Non-O Blood Type Is the Commonest Genetic Risk Factor for VTE: Results from a Meta-Analysis of the Literature

 

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Abstract

It is well known that the ABO blood group exerts a major influence on hemostasis, as O blood group individuals have lower von Willebrand factor and factor VIII levels than non-O blood group subjects. To evaluate the possible clinical implication of the different ABO blood groups on the risk of developing venous thromboembolism (VTE), we conducted a meta-analysis of the existing literature. After an electronic search strategy using Medline and Embase and a manual review of abstract books of the International Society on Thrombosis and Haemostasis and of reference lists of all retrieved articles, we included in the systematic review 38 studies with 10,305 VTE cases. The prevalence of non-O blood group was significantly higher in VTE patients compared with controls with a resulting pooled odds ratio (OR) of 2.09 (95% confidence interval [CI], 1.83, 2.38; p < 0.00001). Similar findings were obtained when the genotypes A₁O/BO/A₂B (OR 1.73, 95% CI, 1.47, 2.05; p < 0.00001) and A₁B/A₁A₁/BB (OR 1.87, 95% CI, 1.84, 2.44; p < 0.00001) were analyzed. The maximum VTE risk was observed in non-O–factor V Leiden patients (OR 7.60, 95% CI, 3.21, 17.99), while for G20210A prothrombin mutation it was not possible to perform a pooled analysis due to a paucity of published studies. Finally, the association between non-O blood group and VTE was weaker when provoked VTE cases were considered (OR 1.33, 95% CI, 1.18, 1.50), while it was substantially unchanged when unprovoked VTE cases were analyzed (OR 1.88, 95% CI, 1.42, 2.50). In conclusion, considering its prevalence, non-O blood group is a candidate to be one of the most important genetic risk factors for venous thrombosis.

• References

• 1 Lowe JB. The blood group-specific human glycosyltransferases. Baillieres Clin Haematol 1993; 6 (2) 465-492
  CrossrefPubMedGoogle Scholar
• 2 Preston AE, Barr A. The plasma concentration of factor VIII in the normal population. Br J Haematol 1964; 10: 238-245
  CrossrefPubMedGoogle Scholar
• 3 Franchini M, Capra F, Targher G, Montagnana M, Lippi G. Relationship between ABO blood group and von Willebrand factor levels: from biology to clinical implications. Thromb J 2007; 5: 14
  CrossrefPubMedGoogle Scholar
• 4 Moeller A, Weippert-Kretschmer M, Prinz H, Kretschmer V. Influence of ABO blood groups on primary hemostasis. Transfusion 2001; 41 (1) 56-60
  CrossrefPubMedGoogle Scholar
• 5 O'Donnell JS, Laffan MA. The relationship between ABO histo-blood group, factor VIII and von Willebrand factor. Transfus Med 2001; 11 (4) 343-351
  CrossrefPubMedGoogle Scholar
• 6 Jenkins PV, O'Donnell JS. ABO blood group determines plasma von Willebrand factor levels: a biologic function after all?. Transfusion 2006; 46 (10) 1836-1844
  CrossrefPubMedGoogle Scholar
• 7 Gastineau DA, Moore SB. How important are ABO-related variations in coagulation factor levels?. Transfusion 2001; 41 (1) 4-5
  CrossrefPubMedGoogle Scholar
• 8 Favaloro EJ, Soltani S, McDonald J, Grezchnik E, Easton L, Favaloro JWC. Reassessment of ABO blood group, sex, and age on laboratory parameters used to diagnose von Willebrand disorder: potential influence on the diagnosis vs the potential association with risk of thrombosis. Am J Clin Pathol 2005; 124 (6) 910-917
  CrossrefPubMedGoogle Scholar
• 9 Gill JC, Endres-Brooks J, Bauer PJ, Marks Jr WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69 (6) 1691-1695
  CrossrefPubMedGoogle Scholar
• 10 Souto JC, Almasy L, Muñiz-Diaz E , et al. Functional effects of the ABO locus polymorphism on plasma levels of von Willebrand factor, factor VIII, and activated partial thromboplastin time. Arterioscler Thromb Vasc Biol 2000; 20 (8) 2024-2028
  CrossrefPubMedGoogle Scholar
• 11 Matsui T, Titani K, Mizuochi T. Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. J Biol Chem 1992; 267 (13) 8723-8731
  PubMedGoogle Scholar
• 12 Sarode R, Goldstein J, Sussman II, Nagel RL, Tsai HM. Role of A and B blood group antigens in the expression of adhesive activity of von Willebrand factor. Br J Haematol 2000; 109 (4) 857-864
  CrossrefPubMedGoogle Scholar
• 13 Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem 1977; 252 (15) 5538-5546
  PubMedGoogle Scholar
• 14 Stroup DF, Berlin JA, Morton SC , et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15) 2008-2012
  CrossrefPubMedGoogle Scholar
• 15 McGinn T, Wyer PC, Newman TB, Keitz S, Leipzig R, For GG ; Evidence-Based Medicine Teaching Tips Working Group. Tips for learners of evidence-based medicine: 3. Measures of observer variability (kappa statistic). CMAJ 2004; 171 (11) 1369-1373
  CrossrefPubMedGoogle Scholar
• 16 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7 (3) 177-188
  CrossrefPubMedGoogle Scholar
• 17 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414) 557-560
  CrossrefPubMedGoogle Scholar
• 18 Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ 2001; 323 (7304) 101-105
  CrossrefPubMedGoogle Scholar
• 19 Antoni G, Morange PE, Luo Y , et al. A multi-stage multi-design strategy provides strong evidence that the BAI3 locus is associated with early-onset venous thromboembolism. J Thromb Haemost 2010; 8 (12) 2671-2679
  CrossrefPubMedGoogle Scholar
• 20 Kodama J, Seki N, Masahiro S , et al. D-dimer level as a risk factor for postoperative venous thromboembolism in Japanese women with gynecologic cancer. Ann Oncol 2010; 21 (8) 1651-1656
  CrossrefPubMedGoogle Scholar
• 21 Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, Doggen CJ. Venous thrombosis of the upper extremity: effect of blood group and coagulation factor levels on risk. Br J Haematol 2010; 149 (1) 118-123
  CrossrefPubMedGoogle Scholar
• 22 Teixeira Mello TB, Machado TF, Montavão SA, Ozello MC, Annichino-Bizzacchi JM. Assessing the coagulation factor levels, inherited thrombophilia, and ABO blood group on the risk for venous thrombosis among Brazilians. Clin Appl Thromb Hemost 2009; 15 (4) 408-414
  CrossrefPubMedGoogle Scholar
• 23 Lima MB, de Oliveira-Filho AB, Campos JF , et al. Increased risk of venous thrombosis by AB alleles of the ABO blood group and Factor V Leiden in a Brazilian population. Genet Mol Biol 2009; 32 (2) 264-267
  CrossrefPubMedGoogle Scholar
• 24 Paiva SG, Sabino AP, Carvalho MG , et al. Polymorphisms in exons 6 and 7 of the ABO locus and their association with venous thrombosis in young Brazilian patients. Blood Coagul Fibrinolysis 2009; 20 (2) 122-128
  CrossrefPubMedGoogle Scholar
• 25 Santos MS, Guimraes DAM, Paiva SG , et al. ABO blood group genotyping and venous thrombosis in Brazilian women using estrogen. Journal of Thrombosis and Haemostasis. Conference: 22nd Congress of the International Society of Thrombosis and Haemostasis Boston, MA United States 2009
  PubMedGoogle Scholar
• 26 Adamczuk YP, Iglesias Varela ML, Martinuzzo ME, Cerrato GS, Forastiero RR. ABO blood group as a risk factor for venous thrombosis. Journal of Thrombosis and Haemostasis. Conference: 22nd Congress of the International Society of Thrombosis and Haemostasis Boston, MA United States 2009
  PubMedGoogle Scholar
• 27 Canonico M, Olié V, Carcaillon L, Tubert-Bitter P, Scarabin PY ; EStrogen and THromboEmbolism Risk (ESTHER) Study Group. Synergism between non-O blood group and oral estrogen in the risk of venous thromboembolism among postmenopausal women: The ESTHER study. Thromb Haemost 2008; 99 (1) 246-248
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 Miñano A, Ordóñez A, España F , et al. AB0 blood group and risk of venous or arterial thrombosis in carriers of factor V Leiden or prothrombin G20210A polymorphisms. Haematologica 2008; 93 (5) 729-734
  CrossrefPubMedGoogle Scholar
• 29 Clark P, Walker ID, Govan L, Wu O, Greer IA. The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes. Br J Haematol 2008; 140 (2) 236-240
  PubMedGoogle Scholar
• 30 Ohira T, Cushman M, Tsai MY , et al. ABO blood group, other risk factors and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE). J Thromb Haemost 2007; 5 (7) 1455-1461
  CrossrefPubMedGoogle Scholar
• 31 Vormittag R, Bencur P, Ay C , et al. Low-density lipoprotein receptor-related protein 1 polymorphism 663 C > T affects clotting factor VIII activity and increases the risk of venous thromboembolism. J Thromb Haemost 2007; 5 (3) 497-502
  CrossrefPubMedGoogle Scholar
• 32 Hiltunen L, Rautanen A, Rasi V , et al. An unfavorable combination of Factor V Leiden with age, weight, and blood group causes high risk of pregnancy-associated venous thrombosis: a population-based nested case-control study. Thromb Res 2007; 119 (4) 423-432
  CrossrefPubMedGoogle Scholar
• 33 Procare-GEHT Group. ABO blood group but not haemostasis genetic polymorphisms significantly influence thrombotic risk: a study of 180 homozygotes for the Factor V Leiden mutation. Br J Haematol 2006; 135 (5) 697-702
  CrossrefPubMedGoogle Scholar
• 34 Tirado I, Mateo J, Soria JM , et al. The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism. Thromb Haemost 2005; 93 (3) 468-474
  PubMedGoogle Scholar
• 35 Larsen TB, Johnsen SP, Gislum M, Møller CA, Larsen H, Sørensen HT. ABO blood groups and risk of venous thromboembolism during pregnancy and the puerperium. A population-based, nested case-control study. J Thromb Haemost 2005; 3 (2) 300-304
  CrossrefPubMedGoogle Scholar
• 36 Mercier B, Oger E, Le Gal G, Mottier D, Ferec C. Phenotypic but not allelic ABO blood group association with risk of venous thrombosis. Thromb Haemost 2005; 93 (2) 388-389
  PubMedGoogle Scholar
• 37 Morelli VM, De Visser MC, Vos HL, Bertina RM, Rosendaal FR. ABO blood group genotypes and the risk of venous thrombosis: effect of factor V Leiden. J Thromb Haemost 2005; 3 (1) 183-185
  CrossrefPubMedGoogle Scholar
• 38 Carter YM, Caps MT, Meissner MH. Deep venous thrombosis and ABO blood group are unrelated in trauma patients. J Trauma 2002; 52 (1) 112-116
  CrossrefPubMedGoogle Scholar
• 39 Robert A, Aillaud MF, Eschwège V, Randrianjohany A, Scarabin Y, Juhan-Vague I. ABO blood group and risk of venous thrombosis in heterozygous carriers of factor V Leiden. Thromb Haemost 2000; 83 (4) 630-631
  Article in Thieme ConnectPubMedGoogle Scholar
• 40 González Ordóñez AJ, Medina Rodriguez JM, Martín L, Alvarez V, Coto E. The O blood group protects against venous thromboembolism in individuals with the factor V Leiden but not the prothrombin (factor II G20210A) mutation. Blood Coagul Fibrinolysis 1999; 10 (5) 303-307
  CrossrefPubMedGoogle Scholar
• 41 Wautrecht JC, Galle C, Motte S, Dereume JP, Dramaix M. The role of ABO blood groups in the incidence of deep vein thrombosis. Thromb Haemost 1998; 79 (3) 688-689
  PubMedGoogle Scholar
• 42 Nordström M, Lindblad B, Bergqvist D, Kjellström T. A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J Intern Med 1992; 232 (2) 155-160
  CrossrefPubMedGoogle Scholar
• 43 Robinson WM, Roisenberg I. Venous thromboembolism and ABO blood groups in a Brazilian population. Hum Genet 1980; 55 (1) 129-131
  CrossrefPubMedGoogle Scholar
• 44 Jick H, Porter J. Thrombophlebitis of the lower extremities and ABO blood type. Arch Intern Med 1978; 138 (10) 1566-1567
  CrossrefPubMedGoogle Scholar
• 45 Johnson R, Green JR, Charnley J. Pulmonary embolism and its prophylaxis following the Charnley total hip replacement. Clin Orthop Relat Res 1977; 127 (127) 123-132
  PubMedGoogle Scholar
• 46 Talbot S, Wakley EJ, Langman MJ. A19 A29 B, and O blood-groups, Lewis blood-groups, and serum triglyceride and cholesterol concentrations in patients with venous thromboembolic disease. Lancet 1972; 1 (7761) 1152-1154
  PubMedGoogle Scholar
• 47 Arthes FG. An epidemiologic survey of hospitalized cases of venous thrombosis and pulmonary embolism in young women. Milbank Mem Fund Q 1972; 50 (Supp 2) 233-243
  CrossrefPubMedGoogle Scholar
• 48 Westerholm B, Wiechel B, Eklund G. Oral contraceptives, venous thromboembolic disease, and ABO blood type. Lancet 1971; 2 (7725) 664
  PubMedGoogle Scholar
• 49 Talbot S, Wakley EJ, Ryrie D, Langman MJ. ABO blood-groups and venous thromboembolic disease. Lancet 1970; 1 (7659) 1257-1259
  PubMedGoogle Scholar
• 50 Jick H, Slone D, Westerholm B , et al. Venous thromboembolic disease and ABO blood type. A cooperative study. Lancet 1969; 1 (7594) 539-542
  PubMedGoogle Scholar
• 51 Dick W, Schneider W, Brockmueller K, Mayer W. Interrelations of thrombo-embolic diseases and blood group distribution. Thromb Diath Haemorrh 1963; 143: 472-474
  PubMedGoogle Scholar
• 52 Koster T, Blann AD, Briët E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345 (8943) 152-155
  CrossrefPubMedGoogle Scholar
• 53 Wu O, Bayoumi N, Vickers MA, Clark P. ABO(H) blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost 2008; 6 (1) 62-69
  PubMedGoogle Scholar
• 54 Rosendaal FR, Reitsma PH. Genetics of venous thrombosis. J Thromb Haemost 2009; 7 (Suppl. 01) 301-304
  CrossrefPubMedGoogle Scholar
• 55 TRégouët DA, Heath S, Saut N , et al. Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach. Blood 2009; 113 (21) 5298-5303
  CrossrefPubMedGoogle Scholar