Thrombophilia
screening in patients taking oral contraceptivesDefinition
The term Thrombophilia describes the familial or acquired disorders of the haemostatic mechanism which are likely to predispose to thrombosis.
Recent developments
Evidence has become available recently that some oral contraceptives are more likely to predispose to thrombosis. Although no national guidelines have been produced, suggestions have been made on the media that women concerned about their risk of thrombosis could have a Thrombophilia screen performed.
Patients who should be investigated for Thrombophilia
The Haemostasis and Thrombosis task Force of the British Committee for Standards in the Haematology have issued guidelines as to which patients should be investigated.
- Venous thromboembolism before the age of 40 - 45 years.
- Recurrent venous thrombosis or thrombophiebitis.
- Thrombosis in an unusual site, e.g. mesenteric vein, cerebral vein, etc.
- Unexplained neonatal thrombosis.
- Skin necrosis particularly if on coumarin.
- Arterial thrombosis before the age of 30.
- Relatives of patients with thrombophilic abnormality. *
- Patients with strong family history of venous thrombosis. *
- Unexplained prolonged activated partial thromboplastin time. **
- Patients with recurrent foetal loss, ITP or SLE. **
The first six conditions listed would probably not be applicable to patients that you were considering starting on an oral contraceptive but the last four conditions may be relevant.
* These patients may need to be investigated for familial thrombophilia (see
below)
** These patients may need to be investigated for evidence of the
antiphospholipid syndrome.
Familial Thrombophilia
The tests normally performed are:
- Antithrombin III measurement
- Protein C antigen
- Protein C activity
- Protein S
- Activated protein C resistance
Except in very unusual cases such patients do not need to be tested for the presence of antiphospholipid antibodies or the lupus anticoagulant.
Activated Protein C resistance
In the last few years this has emerged as the commonest cause of familial thrombophilia. It is present in 3-5% of a general population sample in the Netherlands but the incidence in the UK may be less. It is claimed that women who use oral contraceptive and who have activated protein C resistance may be 30 times more likely to suffer thromboembolism than in who do not have the abnormality and who are not on oral contraceptive
The most common cause of activated protein C resistance is factor V Leiden.
Screening for Antiphospholipid Antibodies
Citrated blood is tested for the presence of the lupus anticoagulant. Clotted blood is used for measurement of antiphospholipid antibody.
Except in very unusual circumstances these patients do not need to be tested for familial thrombophilia.
| Thrombophilia screening tests cannot be done
on blood taken at the surgery. PLEASE NOTE:
|
Causes of thrombophilia
Hereditable thrombophilia
| Increased risk of thrombosis | Prevalence in patients with venous thromboembolism (VTE) (%) | Prevalence in normal population (%) | |
| Factor V Leiden heterozygous (activated
protein C resistance) Factor V Leiden homozygous individuals have 80x risk of VTE |
3-8x | 25-50 | 5.0 |
| Prothrombin G20210A | 3x | 6 | 2.0 |
| Antithrombin deficiency | 25-50x | 1 | 0.02 |
| Protein C deficiency | 10-15x | 3 | 0.3 |
| Protein S deficiciency | 10x | 3 | 2.0 |
| Dysfibrinogeariablenaemia | Variable | Low | Rare |
Acquired thrombophilia
- Antiphospholipid antibodies associated with venous and arterial thrombosis as well as first trimester abortions. Collagenosis, SLE.
- Combined contraceptive pill, HRT, obesity, malignancy and chronic inflammatory conditions all increase the risk of VTE.
Source
Mo Dewar, consultant haemotologist. BHF Factfile 02/2002
References
- Standard Haematology Practice Ed Bryon Roberts 1991, pages 112 - 127.
- Increased risk of venous thrombosis in all contraceptive users who are carriers of Factor V Leiden mutation Vandenbroucke et al. Lancet 1994; 344:1453-57.