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The interpretations below are provided by Donna Castellone, MS, MT (ASCP) SH for Aniara Diagnostica, Inc.

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INTRODUCTION:

Blood groups were discovered in the 20th century by Karl Landsteiner based on the antigenic property of glycophorin, a protein present on the RBC membrane. There are four blood groups: A, B, AB and O. Studies have shown there is variation among ABO groups in relation to bleeding. Blood O group is more likely to hemorrhage, while AB is more likely to have thrombosis. How does this impact coagulation issues and contributing to patients being at an increased risk of bleeding or thrombosis?¹

The incidence of ABO and Rh blood groups varies markedly with geographic and racial variations. In Caucasians of America, the predominant blood group is group O (45%) followed by group A (41%), B (10%) and AB (4%). Native American Indians belong al-most to blood group O. Among western Europeans, group O occurs in the highest frequency (46%) followed by group A (42%), B (9%) and AB (3%). In Eastern Europe, the predominant blood group is group B (40%). In Australia and Britain, the commonest blood groups are group O and A followed by group B and AB. In Indo-Pak sub-continent, group B and O occur in the highest frequency. In Bangladesh, the commonest blood group is blood group B (34.4%) followed by group O (30.4%), A (26.7%) and AB (8.6%).²

The variation of vWF has clinical relevance, reduced level are responsible for the inherited bleeding disorder of VWD, and elevated levels results in a dose dependent risk factor for thrombosis. This variation is genetically determined and up to 30% is influenced by ABO blood group.³ Ethnicity can also account for up to 7% of variation in VWF levels, as well as the prevalence in ABO groups in different races and ethnic groups.³

ROLE OF ABO ANTIGENS

A and B antigens are dominant and are found in blood as complex oligosaccharides with the only difference being their terminal sugars: A having N-acetyl galactosamine and B with galactose.¹ The carbohydrate structures that comprise the ABO blood group system (A, B and H determinants) are expressed on a range of different cell types, including platelets and endothelial cells (ECs). ABH antigens are terminal sugar structures A and B alleles at the ABO locus on chromosome 9 encode either A- or B-glycosyltransferase enzymes. These transferases catalyze the addition of specific sugar residues so that precursor core H glycan structures are converted to form either A antigen or B antigen.³ These antigens are also covalently bound to asparagine which are linked sugar chains of von Willebrand factor (vWF) which is synthesized by endothelial cells and platelets. This is the carrier protein for FVIII and stored in the intracellular granules of megakaryocytes when not in demand. VWF aids in the adhesion and aggregation of platelets. As a result, higher levels of vWF can result in thrombosis and lower levels results in vW disease. ABO gene accounts for 30% of genetic determinations of vWF levels and influence levels. The absence of A and B antigens can indirectly lower the plasma levels of vWF resulting in bleeding tendencies in O blood group which also hastens the clearance of vWF further lowering levels in this blood type.¹

The major effect of ABO on vWF AG levels was investigated by Preston and Barr in 1964. O is 20-30% lower and AB has the highest levels. Its magnitude of effect is pronounced in particular since the ABO(H) glycan determinants differ only with respect to a single terminal sugar moiety and are expressed on only a minority of the N- and O-linked glycans of VWF.³ Group O VWF was cleaved more rapidly by ADAMTS13 compared with non-O VWF. Differences in susceptibility to ADAMTS13 were also observed among the other non-O groups in the order B > A ≥ AB. ADAMTS13 proteolysis is significantly enhanced in individuals with the rare Bombay phenotype, in whom ABO(H) determinants are not expressed.3

IMPACT ON COAGULATION:

When looking at reference ranges by ABO blood groups, a study of a total of 9600 subjects included 2400 subjects in each blood type. The PT, INR, aPTT, thrombin time and fibrinogen were evaluated. There was a significant difference in PT, INR, and aPTT among ABO blood groups. PT and INR varied slightly between ABO blood groups. There was a higher aPTT value in individuals in the O blood group than in those in non‐O blood groups, in both males and females across the included age range. No differences were found in thrombin time and fibrinogen between the ABO blood groups.⁴

Individuals with type O blood had prolonged PT and INR compared with individuals with non‐O blood types. There were no differences in PT and INR between the A, B, and AB blood groups. The differences in PT and INR between females and males were significant in the type A blood group but not in other blood groups. Although there were higher values of PT and INR in individuals with type O blood than in those with non-O blood types, the differences were approximately 0.08 s and 0.008, respectively, which may have no clinical significance. These findings are contrary to previous studies but may be a result of the large sample size.⁴

The concentrations of most coagulation proteins vary significantly with age. It was reported that aPTT was prolonged in infants and children compared with adults.⁴ These results may be due to the association of vWF and FVIII, which are lower in people with blood type O. This can result in a prologation of the aPTT which can be impacted by factor VIII levels.⁴

BLEEDING RISK

Another study of 250 participants (105 male) the bleeding time of greater than 4 minutes was found to be the same in both O and B blood groups and there was no difference in the A and AB groups, however both findings were not statistically significant. However, results were higher in males. A clotting time (CT) of more than 6 minutes were found in both blood groups O and B, followed by A with none in group AB, but CT was higher in females.¹

It has been established that different ABO groups present with higher risks for bleeding. A complication of type A aortic dissection is excessive bleeding. A retrospective analysis of 335 patients with blood group O were compared to non-blood group O patients ( 152 vs 185).⁵ There were no differences in rates of massive bleeding when comparing blood group O and non-O patients. Blood group O patients received more fibrinogen concentrate, but administered units of packed red blood cells, platelets or plasma were similar. This study could not demonstrate any association between blood group and bleeding after surgery for ATAAD. It cannot be ruled out that potential differences were levelled out by blood group O patients receiving significantly more fibrinogen concentrate.⁵

In an analysis of 422 patients with bleeding of unknown causes (BUC), in which 199 (47.2%) were blood group O, 149 (35.3%) blood group A, 49 (11.6%) blood group B, and 25 (5.9%) blood group AB. Blood group O was more prevalent in patients with BUC than in the control group of 23,145 healthy blood donors (37.6%), whereas blood type A was underrepresented. There were no differences in the occurrence of blood types B and AB. Patients with BUC had a higher probability of having blood group O.7 It is believed that the influence of blood group on VWF and FVIII is most likely induced by posttranslational glycosylation stimulated by A and B antigens.⁷

An increased amount of group O patients were seen in patients who presented with bleeding from unknown causes when compared to healthy donors. This was in independent association seen in relation to bleeding severity, in particular oral mucosal bleeding. It was also independent of VWF:Ag, VWF:RCo, and FVIII levels. When blood group O were tested using global hemostasis (ROTEM) results showed increased clot firmness and reduced lysis whereas in platelet function testing (LTA and PFA) there was no difference between group O and non-group O. This study found normal but lower levels of VWF in this cohort, which supports the findings that ABO blood groups on bleeding severity was independent of VWF or FVIII levels.⁶

THROMBOTIC RISK

Additionally, studies have shown that the thrombotic risk is significantly reduced in blood group O subjects, however this mechanism is poorly understood. A possible explanation is that ABO groups significantly influence the formation of the platelet plug in vascular injury. VWF factors are about 25% lower in O subjects compared to non-O. Group O VWF also demonstrates enhanced susceptibility to ADAMTS13 proteolysis as well as decreased interaction with platelets. It appears this is mediated by the ABO(H) carbohydrate structures that are carried on both the N- and O-linked glycans of VWF ABO(H) carbohydrate structures that are carried on both the N- and O-linked glycans of VWF. These are also expressed on several different platelet surfaces. This all supports the hypothesis that ABO groups impact not only the quantitative and qualitative effects of VWF but aspects of platelet function.³

A cause of VTE in hospitalized patients is the Peripherally inserted central catheter (PICC). The relationship between the ABO blood group and the risk of VTE in cancer patients was reviewed. Hypercoagulability or vascular endothelial damage can occur due to chemotherapeutic drugs. This is increased in patients with non-O group patients. Tumor is a high risk for thrombosis being 4 to 7.5 times higher than the general population. Determining the risk of PICC patients and ABO groups may aid in preventing thrombosis.⁷

CONCLUSION:

Understanding the impact of ABO groups on coagulation is important in the assessment of both bleeding and clotting disorders. Blood type should be considered when evaluating risk in patients that is compounded by their clinical picture.

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REFERENCES

1. Jiby Jolly Benjamin1, M Bagavad Geetha1, Study of association of bleeding and clotting time with blood group among young adults, Indian Journal of Clinical Anatomy and Physiology 7(4):350-353, January 2021
2. Afrina Binte Azad1, Qazi Shamima Akhter, Mohammad Aminul Islam, Farzana Yeasmin Mukta, Lily Afroz, Khushbun Nahar Layla, Tahmina Akter, Shamanta Islam, A. Z. M. Adnan, ABO Blood Groups and Their Relationship with Coagulation Factor VIII in Healthy Adults, Journal of Biosciences and Medicines, January 2021 (09) 49-58.
3. Soracha E. Ward, Jamie M. O’Sullivan, James S. O’Donnell , The relationship between ABO blood group, von Willebrand factor, and primary hemostasis, https://ashpublications.org/blood/article/136/25/2864/461790/The-relationship-between-ABO-blood-group-von Blood (2020) 136 (25): 2864–2874.
4. Chen Z, Dai X, Cao J, Tan X, Chen S, Yu M. Reference intervals for coagulation tests in adults with different ABO blood types. J Clin Lab Anal. 2022 Mar;36(3):e24269
5. Guné, Henrik; Larsson, Mårten; Nozohoor, Shahab; Herou, Erik; Luts, Cecilia; Ragnarsson, Sigurdur; Samuelsson, Maria; Sjögren, Johan; Svensson, Peter J.; Zindovic, Igor, Impact of ABO blood group on bleeding complications after surgery for acute type A aortic dissection, Blood Coagulation & Fibrinolysis 32(4):p 253-258, June 2021.
6. Dino Mehic, Stefanie Hofer, Christof Jungbauer, Alexandra Kaider, Helmuth Haslacher, Ernst Eigenbauer, Judit Rejtő, Dieter Schwartz, Bernd Jilma, Cihan Ay, Ingrid Pabinger, Johanna Gebhart, Association of ABO blood group with bleeding severity in patients with bleeding of unknown cause. Blood Adv. 2020 Oct 23;4(20):5157–5164 https://pmc.ncbi.nlm.nih.gov/articles/PMC7594405/
7. Liu, Fangjing MB; Zhang, Qiang MB; Rao, Li MB; Song, Jifang MB. Relationship between ABO blood group and risk of venous thrombosis in cancer patients with peripherally inserted central catheters. Medicine 99(45):p e23091, November 06, 2020.

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