The Course of Experimentally Induced Hemolytic Anemia in a Primaquine-Sensitive Caucasian

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

doi:10.1182/blood.v25.1.92.92

Cited by 39 publications

(24 citation statements)

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“…The only available documented comparative data are on the effect of PQ on (i) subjects with G6PD A-, the variant common in Africa, present in the African-American volunteers in Chicago (see above); and (ii) subjects from Sardinia with G6PD Mediterranean, a variant common in that area, in the Middle East and in India. For the same dose of PQ, by comparison to previous experience with G6PD A-, AHA was considerably more severe with G6PD Mediterranean (Pannacciulli et al, 1965); in addition, with the latter there was little evidence of a 'resistance phase' upon repeated administration (Salvidio et al, 1972). This clinical difference is consistent with the fact that the residual G6PD activity in red cells is about 5% of normal with G6PD Mediterranean, whereas it is 13% of normal with G6PD A- (Luzzatto et al, 2001).…”

Section: Study Day Haemoglobin G/l (+/-Se)mentioning

confidence: 72%

G6PD deficiency: a classic example of pharmacogenetics with on‐going clinical implications

2013

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That primaquine and other drugs can trigger acute haemolytic anaemia in subjects who have an inherited mutation of the glucose 6-phosphate dehydrogenase (G6PD) gene has been known for over half a century: however, these events still occur, because when giving the drug either the G6PD status of a person is not known, or the risk of this potentially life-threatening complication is under-estimated. Here we review briefly the genetic basis of G6PD deficiency, and then the pathophysiology and the clinical features of drug-induced haemolysis; we also update the list of potentially haemolytic drugs (which includes rasburicase). It is now clear that it is not good practice to give one of these drugs before testing a person for his/her G6PD status, especially in populations in whom G6PD deficiency is common. We discuss therefore how G6PD testing can be done reconciling safety with cost; this is once again becoming of public health importance, as more countries are moving along the pathway of malaria elimination, that might require mass administration of primaquine. Finally, we sketch the triangular relationship between malaria, antimalarials such as primaquine, and G6PD deficiency: which is to some extent protective against malaria, but also a genetically determined hazard when taking primaquine.

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Section: Study Day Haemoglobin G/l (+/-Se)mentioning

confidence: 72%

G6PD deficiency: a classic example of pharmacogenetics with on‐going clinical implications

2013

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“…When otherwise healthy G6PDd A- adult volunteers were exposed to daily doses of 15mg or 30mg primaquine, hemolysis typically did not commence until after the third or fourth day, and the nadir of hematocrit occurred on about day 7 or 8 of dosing [ 16 ]. Thereafter hemolysis seemed to cease and subjects recovered normal hematocrit despite continuous daily dosing of 30mg for many weeks [ 17 ]. Only older red blood cells (RBC) were destroyed and the younger RBC replacing them could manage continued primaquine dosing.…”

Section: Introductionmentioning

confidence: 99%

G6PD Deficiency at Sumba in Eastern Indonesia Is Prevalent, Diverse and Severe: Implications for Primaquine Therapy against Relapsing Vivax Malaria

et al. 2015

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Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1%) were phenotypically deficient (<4.6U/gHb; median normal 10U/gHb). The villages were in two distinct ecosystems, coastal and inland. A positive correlation occurred between the prevalence of malaria and G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (P<0.001), and 6.7% and 3.1% for G6PD deficiency (P<0.001) at coastal and inland sites, respectively. The dominant genotypes of G6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm.

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“…Accumulation of "Cr in the spleen is related to red cells destroyed in situ. The existence of such an extracascular haemolytic component in the removal of G-6-PD deficient cells after administration of primaquine, seems well established considering that Heinz-body formation is a constant feature in these haemolytic crises (Beutler et al 1954), and that in Caucasians both old and young G-6-PD deficient cells are destroyed by the drug (Pannacciulli et al 1965).…”

Section: Discussionmentioning

confidence: 99%

“…One wonders whether the spleen in the presence of primaquine does not play a similar role in the destruction of G-6-PD deficient, Heinz-body-loaded erythrocytes in Caucasians. It should also be kept in mind that the destruction of G-6-PD deficient red cells in affected Caucasians seems to involve not only the older cells but also red cells up to 10-16 days of age (Pannacciulli et al 1965, Salvidio et al 1967. It was thought worthwhile therefore to investigate the hepatic and splenic share in the destruction of G-6-PD dificient red cells in normal subjects in whom the cells were transfused, and especially in G-6-PD deficient Causasians treated with primaquine.…”

mentioning

confidence: 99%

Sites of Destruction of Red Cells in G‐6‐PD Deficient Caucasians and in Phenylhydrazine Treated Patients

Tizianello

Pannacciulli

Ajmar

et al. 1968

Scandinavian Journal of Haematology

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The sites of destruction of 51Cr tagged G‐6‐PD deficient red cells in normal and primaquine sensitive Sardinians after drug administration have been studied by means of surface monitoring and, in one case, by direct quantitation after surgery. In practically all cases a liver to spleen ratio of one could be recorded, with a constant splenic participation in the uptake of radioactivity. It was observed that, beside the major role played by the liver in the sequestration and disposal of severely damaged G‐6‐PD deficient red cells after administration of primaquine, also the spleen has a significant share in the disposal of damaged cells.

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The Course of Experimentally Induced Hemolytic Anemia in a Primaquine-Sensitive Caucasian

Cited by 39 publications

References 1 publication

G6PD deficiency: a classic example of pharmacogenetics with on‐going clinical implications

G6PD deficiency: a classic example of pharmacogenetics with on‐going clinical implications

G6PD Deficiency at Sumba in Eastern Indonesia Is Prevalent, Diverse and Severe: Implications for Primaquine Therapy against Relapsing Vivax Malaria

Sites of Destruction of Red Cells in G‐6‐PD Deficient Caucasians and in Phenylhydrazine Treated Patients

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