Hemophilia A patients who are CLEC4M rs868875 G carriers and have the ABO O genotype may experience a faster decay of infused factor VIII (FVIII), according to a new study published in the Journal of Clinical Medicine.

These associations were explored in an Italian cohort of patients diagnosed with hemophilia A (n=26), of whom 15% had the combined genotype CLEC4M rs868875 G-carrier/ABO O. These patients showed shorter half-lives and increased clearance of FVIII in pharmacokinetic (PK) analyses.

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“Since the mean FVIII half-life was approximately half-reduced as compared with all other combined genotypes, and was reflected in a largely increased clearance, this finding deserves to be explored for personalized replacement therapy/prophylaxis,” the study authors suggested.

The analysis of the FVIII PK profiles in the different CLEC4M rs868875 genotypes (ie, AA [n=12], AG [n=12], and GG [n=2]) revealed significant differences in the elimination rate constant K 1-0, transfer from the central to peripheral plasma compartment rate K 1-2, K 1-0 half-life, and beta rate constant. Carriers of the G allele (n=14) showed higher K 1-0 values than AA homozygotes (0.11±0.03 1/h standard error [SE] vs 0.06±0.00 1/h SE; P =.045).

The contribution of the CLEC4M rs868875 polymorphism remained significant for K 1-0, beta, and K 1-0 half-life when investigated together with the ABO genotypes. G carriers with the O blood group showed significantly shorter K 1-0 half-lives than all the other genotype groups, while AA homozygotes presented with similar values regardless of the ABO genotypes.

However, these findings require validation in larger cohorts. “Our observations were obtained in a limited number of [hemophilia A] patients, and the infrequent CLEC4M rs868875 GG homozygous condition does not favor the exploration of the potentially higher influence of this genotype,” the study authors recognized.


Lunghi B, Morfini M, Martinelli N, Linari S, Castaman G, Bernardi F. Combination of CLEC4M rs868875 G-carriership and ABO O genotypes may predict faster decay of FVIII infused in hemophilia A patients. J Clin Med. 2022;11(3):733. doi:10.3390/jcm11030733