European Journal of Internal Medicine 25 (2014) e27–e28

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Letter to the Editor ABO blood groups and venous thromboembolism in a cohort of 65,402 hospitalized subjects Keywords: ABO(H) blood groups Venous thromboembolism Pulmonary embolism

To the Editor: Several studies documented an association between thrombosis and ABO blood groups. In particular, non-O blood groups showed a higher risk of myocardial infarction, angina, peripheral vascular disease, cerebral ischemia, and venous thromboembolism (VTE) than O group [1]. We sought to investigate, in a large sample of hospital admissions, the possible association between blood groups and VTE. The study, approved by our institutional committee, was based on the discharge hospital sheets (DSOs) of patients admitted to the Hospital of Ferrara, region Emilia-Romagna (RER), Italy, between 2000 and 2011, and maintained by the RER general hospitalization database. The DSO contains, for each subject, surname and name, gender, date of birth, date and unit of hospital admission and discharge, main and up to 15 accessory discharge diagnoses, and most important diagnostic procedures, based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM). We selected all patients with first or second discharge ICD-9-CM diagnosis code of: acute pulmonary heart disease (APHD) (415); pulmonary embolism (PE) (415.1); phlebitis and thrombophlebitis (PVT) (451); other venous embolism and thrombosis (OVET) (453). Only the first event was considered for each subject. Total population was divided into subgroups by gender, age, and presence of risk factors: arterial hypertension (401–405), diabetes (250), overweight–obesity (278), dyslipidemia (270–279), homocystinemia (270.4), coagulation defects (286), gout (274), and cancer (140–239). Moreover, we considered all patients in whom, for any reason (i.e., blood donation, transfusion, pregnancy, etc.), a blood group determination was recorded. For analysis, χ2 test, Student t-test, and multiple logistic regression analysis including gender, age, and each of the risk factors reported above, were used. Odds ratios (ORs), with 95% confidence intervals (C.I.), were reported. Significance levels were assumed for p b 0.05. SPSS 13.0 for Windows, SPSS Inc., Chicago, IL, 2004, was used for statistical analysis. During the 12-year period, there were 345,607 admissions to the Hospital of Ferrara, regarding 164,438 different patients. Of these, 65,402 (39.8%) had their blood group determination. Among these patients, 1270 had a PE (mean age = 73 ± 13, 53.5% women), 828 had a PVT (mean age = 72 ± 13, 54.1% women), and 923 had an OVET (mean age = 71 ± 14, 52.5% women). Table 1 shows frequency and VTE risk in different blood groups. In the multivariate analysis, patients

with non-O blood group, and with A-allele, had a significantly higher risk for VTE (Wald = 10.362, p = 0.001, exp B = 1.207, 1.076–1.353) whereas the presence of group O appeared to be protective (p = 0.001, exp B = 0.829, 0.739–0.929). This study shows an increased VTE risk in subjects with non O-group genotypes, ranging from 20% to 35%. The results are in agreement with other studies [2], also regarding subjects with the A-allele. The mechanism by which non-O blood group increases thrombotic risk is unknown. ABO(H) antigens are expressed on red cells and on von Willebrand factor (vWF), and higher levels of factor VIII and vWF have been described in subjects with non-O blood groups [3]. Moreover, blood group may influence VTE in association with factor V Leiden, and non-O blood groups show an additive effect on VTE risk when combined with factor V Leiden and prothrombin mutations [4]. Our study, conducted in a large sample of consecutive hospital admissions, provides further confirmation that non-O blood groups, especially with the A-allele, are independent risk factors for VTE. In the real world of everyday medical practice, the decision of whether to test for thrombophilia patients with VTE is controversial, due to organizational and economic constraints. Thus, given the social utility of having one's own blood group determination, and considering the prevalence of non-O blood groups, this could provide general practitioners a valid, and relatively inexpensive, first-line tool to evaluate thrombophilic risk. Funding The study is supported, in part, by a scientific grant (FAR — Fondo Ateneo Ricerca) from the University of Ferrara, Italy.

Table 1 Frequency and VTE risk of different ABO blood groups. Disease

Blood group

No.

%

Chi square

p

OR

95% lower

C.I. upper

Pulmonary embolism (n = 1270)

O non-O A B AB A-AB B-AB O non-O A B AB A-AB B-AB O non-O A B AB A-AB B-AB

495 775 580 130 65 645 195 300 528 385 95 48 433 143 339 584 453 83 48 501 131

39.0 61.0 45.7 10.2 5.1 50.8 15.4 36.2 63.8 46.5 11.5 5.8 52.3 17.3 36.7 63.3 49.1 9.0 5.2 54.3 14.2

8.32 8.32 6.15 0.20 3.75 10.49 0.50 16.05 16.05 6.17 0.63 6.53 12.15 4.57 15.40 15.40 17.83 2.62 3.15 24.01 00.16

0.003 0.004 0.013 0.676 0.053 0.001 0.478 b0.001 b0.001 0.013 0.425 0.011 0.001 0.032 b0.001 b0.001 0.001 0.105 0.076 0.001 0.687

0.84 1.18 1.15 0.96 1.28 1.20 1.05 0.74 1.33 1.19 1.09 1.46 1.27 1.22 0.76 1.31 1.32 0.83 1.30 1.38 0.96

0.75 1.05 1.03 0.79 0.99 1.07 0.90 0.65 1.15 1.03 0.88 1.09 1.11 1.01 0.66 1.14 1.16 0.66 0.97 1.21 0.79

0.94 1.32 1.28 1.15 1.65 1.34 1.23 0.86 1.54 1.36 1.35 1.96 1.46 1.46 0.87 1.49 1.50 1.04 1.74 1.57 1.16

Phlebitis and thrombophlebitis (n = 828)

Other venous embolism and thrombosis (n = 923)

0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.10.002

e28

Letter to the Editor

Author contributions Dr Gallerani and Dr Reverberi had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Gallerani, Reverberi, and Manfredini Acquisition of data: Gallerani and Reverberi Analysis and interpretation of data: Gallerani, Reverberi, and Manfredini Drafting of the manuscript: Manfredini Critical revision of the manuscript for important intellectual content: Gallerani, Reverberi, and Manfredini Statistical analysis: Gallerani Obtained funding: Gallerani and Manfredini Administrative, technical, or material support: Gallerani and Manfredini Study supervision: Gallerani and Manfredini Conflict of interests The authors state that they have no conflicts of interest.

[2] Dentali F, Sironi AP, Ageno W, Turato S, Bonfanti C, Frattini F, et al. Non-O blood type is the commonest genetic risk factor for VTE: results from a meta-analysis of the literature. Semin Thromb Hemost 2012;38:535–48. [3] Tirado I, Mateo J, Soria JM, Oliver A, Martínez-Sánchez E, Vallvé C, et al. The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism. Thromb Haemost 2005;93:468–74. [4] Spiezia L, Campello E, Bon M, Tison T, Milan M, Simioni P, et al. ABO blood groups and the risk of venous thrombosis in patients with inherited thrombophilia. Blood Transfus 2013;11:250–3.

Massimo Gallerani Department of Medicine, Hospital of Ferrara, Ferrara, Italy Corresponding author at: Department of Medicine, Hospital of Ferrara, Via Aldo Moro 8, I-44121 Cona, Ferrara, Italy. Tel.: +39 0532 236294; fax: +39 0532 236736. E-mail address: [email protected]. Roberto Reverberi Immunohematological and Transfusional Service, Hospital of Ferrara, Ferrara, Italy Roberto Manfredini Clinical Medicine Unit, Hospital and University of Ferrara, Ferrara, Italy

References [1] 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;6:62–9.

29 September 2013

ABO blood groups and venous thromboembolism in a cohort of 65,402 hospitalized subjects.

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