Thrombophilia is a condition of increased possibility of thrombs formation. It can be acquired and inherited. Inherited thrombophilia is the most common cause of chronic venous insufficiency in young people. Because it does not cause any symptoms, the presence of thrombophilia is usually detected quite by accident. In young patients who come to our clinic, and who have problems with venous insufficiency, we always suspect the existence of a genetic predisposition to the disease. The greatest risk factor for venous insufficiency is thrombosis, with damage to the venous valves over time leading to disease onset and progression. Testing for hereditary Thrombophilia screening includes testing for activated protein C resistance/factor V Leiden mutation, prothrombin G20210A gene mutation, deficiencies of natural anticoagulants, such as antithrombin, protein C and protein S, the presence of antiphospholipid antibodies, hyperhomocysteinemia and increased factor VIII activity[1]. Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism is cost-effective and can prevent some complications like fetal loss, and gestational complications [2]. Due to hormonal changes and the fetus in pregnant women there is an increased risk of thrombosis, in combination with thrombophilia can lead to fetal loss.We recommend thrombophilia tests for our young patients who have a previous history of venous thrombosis, suffer from venous insufficiency, and have a family history of venous disease. Significant associations with early and late pregnancy loss are observed for carriers of the heterozygous factor V Leiden mutation, the heterozygous prothrombin-mutation G20210A and anticardiolipin antibodies, while protein S deficiency is significantly associated with late pregnancy loss [2]. The Leiden mutation is the most common inherited thrombophilia, with a heterozygous carrier prevalence from 3–7% in the US and European populations [3]. Some studies suggest that pregnant women without a personal history of thrombosis and a positive family history with at least one relative with first- or second-degree venous thrombosis are poor predictors of the possibility of a genetic mutation present [4].

Case 1

30-years old pregnant woman come for a medical examination. The pregnancy was achieved by in vitro fertilization. The embryo didn’t show heart beat on ultrasound and pregnancy was terminated with dilatation and evacuation. The patient has polycystic ovary syndrome and she and her partner had been trying to conceive for 8 years. She had two previous failed IVFs. The previous year she had laparoscopic ovarian drilling. According to the patient’s medical record, she had negative screening results for infections. The patient reports a positive family history of early-onset chronic venous insufficiency (father and sister).She was reffered in laboratory for detection of mutations / polymorphisms in thrombophilic genes after a history of miscarriage. Test results for mutations / polymorphisms in thrombophilic genes showed heterozyg?sity for Factor XIII V34L and MTHFR A1298C polymorfisams, and homozygosity for PAI-1 5G/4G polymorphisam.Six months after the miscarriage, another in vitro pregnancy was achieved. Because tests results showed mutations and polymorphisms associated with increased risc for thrombophilia low molecular heparin, nodroparin, 0.4ml s.c daily was given to the patient. ?he pregnancy went without significant problems and ended with Caesarean Section delivery at 39 weeks. Anticoagulat therapy with low molecular heparin was stopped 24 hours before elective Cesarean Section.

Case 2

27 years old pregnant women came to gynecology department with vaginal bleeding. She was 7 weeks pregnant with her second pregnancy. Ultrasound showed only residual masses in uterine cavity. Dilatation and evacuation was made. The patient has a positive family history of early-onset chronic venous insufficiency (grandmother and mother). Two months after the miscarriage she was reffered to labarotory for detection of mutations / polymorphisms in thrombophilic genes. Test results for mutations / polymorphisms in thrombophilic genes showed heterozigocity for FGB G/A, Factor XIII V34L, PAI-1 5G/4G, MTHFRC677T, MTHFR A1298C, MTRR A66G and MTR A2576G polymorphisams. Seven months after the miscarriage she became pregnant and because previouse tests results showed mutations and polymorphisms associated with increased risc for thrombophilia low molecular heparin, nodroparin, 0.6ml s.c daily was given to the patient. Pregnancy went without significant problems and she gave birth with caesarean section at 39 weeks.

Currently, no consensus agreement exists on the value of family history for the selection of patients who should be screened for an inherited thrombophilia [4]. Patients without a personal history of venous disease but with a family history of the same, and with complications of pregnancy in the form of miscarriage, IUGR and stillbirth, should be examined. Screening in these women will help prevent further complications. Thrombophilia in combination with pregnancy can be very risky due to the multiple increase in the chances of developing a thrombs. American College of Obstetricians and Gynecologists (ACOG) recommends that screening for thrombophilia should be performed on patients with a personal history of venous thromboembolism that occurred during a transient risk factor like pregnancy, surgery, prolonged immobility, patients presenting with thrombosis at a young age, patients with family history of thrombosis (>2 members), thrombosis at unusual site, more than 3 miscarriages, late miscarriage and foetal death [5]. Conclusively, it is important to recognize these patients in order to prevent all pregnancy complications. Diagnosing early also means starting thromboprophylaxis sooner which lead to increasing better maternal and perinatal outcomes.

1. Margetic S. Diagnostic algorithm for thrombophilia screening. Clin Chem Lab Med. 2010; 48: S27-39. Epub. 2010; 5.
2. Last L, Luxembourg B. Evidence based indications for thrombophilia screening. Vasa. 2008; 37: 19-30.
3. Price DR, Ridker PM. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med. 1997; 127: 895-903.
4. Horton AL, Momirova V, Townson DD, Wenstrom K, Wendel G, Samuels P, et al. Family history of venous thromboembolism and identifying factor V Leiden carriers during pregnancy. Obstet Gynecol. 2010; 115: 521-525.
5. Lockwood C, Wendel G. Practice bulletin no. 124: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2011; 118: 730-740.