rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2008-5-49rmt-658Research ArticleНАРУШЕНИЯ ГОМЕОСТАЗА ПРИ КРИТИЧЕСКИХ СОСТОЯНИЯХDISTURBANCES OF HOMEOSTASIS IN CRITICAL CONDITIONSКоррекция дефицита антитромбина III при диссеминированном внутрисосудистом свертыванииCorrection of Antithrombin III Deficiency in Disseminated Intravascular CoagulationНепорадаЕ. Л.NeporadaYe. L.-ВоробьеваН. А.VorobyevaN. A.-НедашковскийЭ. В.NedashkovskyE. V.-20082010200845Том IV № 5 2008 г.4949Copyright © Непорада Е.Л., Воробьева Н.А., Недашковский Э.В., 20082008Непорада Е.Л., Воробьева Н.А., Недашковский Э.В.Neporada Y.L., Vorobyeva N.A., Nedashkovsky E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/658

Несмотря на то, что терапия концентратом антитромбина III (AT) сопровождается повышенным риском кровотечения, литературные данные свидетельствуют о возможном положительном влиянии препарата на исход при ДВС-син-дроме. Введение свежезамороженной плазмы (СЗП) связано с меньшим риском кровотечения, однако ее влияние на прогноз при ДВС-синдроме не доказано. Цель исследования — сравнить эффекты концентрата АТ и СЗП на активность АТ и клиническое течение ДВС-синдрома. Материал и методы. 43 пациента с диагнозом ДВС-синдрома (по шкале JAAM) и дефицитом АТ<70% включены в рандомизированное клиническое исследование. Критерии исключения: возраст менее 16 и более 75 лет; злокачественные новообразования, кровотечение, применение гемостатической терапии, тромбоцитопения <50Х109/л. Пациенты рандомизированы в 3 группы: А — концентрат АТ 500-1000 МЕ/сут-ки; B — СЗП 10 мл/кг/сутки, С — комбинированная терапия. Введение препаратов производили ежедневно в течение 4 дней при сохраняющемся дефиците АТ<70%. В качестве сопутствующей терапии применяли надропарин (95 МЕ АХа/кг/сутки). Результаты. Активность АТ значительно повышалась в группе А и значимые различия между группами (A и B) сохранялись в течение периода терапии: 69±16 и 51±14%, р=0,007; 72±18 и 56±13%, р=0,02; 73±14 и 57±16%, p=0,03, соответственно. Не было выявлено значимых межгрупповых различий в тяжести дыхательных расстройств, дисфункции других органов, оценке по шкале ДВС-синдрома, частоте кровотечений (2 случая в группе А), аллергических реакций (2 случая крапивницы в группе С) и 30-дневной летальности — 40, 53,3 и 30,8% в группе А, В и С, соответственно. Заключение. При ДВС-синдроме терапия концентратом АТ по сравнению со СЗП и комбинированной терапией обеспечивает более эффективную коррекцию дефицита АТ. Для сравнения влияния трех видов терапии на исход и частоту осложнений при ДВС-синдроме необходимы дальнейшие исследования. Ключевые слова: синдром диссеминированного внутрисосудистого свертывания (ДВС-синдром), диагностические критерии ДВС-син-дрома, дефицит антитромбина III, концентрат антитромбина III, свежезамороженная плазма.

Although antithrombin (AT) III concentrate therapy is attended by an increased risk of hemorrhage, the data available in the literature suggest that the agent may have a positive effect on outcome in disseminated intravascular coagulation (DIC). Administration of fresh frozen plasma (FFP) is associated with a less risk of hemorrhage; however, there is no evidence for its impact on prognosis in DIC. Objective: to compare the effects of AT concentrate and FFP on the activity of AT and on the clinical course of DIC. Subjects and methods. Forty-three patients diagnosed as having as DIC (according to the JAAM scale) and <70% AT deficiency were included into a randomized clinical study. The inclusion criteria were as follows: age less than 16 years and more than 75 years; malignancy; hemorrhage; hemostatic therapy; a thrombocytopenia of <50X109/l. The patients were randomized into 3 groups: A) AT concentrate 500— 1000 IU/day; B) FFP 10 ml/kg/day; C) combined therapy. The agents were daily administered for 4 days in a persistent AT deficiency of 70%. Nadroparin, 95 IU AXa/kg/day, was used as concurrent therapy. Results. The activity of AT substantially increased in Group A and great differences between Groups A and B preserved during therapy: 69±16 and 51±14% (p=0.007); 72±18 and 56±13% (p=0.02); 73±14 and 57±16% (p=0.03), respectively. No significant differences were found in the severity of respiratory disorders, dysfunction of other organs, DIC scale scores, the incidence of hemorrhages (2 cases in Group A), allergic reactions (2 cases of urticaria in Group C) and in 30-day mortality — 40, 53.3, and 30.8% in Groups A, B, and C, respectively. Conclusion. As compared with FFP and combined therapy, AT concentrate therapy for DIC provides a more effective correction of AT deficiency. Further studies are needed to compare the impact of three therapy modalities on the outcome and incidence of complications in DIC. Key words: disseminated intravascular coagulation (DIC), diagnostic criteria for DIC, antithrombin III deficiency, antithrombin III concentrate, fresh frozen plasma.

ReferencesВоробьева Н. А.Воробьева Н. А.Bakhtiari K, Meijers J. C., deJonge E., Levi M.Prospective validation of the International society of thrombosis and haemostasis scoring system for disseminated intravascular coagulation. Crit. Care Med. 2004; 32 (12): 2416—2421.Bakhtiari K, Meijers J. C., deJonge E., Levi M.Prospective validation of the International society of thrombosis and haemostasis scoring system for disseminated intravascular coagulation. Crit. Care Med. 2004; 32 (12): 2416—2421.Cauchie P., Cauchie Ch., Boudjeltia K.Z. et al.Diagnosis and prognosis of overt disseminated intravascular coagulation in a general hospital — meaning of the ISTH score system, fibrin monomers, and lipoprotein-C-reactive protein complex formation. Am. J. Hematol. 2006; 81 (6): 414—419.Cauchie P., Cauchie Ch., Boudjeltia K.Z. et al.Diagnosis and prognosis of overt disseminated intravascular coagulation in a general hospital — meaning of the ISTH score system, fibrin monomers, and lipoprotein-C-reactive protein complex formation. Am. J. Hematol. 2006; 81 (6): 414—419.FurlongМ. А., Conrad S. A., Talavera F. et al.Disseminated intravascular coagulation. Medicine Guidelines 2007; 1.FurlongМ. А., Conrad S. A., Talavera F. et al.Disseminated intravascular coagulation. Medicine Guidelines 2007; 1.Levi M, de Jonge E, van der Poll T.New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology. Ann. Med. 2004; 36 (1): 41—49.Levi M, de Jonge E, van der Poll T.New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology. Ann. Med. 2004; 36 (1): 41—49.Maclean P. S., Tait R. C.Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs 2007; 67 (10): 1429—1440.Maclean P. S., Tait R. C.Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs 2007; 67 (10): 1429—1440.Mesters R. W, Mannucci P. W., Coppola R. et al.Factor VII and antithrombin III activity during sepsis and septic shock in neutropenic patients. Blood 1996; 88: 881—886.Mesters R. W, Mannucci P. W., Coppola R. et al.Factor VII and antithrombin III activity during sepsis and septic shock in neutropenic patients. Blood 1996; 88: 881—886.Mammen E. F.Antithrombin III: its physiologic importance and role in DIC. Semin Thromb. Haemost. 1998; 24: 19—25.Mammen E. F.Antithrombin III: its physiologic importance and role in DIC. Semin Thromb. Haemost. 1998; 24: 19—25.Warren B. L, Eid A., Singer P. et al.KyberSept trial study group. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286(15): 1869—1878. Erratum in: JAMA 2002; 287 (2): 192 (2, 3).Warren B. L, Eid A., Singer P. et al.KyberSept trial study group. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286(15): 1869—1878. Erratum in: JAMA 2002; 287 (2): 192 (2, 3).Kienast J., Juers M., Wiedemann C. J. et al.KyberSept investigators. Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation. J. Thromb. Haemost. 2006; 4 (1): 90—97.Kienast J., Juers M., Wiedemann C. J. et al.KyberSept investigators. Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation. J. Thromb. Haemost. 2006; 4 (1): 90—97.Dara S. I., Rana R., Afessa B. et al.Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit. Care Med. 2005; 33 (11): 2667—2671.Dara S. I., Rana R., Afessa B. et al.Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit. Care Med. 2005; 33 (11): 2667—2671.Palfi M., Berg S., Ernerudh J., Berlin G.A randomized controlled trial of transfusion-related acute lung injury: is plasma from multiparous blood donors dangerous? Transfusion 2001; 41: 317—322.Palfi M., Berg S., Ernerudh J., Berlin G.A randomized controlled trial of transfusion-related acute lung injury: is plasma from multiparous blood donors dangerous? Transfusion 2001; 41: 317—322.Rana R.,. Fernandez-Perez E. R., Khan S. A. et al.Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study. Transfusion 2006; 46: 1478—1483.Rana R.,. Fernandez-Perez E. R., Khan S. A. et al.Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study. Transfusion 2006; 46: 1478—1483.Gando S., Wada H., Asakura H. et al.Evaluation of new Japanese diagnostic criteria for disseminated intravascular coagulation in critically ill patients. Clin. Appl. Thromb. Hemost. 2005; 11: 71—76.Gando S., Wada H., Asakura H. et al.Evaluation of new Japanese diagnostic criteria for disseminated intravascular coagulation in critically ill patients. Clin. Appl. Thromb. Hemost. 2005; 11: 71—76.Gando S., Iba T., Eguchi Y. et al.A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: Comparing current criteria*. Crit. Care Med. 2006; 34 (3): 625—631.Gando S., Iba T., Eguchi Y. et al.A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: Comparing current criteria*. Crit. Care Med. 2006; 34 (3): 625—631.Taylor F. B., Toh C. H., Hoots K. et al.Towards a definition, clinical and laboratory criteria and a scoring system for disseminated intravascular coagulation. Thromb. Haemost. 2001; 86: 1327—1330.Taylor F. B., Toh C. H., Hoots K. et al.Towards a definition, clinical and laboratory criteria and a scoring system for disseminated intravascular coagulation. Thromb. Haemost. 2001; 86: 1327—1330.Kobayashi N., Maekawa T., Takada M. et al.Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. Bibl. Haematol. 1987; 49: 848—852Kobayashi N., Maekawa T., Takada M. et al.Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. Bibl. Haematol. 1987; 49: 848—852Gando S., Sawamura A., Hayakawa M. et al.First day dynamic changes in antithrombin III activity after supplementation have a predictive value in critically ill patients. Am. J. Hematol. 2006; 81 (12): 907—914.Gando S., Sawamura A., Hayakawa M. et al.First day dynamic changes in antithrombin III activity after supplementation have a predictive value in critically ill patients. Am. J. Hematol. 2006; 81 (12): 907—914.

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