in the bilateral posterior aspect of the lung fields due to COVID-19

Table 1

Serial measurement of complete blood picture taken before and after initiation of methylprednisolone therapy for a period of 12 days‡

Investigation	Day 1	Day2	Day3	Day 6	Day9	Day 12
Haemoglobin (g/dl)	3.0	2.9	2.1	4.7	6.6	8.6
Total leucocyte count (/mm3)	12900	13800	14200	12100	7800	8000
Mean corpuscular volume (fL)	148.7	146.7	147.8	146.2	123.1	117.4
Platelet count(lac/mm3)	1.9	1.6	1.6	1.2	1.2	1.6

‡No blood or blood products were transfused during this period

Autoimmune haemolytic anaemia in COVID-19 has been reported in nine cases among which five had malignancy and one had congenital thrombocytopenia.[3] ANK-1 shares an immunogenic antigenic epitope (amino acids LLLQY), present on red cells with 100% identity with the SARS-CoV-2 surface glycoprotein named spike protein, which creates a potential immunological cross-reactivity between ANK-1 and spike protein, contributing to AIHA in patients with COVID-19.[4] Corticosteroids represent the first line of treatment for warm antibody type AIHA and reduce haemolysis and cytokine storm.[5] This case presents a unique scenario of acute anaemia with COVID-19, which was managed conservatively with steroids and no immunosuppressants or plasma therapy or blood transfusion was required. We wish to highlight that the novel SARS-CoV-2 can present with covert symptoms affecting the haematological system.

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Conflicts of interest

There are no conflicts of interest.