Platelet counts in HFE p.C282Y/p.C282Y and wt/wt post-screening clinical evaluation participants

Plain Language Summary What is the context? Hemochromatosis is typically associated with inheritance of two copies of p.C282Y, a common mutation of the HFE gene on chromosome 6p that regulates iron absorption. Platelet counts, age, and serum levels of liver enzymes have been used to estimate risks of cirrhosis in adults with hemochromatosis. Lower platelet counts in Europeans are significantly associated with a mutation in CARMIL1, a gene on chromosome 6p close to HFE. Clinical and laboratory associations of normal platelet counts in adults with HFE p.C282Y/p/C282Y and wt/wt uncomplicated by cirrhosis are unreported. What is new? We studied normal platelet counts in 425 white adults who participated in a primary care-based hemochromatosis screening program. These participants did not have cirrhosis or other conditions that often influence platelet counts. Our analyses of 14 variables identified these significant positive associations with platelet counts, after adjustment for other variables: absolute neutrophil, lymphocyte, and monocyte counts and C-reactive protein levels; and these significant inverse associations: age, TS, and hemoglobin levels. What is the impact? Laboratory and clinical factors significantly associated with platelet counts in adults with HFE p.C282/p.C282Y or wt/wt are similar to those in persons unselected for HFE genotypes or hemochromatosis. It is unlikely that genes that influence platelet counts are closely linked to HFE on chromosome 6p. Adults with hemochromatosis and HFE p.C282/p.C282Y who have abnormal platelet counts should be evaluated for cirrhosis or non-iron platelet disorders. Our aim was to document the effects of genotype HFE p.C282Y/p.C282Y and hemochromatosis-associated laboratory and clinical manifestations on platelet counts (PC). We compiled genotype (p.C282Y/p.C282Y or HFE wt/wt (absence of p.C282Y and p.H63D (rs1799945)), age, sex, body mass index, presence/absence of chronic fatigue, swelling/tenderness of second/third metacarpophalangeal joints, and hyperpigmentation, transferrin saturation (TS), serum ferritin (SF), hemoglobin levels, absolute neutrophil, lymphocyte, and monocyte counts, C-reactive protein levels, and PC of non-Hispanic white participants in a hemochromatosis and iron overload post-screening clinical examination. There were 171 men and 254 women (141 p.C282Y/p.C282Y, 284 wt/wt) of median age 53 y. Median TS and SF were higher in p.C282Y/p.C282Y than wt/wt participants grouped by sex (p < .0001, all comparisons). Median PC by genotype was lower in men than women (p < .0001, both comparisons). Regression on PC using 14 independent variables identified these significant positive associations: absolute neutrophil, lymphocyte, and monocyte counts and C-reactive protein levels and these significant inverse associations: age, TS, and hemoglobin levels. We conclude that PC is significantly associated with absolute neutrophil, lymphocyte, and monocyte counts, and C-reactive protein (positive) and age, TS, and hemoglobin (inverse), after adjustment for other variables. HFE genotypes we studied were not significantly associated with PC.

Automated summary

This study examined the association between platelet counts and various factors in white adults with hemochromatosis. The results showed that platelet counts were positively associated with neutrophil, lymphocyte, and monocyte counts, as well as C-reactive protein levels. They were inversely associated with age, transferrin saturation, and hemoglobin levels. HFE genotypes were not significantly associated with platelet counts.