The risk of a pregnant woman suffering a thrombotic event or gestational complications increases if she has a thrombophilia.

Thrombophilia classification	Thrombophilia defects
Inherited due to plasma deficiency	AT deficiency APCR Protein C Protein S
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

Clinical Criteria
Vascular thrombosis	Venous Arterial Small vessel
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.

Laboratory Criteria 2 determinations 12 weeks apart
Lupus anticoagulant
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)  Re-occurrence of early miscarriages (3 or more before the 10th week), one or more in second trimester. Abruptio, late foetal loss, IGR and pre-eclampsia

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

High Risk
Antithrombin deficiency
Homozygote mutation Factor V Leiden or of prothrombin 20210A
Double homozygote Factor V Leiden and prothrombin 20210A
Combined defects
Antiphospholipid antibodies (APA): Lupus anticoagulant. Anticardiolipin antibodies IgG or IgMm. Anti-B2 GP1 antibodies IgG or IgM.

Moderate Risk
Protein C / Protein S deficiency

Low Risk
Heterozygote mutation Factor V Leiden or of prothrombin G20210A

Lecumberri R, Casellas M, Fontcuberta J, et al. La Trombosis en embarazo y parto .Madrid. Acción Médica. 2008
Lecumberri R. Enfermedad tromboembólica venosa y embarazo. Trombosis update. vol 4, 8 Enero 2011

Study of inherited genetic thrombophilia: at any time, it does not interfere with the pregnancy situation.
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

*if Screening in pregnancy is necessary cutoff values for free protein S antigen levels in the second and third trimesters have been identified at less than 30% and less than 24%, respectively.
ACOG Inherited Thrombophilias in Pregnancy .Practice Bulletin 138 September 2013.

Thrombophilia	Testing method	Reliable during pregnancy?	Reliable during acute thrombosis??	Reliable with anti-coagulation?
Factor V Leiden mutation	Genetic and/or Coagulation (APCR)	Yes	Yes	Yes
Prothrombin mutation	Genetic	Yes	Yes	Yes
Protein C activity (<60%)	Coagulation	Yes	No	No
Protein S functional (<55%)*	Coagulation	No*	No	No
Antithrombin activity (<60%)	Coagulation	Yes	No	No
APCR (ratio<2)	Coagulation	Yes	Yes	No
APA**(LA,ACA,B2GPI)	Coagulation immunological LA	Yes	Yes	No coagulation tests

*Protein S can be reduced physiologically during pregnancy (up to levels of 30-24% in the second and third trimester, respectively.
**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
Antithrombin: - 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.
Protein C: - Inherited Physiological anticoagulant deficiency - AD Legacy.	Protein C deficiency due to other causes: - Drugs: SIntrom® Warfarin® - Hepatopathy. - Acute episode of thrombosis, CID, Sepsis.
Protein S: - Physiological anticoagulant deficiency. - AD Legacy.	Protein S deficiency due to other causes: - Physiological during gestation (30-24% in 2nd-3rd trimester). - Hepatopathy. - Nephrotic syndrome, HIV, chemotherapy and contraceptives.
APCR: 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.
ACQUIRED thrombophilia
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.

Favaloro EJ, McDonald D, Lippi G.Semin Thromb Hemos vol 35, nº7, 2009. p 695-710

	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 %	< 0,3	10	40
Homozygote Factor V Leiden	< 1	1,5	17	2
Heterozygote mutation A20210G of the Prothrombin gene	2 - 5	< 0,5	> 10	17
Homozygote mutation A20210G of the Prothrombin gene	< 1	2,8	> 17	0,5
Factor V Leiden + double heterozygote mutation A20210G	0,01	4,7	> 20	1 - 3
Antithrombin activity III (<60 %)	0,02	3 - 7	40	1
Protein C activity (<50 %)	0,2 - 0,4	0,1 - 0,8	4 - 17	14
Protein S free antigen (<55 %)*	0,03 - 0,13	0,1	0 - 22	3

VTE: Venous thromboembolic disease.
*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.