Hypofibrinolysis as a Risk Factor for Venous Thrombosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 272-272 ◽  
Author(s):  
Mirjam E. Meltzer ◽  
Carine J.M. Doggen ◽  
Philip G. de Groot ◽  
Frits R. Rosendaal ◽  
Ton Lisman
Keyword(s):  
Risk Factors ◽  
The Netherlands ◽  
Venous Thrombosis ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Control Subjects ◽  
Fourth Quartile ◽  
Prothrombin 20210A

Abstract Several genetic and acquired risk factors are known to increase the risk of venous thrombosis (VT). The occurrence of multiple risk factors in a single patient may be associated with a thrombotic risk which exceeds the sum of the individual risks, as is for example seen with oral contraceptive use and factor V Leiden. Previously we have shown that reduced fibrinolytic potential a measured by a plasma-based assay increases the risk of VT. Here, we investigated the thrombotic risk in individuals with hypofibrinolysis overall and in combination with the factor V Leiden and prothrombin 20210A mutation, in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a large population-based case-control study. In the present analyses, 2420 patients with a first episode of deep vein thrombosis of the leg or a pulmonary embolism and 2943 control subjects (partners and randomly selected individuals) between 18 and 70 years were included. Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was studied by monitoring changes in turbidity during clot formation and subsequent lysis. Using quartiles of clot lysis time (CLT) based on the values found in the control subjects, we found an increase in risk of VT with each increasing quartile of CLT. The odds ratio (OR) (95% confidence interval (CI)) for individuals in the fourth quartile of CLT compared to individuals in the first quartile was 1.8 (1.5–2.1), after adjustment for age and sex. In younger subjects and women these ORs were slightly elevated (table). In individuals with hypofibrinolysis (i.e., the highest quartile of CLT) and without the factor V Leiden mutation an OR of 1.8 (1.5–2.1) was found compared to those without the mutation and with the lowest CLTs (i.e., in the lowest quartile). Individuals with the factor V Leiden mutation with the lowest CLTs had a risk of VT that was 3.6 (2.4–5.4) times increased, compared to those without the mutation and with the lowest CLTs. The risk of VT increased 6.2–fold (4.2–9.2) for individuals in the fourth quartile of CLT with the factor V Leiden mutation compared to people in the first quartile without the mutation. The same analyses for the prothrombin 20210A mutation gave ORs of 1.8 (1.5–2.1) for hypofibrinolysis only, 3.6 (1.4–9.5) for the mutation only, and 3.2 (1.9–5.3) for the combination. Our study confirms the increased risk of VT in individuals with hypofibrinolysis. This risk is especially pronounced in women and younger individuals. The combination of hypofibrinolysis and the factor V Leiden or prothrombin mutation does not appear to enhance the risk of VT. This study was supported by the Netherlands Heart Foundation (NHF) (Grant no. 2005B060 and 98.113) and the Netherlands Organisation for Scientific research (NWO) (Grant no. 912-03-033/2003). Risk of VT for individuals in the fourth quartile (Q4) of CLT overall <49 years >49 years women men * Q1 is reference # cases(Q1/Q4) 452/784 275/285 177/499 261/385 191/398 #controles (Q1/Q4) 733/733 458/248 274/485 430/357 303/376 OR (95% CI)* 1.8 (1.5–2.1) 2.5 (1.9–3.2) 1.7 (1.4–2.2) 2.7 (2.1–3.4) 1.6 (1.3–2.1)

Polymorphisms in the protein C gene as risk factor for venous thrombosis

2009 ◽  
Vol 101 (01) ◽  
pp. 62-67 ◽  
Author(s):  
Carine Doggen ◽  
Hans Vos ◽  
Pieter Reitsma ◽  
Frits Rosendaal ◽  
Elisabeth Pomp
Keyword(s):  
Oral Contraceptive ◽  
Venous Thrombosis ◽  
Protein C ◽  
Contraceptive Use ◽  
Factor V Leiden ◽  
Factor V ◽  
Thrombotic Risk ◽  
Control Subjects ◽  
Oral Contraceptive Use ◽  
Increased Risk

SummaryProtein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2055-2061 ◽  
Author(s):  
Elizabeth F. W. van Vlijmen ◽  
Nic J. G. M. Veeger ◽  
Saskia Middeldorp ◽  
Karly Hamulyák ◽  
Martin H. Prins ◽  
...  
Keyword(s):  
Risk Factors ◽  
Oral Contraceptive ◽  
Factor V Leiden ◽  
Informed Choice ◽  
Rational Approach ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractCurrent guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0.13 (95% confidence interval 0.08-0.21), 0.35 (0.22-0.53), and 0.94 (0.47-1.67) per 100 person-years, while these were 0.19 (0.07-0.41), 0.49 (0.18-1.07), and 0.86 (0.10-3.11) during COC use, and 0.73 (0.30-1.51), 1.97 (0.94-3.63), and 7.65 (3.08-15.76) during pregnancy. COC use and pregnancy were independent risk factors for VTE, with highest risk during pregnancy postpartum, as demonstrated by adjusted hazard ratios of 16.0 (8.0-32.2) versus 2.2 (1.1-4.0) during COC use. Rather than strictly contraindicating COC use, we advocate that detailed counseling on all contraceptive options, including COCs, addressing the associated risks of both VTE and unintended pregnancy, enabling these women to make an informed choice.

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

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3393-3393 ◽  
Author(s):  
Suely M Rezende ◽  
Willem M. Lijfering ◽  
Frits R. Rosendaal ◽  
Suzanne C. Cannegieter
Keyword(s):  
Risk Factors ◽  
The Netherlands ◽  
Venous Thrombosis ◽  
Second Generation ◽  
Large Population ◽  
Factor V Leiden ◽  
Population Based ◽  
Factor V ◽  
Southeast Asians ◽  
Second Generation Immigrants

Abstract Abstract 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. Disclosures: No relevant conflicts of interest to declare.

Follow-up von Patienten mit persistierender APC-Resistenz ohne Faktor V Leiden

VASA ◽  
2001 ◽  
Vol 30 (1) ◽  
pp. 24-27 ◽  
Author(s):  
T. Schwarz ◽  
G. Siegert ◽  
U. Mikulin ◽  
S. Gehrisch ◽  
E. Runge ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Genetic Defect ◽  
Factor V Leiden ◽  
Arterial Disease ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Apc Resistance

Background: Activated protein C (APC) resistance and factor V Leiden mutation are major risk factors for deep venous thrombosis. Previous work has led to the view that the coagulation phenotype and the genetic defect are associated in almost all patients. It has been reported about single APC-resistant patients without associated factor V Leiden, but significance and thrombotic risk of this constellation have not yet been established. Patients and methods: We tested 486 consecutive patients with deep venous thrombosis, arterial disease or other than vascular disease for APC-resistance with a factor VIII based assay. Results: 149 patients (31%) showed a pathological APC-ratio. Sensitivity and specificity for detection of factor V Leiden were 100% and 40%, respectively. At 6 months follow-up APC-ratio returned to normal in 55% of the patients with initial pathological APC-resistance. At 12 months follow-up 91% of the patients with persistent APC-resistance showed a pathological ratio as well. Conclusions: Patients with APC-resistance not due to factor V Leiden can be attributed to one subset with reversible APC-resistance – possibly due to a hypercoagulable state in an acute thrombotic situation, and to another with persistent APC-resistance.

Venous Thrombotic Risk in Family Members of Unselected Individuals with Factor V Leiden

2000 ◽  
Vol 83 (06) ◽  
pp. 817-821 ◽  
Author(s):  
R. P. M. Lensen ◽  
R. M. Bertina ◽  
H. de Ronde ◽  
J. P. Vandenbroucke ◽  
F. R. Rosendaal
Keyword(s):  
Risk Factors ◽  
Positive Family History ◽  
Family Members ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Asymptomatic Carriers ◽  
Kaplan Meier ◽  
Increased Risk

SummaryThe factor V Leiden mutation (FVL) leads to a seven-fold increased risk of venous thromboembolism (VTE). In thrombophilic families, 25% of carriers have experienced thrombosis before the age of 40 years. Aim of our study was to assess the association of FVL with VTE in first-degree family members of unselected symptomatic and asymptomatic carriers of FVL.We tested 197 relatives of consecutive thrombosis patients with FVL and 36 relatives of asymptomatic carriers on the presence of FVL and the occurrence of VTE.The incidence of VTE in relatives with FVL of symptomatic carriers was 0.34%/year. This was similar to the incidence in relatives with FVL of asymptomatic carriers. Kaplan Meier analysis in relatives of symptomatic propositi showed that at the age of 58 years, thrombosisfree survival was reduced to 75% in carriers and 93% in non-carriers (P < 0.05). Carriers of FVL had a three times higher thrombotic risk than non-carriers. In combination with environmental risk factors, FVL clearly adds to the risk of VTE. The thrombotic incidence rate in these unselected relatives with FVL, however, is considerably lower than was seen in carriers of thrombophilic families (1.7%/year). Therefore, special care should be paid to individuals with a positive family history of venous thrombosis while exposed to these risk factors.

Thrombotic risk factors in Chinese Budd-Chiari syndrome patients

2013 ◽  
Vol 109 (05) ◽  
pp. 878-884 ◽  
Author(s):  
Chuangye He ◽  
Zhanxin Yin ◽  
Jing Niu ◽  
Ming Bai ◽  
Zhiping Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myeloproliferative Neoplasms ◽  
Factor V Leiden ◽  
Jak2 V617f ◽  
Paroxysmal Nocturnal Haemoglobinuria ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

SummaryIn Western countries, thrombotic risk factors for Budd-Chiari syndrome (BCS) are very common, including factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, paroxysmal nocturnal haemoglobinuria, etc. However, the data regarding thrombotic risk factors in Chinese BCS patients are extremely limited. An observational study was conducted to examine this issue. A total of 246 BCS patients who were consecutively admitted to our department between July 1999 and December 2011 were invited to be examined for thrombotic risk factors. Of these, 169 patients were enrolled. Neither factor V Leiden mutation nor prothrombin G20210A mutation was found in any of 136 patients tested. JAK2 V617F mutation was positive in four of 169 patients tested. Neither MPL W515L/K mutation nor JAK2 exon 12 mutation was found in any of 135 patients tested. Overt myeloproliferative neoplasms were diagnosed in five patients (polycythemia vera, n=3; essential thrombocythemia, n=1; idiopathic myelofibrosis, n=1). Two of them had positive JAK2 V617F mutation. Both CD55 and CD59 deficiencies were found in one of 166 patients tested. This patient had a previous history of paroxysmal nocturnal haemoglobinuria before BCS. Anticardiolipin IgG antibodies were positive or weakly positive in six of 166 patients tested. Hyperhomocysteinaemia was found in 64 of 128 patients tested. 5,10-methylenetetrahydrofolate reductase C677T mutation was found in 96 of 135 patients tested. In conclusion, factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, and paroxysmal nocturnal haemoglobinuria are very rare in Chinese BCS patients, suggesting that the etiological distribution of BCS might be different between Western countries and China.

scholarly journals On the Absence of Calreticulin (CALR) Mutations in Chronic Myeloprolierative Neoplasms (MPNs) with Splanchnic Venous Thrombosis (SVT): Experience from a Single Institution

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3198-3198 ◽  
Author(s):  
Bruno Martino ◽  
Corrado Mammì ◽  
Claudia Labate ◽  
Martino Enrica Antonia ◽  
Francesca Ronco ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thrombosis ◽  
Factor V Leiden ◽  
Factor V ◽  
Jak2 Mutation ◽  
Thrombotic Risk ◽  
Thrombotic Risk Factor ◽  
Prothrombotic Risk Factors ◽  
Calr Mutations

Abstract Background: According to recent findings, the management of myeloproliferative neoplasms (MPNs) is highly dependent on presence or absence of thrombotic events. The JAK2 mutation has been identified as a marker of MPNs. It is also an occult marker in several patients with splanchnic venous thrombosis (SVT), but its contribution as an additional thrombotic risk factor in MPNs is still under discussion. Moreover, a pro-thrombotic risk factor, either inherited or acquired (Factor V Leiden mutation, deficiencies in protein C, protein S and Prothrombin mutation 20210) can be identified in these patients. Recently, another milestone in the molecular diagnosis of MPNs, somatic mutations in the CALR gene, has been reported. A total of 36 types of frame-shifting insertions and deletions were detected in the exon 9 of CALR gene, which encodes a Ca2+ binding protein in endoplasmic reticulum called calreticulin. Type-1, 52-bp deletion (p.L367fs*46), and type-2, 5-bp TTGTC insertion (p.K385fs*47) variants constitute more than 80% of these mutations These mutations were reported to have a incidence of over 60% to 80% in JAK2 and MPLmutation-negative Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) patients. Compared to those with JAK2 mutation, CALR-mutated ET patients are younger and have a lower leukocyte count and higher platelet count. CARL mutations have been also reported as a favorable prognostic factor on thrombosis-free survival (TFS) for ET patients. Aims: In this study, we evaluated the incidence of SVT, JAK2 and CALR mutations, and prothrombotic risk factors in patients with MPNs observed in our center from January 2000 to January 2014. Methods: We performed a retrospective review of clinical charts of 466 Ph1 negative MPN patients followed in our center, classified according to the WHO 2008 classification. Patient and disease characteristics, including JAK2V617F, MPL and CALR mutations and thrombotic risk factors were recorded. Results: The median age of patients with diagnosis of MPN was 43 years. Fourteen patients (13 females, 1 male; 3%) of median age 46 years presented a SVT. Three had a Budd Chiari syndrome and 11 a portal venous thrombosis. According to a histological review, these patients were classified as follows: ET, 2 cases, PMF, 3 cases, Polycythemia Vera (PV) 1 case, Myelofibrosis in a prefibrotic phase (MF0) 8 cases. Classification of 11 cases with Myelofibrosis according to the IPSS identified 7 as INT1, 1 as INT2 and 3 as low risk. Among all 14 patients diagnosed with SVT, 12 were JAK2V617F positive with a median allelic burden of 30%, 1 patient was MPL positive, and 1 patient was triple-negative. CALR mutation was not observed in any of the patients. Two cases were diagnosed with MPN 30 months after SVT, 3 patients experienced SVT after a median follow-up of 108 months from MPN diagnosis while in 9 patients the diagnosis of MPN was concomitant to SVT. In the latter patients, median Hb levels were 12.4 g/dL , WBC 8260 /µL, HCT 36.3%, PLT 337.000/ µL and a modest hepatomegaly and splenomegaly were documented. Prothrombotic risk factors were found in 9 of 13 patients. Two patients experienced a thrombotic episode prior to the diagnosis of SVT and two subsequently during the follow-up. Interestingly, 9 (70%) of MPN patients with SVT exhibited at least one prothromobtic risk factor, such as factor V Leiden, Protein C deficiency, hyperhomocystinemia and 50% had two or more associated defects. Thirteen of the 14 patients are currently being treated as follows hydroxyurea (9), interferon (1), and ruxolitinib (3). All patients received oral anticoagulant treatment except for three who are on antiplatelet therapy. MPN patients without SVT had a lower prevalence of prothrombotic risk factors and developed venous thrombosis in different anatomical sites: in these cases WBC count, platelet values and the presence of JAK2V617F mutation correlated with the development of the thrombotic event. Conclusions: Although SVT has a low incidence in MPN patients, a potential benefit of testing for mutations in CALR gene and for additional prothrombotic risk factors is suggested in the whole MPN population for the prevention and treatment of this complication. Disclosures No relevant conflicts of interest to declare.

Inherited Prethrombotic Disorders and Infectious Purpura

1996 ◽  
Vol 75 (06) ◽  
pp. 899-901 ◽  
Author(s):  
Rudi G J Westendorp ◽  
Pieter H Reitsma ◽  
Rogier M Bertina
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Disease Course ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
C Protein ◽  
Severity Of The Disease

SummaryPatients with severe meningococcal infection are characterized by extensive microvascular thrombosis, consumption coagulopathy and secondary hemorrhages. The contribution of the inherited prethrombotic disorders to the severity of the disease course is not established yet. Here, we report on the levels of protein C, protein S, antithrombin and the presence of the factor V Leiden mutation (R506Q) in 50 patients with meningococcal disease, as determined 6 to 58 months after hospital discharge. In addition, we recalled the parents of 16 deceased patients to screen for the mutation in factor V, an abnormality which results in resistance to activated protein C. Among the patients, the prevalence of the genetic risk factors for thrombosis was not higher than expected on the basis of their prevalence in the general population. Moreover, the prevalence of the factor V Leiden mutation was not increased among the parents of the deceased patients. The individual plasma levels of protein C, protein S, and antithrombin did not differ between the patients with or without severe purpura. The present data constitute circumstantial evidence that primary defects in the natural anticoagulant systems do not play a major role in the severity of the disease course. Screening of patients with infectious purpura for inherited thrombotic risk factors is therefore not indicated.

scholarly journals Minor Events and the Risk of Deep Venous Thrombosis

2000 ◽  
Vol 83 (03) ◽  
pp. 408-411 ◽  
Author(s):  
E. M. W. Eekhoff ◽  
J. P. Vandenbroucke ◽  
F. R. Rosendaal
Keyword(s):  
Risk Factors ◽  
Confidence Interval ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Common Disease ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Synergy Index

SummaryBackground Deep venous thrombosis is a common disease, with genetic and acquired risk factors. Many patients have a history of minor events (short periods of immobilisation such as prolonged travel, short illness, minor surgery or injuries) before onset of venous thrombosis. However, the role of these minor events has received little formal study. Also, we do not know how minor events might interact with the presence of genetic prothrombotic defects (factor V Leiden mutation, factor II mutation, protein C, S and antithrombin deficiency). Patients and Methods On the basis of case-control data from a thrombosis service in the Netherlands, we added a follow-up period for a casecross-over analysis of minor events as risk factors, and a case-only analysis for the interaction with factor V Leiden. A total of 187 patients with first, objectively diagnosed venous thrombosis of the legs, aged 15–70, without underlying malignancies and without major acquired risk factors entered the study. For the analysis of minor events in the case-cross-over analysis, we used a matched odds ratio; in the caseonly analysis, we used the multiplicative synergy index. Results In 32.6% of the 187 patients with deep venous thrombosis who did not have major acquired risk factors, minor events were the only external risk factors. Minor events increased the risk of thrombosis about 3-fold, as estimated in the case-cross-over analysis (odds ratio 2.9, 95% confidence interval 1.5–5.4). The synergy index between minor events and factor V Leiden mutation in the case-only analysis was 0.7 (95% confidence interval 0.3–1.5). Therefore, persons with factor V Leiden mutation who experience a minor event will have an estimated risk increase of about 17-fold, which exceeds the sum of the individual risk factors. Conclusions Minor events are likely to play an important role in the development of deep venous thrombosis, especially in the presence of genetic prothrombotic conditions.

scholarly journals Retinal vein occlusion: A form of venous thrombosis or a complication of atherosclerosis?

2005 ◽  
Vol 93 (06) ◽  
pp. 1021-1026 ◽  
Author(s):  
Martin den Heijer ◽  
Johannes Cruysberg ◽  
Hub Wollersheim ◽  
Sebastian Bredie ◽  
Mirian Janssen
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Gene Mutation ◽  
Factor V Leiden ◽  
Anticardiolipin Antibodies ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Vein Occlusion ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

SummaryPrevious studies have shown an increased risk of retinal vein occlusion (RVO) in patients with hypertension, hypercholesterolemia and diabetes mellitus. Literature on the association between thrombophilic factors and RVO consists of small studies and case reports. The objective was to determine the relationship between thrombophilic risk factors and RVO. Thrombophilic risk factors analyzed were hyperhomocysteinemia, MTHFR gene mutation, factor V Leiden mutation, protein C and S deficiency, antithrombin deficiency, prothrombin gene mutation, anticardiolipin antibodies and lupus anticoagulant. For all currently known thrombophilic risk factors odds ratios for RVO were calculated as estimates of relative risk. The odds ratios were 8.9 (95% CI 5.7 –13.7) for hyperhomocysteinemia, 3.9 (95% CI 2.3 – 6.7) for anticardiolipin antibodies, 1.2 (95% CI 0.9 –1.6) for MTHFR, 1.5 (95% CI 1.0 – 2.2) for factor V Leiden mutation and 1.6 (95% CI 0.8 – 3.2) for prothrombin gene mutation. In conclusion, regarding thrombophilic risk factors and RVO there is only evidence for an association with hyperhomocysteinemia and anticardiolipin antibodies, factors that are known as risk factors for venous thrombosis as well as for arterial vascular disease. The minor effect of factor V Leiden mutation and the protrombin gene mutation (risk factors for venous thrombosis only) suggests that atherosclerosis might be an important factor in the development of CRVO.

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