non-O Group Research Articles

The Risk of Venous Thrombosis in Different Immigrant Groups in the Netherlands

AbstractAbstract 3393 Background:Ethnic differences in the incidence of venous thrombosis have been appreciated for many years. However, with few exceptions, most of the studies on this subject were based on administrative databases from North America and China. The aim of this study was to investigate the risk of venous thrombosis in different first and second generation immigrant groups included in a large population-based case-control study, performed in the Netherlands. Methods:This study was performed using data from the MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis-study), a large, population based case-control study on risk factors for venous thrombosis from the Netherlands. Inclusion criteria consisted of patients and controls whom information were available on the country of birth. For the analysis related to immigration background, patients were compared with random digit dialing (RDD) controls. First generation immigrants were classified as those who were born outside the Netherlands. Second generation immigrants were similarly defined as first generation immigrants, except that second immigrants were born in the Netherlands, while both parents were born in one of aforementioned other countries. In total, 6899 participants were included, of whom 4300 patients and 2599 RDD controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated as estimates of the relative risk, and were adjusted for age, sex, body mass index, smoking, hormonal factors, alcohol consumption, physical activity and malignancy by unconditional logistic regression. Results:The risk of venous thrombosis varied according to the region of birth (Table 1). When compared with the Dutch, Eastern Europeans reached the highest and East/Southeast Asians the lowest risk of venous thrombosis with OR of 2.35, (95% CI, 1.09–4.59) and 0.44 (95% CI, 0.29–0.68), respectively after multivariate adjustments. Caribeans showed an intermediate lower risk of 0.69 (95% CI, 0.36–1.30) after multivariate adjustments (Table 1). We did not observe a major difference on the risk for VT between first and second generation immigrants, although the number of second generation immigrants was small for some groups. Subgroup analysis did not show major differences according to immigration groups, except for Eastern Europeans, who had a higher risk for unprovoked event with OR of 3.79 (95% CI, 1.44–9.97) and East/Southeast Asians with higher risk for pulmonary embolism with OR of 0.60 (95% CI, 0.36–1.0) (Table 2). In comparison with Dutch controls, East/Southeast Asians controls had lower prevalence of factor V Leiden (6% and 1%, respectively) and prothrombin mutation (2% and 1%, respectively) but higher blood group non-O (54% and 62%, respectively). Risk of VT in East/Southeast Asians adjusted for age, sex, factor V Leiden and blood group non-O was 0.53 (95% CI, 0.35–0.80). Analysis of a panel of procoagulant, anticoagulant, profibrinolytic and genetic factors are underway and is expected to be available before the ASH conference of 2012. Conclusions:The risk of VT varies in different populations. The risk of VT in East/Southeast Asians was the lowest and was virtually unchanged after adjustment for several environmental and genetic known risk factors for VT. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

ABO blood group system and gastric cancer: a case-control study and meta-analysis.

This study focuses on the association between the ABO blood group system and the risk of gastric cancer or Helicobacter pylori infection. The data for the ABO blood group was collected from 1045 cases of gastric cancer, whereby the patient underwent a gastrectomy in Ruijin Hospital, Shanghai. The information on the ABO blood group from 53,026 healthy blood donors was enrolled as control. We searched the Pubmed database on the relationship between ABO blood groups and gastric cancer risk for meta-analysis. In our case-control study, the risk of gastric cancer in blood group A was significantly higher than that in non-A groups (O, B and AB) (odd ratio, OR1.34; 95% confidential interval, CI 1.25–1.44). Compared with non-O groups (A, B and AB), individuals with blood group O demonstrated a reduced risk of gastric cancer (OR = 0.80; 95% CI 0.72–0.88). The proportion of H. pylori infection in blood group A individuals was significantly higher than that in non-A blood groups (OR = 1.42; 95% CI 1.05–1.93). We further combined our data with the published data of others, and crossreferenced the risk of gastric cancer with the blood type, finding consistent evidence that gastric cancer risk in the blood A group was higher than that in the non-A groups (OR = 1.11; 95% CI 1.07–1.15), and that blood type O individuals were consistently shown gastric cancer risk reduction (OR = 0.91; 95% CI 0.89–0.94). Our study concluded that there was a slightly increased risk of gastric cancer in blood group A individuals, and people with blood type A are more prone to be infected by H. pylori than other ABO blood type individuals, whereas, a slightly decreased risk of gastric cancer was identified in blood type O individuals.

ABO blood groups and the risk of venous thrombosis in patients with inherited thrombophilia.

Although having a non-O blood type is now regarded as a risk factor for venous thromboembolism, the strength of this association is poorly defined, as is its interaction with inherited thrombophilia. The prevalence of non-O blood group and inherited thrombophilia (deficiencies of natural anticoagulants, factor V Leiden and prothrombin G20210A mutation) was assessed in a series of 712 consecutive patients with proximal deep vein thrombosis of the lower limbs who were referred to our Institution between 2004 and 2010, and in 712 age- and gender-matched healthy volunteers. Odds ratios (OR) of deep vein thrombosis and their 95% confidence intervals (CI) were computed for non-O group and thrombophilia, both separately and in combination. A non-O blood group was present in 492 cases and 358 controls (OR 2.21; 95% CI, 1.78 to 2.75). A thrombophilic abnormality was present in 237 cases and 105 controls (OR 2.82; 2.18 to 3.66). The combination of non-O group and thrombophilia was present in 152 cases and 51 controls (OR 7.06; 4.85 to 10.28). Having a non-O blood group is associated with an increased risk of proximal deep vein thrombosis of the lower limbs with or without pulmonary embolism. The addition of inherited thrombophilia increases the thrombotic risk conferred by non-O group alone by almost 3-fold.

Non-O blood group: an important genetic risk factor for venous thromboembolism.

Non-O blood group: an important genetic risk factor for venous thromboembolism.

ABO blood groups and abdominal aortic aneurysm

Earlier studies have indicated an association between blood group non-O and atherosclerosis related vascular diseases. Abdominal aortic aneurysm (AAA) is traditionally regarded as a consequence of atherosclerosis. The aim of the present study was to investigate the association between ABO blood groups and AAA with special regard to a relation to AAA rupture. Prospectively, 504 patients operated on for AAA were investigated. Patients operated on for AAA have similar ABO blood group distributions as a population based control group. Furthermore, there was no significant difference in distribution of ABO blood group between patients operated on for ruptured AAA (n=174) and non-ruptured AAA (n=330). In conclusion, this study fails to demonstrate an association between ABO blood groups and AAA.

The relationship between body mass index, activated protein C resistance and risk of venous thrombosis

High body mass index (BMI) is associated with an increased risk of venous thrombosis (VT). Clotting factor VIII levels are increased in obese subjects, possibly because of a chronic inflammatory state, which increases activated protein C (APC) resistance. The APC resistance in FV Leiden carriers could be aggravated and further worsened by high FVIII levels in blood group non-O carriers. We hypothesized that an association exists between BMI and APC resistance, and that this is amplified by the presence of FV Leiden and/or blood group non-O. We used the Leiden Thrombophilia Study (LETS) to determine whether an association exists between BMI and APC resistance, and whether the combination of high BMI and APC resistance increases the risk of VT. In a pooled analysis of LETS and a Norwegian case-cohort study (TROL), we verified whether FV Leiden modified the risk of the occurrence of VT with increasing BMI, and whether this risk was further increased by blood group non-O. APC resistance increased linearly with increasing BMI, partly because of a concurrent rise in FVIII. A BMI in the median or upper tertile was associated with a 1.9-fold (95% confidence interval [CI] 1.0-2.5) and 2.2-fold (95% CI 1.4-3.4) increased risk as compared with the lowest tertile. Both relative risks decreased slightly after FVIII and APC resistance adjustments. The effect of BMI on VT risk was enhanced two-fold to 10-fold in FV Leiden or blood group non-O carriers. The increased risk of VT in individuals with high BMI is partly mediated by FVIII-related APC resistance. This risk is more pronounced when other causes of increased APC resistance are also present.

Blood group phenotypes A and B are risk factors for cerebral malaria in Odisha, India

There is increasing evidence that the ABO blood group phenotypes modulates Plasmodium falciparum rosetting and may influence the clinical manifestation of severe malaria. Whether blood group phenotypes are associated with risk of severe falciparum malaria in Odisha, we analyzed 343 adult malaria patients. The results showed high prevalence of blood group B in both mild (n=110) and severe malaria (cerebral malaria [CM]; n=130 and non-cerebral severe malaria [NCSM]; n=103) categories among the non-O group and while type O is significantly associated with protection against CM, patients with type A and B group had increased risk for developing CM. Further, the strength of association for B group (p=< 0.0001) was high and has double the risk of (OR=5.0) of developing CM compared to blood group A (OR=2.5). Such findings may probably be due to strain specific blood group preferences of P. falciparum and high prevalence of B group. However, the ABO blood group distribution of mild malaria was comparable with that of the NCSM group of patients. The lack of association of ABO phenotypes with NCSM is evidence for the hypothesis that the underlying pathogenesis cascades are different in CM and NCSM clinical presentations.

No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes

IntroductionThe ABO blood group system is encoded by one gene, ABO. Previous studies have reported an association between blood group non-O (i.e. phenotype A, B or AB) and myocardial infarction. Studies on stroke and ABO are, however, more scarce. Therefore, we aimed to investigate whether ABO phenotype or genotype is associated with ischemic stroke and/or etiologic subtypes of ischemic stroke. Materials and methodsThe study was performed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 600 patients with ischemic stroke before the age of 70years, and 600 matched controls. Patients were classified according to the TOAST criteria. ResultsThere was no significant association between ABO phenotype (blood group O vs. non-O) and overall ischemic stroke (multivariable odds ratio of 0.9, 95% confidence interval 0.7-1.2). This was also true for blood group O vs. A and O vs. B. Furthermore, no association between ABO genotypes and ischemic stroke was detected. The ischemic stroke subtype analysis was confined to large-vessel disease, small-vessel disease, cardioembolic stroke and cryptogenic stroke. In this analysis, there was no significant association between any ischemic stroke subtype and ABO phenotype or genotype. ConclusionsThe findings in this study suggest that ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes.

The Risk for Venous Thrombosis in Patients with Increased Body Mass Index and Interactions with Other Genetic and Acquired Risk Factors: The MEGA Study

Abstract 1234 Background:Obesity (prevalence of 20–25% in Western populations), blood group non-O (present in 50% of Western populations) and factor V Leiden (present in 5% of Caucasian populations) are frequent prothrombotic risk factors and may therefore have a considerable impact on the overall incidence of venous thrombosis. We previously reported that the increased risk of venous thrombosis in individuals with a high BMI is mediated by factor VIII induced APC-resistance, and that the combination of blood group non-O with a high BMI or factor V Leiden leads to higher venous thrombosis risks than expected when these prothrombotic factors are analyzed separately (ASH Annual Meeting Abstracts. 2009;114:453). However, small numbers did not enable us to sufficiently study the risk of venous thrombosis for the combination of a high BMI with factor V Leiden and blood group non-O, or to study these effects in subgroups. Objectives:To investigate whether the presence of factor V Leiden with blood group non-O can modify the risk for venous thrombosis in individuals with different body mass index strata in a larger population based study than previously reported. To evaluate the presence of gene-environment interactions in specific subgroups. Methods:MEGA study: 4956 consecutive patients aged 18–70 years with a first episode of venous thrombosis, and 6297 age- and sex-matched controls were included. Information about BMI, blood group and factor V Leiden was available in 4062 patients and 4659 controls. Odds ratios for venous thrombosis and their 95% confidence intervals (95% CIs) were calculated for BMI tertiles with logistic regression and adjusted for age and sex (matching factors). An interaction analysis among the BMI tertiles, factor V Leiden and blood group non-O was performed. Subgroup analyses involved stratification by venous thrombosis place (i.e. deep vein thrombosis or pulmonary embolism), sex, and presence or absence of acquired venous thrombosis risk factors. Results:A progressive increase in BMI was associated with an increased risk for venous thrombosis, odds ratios 1.1 (95% CI, 0.9–1.3) for those with a BMI in the median tertile, and 1.9- (95% CI, 1.6–2.3) for those in the upper tertile, as compared to individuals in the first BMI tertile, blood group O, and no factor V Leiden (i.e. the reference group). The addition of factor V Leiden and blood group non O in the model increased the risk in all BMI tertiles; odds ratios for venous thrombosis were 3.8 (95% CI, 3.2–4.6) in the third BMI tertile of individuals with blood group non-O, and 5.4 (95% CI, 3.5–8.5) in the third BMI tertile of individuals with factor V Leiden, respectively. When both factor V Leiden and blood group non-O were present, odds ratios for venous thrombosis were 9.1 (95% CI, 5.9–14.0) in the first BMI tertile, 9.4 (95% CI, 6.6–13.5) in the second BMI tertile, and 12.5 (95% CI, 8.9–17.6) in the BMI third BMI tertile as compared to the reference group. Subgroup analyses revealed similar joint interactions of BMI with blood group non-O and factor V Leiden on venous thrombosis risk. Disclosures:No relevant conflicts of interest to declare.

Increased risk of venous thrombosis in persons with clinically diagnosed superficial vein thrombosis: results from the MEGA study

AbstractSuperficial vein thrombosis (SVT) is regarded a self-limiting disorder, although the authors of recent studies showed that ultrasonographically diagnosed SVT is a precursor for venous thrombosis. We aimed to determine whether the same holds true for clinically diagnosed SVT and to what extent it is associated with thrombophilia in a population-based case-control study (ie, Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). We found that a history of clinical SVT was associated with a 6.3-fold (95% confidence interval [CI] 5.0-8.0) increased risk of deep-vein thrombosis and a 3.9-fold (95% CI 3.0-5.1) increased risk of pulmonary embolism. Blood group non-O and factor V Leiden showed a small increase in SVT risk in controls, with odds ratios of 1.3 (95% CI 0.9-2.0) and 1.5 (95% CI 0.7-3.3), respectively. In conclusion, clinically diagnosed SVT was a risk factor for venous thrombosis. Given that thrombophilia was only weakly associated with SVT, it is likely that other factors (varicosis, obesity, stasis) also play a role in its etiology.

The Role of ABO Blood Group In TTP Prevalence and Disease Outcome

AbstractAbstract 4671TTP results from deficiency of ADAMTS13 that leads to accumulation of high molecular weight multimers (HMWM) of von Willebrand factor (VWF) and thrombosis in the microvasculature. Previous studies have shown that HMWM VWF purified from blood group O individuals were cleaved faster by ADAMTS13 compared to HMWM VWF from non-O blood group individuals. We hypothesized that blood group O patients have lower prevalence of TTP and/or less severe form of TTP. We conducted a retrospective chart review of all TTP patients treated at our institution from 1993 to 2010. The patients were identified from the review of plasmapheresis treatment records. Any patients with missing charts were excluded. The diagnosis of TTP was made on the basis of laboratory evidence of microangiopathic hemolytic anemia and thrombocytopenia and neurologic and/or renal abnormalities, following exclusion of alternative diagnoses. ADAMTS13 levels were determined by collagen binding assay in select patients. 94 patients were included in the study. The patient characteristics were as follows: 32 males versus 62 females, mean age 45.4 years. 37/94 (39%) patients had ADAMTS13 analyzed with the following results: low ADAMTS13 (21 patients), normal ADAMTS13 (15 patients), equivocal 1. Presentation laboratory investigations were available for 91 patients and were as follows: median platelet count 16×109/L (min 3, max 274) and median hemoglobin 89 g/L (min 48, max 152). At presentation, 19/91 (20.9%) patients had fever (>38C) and 43/91 (47%) had neurological abnormalities (ranging in severity from headache to seizures and decreased level of consciousness). The blood group distribution in the TTP cohort was blood group O 41 patients, non-O 48 patients, data not available 5 patients. All patients received plasmapheresis with cryosupernatant plasma (CSP) or FFP, with some also receiving steroids and other therapies. The patients received a median of 12 (min 1, max 67) plasmapheresis treatments. Overall mortality rate was 22%. The other outcomes were as follows: death at 6 months follow-up 19%; death at 6 months or relapse 20%, death during treatment or permanent dialysis or permanent neurological disability 21%. The prevalence of blood group O versus non-O in our TTP cohort (n=89) was not significantly different from the prevalence of blood group O versus non-O in the general patient population of our institution over 2000–2010 (n=24,852; p=0.71). As illustrated below, in univariate analysis, TTP patients with blood group O did not have significantly different outcomes compared to TTP patients with non-O group blood.OutcomesGroup O patientsNon-group O patientsp-valuesDeath at 6 months6/4111/480.32Death at 6 months or relapse13/4120/480.16Death during treatment/permanent disability/permanent dialysis dependence7/4110/480.38 Conclusion:The prevalence of blood group O vs. non-O was not significantly different between the TTP cohort and our general patient population. Although there appeared to be a trend towards worse outcomes in patients with non-O blood group, there were no statistically significant differences in the outcomes in the patients with blood group O vs. non-O. The outcomes assessed in our study included death at 6 months, death at 6 months or relapse, and death during treatment/permanent neurological disability/permanent dialysis dependence. Disclosures:No relevant conflicts of interest to declare.

ABO blood group alleles: A risk factor for coronary artery disease. An angiographic study

Objectives To analyze the impact of ABO groups on coronary heart disease risk factors, coronary involvement and prognosis. Methods An observational single center study was conducted to examine 4901 consecutive patients with heart disease receiving coronary angiography and ABO group determination at National Research Council Institute of Clinical Physiology between January 1993 and December 2003, with maximum 10 years follow-up. All-cause death and cardiac death, were the considered end points. Results When compared to the official distribution of ABO groups in the Italian population (O 40%, A 36%, B 17%, AB 7%), a substantially different distribution was observed in the study population (O 43.3%, A 41.4%, B 11.2%, AB 4.1%). In addition, a significant association was found between group non-O and family history of ischemic heart disease, hypercholesterolemia and presence of coronary atherosclerosis. Higher prevalence of A and B alleles was found in patients with myocardial infarction ( P < 0.05). Group non-O was a powerful predictor of cardiac mortality in patients aged <65 years, particularly in women (HR 1.53, 95% CI 1.06–2.21 and HR 5.29, 95% CI 1.57–17.82, respectively). Conclusions Group non-O is associated with increased mortality in patients with ischemic heart disease. Group non-O increases the risk for cardiac death in non-elderly patients, particularly in younger females, and groups A and B prevail in myocardial infarction. ABO group determination might aid in genetic screening for ischemic heart disease and become relevant in the management of risk factor control.

Venous thrombosis of the upper extremity: effect of blood group and coagulation factor levels on risk

Venous thrombosis of the upper extremity is a rare form of thrombosis, accounting for around 4% of all venous thromboses, and for which only a few risk factors are known. This case-control study investigated the effect of coagulation factors on risk of venous thrombosis of the upper extremity. Patients with venous thrombosis of the arm and partner controls were selected from the Multiple Environmental and Genetic Assessment study, a large population-based case-control study. Participants with a malignancy were excluded. Odds ratios (OR) were estimated for elevated levels of factor II, VII, VIII, IX, X, XI, von Willebrand Factor (VWF), and fibrinogen, low levels of protein C, protein S, and antithrombin, and for blood group non-O. Substantially increased risks of venous thrombosis of the upper extremity were found for patients with high levels (above 90th percentile versus below) of factor VIII (OR: 4.2, 95% confidence interval (CI): 2.2-7.9), VWF (OR: 4.0, 95% CI: 2.1-7.8), fibrinogen (OR: 2.9, 95% CI, 1.5-5.7), and for blood group non-O compared to O (OR: 2.1, 95% CI, 1.3-3.6). The other factors were not associated with an increased risk. Elevated levels of several procoagulant factors are associated with a strongly increased risk of venous thrombosis of the upper extremity.

The Risk of Venous Thrombosis Related to Increase in Body Mass Index Is Mediated by Factor VIII Induced APC-Resistance.

Abstract 453 Background:The reason why a high BMI predisposes to venous thrombosis is not clarified. People with overweight or obesity tend to be more immobile which may lead to clot formation through stasis. It is also possible that these subjects acquire a prothrombotic state. Factor (F) VIII can be released by adipose tissue through inflammatory cytokines, which consequently might induce APC-resistance. This APC-resistance could be aggravated in case FV Leiden is also present. In addition, presence of high levels of FVIII in non-O blood group subjects could worsen this further. Objective:To determine whether an association exists between BMI and APC-resistance, and whether the combination of both high BMI and APC-resistance increased the risk of venous thrombosis in the Leiden Trombophilia Study (LETS). Whether increasing FVIII levels induced APC-resistance was also studied. In a pooled analysis of LETS and a Norwegian case-cohort study (TROL), we verified if FV Leiden modified the risk of increasing BMI on the occurence of venous thrombosis and whether these risks were further increased by blood group non-O. Methods:Linear regression was used to determine the relation between increasing APC-resistance and BMI, increasing FVIII levels and BMI, increasing APC-resistance and FVIII levels, and between increasing APC-resistance and BMI adjusted for FVIII levels. Cut-off points needed to create tertile categories of APC-resistance were derived from the control-group of the LETS and the TROL population separately. Logistic regression was used to calculate odds ratios and their 95% confidence intervals, adjusted for age and sex. To make the TROL and LETS population more similar for the current analysis, we restricted the analysis in the TROL subjects to those who were younger than 70 and to those who had a DVT only (n=183 cases and n=696 controls). Results:APC-resistance increased linearly with increasing BMI. A same phenomenon was observed for FVIII, i.e. an increase of BMI led to higher FVIII levels. Increased APC-resistance was in its turn associated with an increase of FVIII levels. FVIII explained part of the relation between APC and BMI, as the slope of the regression line of APC-resistance on BMI levels decreased after adjustment for FVIII. To examine the effect of increasing BMI, independent of existing APC-resistance, on the risk of venous thrombosis, we restricted the analysis to subjects from the LETS in whom APC-resistance was not related to other factors such as FV Leiden or oral contraceptive use. In these subjects (n=237 cases and n=369 controls), the risk of venous thrombosis increased 1.4-fold for those with a BMI in the median tertile (odds ratio 1.4; 95% CI, 0.9-2.3) and 2.5-fold for those in the upper tertile (odds ratio 2.5; 95% CI, 1.6-3.9), as compared to subjects in the lowest tertile. Adjustment for APC-resistance or FVIII led to a slight decrease in these relative risk estimates. Non-FV Leiden-carriers with blood group O were only at risk of venous thrombosis when they had a BMI in the upper tertile compared to non-FV Leiden-carriers with blood group O and a BMI in the lowest tertile; (adjusted odds ratio 1.9). This risk was modestly increased when non FV Leiden carriers with non-O blood group were compared with this reference group, with adjusted odds ratios of 1.5, 2.4 and 3.4, respectively, within the BMI tertiles. This risk was strongly increased when FV Leiden carriers with blood group O were compared to the reference group, with adjusted odds ratios of 3.0, 8.3 and 9.7, respectively, within the BMI tertiles. Risk of FV Leiden carriers with non-O blood group showed the highest risk of venous thrombosis compared to the reference group, no longer in a dose-response way, with adjusted odds ratios of 40.6, 23.3 and 25.2, respectively, within the BMI tertiles. Conclusion:The increased risk of venous thrombosis in subjects with high BMI is mediated by FVIII induced APC-resistance. Subjects with FV Leiden and increasing BMI had a higher risk of venous thrombosis compared to non-carriers, and this risks was more than 20 fold increased in carriers of blood group non-O and FV Leiden. Future studies are needed to show if these risks can be downgraded by weight loss. Disclosures:No relevant conflicts of interest to declare.

Genetic Risk Factors of Thrombosis.

Abstract SCI-43Venous thrombosis is a common episodic disease with a steep age gradient. Interactions between various risk factors determine the development of the disease, and the proportion of variance attributable to genetic factors may be as high as 50-60%. There are six (moderately) strong genetic risk factors. First there are heterozygous deficiencies of the natural anticoagulants protein C, protein S, and antithrombin. These deficiency states are quite rare in the general population (in all races) and their genetic architecture is complex with hundreds of documented mutations. The risk for the development of venous thrombosis may be increased 10-20-fold in these deficiency states. There is no consistent evidence that deficiencies of other members of the anticoagulant systems - such as thrombomodulin, EPCR, and heparin co-factor II - are also strong risk factors for venous thrombosis, possibly because these natural anticoagulants are associated with other episodic or chronic diseases. Secondly there are three genetic factors associated with an increase, directly or indirectly, in the procoagulant potential of the coagulation system: blood group non-O, factor V Leiden and prothrombin G20201A. The genetic architecture of these risk factors is extremely simple. The prevalence in the general Caucasian population is modest for prothrombin G20210A and factor V Leiden; in other races these two risk factors are extremely rare. The increase in thrombotic risk is about 3-fold or 7-fold for prothrombin G20210 and Factor V Leiden respectively. Blood group non-O is the most common of the prothrombotic genetic risk factors and approximately doubles the risk of venous thrombosis, and may do so in all races. In addition to these six ‘classical' risk factors, a growing list of weak genetic risk factors has been discovered. Almost without exception, these weak risk factors are common single nucleotide polymorphisms in coagulation factor genes - e.g. those encoding for fibrinogen, factor XIII, factor IX, et cetera - that have a small effect on gene function, and consequently a small effect on thrombotic risk. This list of weak but common risk factors is expected to grow considerably in the near future as the large-scale genome wide association studies that are currently under way deliver their results. Moreover, deep resequencing studies are expected to start soon, whether based on a candidate gene approach or genome-wide, which will yield unprecedented insight in the extend to which rare genetic variation determines individual thrombotic risk. DisclosuresNo relevant conflicts of interest to declare.

Ossification does not cause any complication when a bronchial stump is reinforced with an intercostal muscle flap

An intercostal muscle (ICM) flap is used to buttress the bronchial stump or bronchial anastomosis during thoracic surgery for airway reconstruction. Such flaps sometimes show ossification after surgery. Previous reports have suggested that such ossification requires a functional periosteum and good vascularization. We examined the background of ICM flap ossification and its relationship with complications and pain after surgery. We surveyed the clinical records of 47 patients who underwent bronchial stump reinforcement with an ICM flap during thoracic surgery at Kansai Medical University Hospital between January 2003 and December 2005. We reviewed the post-surgical chest computed tomography (CT) scans of 42 patients, and examined the degree of ICM ossification. We classified patients into two groups: those with ossification of the ICM flap (O group) and those without (non-O group). We compared the two groups for age, gender, the site of ICM flap placement, disease, type of lymph node dissection, and pretreatment. We also compared the two groups for pain levels and complications after surgery. Eight (19%) of the 42 patients showed ossification of the ICM after surgery. There were statistically significant differences between the O and non-O groups in gender (p=0.029), lymph node dissection (p=0.024) and pain levels after surgery (p=0.034). There were no complications attributable to ICM ossification in this series. Ossification of an ICM flap may be related to gender, lymph node dissection and pain after surgery. Ossification does not cause any complication after surgery when an ICM is used to reinforce bronchial stumps.

Effect of Endogamy and Consanguinity on the Development of LabialVenous Malformations in rea of Tlemcen (West Algeria)

Background: Vascular malformation is extremely rare, yet has a profound impact on quality of life, aesthetic and functional disorders. Aim: To show that endogamy and consanguinity may represent risk factors for labial venous malforma- tion (LVM) development. Materials and Methodology: Among the 18093 scrutinized families on a 20 years back period from marriage registers, five families with a child presenting LVM were recruited from two geographic areas, one highly endoga- mous (Nedroma), the other slightly endogamous (Maghnia). These families were recruited for a retrospective descriptive es- say at the Pathology and Oral Surgery Department of Tlemcen University Hospital Center (north-west of Algeria). Results: Four cases of LVM were from the Nedroma region, the fifth one from the Maghnia region. High consanguinity level was reg- istered in patient families from Nedroma. On the other hand, the blood group O frequency was slightly higher compared to that of the blood group non-O. Conclusions: The present study suggests that consanguinity could beget LVM and that endog- amy could increase its prevalence. The postulated association between this genetic disease and the OO genotype seems to be not confirmed. Therefore, it would be interesting to seek the SNP markers in this region.

ABO blood group, other risk factors and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE).

Numerous case-control studies have reported higher prevalence of non-O blood type among venous thromboembolism (VTE) patients than controls, but potential mechanisms or effect modifiers for the association are not fully established. Using a nested case-control design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, ABO blood type and other VTE risk factors were measured on pre-event blood samples of 492 participants who subsequently developed VTE and 1008 participants who remained free of VTE. A total of 64.4% of cases and 52.5% of controls had non-O blood type. Among controls, mean values of factor VIIIc (FVIIIc) and von Willebrand factor among the non-O blood type group were higher than among the O group. Compared with O blood type, the age-adjusted odds ratio (OR) of VTE for non-O blood type was 1.64 (95% CI, 1.32-2.05) and was similar for the two parent studies and race groups. Further adjustment for sex, race, body mass index, diabetes mellitus and FVIIIc reduced the OR: 1.31 (95% CI, 1.02-1.68). Factor V Leiden (FV Leiden) appeared to modify the non-O blood type association with VTE in a supra-additive fashion, with an age-, sex- and race-adjusted OR of 6.77 (95% CI, 3.65-12.6) for having both risk factors. Non-O blood type was independently associated with risk of VTE, and added to the risk associated with FV Leiden.

Clearance mechanisms of von Willebrand factor and factor VIII.

Clearance mechanisms of von Willebrand factor and factor VIII.

The Hemostatic Profiles of Patients with Type O and Non-O Blood After Acute Normovolemic Hemodilution with 6% Hydroxyethyl Starch (130/0.4)

Individuals with Type O blood have been reported to have a tendency toward reduced Factor VIII and von Willebrand Factor (vWF) levels. If this is true, patients with Type O blood might be vulnerable to coagulopathy during acute normovolemic hemodilution using hydroxyethyl starch (HES), both from hemodilution as well as HES-related coagulopathy. Thirty non-O and 15 type O ASA 1 or 2 patients scheduled for spinal surgery involving more than two spinal levels were enrolled for the study. After anesthesia induction, 30% of the estimated blood volume was removed, and the volume was simultaneously replaced with 6% HES (130/0.4). Coagulation profiles were measured before (T0) and 30 min after acute normovolemic hemodilution (T30). Factor VIII activity, vWF antigen levels (vWF:ag), and vWF ristocetin cofactor activity (vWF:RCof) were lower in the O group than in the non-O group before and after acute normovolemic hemodilution, and decreased below the normal range in the O group after acute normovolemic hemodilution. The decrease was beyond that expected from hemodilution alone. Maximum amplitude and coagulation index of the thromboelastogram decreased below the normal range in the O group after acute normovolemic hemodilution. The decrease in vWF:ag was related to the degree of blood loss, and was greater in patients in the O group. Patients with Type O blood may have increased coagulation compromise, and greater dilution of Factor VIII activity, vWF:ag, and vWF:RCof after acute normovolemic hemodilution with HES.