bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2020-65-2-174-189bloodjour-209Research ArticleКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯCASE REPORTSСлучай массового отравления антикоагулянтными родентицидамиOutbreak of mass poisoning with anticoagulant rodenticideshttps://orcid.org/0000-0001-8818-8949ГалстянГ. М.GalstyanG. M.

Галстян Геннадий Мартинович, доктор медицинских наук, заведующий отделением реанимации и интенсивной терапии 

тел.: +7 (495) 612-48-59. 125167, Москва, Новый Зыковский проезд, 4.

Gennadiy M. Galstyan, Dr. Sci. (Med.), Head of the Resuscitation and Intensive Care Unit

tel.: +7 (495) 612-48-59. 125167, Moscow, Novyy Zykovskiy proezd, 4

gengalst@gmail.comhttps://orcid.org/0000-0003-0645-7645ДавыдкинИ. Л.DavydkinI. L.

Давыдкин Игорь Леонидович, доктор медицинских наук, профессор, заведующий кафедрой и клиникой госпитальной терапии с курсами поликлинической терапии и трансфузиологии, проректор по научной работе 

директор НИИ гематологии 

тел.: +7 (846) 333-61-35

Igor L. Davydkin, Dr. Sci. (Med.), professor, Vice-rector for Reseach work, the Head of the Department and Clinics of Hospital Therapy. Director of Scientifi c Research Institute of Hematology

tel.: +7 (846) 333-61-35

dagi2006@rambler.ruhttps://orcid.org/0000-0002-3185-7934НиколаеваА. С.NikolaevaA. S.

Николаева Анна Сергеевна, заведующая гематологическим отделением

Anna S. Nikolaeva, Head of hematology Department

elufann@mail.ruhttps://orcid.org/0000-0002-1032-9083ВеховаН. И.VekhovaN. I.

Вехова Наталья Ивановна, заведующая отделением токсикологии

главный внештатный специалист по токсикологии Министерства здравоохранения Самарской области

Natalya I. Vekhova, Head of toxiсology Department

Chief external specialist in toxicology of the Ministry of Health of the Samara region

VehovaNI@sokb.ruhttps://orcid.org/0000-0002-4264-5718ПавловаЖ. Е.PavlovaZ. E.

Павлова Жанна Евгеньевна, кандидат медицинских наук, заведующая отделением острых отравлений

Zhanna E. Pavlova, Cand. Sci. (Med.), Head of the Department of acute poisoning

D.medic@mail.ruhttps://orcid.org/0000-0001-9352-7765ПономаренкоИ. С.PonomarenkoI. S.

Пономаренко Игнат Сергеевич, заведующий отделением токсикологии Г

главный внештатный специалист-токсиколог министерства здравоохранения Ульяновской области

тел.: + 7 (8422) 44-49-87

Ignat S. Ponomarenko, Head of toxicology Department

Chief external specialist in toxicology of the Ministry of Health of the Ulyanovsk Region

tel.: + 7 (8422) 44-49-87

ponomarenko.ignat@mail.ruhttps://orcid.org/0000-0002-8141-9422КлебановаЕ. Е.KlebanovaE. E.

Клебанова Елизавета Евгеньевна, врач отделения реанимации и интенсивной терапии

тел.: +7 (495) 612-48-59

Elizaveta E. Klebanova, Physician, Resuscitation and Intensive Care Unit

tel.: + 7 (495) 612-48-59

klebanova.liza@yandex.ruhttps://orcid.org/0000-0001-8188-5557СавченкоВ. Г.SavchenkoV. G.

Савченко Валерий Григорьевич, академик РАН, доктор медицинских наук, профессор, генеральный директор

Valery G. Savchenko, Dr. Sci. (Med.), RAS Academician, Professor, Head

director@blood.ruФГБУ «Национальный медицинский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for HematologyRussian FederationФГБУ ВО «Самарский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияSamara State Medical UniversityRussian FederationСамарская областная клиническая больница имени В. Д. СередавинаРоссияSamara Regional Clinical Hospital named after V.D. SeredavinRussian FederationГБУЗ СО «Тольяттинская городская клиническая больница № 1»РоссияTolyatti city clinical hospital № 1Russian FederationГУЗ «Ульяновский областной клинический центр специализированных видов медицинской помощи имени Е.М. Чучкалова»РоссияUlyanovsk Regional Clinical Center of Specialized types of medical care named after E.M. ChuchkalovRussian Federation202021052020652174189Copyright © Галстян Г.М., Давыдкин И.Л., Николаева А.С., Вехова Н.И., Павлова Ж.Е., Пономаренко И.С., Клебанова Е.Е., Савченко В.Г., 20202020Галстян Г.М., Давыдкин И.Л., Николаева А.С., Вехова Н.И., Павлова Ж.Е., Пономаренко И.С., Клебанова Е.Е., Савченко В.Г.Galstyan G.M., Davydkin I.L., Nikolaeva A.S., Vekhova N.I., Pavlova Z.E., Ponomarenko I.S., Klebanova E.E., Savchenko V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/209Введение

Введение. Родентициды — средства, используемые для борьбы с грызунами. В России к применению разрешены лишь родентициды антикоагулянтного действия.

Цель работы — описать случай массового отравления антикоагулянтными родентицидами.

Основные сведения

Основные сведения. Приведено наблюдение отравления антикоагулянтными родентицидами 80 человек вследствие потребления подсолнечного масла, произведенного из  семечек, подвергшихся обработке родентицидами. У пострадавших был выраженный геморрагический синдром: у всех — экхимозы, у 79 % — макрогематурия, у 1 — маточное кровотечение, у 3 — внутрибрюшные кровоизлияния, у 16 — носовые кровотечения, у 2 — желудочнокишечные кровотечения, у  2  — внутримозговые кровоизлияния. Международное нормализованное отношение (МНО) не удалось определить у 56 больных, у оставшихся медиана МНО составила 3,9 (колебания от 1,29 до 16,2). Активированное частичное тромбопластиновое время (АЧТВ) у 7 больных не определялось, у остальных медиана АЧТВ составила 65 с. Умерли от геморрагического синдрома 3 пострадавших. Анализируется проводимая терапия. При угрожающем жизни геморрагическом синдроме препаратами выбора являются концентраты протромбинового комплекса и рекомбинантный активированный фактор свертывания VII, но не свежезамороженная плазма и викасол. Для длительной терапии следует использовать витамин К1.

Конфликт интересов

Конфликт интересов: авторы заявляют об отсутствии конфликта интересов.

Introduction

Introduction. Rodenticides are pesticides used in the control of rodents. In Russia, only anticoagulant rodenticides are allowed to be used.

Aim

Aim: describe a case of mass poisoning with anticoagulant rodenticides.

Main findings

Main findings. An observation is given of poisoning with anticoagulant rodenticides in 80 people due to the consumption of sunflower oil produced from seeds that have been treated with rodenticides. The victims had a pronounced hemorrhagic syndrome: all had ecchymosis, 79 % had macrohematuria, 1 had uterine bleeding, 3 had intra-abdominal hemorrhages, 16 had nosebleeds, 2 had gastrointestinal bleeding, and 2 had intracerebral hemorrhages. The international normalized ratio (INR) was not definable in 56 patients, while the remaining patients had a median INR of 3.9 (fluctuations from 1.29 to 16.2). Activated partial thromboplastin time (APTT) was not definable in 7 patients; the remaining patients had the median APTT of 65 seconds. Three of the victims died of hemorrhagic syndrome. This article analyzes the conducted therapy. In life-threatening hemorrhagic syndrome induced by rodenticide poisoning or warfarin overdose the drugs of choice are prothrombin complex concentrates and recombinant activated clotting factor VII, but not fresh frozen plasma and vicasol. For long-term therapy, vitamin K1 should be used.

Conflict of interest

Conflict of interest: the authors declare no conflict of interest.

родентицидыотравлениевитамин Кконцентрат протромбинового комплексарекомбинантный активированный фактор свертывания VIIкоагулопатияrodenticidespoisoningvitamin Kprothrombin complex concentraterecombinant activated clotting factor VIIcoagulopathyФинансирование: работа не имела спонсорской поддержки, однако для части больных безвозмездно препараты предоставили компании «Октафарма», «Генериум» и «Кедрион», а также Фонд борьбы с лейкемией и Региональный благотворительный общественный фонд «Гематология и интенсивная терапия». Благодарность: авторы выражают благодарность компаниям «Октафарма», «Генериум» и «Кедрион», а также Фонду борьбы с лейкемией и Региональному благотворительному общественному фонду «Гематология и интенсивная терапия» за безвозмездное предоставление препаратов для лечения пострадавших.Financial disclosure: no financial support was received for this study; however, for some patients, the drugs were provided free of charge by the companies “Octapharma”, “Generium” and “Kedrion”, as well as by the Leukemia Fund and the Regional charitable public foundation “Hematology and Intensive Care” Acknowledgements: the authors express their appreciation to the companies “Octapharma”, “Generium” and “Kedrion”, as well as to the Leukemia Fund and the Regional charitable public foundation “Hematology and Intensive Care” for the free provision of drugs for the treatment of patients.ReferencesЯковлев А.А., Бабич Н.В. Родентициды. СПб.: ВИЗР; 2011: 63.Yakovlev A.A., Babich N.V. Rodenticides. Saint-Petersburg. VIZR; 2011: 63 (In Russian).Яковлев А.А., Бабич Н.В. Родентициды. Защита и карантин растений. 2011; (10): 42–4.Yakovlev A.A., Babich N.V. Rodenticides. Plant protection and quarantine. 2011; (10): 42–4 (In Russian).Tasheva M. Anticoagulant Rodenticides. Geneva: WHO; 1995: 123.Tasheva M. Anticoagulant Rodenticides. Geneva: WHO; 1995: 123.Huckle K.R., Hutson D.H., Warburton P.A. Elimination and accumulation of the rodenticide fl ocoumafen in rats following repeated oral administration. Xenobiotica. 1988; 18(12): 1465–79. DOI: 10.3109/00498258809042269.Huckle K.R., Hutson D.H., Warburton P.A. Elimination and accumulation of the rodenticide fl ocoumafen in rats following repeated oral administration. Xenobiotica. 1988; 18(12): 1465–79. DOI: 10.3109/00498258809042269.Caravati E.M., Erdman A.R., Scharman E.J., et al. Long-acting anticoagulant rodenticide poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol. 2007; 45(1): 1–22. DOI: 10.1080/15563650600795487.Caravati E.M., Erdman A.R., Scharman E.J., et al. Long-acting anticoagulant rodenticide poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol. 2007; 45(1): 1–22. DOI: 10.1080/15563650600795487.Chua D.J., Friedenberg W.R. Superwarfarin poisoning. Arch Intern Med. 1998; 158: 1929–32. DOI: 10.1016/s0140-6736(05)70808-4.Chua D.J., Friedenberg W.R. Superwarfarin poisoning. Arch Intern Med. 1998; 158: 1929–32. DOI: 10.1016/s0140-6736(05)70808-4.Parmar G., Bratt H., Moore R., et al. Evidence for common binding site in vivo for the retention of anticoagulants in rat liver. Hum Toxicol. 1987; 6: 431–2.Parmar G., Bratt H., Moore R., et al. Evidence for common binding site in vivo for the retention of anticoagulants in rat liver. Hum Toxicol. 1987; 6: 431–2.Laas F.J., Forss D.A., Goodfrey M.E.R. Retention of brodifacoum in sheep tissues and excretion in faeces. N Z J Agric Res. 1985; 28: 357–9.Laas F.J., Forss D.A., Goodfrey M.E.R. Retention of brodifacoum in sheep tissues and excretion in faeces. N Z J Agric Res. 1985; 28: 357–9.Bachmann K.A., Sullivan T.J. Dispositional and pharmacodynamic characteristics of brodifacoum in warfarin-sensitive rats. Pharmacology. 1983; 27: 281–8.Bachmann K.A., Sullivan T.J. Dispositional and pharmacodynamic characteristics of brodifacoum in warfarin-sensitive rats. Pharmacology. 1983; 27: 281–8.Weitzel J.N., Sadowski J.A., Furie B.C., et al. Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: Clinical and metabolic studies of three cases. Blood. 1990; 76(12): 2555–9. DOI: 10.1182/blood.v76.12.2555.bloodjournal76122555.Weitzel J.N., Sadowski J.A., Furie B.C., et al. Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: Clinical and metabolic studies of three cases. Blood. 1990; 76(12): 2555–9. DOI: 10.1182/blood.v76.12.2555.bloodjournal76122555.Stanton T., Sowray P., Mcwaters D., et al. Prolonged anticoagulation with long-acting Coumadin derivatives: Case report of a brodifacoum poisoning with pharmacokinetic data. Blood. 1988; 72: 310A.Stanton T., Sowray P., Mcwaters D., et al. Prolonged anticoagulation with long-acting Coumadin derivatives: Case report of a brodifacoum poisoning with pharmacokinetic data. Blood. 1988; 72: 310A.Bruno G.R., Howland M.A., McMeeking A., et al. Long-acting anticoagulant overdose: Brodifacoum kinetics and optimal vitamin K dosing. Ann Emerg Med. 2000; 36(3): 262–7. DOI: 10.1067/mem.2000.108317.Bruno G.R., Howland M.A., McMeeking A., et al. Long-acting anticoagulant overdose: Brodifacoum kinetics and optimal vitamin K dosing. Ann Emerg Med. 2000; 36(3): 262–7. DOI: 10.1067/mem.2000.108317.Lefebvre S., Fourel I., Queffélec S., et al. Poisoning by Anticoagulant Rodenticides in Humans and Animals: Causes and Consequences. In: Malangu N, editor. Poisoning — From Specifi c Toxic Agents to Novel Rapid and Simplifi ed Techniques for Analysis. IntechOpen; 2017: 11–32. DOI: 10.5772/intechopen.69955.Lefebvre S., Fourel I., Queffélec S., et al. Poisoning by Anticoagulant Rodenticides in Humans and Animals: Causes and Consequences. In: Malangu N, editor. Poisoning — From Specifi c Toxic Agents to Novel Rapid and Simplifi ed Techniques for Analysis. IntechOpen; 2017: 11–32. DOI: 10.5772/intechopen.69955.Mowry J.B., Spyker D.A., Brooks D.E., et al. 2015 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd Annual Report. Clinical Toxicology. Toxicology. 2016; 54(10): 925–1109.Mowry J.B., Spyker D.A., Brooks D.E., et al. 2015 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd Annual Report. Clinical Toxicology. Toxicology. 2016; 54(10): 925–1109.Колосова И.В., Галстян Г.М., Орел Е.Б. и др. Терапия геморрагического синдрома, вызванного дефицитом витамин К-зависимых факторов свертывания крови. Гематол. трансфузиол. 2012; 57(2): 22–30.Kolosova I.V., Galstyan G.M., Orel E.B., et al. Therapy for the hemorrhagic syndrome caused by defi ciency of vitamin K-dependent coagulation factors (analysis of clinical cases). Gematologiya i transfusiologiya. 2012; 57(2): 22–30 (In Russian).O’Reilly R.A., Aggeler P.M., Gibbs J.O. Hemorrhagic state due to surreptitious ingestion of bishydroxycoumarin. A detailed case study. N Engl J Med. 1962; 267(1): 19–24. DOI: 10.1056/NEJM196207052670105.O’Reilly R.A., Aggeler P.M., Gibbs J.O. Hemorrhagic state due to surreptitious ingestion of bishydroxycoumarin. A detailed case study. N Engl J Med. 1962; 267(1): 19–24. DOI: 10.1056/NEJM196207052670105.Андреев Н. За смерть ульяновцев от отравления кустарным маслом может ответить сызранский «Посад». https://73online.ru/r/za_smert_ulyanovcev_ot_otravleniya_kustarnym_maslom_mozhet_otvetit_syzranskiy_posad-72098.Andreev N. For the death of the Ulyanians from poisoning with artisanal oil can answer Syzran “Posad”. https://73online.ru/r/za_smert_ulyanovcev_ot_otravleniya_kustarnym_maslom_mozhet_otvetit_syzranskiy_posad-72098 (In Russian).Ермаков В.В., Болоховец М.Ф. Методические указания по определению зоокумарина в тканях и крови животных в приманках и препарате (пенокумарин) хроматографическими и спектрофотометрическими методами. № 1550-76 от 20.12.1976 г. В кн. под ред. Клисенко М.А. Методы определения пестицидов в продуктах питания, кормах и внешней среде. Справочное издание. М.: Колос; 1983: 227–30.Ermakov V.V., Bolochоvets M.F. Methodological instructions for the determination of zoocoumarin in animal tissues and blood in bait and preparation (penocoumarin) by chromatographic and spectrophotometric methods. № 1550-76 from 20.12.1976 In Methods for determining pesticides in food, feed and environment. Reference publication. Ed. Klisenko M.A. Moscow: Kolos; 1983: 227–30 (In Russian).Spahr J.E., Maul J.S., Rodgers G.M. Superwarfarin Poisoning: A Report of Two Cases and Review of the Literature. Am J Hematol. 2007; 82(9): 656–60. DOI: 10.1002/ajh.20784.Spahr J.E., Maul J.S., Rodgers G.M. Superwarfarin Poisoning: A Report of Two Cases and Review of the Literature. Am J Hematol. 2007; 82(9): 656–60. DOI: 10.1002/ajh.20784.Othman N., Chan C.K., Lau F.L. The epidemiology of household rodenticides poisoning in Hong Kong and its risk factors for developing coagulopathy. Hong Kong J Emerg Med. 2014; 21(6): 339–45. DOI: 10.1177/102490791402100601.Othman N., Chan C.K., Lau F.L. The epidemiology of household rodenticides poisoning in Hong Kong and its risk factors for developing coagulopathy. Hong Kong J Emerg Med. 2014; 21(6): 339–45. DOI: 10.1177/102490791402100601.Chong Y.-K., Mak T.W.-L. Superwarfarin (Long-Acting Anti-coagulant Rodenticides) Poisoning: from Pathophysiology to Laboratory-Guided Clinical Management. Clin Biochem Rev. 2019; 40(4): 175–85. DOI: 10.33176/aacb19-00029.Chong Y.-K., Mak T.W.-L. Superwarfarin (Long-Acting Anti-coagulant Rodenticides) Poisoning: from Pathophysiology to Laboratory-Guided Clinical Management. Clin Biochem Rev. 2019; 40(4): 175–85. DOI: 10.33176/aacb19-00029.Goldenberg N.A., Manco-Johnson M.J. Protein C defi ciency. Haemophilia. 2008; 14(6): 1214–21. DOI: 10.1111/j.1365-2516.2008.01838.x.Goldenberg N.A., Manco-johnson M.J. Protein C defi ciency. Haemophilia. 2008; 14(6): 1214–21. DOI: 10.1111/j.1365-2516.2008.01838.x.Umemura Y., Yamakawa K., Kiguchi T., et al. Design and evaluation of new unifi ed criteria for disseminated intravascular coagulation based on the Japanese Association for acute medicine criteria. Clin App Thromb Hemost. 2016; 22(2): 153–60. DOI: 10.1177/1076029615591169.Umemura Y., Yamakawa K., Kiguchi T., et al. Design and evaluation of new unifi ed criteria for disseminated intravascular coagulation based on the Japanese Association for acute medicine criteria. Clin App Thromb Hemost. 2016; 22(2): 153–60. DOI: 10.1177/1076029615591169.Hayakawa M., Yamakawa K., Kudo D., et al. Optimal Antithrombin Activity Threshold for Initiating Antithrombin Supplementation in Patients With SepsisInduced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study. Clin App Thromb Hemost. 2018; 24(6): 874–83. DOI: 10.1177/1076029618757346.Hayakawa M., Yamakawa K., Kudo D., et al. Optimal Antithrombin Activity Threshold for Initiating Antithrombin Supplementation in Patients With SepsisInduced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study. Clin App Thromb Hemost. 2018; 24(6): 874–83. DOI: 10.1177/1076029618757346.Saja M.F., Abdo A.A., Sanai F.M., et al. The coagulopathy of liver disease: Does vitamin K help? Blood Coagul Fibrinolysis. 2013; 24(1): 10–7. DOI: 10.1097/MBC.0b013e32835975ed.Saja M.F., Abdo A.A., Sanai F.M., et al. The coagulopathy of liver disease: Does vitamin K help? Blood Coagul Fibrinolysis. 2013; 24(1): 10–7. DOI: 10.1097/MBC.0b013e32835975ed.Roberts J.R., Reigart J.R. Recognition and management of pesticide poisonings. 6th ed. Washington: EPA; 2013: 272.Roberts J.R., Reigart J.R. Recognition and management of pesticide poisonings. 6th ed. Washington: EPA; 2013: 272.Chen T.W., Deng J.F. A brodifacoum intoxication case of mouthful amount. Vet Hum Toxicol. 1986; 22: 488.Chen T.W., Deng J.F. A brodifacoum intoxication case of mouthful amount. Vet Hum Toxicol. 1986; 22: 488.Donovan J.W., Ballard J.O., Murphy M.J. Brodifacoum therapy with activated charcoal: effect on elimination kinetics. Vet Hum Toxicol. 1990; 32: 350.Donovan J.W., Ballard J.O., Murphy M.J. Brodifacoum therapy with activated charcoal: effect on elimination kinetics. Vet Hum Toxicol. 1990; 32: 350.Goldstein J.N., Thomas S.H., Frontiero V., et al. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke. 2006; 37(1): 151–5. DOI: 10.1161/01.STR.0000195047.21562.23.Goldstein J.N., Thomas S.H., Frontiero V., et al. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke. 2006; 37(1): 151–5. DOI: 10.1161/01.STR.0000195047.21562.23.Holland L.L., Brooks J.P. Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results. Am J Clin Pathol. 2006; 126(1): 133–9. DOI: 10.1309/NQXHUG7HND78LFFK.Holland L.L., Brooks J.P. Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results. Am J Clin Pathol. 2006; 126(1): 133–9. DOI: 10.1309/NQXHUG7HND78LFFK.Lee S.B., Manno E.M., Layton K.F., et al. Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP. Neurology. 2006; 67(7): 1272–4. DOI: 10.1212/01.wnl.0000238104.75563.2f.Lee S.B., Manno E.M., Layton K.F., et al. Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP. Neurology. 2006; 67(7): 1272–4. DOI: 10.1212/01.wnl.0000238104.75563.2f.Makris M., Greaves M., Phillips W.S., et al. Emergency oral anticoagulant reversal: The relative effi cacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost. 1997; 77(3): 477–80. DOI: 10.1055/s-0038-1655992.Makris M., Greaves M., Phillips W.S., et al. Emergency oral anticoagulant reversal: The relative effi cacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost. 1997; 77(3): 477–80. DOI: 10.1055/s-0038-1655992.Hellstern P. Production and composition of prothrombin complex concentrates: correlation between composition and therapeutic effi ciency. Thromb Res. 1999; 95(4, suppl 1): S7–S12.Hellstern P. Production and composition of prothrombin complex concentrates: correlation between composition and therapeutic effi ciency. Thromb Res. 1999; 95(4, suppl 1): S7–S12..Boulis N.M., Bobek M.P., Schmaier A., et al. Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery. 1999; 45(5): 1113–8.Boulis N.M., Bobek M.P., Schmaier A., et al. Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery. 1999; 45(5): 1113–8.Riess H.B., Meier-Hellmann A., Motsch J., et al. Prothrombin complex concentrate (Octaplex®) in patients requiring immediate reversal of oral anticoagulation. Thromb Res. 2007; 121(1): 9–16. DOI: 10.1016/j.thromres.2007.02.009.Riess H.B., Meier-Hellmann A., Motsch J., et al. Prothrombin complex concentrate (Octaplex®) in patients requiring immediate reversal of oral anticoagulation. Thromb Res. 2007; 121(1): 9–16. DOI: 10.1016/j.thromres.2007.02.009.Pabinger I., Brenner B., Kalina U., et al. Prothrombin complex concentrate (Beriplex® P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost. 2008; 6(4): 622–31. DOI: 10.1111/j.1538-7836.2008.02904.x.Pabinger I., Brenner B., Kalina U., et al. Prothrombin complex concentrate (Beriplex® P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost. 2008; 6(4): 622–31. DOI: 10.1111/j.1538-7836.2008.02904.x.Preston F.E., Laidlaw S.T., Sampson B., et al. Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): effi cacy and safety in 42 patients. Br J Haematol. 2002; 116(3): 619–24.Preston F.E., Laidlaw S.T., Sampson B., et al. Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): effi cacy and safety in 42 patients. Br J Haematol. 2002; 116(3): 619–24.Imberti D., Barillari G., Biasioli C., et al. Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage. Blood Transfus. 2011; 9(2): 148–55. DOI: 10.2450/2011.0065-10.Imberti D., Barillari G., Biasioli C., et al. Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage. Blood Transfus. 2011; 9(2): 148–55. DOI: 10.2450/2011.0065-10.Herzog E., Kaspereit F., Krege W., et al. Four-Factor Prothrombin Complex Concentrate (4F-PCC) Is Superior to Three-Factor Prothombin Comlex Concentrates (3F-PCC) for Reversal of Coumarin Anticoagulation. Blood. 2014; 124(21): 1472.Herzog E., Kaspereit F., Krege W., et al. Four-Factor Prothrombin Complex Concentrate (4F-PCC) Is Superior to Three-Factor Prothombin Comlex Concentrates (3F-PCC) for Reversal of Coumarin Anticoagulation. Blood. 2014; 124(21): 1472.Holland L., Warkentin T.E., Refaai M., et al. Suboptimal effect of a threefactor prothrombin complex concentrate (Profi lnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion. 2009; 49(6): 1171–7. DOI: 10.1111/j.1537-2995.2008.02080.x.Holland L., Warkentin T.E., Refaai M., et al. Suboptimal effect of a threefactor prothrombin complex concentrate (Profi lnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion. 2009; 49(6): 1171–7. DOI: 10.1111/j.1537-2995.2008.02080.x.Yuan S., Ferrell C., Chandler W.L. Comparing the prothrombin time INR versus the APTT to evaluate the coagulopathy of acute trauma. Thromb Res. 2007; 120(1): 29–37. DOI: 10.1016/j.thromres.2006.07.002.Yuan S., Ferrell C., Chandler W.L. Comparing the prothrombin time INR versus the APTT to evaluate the coagulopathy of acute trauma. Thromb Res. 2007; 120(1): 29–37. DOI: 10.1016/j.thromres.2006.07.002.Makris M., Van Veen J.J. Three or four factor prothrombin complex concentrate for emergency anticoagulation reversal? Blood transfus. 2011; 9(2): 117–9. DOI: 10.2450/2011.0111-10.Makris M., Van Veen J.J. Three or four factor prothrombin complex concentrate for emergency anticoagulation reversal? Blood transfus. 2011; 9(2): 117–9. DOI: 10.2450/2011.0111-10.Blacker D.J. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust. 2005; 182(7): 365.Blacker D.J. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust. 2005; 182(7): 365.Negrier C., Gomperts E., Oldenburg J. The history of FEIBA: a lifetime of success in the treatment of haemophilia complicated by an inhibitor. Haemophilia. 2006; 12(S5): 4–13.Negrier C., Gomperts E., Oldenburg J. The history of FEIBA: a lifetime of success in the treatment of haemophilia complicated by an inhibitor. Haemophilia. 2006; 12(S5): 4–13.Skolnick B.E., Mathews D.R., Khutoryansky N.M., et al. Exploratory study on the reversal of warfarin with rFVIIa in healthy subjects. Blood. 2010; 116(5): 693–701. DOI: 10.1182/blood-2009-11-253492.Skolnick B.E., Mathews D.R., Khutoryansky N.M., et al. Exploratory study on the reversal of warfarin with rFVIIa in healthy subjects. Blood. 2010; 116(5): 693–701. DOI: 10.1182/blood-2009-11-253492.Sørensen B., Johansen P., Nielsen G.L., et al. Reversal of the International Normalized Ratio with recombinant activated factor VII in central nervous system bleeding during warfarin thromboprophylaxis: clinical and biochemical aspects. Blood Coagul Fibrinol. 2003; 14(5): 469–77. DOI: 10.1097/00001721-200307000-00007.Sørensen B., Johansen P., Nielsen G.L., et al. Reversal of the International Normalized Ratio with recombinant activated factor VII in central nervous system bleeding during warfarin thromboprophylaxis: clinical and biochemical aspects. Blood Coagul Fibrinol. 2003; 14(5): 469–77. DOI: 10.1097/00001721-200307000-00007.Галстян Г.М. Применение концентратов протромбинового комплекса по утвержденным и неутвержденным показаниям: новые перспективы старых препаратов. Гематол трансфузиол. 2018; 63(1): 78–91. DOI: 10.25837/HAT.2018.30.1.008.Galstyan G.M. Label and off-label applications of prothrombin complex concentrates. New perspectives of old drugs. Gematologiya i transfusiologiya. 2018; 63(1): 78–91 (In Russian). DOI: 10.25837/HAT.2018.30..1..008.Schulman S., Furie B. How I treat poisoning with vitamin K antagonists. Blood. 2015; 125(3): 438–42. DOI: 10.1182/blood-2014-08-597781.Schulman S., Furie B. How I treat poisoning with vitamin K antagonists. Blood. 2015; 125(3): 438–42. DOI: 10.1182/blood-2014-08-597781.James D.F. Clinical studies on dicumarol hypoprothrombinemia and vitamin K preparations. Arch Intern Med. 1949; 83(6): 632–56.James D.F. Clinical studies on dicumarol hypoprothrombinemia and vitamin K preparations. Arch Intern Med. 1949; 83(6): 632–56. 50. Udall J.A. Don вЂTM t Use the Wrong Vitamin K. Calif Med. 1970; 112(4): 65–7.Udall J.A. Don вЂTM t Use the Wrong Vitamin K. Calif Med. 1970; 112(4): 65–7.Dart R. Medical Toxicology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004: 1914.Dart R. Medical Toxicology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004: 1914.Pereslegina I.O., Dubrovina T.S., Zotova S.N. Poisoning of the dog with anticoagulant rodenticide: a clinical case. Veterinaria i kormlenie. 2018; (5): 48–50. DOI: 10.30917/att-vk-1814-9588-2018-5-17 (In Russian).Переслегина И.О., Дубровина Т.С., Зотова С.Н. Клинический случай отравления собаки антикоагулянтным родентицидом. Ветеринария и кормление. 2018; (5): 48–50. DOI: 10.30917/att-vk-1814-9588-2018-5-17.Watson H.G., Baglin T., Laidlaw S.L., et al. A comparison of the effi cacy and rate of response to oral and intravenous Vitamin K in reversal of over-anticoagulation with warfarin. Br J Haematol. 2001; 115(1): 145–9. DOI: 10.1046/j.1365-2141.2001.03070.x.Watson H.G., Baglin T., Laidlaw S.L., et al. A comparison of the effi cacy and rate of response to oral and intravenous Vitamin K in reversal of over-anticoagulation with warfarin. Br J Haematol. 2001; 115(1): 145–9. DOI: 10.1046/j.1365-2141.2001.03070.x.DeZee K.J., Shimeall W.T., Douglas K.M., et al. Treatment of excessive anticoagulation with phytonadione (vitamin K): A meta-analysis. Arch Intern Med. 2006; 166(4): 391–7. DOI: 10.1001/.391.DeZee K.J., Shimeall W.T., Douglas K.M., et al. Treatment of excessive anticoagulation with phytonadione (vitamin K): A meta-analysis. Arch Intern Med. 2006; 166(4): 391–7. DOI: 10.1001/.391.Nee R., Doppenschmidt D., Donovan D.J., et al. Intravenous versus subcutaneous vitamin K1 in reversing excessive oral anticoagulation. Am J Cardiol. 1999; 83(2): 286–8. DOI: 10.1016/S0002-9149(98)00842-X.Nee R., Doppenschmidt D., Donovan D.J., et al. Intravenous versus subcutaneous vitamin K1 in reversing excessive oral anticoagulation. Am J Cardiol. 1999; 83(2): 286–8. DOI: 10.1016/S0002-9149(98)00842-X.Hou Y.C., Lin J.L., Huang W.H., et al. Outcomes of patients with acetaminophen-associated toxic hepatitis at a far east poison center. SpringerPlus. 2013; 2(1): 1–7. DOI: 10.1186/2193-1801-2-674.Hou Y.C., Lin J.L., Huang W.H., et al. Outcomes of patients with acetaminophen-associated toxic hepatitis at a far east poison center. SpringerPlus. 2013; 2(1): 1–7. DOI: 10.1186/2193-1801-2-674.Basic report 35205. Stinging nettles, blanched (Northern Plains Indians). National Nutrient Database for Standard Reference Legacy. USDA website. https: //ndb.nal.usda.gov/ndb/foods/show/306720.2018.Basic report 35205. Stinging nettles, blanched (Northern Plains Indians). National Nutrient Database for Standard Reference Legacy. USDA website. https: //ndb.nal.usda.gov/ndb/foods/show/306720. 2018.Bauman H., Perez J. Food as Medicine: Stinging Nettle (Urtica dioica, Urticaceae). HerbalEGram. 2018; 15(7).Bauman H., Perez J. Food as Medicine: Stinging Nettle (Urtica dioica, Urticaceae). HerbalEGram. 2018; 15(7).Bauman H., Perez J. Food as Medicine: Stinging Nettle (Urtica dioica, Urticaceae). HerbalEGram. 2018; 15(7).

The authors declare that there are no conflicts of interest present.