Tests & Clinical Applications, Thrombophilia, What is the origin of the disease?
Congenital thrombophilia may be shown to have a genetic cause in around one in every two patients presenting with DVT.
The abnormalities are due to deficiencies in physiological inhibitors of coagulation or, conversely, and far less frequently, to hypofibrinolysis. This may be caused by an excessive level of inhibitor to tissue plasminogen activator and urokinase (PAI-1) or to a defect in tissue plasminogen activator (tPA). However, screening is rarely carried out to establish the causes of hypofibrinolysis in standard practice, and such testing must be performed at specialised centres.
The main biological risk factors for congenital thrombophilia are shown in the following table.
| Risk factor | Prevalence in the general population | Prevalence in patients presenting an initial thromboembolic episode | relative risk |
|---|---|---|---|
| Antithrombin deficiency | 0.1 – 0.3 % | 1 – 2 % | 15 – 20 |
| Protein C deficiency | 0.2 – 0.5 % | 2 – 3 % | 15 – 20 |
| Protein S deficiency | 0.2 – 0.5 % | 2 – 3 % | 15 – 20 |
| Heterozygous factor V Leiden | 3 – 7 % | 10 – 20 % | 5 – 7 |
| Heterozygous factor II gene mutation G20210A | 1 – 3 % | 5 – 6 % | 2 – 3 |
| Hyperhomocysteinaemia* | ? | ? | 1.5 – 2.5 |
| Elevated factor VIII* | ? | ? | 3 – 5 |
| Certain types of dysfibrinogenaemia* | ? | ? | ? |
*Risk factors of mixed origin: constitutional and/or acquired
(Merriman L, Greaves M. Postgrad Med J 2006; Lifjering WM, Rosendaal FR, Cannegieter SC. Br J Haematol 2010)