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ABO Blood Group and Vascular Disease: An Update Francesco Dentali, MD1 Anna Paola Sironi, MD1 Massimo Franchini, MD2
Walter Ageno, MD1
1 Department of Clinical and Experimental Medicine, University of
Insubria, Varese, Italy 2 Department of Transfusion Medicine and Hematology, “C. Poma” Hospital, Mantova, Italy
Silvia Crestani, MD2
Address for correspondence Francesco Dentali, MD, U.O. Medicina Interna, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy (e-mail: [email protected]).
Abstract
Keywords
► ABO blood group ► cardiovascular disease ► coronary artery disease ► myocardial infarction ► cerebrovascular disease
It has been well known for many years that the ABO blood group has a major influence on hemostasis, through its influence on von Willebrand factor and, consequently, factor VIII plasma levels. Although the relationship between non-O blood type and the risk of venous thromboembolism is nowadays also well established, the association with arterial thrombotic events (i.e., myocardial infarction [MI] and ischemic stroke) is less well characterized. To elucidate the latter issue, we have conducted a systematic review and 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, 28 studies were finally included in our systematic review. The prevalence of non-O blood group was significantly higher in patients with MI (pooled odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.17–1.40; p < 0.001) and ischemic stroke (pooled OR: 1.17, 95% CI: 1.01–1.35; p ¼ 0.03) than in controls. The restriction of the analysis to high quality studies only confirmed the association with MI (pooled OR: 1.17, 95% CI: 1.03– 1.32) but not with ischemic stroke (pooled OR: 1.28, 95% CI: 0.94–1.74). In conclusion, the results of our meta-analysis confirm the existing literature evidence of a weak association between non-O blood group and vascular arterial thrombosis, in particular myocardial ischemia.
The antigens of the ABO blood group system were the first to be discovered and the knowledge of their structure and function has greatly improved, thanks to more than a century of research.1–3 ABO blood groups are defined by carbohydrate moieties on the extracellular surface of the red blood cell (RBC) membranes.1 However, along with their expression on RBCs, ABO antigens are also highly expressed on the surface of a variety of human cells and tissues, including the epithelium, sensory neurons, platelets, and the vascular endothelium.4 The clinical significance of the ABO blood group system extends beyond transfusion medicine as several reports have suggested an important involvement in the development of neoplastic and cardiovascular disorders.2,3,5 In par-
ticular, the association between ABO blood group and thrombosis has a long history, suggesting that non-O blood group subjects have a higher risk of developing thrombotic episodes of venous or arterial origin.6–9 However, while the key role of non-O blood type as a risk factor for venous thromboembolism (VTE) is nowadays well established,10 no consensus exists regarding its association with arterial thrombosis (i.e., coronary artery disease and cerebrovascular disease).11 Thus, to elucidate these relatively unexplored issues, we have performed an updated systematic review and meta-analysis of the studies reporting the association between ABO blood group and vascular thrombosis, focusing on studies reporting arterial thrombotic events.
published online December 31, 2013
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
Issue Theme Hot Topics V; Guest Editor, Emmanuel J. Favaloro, PhD, FFSc (RCPA).
DOI http://dx.doi.org/ 10.1055/s-0033-1363460. ISSN 0094-6176.
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Semin Thromb Hemost 2014;40:49–59.
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Methods A protocol was prospectively developed, detailing the specific objectives, criteria for study selection, approach to assess study quality, outcomes, and statistical methods. The results of this meta-analysis are presented according to the Metaanalysis of Observational Studies in Epidemiology (MOOSE) group guidelines on reporting meta-analyses of observational studies.12
Data Extraction and Study Validity Assessment
Study Identification We tried to identify all published studies that evaluated the association between ABO(H) blood group and arterial vascular events (myocardial infarction [MI] and stroke) using the MEDLINE (1946–July week 3, 2013) and EMBASE (1980–July week 3, 2013) databases. The search strategy was developed without any language restriction and used the keywords and subject headings presented in ►Table 1. We supplemented our search by manually reviewing abstracts books from the Congress of the International Society on Thrombosis and Haemostasis (ISTH) (2009–2013) and the reference lists of all retrieved articles, manually searching recent issues of journals on thrombosis and hemostasis, recent reviews on this topic for additional published, or unpublished trials.
Study Selection Study selection was performed independently by two reviewers, with disagreements resolved through discussion, and by the opinion of a third reviewer, if necessary. Studies were included if they met the following criteria: (1) the study included patients with MI or stroke; (2) Stroke and MI were objectively diagnosed (e.g., stroke diagnosed with brain computed tomography, magnetic resonance or angiography; MI diagnosed according to the commonly accepted criteria for MI at the time of study publication); (3) the study population had been ABO(H) typed; (4) separate data for patients with or without arterial cardiovascular events were provided; and (5) data defining the blood groups as either A, B, AB, and O, group O, and non-O group, or group A and non-A group were extractable. Studies including patients with arterial cardiovascular events diagnosed only on clinical basis and studies including patients with angina and transient ischemic attack
Table 1 MEDLINE search strategy Database: Ovid MEDLINE(R) (1946 to July Week 3, 2013) 1. Blood group antigens/(14863) 2. exp ABO blood group system/(13313) 3. Myocardial infarction/(140375) 4. Myocardial ischemia.tw.(20113) 5. Acute coronary syndrome/(6773) 6. Stroke/(56210) 7. Brain ischemia/(35671) 8. 1 or 2 (26526) 9. 3 or 4 or 5 or 6 or 7 (240714) 10. 8 and 9 (85)
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(TIA) were not included in the meta-analysis. Case reports, case series of patients, reviews, and nonhuman studies were also excluded. When multiple studies on a single study had been published, we decided to use the latest publication and to supplement it, if necessary, with data from the earlier publications. To assess the agreement between reviewers for study selection, we used the kappa (κ) statistic, which measures agreement beyond chance.13
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Data Extraction Two reviewers independently extracted the following data: (1) study characteristics (year of publication, design, and study center); (2) patients’ and controls’ characteristics (number of subjects studied, mean age, variation in age, gender, and race); (3) prevalence of blood group in patients with arterial cardiovascular events and in controls. Disagreement was resolved by consensus and by the opinion of a third reviewer, if necessary. We did not attempt to contact the authors of the studies to obtain the unpublished data.
Sensitivity Analyses We used the Newcastle–Ottawa Scale (NOS) to assess the methodological quality of each study.14 We awarded cohort studies a maximum of 4 stars for selection, 2 stars for comparability, and 3 stars for outcome assessment, with more stars indicating better quality. For case-control studies, the maximum score for selection, comparability, and exposure assessment was 4, 2, and 3, respectively. The maximum possible score was 9. Furthermore, as additional quality item we also considered the publication separately prospective and retrospective studies.
Data Synthesis and Data Analyses Statistical Analyses The pooled odds ratio (OR) of the association among different blood groups and genotypes, and arterial cardiovascular events was calculated using Review Manager (RevMan; version 5.0 for Windows, Oxford, England; The Cochrane Collaboration, 2008). OR and 95% confidence intervals (CIs) were calculated using a random effects model (DerSimonian and Laird method).15 The appropriateness of pooling data across studies was assessed with the use of the Cochran Q and the I2 test for heterogeneity, which measures the inconsistency across study results and describes the proportion of total variation in study estimates that is due to heterogeneity rather than sampling error.16 The I2 value provides an estimate of the amount of variance across studies due to heterogeneity rather than chance. I2 < 30% indicates mild heterogeneity, 30 to 50% indicates moderate, and more than 50% indicates severe heterogeneity. When heterogeneity was present, we planned to repeat the analyses removing one study at a time to assess the source of heterogeneity. Sensitivity analyses, including high quality studies (studies with NOS 6) and prospective studies, were performed.
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The proportion arterial cardiovascular events in the population that could be attributed to non-O blood group (population attributable risk [PAR]) were estimated as follows: PAR ¼ 100 (prevalence [OR – 1]/prevalence [OR – 1] þ 1) 0.1074 For this calculation, we used the fixed effects model, and we estimated the prevalence of exposure as the genotype frequency among control subjects as previously described.17 Presence of publication bias was explored using funnel plots of effect size against standard error.18
Results
Dentali et al.
p < 0.001), ►Fig. 1A. Heterogeneity among the studies was significant (Cochran Q < 0.001; I2 ¼ 68%). When we repeated the analyses removing one study at a time, heterogeneity did not significantly change (data not shown). Funnel plot of OR versus standard appeared symmetric, thus suggesting the absence of a publication bias, (►Fig. 2A). Sensitivity analysis including only high quality studies gave a significant but slightly lower association between non-O blood groups and MI with a pooled OR of 1.17 (95% CI: 1.03–1.32). The same was true for the sensitivity analysis including only prospective that gave a significant but low association between non-O blood groups and MI with a pooled OR of 1.09 (95% CI: 1.02–1.16). Among patients with an MI, the estimated attributable risk conferred by non-O blood group was 9.7%.
Study Identification and Selection We identified 182 studies using our search strategy: 85 from MEDLINE and 97 from EMBASE. No additional unpublished studies were identified using ISTH abstracts books. We excluded 137 studies after screening the title and abstract using the predefined inclusion and exclusion criteria and deleting duplicates; 45 studies were retrieved for more detailed evaluation. The interobserver agreement for the study selection was good, with a κ of 0.84. Ten studies were identified through manual review of the references of included studies and recent reviews. Of the 55 retrieved studies, 27 were subsequently excluded because they did not provide separate data on the prevalence of blood group in patients with cardiovascular complications and in controls, lacked a control population, or did not contain original data. Therefore, 28 studies were finally included in our systematic review.19–46
Study Characteristics Twenty two studies included patients with MI and six studies included patients with stroke. The number of patients with MI ranged from 29 to 2,708 and the number of controls in these studies (including blood donors) ranged from 51 to 177,000 for a total of more than 10,000 MI patients and more than 500,000 controls. The number of patients with stroke ranged from 50 to 600 and the number of controls in these studies (including blood donors) ranged from 88 to 14,304 for a total of more than 1,800 stroke patients, and nearly 17,500 controls. Baseline characteristics of included studies are summarized in ►Table 2.
Study Quality ►Table 3 shows the assessment of methodological quality for the 22 studies included in the systematic review. The total scores ranged from 0 to 8. Higher scores indicate better quality. Three received 0 points in each item. Only one study received 8 points.
ABO Blood Group and Myocardial Infarction Non-O blood group was present in 6,470 of the 10,412 patients with MI (62.1%) and in 282,465, of the 526,356 (53.7%) controls, thus resulting in a significantly higher prevalence of non-O blood group in cases than in controls with a pooled OR of 1.28 (95% CI: 1.17–1.40;
ABO Blood Group and Ischemic Stroke All the six studies evaluating the association between ABO blood group and ischemic stroke were case-control studies. Non-O blood group was present in 1,075 of the 1,819 patients with ischemic stroke (62.5%) and in 10,176 of the 17,305 (53.7%) controls, thus resulting in a significantly higher prevalence of non-O blood group in cases than in controls with a pooled OR of 1.17 (95% CI: 1.01–1.35; p ¼ 0.03), ►Fig. 1B. Heterogeneity among the studies was not significant (Cochran Q ¼ 0.30; I2 18%). Funnel plot of OR versus standard appeared asymmetric, with an absence of studies in the bottom left hand corner, (►Fig. 2B). When we repeated the analysis including only high quality studies (NOS 6) prevalence of non-O blood group was not anymore significant with a resulting a pooled OR of 1.28 (95% CI: 0.94–1.74) Among patients with an ischemic stroke, the estimated attributable risk conferred by non-O blood group was 7.45%.
Discussion It has been known for many years that the ABO blood type has a profound influence on hemostasis, being a major determinant of the von Willebrand factor (VWF) and, consequently, of factor VIII (FVIII) plasma levels.47–49 In particular, VWF levels are approximately 25% higher in individuals who are blood group other than O.50 Thus, as VWF and FVIII are well established risk factors for thrombosis,51–54 it is reasonable that several experimental and clinical studies have assessed so far whether ABO blood type could influence the risk of developing arterial or venous thrombotic events.2,3 However, while the positive association between non-O blood group and the risk of developing VTE is now well known and has been finally established in two recent meta-analyses,10,11 the non-O blood group-related increase in arterial thrombotic risk is not so clear, probably due to the scarcity of well-designed studies. In 2008, Wu et al11 published a systematic review and meta-analysis on the link between vascular disease and ABO blood group and observed also a consistent relation with MI (OR: 1.25, 95% CI: 1.14–1.36). More recently, He et al55 conducted a meta-analysis of data from the Health Professionals Follow-up Study (HPFS), Nurses’ Health Study (NHS) and five other prospective cohort studies in which several Seminars in Thrombosis & Hemostasis
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Controls with no history of vascular disease Healthy age- and sex-matched control subjects of a similar racial/social class mix to the patient group with no history of stroke, TIA, peripheral vascular, or ischemic heart disease. NS
Danish blood donors
Patients with stroke confirmed with brain CT.
Consecutive patients with acute stroke or TIA of arterial origin who underwent a brain CT.
Patients with clinical diagnosis confirmed by unspecified neuroradiology.
Patients with clinical diagnosis of stroke confirmed by carotid angiography.
White patients of Danish descent selected from 2 prospective studies (Copenhagen General Population Study, Copenhagen City Heart Study) who developed an MI (defined basing on ICD codes).
Bayoumi et al (2006)43
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Clark et al (2005)44
Sostarić et al (1991)45
Larsen et al (1977)46
Sode et al (2013)19
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2,708/63,279
481/14,304
–
Patients with events before 1977
50/1,883
148/88
445/327
94/103 45♂, 49♀ 52♂, 51♀
600/600 385♂, 215♀
n° C/Ctrl (gender if specified)
NS
Patients with atrial fibrillation, valvular heart disease, connective tissue disease, or thrombus on echocardiography
NS
Patients with a definite nonatherosclerotic cause of the stroke, such as a mechanical heart valve, endocarditis, or dissection, as well as patients older than 75 years or using oral anticoagulants and patients with hemorrhagic stroke.
–
Exclusion criteria
20–100
NS
NS
58.3 (range 25–70) vs. 57 (range 24–71)
NS
55 (12) vs. 56 (12)
56 (10)
Mean age and/or age range
ABO Blood Group and Vascular Disease
Patients from the same cohorts of cases who did not develop an MI
Population controls, that is, neighbors or friends of the patients. They were age and sex matched, did not have a history of stroke, and were not related to the patient
White patients without clinical atherothrombotic disease, matched for age ( 1 year), sex, and geographical residence area randomly selected from participants in a populationbased health survey
White patients presenting with new or recurrent objectively diagnosed (with CT) of acute ischemic stroke before the age of 70 years.
Consecutive patients with a first episode of atherosclerotic stroke or transient ischemic attack (included only if the neurologic deficit was witnessed by a neurologist) who underwent a CT of the brain.
Controls
Cases
Patients’ description
van Schie et al (2010)42
Hanson et al (2012)41
Study year, reference
Table 2 Baseline characteristics
52 Dentali et al.
175/3,146
172/1,011
History of overt cardiovascular disease at baseline Patients with a previous MI
Women contacted by random-digit dialing, stratified for age, index year of MI and area of residence. Consecutive patients with coronary arteries angiographically normal or with stenoses of less than 10% and with neither symptoms nor signs of old or acute MI Healthy Caucasian people without a history of thromboembolic events or tendency to bleed matched to the cases by age and sex Subjects form the study who did not have an MI
Participants at the Northwick Park Heart Study (males) who did not experience an MI and sudden coronary death during follow up
Population from RATIO study. Young women with a first acute MI from university and regional hospitals.
Consecutive patients angiographically examined with either prior or acute MI.
Survivors of an acute MI occurred at least 2 months before inclusion in the study.
Survivors from a prospective study (Copenhagen Male Study) who had MI during follow-up.
Participants at the Northwick Park Heart Study (males) who experienced an MI and sudden coronary death during follow-up.
von Beckerath et al (2004)23
Nydegger et al (2003)24
Suadicani et al (2000)25
Meade et al (1994)26
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177/89 155♂, 22♀ 79♂, 10♀
793/340 614♂, 179♀ 257♂, 83♀
200/626
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NS
NS
NS
476/203 382♂, 94♀ 168♂, 35♀
Tanis et al (2006)22
NS
Age and sex-matched blood donors Free of known CAD: detailed medical history and physical examination was performed to exclude the possibility of CAD
Patients with acute ST elevation MI and without known CAD.
170/170
Sari et al (2008)21
NS
Subjects without MI
Patients with confirmed MI.
n° C/Ctrl (gender if specified)
Sheikh et al (2009)20
Exclusion criteria
Controls
Patients’ description
Cases
Study year, reference
Table 2 (Continued)
40–64
63 53–75
57 32–72
(Continued)
Case: 62,6 11,6 Ctrl: 63,4 10,3
18–49
56.7 11.7
NS
Mean age and/or age range
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NS
NS
Patients of similar age discharged from same hospital for non-MI diagnosis. Subjects who were otherwise healthy. Blood donors from Copenhagen
Individuals from Belgian army and police staff without MI
Women younger than 46 years at the time of diagnosis who were hospitalized during the first 6 months of 1975 with a discharge diagnosis of MI (ICD codes).
Consecutive in patients with acute MI (1967–1970), who were blood grouped after admission. MI was diagnosed with 2 of 3 of the following criteria: characteristic history, ECG, or raised serum transaminase. In fatal cases the diagnosis was verified by autopsy.
Patients from Belgian army and police staff with possible angina and MI identified with a questionnaire and revaluated with medical examination.
Patients with MI from the Israeli Ischemic Heart Disease Project (Jewish male government employees, 40 years, designated as being “at risk” for MI in 1963) followed up for 5 years.
Jick et al (1978)30
Viskum et al (1975)31
Van Houte et al (1972)32
Medalie et al (1971)33
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415/9,057
643/24,511
950/14,304 558♂, 392 ♀
29/51
255/802
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NS
NS
197/81,985
481/7,181
n° C/Ctrl (gender if specified)
40
NS
NS
< 46
44 (cases), 42 (controls) 25–49
NS
40–59
Mean age and/or age range
ABO Blood Group and Vascular Disease
Subjects from the same cohort without MI at the end of follow-up.
History of a serious chronic illness or an illness that contraindicates oral contraceptive use.
Women with similar age and from the same area without MI
Women younger than 50 years admitted with acute MI.
Rosenberg et al (1983)28
NS
Sample of the German population
Patients hospitalized with MI.
Platt et al (1985)29
Men whose longest held occupation was in the armed services or with occupation not known.
Patients included in the British regional heart study (men randomly selected from the age-sex registers of group general practices in 24 towns) who did not develop a fatal or nonfatal MI
Patients included in the British regional heart study (men randomly selected from the age-sex registers of group general practices in 24 towns) who developed a fatal or nonfatal MI.
Whincup et al (1990)27
Exclusion criteria
Controls
Patients’ description
Cases
Study year, reference
Table 2 (Continued)
54 Dentali et al.
NS
Cases with incomplete records (no ECG) and atypical clinical features. Coexistent diseases such as aortic-valve disease, diabetes mellitus, polycythemia, hypothyroidism.
Blood donors from the same area Consecutively registered blood donors from Aberdeen city New donors in the same area
General population (Australian Defense Force, 1950) Random sample from company employees. Matched by age, sex, payroll classification (i.e., wage or salary), and geographical location
Patients with CHD admitted to hospital or seen in private consultant practice.
Patients from Aberdeen with MI
Patients with MI sampled from anticoagulant clinics and private patients attending clinical pathologists in private practice.
Patients from a trial of long-term treatment with anticoagulants for an MI.
Employees of the DuPont company (1956–1958) who developed an MI.
Maurer et al (1969)35
Allan et al (1968)37
Bronte-Stewart et al (1962)38
Denborough et al (1962)39
Pell et al (1961)40
226/245
17–64
NS
NS
632/6,366
205/177,000
NS
NS
NS
NS
Mean age and/or age range
202/7,092
286/117,287
204/5,000
816/6,611
n° C/Ctrl (gender if specified)
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Abbreviations: C, cases; Ctrl, controls; CT, computed tomography; CPHA, The Commission on Professional and Hospital Activities; ICD, International Classification of Diseases; MI, myocardial infarction; M-a, metaanalysis; NS, not specified; RATIO, Risk of Arterial Thrombosis in relation with Oral contraceptive use study; OC, oral contraceptive; WHO, World Health Organization.
Previous MI
NS
NS
NS
Local blood donor data
Consecutive male patients admitted for acute MI (from May to July 1954).
Oliver et al (1969)34
NS
Other US Army men (patients with nonvascular conditions or healthy)
Military records of men who had MI while serving in the US army during 1939–1945 World War.
Nefzger et al (1969)36
Exclusion criteria
Controls
Patients’ description
Cases
Study year, reference
Table 2 (Continued)
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Table 3 Newcastle-Ottawa Scale Case–control studies Study (year), reference
Selection (max 4)
Comparability (max 2)
Exposure (max 3)
Total
STROKE Hanson et al (2012)41 Van Schie et al (2009)
42
Clark et al (2005)44 Bayoumi et al (2006) Sostarić et al (1991)
43
45
Larsen et al (1977)46
4
2
3
9
4
1
1
6
4
2
1
7
1
0
1
2
1
0
1
2
1
0
1
2
MI Sheikh et al (2009) Sari et al (2008)
20
21
Tanis et al (2006)22 Von Beckerath et al (2004) Nydegger et al (2003)
23
24
Platt et al (1985)29 Rosenberg et al (1983) Jick et al (1978)
28
30
0
0
0
0
3
2
2
7
2
2
1
5
2
1
3
6
1
0
0
1
1
0
1
2
1
1
3
5
2
1
3
6
31
3
0
1
4
Maurer et al (1969)35
1
0
1
2
1
0
0
1
1
0
3
4
3
0
1
4
3
1
1
5
1
0
0
1
3
1
2
6
2
2
1
5
Outcome (max 3)
Total
Viskum et al (1975)
Nefzger et al (1969)
36
Van Houte et al (1972)
32
Oliver et al (1969)34 Allan et al (1968)
37
Denborough et al (1962)
39
Bronte-Stewart et al(1962)38 Pell et al (1961)
40
Cohort studies Study (year), reference
Selection (max 4)
Comparability (max 2) MI
Sode et al (2013)19 Suadicani et al (2000)
25
Meade et al (1994)26 Whincup et al (1990) Medalie et al (1971)
27
33
4
2
2
8
4
1
1
6
4
1
2
7
3
2
1
6
2
1
1
4
thousands of participants were enrolled and they concluded that individuals with non-O blood group had an 11% (RR 1.11, 95% CI: 1.05–1.18, p ¼ 0.001) increased risk of developing coronary heart disease (CHD) as compared with O blood group individuals. The results of our meta-analysis are in line with these two previous observations: indeed, among the 22 studies included in the analysis, we found a significantly higher prevalence of non-O blood group in MI cases than in controls (pooled OR: 1.28, 95% CI: 1.17–1.40), which was still present after considering only high quality and prospective Seminars in Thrombosis & Hemostasis
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studies (pooled OR: 1.17 [95% CI: 1.03–1.32] and 1.09 [95% CI: 1.02–1.16], respectively). As regarding the association between ABO blood type and ischemic stroke, the published literature evidences are even scarcer. The largest published study is that by Hanson et al,41 who recently performed a case–control study on 600 cases and controls, and did not find an association between ABO phenotype or genotype and stroke (OR: 0.9, 95% CI: 0.7–1.2). Their results were in contrast with the above mentioned metaanalysis,11 who observed a slight but statistically significant
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Dentali et al.
Fig. 1 Forest plot evaluating the association between (A) MI (B) or ischemic stroke and the prevalence of non-0 blood group. MI, myocardial infarction.
Fig. 2 Funnel plot of odds ratio versus standard error for ABO blood group for (A) MI or (B) ischemic stroke. MI, myocardial infarction.
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association (OR: 1.14, 95% CI: 1.01–1.27). The pooled OR (1.17, 95% CI: 1.01–1.35) calculated evaluating the six studies included in our meta-analysis is almost identical to that by Wu et al.11 However, the lack of significance after inclusion of only high quality studies (OR: 1.28, 95% CI: 0.94–1.74) underlines the weakness of this association. Our meta-analysis has some potential limitations. First, the application of formal meta-analytic methods to observational studies is controversial, because bias implicit in the study design may misrepresent the strength of associations within the data.12 To minimize this potential bias, we included only studies in which the diagnosis of arterial cardiovascular event was objectively confirmed. Second, studies included in our meta-analysis have different inclusion and exclusion criteria, and to combine results across studies may be inappropriate. Furthermore, the heterogeneity among the studies was significant, suggesting caution in the interpretation of the results. However, we decided to combine our results using the random-effect model, an approach that takes into account the variance among the studies. Finally, since we did not find unpublished studies, the presence of publication bias could not be excluded. In the stroke studies, the funnel plot of OR versus standard error was slightly asymmetric with an absence of studies in the bottom left hand corner suggesting that a few small studies finding a higher prevalence of O blood group in stroke patients compared with controls were not published. Thus, publication of these studies would affect the magnitude of association between non-O blood group and stroke. In conclusion, the results of our systematic review and meta-analysis document the existence of an association between non-O blood group and the arterial vascular risk. However, such association seems to be less strong than that between non-O blood group and VTE.10 This is particularly evident for ischemic stroke where the already weak association lacks of significance after the restriction of the analysis to only high quality studies. Further prospective studies on large populations of patients are required to better clarify the role of ABO blood type in the vascular thrombotic risk. Such studies should also unravel the interaction of ABO blood type with other concomitant risk factors for arterial thrombosis.
7 Jick H, Slone D, Westerholm B, et al. Venous thromboembolic
8
9 10
11
12
13
14
15 16 17
18
19
20
21
22
23
References 1 Storry JR, Olsson ML. The ABO blood group system revisited: a 2
3
4 5
6
review and update. Immunohematol 2009;25(2):48–59 Franchini M, Favaloro EJ, Targher G, Lippi G. ABO blood group, hypercoagulability, and cardiovascular and cancer risk. Crit Rev Clin Lab Sci 2012;49(4):137–149 Franchini M, Liumbruno G. Beyond immunohaematology: the role of ABO blood group in human diseases. Clin Chem Lab Med 2013; doi: 10.2450/2013.0152-13 Eastlund T. The histo-blood group ABO system and tissue transplantation. Transfusion 1998;38(10):975–988 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 Bronte-Stewart B, Botha MC, Krut LH. ABO blood groups in relation to ischaemic heart disease. BMJ 1962;1(5293):1646–1650
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25
26
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disease and ABO blood type. A cooperative study. Lancet 1969; 1(7594):539–542 Westerholm B, Wiechel B, Eklund G. Oral contraceptives, venous thromboembolic disease, and ABO blood type. Lancet 1971; 2(7725):664 Mourant AE, Kopeć AC, Domaniewska-Sobczak K. Blood-groups and blood-clotting. Lancet 1971;1(7692):223–227 Dentali F, Sironi AP, Ageno W, 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(5):535–548 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 Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Metaanalysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283(15):2008–2012 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 Wells GA, Shea B, O’Connell D, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in metaanalyses. Available at:http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed August 14, 2013 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7(3):177–188 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557–560 Dentali F, Gianni M, Agnelli G, Ageno W. Association between inherited thrombophilic abnormalities and central venous catheter thrombosis in patients with cancer: a meta-analysis. J Thromb Haemost 2008;6(1):70–75 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 Sode BF, Allin KH, Dahl M, Gyntelberg F, Nordestgaard BG. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ 2013;185(5):E229–E237 Sheikh MK, Bahari MB, Yusoff NM, Knight A. Association of ABO blood group B with myocardial infarction. J Coll Physicians Surg Pak 2009;19(8):514–517 Sari I, Ozer O, Davutoglu V, Gorgulu S, Eren M, Aksoy M. ABO blood group distribution and major cardiovascular risk factors in patients with acute myocardial infarction. Blood Coagul Fibrinolysis 2008;19(3):231–234 Tanis B, Algra A, van der Graaf Y, Helmerhorst F, Rosendaal F. Procoagulant factors and the risk of myocardial infarction in young women. Eur J Haematol 2006;77(1):67–73 von Beckerath N, Koch W, Mehilli J, et al. ABO locus O1 allele and risk of myocardial infarction. Blood Coagul Fibrinolysis 2004;15(1):61–67 Nydegger UE, Wuillemin WA, Julmy F, Meyer BJ, Carrel TP. Association of ABO histo-blood group B allele with myocardial infarction. Eur J Immunogenet 2003;30(3):201–206 Suadicani P, Hein HO, Gyntelberg F. Socioeconomic status, ABO phenotypes and risk of ischaemic heart disease: an 8-year followup in the Copenhagen Male Study. J Cardiovasc Risk 2000;7(4): 277–283 Meade TW, Cooper JA, Stirling Y, Howarth DJ, Ruddock V, Miller GJ. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 1994;88(3):601–607 Whincup PH, Cook DG, Phillips AN, Shaper AG. ABO blood group and ischaemic heart disease in British men. BMJ 1990;300(6741): 1679–1682 Rosenberg L, Miller DR, Kaufman DW, et al. Myocardial infarction in women under 50 years of age. JAMA 1983;250(20):2801–2806
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29 Platt D, Mühlberg W, Kiehl L, Schmitt-Rüth R. ABO blood group
44 Clark P, Meiklejohn DJ, O’Sullivan A, Vickers MA, Greaves M. The
system, age, sex, risk factors and cardiac infarction. Arch Gerontol Geriatr 1985;4(3):241–249 Jick H, Dinan B, Herman R, Rothman KJ. Myocardial infarction and other vascular diseases in young women. Role of estrogens and other factors. JAMA 1978;240(23):2548–2552 Viskum K, Astvad K, Fabricius-Bjerre N, Kjaerulff J. ABO blood groups and acute myocardial infarction. Dan Med Bull 1975;22(3):126–128 Van Houte O, Kesteloot H. An epidemiological survey of risk factors for ischemic heart disease in 42,804 men. I. Serum cholesterol value. Acta Cardiol 1972;27(5):527–564 Medalie JH, Levene C, Papier C, et al. Blood groups, myocardial infarction and angina pectoris among 10,000 adult males. N Engl J Med 1971;285(24):1348–1353 Oliver MF, Geizerova H, Cumming RA, Heady JA. Serum-cholesterol and ABO and rhesus blood-groups. Lancet 1969;2(7621):605–606 Maurer B, Hickey N, Mulcahy R. ABO and Rh blood groups in patients with coronary heart disease. Ir J Med Sci 1969;8(3):105–108 Nefzger MD, Hrubec Z, Chalmers TC. Venous thromboembolism and blood-group. Lancet 1969;1(7600):887 Allan TM, Dawson AA. ABO blood groups and ischaemic heart disease in men. Br Heart J 1968;30(3):377–382 Bronte-Stewart B, Botha MC, Krut LH. ABO blood groups in relation to ischaemic heart disease. BMJ 1962;1(5293):1646–1650 Denborough M. Blood groups and ischaemic heart disease. BMJ 1962;II:927 Pell S, D’Alonzo CA. A three-year study of myocardial infarction in a large employed population. JAMA 1961;175:463–470 Hanson E, Karlsson S, Jood K, Nilsson S, Blomstrand C, Jern C. No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes. Thromb Res 2012;130(3):339–342 van Schie MC, de Maat MP, de Groot PG, et al. Active von Willebrand factor and the risk of stroke. Atherosclerosis 2010; 208(2):322–323 Bayoumi NA, Macleod MJ, Greaves M, Vickers MA. ABO blood groups in cerebrovascular accident patients. Br J Haematol 2006; 133(S1):51
relationships of ABO, Lewis and Secretor blood groups with cerebral ischaemia of arterial origin. J Thromb Haemost 2005; 3(9):2105–2108 Sostarić V, Bozicević D, Brinar V, Grbavac Z. Hereditary antigen characteristics of blood in ischemic cerebrovascular accident. Neurol Croat 1991;40(1):3–11 Larsen S, Anthonisen B, Marquardsen J. Cerebral infarction, cerebral haemorrhage, and ABO blood-groups. Lancet 1977;1(8020): 1064 Preston AE, Barr A. The plasma concentration of factor VIII in the normal population. Br J Haematol 1964;10:238–245 Moeller A, Weippert-Kretschmer M, Prinz H, Kretschmer V. Influence of ABO blood groups on primary hemostasis. Transfusion 2001;41(1):56–60 O’Donnell JS, Laffan MA. The relationship between ABO histoblood group, factor VIII and von Willebrand factor. Transfus Med 2001;11(4):343–351 Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ Jr, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987;69(6):1691–1695 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 Folsom AR, Wu KK, Rosamond WD, Sharrett AR, Chambless LE. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997;96(4):1102–1108 Whincup PH, Danesh J, Walker M, et al. von Willebrand factor and coronary heart disease: prospective study and meta-analysis. Eur Heart J 2002;23(22):1764–1770 Franchini M, Makris M. Non-O blood group: an important genetic risk factor for venous thromboembolism. Blood Transfus 2013; 11(2):164–165 He M, Wolpin B, Rexrode K, et al. ABO blood group and risk of coronary heart disease in two prospective cohort studies. Arterioscler Thromb Vasc Biol 2012;32(9):2314–2320
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ABO Blood Group and Vascular Disease
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ABO Blood Group and Vascular Disease: An Update Francesco Dentali, MD1 Anna Paola Sironi, MD1 Massimo Franchini, MD2
Walter Ageno, MD1
1 Department of Clinical and Experimental Medicine, University of
Insubria, Varese, Italy 2 Department of Transfusion Medicine and Hematology, “C. Poma” Hospital, Mantova, Italy
Silvia Crestani, MD2
Address for correspondence Francesco Dentali, MD, U.O. Medicina Interna, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy (e-mail: [email protected]).
Abstract
Keywords
► ABO blood group ► cardiovascular disease ► coronary artery disease ► myocardial infarction ► cerebrovascular disease
It has been well known for many years that the ABO blood group has a major influence on hemostasis, through its influence on von Willebrand factor and, consequently, factor VIII plasma levels. Although the relationship between non-O blood type and the risk of venous thromboembolism is nowadays also well established, the association with arterial thrombotic events (i.e., myocardial infarction [MI] and ischemic stroke) is less well characterized. To elucidate the latter issue, we have conducted a systematic review and 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, 28 studies were finally included in our systematic review. The prevalence of non-O blood group was significantly higher in patients with MI (pooled odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.17–1.40; p < 0.001) and ischemic stroke (pooled OR: 1.17, 95% CI: 1.01–1.35; p ¼ 0.03) than in controls. The restriction of the analysis to high quality studies only confirmed the association with MI (pooled OR: 1.17, 95% CI: 1.03– 1.32) but not with ischemic stroke (pooled OR: 1.28, 95% CI: 0.94–1.74). In conclusion, the results of our meta-analysis confirm the existing literature evidence of a weak association between non-O blood group and vascular arterial thrombosis, in particular myocardial ischemia.
The antigens of the ABO blood group system were the first to be discovered and the knowledge of their structure and function has greatly improved, thanks to more than a century of research.1–3 ABO blood groups are defined by carbohydrate moieties on the extracellular surface of the red blood cell (RBC) membranes.1 However, along with their expression on RBCs, ABO antigens are also highly expressed on the surface of a variety of human cells and tissues, including the epithelium, sensory neurons, platelets, and the vascular endothelium.4 The clinical significance of the ABO blood group system extends beyond transfusion medicine as several reports have suggested an important involvement in the development of neoplastic and cardiovascular disorders.2,3,5 In par-
ticular, the association between ABO blood group and thrombosis has a long history, suggesting that non-O blood group subjects have a higher risk of developing thrombotic episodes of venous or arterial origin.6–9 However, while the key role of non-O blood type as a risk factor for venous thromboembolism (VTE) is nowadays well established,10 no consensus exists regarding its association with arterial thrombosis (i.e., coronary artery disease and cerebrovascular disease).11 Thus, to elucidate these relatively unexplored issues, we have performed an updated systematic review and meta-analysis of the studies reporting the association between ABO blood group and vascular thrombosis, focusing on studies reporting arterial thrombotic events.
published online December 31, 2013
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
Issue Theme Hot Topics V; Guest Editor, Emmanuel J. Favaloro, PhD, FFSc (RCPA).
DOI http://dx.doi.org/ 10.1055/s-0033-1363460. ISSN 0094-6176.
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Semin Thromb Hemost 2014;40:49–59.
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Methods A protocol was prospectively developed, detailing the specific objectives, criteria for study selection, approach to assess study quality, outcomes, and statistical methods. The results of this meta-analysis are presented according to the Metaanalysis of Observational Studies in Epidemiology (MOOSE) group guidelines on reporting meta-analyses of observational studies.12
Data Extraction and Study Validity Assessment
Study Identification We tried to identify all published studies that evaluated the association between ABO(H) blood group and arterial vascular events (myocardial infarction [MI] and stroke) using the MEDLINE (1946–July week 3, 2013) and EMBASE (1980–July week 3, 2013) databases. The search strategy was developed without any language restriction and used the keywords and subject headings presented in ►Table 1. We supplemented our search by manually reviewing abstracts books from the Congress of the International Society on Thrombosis and Haemostasis (ISTH) (2009–2013) and the reference lists of all retrieved articles, manually searching recent issues of journals on thrombosis and hemostasis, recent reviews on this topic for additional published, or unpublished trials.
Study Selection Study selection was performed independently by two reviewers, with disagreements resolved through discussion, and by the opinion of a third reviewer, if necessary. Studies were included if they met the following criteria: (1) the study included patients with MI or stroke; (2) Stroke and MI were objectively diagnosed (e.g., stroke diagnosed with brain computed tomography, magnetic resonance or angiography; MI diagnosed according to the commonly accepted criteria for MI at the time of study publication); (3) the study population had been ABO(H) typed; (4) separate data for patients with or without arterial cardiovascular events were provided; and (5) data defining the blood groups as either A, B, AB, and O, group O, and non-O group, or group A and non-A group were extractable. Studies including patients with arterial cardiovascular events diagnosed only on clinical basis and studies including patients with angina and transient ischemic attack
Table 1 MEDLINE search strategy Database: Ovid MEDLINE(R) (1946 to July Week 3, 2013) 1. Blood group antigens/(14863) 2. exp ABO blood group system/(13313) 3. Myocardial infarction/(140375) 4. Myocardial ischemia.tw.(20113) 5. Acute coronary syndrome/(6773) 6. Stroke/(56210) 7. Brain ischemia/(35671) 8. 1 or 2 (26526) 9. 3 or 4 or 5 or 6 or 7 (240714) 10. 8 and 9 (85)
Seminars in Thrombosis & Hemostasis
(TIA) were not included in the meta-analysis. Case reports, case series of patients, reviews, and nonhuman studies were also excluded. When multiple studies on a single study had been published, we decided to use the latest publication and to supplement it, if necessary, with data from the earlier publications. To assess the agreement between reviewers for study selection, we used the kappa (κ) statistic, which measures agreement beyond chance.13
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Data Extraction Two reviewers independently extracted the following data: (1) study characteristics (year of publication, design, and study center); (2) patients’ and controls’ characteristics (number of subjects studied, mean age, variation in age, gender, and race); (3) prevalence of blood group in patients with arterial cardiovascular events and in controls. Disagreement was resolved by consensus and by the opinion of a third reviewer, if necessary. We did not attempt to contact the authors of the studies to obtain the unpublished data.
Sensitivity Analyses We used the Newcastle–Ottawa Scale (NOS) to assess the methodological quality of each study.14 We awarded cohort studies a maximum of 4 stars for selection, 2 stars for comparability, and 3 stars for outcome assessment, with more stars indicating better quality. For case-control studies, the maximum score for selection, comparability, and exposure assessment was 4, 2, and 3, respectively. The maximum possible score was 9. Furthermore, as additional quality item we also considered the publication separately prospective and retrospective studies.
Data Synthesis and Data Analyses Statistical Analyses The pooled odds ratio (OR) of the association among different blood groups and genotypes, and arterial cardiovascular events was calculated using Review Manager (RevMan; version 5.0 for Windows, Oxford, England; The Cochrane Collaboration, 2008). OR and 95% confidence intervals (CIs) were calculated using a random effects model (DerSimonian and Laird method).15 The appropriateness of pooling data across studies was assessed with the use of the Cochran Q and the I2 test for heterogeneity, which measures the inconsistency across study results and describes the proportion of total variation in study estimates that is due to heterogeneity rather than sampling error.16 The I2 value provides an estimate of the amount of variance across studies due to heterogeneity rather than chance. I2 < 30% indicates mild heterogeneity, 30 to 50% indicates moderate, and more than 50% indicates severe heterogeneity. When heterogeneity was present, we planned to repeat the analyses removing one study at a time to assess the source of heterogeneity. Sensitivity analyses, including high quality studies (studies with NOS 6) and prospective studies, were performed.
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The proportion arterial cardiovascular events in the population that could be attributed to non-O blood group (population attributable risk [PAR]) were estimated as follows: PAR ¼ 100 (prevalence [OR – 1]/prevalence [OR – 1] þ 1) 0.1074 For this calculation, we used the fixed effects model, and we estimated the prevalence of exposure as the genotype frequency among control subjects as previously described.17 Presence of publication bias was explored using funnel plots of effect size against standard error.18
Results
Dentali et al.
p < 0.001), ►Fig. 1A. Heterogeneity among the studies was significant (Cochran Q < 0.001; I2 ¼ 68%). When we repeated the analyses removing one study at a time, heterogeneity did not significantly change (data not shown). Funnel plot of OR versus standard appeared symmetric, thus suggesting the absence of a publication bias, (►Fig. 2A). Sensitivity analysis including only high quality studies gave a significant but slightly lower association between non-O blood groups and MI with a pooled OR of 1.17 (95% CI: 1.03–1.32). The same was true for the sensitivity analysis including only prospective that gave a significant but low association between non-O blood groups and MI with a pooled OR of 1.09 (95% CI: 1.02–1.16). Among patients with an MI, the estimated attributable risk conferred by non-O blood group was 9.7%.
Study Identification and Selection We identified 182 studies using our search strategy: 85 from MEDLINE and 97 from EMBASE. No additional unpublished studies were identified using ISTH abstracts books. We excluded 137 studies after screening the title and abstract using the predefined inclusion and exclusion criteria and deleting duplicates; 45 studies were retrieved for more detailed evaluation. The interobserver agreement for the study selection was good, with a κ of 0.84. Ten studies were identified through manual review of the references of included studies and recent reviews. Of the 55 retrieved studies, 27 were subsequently excluded because they did not provide separate data on the prevalence of blood group in patients with cardiovascular complications and in controls, lacked a control population, or did not contain original data. Therefore, 28 studies were finally included in our systematic review.19–46
Study Characteristics Twenty two studies included patients with MI and six studies included patients with stroke. The number of patients with MI ranged from 29 to 2,708 and the number of controls in these studies (including blood donors) ranged from 51 to 177,000 for a total of more than 10,000 MI patients and more than 500,000 controls. The number of patients with stroke ranged from 50 to 600 and the number of controls in these studies (including blood donors) ranged from 88 to 14,304 for a total of more than 1,800 stroke patients, and nearly 17,500 controls. Baseline characteristics of included studies are summarized in ►Table 2.
Study Quality ►Table 3 shows the assessment of methodological quality for the 22 studies included in the systematic review. The total scores ranged from 0 to 8. Higher scores indicate better quality. Three received 0 points in each item. Only one study received 8 points.
ABO Blood Group and Myocardial Infarction Non-O blood group was present in 6,470 of the 10,412 patients with MI (62.1%) and in 282,465, of the 526,356 (53.7%) controls, thus resulting in a significantly higher prevalence of non-O blood group in cases than in controls with a pooled OR of 1.28 (95% CI: 1.17–1.40;
ABO Blood Group and Ischemic Stroke All the six studies evaluating the association between ABO blood group and ischemic stroke were case-control studies. Non-O blood group was present in 1,075 of the 1,819 patients with ischemic stroke (62.5%) and in 10,176 of the 17,305 (53.7%) controls, thus resulting in a significantly higher prevalence of non-O blood group in cases than in controls with a pooled OR of 1.17 (95% CI: 1.01–1.35; p ¼ 0.03), ►Fig. 1B. Heterogeneity among the studies was not significant (Cochran Q ¼ 0.30; I2 18%). Funnel plot of OR versus standard appeared asymmetric, with an absence of studies in the bottom left hand corner, (►Fig. 2B). When we repeated the analysis including only high quality studies (NOS 6) prevalence of non-O blood group was not anymore significant with a resulting a pooled OR of 1.28 (95% CI: 0.94–1.74) Among patients with an ischemic stroke, the estimated attributable risk conferred by non-O blood group was 7.45%.
Discussion It has been known for many years that the ABO blood type has a profound influence on hemostasis, being a major determinant of the von Willebrand factor (VWF) and, consequently, of factor VIII (FVIII) plasma levels.47–49 In particular, VWF levels are approximately 25% higher in individuals who are blood group other than O.50 Thus, as VWF and FVIII are well established risk factors for thrombosis,51–54 it is reasonable that several experimental and clinical studies have assessed so far whether ABO blood type could influence the risk of developing arterial or venous thrombotic events.2,3 However, while the positive association between non-O blood group and the risk of developing VTE is now well known and has been finally established in two recent meta-analyses,10,11 the non-O blood group-related increase in arterial thrombotic risk is not so clear, probably due to the scarcity of well-designed studies. In 2008, Wu et al11 published a systematic review and meta-analysis on the link between vascular disease and ABO blood group and observed also a consistent relation with MI (OR: 1.25, 95% CI: 1.14–1.36). More recently, He et al55 conducted a meta-analysis of data from the Health Professionals Follow-up Study (HPFS), Nurses’ Health Study (NHS) and five other prospective cohort studies in which several Seminars in Thrombosis & Hemostasis
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Controls with no history of vascular disease Healthy age- and sex-matched control subjects of a similar racial/social class mix to the patient group with no history of stroke, TIA, peripheral vascular, or ischemic heart disease. NS
Danish blood donors
Patients with stroke confirmed with brain CT.
Consecutive patients with acute stroke or TIA of arterial origin who underwent a brain CT.
Patients with clinical diagnosis confirmed by unspecified neuroradiology.
Patients with clinical diagnosis of stroke confirmed by carotid angiography.
White patients of Danish descent selected from 2 prospective studies (Copenhagen General Population Study, Copenhagen City Heart Study) who developed an MI (defined basing on ICD codes).
Bayoumi et al (2006)43
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Clark et al (2005)44
Sostarić et al (1991)45
Larsen et al (1977)46
Sode et al (2013)19
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2,708/63,279
481/14,304
–
Patients with events before 1977
50/1,883
148/88
445/327
94/103 45♂, 49♀ 52♂, 51♀
600/600 385♂, 215♀
n° C/Ctrl (gender if specified)
NS
Patients with atrial fibrillation, valvular heart disease, connective tissue disease, or thrombus on echocardiography
NS
Patients with a definite nonatherosclerotic cause of the stroke, such as a mechanical heart valve, endocarditis, or dissection, as well as patients older than 75 years or using oral anticoagulants and patients with hemorrhagic stroke.
–
Exclusion criteria
20–100
NS
NS
58.3 (range 25–70) vs. 57 (range 24–71)
NS
55 (12) vs. 56 (12)
56 (10)
Mean age and/or age range
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Patients from the same cohorts of cases who did not develop an MI
Population controls, that is, neighbors or friends of the patients. They were age and sex matched, did not have a history of stroke, and were not related to the patient
White patients without clinical atherothrombotic disease, matched for age ( 1 year), sex, and geographical residence area randomly selected from participants in a populationbased health survey
White patients presenting with new or recurrent objectively diagnosed (with CT) of acute ischemic stroke before the age of 70 years.
Consecutive patients with a first episode of atherosclerotic stroke or transient ischemic attack (included only if the neurologic deficit was witnessed by a neurologist) who underwent a CT of the brain.
Controls
Cases
Patients’ description
van Schie et al (2010)42
Hanson et al (2012)41
Study year, reference
Table 2 Baseline characteristics
52 Dentali et al.
175/3,146
172/1,011
History of overt cardiovascular disease at baseline Patients with a previous MI
Women contacted by random-digit dialing, stratified for age, index year of MI and area of residence. Consecutive patients with coronary arteries angiographically normal or with stenoses of less than 10% and with neither symptoms nor signs of old or acute MI Healthy Caucasian people without a history of thromboembolic events or tendency to bleed matched to the cases by age and sex Subjects form the study who did not have an MI
Participants at the Northwick Park Heart Study (males) who did not experience an MI and sudden coronary death during follow up
Population from RATIO study. Young women with a first acute MI from university and regional hospitals.
Consecutive patients angiographically examined with either prior or acute MI.
Survivors of an acute MI occurred at least 2 months before inclusion in the study.
Survivors from a prospective study (Copenhagen Male Study) who had MI during follow-up.
Participants at the Northwick Park Heart Study (males) who experienced an MI and sudden coronary death during follow-up.
von Beckerath et al (2004)23
Nydegger et al (2003)24
Suadicani et al (2000)25
Meade et al (1994)26
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177/89 155♂, 22♀ 79♂, 10♀
793/340 614♂, 179♀ 257♂, 83♀
200/626
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NS
NS
NS
476/203 382♂, 94♀ 168♂, 35♀
Tanis et al (2006)22
NS
Age and sex-matched blood donors Free of known CAD: detailed medical history and physical examination was performed to exclude the possibility of CAD
Patients with acute ST elevation MI and without known CAD.
170/170
Sari et al (2008)21
NS
Subjects without MI
Patients with confirmed MI.
n° C/Ctrl (gender if specified)
Sheikh et al (2009)20
Exclusion criteria
Controls
Patients’ description
Cases
Study year, reference
Table 2 (Continued)
40–64
63 53–75
57 32–72
(Continued)
Case: 62,6 11,6 Ctrl: 63,4 10,3
18–49
56.7 11.7
NS
Mean age and/or age range
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NS
NS
Patients of similar age discharged from same hospital for non-MI diagnosis. Subjects who were otherwise healthy. Blood donors from Copenhagen
Individuals from Belgian army and police staff without MI
Women younger than 46 years at the time of diagnosis who were hospitalized during the first 6 months of 1975 with a discharge diagnosis of MI (ICD codes).
Consecutive in patients with acute MI (1967–1970), who were blood grouped after admission. MI was diagnosed with 2 of 3 of the following criteria: characteristic history, ECG, or raised serum transaminase. In fatal cases the diagnosis was verified by autopsy.
Patients from Belgian army and police staff with possible angina and MI identified with a questionnaire and revaluated with medical examination.
Patients with MI from the Israeli Ischemic Heart Disease Project (Jewish male government employees, 40 years, designated as being “at risk” for MI in 1963) followed up for 5 years.
Jick et al (1978)30
Viskum et al (1975)31
Van Houte et al (1972)32
Medalie et al (1971)33
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415/9,057
643/24,511
950/14,304 558♂, 392 ♀
29/51
255/802
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NS
NS
197/81,985
481/7,181
n° C/Ctrl (gender if specified)
40
NS
NS
< 46
44 (cases), 42 (controls) 25–49
NS
40–59
Mean age and/or age range
ABO Blood Group and Vascular Disease
Subjects from the same cohort without MI at the end of follow-up.
History of a serious chronic illness or an illness that contraindicates oral contraceptive use.
Women with similar age and from the same area without MI
Women younger than 50 years admitted with acute MI.
Rosenberg et al (1983)28
NS
Sample of the German population
Patients hospitalized with MI.
Platt et al (1985)29
Men whose longest held occupation was in the armed services or with occupation not known.
Patients included in the British regional heart study (men randomly selected from the age-sex registers of group general practices in 24 towns) who did not develop a fatal or nonfatal MI
Patients included in the British regional heart study (men randomly selected from the age-sex registers of group general practices in 24 towns) who developed a fatal or nonfatal MI.
Whincup et al (1990)27
Exclusion criteria
Controls
Patients’ description
Cases
Study year, reference
Table 2 (Continued)
54 Dentali et al.
NS
Cases with incomplete records (no ECG) and atypical clinical features. Coexistent diseases such as aortic-valve disease, diabetes mellitus, polycythemia, hypothyroidism.
Blood donors from the same area Consecutively registered blood donors from Aberdeen city New donors in the same area
General population (Australian Defense Force, 1950) Random sample from company employees. Matched by age, sex, payroll classification (i.e., wage or salary), and geographical location
Patients with CHD admitted to hospital or seen in private consultant practice.
Patients from Aberdeen with MI
Patients with MI sampled from anticoagulant clinics and private patients attending clinical pathologists in private practice.
Patients from a trial of long-term treatment with anticoagulants for an MI.
Employees of the DuPont company (1956–1958) who developed an MI.
Maurer et al (1969)35
Allan et al (1968)37
Bronte-Stewart et al (1962)38
Denborough et al (1962)39
Pell et al (1961)40
226/245
17–64
NS
NS
632/6,366
205/177,000
NS
NS
NS
NS
Mean age and/or age range
202/7,092
286/117,287
204/5,000
816/6,611
n° C/Ctrl (gender if specified)
Seminars in Thrombosis & Hemostasis
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Abbreviations: C, cases; Ctrl, controls; CT, computed tomography; CPHA, The Commission on Professional and Hospital Activities; ICD, International Classification of Diseases; MI, myocardial infarction; M-a, metaanalysis; NS, not specified; RATIO, Risk of Arterial Thrombosis in relation with Oral contraceptive use study; OC, oral contraceptive; WHO, World Health Organization.
Previous MI
NS
NS
NS
Local blood donor data
Consecutive male patients admitted for acute MI (from May to July 1954).
Oliver et al (1969)34
NS
Other US Army men (patients with nonvascular conditions or healthy)
Military records of men who had MI while serving in the US army during 1939–1945 World War.
Nefzger et al (1969)36
Exclusion criteria
Controls
Patients’ description
Cases
Study year, reference
Table 2 (Continued)
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ABO Blood Group and Vascular Disease
Dentali et al.
Table 3 Newcastle-Ottawa Scale Case–control studies Study (year), reference
Selection (max 4)
Comparability (max 2)
Exposure (max 3)
Total
STROKE Hanson et al (2012)41 Van Schie et al (2009)
42
Clark et al (2005)44 Bayoumi et al (2006) Sostarić et al (1991)
43
45
Larsen et al (1977)46
4
2
3
9
4
1
1
6
4
2
1
7
1
0
1
2
1
0
1
2
1
0
1
2
MI Sheikh et al (2009) Sari et al (2008)
20
21
Tanis et al (2006)22 Von Beckerath et al (2004) Nydegger et al (2003)
23
24
Platt et al (1985)29 Rosenberg et al (1983) Jick et al (1978)
28
30
0
0
0
0
3
2
2
7
2
2
1
5
2
1
3
6
1
0
0
1
1
0
1
2
1
1
3
5
2
1
3
6
31
3
0
1
4
Maurer et al (1969)35
1
0
1
2
1
0
0
1
1
0
3
4
3
0
1
4
3
1
1
5
1
0
0
1
3
1
2
6
2
2
1
5
Outcome (max 3)
Total
Viskum et al (1975)
Nefzger et al (1969)
36
Van Houte et al (1972)
32
Oliver et al (1969)34 Allan et al (1968)
37
Denborough et al (1962)
39
Bronte-Stewart et al(1962)38 Pell et al (1961)
40
Cohort studies Study (year), reference
Selection (max 4)
Comparability (max 2) MI
Sode et al (2013)19 Suadicani et al (2000)
25
Meade et al (1994)26 Whincup et al (1990) Medalie et al (1971)
27
33
4
2
2
8
4
1
1
6
4
1
2
7
3
2
1
6
2
1
1
4
thousands of participants were enrolled and they concluded that individuals with non-O blood group had an 11% (RR 1.11, 95% CI: 1.05–1.18, p ¼ 0.001) increased risk of developing coronary heart disease (CHD) as compared with O blood group individuals. The results of our meta-analysis are in line with these two previous observations: indeed, among the 22 studies included in the analysis, we found a significantly higher prevalence of non-O blood group in MI cases than in controls (pooled OR: 1.28, 95% CI: 1.17–1.40), which was still present after considering only high quality and prospective Seminars in Thrombosis & Hemostasis
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studies (pooled OR: 1.17 [95% CI: 1.03–1.32] and 1.09 [95% CI: 1.02–1.16], respectively). As regarding the association between ABO blood type and ischemic stroke, the published literature evidences are even scarcer. The largest published study is that by Hanson et al,41 who recently performed a case–control study on 600 cases and controls, and did not find an association between ABO phenotype or genotype and stroke (OR: 0.9, 95% CI: 0.7–1.2). Their results were in contrast with the above mentioned metaanalysis,11 who observed a slight but statistically significant
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Dentali et al.
Fig. 1 Forest plot evaluating the association between (A) MI (B) or ischemic stroke and the prevalence of non-0 blood group. MI, myocardial infarction.
Fig. 2 Funnel plot of odds ratio versus standard error for ABO blood group for (A) MI or (B) ischemic stroke. MI, myocardial infarction.
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ABO Blood Group and Vascular Disease
ABO Blood Group and Vascular Disease
Dentali et al.
association (OR: 1.14, 95% CI: 1.01–1.27). The pooled OR (1.17, 95% CI: 1.01–1.35) calculated evaluating the six studies included in our meta-analysis is almost identical to that by Wu et al.11 However, the lack of significance after inclusion of only high quality studies (OR: 1.28, 95% CI: 0.94–1.74) underlines the weakness of this association. Our meta-analysis has some potential limitations. First, the application of formal meta-analytic methods to observational studies is controversial, because bias implicit in the study design may misrepresent the strength of associations within the data.12 To minimize this potential bias, we included only studies in which the diagnosis of arterial cardiovascular event was objectively confirmed. Second, studies included in our meta-analysis have different inclusion and exclusion criteria, and to combine results across studies may be inappropriate. Furthermore, the heterogeneity among the studies was significant, suggesting caution in the interpretation of the results. However, we decided to combine our results using the random-effect model, an approach that takes into account the variance among the studies. Finally, since we did not find unpublished studies, the presence of publication bias could not be excluded. In the stroke studies, the funnel plot of OR versus standard error was slightly asymmetric with an absence of studies in the bottom left hand corner suggesting that a few small studies finding a higher prevalence of O blood group in stroke patients compared with controls were not published. Thus, publication of these studies would affect the magnitude of association between non-O blood group and stroke. In conclusion, the results of our systematic review and meta-analysis document the existence of an association between non-O blood group and the arterial vascular risk. However, such association seems to be less strong than that between non-O blood group and VTE.10 This is particularly evident for ischemic stroke where the already weak association lacks of significance after the restriction of the analysis to only high quality studies. Further prospective studies on large populations of patients are required to better clarify the role of ABO blood type in the vascular thrombotic risk. Such studies should also unravel the interaction of ABO blood type with other concomitant risk factors for arterial thrombosis.
7 Jick H, Slone D, Westerholm B, et al. Venous thromboembolic
8
9 10
11
12
13
14
15 16 17
18
19
20
21
22
23
References 1 Storry JR, Olsson ML. The ABO blood group system revisited: a 2
3
4 5
6
review and update. Immunohematol 2009;25(2):48–59 Franchini M, Favaloro EJ, Targher G, Lippi G. ABO blood group, hypercoagulability, and cardiovascular and cancer risk. Crit Rev Clin Lab Sci 2012;49(4):137–149 Franchini M, Liumbruno G. Beyond immunohaematology: the role of ABO blood group in human diseases. Clin Chem Lab Med 2013; doi: 10.2450/2013.0152-13 Eastlund T. The histo-blood group ABO system and tissue transplantation. Transfusion 1998;38(10):975–988 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 Bronte-Stewart B, Botha MC, Krut LH. ABO blood groups in relation to ischaemic heart disease. BMJ 1962;1(5293):1646–1650
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Vol. 40
No. 1/2014
24
25
26
27
28
disease and ABO blood type. A cooperative study. Lancet 1969; 1(7594):539–542 Westerholm B, Wiechel B, Eklund G. Oral contraceptives, venous thromboembolic disease, and ABO blood type. Lancet 1971; 2(7725):664 Mourant AE, Kopeć AC, Domaniewska-Sobczak K. Blood-groups and blood-clotting. Lancet 1971;1(7692):223–227 Dentali F, Sironi AP, Ageno W, 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(5):535–548 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 Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Metaanalysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283(15):2008–2012 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 Wells GA, Shea B, O’Connell D, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in metaanalyses. Available at:http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed August 14, 2013 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7(3):177–188 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557–560 Dentali F, Gianni M, Agnelli G, Ageno W. Association between inherited thrombophilic abnormalities and central venous catheter thrombosis in patients with cancer: a meta-analysis. J Thromb Haemost 2008;6(1):70–75 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 Sode BF, Allin KH, Dahl M, Gyntelberg F, Nordestgaard BG. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ 2013;185(5):E229–E237 Sheikh MK, Bahari MB, Yusoff NM, Knight A. Association of ABO blood group B with myocardial infarction. J Coll Physicians Surg Pak 2009;19(8):514–517 Sari I, Ozer O, Davutoglu V, Gorgulu S, Eren M, Aksoy M. ABO blood group distribution and major cardiovascular risk factors in patients with acute myocardial infarction. Blood Coagul Fibrinolysis 2008;19(3):231–234 Tanis B, Algra A, van der Graaf Y, Helmerhorst F, Rosendaal F. Procoagulant factors and the risk of myocardial infarction in young women. Eur J Haematol 2006;77(1):67–73 von Beckerath N, Koch W, Mehilli J, et al. ABO locus O1 allele and risk of myocardial infarction. Blood Coagul Fibrinolysis 2004;15(1):61–67 Nydegger UE, Wuillemin WA, Julmy F, Meyer BJ, Carrel TP. Association of ABO histo-blood group B allele with myocardial infarction. Eur J Immunogenet 2003;30(3):201–206 Suadicani P, Hein HO, Gyntelberg F. Socioeconomic status, ABO phenotypes and risk of ischaemic heart disease: an 8-year followup in the Copenhagen Male Study. J Cardiovasc Risk 2000;7(4): 277–283 Meade TW, Cooper JA, Stirling Y, Howarth DJ, Ruddock V, Miller GJ. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 1994;88(3):601–607 Whincup PH, Cook DG, Phillips AN, Shaper AG. ABO blood group and ischaemic heart disease in British men. BMJ 1990;300(6741): 1679–1682 Rosenberg L, Miller DR, Kaufman DW, et al. Myocardial infarction in women under 50 years of age. JAMA 1983;250(20):2801–2806
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
58
Dentali et al.
29 Platt D, Mühlberg W, Kiehl L, Schmitt-Rüth R. ABO blood group
44 Clark P, Meiklejohn DJ, O’Sullivan A, Vickers MA, Greaves M. The
system, age, sex, risk factors and cardiac infarction. Arch Gerontol Geriatr 1985;4(3):241–249 Jick H, Dinan B, Herman R, Rothman KJ. Myocardial infarction and other vascular diseases in young women. Role of estrogens and other factors. JAMA 1978;240(23):2548–2552 Viskum K, Astvad K, Fabricius-Bjerre N, Kjaerulff J. ABO blood groups and acute myocardial infarction. Dan Med Bull 1975;22(3):126–128 Van Houte O, Kesteloot H. An epidemiological survey of risk factors for ischemic heart disease in 42,804 men. I. Serum cholesterol value. Acta Cardiol 1972;27(5):527–564 Medalie JH, Levene C, Papier C, et al. Blood groups, myocardial infarction and angina pectoris among 10,000 adult males. N Engl J Med 1971;285(24):1348–1353 Oliver MF, Geizerova H, Cumming RA, Heady JA. Serum-cholesterol and ABO and rhesus blood-groups. Lancet 1969;2(7621):605–606 Maurer B, Hickey N, Mulcahy R. ABO and Rh blood groups in patients with coronary heart disease. Ir J Med Sci 1969;8(3):105–108 Nefzger MD, Hrubec Z, Chalmers TC. Venous thromboembolism and blood-group. Lancet 1969;1(7600):887 Allan TM, Dawson AA. ABO blood groups and ischaemic heart disease in men. Br Heart J 1968;30(3):377–382 Bronte-Stewart B, Botha MC, Krut LH. ABO blood groups in relation to ischaemic heart disease. BMJ 1962;1(5293):1646–1650 Denborough M. Blood groups and ischaemic heart disease. BMJ 1962;II:927 Pell S, D’Alonzo CA. A three-year study of myocardial infarction in a large employed population. JAMA 1961;175:463–470 Hanson E, Karlsson S, Jood K, Nilsson S, Blomstrand C, Jern C. No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes. Thromb Res 2012;130(3):339–342 van Schie MC, de Maat MP, de Groot PG, et al. Active von Willebrand factor and the risk of stroke. Atherosclerosis 2010; 208(2):322–323 Bayoumi NA, Macleod MJ, Greaves M, Vickers MA. ABO blood groups in cerebrovascular accident patients. Br J Haematol 2006; 133(S1):51
relationships of ABO, Lewis and Secretor blood groups with cerebral ischaemia of arterial origin. J Thromb Haemost 2005; 3(9):2105–2108 Sostarić V, Bozicević D, Brinar V, Grbavac Z. Hereditary antigen characteristics of blood in ischemic cerebrovascular accident. Neurol Croat 1991;40(1):3–11 Larsen S, Anthonisen B, Marquardsen J. Cerebral infarction, cerebral haemorrhage, and ABO blood-groups. Lancet 1977;1(8020): 1064 Preston AE, Barr A. The plasma concentration of factor VIII in the normal population. Br J Haematol 1964;10:238–245 Moeller A, Weippert-Kretschmer M, Prinz H, Kretschmer V. Influence of ABO blood groups on primary hemostasis. Transfusion 2001;41(1):56–60 O’Donnell JS, Laffan MA. The relationship between ABO histoblood group, factor VIII and von Willebrand factor. Transfus Med 2001;11(4):343–351 Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ Jr, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987;69(6):1691–1695 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 Folsom AR, Wu KK, Rosamond WD, Sharrett AR, Chambless LE. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997;96(4):1102–1108 Whincup PH, Danesh J, Walker M, et al. von Willebrand factor and coronary heart disease: prospective study and meta-analysis. Eur Heart J 2002;23(22):1764–1770 Franchini M, Makris M. Non-O blood group: an important genetic risk factor for venous thromboembolism. Blood Transfus 2013; 11(2):164–165 He M, Wolpin B, Rexrode K, et al. ABO blood group and risk of coronary heart disease in two prospective cohort studies. Arterioscler Thromb Vasc Biol 2012;32(9):2314–2320
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31 32
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34 35 36 37 38 39 40 41
42
43
45
46
47 48
49
50
51
52
53
54
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