Defined as an acquired or congenital abnormality of hemostasis predisposing to thrombosis.
Contributes to venous thromboembolism, but its association with arterial thrombosis is controversial.
The term has been expanded to encompass patients with laboratory abnormalities associated with excessive thrombosis: Therefore patients who have never experienced venous thromboembolism can be diagnosed with thrombophilia.
Approximatley 5-10% of the general population has thrombophilia, with the vast majority not diagnosed.
Inherited thrombophilia is more common among people with European ancestry than among other ethnic groups, with the prevalence of up to 15%.
Most accepted inherited hemostatic abnormalities linked with venous thromboembolism are factor V Leiden, prothrombin G20210A mutation, deficiencies of antithrombin, protein C and protein S.
Risk for patients with thrombophilia increases with age, particularly after the age of 60 years.
Prevalence is strongly dependent on the patient population being tested.
In patients who never experienced VTE (venothrombembolism) the relative risk of VTE is 5-10 for deficiencies of anti-thrombin, protein C, protein S, and 2-5 for factor V Leiden or prothrombin gene 20210A.
The prevalence of thrombophilia in the general population is low: 5-10% in Whites, and 1-5% in nonwhites.
Prevalence is much higher in patients who’ve had at least one episode of spontaneous venous thromboembolism, at 34%.
Prevalence is elevated in first-degree family members of thrombophilic patients, at 17%.
Most tests include analysis for antithrombin, protein C, protein S, factor V Leiden, prothrombin G20210A mutation, homocysteine, fibrinogen, factor VIII, Factor XI, plasminogen, activated protein C resistance, prothrombin fragment 1,2, thrombin:antithrombin complex and d-dimer levels.
Rare inhibitor deficiencies, such as protein C, protein S, and antithrombin deficiencies, together account for only approximately 10%–15% of all cases of venous thrombosis.
Deficiencies of protein C, S, and anti-thrombin III are rarer then factor V Leiden and prothrombin G20210A, are seen in all ethnic groups, and mutations occur at multiple sites.
Decreased levels of protein C, S, and antithrombin may be seen with certain medical conditions and/or exposure to medications.
Elevated factor VIII activity may be seen in thrombophilia.
Persistently elevated factor VIII of levels greater than 150% of normal, associated with a 2-11 fold increased risk of VTE.
Factor VIII levels are genetically determined, and patients with type A or B blood have factor VIII levels 22% higher than those patients with type O blood.
Allelic variants in coagulation factor genes appear to account for a much larger fraction of venous thrombosis cases; the prothrombin 20210 G/A polymorphism and factor V Leiden present in approximately 2% and 5% of Caucasians, respectively, account for approximately 50% of cases in the Caucasian population.
Inherited thrombophilias are risk factors for people with venous thromboembolism in unusual sites including cerebral vein thrombosis, portal vein thrombosis and even superficial thrombophlebitis.
Factor V Leiden and prothrombin G20220A mutation have low clinical penetrance of venous thrombosis and have only a 5-10% risk that they will ever have a clot in their lifetime.
Hyperhomocysteinemia has an increase risk for VTE, however testing is no longer felt to be necessary because treatment with vitamin D supplements or folate does not reduce the risk of blood clots.
In women who do not have a positive family history VTE, the absolute risk is too small to advise against oral contraception in women with thrombophilia.
Women with thrombophilia and a family history of first degree relatives with VTE alternative contraception should be considered.
Studies of asymptomatic first-degree family members of VTE patients with antithrombin, protein C, protein S deficiency have shown that deficientfamily membershave a risk of VTE of 4.3% per year compared with 0.7% per year in non-deficient family members.
439 women with factor V Leiden would need to refrain from oral contraceptives to prevent single case ofof DVT.
Thrombophilia-
relative risk (rr) of venous thrombosis-normal-1
rr of venous thrombosis-oral contraceptive (OC) use-4
rr of venous thrombosis- Factor V Leiden heterozygous-5-7
rr of venous thrombosis- Factor V Leiden hetero +OC-30-35
rr of venous thrombosis- Factor V Leiden homozygous-80
rr of venous thrombosis- Factor V Leiden homo +OC->100
rr of venous thrombosis- Prothromb Gene Mutation hetero-3
rr of venous thrombosis- Prothromb Gene Mutation hetero+OC-16
rr of venous thrombosis- Protein C deficiency heterozyg-7
rr of venous thrombosis- Antithrombin deficiency hetero-5
rr of venous thrombosis- Hyperhomocysteinemia-2-4