The impact of using primaquine without prior G6PD testing: a case series describing the obstacles to the medical management of haemolysis

Abstract

Radical cure of malaria in glucose-6-phosphate Plasmodium vivax dehydrogenase (G6PD) deficient individuals employs weekly primaquine dosing. This is the only recommended regimen for this patient sub-group. If national malaria programs mandate daily primaquine dosing (the recommended regimen for G6PD normal individuals), then G6PD testing before prescription is necessary to avoid iatrogenic haemolysis in G6PD deficient individuals. In this case series, two infected patients with P. vivax unknown G6PD status from two different countries were prescribed primaquine as per national malaria program guidelines. During treatment both patients presented to the clinic with symptoms of anaemia after taking primaquine incorrectly. The clinical management of the iatrogenic severe haemolysis that occurred in these patients demonstrates the various adverse effects primaquine can cause, that other common medical treatments also have haemolytic potential, and how the diagnosis of G6PD deficiency can be elusive during acute haemolysis. Health care providers should provide careful instructions about primaquine dosing, be watchful for haemolysis, and have a high index of suspicion for G6PD deficiency in the presence of haemolysis if the G6PD status is previously unknown.

Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening

“…In two of the cases reported here (Cases 1 and 4), the haemolytic crisis did not halt with the cessation of dosing but continued for the 2–3 days leading up to hospitalization and transfusion. This has been observed by others [ 29 , 30 , 31 ]. In the instance of Case 5, the crisis progressed so rapidly that transfusion occurred on the same day of PQ cessation ( Figure 2 ).…”

Plasmodium knowlesi: the game changer for malaria eradication

“…P. knowlesi patients were given treatment with primaquine, which is a radical cure to clear hypnozoites (dormant liver stage) of P. vivax . This resulted in unnecessary increase of treatment cost and potential health risks to individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency if G6PD testing was not performed prior to the treatment, which could lead to severe acute haemolytic anaemia [ 94 ]. Therefore, differential diagnosis is essential in distinguishing knowlesi malaria from malaria caused by other species of Plasmodium , by taking into considerations the parasite’s morphology and patient’s travel history prior to the infection.…”

Haematological profile of malaria patients with G6PD and PKLR variants (erythrocytic enzymopathies): a cross-sectional study in Thailand

“…In erythrocytes with the G6PD Mahidol 487A mutation, oxidation of membrane proteins causes the cells to rigid, nondeformable, and finally haemolysis. A recent report has indicated that patients with G6PD Mahidol G487A presented symptoms of acute haemolytic anaemia after taking an incorrect dose of PQ [ 44 ]. Although this study had no haematological data to support the clinical impact of anti-malarial drugs on patients with G6PD Mahidol G487A and other mutations, these findings provided evidence for malaria infection-induced haemolysis in patients with G6PD deficiency.…”