Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2019; 18: 34-42
Эффективность антитромботической терапии тромбозов глубоких вен у детей с заболеваниями крови
https://doi.org/10.24287/1726-1708-2019-18-1-34-42Аннотация
Тромботические осложнения - распространенное явление в детской онкогематологической практике. Краеугольным камнем в лечении тромбозов глубоких вен (ТГВ) у детей является проведение антитромботической терапии, тем не менее влияние такой терапии и ее режимов на исход ТГВ практически не изучено. Цель исследования: оценить эффективность антитромботической терапии у пациентов детского возраста с заболеваниями крови; сравнить частоту благоприятных и неблагоприятных исходов венозных тромбозов (ВТ) в зависимости от проведенного лечения. Данное исследование поддержано Независимым этическим комитетом и утверждено решением Ученого совета НМИЦ ДГОИ. Проанализированы данные историй болезни 429 пациентов с объективно подтвержденным ТГВ, получавших стационарное лечение в НМИЦ ДГОИ им. Дмитрия Рогачева в период 01.01.2013-31.12.2017. Изучена гемодинамическая характеристика тромбов, разработаны критерии корректности ведения, корректности терапии, критерии исходов ТГВ. С учетом этих критериев мы оценивали влияние антитромботической терапии на частоту реканализаций асимптоматических (аТГВ) и симптоматических тромбозов (сТГВ). Исследование включало 122 случая сТГВ и 408 случаев аТГВ. Исходы лечения проанализированы в 424 (80%) случаях ТГВ. Количество положительных исходов при назначении терапии при сТГВ было выше, чем при аТГВ (77,9 и 57,9% соответственно; р < 0,001) за счет случаев полной реканализации (50,0 и 35,3% соответственно; р < 0,05). При проведении корректной терапии в группе сТГВ возрастало количество благоприятных исходов (66,7% - без лечения; 77,9% - в случае получения терапии и 84,0% - при корректном проведении терапии тромбоза; р < 0,05). В группе аТГВ четкой зависимости от корректности проведенного лечения не обнаружено (45,2; 57,9 и 57,2% соответственно; p = 0,09). Корректно проведенная терапия позволила повысить частоту благоприятных исходов сТГВ почти на 20%. При аТГВ исходы тромбозов не зависели от проведенной терапии и ее корректности. Этот факт, вероятно, указывает на особенности природы аТГВ и их клиническое значение. Требуются дальнейшие исследования для определения оптимальной терапевтической стратегии ведения пациентов детского возраста гематологического профиля с сТГВ и аТГВ.
Список литературы
1. Andrew M., David M., Adams M., Ali K., Anderson R., Barnard D., et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994; 83: 1251-7.
2. van Ommen C.H., Heijboer H., Buller H.R., Hirasing R.A., Heijmans H.S., Peters M. Venous thromboembolism in childhood: a prospective two-year registry in the Netherlands. J Pediatr 2001; 139 (5): 676-81.
3. Nowak-Gotti U., von Kries R., Gobel U. Neonatal symptomatic thromboembolism in Germany: two year survey. Arch. Dis. Child. Fetal. Neonatal Ed 1997; 76 (3): 163-7.
4. Mitchell L., Andrew M., Hanna K., Abshire T., Halton J., Wu J., et al. Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study. Thromb Haemost 2003; 90 (2): 235-44.
5. Athale U.H., Chan A.K. Thrombosis in children with acute lymphoblastic leukemia: part I. Epidemiology of thrombosis in children with acute lymphoblastic leukemia. Thromb Res 2003; 111 (3): 125-31.
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10. Louzada M.L., Carrier M., Lazo-Lang-ner A., Vi Dao, Kovacs M.J., Ramsay T.O., et al. Development of a Clinical Prediction Rule for Risk Stratification of Recurrent Venous Thromboembolism in Patients With Cancer-Associated Venous Thromboembolism. Circulation 2012; 126: 448-54.
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12. Kwon J., Koh Y., Yoon J., Yu S.J. Anticoagulation Treatment with Low Molecular-Weight Heparin for Portal Vein Thrombosis in Liver Cirrhosis: Efficacy and Risk of Hemorrhagic Complications. Blood 2016; 128 (22): 1435.
13. Pesavento R., Filippi L., Pagnan A., Visona A., Pauletto P., Vescovo G., et al. Unexpectedly High Recanalization Rate in Patients with Pulmonary Embolism Treated with Anticoagulants Alone. American Journal of Respiratory and Critical Care Medicine 2014; 189: 1277-9.
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16. Румянцев А.Г., Масчан М.А., Жарков П.А., Свирин П.В Федеральные клинические рекомендации по диагностике, профилактике и лечению тромбозов у детей и подростков. Детская гематология: сборник клинических рекомендаций 2015: 283-317.
17. Greene L., Goldenberg N. Deep Vein Thrombosis: Thrombolysis in the Pediatric Population. Seminars in Interventional Radiology 2012; 29 (01): 036-043. Doi: 10.1055/s-0032-1302450
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19. Goldenberg N.A., Durham J.D., Knapp-Clevenger R., Manco-Johnson M.J. A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children. Blood 2007; 110 (1): 45-53. Doi: 10.1182/blood-2006-12-061234
20. Goldenberg N.A. Long-term outcomes of venous thrombosis in children. Current Opinion in Hematology 2005; 12 (5): 370-6. Doi: 10.1097/01.moh.0000160754.55131.14
21. Goldenberg N.A., Donadini M.P., Kahn S.R., Crowther M., Kenet G., Nowak-Gottl U., Manco-Johnson M.J. Post-thrombotic syndrome in children: A systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica 2010; 95 (11): 1952-9. Doi: 10.3324/hae-matol.2010.026989
22. Tousovska K., Zapletal O., Skotako-va J., Bukac J., Sterba J. Treatment of deep venous thrombosis with low molecular weight heparin in pediatric cancer patients: Safety and efficacy. Blood Coagulation & Fibrinolysis 2009; 20 (7): 583-9. Doi: 10.1097/mbc.0b013e32832ff577
23. Sule A., Chin T., Handa P., Earnest A. Should symptomatic, isolated distal deep vein thrombosis be treated with anticoagulation? International Journal of Angiology 2009; 18 (02): 83-7. Doi: 10.1055/s-0031-1278332
24. Fedorova D., Zharkov P., Pshonkin A. Thrombotic occlusions on central venous catheters as a risk factor of development of deep vein catheter-associated thrombosis. Voprosy Gematologii/onkologii I Immunopato-logii v Pediatrii 2016; 15 (2): 20-6. Doi: 10.20953/1726-1708-2016-2-20-26
Pediatric Hematology/Oncology and Immunopathology. 2019; 18: 34-42
Therapeutic aspects, determining the outcome of deep veins thrombosis (dvt) in children with hematological diseases
https://doi.org/10.24287/1726-1708-2019-18-1-34-42Abstract
Deep venous thrombosis (DVT) is a frequent complication in hospitalized children with hematological cancer. Antithrombotic therapy is a main treatment option in these cases, but there is still a lack of data on its influence on DVT outcomes in children. Objective: to compare the frequency of favorable and unfavorable outcomes of DVT in children with hematological and hemato-oncological diseases, depending on the antithrombotic therapy performed. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. 429 medical charts of patients, who received inpatient treatment in the Dmitry Rogachev National Research Center from 01/01/2013 - 12/31/17 were analyzed. There were used hemodynamic characteristics of DVT, also criteria for the correctness of management approach, therapy approach and criteria for DVT outcomes were developed. There were 122 symptomatic DVT (sDVT) and 408 asymptomatic DVT (aDVT). The treatment outcomes were analyzed in 424 (80%) cases of DVT, depending on the correctness of the therapy. In the group of sDVT, the number of favorable outcomes increases with correct therapy (66.7% for sDVT without treatment, 77.9% for treated sDVT, and 84.0% for sDVT, treated correctly, p < 0.05). In the group of aDVT there were no clear dependence between correctness of the treatment and thrombosis outcomes (45.2%, 57.9%, 57.2%, respectively, p = 0.09). Correctly performed antithrombotic treatment rises the favorable outcome rates by more than 20%. In contrast to sDVT, in cases of aDVT outcomes don't depend on therapy or its correctness. This fact could potentially rise the question of aDVT's nature and clinical significance. To determine the best therapy strategy, further research is needed.
References
1. Andrew M., David M., Adams M., Ali K., Anderson R., Barnard D., et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994; 83: 1251-7.
2. van Ommen C.H., Heijboer H., Buller H.R., Hirasing R.A., Heijmans H.S., Peters M. Venous thromboembolism in childhood: a prospective two-year registry in the Netherlands. J Pediatr 2001; 139 (5): 676-81.
3. Nowak-Gotti U., von Kries R., Gobel U. Neonatal symptomatic thromboembolism in Germany: two year survey. Arch. Dis. Child. Fetal. Neonatal Ed 1997; 76 (3): 163-7.
4. Mitchell L., Andrew M., Hanna K., Abshire T., Halton J., Wu J., et al. Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study. Thromb Haemost 2003; 90 (2): 235-44.
5. Athale U.H., Chan A.K. Thrombosis in children with acute lymphoblastic leukemia: part I. Epidemiology of thrombosis in children with acute lymphoblastic leukemia. Thromb Res 2003; 111 (3): 125-31.
6. Caruso V., lacoviello L., Di Castelnuovo A., Storti S., Mariani G., de Gaetano G., Donati M.B. Thrombotic complications in childhood acute lym-phoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood 2006; 108 (7): 2216-22.
7. Athale U., Siciliano S., Thabane L., Pai N., Cox S., Lathia A., et al. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer 2008; 51 (6): 792-77.
8. Kearon C., Akl E.A., Ornelas J., Blai-vas A., Jimenez D., Bounameaux H., et al. COL Lisa Moores Antithrombotic Therapy for VTE Disease CHEST Guideline and Expert Panel Report, CHEST FEBRUARY 2016; 149 (2): 315-52.
9. Khorana A.A., Carrier M., Garcia D.A., Lee A.Y.Y. Guidance for the prevention and treatment of cancerassociated venous thromboembolism. J Thromb Thrombol 2016; 41: 81-91.
10. Louzada M.L., Carrier M., Lazo-Lang-ner A., Vi Dao, Kovacs M.J., Ramsay T.O., et al. Development of a Clinical Prediction Rule for Risk Stratification of Recurrent Venous Thromboembolism in Patients With Cancer-Associated Venous Thromboembolism. Circulation 2012; 126: 448-54.
11. Tullius B.P., Athale U., van Ommen C.H., Chan A.K.C., Palumbo J.S., Balag-tas J.M.S. The identification of at-risk patients and prevention of venous thromboembolism in pediatric cancer: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 15: 1-6.
12. Kwon J., Koh Y., Yoon J., Yu S.J. Anticoagulation Treatment with Low Molecular-Weight Heparin for Portal Vein Thrombosis in Liver Cirrhosis: Efficacy and Risk of Hemorrhagic Complications. Blood 2016; 128 (22): 1435.
13. Pesavento R., Filippi L., Pagnan A., Visona A., Pauletto P., Vescovo G., et al. Unexpectedly High Recanalization Rate in Patients with Pulmonary Embolism Treated with Anticoagulants Alone. American Journal of Respiratory and Critical Care Medicine 2014; 189: 1277-9.
14. Dabbous M.K., Sakr F.R., Malaeb D.N. Anticoagulant therapy in pediatrics. Journal of Basic and Clinical Pharmacy 2014; 5: 27-33.
15. Schapkaitz E., Sherman G.G., Jacobson B.F., Haas S., Buller H.R., Davies V., et al. Paediatric Anticoagulation Guidelines. S Afr Med J 2012 Feb 23; 102 (3, Pt 1): 171-5.
16. Rumyantsev A.G., Maschan M.A., Zharkov P.A., Svirin P.V Federal'nye klinicheskie rekomendatsii po diagnostike, profilaktike i lecheniyu trombozov u detei i podrostkov. Detskaya gematologiya: sbornik klinicheskikh rekomendatsii 2015: 283-317.
17. Greene L., Goldenberg N. Deep Vein Thrombosis: Thrombolysis in the Pediatric Population. Seminars in Interventional Radiology 2012; 29 (01): 036-043. Doi: 10.1055/s-0032-1302450
18. Manco-Johnson M.J. How I treat venous thrombosis in children. Blood 2006; 107 (1): 21-9. Doi: 10.1182/blood-2004-11-4211
19. Goldenberg N.A., Durham J.D., Knapp-Clevenger R., Manco-Johnson M.J. A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children. Blood 2007; 110 (1): 45-53. Doi: 10.1182/blood-2006-12-061234
20. Goldenberg N.A. Long-term outcomes of venous thrombosis in children. Current Opinion in Hematology 2005; 12 (5): 370-6. Doi: 10.1097/01.moh.0000160754.55131.14
21. Goldenberg N.A., Donadini M.P., Kahn S.R., Crowther M., Kenet G., Nowak-Gottl U., Manco-Johnson M.J. Post-thrombotic syndrome in children: A systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica 2010; 95 (11): 1952-9. Doi: 10.3324/hae-matol.2010.026989
22. Tousovska K., Zapletal O., Skotako-va J., Bukac J., Sterba J. Treatment of deep venous thrombosis with low molecular weight heparin in pediatric cancer patients: Safety and efficacy. Blood Coagulation & Fibrinolysis 2009; 20 (7): 583-9. Doi: 10.1097/mbc.0b013e32832ff577
23. Sule A., Chin T., Handa P., Earnest A. Should symptomatic, isolated distal deep vein thrombosis be treated with anticoagulation? International Journal of Angiology 2009; 18 (02): 83-7. Doi: 10.1055/s-0031-1278332
24. Fedorova D., Zharkov P., Pshonkin A. Thrombotic occlusions on central venous catheters as a risk factor of development of deep vein catheter-associated thrombosis. Voprosy Gematologii/onkologii I Immunopato-logii v Pediatrii 2016; 15 (2): 20-6. Doi: 10.20953/1726-1708-2016-2-20-26
