Hydroxychloroquine

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 57-year-old man developed acute haemolytic anaemia direct Coombs negative during off-label treatment with hydroxychloroquine for COVID-19.

The man presented to an emergency department with a 4-day history of nausea, fatigue, anorexia and chills. He had underlying hypertension, non-insulin dependent diabetes, gastro-oesophageal reflux disease, hypercholesterolaemia and glaucoma. At admission, he had mild anaemia [aetiology not stated], without known haematological history. He required oxygen supplementation. Laboratory tests suggested diabetic ketoacidosis (DKA) secondary to a community acquired pneumonia (differential diagnosis). He responded well to the DKA protocol comprising 6L of fluid in first 24 hours while receiving a fixed insulin infusion. Initially, he received piperacillin/tazobactam for pneumonia. On the hospitalisation day 2, the result of his COVID-19 swab was positive. Therefore, he started receiving off-label treatment with hydroxychloroquine [route and dosage not stated], azithromycin and ceftriaxone. Thereafter, daily drop in haemoglobin levels was observed on laboratory tests. Haemoglobin levels reached nadir point of 6.6 g/dL on day 8.

Therefore, the man received two units of red cell concentrates. At that time he had mildly elevated bilirubin, LDH of 1636 U/L and a ferritin of 9379 µg/L. A haemolytic screen results obtained on hospitalisation day 7 showed reticulocytes of 68.2x 10⁹/L, negative direct coombe's test and haptoglobin levels of <0.10 g/L. A review of his blood film obtained at the time of hospitalisation revealed irregularly contracted cells and hemi-ghost cells. Therefore, a possible underlying glucose 6-phosphate dehydrogenase deficiency (G6PD) was considered. A blood sample analysis of his G6PD levels confirmed G6PD. Repeated testing showed a level of 2.8 IU/gHb indicating deficiency of G6PD. He was considered to have acute haemolytic anaemia direct Coombs negative triggered by hydroxychloroquine in the background of G6PD.