Blood Group O Protects against Inhibitor Development in Severe Hemophilia A Patients.
Increasing evidence supports the link between ABO(H) blood group determinants and hemostasis. In particular, the ABO-related different glycosylation patterns of von Willebrand factor strongly influence its clearance and functional levels, and this may contribute to the inter-individual variations in the half-life of infused Factor VIII (FVIII) in hemophilia A (HA) patients. We investigated the role of ABO blood groups in regulating FVIII immunogenicity by evaluating their distribution in patients with severe (FVIII < 1 IU/dL) HA according to inhibitor development and other known relevant factors. In a cohort of Italian severe HA patients (n= 209), the ABO blood group distribution was similar to that in the healthy general population. However, the distribution of inhibitors, developed in 56 patients overall (26.8%), was significantly different in the four ABO phenotypes (O, 18.2%; A, 31.9%; B, 39.1%, AB, 25%;p= 0.033); this difference seemed more pronounced when only high-titer inhibitors (overall, 21.1%) were considered (O, 11.4%; A, 27.7%; B, 34.8%;p= 0.011). Relative risks in O versus non-O blood group were 0.55 (95% CI: 0.33-0.92) and 0.40 (95% CI: 0.21-0.77) for any and high-titer inhibitors, respectively. In a multivariate logistic regression, O blood group was shown to lower (approximately twofold) inhibitor risk, similarly with plasma-derived FVIII, whereas high-riskF8mutations were associated with increased risk. However, the estimated effect of O blood type on inhibitor development was free from any significant correlation to other covariates, including presence of high-riskF8mutations and type of replacement FVIII used. In this retrospective cohort of severe hemophiliacs, blood group O appears to protect against inhibitor development, with independent effects from other covariates. Larger prospective studies are needed to confirm this finding and to delve deeper into its pathophysiologic mechanisms.
Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, Mantova, Italy.
Massimo
M
Franchini
Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples, Italy.
Antonio
A
Coppola
University of Padua, Padua, Italy.
Carlo
C
Mengoli
Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Parma, Italy.
Gianna Franca
GF
Rivolta
Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Parma, Italy.
Federica
F
Riccardi
Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples, Italy.
Giovanni Di
GD
Minno
Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Parma, Italy.
Annarita
A
Tagliaferri
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation; D001789:Blood Group Antigens / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006467:Hemophilia A / Q000097:blood*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
D001789:Blood Group Antigens