Endogenous heparin-like syndrome in a patient after intrauterine spina bifida repair
Beznoshchenko O.S., Ostrik K.A., Silaev B.V., Shmakov R.G., Pyregov A.V.
Background: Endogenous heparin-like syndrome (HLS) in obstetrics is a rare complication most practicing physicians are unfamiliar with. Glycosaminoglycans (GAGs) circulating in the bloodstream, mostly of endothelial origin, play the role of endogenous heparins. Liver disease, systemic inflammatory response, and infectious diseases are associated with the HLS development. The incidence of HLS varies according to pathology; for instance, it is 5% in trauma, and in liver transplantation it can be as high as 100%. The incidence of HLS in obstetrics remains unclear. The difficulty in the correction of the hemorrhagic syndrome associated with HLS is the lack of a uniform approach to therapy.
Case report: This article presents the first clinical observation of the HLS development in a pregnant woman after intrauterine correction of fetal spina bifida by open fetal surgery. Severe HLS was detected by thromboelastometry (CTINTEM /CTHEPTEM ratio >2); Laboratory parameters (activated partial thromboplastin time, thrombin time) showed hypocoagulation due to the presence of GAGs in the blood.
Conclusion: Monitoring of the hemostasis system in the perioperative period in obstetric patients can help timely recognize HLS and reduce the incidence of bleeding caused by the presence of endogenous GAGs. Further study is required to better understand how to diagnose and treat HLS effectively.
Authors’ contributions: Shmakov R.G., Pyregov A.V., Silaev B.V. – review of the content, approval of the manuscript for publication; Ostrik K.A. – collecting clinical material and writing the manuscript; Beznoshchenko O.S. – performing laboratory tests, reviewing publications on the subject of the article, analyzing and interpreting data, writing the manuscript.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: The study was conducted without sponsorship.
Patient Consent for Publication: The patient provided an informed consent for the publication of her data related to the clinical research.
For citation: Beznoshchenko O.S., Ostrik K.A., Silaev B.V., Shmakov R.G., Pyregov A.V.
Endogenous heparin-like syndrome in a patient after intrauterine spina bifida repair.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (10): 184-190 (in Russian)
https://dx.doi.org/10.18565/aig.2024.104
Keywords
References
- Морозов С.Л., Полякова О.В., Яновская Н.В., Зверева А.В., Длин В.В. Spina Bifida. Современные подходы и возможности к диагностике, лечению и реабилитации. Практическая медицина. 2020; 18(3): 32-7. [Morozov S.L., Polyakova O.V., Yanovskaya N.V., Zvereva A.V., Dlin V.V. Spina Bifida. Modern approaches and opportunities for diagnosis, treatment and rehabilitation. Practical Medicine. 2020; 18(3): 32-7. (in Russian)]. https:// dx.doi.org/10.32000/2072-1757-2020-3-32-37.
- Copp A.J., Adzick N.S., Chitty L.S. Fletcher J.M., Holmbeck G.N., Shaw G.M. Spina Bifida. Nat. Rev. Dis. Primers. 2015; 1: 15007. https://dx.doi.org/10.1038/NRDP.2015.7.
- Sacco A., Ushakov F., Thompson D., Peebles D., Pandya P., De Coppi P. et al. Fetal surgery for open spina bifida. Obstet. Gynaecol. 2019; 21(4): 271-82. https:// dx.doi.org/10.1111/tog.12603.
- Adzick N.S., Thom E.A., Spong C.Y., Brock J.W., Burrows P.K., Johnson M.P. et al.; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N. Engl. J. Med. 2011; 364(11): 993-1004. https:// dx.doi.org/10.1056/NEJMoa1014379.
- Буланов А.Ю., Яцков К.В., Шулутко Е.М., Глухова Т.Е., Адрейченко С.А. Эндогенный гепариноподобный синдром: анализ клинических наблюдений. Анестезиология и реаниматология. 2012; 3: 51-4. [Bulanov A.Yu., Yatskov K.V., Shulutko E.M., Glukhova T.E., Andreychenko S.A. Endogenous heparin-like syndrome: clinical observations analysis. Russian Journal of Anesthesiology and Reanimatology. 2012; (3): 51-4. (in Russian)].
- Schött U. Solomon C., Fries D., Bentzer P. The endothelial glycocalyx and its disruption, protection and regeneration: A narrative review. Scand. J. Trauma. Resusc. Emerg. Med. 2016; 24(1): 1-8. https://dx.doi.org/10.1186/S13049-016-0239-y/tables/2.
- Villalba N., Baby S., Yuan S. The endothelial glycocalyx as a double-edged sword in microvascular homeostasis and pathogenesis. Front. Cell Dev. Biol. 2021; 9: 1-14. https://dx.doi.org/10.3389/fcell.2021.711003.
- Giri T.K., Tollefsen D.M. Placental dermatan sulfate: isolation, anticoagulant activity, and association with heparin cofactor II. Blood. 2006; 107(7): 2753-8. https://dx.doi.org/10.1182/blood-2005-09-3755.
- Yu Y., Bruzdoski V., Kostousov K., Hensch V., Hui L., Siddiqui Sh. et al. Structural characterization of a clinically described heparin-like substance in plasma causing bleeding. Carbohydr. Polym. 2020; 244: 116443. https://dx.doi.org/10.1016/j.carbpol.2020.116443.
- Patterson E.K., Cepinskas G., Fraser D.D. Endothelial glycocalyx degradation in critical illness and injury. Front. Med. 2022; 9: 898592. https://dx.doi.org/10.3389/fmed.2022.898592.
- Senzolo M., Cholongitas E., Thalheimer U., Riddell A., Agarwal S., Mallett S. et al. Heparin-like effect in liver disease and liver transplantation. Clin. Liver Dis. 2009; 13(1): 43-53. https://dx.doi.org/10.1016/j.cld.2008.09.004.
- Wang S., Chao Q., Zhicheng L., Ting X., Chunyan Y. Endogenous Heparin-like substances may cause coagulopathy in a patient with severe postpartum hemorrhage. Transfus. Med. Hemotherapy. 2020; 47(40): 337-43. https://dx.doi.org/10.1159/000504610.
- Yan T., Fei H., Changfu J., Dong L., Weng C.-F. Manifestation of high endogenous heparinization in postpartum hemorrhage patient using thromboelastography: new avenue of coagulopathy monitoring. Arch. Clin. Med. 2023; 07(01): 82-8. https://dx.doi.org/10.26502/acmcr.96550578.
- Ferschl M., Ball R., Lee H., Rollins M. Anesthesia for in utero repair of myelomeningocele. Anesthesiology. 2013; 118(5): 1211-23. https://dx.doi.org/10.1097/aln.0b013e31828ea597.
- Senzolo M., Coppell J., Cholongitas E., Riddell A., Triantos C. K., Perry D. et al. The effects of glycosaminoglycans on coagulation: a thromboelastographic study. Blood Coagul. Fibrinolysis. 2007; 8(3): 227-36. https://dx.doi.org/10.1097/mbc.0b013e328010bd3d.
- Yassen K.A., Refaat E.K., Helal S.M., Metwally A.A., Youssef S.D., Görlinger K. Detection and quantification of perioperative heparin-like effects by rotational thromboelastometry in living-donor liver transplant recipients: a prospective observational study. J. Anaesthesiol. 2023; 39(2): 285-91. https://dx.doi.org/10.4103/joacp.joacp_521_21.
- Руководство по эксплуатации тромбоэластометра ROTEM Delta. Tem Innovations GmbH. Germany. 2016: 1-265. [ROTEM Delta Thromboelastometer Operating Manual. Tem Innovations GmbH. Germany. 2016: 1-265. (in Russian)].
- Görlinger K., Dirkmann D., Hanke A. Rotational thromboelastometry (ROTEM®). In: Trauma Induced Coagulopathy. 2016: 267-98. https://dx.doi.org/10.1007/978-3-319-28308-1_18.
- Yoon U. Native whole blood (TRUE-NATEM) and recalcified citrated blood (NATEM) reference value validation with ROTEM delta. Semin. Cardiothorac. Vasc. Anesth. 2023; 27(3): 199-207. https://doi.org/10.1177/10892532231151528.
- Senzolo M.,Agarwal S., Zappoli P.,Vibhakorn S.,Mallett S., Burroughs A. Heparin-like effect contributes to the coagulopathy in patients with acute liver failure undergoing liver transplantation. Liver Int. 2009; 29(5): 754-9. https://doi.org/10.1111/j.1478-3231.2009.01977.x.
- Durila M., Pavlicek P., Hadacova I., Nahlovsky J., Janeckova D. Endogenous heparinoids may cause bleeding in mucor infection and can be detected by nonactivated thromboelastometry and treated by recombinant activated factor VII: a case report. Medicine (Baltimore). 2016; 95(8): e2933. https://doi.org/10.1097/md.0000000000002933.
- Галстян Г.М., Полеводова О.А., Берковский А.Л., Сергеева Е.В. Тромбоэластография : сравнение полибрена и гепариназы для инактивации гепарина. Анестезиология и реаниматология. 2018; (5): 60-9. [Galstyan G.M., Polevodova O.A., Berkovskiy A.L., Sergeeva E.V. Thromboelastography: a comparison of polybrene and heparinase for the inactivation of heparin. Russian Journal of Anesthesiology and Reanimatology. 2018; (5): 60-9. (in Russian)]. https://doi.org/10.17116/anaesthesiology201805160.
- Nacoti M., Cantù D., Bonacina D., Lussana F., Bonanomi E., Marchetti M. et al. Heparin-like effect resistant to protamine in a child with haemorrhagic shock. Do we need heparinase? Blood Transfus. 2018; 16(4): 394-6. https://doi.org/10.2450/2017.0088-17.
- Руководство по эксплуатации. Анализатор гемостаза Teg® 5000. 2008. Haemonetics Corporation. [Operation manual. Teg® 5000 hemostasis analyzer. 2008. Haemonetics Corporation. (in Russian)].
- Kumano O., Ieko M., Naito S., Yoshida M., Takahashi N. APTT reagent with ellagic acid as activator shows adequate lupus anticoagulant sensitivity in comparison to silica‐based reagent. J. Thromb. Haemost. 2012; 10(11): 2338-43. https://doi.org/10.1111/j.1538-7836.2012.04906.x.
- HemosIL® Reagents | Werfen North America. Available at: https://www.werfen.com/na/en/hemostasis/hemosil-reagents
- Ichikawa J., Kodaka M.,Nishiyama K., Hirasaki Y.,Ozaki M., Komori M. Reappearance of circulating heparin in whole blood heparin concentration-based management does not correlate with postoperative bleeding after cardiac surgery. J. Cardiothorac. Vasc. Anesth. 2014; 28(4): 1003-7. https://doi.org/10.1053/j.jvca.2013.10.010.
- Song Y., Zhang F., Linhardt R.J. Glycosaminoglycans. Adv. Exp. Med. Biol. 2021; 1325: 103-16. https://doi.org/10.1007/978-3-030-70115-4_4/figures/2.
- Kantarcioglu B., Mehrotra S., Papineni C., Siddiqui F.,Kouta A., Hoppensteadt D. et al. Endogenous glycosaminoglycans in various pathologic plasma samples asmeasured by a fluorescent quenching method. Clin. Appl. Thromb. 2022; 28: 10760296221144047. https://doi.org/10.1177/10760296221144047.
- Achur R.N., Valiyaveettil M., Alkhalil A., Ockenhouse C.F., Gowda D.C. Characterization of proteoglycans of human placenta and identification of unique chondroitin sulfate proteoglycans of the intervillous spaces that mediate the adherence of Plasmodium falciparum-infected erythrocytes to the placenta. J. Biol. Chem. 2000; 275(51): 40344-56. https://doi.org/10.1074/JBC.M006398200.
- Said J.M. The role of proteoglycans in contributing to placental thrombosis and fetal growth restriction. J. Pregnancy. 2011; 2011: 928381. https://doi.org/10.1155/2011/928381.
- Zhang Q.,Yan C., Xu L., Xie W., Li J., Zhang W. et al. The treatment effect of protamine on severe coagulopathy in Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis: case reports and literature review. Indian J. Hematol. 2021; 37(1): 90. https://doi.org/10.1007/S12288-020-01308-6.
- Shen H., Wu C., Chen L., Zhang R. Acquired heparin-like anticoagulation process in a patient with multiple myeloma: a case report and literature review. Transl. Cancer Res. 2020; 9(11): 7366-71. https://doi.org/10.21037/tcr-20-1968.
Received 24.04.2024
Accepted 30.09.2024
About the Authors
Olga S. Beznoshchenko, PhD, Researcher at the Institute of Anesthesiology, Reanimatology and Transfusiology, clinical laboratory diagnostics doctor at the Department of Anesthesiology and Intensive Care, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 177997, Russia, Moscow, Ac. Oparin str., 4, o_beznoshchenko@oparina4.ru, https://orcid.org/0000-0003-4645-8976Kirill A. Ostrik, anesthesiologist-resuscitator at the Department of Anesthesiology and Intensive Care, Academician V.I. Kulakov National Medical Research
Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 177997, Russia, Moscow, Ac. Oparin str., 4, k_ostrik@oparina4.ru,
https://orcid.org/0009-0005-6064-665X
Borislav V. Silaev, PhD, Head of the Department of Anesthesiology-Intensive Care, Director of the Institute of Anesthesiology-Intensive Care and Transfusiology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 177997, Russia, Moscow, Ac. Oparin, str. 4; Associate Professor at the Department of Anesthesiology and Intensive Care, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia,
b_silaev@oparina4.ru, https://orcid.org/0000-0002-9698-3915
Roman G. Shmakov, Dr. Med. Sci., Professor of the Russian Academy of Sciences, Director, Academician V.I. Krasnopolsky Moscow Regional Research Institute of Obstetrics and Gynecology, 101000, Russia, Moscow, Pokrovka str., 22а; Professor at the Department of Obstetrics and Gynecology named after Academician G.M. Savelyeva of Pediatric Faculty, Pirogov Russian National Research Medical University, Ministry of Health of Russia; Chief Freelance Specialist in Obstetrics of the Ministry of Health of Russia, mdshmakov@mail.ru, https://orcid.org/0000-0002-2206-1002
Alexey V. Pyregov, Dr. Med. Sci., Professor, Deputy Chief Physician for Anesthesiology and Resuscitation, Moscow Regional Perinatal Center, 143900, Russia, Moscow Region, Balashikha, Shosse Entuziastov, 12; Chief Freelance Specialist in Anesthesiology and Resuscitation in Obstetrics of the Ministry of Health of the Moscow Region,
pyregov@mail.ru, https://orcid.org/0000-0001-8382-9671