Acquired thrombophilia is a group of diseases or states in which acquired risk factors, such as surgical trauma, braking, oral contraceptives, maternal immune diseases, malignancies, and certain medical comorbidities, cause acquired abnormalities in coagulation factors, anticoagulant proteins, and fibrinolytic proteins, leading to thromboembolism. Acquired thrombophilia is often a predisposing factor for thromboembolism in patients with hereditary thrombophilia, and the two are often combined, and thromboembolism is more likely to occur when several acquired thrombophilia coexist. During pregnancy, women tend to have enhanced coagulation function, which results in a high level of dynamic balance between coagulation and fibrinolysis, leading to a hypercoagulable state, which facilitates hemostasis of the placental abruptive surface and reduces postpartum hemorrhage. At the same time, the pelvic and lower limb blood vessels are dilated by uterine compression and hormonal influence during pregnancy, resulting in slow blood flow, elevated venous pressure, increased coagulation factors and fibrinogen, and relatively lower fibrinolytic system activity; delivery or cesarean section may cause damage to the vascular endothelium, so there is a significant tendency of thrombosis in the blood system during pregnancy, resulting in an increased chance of deep vein thrombosis (DVT) and obstetric complications.
1. Risk factors for pregnancy-acquired thrombophilia
1.1 Physiological risk factors Advanced age (age ≥ 35 years), smoking, obesity (BMI > 27.0 kg/m2), weight gain of more than 15 kg during pregnancy, acquired high coagulation factor levels (VIII), hyperhomocysteinemia, acquired activated protein C resistance (APCR), high D-dimer concentration (D-D).
1.2 Pathological risk factors: diabetes mellitus, renal disease, chronic wasting disease, abnormal lipid metabolism, acute spinal cord injury or lower limb paralysis, family history of hypertension, diabetes mellitus, previous history of venous thrombosis or their family history.
1.3 Obstetric risk factors Pre-eclampsia and eclampsia, HELLP syndrome, placental abruption, fetal growth restriction (FGR); low amniotic fluid; history of adverse pregnancy and childbirth such as polycystic ovary syndrome (PCOS), multiple pregnancies, stillbirth and stillbirth, recurrent miscarriage; puerperal infection, postpartum hemorrhage.
1.4 Immunological risk factors Systemic lupus erythematosus (SLE), positive antiphospholipid antibodies (including anti-cardiolipin antibodies or lupus anticoagulant), idiopathic thrombocytopenia, immune nephropathy.
1.5 Medical risk factors: post-IVF-ET, ovarian hyperstimulation syndrome (OHSS), transfusion for postpartum hemorrhage, cesarean or vaginal assisted delivery and uterine rupture, postoperative haemostatic drugs, postpartum oestrogen withdrawal, oral contraceptives and hormone replacement therapy.
1.6 Other Braking for more than 3 days, long distance travel or economy class syndrome, etc.
2. Effects of acquired embolism on mother and child
Acquired ecthymia can cause a shift in the balance of coagulation, anticoagulation, and fibrinolysis, resulting in a relative enhancement of coagulation, causing placental microthrombosis, villi infarction, and fibrinoid necrosis of the meconium vessels, leading to a decrease in placental perfusion and causing complications that seriously affect maternal and child health.
2.1 Impact on maternal health Pregnancy and the puerperium are among the risk factors for acquired ecthymia. Maternal tendency to thrombosis is aggravated by various factors such as obstetric complications and autoimmune diseases, which predispose to various complications such as hypertensive disorders in pregnancy, placental abruption, antiphospholipid syndrome, recurrent miscarriage, and deep vein thrombosis. Acquired thrombophilia often interacts with various risk factors to produce adverse pregnancy outcomes. Statistically, 49% to 65% of women with pregnancy complications have a propensity for thrombosis. The incidence of obstetric complications is 8 to 40 times higher in women with thrombophilia than in those without thrombophilia.
2.1.1 Pre-eclampsia Vasospasm, platelet aggregation, endothelial damage and microthrombosis in patients with pre-eclampsia cause impaired microcirculation in the uterus, resulting in placental infarction and a series of clinical manifestations of pre-eclampsia. It was found that 40-72% of pregnant women with preeclampsia had at least one factor that promoted thrombogenic tendencies, compared to 8-20% of pregnant women without preeclampsia. Another study found that pregnant women with acquired APCR had a 3-fold higher risk of developing preeclampsia than women with normal pregnancies. Pregnant women with hyperhomocysteinemia have a 4- to 5-fold increased risk of preeclampsia compared with normal pregnancies.
2.1.2 Placental abruption Placental abruption is a more serious complication of acquired eclampsia during pregnancy. The study found that 70% of women with placental abruption had at least one risk factor for acquired thrombophilia, while only 18% of those without placental abruption had these risk factors.
2.1.3 Recurrent miscarriage Acquired thrombophilia is an important factor for recurrent miscarriage in pregnant women, which can lead to shallow placental implantation and placental microthrombosis, causing placental malfunction and affecting embryonic development. Robertson et al. (2006) studied 7167 early miscarriages and 4038 late miscarriages and found that genetic and acquired thrombophilia were associated with poor pregnancy outcomes: (i) both FVL mutations and heterozygous mutations in PT G20210A were associated with early miscarriages; (ii) early miscarriages were significantly associated with anticardiolipin antibodies. (2) Early miscarriage and anti-cardiolipin antibodies have significant correlation.
2.1.4 Venous thrombosis The risk of thromboembolism is greatly increased when multiple thrombotic tendencies (including genetic and environmental factors) coexist, and is more likely to occur during early and late pregnancy and the puerperium. The clinical manifestations are mainly venous thrombosis, among which DVT is more dangerous, including lower limb venous embolism, pulmonary embolism and cerebral embolism. DVT in pregnancy is common in the left lower extremity, often starting from the peroneal vein or the iliac and femoral veins. Pulmonary embolism (PE) is a common and serious complication of DVT and a major cause of sudden maternal death due to venous thrombosis. The cerebral venous sinus interconnects with the pelvic vein, vertebral vein and intracranial vein, so DVT can also lead to intracranial venous sinus thrombosis, headache, hemiparesis and epilepsy, which seriously affects the quality of life of patients.
2.2 Effects on fetus
2.2.1 Fetal growth restriction The hypercoagulable state of blood and local infarction of placenta in patients with acquired thrombophilia are closely related to the occurrence of FGR, and the small spiral arteries of placenta may show vascular sclerosis, fibrin deposition and thrombosis, placental infarction, reduction of vascular bed in placental villi, and restriction of intervascular transfer of substances between villi, resulting in the reduction of nutrients to the fetus and affecting fetal growth and development. At present, many scholars at home and abroad have conducted more in-depth studies on the relationship between APCR and thrombosis, and the research results show that APCR is the most important cause of venous thrombosis due to coagulation system dysfunction.
2.2.2 Amniotic fluid hypoamnioticism is a common complication in the middle and late stages of pregnancy, accounting for 3.9% of pregnancies, and it can cause FGR in mild cases and fetal lung dysplasia, skeletal malformation and even death in severe cases. In our experience of treating hypohydramnios, we found that in patients with hypohydramnios without obvious fetal malformations, heparin anticoagulation and amino acid nutritional therapy could significantly improve the S/D ratio of amniotic fluid index and umbilical blood flow, thus improving the fetal prognosis. Thus, it is hypothesized that hypohydramnios caused by placental dysfunction may be associated with acquired eclampsia.
3. How to reduce the impact of acquired embolism on the mother and child
3.1 Pre-conception Acquired embolism patients should stop smoking and abstain from taking contraceptive pills in the first 6 months of pregnancy. Promptly manage primary diseases such as hypertension, diabetes mellitus and abnormal lipid metabolism, and standardize the indications for ovulation promotion therapy. Receive preconception education and pregnancy under the guidance of physicians. High-risk patients should receive anticoagulation therapy as early as possible.
3.2 Pregnancy Strengthen maternal management, improve lifestyle, pay attention to exercise, balanced nutrition, prevent excessive weight gain, avoid braking, and avoid long distance travel as much as possible. Reduce the generation of high-risk groups of medical origin, standardize the indications for cesarean section, and take oral multivitamins, calcium and iron supplements during pregnancy.
3.2.1 Monitoring of the mother Dynamic monitoring of maternal coagulation, anticoagulation and changes in the fibrinolytic system to prevent the occurrence of embolic diseases.
3.2.2 Monitoring of fetus ①Counting of fetal movement by pregnant women; ②Monitoring of placental function: dynamic monitoring of blood estriol (E3) and human placental lactogen (HPL); ③Fetal biophysical score: it can provide timely information on fetal development, which is meaningful for guiding the timing of treatment and delivery; ④Color Doppler fetal umbilical flow measurement: if the systolic/diastolic ratio (S/D) of umbilical artery blood flow is increased, it may indicate placental dysfunction, FGR, etc. If the fetal umbilical cord blood flow is cut off or reversed at the end of diastole, it is a sign of fetal death, and the pregnancy should be terminated as soon as possible.
3.3 Puerperium Oral contraceptives and hormone replacement therapy are contraindicated in high-risk patients, and postpartum hemostatic drugs and estrogen return are contraindicated.
3.4 Pharmacological prophylaxis The current prophylactic use of heparin, low-molecular heparin and low-dose aspirin for antithrombotic management, combined with instrumental prophylaxis (e.g., compression stockings) when appropriate, can significantly improve pregnancy outcomes. However, the use of glucocorticoids for immunoprophylaxis is not beneficial.