Prognostic value of standard coagulogram indicators for assessing the risk of thrombosis in pregnant women with coronavirus infection
AbstractPregnant women infected with SARS-CoV-2 should be considered at high-risk group of severe morbidity and mortality, including the risk of thrombosis.
The aim of the study was to identify daily changes in standard coagulogram parameters in order to assess the prognostic significance of the risk of thrombotic complications in pregnant women with SARS-CoV-2.
Study subject: standard coagulogram parameters of pregnant patients with a new coronavirus infection.
Material and methods. Retrospective analysis of data from 230 case histories of pregnant women with coronavirus infection who underwent inpatient care at the State Budgetary Healthcare Institution «Samara Regional Clinical Hospital named after V.D. Seredavin» in 2021. According to the eligibility criteria, 99 case histories of women in the III trimester of pregnancy with infection verified with PCR-test were selected. Thrombosis developed in 5 patients (study group), 94 women (control group) suffered an infection without developing thrombosis. A comparative analysis of coagulogram data in the study groups and a correlation analysis of the identified changes with the day of illness and the moment of blood clot organization were carried out.
Results. Prothrombin time (PT) in patients with thrombosis was higher (p<0.001), the interquartile range of aPTT (activated partial thromboplastin time) was supernormal (Me 36.10 [Q1–Q3 30.10–44.50] sec). Quick PT and fibrinogen levels were lower (p<0.001) in the group of women without thrombosis. In women with thrombosis, hypofibrinogenemia was recorded on days 12–15 of the disease (Me 2.52 [Q1–Q3 1.96–3.25] g/l); by the period of 16–23 days: INR (international normalized ratio) and prothrombin time values reached their maximum (Me 1.22 [Q1–Q3 1.08–1.39] p<0.001 and Me 13.50 [Q1–Q3 11.70–15.80] sec, p<0.001, respectively), the lowest prothrombin values according to Quick PT (Me 68.20 [Q1–Q3 56.90–82.50] %) and an expressed decrease in fibrinogen levels were observed (Me 1.20 [Q1–Q3 0.71–2.48] g/l). After 24 days of illness, INR values decreased (Me 1.20 [Q1–Q3 1.09–1.33], p<0.004); the maximum median values were achieved at aPTT (Me 38.00 [Q1–Q3 34.10–46.90] sec), and Quick PT increased slightly (Me 69.05 [Q1–Q3 63.43-85.60] %) and fibrinogen levels returned to normal values (Me 3.87 [Q1–Q3 3.54–4.36] g/l).
In pregnant women with thrombosis, correlations with the day of the disease were revealed: INR (r=0.327, p=0.006), prothrombin time (r=0.310, p=0.010), fibrinogen levels (r=0.243, p<0.071) and Quick PT (r=-0.252, p=0.037). In pregnant women without thrombosis, correlations with the day of illness were revealed in: INR (r=0.164, p=0.009), prothrombin time (r=0.155, p=0.016), aPTT (r=-0.295, p<0.001).
Conclusion. In patients with thrombosis in the period from the 16th to the 23rd day of the disease, corresponding to the occurrence of thrombotic complications, a state of hypocoagulation was recorded according to a standard coagulogram. However, despite the hypocoagulation achieved during heparin therapy, thrombosis still occurred. For this reason, the use of a coagulogram to predict the development of thrombosis during coronavirus infection that occurs during pregnancy is not effective.
Keywords:coronavirus infection; pregnancy; coagulogram; thrombosis
Funding. The study had no sponsor support.
Conflict of interest. The authors declare no conflict of interest.
Сontribution. All authors contributed equally to the writing and preparation of the manuscript. All authors read and approved the final version of the manuscript.
For citation: Spiridonova N.V., Gritcenko T.A., Khurtova E.F. Prognostic value of standard coagulogram indicators for assessing the risk of thrombosis in pregnant women with coronavirus infection. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2024; 12 (2): 50–8. DOI: https://doi.org/10.33029/2303-9698-2024-12-2-50-58 (in Russian)
REFERENCES
1. Hemostasis system during pregnancy: symptoms, norm features and pathologies. Textbook. In: A.G. Yashchuk, A.V. Maslennikov, Sh.N. Galimov, R.A. Naftulovich, R.M. Zaynullina, A.M. Ziganshin, et al. (comp.) Ufa: Pervaya tipografiya, 2018: 74 p. (in Russian)
2. ACOG Practice Bulletin No. 196: Thromboembolism in pregnancy. Obstet Gynecol. 2018; 132 (1): e1.
3. O’Herlihy C. Reviewing maternal deaths to make motherhood safer: 2006–2008. BJOG. 2011; 118 (11): 1403–4.
4. Heit J., Kobbervig C.E., James A.H., Petterson T.M., Bailey K.R., Melton L.J. 3rd. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005; 143 (10): 697–706.
5. Tezikov Yu.V., Lipatov I.S., Yakusheva A.O. New coronavirus infection and pregnancy: features of gestation and the possibility of COVID-19 severity progression predicting in pregnant women. Rossiyskiy vestnik akushera-ginecologa [Russian Bulletin of Obstetrician-Gynecologist]. 2023; 23 (1): 30–8. DOI: https://doi.org/10.17116/rosakush20232301130 (in Russian)
6. Belokrinitskaya T.E., Artymuk N.V., Filippov O.S., Frolova N.I. Clinical course, maternal and perinatal outcomes of 2019 novel coronavirus infectious disease (COVID-19) in pregnant women in Siberia and Far East. Akusherstvo i Ginekologiya [Obstetrics and Gynecology]. 2021; 2: 48–54. DOI: https://dx.doi.org/10.18565/aig.2021.2 (in Russian)
7. Organization of medical care for pregnant women, women in labor, postpartum women and newborns with the new coronavirus infection COVID-19. Guidelines. Version 5. Minzdrav RF, 28.12.2021: 135 p. (in Russian)
8. Helms J., Tacquard C., Severac F., et al.; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Rеsearch in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46 (6): 1089–98. DOI: https://doi.org/10.1007/s00134-020-06062-x
9. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18 (4): 844–7.
10. Petrov V.I., Gerasimenko A.S., Kulakova I.S., Shatalova O.V., Amosov A.A., Gorbatenko V.S. COVID-19 development mechanisms associated coagulopathy. Diagnostics. Treatment. Lekarstvenniy vestnik [Medicinal Bulletin]. 2021; 15 [2 (82)]: 21–7. (in Russian)
11. Connors J.M., Levy J.H. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020; 135 (23): 2033–40. DOI: https://doi.org/10.1182/blood.2020006000 PMID: 32339221; PMCID: PMC7273827.
12. Ministry of Health of the Russian Federation. Clinical guidelines (protocol) Venous complications during pregnancy and postpartum period. Obstetric thromboembolism. Minzdrav RF, 2021. (in Russian)
13. Hamaliaka A. Antiphospholipid syndrome. Diagnosis and treatment. A textbook. 2013.
14. Motokawa S., Torigoshi T., Maeda Y., et al. IgG-class anti-PF4/heparin antibodies and symptomatic DVT in orthopedic surgery patients receiving different anti-thromboembolic prophylaxis therapeutics. BMC Musculoskelet Disord. 2011; 12: 22–34.
15. Spiridonova N.V., Gritsenko T.A., Khurtova E.F. Platelets and platelet indices characteristics during COVID‑19 in pregnant women, depending on the presence of thrombus formation. Akusherstvo, ginekologiya i reproduktsiya [Obstetrics, Gynecology and Reproduction]. 2023; 17 (5): 597–606. DOI: https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.429 (in Russian)
16. Akhmadzhonova G.M., Ismailova Z.U. Clinical and laboratory parameters features in patients with antiphospholipid syndrome and the algorithm for pregravid preparation. In: Medicine and Healthcare. Materials of the VI International scientific conference (Kazan, March 2018). Kazan’: Molodoy uchoniy, 2018: 12–4. URL: https://moluch.ru/conf/med/archive/303/13534/ (date of access August 05, 2023). (in Russian)
17. Khalimova F.T., Gulin A.V., Malysheva E.V., Nazirova A.A. Parameters characteristic of blood clotting in antiphospholipid syndrome. Bulletin of Russian Universities. Mathematics. 2012; 5. URL: https://cyberleninka.ru/article/n/harakteristika-parametrov-svertyvaniya-krovi-pri-antifosfolipidnom-sindrome (date of access: 05.08.2023).
18. Butt A., Erkan D., Lee A.I. COVID-19 and antiphospholipid antibodies. Best Pract Res Clin Haematol. 2022; 35 (3): 101402. DOI: https://doi.org/10.1016/j.beha.2022.101402 Epub 2022 Oct 15. PMID: 36494152; PMCID: PMC9568270.
19. Bitsadze V.O., Khizroeva D.Kh., Idrisova L.E., Abramyan R.R., Andreeva M.D., Makatsaria A.D. Catastrophic antiphospholipid syndrome. Pathogenesis questions. Akusherstvo, ginekologiya i reproduktsiya [Obstetrics, Gynecology and Reproduction]. 2015; 9 (2): 32–53. (in Russian)
20. Bitterman L., Solhjoo M., Shah V., Kwon S.M., Torralba K., Kazbour H. Catastrophic antiphospholipid syndrome as a complication of COVID-19 infection. J Investig Med High Impact Case Rep. 2023; 11. DOI: https://doi.org/10.1177/23247096231165736
21. Maria A.T.J., Diaz-Cau I., Benejean J.M., Nutz A., Schiffmann A., Biron-Andreani C., et al. Flare of antiphospholipid syndrome in the course of COVID-19. TH Open. 2020; 4 (3): e207–10.
22. Krechetova L.V., Nechipurenko D.Yu., Shpilyuk M.A., Beznoshchenko O.S., Beresneva E.A., Markelov M.I., et al. Thrombodynamics test use in the diagnosis of hemostasis disorders in covid-19 patients of varying severity. Klinicheskaya praktika [Clinical Practice]. 2021; (4). URL: https://cyberleninka.ru/article/n/ispolzovanie-testa-trombodinamiki-v-diagnostike-narusheniy-gemostaza-u-bolnyh-covid-19-raznoy-stepeni-tyazhesti (date of access August 06, 2023). (in Russian)
23. Abdulganieva D.I., Mukhametova D.D., Shamsutdinova N.G., Galieva A.M. Changes in liver function tests in patients with COVID-19. Eksperimental’naya i klinicheskaya gastoenterologiya [Experimental and Clinical Gastroenterology]. 2022; (7): 123–30. DOI: https://doi.org/10.31146/1682-8658-ecg-203-7-123-130 (in Russian)
24. Kostyuk S.A., Simirsky V.V., Gorbich Yu.L., Anisko L.A., Poluyan O.S. Cytokine storm during COVID-19. Meditsinskie novosti [Medical News]. 2020; 10 (313): 4–8. URL: https://cyberleninka.ru/article/n/tsitokinovyy-shtorm-pri-covid-19-1 (date of access August 06, 2023). (in Russian)
25. Huan H., Lan Y., Liu R., et al. Prominent changes in blood coagulation of patients with SARS-Cov2 infection. Clin Chem Lab Med. 2020; 58 (7): 1116–20. DOI: https://doi.org/10/1515/cclm-2020-0188
26. Nekaeva E.S., Bol’shakova A.E., Malysheva E.S., Galova E.A., Belikina D.V., Fedotov V.D., et al. Endothelial dysfunction markers study and hemorheological disorders study in patients with COVID-19. Sovremennye problemy nauki i obrazovaniya [Modern Problems of Science and Education]. 2021; (6). URL: https://science-еducation.ru/ru/article/view?id=31221 (date of access August 08, 2023). (in Russian)
27. Thachil J. The protective rather than prothrombotic fibrinogen in COVID-19 and other inflammatory states. J Thromb Haemost. 2020; 18: 1849–52. DOI: https://doi.org/10.1111/jth.14942
28. Garrido I., Liberal R., Macedo G. Review article: COVID-19 and liver disease – what we know on 1st May 2020. Aliment Pharmacol Ther. 2020; 52: 267–75. DOI: https://doi.org/10.1111/apt.15813
29. Chau T.-N., Lee K.-C., Yao H., et al. SARS-associated viral hepatitis caused by a novel coronavirus; report of three cases. Hepatology. 2004; 39: 302–10.
30. Хu L., Lu J. Yang D., Zheng X. Liver injury highly pathogenetic human coronavirus infections. Liver Int. 2020; 40: 998–1004.