Blood Res 2023; 58(1):
Published online March 31, 2023
https://doi.org/10.5045/br.2023.2022197
© The Korean Society of Hematology
Correspondence to : Narender Kumar, M.D.
Department of Hematology, PGIMER, Madhya Marg, Sector 12, Chandigarh 160012, India
E-mail: narenderkalson@gmail.com
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
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.
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
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
Table 1 . Clinicopathological characteristics of study population..
Clinicopathological parameters | All cases (N=592) | Mild HA (N=41, 6.9%) | Moderate HA (N=72, 12.2%) | Severe HA (N=479, 80.9%) | |||
---|---|---|---|---|---|---|---|
Mild vs. moderate | Moderate vs. severe | Mild 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%) | 0.69 | 0.44 | >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) | 0.61 | 0.58 | 0.66 |
vWFGPIbR level (%)a) | 106.8 (87–187.2) | 107.5 (85–188.7) | 105.1 (84.5–184.7) | 106.2 (86.4–187) | >0.99 | 0.72 | 0.35 |
Consanguinityb) | 28 (4.7%) | 1 (2.4%) | 2 (2.8%) | 25 (5.2%) | >0.99 | 0.56 | 0.71 |
Blood groupc) | |||||||
A | 104 (17.6%) | 8 (19.5%) | 13 (18.1%) | 83 (17.3%) | |||
B | 179 (30.2%) | 14 (34.2%) | 22 (30.6%) | 143 (29.9%) | |||
O | 203 (34.3%) | 11 (26.8%) | 24 (33.2%) | 168 (35.1%) | 0.91 | 0.99 | 0.76 |
AB | 106 (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%) | 0.04 | 0.45 | 0.002d) |
Traumatic bleedb) | 499 (84.3%) | 32 (78%) | 59 (81.9%) | 408 (85.2%) | 0.63 | 0.48 | 0.26 |
Statistical tests were used for calculation of
a)Kruskal–Wallis test with Dunn’s correction for multiple comparisons. b)Fisher’s exact test. c)Chi-squared test. d)Statistically significant
Table 2 . ABO blood groups and risk of inhibitor development..
Blood group | Inhibitor-positive (N=35) | Inhibitor-negative (N=557) | Odds ratio (95% CI) | |
---|---|---|---|---|
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%) |
Table 3 . Risk factors for development of inhibitors (N=592)..
Characteristic | Patients with inhibitors (N=35) | Patients without inhibitors (N=557) | Univariate predictor of inhibitor | Multivariate predictor of inhibitor |
---|---|---|---|---|
Age at onset of bleeding | 3 (1–12) yr | 2 (1–8) yr | 0.26 | 0.69 |
FVIII transfusion with or without FFP | 34 (97.1%) | 445 (79.8%) | 0.007 | <0.001a) |
Age at first FVIII transfusion | 4 (1–7) yr | 6 (4–8) yr | 0.17 | 0.10 |
Severe HA | 32 (91.4%) | 447 (80.3%) | 0.12 | 0.07 |
Blood group A | 13 (37.1%) | 91 (16.3%) | 0.003 | 0.04a) |
a)Statistically significant
Table 4 . Association of various blood groups and inhibitor development among HA patients in different studies..
Parameters | Arshad | Fanchino | Franchino | Present study | ||||
---|---|---|---|---|---|---|---|---|
Total HA patients | 300 | 209 | 287 | 592 | ||||
HA patients with inhibitors (N, %) | 29 (9.6%) | 56 (26.8%) | 85 (29.6%) | 35 (5.9%) | ||||
Low titer inhibitor | 17 (58.6%) | 12 (5.7%) | 21 (24.7%) | 7 (20%) | ||||
High titer inhibitor | 12 (41.4%) | 44 (21.1%) | 64 (75.3%) | 28 (80%) | ||||
ABO blood group, N (%) | With inhibitor | Without inhibitor | With inhibitor | Without inhibitor | With inhibitor | Without inhibitor | With inhibitor | Without inhibitor |
A | 19 (65.5%) | 54 (20%) | 30 (31.9%) | 64 (68.1%) | 39 (45.9%) | 62 (30.7%) | 13 (37.5%) | 196 (95.6%) |
B | 2 (6.8%) | 98 (36.1%) | 9 (39.1%) | 14 (60.9%) | 13 (15.3%) | 23 (11.4%) | 8 (22.9%) | 173 (30.6%) |
AB | 2 (6.8%) | 43 (16%) | 1 (25.0%) | 3 (75.0%) | 7 (8.2%) | 6 (3.0%) | 5 (14.3%) | 104 (18.4%) |
O | 6 (20.6%) | 76 (28%) | 16 (18.2%) | 72 (81.8%) | 26 (30.6%) | 111 (55.0%) | 9 (25.7%) | 196 (95.6%) |
O 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 | <0.001 | O 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
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