Special tendency to thrombosis as a result of inherited or acquired haemostatic disorders.
The risk of a pregnant woman suffering a thrombotic event or gestational complications increases if she has a thrombophilia.
- Inherited (or hereditary) thrombophilia includes:
- Acquired thrombophilia
|Thrombophilia classification||Thrombophilia defects|
|Inherited due to plasma deficiency||AT deficiency
|Inherited due to genetic mutations||Mutation G1691A of the Factor V Leiden (FVL)
Mutation G20210A of the Prothrombin gene (FII)
|Acquired by Antiphospholipid antibodies||Lupus anticoagulant (LA)
Anticardiolipin antibodies or ACA
Anti-β2 GPI antibodies
|Obstetric pathology||1 or more foetal deaths at or beyond the 10th week.
3 or more consecutive miscarriages before the 10th week.
Premature birth (<34 weeks) due to eclampsia, pre-eclampsia or placental insufficiency.
2 determinations 12 weeks apart
|Anticardiolipin antibodies IgG or IgM|
|Anti-B2 GP1 antibodies IgG or IgM|
|Venous thromboembolic disease (VTE), before the age of 50, idiopathic or recurrent.|
|Venous thromboembolic disease (VTE), with atypical location (hepatic, mesenteric, portal, cerebral).|
|Recurrent superficial thrombophlebitis in absence of neoplasia.|
|Purpura fulminans in neonates or children.|
|Skin necrosis in patients with anticoagulant treatments.|
|First degree family history (parents and siblings) of high risks thrombophilia and/or venous thromboembolic disease (VTE) before the age of 50, idiopathic or caused by pregnancy or contraceptives .|
|Gestational vascular complications (GVC): request antiphospholipid antibodies. With personal or family history of VTE, consider inherited thrombophilia (there is no scientific evidence)
|1.-Favaloro EJ. Laboratory Investigation of Thrombophilia: the good, the bad, and the ugly. Semin Thromb Hemost 2009;35:695-710
2.-Baglin T. Clinical guidelines for testing for heritable thrombophilia.Br J Haematol 2010;149:209-220
3.-Royal College of Obstetricians and Gynaecologists 2011.
4.-Bates SM. ACCP Evidence -Based Clinical Practice Guidelines 2012;141:e691S-e736S
|Homozygote mutation Factor V Leiden or of prothrombin 20210A|
|Double homozygote Factor V Leiden and prothrombin 20210A|
|Antiphospholipid antibodies (APA):
|Protein C / Protein S deficiency|
|Heterozygote mutation Factor V Leiden or of prothrombin G20210A|
Lecumberri R. Enfermedad tromboembólica venosa y embarazo. Trombosis update. vol 4, 8 Enero 2011
Study of inherited plasma thrombophilia: this can be carried out at any time, outside the acute or recent episode of thrombosis. In the case of pregnancy or puerperium, bear in mind that protein S can be reduced physiologically during pregnancy (up to levels of 30-24% in the second and third trimester, respectively) . In the event of a deficiency of any protein, the determination must be repeated for confirmation. The AT and PC levels do not decrease but the APCR can be modified during the pregnancy.
Study of acquired thrombophilia: the antiphospholipid antibodies (LA, ACA, antiβ2GPI) can be requested during pregnancy. Positivity must be verified by repeating the determination within a 12-week interval. If negative, and the clinical suspicion persists due to bad obstetric result, the determination should be repeated.
|Thrombophilia||Testing Method||¿Reliable during pregnancy?||¿Reliable during acute Thrombosis?||¿Reliable with anticoagulation?|
|Factor V Leiden Mutation||Activated Protein C resistance assay (secont generation)||Yes||Yes||No|
|If abnormal: DNA analysis||Yes||Yes||Yes|
|Prothrombin G20210A Mutation||DNA Analysis||Yes||Yes||Yes|
|Protein C deficiency||Protein C activity (<60%)||Yes||No||No|
|Proteina S deficiency||Functional assay (<55%)||No*||No||No|
|Antithrombin deficiency||Antithrombin activity (<60%)||Yes||No||No|
ACOG Inherited Thrombophilias in Pregnancy .Practice Bulletin 138 September 2013.
|Reliable during acute thrombosis??||Reliable with anti-coagulation?|
|Factor V Leiden mutation||Genetic and/or|
|Protein C activity (<60%)||Coagulation||Yes||No||No|
|Protein S functional (<55%)*||Coagulation||No*||No||No|
|Antithrombin activity (<60%)||Coagulation||Yes||No||No|
|APA**(LA,ACA,B2GPI)||Coagulation immunological LA||Yes||Yes||No coagulation tests|
**antiphospholipid antibodies (LA, ACA, antiβ2GPI) must be verified for positivity within a 12-week interval. If negative, with clinical suspicion due to obstetric complication, repeat the determination.
|GENETIC inherited thrombophilia|
|Factor V Leiden mutation.|
|Factor II G20210A mutation.|
|PLASMA INHERITED thrombophilia|
- Inherited Physiological anticoagulant deficiency.
- AD Legacy.
|Antithrombin deficiency due to other causes:
- Drugs: heparin, chemotherapy, contraception.
- Acute episode of thrombosis, CID.
- Hepatopathy, Nephrotic syndrome, Sepsis.
- Inherited Physiological anticoagulant deficiency
- AD Legacy.
|Protein C deficiency due to other causes:
- Drugs: SIntrom® Warfarin®
- Acute episode of thrombosis, CID, Sepsis.
- Physiological anticoagulant deficiency.
- AD Legacy.
|Protein S deficiency due to other causes:
- Physiological during gestation (30-24% in 2nd-3rd trimester).
- Nephrotic syndrome, HIV, chemotherapy and
RResistance to PC inhibition due to mutation Factor V Leiden (FVL), FV not Leiden (HR2) and other unidentified ones.
|P C resistance activated due to other causes:
- Increase in Factor VIII.
- Lupus anticoagulant .
- Oral anticoagulants, Pregnancy, Contraceptives.
|Antiphospholipid antibodies or APA:|
- Lupus anticoagulant (DRVVT).
- Anti-cardiolipin and anti-B2GP1 antibodies.
|Cause ACQUIRED by:
- Lupus, Behcet syndrome, infections and drugs and sometimes with no justifying cause.
- Antiphospholipid Syndrome or APS: When APA is associated with thrombosis or GVC.
Prevalence in general population (%)
VTE risk in pregnancy with no history of thrombosis (%)
VTE risk in pregnancy with history of thrombosis (%)
Percentage of all VTE (%)
|Heterozygote Factor V Leiden|
1 - 15 %
|Homozygote Factor V Leiden|
|Heterozygote mutation A20210G of the Prothrombin gene|
2 - 5
|Homozygote mutation A20210G of the Prothrombin gene|
|Factor V Leiden + double heterozygote mutation A20210G|
1 - 3
|Antithrombin activity III (<60 %)|
3 - 7
|Protein C activity (<50 %)|
0,2 - 0,4
0,1 - 0,8
4 - 17
|Protein S free antigen (<55 %)*|
0,03 - 0,13
0 - 22
*Modification: Loockwood C, Wendel G; Committee on Practice Bulletins Obstetrics. Practice bulletins no. 124: inherited thrombophilias in pregnancy. Obstet Gynecol; 2011 Sept: 118(3): 730-40.