Causes of venous thrombosis Rosendaal, F R
Thrombosis journal,
10/2016, Letnik:
14, Številka:
Suppl 1
Journal Article
Recenzirano
Odprti dostop
Venous thrombosis which mainly manifests as deep vein thrombosis of the leg or pulmonary embolism occurs in 1 per 1000 per year. It occurs due to interacting genetic, environmental and behavioral ...risk factors. The strongest risk factors are certain types of surgery and malignancies. Over the last decade many new risk factors for venous thrombosis have been identified. Venous thrombosis has a high recurrence rate, of around 5 % per year. Whereas clinically it would be most important to identify patients at risk of recurrence, only male sex and a previous unprovoked thrombosis are established determinants of recurrent thrombosis.
Genetics of venous thrombosis Rosendaal, F R; Reitsma, P H
Journal of thrombosis and haemostasis,
July 2009, Letnik:
7 Suppl 1
Journal Article
Recenzirano
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Venous thrombosis (deep vein thrombosis, pulmonary embolism) is a common and serious disorder, with genetic and acquired risk factors. The genetic risk factors can be subdivided in to those that are ...strong, moderate and weak. Strong risk factors are deficiencies of antithrombin, protein C and protein S. Moderately strong are factor V Leiden, prothrombin 20210A, non-O blood group and fibrinogen 10034T. There are many weak genetic risk factors, including fibrinogen, factor XIII and factor XI variants. Even for moderately strong risk factors (relative risks 2-5), the majority of carriers will never develop thrombosis.
The risk factors for venous thrombosis differ from those for arterial vascular disease. During the past 5 years, knowledge about the aetiology of venous thrombosis has advanced with the discovery of ...several factors that contribute to the incidence of thrombosis, particularly the role of coagulation abnormalities. These abnormalities are common in the general population and therefore will be present simultaneously in some individuals. The resultant genegene and gene-environment interactions between risk factors are the key to the understanding of why a certain person develops thrombosis at a specific point in time.
The incidence of venous thrombosis (VT) increases sharply with age: it is very rare in young individuals (<1 per 10,000 per year) but increases to ∼ 1% per year in the elderly, which indicates that ...aging is one of the strongest and most prevalent risk factor for venous thrombosis. The cause of this steep age gradient is as yet, unexplained. The aim of this review was to provide an overview of studies on the effect of conventional risk factors as well as age-specific risk factors for thrombosis in the elderly. Limited data are available on risk factors for thrombosis in the elderly, i.e. all results are based on small study groups. Results indicate that, of the conventional risk factors, malignant disease, the presence of co-morbidities and the genetic risk factors factor (F)V Leiden and the prothrombin mutation seem to be associated with an increased risk of venous thrombosis. In the elderly, the population attributable risk (PAR) of malignancy is approximately 35%, for co-morbidities a PAR up to 25% is found, and the contribution of genetic risk factors to the thrombosis incidence is estimated to be 7-22%. Age-specific risk factors of thrombosis, i.e. endothelial dysfunction and frailty may be important in the explanation of the increased incidence of VT in the elderly. In conclusion, as aging is a major risk factor for thrombosis, further identification of the risk factors for thrombosis in the elderly is needed to elucidate the age gradient of the incidence of VT and to target preventive measures.
The European Network of Rare Bleeding Disorders (EN-RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs.
To explore the relationship between ...coagulation factor activity level and bleeding severity in patients with RBDs.
Cross-sectional study using data from 489 patients registered in the EN-RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity.
The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL(-1); FV, 12 U dL(-1); combined FV + VIII, 43 U dL(-1); FVII, 25 U dL(-1); FX, 56 U dL(-1) ; FXI, 26 U dL(-1); FXIII, 31 U dL(-1). Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL(-1) for combined FV + VIII; < 8 U dL(-1) for FVI; < 10 U dL(-1) for FX; and < 25 U dL(-1) for FXI.
There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies.
Essentials Elevated procoagulant levels are associated with an increased risk of venous thrombosis (VT). The dependency on concurrent increased factor levels and VT was analyzed in a large study. ...Factor VIII (FVIII) and von Willebrand factor (VWF) were associated with the highest VT risk. The risks for other procoagulant factor levels were largely explained by FVIII and VWF. SUMMARY: Background Coagulation factors are essential for robust clot formation. However, elevated levels of procoagulant factors are associated with an increased risk of venous thrombosis (VT). The precise contribution of these factors to the development of VT is not yet understood. Objectives We determined the thrombosis risk for the highest levels of eight selected coagulation factors. Furthermore, we analyzed which of these coagulation factors had the strongest impact on the supposed association. Methods We used data of 2377 patients with a first VT and 2940 control subjects in whom fibrinogen, von Willebrand factor (VWF), factor II, FVII, FVIII, FIX, FX and FXI levels were measured. Results The odds ratios (ORs) for the various coagulation factor levels (> 99th percentile versus ≤ 25th percentile) varied between 1.8 and 4, except for FVIII (OR 23.0; 95% confidence interval CI 14.7-36.0) and VWF (OR 24.0; 95% CI 15.3-37.3). Adjustment for FVIII and VWF in a mediation analysis reduced the risks of the other factors to unity, with the exception of FIX and FXI (remaining ORs between 1.7 and 1.9). Conversely, the ORs for FVIII and VWF levels remained high after adjustment for all other procoagulant factors (FVIII: 16.0; 95% CI 9.7-26.3; VWF: 17.6; 95% CI 10.7-28.8). Conclusions Our results imply that the observed relationship between VT and coagulation factor levels can be largely explained by FVIII and VWF. FVIII and VWF levels were also associated with the highest VT risk.
Female hormones and thrombosis Rosendaal, F R; Helmerhorst, F M; Vandenbroucke, J P
Arteriosclerosis, thrombosis, and vascular biology,
2002-February, Letnik:
22, Številka:
2
Journal Article
Recenzirano
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Exogenous hormones are used by more than a hundred million women worldwide as oral contraceptives or for postmenopausal hormone replacement. Oral contraceptives increase the risk of venous ...thrombosis, of myocardial infarction, and of stroke. The risk is highest during the first year of use. The venous thrombotic risk of oral contraceptives is high among women with coagulation abnormalities and with so-called third-generation contraceptives (containing desogestrel or gestodene). The risk of myocardial infarction does not appear to depend on coagulation abnormalities or the type of oral contraceptive. Hormone replacement therapy increases the risk of venous thrombosis. This risk is also highest in the first year of use and among women with coagulation abnormalities. The risk becomes very high in women with a previous venous thrombosis. Randomized trials have not confirmed a beneficial effect of postmenopausal hormones on the occurrence of myocardial infarction.
Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT).
To determine the risk of PTS after DVT and to assess risk factors for PTS.
Patients were recruited from the ...Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Consecutive patients who suffered a first DVT of the leg were included in a follow-up study. All patients completed a questionnaire and DNA was obtained. PTS was ascertained in a structured interview using a clinical classification score.
The 1-year cumulative incidence of PTS was 25% and 7% for severe PTS. Elastic compression stockings were prescribed in 1412 (85%) patients. The majority used their stockings every day. Women were at an increased risk compared with men risk ratio (RR) 1.5, 95% confidence interval (CI) 1.3-1.8. Similarly, obese patients had a 1.5-fold increased risk of PTS compared with normal weight patients (RR 1.5, 95% CI 1.2-1.9), with a 1-year cumulative incidence of 34% compared with 22%. Patients who already had varicose veins had an increased risk (RR 1.5, 95% CI 1.2-1.8) of PTS. DVT in the femoral and iliac vein was associated with a 1.3-fold increased risk of PTS compared with popliteal vein thrombosis (RR 1.3, 95% CI 1.1-1.6). Patients over 60 years were less likely to develop PTS than patients below the age of 30 (RR 0.6, 95% CI 0.4-0.9). Malignancy, surgery, minor injury, plaster cast, pregnancy or hormone use did not influence the risk of PTS neither did factor (F)V Leiden nor the prothrombin 20210A mutation.
PTS is a frequent complication of DVT, despite the widespread use of elastic compression stockings. Women, obese patients, patients with proximal DVT and those with varicose veins have an increased risk of PTS, whereas the elderly appeared to have a decreased risk.
Estimates of the incidence of venous thrombosis (VT) vary, and data on mortality are limited.
We estimated the incidence and mortality of a first VT event in a general population.
From the residents ...of Nord-Trøndelag county in Norway aged 20 years and older (n = 94 194), we identified all cases with an objectively verified diagnosis of VT that occurred between 1995 and 2001. Patients and diagnosis characteristics were retrieved from medical records.
Seven hundred and forty patients were identified with a first diagnosis of VT during 516,405 person-years of follow-up. The incidence rate for all first VT events was 1.43 per 1000 person-years 95% confidence interval (CI): 1.33-1.54, that for deep-vein thrombosis (DVT) was 0.93 per 1000 person-years (95% CI: 0.85-1.02), and that for pulmonary embolism (PE) was 0.50 per 1000 person-years (95% CI: 0.44-0.56). The incidence rates increased exponentially with age, and were slightly higher in women than in men. The 30-day case-fatality rate was higher in patients with PE than in those with DVT 9.7% vs. 4.6%, risk ratio 2.1 (95% CI: 1.2-3.7); it was also higher in patients with cancer than in patients without cancer 19.1% vs. 3.6%, risk ratio 3.8 (95% CI 1.6-9.2). The risk of dying was highest in the first months subsequent to the VT, after which it gradually approached the mortality rate in the general population.
This study provides estimates of incidence and mortality of a first VT event in the general population.
The incidence of venous thrombosis (VT) for cancer patients is increased compared with patients without cancer, but estimations of the incidence for different types of cancer have rarely been made ...because of the low incidence of various types of cancer. Large registries offer an opportunity to study the risk of VT in large cohorts of cancer patients, which is essential in decisions on prophylactic anti-coagulant treatment.
This cohort study estimates the incidence of VT in cancer patients by using record linkage of a Cancer Registry and an Anticoagulation Clinic database in the Netherlands. Cumulative incidences in patients with different types of malignancies were estimated. We calculated relative risks (RRs) in relation to the presence of distant metastases and treatment.
Tumors of the bone, ovary, brain, and pancreas are associated with the highest incidence of VT (37.7, 32.6, 32.1, and 22.7/1000/0.5 year). Patients with distant metastases had a 1.9-fold increased risk RRadj: 1.9; 95% confidence interval (CI): 1.6-2.3. Chemotherapy leads to a 2.2-fold increased risk (RR(adj): 2.2; 95% CI: 1.8-2.7) and hormonal therapy leads to a 1.6-fold increased risk (RRadj: 1.6; 95% CI: 1.3-2.1) compared with patients not using these treatment modalities. Patients with radiotherapy or surgery did not have an increased risk.
We compared the overall incidences of VT in the first half year in our study to the risk of major bleeding as described in the literature. For patients with distant metastases, for several types of cancer, prophylactic anti-thrombotic treatment could be beneficial.
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