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Главная / Архив / 2023 год / MEDICUS № 6 (54), November / THROMBOEMBOLISM IN PREGNANCY – PATHOPHYSIOLOGY AND CLINICAL IMPLICATIONS

THROMBOEMBOLISM IN PREGNANCY – PATHOPHYSIOLOGY AND CLINICAL IMPLICATIONS

Дата публикации: 04.11.2023

UDC 61

 

THROMBOEMBOLISM IN PREGNANCY – PATHOPHYSIOLOGY

AND CLINICAL IMPLICATIONS

 

H. Capros, PhD, Associate Professor,

Obstetrics, Gynecology Department,

State Medical University of Medicine and Pharmacy “Nicolae Testemitanu”

(MD 2001, Republic of Moldova, Chişinău, bd. Ştefan cel Mare, 165)

Email: hristiana.capros@usmf.md

 

D. Mitriuc, Associate Professor,

Obstetrics, Gynecology Department,

State Medical University of Medicine and Pharmacy “Nicolae Testemitanu”

(MD 2001, Republic of Moldova, Chişinău, bd. Ştefan cel Mare, 165)

Email: hristiana.capros@usmf.md

 

V. Voloceai, Associate Professor,

Obstetrics, Gynecology Department,

State Medical University of Medicine and Pharmacy “Nicolae Testemitanu”

(MD 2001, Republic of Moldova, Chişinău, bd. Ştefan cel Mare, 165)

Email: hristiana.capros@usmf.md

 

V. Cotelea, Associate Professor,

Obstetrics, Gynecology Department,

State Medical University of Medicine and Pharmacy “Nicolae Testemitanu”

(MD 2001, Republic of Moldova, Chişinău, bd. Ştefan cel Mare, 165)

Email: hristiana.capros@usmf.md

 

Iu. Dondiuc, PhD, Professor,

Obstetrics, Gynecology Department,

State Medical University of Medicine and Pharmacy “Nicolae Testemitanu”

(MD 2001, Republic of Moldova, Chişinău, bd. Ştefan cel Mare, 165)

Email: hristiana.capros@usmf.md

 

Abstract. The development of thromboembolic complications, including deep vein thrombosis and pulmonary embolism, in pregnancy is a major issue of obstetrical interest because its potential developmental complication increases maternal mortality. From conception till birth, gestation is linked to the natural rise in clotting factors such von Willebrand factor, fibrinogen, and factors II, VII, VIII, IX, and X as well as the progressive development of a hypercoagulable condition. The last findings in physiopathology justify careful evaluation of all pregnant women subjects to develop thrombosis throughout pregnancy.

Keywords: thromboembolism in pregnancy, hypercoagulation, clotting factors assessment.

 

Introduction.

Maternal mortality is frequently attributed to venous thromboembolism, which includes pulmonary embolism and deep vein thrombosis. When combined with inherited and acquired risk factors from the patient, normal physiological changes of pregnancy enhance coagulability.

Pathophysiology.

From conception till birth, gestation is linked to the natural rise in clotting factors such von Willebrand factor, fibrinogen, and factors II, VII, VIII, IX, and X as well as the progressive development of a hypercoagulable condition. Fibrinogen levels noticeably increase to 50 %. Prothrombin time (PT) and partial thromboplastin time (PTT) are impacted by these physiological changes, which seek to assist hemostasis following delivery but may also make it more difficult to evaluate pregnant women's anticoagulation. Pregnancy hyperestrogenicity reduces the activity of protein S, which typically interacts with protein C to directly inactivate factors Va and VIIIa through reduced synthesis and indirectly through an increase in the C4b binding protein. Moreover, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and plasminogen activator inhibitor-2 are active at higher levels and prevent fibrinolysis. Throughout gestation, childbirth, and postpartum period, the following three variables are particularly significant in causing venous stasis and venous hypertension: The inferior vena cava and iliac veins are compressed by the gravid uterus, and endothelial damage to the pelvic veins occurs throughout delivery. These factors include I decreased venous tone caused by endothelial mediators like nitric oxide, which is activated by estradiol, and vasodilating prostaglandins like PGI2 [1].

 

Virchow's triangle, which divides the pathophysiology of VTE into three primary groups-venous stasis, vascular injury, and hypercoagulability is the theory that best explains the causative relationship involving pregnancy and VTE. It is believed that pelvic venous compression by a gravid uterus, progesterone-induced venodilation, and pulsatile compression of the left iliac vein by the right iliac artery are the three main causes of venous stasis, which starts in the first trimester and maximum at 36 weeks. That could contribute to the pregnancy-related increased predisposition for left-leg DVT (above 80 %). There is a greater tendency for localized iliac vein thrombosis and iliofemoral thrombosis in pregnant patients with DVT because it indicates that proximal veins (iliac and femoral) instead of the normal site in non-pregnant individuals are where DVT in pregnancy most frequently develops. Pregnancy-related DVT is more likely to be linked to lengthy post-phlebitic syndrome as a result of this former condition. Because of the venous distension throughout pregnancy, and even during natural vaginal births, assisted vaginal births, or cesarean sections, the pelvic vessels may sustain vascular injury. In order to prepare pregnant women for the hemostatic demands of childbirth, the hemostatic system is gradually engaged, which causes hypercoagulability. Peripartum hemorrhage, which seems to be the main reason of mother mortality across human development, is still the leading factor of maternal death in the poor world, which serves as an example of this hemostatic problem [2].

 

An elevated risk of VTE is a contemporary adverse consequence of this teleological maternal hypercoagulable condition. The modifications to the hemostatic system that are responsible for this state's biological processes are as follows: Protein S's anticoagulant activity declines, and protein C's resistance is elevated. Procoagulant activity is also increased through higher levels of fibrinogen and factors V, IX, X, and VIII, which increases thrombin development as shown by elevated levels of thrombin/anti-thrombin complexes, soluble fibrin, and F 1.2. Finally, thrombus dispersion is declined through declining fibrinolysis because of elevated levels of plasminogen activator inhibitor. The pro-coagulant maternal hemostatic system progressively rebounds to the nulliparous condition throughout the postpartum, which is the six weeks after birth. This is demonstrated by the continuous restoration of indicators of coagulation activation to levels seen before pregnancy [3].

 

Clinical implication of inherited thrombophilia.

 

Factor v r506q (Leiden) and activated protein C resistance.

A common Mutated Gene called factor v leiden makes its carriers more susceptible to venous thromboembolism. A significantly higher chance of serious and recurring pregnancy problems whenever the hypercoagulable condition that is typical of pregnancy is added. Pregnancy-related both initial and ongoing venous thromboembolism has been most frequently caused by factor V Leiden. Pregnancy-related HELLP syndrome and early-onset gestational hypertension have both been linked to factor V Leiden carriage. Fetal development problems and serious placental abruption are also linked to maternal factor V Leiden carriage. It is unknown if factor V Leiden increases the chance of abortion in the first trimester, however it is linked to stillbirth and placental infarction. Tests for factor V Leiden and other hereditary and acquired thrombophilias must be carried out on women who have significant pregnancy problems or venous thromboembolism. Pregnancy-related acute thromboembolic episodes necessitate therapeutic heparin. Depending on their degree of risk, patients having factor V Leiden with a history of venous thromboembolism could be given preventive or therapeutic heparin [4].

There is a significantly higher incidence chance of having a miscarriage in people who have the factor V Leiden mutation. The likelihood of numerous miscarriages in the 2nd or 3rd trimester is between two and three times greater in women with such a mutation. According to a certain study, the factor V Leiden mutation may indeed raise the risk of other pregnancy-related issues, such as hypertension, delayed fetal development, and early placental abruption. The factor V Leiden mutation is not linked with these issues, though, according to research. Factor V Leiden thrombophilia sufferers often experience typical pregnancies [5].

Prior until 1993, testing for protein C, protein S, or antithrombin insufficiency in plasma-based examinations of whom are present in even less than 10 % of those suffering from acute VTE was the only method available for evaluating hereditary thrombophilia. Once Dahlback and colleagues introduced the concept of familial thrombophilia, inherited resistance to stimulated protein C, which is determined by assessing the proportion of the activated partial thromboplastin time (aPTT) clotting time, regardless of the addition of exogenous activated protein C, the experimental approach to thrombophilia testing changed in 1993. (APC). The aPTT-based test revealed APC resistance in other clinically afflicted relatives of the probands, indicating that the condition was hereditary [6].

 

A solitary well-conserved G to A point mutations at factor V gene nucleotide 1691, which was later identified by a variety of labs, is the precise genetic error that causes APC resistance. Among the three locations where APC often breaks down proteins and downregulates procoagulant factor Va is exactly in which the ensuing amino acid substitution, arginine (R) to glutamine (Q) at amino acid 506, takes place. This one amino acid alteration renders activated FVL somewhat resistant to the anticoagulant effects of APC and causes it to inactivate at a pace that is roughly ten times slower than usual. This leads to enhanced thrombin production and a prothrombotic condition. In comparison to individuals with protein C, S, or coagulation factor insufficiency, who show genetic variability, 90 % to 95 % of people with active APC resistance, as determined by the clotting time test, share an identical factor V R506Q (Leiden) missense mutation. In a small percentage of instances, genetic defects unrelated to the factor V R506Q mutation might cause the APC resistance phenotype or affect how it manifests in factor V R506Q heterozygotes. Unidentified causes of APC resistance were reported in several cases .

Antithrombotic agents like protein C and protein S become less effective during pregnancy. The patient's susceptibility for VTE is additionally increased by thrombophilia, which can worsen these alterations in clotting proteins. Moreover, when the iliac arteries and lower limb veins enlarge and the gravid uterus compresses the veins, venous stasis rises. Circumstances involving restricted movement may make these concerns worse. Endothelial damage might occur during childbirth. Several elements combine to raise the risk of VTE in postpartum and pregnant patients [7].

Like the FVL mutation results in a coagulation factor V that is ten times fewer vulnerable to APC-induced inactivation, functional tests for this change use a variety of techniques to examine how exogenously added APC affects functional coagulation dynamics. The initial "APC resistance" test, which has now largely been replaced by more effective techniques, calculated the ratio of aPTT clotting times in the presence and absence of a set quantity of exogenous APC. The first generation test is based on the idea that adding APC to normal plasma inactivates factor Va (and perhaps factor VIIIa), which delays coagulation and lengthens the aPTT. A modest reaction to APC-induced aPTT extension and a slightly reduced ratio define the APC-resistant phenotype.

Even though the first-generation test has a variable specificity for the FVL mutation and cannot reliably differentiate between heterozygotes and homozygotes, it is very effective for the APC resistance phenotype in some experiments. Additional restrictions include the inability to use it in individuals with extended baseline aPTT caused by warfarin or heparin anticoagulation, other coagulation abnormalities, or a lupus inhibitor, and the possibility that childbirth, oral contraceptive usage, or acute thrombosis might affect the findings. The clinical usefulness of this first-generation functional test is constrained by the rising prevalence of these factors in individuals being assessed for thrombophilia [8].

A new and commonly used second generation APC resistance functional test that addresses the shortcomings of the first generation analysis (with Food and Drug Administration approval). The patient's plasma is first diluted with factor V-deficient plasma containing a heparin neutralizer for this test. When factor V-deficient plasma is added, deficits in other coagulation proteins are formed, therapeutic heparin doses are neutralized, and the effects of certain lupus inhibitors are removed. The altered experiment has an extremely high degree of sensitivity and specificity for FVL, can precisely differentiate between heterozygotes and homozygotes, and can be understood properly in patients taking heparin or warfarin, in several patients taking lupus inhibitors, as well as in the presence of acute thrombosis, pregnancy, or inflammation. The unusual patient with APC resistance not brought on by factor V anomalies won't be detected, thus each research facility must establish its reference interval limits [9].

Use of oral contraceptives raises the actual risk of venous thromboembolism by a negligible amount, but elevates the incidence rate by nearly a factor of four (from 1 case per 10 000 woman-years in non–pill users to 3 cases per 10 000 woman-years in pill users). Nevertheless, in those who have undiagnosed thrombophilic abnormalities, using oral contraceptives can result in VTE. The activated protein C resistance (APCR)-causing R506Q mutation in the factor V gene (FV Leiden) and the G20120A polymorphism in the prothrombin gene are the two most prevalent thrombophilic abnormalities in white people. In heterozygotes and homozygotes, factor V Leiden raises the risk of thrombotic problems with oral contraceptive by 30- to 40-fold and by 100-fold, respectively. The risk of cerebral vein thrombosis while OC is 150 times higher in those who carry the prothrombin mutation G20120A. In order to determine which women may not be candidates for OC because of their greater risk of thrombotic problems, selective thrombophilia screening has only been advised in those with a personal or familial history of VTE [10].

In comparison to non-pregnant women of the same age, overall incidence of VTE is five- to six-times greater throughout pregnancy, and it is much greater during the postpartum period. There is clear indication connecting FVL to a higher risk of VTE throughout pregnancy as well as after delivery. Up to 60 % of women with a history of VTE throughout pregnancy were shown to have resistance to APC using a first-generation test, as opposed to 10 % of control women who were not pregnant. In longitudinal cohort series and research reports, the FVL mutation was discovered in 20 % to 46 % of pregnant women who had VTE. According to the information at hand, FVL is linked to a 7-16-fold higher thrombotic risk throughout pregnancy and the puerperium. In a new analysis, FVL was discovered in 44 % of pregnant women who had previously experienced VTE comparing to 8 % of their comparable control participants, and it was linked to a 9-fold rise in thrombotic risk. Women with both FVL and the prothrombin G20210A mutation experienced a relative risk of thrombosis throughout gestation that was more than 100 times higher, demonstrating the substantial rise in total risk that results from the combination of thrombophilic mutations. A greater risk of VTE associated with pregnancy exists in women who've had homozygous FVL. In one research of relations of symptomatic probands with FVL, venous thrombosis involved 16 % of pregnancies in homozygous women compared to 0.5 % of those in unaffected relatives, resulting in a 40-fold rise in average thrombotic chance [11].

Despite the fact that FVL raises the incidence of VTE in the puerperium as well as during pregnancy, the real risk in infected patients is unclear. Assessments of the risk of developing thrombosis are generally based on historical scenario and cohort studies, which may exaggerate the risk in carriers who do not have symptoms. In just 1.1 % of FVL carriers thrombotic problems emerge. In a recent large investigation involving more than 72 000 pregnant, unselected women, the estimated risk of VTE throughout gestation and the puerperium among FVL carriers ranged from 1 in 400 to 500 pregnancies. One in 400 FVL pregnancies were estimated to have thrombosis in some other case series. These research' findings do not justify routinely evaluating all pregnant women with this mutation and point to a relatively low incidence of FVL-related thrombosis throughout pregnancy. The overall risk of VTE related to pregnancy in FVL carriers is estimated by a number of recent studies. Unselected pregnant women were tested for FVL in one prospective research, and they were then monitored for the duration of pregnancy. According to estimates, the number of fatal bleeding cases likely match and potentially surpass the number of fatal pulmonary emboli avoided if regular maintenance anticoagulation of FVL carriers was implemented as a consequence of evaluating all pregnant women [12].

Sometimes in women who do not have any other risk factors, gestation increases the likelihood that VTE may occur. In comparison to a non-pregnant patient, the incidence of VTE is said to be 4 to 6 times higher during the prenatal period and up to 60 times higher during the postpartum era. The enhanced hypercoagulable condition of pregnancy, which is thought to have developed to protect women from serious bleeding throughout delivery and abortion, is responsible for the pregnancy's enhanced danger of VTE. The hormonally driven decline in vascular function and restriction of venous circulation by the growing uterus cause venous stasis, which is most pronounced between 25 and 29 weeks of gestation and lasts until six weeks after delivery. When giving birth or as a result of venous hypertension, endothelial injury may develop in the pelvic veins. Nitric oxide produced by endothelial cells during normal pregnancy causes vasodilation the fetal placental vascular channel to promote feto-maternal interaction. When there is localized damage, the synthesis of angiogenic and anti-angiogenic factors is changed, which causes systemic cell damage, systemic inflammatory response, endothelial activation, and changed endothelium generation of nitric oxide. Moreover, the pregnancy's hypercoagulable condition, which comprises elevated amounts of coagulation factors II, VII, VIII, and X, decreased levels of protein S, and resistance to activated protein C, plays a significant role in the mechanistic causes of thrombosis in pregnant women [13].

Hereditary thrombophilia is linked to around 50 % of VTEs that occur during pregnancy. According to a comprehensive analysis of 79 investigations, in which 9 studies with 2526 patients evaluated the risk of VTE linked with hereditary thrombophilia in pregnancy, people with thrombophilia had an odds ratio (OR) of 0.74 to 34.40 for getting VTE. The overall risk of VTE is still minimal even if pregnant women with thrombophilia have a higher relative chance of getting it. In addition to maternal factors, variables relating to the gestation or the fetus also increase the risk of VTE. One case-control research, for instance, found that deliveries of premature babies were three times more likely to experience postpartum VTE. Stillbirth is a distinct risk factor for VTE, according to several significant cohort studies. VTE risk is almost five times higher in preeclampsia. Similarly, compared to women who conceive naturally, women who become pregnant using assisted reproductive methods have a slightly increased risk of thrombosis. An individual potential risk for thrombosis within those women is the emergence of ovarian stimulation syndrome [14].

One or more of the following single risk factors, such as "intense" inherited thrombophilia, acquired thrombophilia, or a prior VTE event, is linked to an elevated chance of the occurrence of a PA-VTE. These elements may increase the overall risk of VTE by more than 1 %. In comparison to the general population, women with hereditary thrombophilias had a greater chance of developing antepartum VTE [15].

Conclusion.

The incidence of thromboembolism is higher during the prenatal period and postpartum period. The enhanced hypercoagulable condition of pregnancy, which is thought to have developed to protect women from serious bleeding throughout delivery and abortion, is responsible for the pregnancy's enhanced danger of thromboembolism. Knowledge of physiopathological mechanisms lead to understanding of disease manifestation and, as a resul, correct management of patients.

 

REFERENCES

  1. Adcock, D.M., Fink L., Marlar R.A. A laboratory approach to the evaluation of hereditary hypercoagulability. Am J Clin Pathol, vol. 108, no. 4, pp. 434–449, 1997, doi: 10.1093/AJCP/108.4.434.
  2. Bloomenthal, D., von Dadelszen P., Liston R. The effect of factor V Leiden carriage on maternal and fetal health. CMAJ: Canadian Medical Association Journal, vol. 167, no. 1, p. 48, Jul. 2002, Accessed: Feb. 25, 2023. [Online]. Available: /pmc/articles/PMC116643/
  3. Calderwood, C., Greer I. The Role of Factor V Leiden in Maternal Health and the Outcome of Pregnancy. Curr Drug Targets, vol. 6, no. 5, pp. 567–576, Jul. 2005, doi: 10.2174/1389450054546024.
  4. Cosmi, B., Legnani C., Bernardi F., et al. Role of Family History in Identifying Women With Thrombophilia and Higher Risk of Venous Thromboembolism During Oral Contraception. Arch Intern Med, vol. 163, no. 9, pp. 1105–1109, May 2003, doi: 10.1001/ARCHINTE.163.9.1105.
  5. Dahlbäck, B. Inherited resistance to activated protein C, a major cause of venous thrombosis, is due to a mutation in the factor V gene. Pathophysiol Haemost Thromb, vol. 24, no. 2, pp. 139–151, 1994, doi: 10.1159/000217094.
  6. Dahlback, B., Carlsson M., Svensson P.J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A, vol. 90, no. 3, pp. 1004–1008, 1993, doi: 10.1073/PNAS.90.3.1004.
  7. Edebiri, O., Áinle F.N. Risk factors, diagnosis and management of venous thromboembolic disease in pregnancy. Breathe, vol. 18, no. 2, Jun. 2022, doi: 10.1183/20734735.0018-2022.
  8. Hellgren, M. Hemostasis during normal pregnancy and puerperlum. Semin Thromb Hemost, vol. 29, no. 2, pp. 125–130, Apr. 2003, doi: 10.1055/s-2003-38897.
  9. Kalaitzopoulos, D.R. et al. Management of venous thromboembolism in pregnancy. Thromb Res, vol. 211, pp. 106–113, Mar. 2022, doi: 10.1016/J.THROMRES.2022.02.002.
  10. Orfanoudaki, I.M. Review article: pulmonary embolism in pregnancy: suspicion, diagnosis and therapy. 2019, doi: 10.15406/ogij.2019.10.00407.
  11. Othman, M. Issues in Haemostasis and Pregnancy.
  12. Press, R.D., Bauer K.A., Kujovich J.L., et al. Clinical Utility of Factor V Leiden (R506Q) Testing for the Diagnosis and Management of Thromboembolic Disorders. Arch Pathol Lab Med, vol. 126, no. 11, pp. 1304–1318, Nov. 2002, doi: 10.5858/2002-126-1304-CUOFVL.
  13. Rodger, M. Evidence Base for the Management of Venous Thromboembolism in Pregnancy. Hematology, vol. 2010, no. 1, pp. 173–180, Dec. 2010, doi: 10.1182/ASHEDUCATION-2010.1.173.
  14. Rosenkranz, A. et al. Calibrated automated thrombin generation in normal uncomplicated pregnancy. Thromb Haemost, vol. 99, no. 2, pp. 331–337, Feb. 2008, doi: 10.1160/TH07-05-0359.
  15. Trossaërt, M. et al. Modified APC resistance assay for patients on oral anticoagulants. Lancet, vol. 344, no. 8938, p. 1709, Dec. 1994, doi: 10.1016/S0140-6736(94)90494-4.

 

REFERENCES

  1. Adcock D.M., Fink L., Marlar R.A. A laboratory approach to the evaluation of hereditary hypercoagulability. Am J Clin Pathol, vol. 108, no. 4, pp. 434–449, 1997, doi: 10.1093/AJCP/108.4.434 (In English).
  2. Bloomenthal D., von Dadelszen P., Liston R. The effect of factor V Leiden carriage on maternal and fetal health. CMAJ: Canadian Medical Association Journal, vol. 167, no. 1, p. 48, Jul. 2002, Accessed: Feb. 25, 2023. [Online]. Available: /pmc/articles/PMC116643/ (In English).
  3. Calderwood C., Greer I. The Role of Factor V Leiden in Maternal Health and the Outcome of Pregnancy. Curr Drug Targets, vol. 6, no. 5, pp. 567–576, Jul. 2005, doi: 10.2174/1389450054546024. (In English).
  4. Cosmi B., Legnani C., Bernardi F., et al. Role of Family History in Identifying Women With Thrombophilia and Higher Risk of Venous Thromboembolism During Oral Contraception. Arch Intern Med, vol. 163, no. 9, pp. 1105–1109, May 2003, doi: 10.1001/ARCHINTE.163.9.1105. (In English).
  5. Dahlbäck B. Inherited resistance to activated protein C, a major cause of venous thrombosis, is due to a mutation in the factor V gene. Pathophysiol Haemost Thromb, vol. 24, no. 2, pp. 139–151, 1994, doi: 10.1159/000217094. (In English).
  6. Dahlback B., Carlsson M., Svensson P.J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A, vol. 90, no. 3, pp. 1004–1008, 1993, doi: 10.1073/PNAS.90.3.1004. (In English).
  7. Edebiri O., Áinle F.N. Risk factors, diagnosis and management of venous thromboembolic disease in pregnancy. Breathe, vol. 18, no. 2, Jun. 2022, doi: 10.1183/20734735.0018-2022. (In English).
  8. Hellgren M. Hemostasis during normal pregnancy and puerperlum. Semin Thromb Hemost, vol. 29, no. 2, pp. 125–130, Apr. 2003, doi: 10.1055/s-2003-38897. (In English).
  9. Kalaitzopoulos D.R. et al. Management of venous thromboembolism in pregnancy. Thromb Res, vol. 211, pp. 106–113, Mar. 2022, doi: 10.1016/J.THROMRES.2022.02.002. (In English).
  10. Orfanoudaki I.M. Review article: pulmonary embolism in pregnancy: suspicion, diagnosis and therapy. 2019, doi: 10.15406/ogij.2019.10.00407. (In English).
  11. Othman M. Issues in Haemostasis and Pregnancy. (In English).
  12. Press R.D., Bauer K.A., Kujovich J.L., et al. Clinical Utility of Factor V Leiden (R506Q) Testing for the Diagnosis and Management of Thromboembolic Disorders. Arch Pathol Lab Med, vol. 126, no. 11, pp. 1304–1318, Nov. 2002, doi: 10.5858/2002-126-1304-CUOFVL. (In English).
  13. Rodger M. Evidence Base for the Management of Venous Thromboembolism in Pregnancy. Hematology, vol. 2010, no. 1, pp. 173–180, Dec. 2010, doi: 10.1182/ASHEDUCATION-2010.1.173. (In English).
  14. Rosenkranz A. et al. Calibrated automated thrombin generation in normal uncomplicated pregnancy. Thromb Haemost, vol. 99, no. 2, pp. 331–337, Feb. 2008, doi: 10.1160/TH07-05-0359. (In English).
  15. Trossaërt M. et al. Modified APC resistance assay for patients on oral anticoagulants. Lancet, vol. 344, no. 8938, p. 1709, Dec. 1994, doi: 10.1016/S0140-6736(94)90494-4. (In English).

 

Материал поступил в редакцию 13.10.23

 

ТРОМБОЭМБОЛИЯ ВО ВРЕМЯ БЕРЕМЕННОСТИ – ПАТОФИЗИОЛОГИЯ

И КЛИНИЧЕСКИЕ ПОСЛЕДСТВИЯ

 

К. Капрос, PhD, доцент,

Кафедра акушерства и гинекологии

Государственный университет медицины и фармации имени Николая Тестемицану

(MD 2001, Республика Молдова, г. Кишинев, бул. Штефана чел Маре, 165)

Email: hristiana.capros@usmf.md

 

Д. Митрюк, доцент,

Кафедра акушерства и гинекологии

Государственный университет медицины и фармации имени Николая Тестемицану

(MD 2001, Республика Молдова, г. Кишинев, бул. Штефана чел Маре, 165)

Email: hristiana.capros@usmf.md

 

В. Волоцяи, доцент,

Кафедра акушерства и гинекологии

Государственный университет медицины и фармации имени Николая Тестемицану

(MD 2001, Республика Молдова, г. Кишинев, бул. Штефана чел Маре, 165)

Email: hristiana.capros@usmf.md

 

В. Котеля, доцент,

Кафедра акушерства и гинекологии

Государственный университет медицины и фармации имени Николая Тестемицану

(MD 2001, Республика Молдова, г. Кишинев, бул. Штефана чел Маре, 165)

Email: hristiana.capros@usmf.md

 

Ю. Дондюк, PhD, профессор,

Кафедра акушерства и гинекологии

Государственный университет медицины и фармации имени Николая Тестемицану

(MD 2001, Республика Молдова, г. Кишинев, бул. Штефана чел Маре, 165)

Email: hristiana.capros@usmf.md

 

Аннотация. Развитие тромбоэмболических осложнений, включая тромбоз глубоких вен и тромбоэмболию легочной артерии, во время беременности является серьезной проблемой, представляющей интерес для акушеров, поскольку это потенциальное осложнение увеличивает материнскую смертность. От зачатия до рождения беременность связана с естественным повышением уровня факторов свертывания крови, таких как фактор Виллебранда, фибриноген и факторы II, VII, VIII, IX и X, а также с прогрессирующим развитием гиперкоагуляционного состояния. Последние данные в области физиопатологии оправдывают тщательное обследование всех беременных женщин на предмет развития тромбоза на протяжении всей беременности.

Ключевые слова: тромбоэмболия во время беременности, гиперкоагуляция, оценка факторов свертывания крови.