Original Article

Split Viewer

Blood Res 2023; 58(1):

Published online March 31, 2023

https://doi.org/10.5045/br.2023.2022197

© The Korean Society of Hematology

Impact of ABO blood group antigens on residual factor VIII levels and risk of inhibitor development in hemophilia A

Debadrita Ray1, Narender Kumar1, Chander Hans1, Anita Kler1, Richa Jain2, Deepak Bansal2, Amita Trehan2, Arihant Jain3, Pankaj Malhotra3, Jasmina Ahluwalia1

1Department of Hematology, 2Department of Paediatrics, 3Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence to : Narender Kumar, M.D.
Department of Hematology, PGIMER, Madhya Marg, Sector 12, Chandigarh 160012, India
E-mail: narenderkalson@gmail.com

Received: September 29, 2022; Revised: February 2, 2023; Accepted: March 10, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background
The clinical phenotype of hemophilia A (HA) does not always correlate with severity. Similarly, the presence of inhibitors does not necessarily increase the risk of bleeding. This paradox between clinical and laboratory findings may be partially attributed to non-modifiable factors, such as blood group, which is known to influence FVIII levels in healthy individuals. Our aim was to assess the effect of ABO blood group antigens on FVIII levels across the severity spectrum of HA and risk of inhibitor development.
Methods
Data of consecutive patients with HA who visited the coagulation unit of a northern Indian tertiary care hospital between 2010‒2021 were reviewed. Patients with missing blood group data, transfusion histories, or baseline FVIII levels were excluded.
Results
Mild, moderate, and severe HA was present in 41 (6.9%), 72 (12.2%), and 479 (80.9%) patients, respectively. There were no differences in the FVIII levels among the various blood groups across the HA severity spectrum. Inhibitors were administered to 35 patients (5.9%). In the multivariate analysis, blood group A was an independent risk factor for the development of inhibitors (adjusted odds ratio 2.70, P=0.04) after adjusting for age at onset of bleeding, FVIII transfusion, age at first FVIII transfusion, and severity of HA.
Conclusion
Unlike what is observed in healthy individuals, blood group did not influence residual FVIII levels across the severity spectrum of HA. Patients in group A had a higher risk of developing inhibitors.


Keywords: Hemophilia, Blood group, Bleeding disorder, Factor VIII inhibitors

Article

Original Article

Blood Res 2023; 58(1): 61-70

Published online March 31, 2023 https://doi.org/10.5045/br.2023.2022197

Copyright © The Korean Society of Hematology.

Impact of ABO blood group antigens on residual factor VIII levels and risk of inhibitor development in hemophilia A

Debadrita Ray1, Narender Kumar1, Chander Hans1, Anita Kler1, Richa Jain2, Deepak Bansal2, Amita Trehan2, Arihant Jain3, Pankaj Malhotra3, Jasmina Ahluwalia1

1Department of Hematology, 2Department of Paediatrics, 3Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence to:Narender Kumar, M.D.
Department of Hematology, PGIMER, Madhya Marg, Sector 12, Chandigarh 160012, India
E-mail: narenderkalson@gmail.com

Received: September 29, 2022; Revised: February 2, 2023; Accepted: March 10, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
The clinical phenotype of hemophilia A (HA) does not always correlate with severity. Similarly, the presence of inhibitors does not necessarily increase the risk of bleeding. This paradox between clinical and laboratory findings may be partially attributed to non-modifiable factors, such as blood group, which is known to influence FVIII levels in healthy individuals. Our aim was to assess the effect of ABO blood group antigens on FVIII levels across the severity spectrum of HA and risk of inhibitor development.
Methods
Data of consecutive patients with HA who visited the coagulation unit of a northern Indian tertiary care hospital between 2010‒2021 were reviewed. Patients with missing blood group data, transfusion histories, or baseline FVIII levels were excluded.
Results
Mild, moderate, and severe HA was present in 41 (6.9%), 72 (12.2%), and 479 (80.9%) patients, respectively. There were no differences in the FVIII levels among the various blood groups across the HA severity spectrum. Inhibitors were administered to 35 patients (5.9%). In the multivariate analysis, blood group A was an independent risk factor for the development of inhibitors (adjusted odds ratio 2.70, P=0.04) after adjusting for age at onset of bleeding, FVIII transfusion, age at first FVIII transfusion, and severity of HA.
Conclusion
Unlike what is observed in healthy individuals, blood group did not influence residual FVIII levels across the severity spectrum of HA. Patients in group A had a higher risk of developing inhibitors.

Keywords: Hemophilia, Blood group, Bleeding disorder, Factor VIII inhibitors

Fig 1.

Figure 1.FVIII levels in different blood groups across the severity spectrum of HA (P-value calculated using Kruskal–Wallis test with Dunn’s correction).
Blood Research 2023; 58: 61-70https://doi.org/10.5045/br.2023.2022197

Table 1 . Clinicopathological characteristics of study population..

Clinicopathological parametersAll cases (N=592)Mild HA (N=41, 6.9%)Moderate HA (N=72, 12.2%)Severe HA (N=479, 80.9%)P
Mild vs. moderateModerate vs. severeMild vs. severe
Age at onset of bleeding (yr)a)3 (2–8)8 (4–12)6 (3–8)2 (1–3)0.11<0.001<0.001d)
Family history of HAb)333 (56.3%)23 (56.1%)44 (61.1%)266 (55.5%)0.690.44>0.99
FVIII levelsa)0.8 (0.3–0.9)10.7 (7.1–16.58)1.6 (1.2–2.5)0.25 (0.1–0.6)<0.001<0.001<0.001d)
vWF antigen (%)a)147.8 (98.6–192)146.0 (104.3–193.1)140.8 (99.1–189.5)141.1 (98.95–194)0.610.580.66
vWFGPIbR level (%)a)106.8 (87–187.2)107.5 (85–188.7)105.1 (84.5–184.7)106.2 (86.4–187)>0.990.720.35
Consanguinityb)28 (4.7%)1 (2.4%)2 (2.8%)25 (5.2%)>0.990.560.71
Blood groupc)
A104 (17.6%)8 (19.5%)13 (18.1%)83 (17.3%)
B179 (30.2%)14 (34.2%)22 (30.6%)143 (29.9%)
O203 (34.3%)11 (26.8%)24 (33.2%)168 (35.1%)0.910.990.76
AB106 (17.9%)8 (19.5%)13 (18.1%)85 (17.7%)
Spontaneous bleedingb)262 (44.2%)9 (21.9%)30 (41.6%)223 (46.6%)0.040.450.002d)
Traumatic bleedb)499 (84.3%)32 (78%)59 (81.9%)408 (85.2%)0.630.480.26

Statistical tests were used for calculation of P-values..

a)Kruskal–Wallis test with Dunn’s correction for multiple comparisons. b)Fisher’s exact test. c)Chi-squared test. d)Statistically significant P-value<0.05..


Table 2 . ABO blood groups and risk of inhibitor development..

Blood groupInhibitor-positive (N=35)Inhibitor-negative (N=557)Odds ratio (95% CI)P
O (N=203)9 (4.4%)194 (95.6%)0.65 (0.30 to 1.41)0.28
Non-O (N=389)26 (6.7%)363 (93.3%)
B (N=179)8 (4.5%)171 (95.5%)0.67 (0.30 to 1.50)0.33
Non-B (N=413)27 (6.5%)386 (93.5%)
A (N=104)13 (12.5%)91 (87.5%)3.03 (1.48 to 6.23)0.003
Non-A (N=488)22 (4.5%)466 (95.5%)
AB (N=106)5 (4.7%)101 (95.3%)0.75 (0.29 to 1.99)0.57
Non-AB (N=486)30 (6.2%)456 (93.8%)

P-values were calculated using Fisher’s exact test..


Table 3 . Risk factors for development of inhibitors (N=592)..

CharacteristicPatients with inhibitors (N=35)Patients without inhibitors (N=557)Univariate predictor of inhibitor
P-value
Multivariate predictor of inhibitor
P-value
Age at onset of bleeding3 (1–12) yr2 (1–8) yr0.260.69
FVIII transfusion with or without FFP34 (97.1%)445 (79.8%)0.007<0.001a)
Age at first FVIII transfusion4 (1–7) yr6 (4–8) yr0.170.10
Severe HA32 (91.4%)447 (80.3%)0.120.07
Blood group A13 (37.1%)91 (16.3%)0.0030.04a)

a)Statistically significant P-value<0.05..


Table 4 . Association of various blood groups and inhibitor development among HA patients in different studies..

ParametersArshad et al. 2018 [11]Fanchino et al. 2016 [10]Franchino et al. 2021 [9]Present study
Total HA patients300209287592
HA patients with inhibitors (N, %)29 (9.6%)56 (26.8%)85 (29.6%)35 (5.9%)
Low titer inhibitor17 (58.6%)12 (5.7%)21 (24.7%)7 (20%)
High titer inhibitor12 (41.4%)44 (21.1%)64 (75.3%)28 (80%)
ABO blood group, N (%)With inhibitorWithout inhibitorWith inhibitorWithout inhibitorWith inhibitorWithout inhibitorWith inhibitorWithout inhibitor
A19 (65.5%)54 (20%)30 (31.9%)64 (68.1%)39 (45.9%)62 (30.7%)13 (37.5%)196 (95.6%)
B2 (6.8%)98 (36.1%)9 (39.1%)14 (60.9%)13 (15.3%)23 (11.4%)8 (22.9%)173 (30.6%)
AB2 (6.8%)43 (16%)1 (25.0%)3 (75.0%)7 (8.2%)6 (3.0%)5 (14.3%)104 (18.4%)
O6 (20.6%)76 (28%)16 (18.2%)72 (81.8%)26 (30.6%)111 (55.0%)9 (25.7%)196 (95.6%)
PO vs. A: 0.02a)
O vs. B: 0.12
O vs. AB: 0.52
A vs. B: 0.005a)
A vs. AB: 0.49
B vs. AB: 0.05
O vs. A: 0.033
O vs. B: 0.032
O vs. non-O: 0.017
<0.001O vs. non-O: 0.28
A vs. non-A: 0.003a)
B vs. non-B: 0.33
AB vs. non-AB: 0.57

a)Statistically significant P-value<0.05..


Blood Res
Volume 59 2024

Supplementary File

Stats or Metrics

Share this article on

  • line

Related articles in BR

Blood Research

pISSN 2287-979X
eISSN 2288-0011
qr-code Download