A Retrospective Assessment of Thrombophilia in Pregnant Women with First and Second Trimester Pregnancy Loss

Abstract

Recurrent Pregnancy Loss (RPL) affects between 1% to 5% of women of reproductive age. It is widely believed that RPL is a complex disorder that is influenced by chromosomal abnormalities, genetic mutations, uterine anatomic deformity, endocrine dysfunction, immunologic factors, infections, and the environment. Thrombotic disorders are a frequent cause of RPL, accounting for almost half of all cases; however, in the rest of the cases, the cause of RPL remains unclear. Therefore, in this study, it was planned to determine the genetic mutations involved in RPL during the first and second trimester of pregnancy. An observational retrospective cohort study was conducted in 2021, collecting data from 157 first trimester miscarriages and 54 s trimester pregnancies. All patients with a panel of laboratory and genetic analysis for thrombophilia were included for data analysis. It was observed that four factors were significantly more prevalent in one of the groups. Factor V Leiden (FVL) homozygosity and antiphospholipid syndrome (APS) antibodies were statistically significantly more common in pregnant women who suffered first trimester pregnancy losses. On the other hand, Protein C deficiency and Glycoprotein Ia polymorphism were statistically significantly more frequent in the second trimester group. The strongest independent risk factors for first trimester pregnancy loss were FVL and prothrombin (PT) compound mutations (OR = 3.11), followed by FVL homozygous mutation (OR = 3.66), and APS antibodies (OR = 4.47). Regarding second trimester pregnancy loss risk factors, the strongest were FVL and PT compound (OR = 3.24), followed by Glycoprotein Ia polymorphism (OR = 3.61), and respectively, APS antibodies (OR = 3.85). Numerous thrombophilic risk factors for early and late pregnancy loss have been found, including several mutations that seem to occur more often either during the first or the second trimester. Even though we are aware of risk-free and efficient diagnostics for thrombophilia abnormalities, no intervention has been proved to be clearly successful after the detection of these variables.

Influence of Antiphospholipid Antibody-Associated Thrombophilia on the Risk of Preterm Birth: A Systematic Review

“…Among the included studies [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], two different study designs were utilized: cohort studies, either retrospective or prospective, and case–control studies. Specifically, two studies followed a prospective cohort design [ 22 , 24 ], five studies adopted a retrospective cohort design [ 21 , 25 , 26 , 27 ], and one study was a case–control study [ 28 ].…”

A study examining the correlation between serum 25-OH-VitD levels, CD3-CD19+ B lymphocytes, and the risk of early spontaneous abortion in pregnant women

“…Deficient women have a higher risk of forming blood clots in the placenta, causing placental insufficiency, microthrombi formation in uterine spiral arteries or villus vessels, or even multiple placental infarction, resulting in poor perfusion of utero-placental circulation and an increased risk of fetal death and abortion. [12] Currently, more studies believe that lower Protein S is closely related to recurrent abortion, but it is uncertain whether it is significant in early pregnancy spontaneous abortion. Mukhtar B [16] compared Protein C and Protein S levels in pregnant women with recurrent abortion in the first and second trimesters of pregnancy and women with normal pregnancy for over a year, and found that Protein S deficiency was more common than Protein C in the first trimester.…”

Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage

“…Recurrent miscarriage (RM), unlike sporadic pregnancy loss, necessitates additional attention, monitoring, and follow-up in subsequent pregnancies to be successful [ 1 , 2 ]. RM is a disappointing experience that negatively impacts couples’ psychological status and worsens their social discomfort [ 3 ].…”

“…RM is defined by the American Society of Reproductive Medicine (ASRM) and the European Society for Human Reproductive and Embryology (ESHRE) as the loss of two or more consecutive pregnancies from conception to 24 weeks of gestation [ 1 , 4 – 9 , 11 , 13 – 17 ]. While the World Health Organization (WHO) and the Royal College of Obstetricians and Gynecologists (RCOG) define RM as three or more miscarriages verified by ultrasonography or histology up to 24 weeks of gestation [ 2 , 4 , 5 , 15 , 16 , 18 – 20 ]. As a result, several measurements and recommendations were developed and implemented to reach standardization for appropriate inquiry and treatment approaches [ 1 , 15 ].…”

“…In normal pregnancy, the hemostatic system is modified to a hypocoagulable condition to preserve oxygen and nutrition transmission via the placenta for fetal survival, then changed to a hypercoagulable state to prevent excessive bleeding following birth [ 2 , 6 , 10 , 21 – 23 ]. Because of the interaction of various risk factors that play a role in RM such as maternal age, lifestyle behaviors (stress, smoking, and excessive alcohol consumption), history of miscarriage, antiphospholipid syndrome, uterine malformation, endometritis, endocrinological, abnormal parental karyotypes, obesity, genetic factors, and thrombophilia with other unknown factors, RM is considered a multifactorial condition [ 1 – 5 , 7 – 9 , 11 , 12 , 14 , 15 , 17 , 19 , 24 , 25 ].…”