Ten to 15 percent of Western population has thrombophilia and these disorders are responsible, at least in part, for approximately one-half of cases of maternal thromboembolism related to pregnancy.
Acquired (See Antiphospholipid Syndrome
Inherited (Discussed Here)
Inherited thrombophilias are genetic conditions that increase the risk of thromboembolic disease.
During pregnancy, the thrombogenic potential of these disorders is enhanced because of pregnancy-associated changes in several coagulation factors, producing a hyper coagulable state.
Women should be recommended screening for thrombophilia:
- Resistance to activated protein C increases in the second and third trimesters (false positive)
- Protein S decreases, about 50 %.
- Fibrinogen, Factors II, VII, VIII, X and XII increase
- Activity of the fibrinolytic inhibitors PAI-1 and PAI-2 increases
If previous thrombosis, and first degree relatives with documented thromboemboli before age 50, severe early onset preeclampsia, severe or recurrent abruption, severe IUGR < 5 percentile, fetal death after 10 weeks of gestation with placental thrombosis and/or infection. Thrombosis in the fetus.
Types of inherited thrombophilias.
The most common:
- Heterozygote for Factor V Leiden Mutation (most common)
- Mutation of the prothrombin gene (G20120A)
- Homocygosety for Methylenetetrahydrofolate reductase which tends to increase plasma homocysteine.
- Polymorphism of the PA1-gene (4G/4G)
Heterozygocity for the Factor V Leiden mutation accounts for 90-95 % of the activated protein C resistance (APC). Activated partial thromboplastin time (aPTT) - based assays serve as a screening test for APC resistance.
- Antithrombin (AT) deficiency
- Protein S or protein C deficiency
- Protein S deficiency and antibodies to Protein S
- Platelet collagen receptor alpha2-beta 1 C807T.
Heterocygosety for Factor V Leiden is highest among Caucasians 5-8 % and lowest among Asians 0,5 %.
Homozygosity for Factor V Leiden is 1 % of patient with the factor V Leiden Mutation.
Patients should be tested for thrombocytia openia associated with antiphosphollpid Syndrom (aquired thrombophilia).
Estimated prevalence of thrombophilic disorders and risk of pregnancy loss
Probability of thromboembolism in pregnant women:
VTE: Venous thromboembolism
||% of general population
||% of patients with first VTE
||Risk of VTE (OR)
||Risk of pregnancy loss (OR)
|Protein C deficiency*
|Protein S deficiency*
|Factor V-Leiden (heterozygous)
|Factor V-Leiden (homozygous)
|Prothrombin gene mutation
|Homozygous MTHFR C677T
|Acquired APC resistance (without FV Leiden)
* Established associations with fetal death
* Established associations with preeclampsi
APC is thus not the same as Factor V-Leiden, but is very good screening test to identify those who may have Factor V-Leiden as it is cheap to do.
Pregnancy Related Thrombosis in Women with Inherited Thrombophilia?
High Risk of VTE
||Risk if no personal or Family history of Thrombosis, percent
||Risk if personal or family history of thrombosis, percent
|| <= 3
||11 to 60
||3 to 19
||0 to 7
||0 to 22
Intermediate Risk of VTE
- Life long Anticoagulation Treatment
- Antithrombin deficiency
- Homozygotes for the Factor V Leiden mutation
- Homozygous for the prothrombin G20210A mutation
- Double heterozygotes for Factor V Leiden and prothrombin G20210A mutations
Low Risk of VTE
- A previous thromboembolic event and either congenital thrombophilia or familiar predisposition for VTE
- Heterozygote protein S and C deficiency
- Homozygote for Factor V-Leiden or prothrombin G2021A, mutation
- Combined heterozygote
- Heterozygote Factor V-Leiden or Prothrombin G2021A mutation with previous thrombosis
- Homocysteinemia despite folic acid/B6/B12 supplement
Additional Risk Factors
- Heterozygote Factor V-Leiden or Prothrombin G2021A mutation without previous thrombosis
- Homocysteinemia without folic acid/B6/B12 Supplement
Caesarean Section and immobilization, BMI > 30 (age > 35 years, para 4, multipregnancy, preeclampsia)
Prophylactic Heparin should be considered in case of previous severe preeclampsia intrauterine fetal death, severe IUGR or abruption of the placenta.
Treatment: See Thromboembolism and Prophylaxis
(1) James, AH. Preventure and management of veneous thromboembolia in pregnancy. Am J Med 2007;1280:26-34.
(2) Kujovich JL. Thrombophilia and pregnancy complications. Am J Am J Obstet Gynecol 2004:191:412-24
(3) Nielson-Pierce C. Handbook of Obstetrics Medicine. 2002 Edition.
(4) Robertson L, Greer J. Thromboembolism in pregnancy. Cur Opin Obstet Gynecol 2005;17:113-16.
(5) www.uptodate.com 2007
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