Nature of Hemolytic Crises and the Fate of G6PD Deficient, Drug-Damaged Erythrocytes in Sardinians

Salvidio, E; Pannacciulli, I; Tizianello, A; Ajmar, Franco

doi:10.1056/nejm196706152762402

Cited by 40 publications

(26 citation statements)

References 17 publications

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“…18 Other similar study by Salvidio E et al reported severe hemolysis among G6PD deficient Sardinians with a single dose of 30 mg of primaquine. 19 Similarly, in Burma, Batu AT et al reported 34-48% haemolysis of labelled G6PD deficient erythrocytes that had been injected into the normal Burmese adult males who were given a course of 15 mg daily. The degree of heamolysis in these individuals was equal to that induced by 30 mg daily in the G6PD deficient Negroes reported by Alving et al 20 In Thailand, Charoenlarp et al found heamolysis of upto 18% of erythrocytes in individuals receiving single doses of 45 mg of primaquine but in both Malaysia and Thailand it has been concluded that the daily 15 mg and the weekly 45 mg course may be given without fear of haemolysis, except in a very small number of individuals.…”

Section: Discussionmentioning

confidence: 97%

The potential nephrotoxic effect of single tablet of 15 mg primaquine in G6PD deficient Hadoti region population of India

et al. 2017

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Primaquine is used in prevention of relapse of plasmodium vivax and ovale. It is known to cause haemolysis induced acute kidney injury in patients with glucose-6-phosphate dehydrogenase (G-6-PD) enzyme deficiency. Primaquine is widely used in the remote areas of Hadoti region of India by many non-registered practitioners for treatment of febrile illnesses without prior testing of G-6-PD status. Due to this practice, many patients land up with the grave consequences with significant health care burden. We report 8 such cases, which were referred to our hospital, New hospital medical college, Kota, Rajasthan, India. Our study included a series of 8 cases which were referred to our hospital with significantly deranged renal function test due to use of primaquine without prior testing of G-6-PD status. Routine blood investigations including renal function tests and G-6-PD status were measured. In our study, we found that patients with febrile illness and G-6-PD deficiency developed acute kidney injury even with a single tablet of 15 mg of primaquine. The use of even a single dose of 15 mg primaquine may not be safe in population of Hadoti region of India. Hence they should not be exposed to primaquine without prior G-6-PD testing.

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Section: Discussionmentioning

confidence: 97%

The potential nephrotoxic effect of single tablet of 15 mg primaquine in G6PD deficient Hadoti region population of India

et al. 2017

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“…G-6-PD A-containing blood withstands refri gerated storage as well as does normal blood [9]. The most extensive studies of hemolysis in White G-6-PD-deficient subjects have been done in Sardinia, but complete characterization of the variants there has not been reported [11], It has been presumed to be G-6-PD Mediterranean. These White males tended to lyse all their cells when given a similar course of primaquine.…”

Section: Discussionmentioning

confidence: 99%

Glucose-6-Phosphate Dehydrogenase Deficiency and Blood Transfusion

McCurdy¹,

Morse²

1975

Vox Sanguinis

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Seven White American male blood donors with Italian surnames were found to have red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency among 1,285 with Greek or Italian surnames screened. Five different genetic variants were found: G-6-PDs Mediterranean (2), ‘Athens-like’ (2), San Juan, Columbus and ‘Canton-like’. Clinical evaluation of 23 patients who received 24 units of G-6-PD-deficient blood (G-6-PD A—) failed to reveal any deleterious effects. Screening of Black donors for G-6-PD deficiency is believed unnecessary; further data are needed before a recommendation can be made concerning screening for non-Black donors.

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“…Although the MF test bears the closest physiological resemblance of all currently available in vitro models to red cell fragmentation in vivo [17,19,26], MF has been neglected as a tool for investigating the mechanisms responsible for breakage of normal and G-6-PD deficient erythrocytes. The more popular osmotic fragility test was also employed in our previous studies [8,9] but failed to reveal effects of the model drug metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…The time required for GSH depletion to be reflected in increased MF and hemolysis would depend on the external environment of the cell, the extent of oxidant damage that was imposed by this environment, and the internal environment of the cell, including the state of its membranes and its metabolic capacity to maintain ionic gradients and to keep glutathione in a reduced state. How ever, any test for hemolytic potential in vivo based entirely on procedures in vitro fails to reflect the complexity of in vivo mechanisms which depend also on events such as splenic and hepatic sequestration [10,11,17]. Hemolytic processes may result from metabolic or structural injury and erythrophagocytosis appears to be a secondary rather than primary event [11].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Normal and G-6-PD Deficient Human Erythrocytes of Various Ages after Exposure to Metabolites of Hemolytic Drugs

Fraser¹,

Tilton²,

Vesell³

1971

Pharmacology

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Since in vivo studies indicate that older erythro cytes hemolyze preferentially in drug-induced hemolysis, differential centrifugation was used to separate young and old normal and G-6-PD deficient erythrocytes. Older cells were identified by their lower level of G-6-PD activity; in corporation of ⁵⁹Fe into erythrocytes confirmed this division of cells by age. Mechanical fragility (MF) of old cells was greater than that of young cells. Effects of 8-amino-5,6-quino linediol (AQD) (a possible primaquine metabolite) and of 2-hydroxyphenetidine (HP) (a phenacetin metabolite) on hemolysis, MF and reduced glutathione (GSH) and methemoglobin content were examined in vitro. AQD (2.5 × 10^–4 m) did not produce hemolysis but selectively increased MF of old G-6-PD deficient cells. HP (5 × 10^–4 m) produced considerable hemolysis of both normal and G-6-PD deficient cells with a selective effect in old G-6-PD deficient cells. HP also selectively increased the MF of old G-6-PD deficient cells. Incubation with AQDor HP depleted GSH content more in old than in young G-6-PD deficient cells. This depletion of GSH was followed by increased MF of old G-6-PD deficient cells. Hemolysis of normal cells occurred without GSH depletion but was accompanied by GSH depletion in G-6-PD deficient cells. Smaller differences in methemoglobin formation occurred but were not well correlated with hemolysis or increased MF. Although not applicable as a routine diagnostic test in the clinical laboratory, increased MF in vitro of old G-6-PD deficient erythrocytes is suggested as a useful research tool in assessing the potential of drugs or drug metabolites to cause hemolysis in vivo, particularly in combination with parallel studies of glutathione depletion.

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Nature of Hemolytic Crises and the Fate of G6PD Deficient, Drug-Damaged Erythrocytes in Sardinians

Cited by 40 publications

References 17 publications

The potential nephrotoxic effect of single tablet of 15 mg primaquine in G6PD deficient Hadoti region population of India

The potential nephrotoxic effect of single tablet of 15 mg primaquine in G6PD deficient Hadoti region population of India

Glucose-6-Phosphate Dehydrogenase Deficiency and Blood Transfusion

Alterations in Normal and G-6-PD Deficient Human Erythrocytes of Various Ages after Exposure to Metabolites of Hemolytic Drugs

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