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Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on the risk of a first venous thrombosis.

Meltzer ME, Lisman T, Doggen CJ, de Groot PG, Rosendaal FR - PLoS Med. (2008)

Bottom Line: Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk.All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.

ABSTRACT

Background: Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.

Methods and findings: Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors. Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.

Conclusions: The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.

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Related in: MedlinePlus

Risk of Venous Thrombosis for Deciles of Clot Lysis TimeThe odds ratios are adjusted for age and sex. Error bars, 95% CI; nc, number of control participants (all); np, number of patients; Ref., reference category.
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pmed-0050097-g001: Risk of Venous Thrombosis for Deciles of Clot Lysis TimeThe odds ratios are adjusted for age and sex. Error bars, 95% CI; nc, number of control participants (all); np, number of patients; Ref., reference category.

Mentions: The association between CLT and the risk of venous thrombosis is shown in Figure 1. Using deciles of CLT based on the values found in all control participants, we found a clear dose-response relation between CLT and the risk of venous thrombosis. The ORadj for individuals in the tenth decile of CLT compared with individuals in the first decile was 2.9 (95% CI 2.2 to 3.8). In Table 1 the risk of venous thrombosis is presented in quartiles. Individuals with hypofibrinolysis, i.e., CLTs in the highest quartile, had an increased relative risk of venous thrombosis of 2.4 (95% CI 2.0 to 2.8) compared with individuals in the lowest quartile of CLT. Adjustment for age and sex did not change this result (ORadj 2.4, 95% CI 2.0 to 2.8). Using only the random control group yielded an ORadj of 2.5 (95% CI 2.1 to 3.1), and the matched analysis with only partner controls resulted in a similar ORadj of 2.0 (95% CI 1.5 to 2.6) for those with hypofibrinolysis.


Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on the risk of a first venous thrombosis.

Meltzer ME, Lisman T, Doggen CJ, de Groot PG, Rosendaal FR - PLoS Med. (2008)

Risk of Venous Thrombosis for Deciles of Clot Lysis TimeThe odds ratios are adjusted for age and sex. Error bars, 95% CI; nc, number of control participants (all); np, number of patients; Ref., reference category.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2365975&req=5

pmed-0050097-g001: Risk of Venous Thrombosis for Deciles of Clot Lysis TimeThe odds ratios are adjusted for age and sex. Error bars, 95% CI; nc, number of control participants (all); np, number of patients; Ref., reference category.
Mentions: The association between CLT and the risk of venous thrombosis is shown in Figure 1. Using deciles of CLT based on the values found in all control participants, we found a clear dose-response relation between CLT and the risk of venous thrombosis. The ORadj for individuals in the tenth decile of CLT compared with individuals in the first decile was 2.9 (95% CI 2.2 to 3.8). In Table 1 the risk of venous thrombosis is presented in quartiles. Individuals with hypofibrinolysis, i.e., CLTs in the highest quartile, had an increased relative risk of venous thrombosis of 2.4 (95% CI 2.0 to 2.8) compared with individuals in the lowest quartile of CLT. Adjustment for age and sex did not change this result (ORadj 2.4, 95% CI 2.0 to 2.8). Using only the random control group yielded an ORadj of 2.5 (95% CI 2.1 to 3.1), and the matched analysis with only partner controls resulted in a similar ORadj of 2.0 (95% CI 1.5 to 2.6) for those with hypofibrinolysis.

Bottom Line: Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk.All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.

ABSTRACT

Background: Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.

Methods and findings: Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors. Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.

Conclusions: The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.

Show MeSH
Related in: MedlinePlus