Hemorrhagic Microthrombovasculitis: Primary Hemostasis and Immunological Parameters

SYSTEMIC VASCULITES , , , , , , , ,

AR Raimzhanov, OA Dzhakypbaev

Kyrgyz Scientific Center for Hematology, 4 Shakirov str., Bishkek, Kyrgyz Republic, 720055

For correspondence: Abdukhalim Raimzhanovich Raimzhanov, DSci, Professor, Academician of National Academy of Sciences of the Kyrgyz Republic, 4 Shakirov str., Bishkek, Kyrgyz Republic, 720055; Tel.: 0(312)54-81-20; e-mail: ab_raim@mail.ru

For citation: Raimzhanov AR, Dzhakypbaev OA. Hemorrhagic Microthrombovasculitis: Primary Hemostasis and Immunological Parameters. Clinical oncohematology. 2016;9(1):70–4 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-70-74

ABSTRACT

Background & Aims. Hemorrhagic microthrombovasculitis (HMTV) is the most common disease among hypersensitive immunocomplex systemic vasculites. The high prevalence of the disease and increasing growth of the number of HMTV patients, the severity of the clinical course, and frequent joint, GIT, and kidney involvement (30–50 %) demonstrate the important social and economic significance of this problem and the need in further specification and evaluation of unspecified pathogenetic factors with development of new treatment approaches. The aim of this work is to evaluate the ristomycin-induced platelet aggregation, cytokines and homocysteine levels in HMTV patients.

Methods. 48 HMTV patients treated in the Kyrgyz Scientific Center for Hematology over the period from September, 2013, till March, 2015, were enrolled in the study (25 men and 23 women). The age median was 23 years. In all patients, the disease was diagnosed based on clinical data and lab test findings. The following lab tests were performed: ristomycin-induced platelet aggregation, cytokines and homocysteine levels in HMTV patients. The basic treatment options included the use of anticoagulants, antiaggregants, fibrinolysis activators, and prostacyclin; in case of II–III activity degree of the autoimmune/immunocomplex process, medium doses corticosteroids with anticoagulants, antiaggregants, and therapeutic plasmapheresis are used.

Results. The study demonstrated that patients with a high degree of activity of the autoimmune inflammation presented increased ristomycin-induced platelet aggregation, increased concentrations of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) and hyperhomocysteinemia. After the treatment, in patients with generalized HMTV, the concentrations of IL-6 and TNF-a reduced by 10 % and 18.3 %, respectively, but the IL-6 level remained above the normal limits.

Conclusion. The data presented here demonstrate the importance of testing platelet aggregation upon the effect of specific inducers, as well as concentrations of proinflammatory cytokines and homocysteine in HMTV patients.

Keywords: hemorrhagic microthrombovasculitis, ristomycin-induced platelet aggregation, interleukins (IL-1b, IL-2, IL-6), tumor necrosis factor-a, homocysteine, heparin, dexamethasone, azathioprine, therapeutic plasmapheresis.

Received: July 10, 2015

Accepted: October 8, 2015

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  18. Баркаган З.С., Костюченко Г.И., Котовщикова Е.Ф. Гипергомоцистеинемия как самостоятельный фактор риска поражения и тромбоза кровеносных сосудов. Патология кровообращения и кардиохирургия. 2002;1:65–71.
    [Barkagan ZS, Kostyuchenko GI, Kotovshchikova EF. Hyperhomocystenemia as an independent risk factor of injury and thrombosis of blood vessels. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2002;1:65–71. (In Russ)]
  19. Тадтаева З.С., Кацадзе Ю.Л. Генетические признаки тромбофилии и уровень гомоцистеина в крови при мигрени и остром нарушении мозгового кровообращения у детей. Тромбоз, гемостаз и реология. 2004;4(20):38–44.
    [Tadtaeva ZS, Katsadze YuL. Genetic signs of thrombophilia and homocystein blood level in migraine and acute cerebrovascular episode in children. Tromboz, gemostaz i reologiya. 2004;4(20):38–44. (In Russ)]
  20. Кузник Б.И., Стуров В.Г., Максимова О.Г. Геморрагические и тромботические заболевания и синдромы у детей. Новосибирск: Наука, 2012. 456 с.
    [Kuznik BI, Sturov VG, Maksimova OG. Gemorragicheskie i tromboticheskie zabolevaniya i sindromy u detei. (Hemorrhagic and thrombotic diseases and syndromes in children.) Novosibirsk: Nauka Publ.; 2012. 456 p. (In Russ)]
  21. Кузник Б.И. Клеточные и молекулярные механизмы регуляции системы гемостаза в норме и патологии. Чита: Экспресс-издательство, 2010. 828 с.
    [Kuznik BI. Kletochnye i molekulyarnye mekhanizmy regulyatsii sistemy gemostaza v norme i patologii. (Cellular and molecular mechanisms of hemostasis system regulation under normal and pathological conditions.) Chita: Ekspress-izdatel’stvo Publ.; 2010. 828 p. (In Russ)]
  22. Smyth SS, Joneckis CC, Parise LV. Regulation of vascular integrins. Blood. 1993;81:2827–43. doi: 10.1042/bj2920749.
  23. Brattstrom L, Wilcken DEL. Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr. 2000;7:315–23. doi: 10.1007/978-94-017-1789-2_2.
  24. Coker A. Heparin-induced thrombocytopenia (HIT) in 2011: An epidemic of overdiagnosis. Thromb Haemost. 2011;106(6):2201–630. doi: 10.1160/th11-09-0677.
  25. McCully KS. Homocysteine, vitamins and prevention of vascular disease. Mil Med. 2004;169(4):325–9. doi: 10.7205/milmed.169.4.325.

 

ЛИТЕРАТУРА

  1. Баркаган З.С. Геморрагические заболевания и синдромы. М.: Медицина, 1988. 463 с.
    [Barkagan ZS. Gemorragicheskie zabolevaniya i sindromy. (Hemorrhagic diseases and syndromes.) Moscow: Meditsina Publ.; 1988. 463 p. (In Russ)]
  2. Баркаган З.С., Момот А.П. Основы диагностики нарушений гемостаза. М.: Ньюдиамед, 1999. 216 с.
    [Barkagan ZS, Momot AP. Osnovy diagnostiki narushenii gemostaza. (Fundamentals of diagnosis of hemostatic disorders.) Moscow: Newdiamed Publ.; 1999. 216 p. (In Russ)]
  3. Джакыпбаев О.А. Клиническая картина, показатели гемостаза и иммунной системы у больных геморрагическим васкулитом в процессе комбинированного лечения низкомолекулярным гепарином и сеансами лечебного плазмафереза: Автореф. дис. ¼ канд. мед. наук. Бишкек, 2002. 22 с.
    [Dzhakypbaev OA. Klinicheskaya kartina, pokazateli gemostaza i immunnoi sistemy u bol’nykh gemorragicheskim vaskulitom v protsesse kombinirovannogo lecheniya nizkomolekulyarnym geparinom i seansami lechebnogo plazmafereza. (Clinical presentation, parameters of hemostasis and immune system in patients with hemorrhagic vasculitis during combined treatment with low molecular weight heparin and therapeutic plasmapheresis.) [dissertation] Bishkek; 2002. 22 p. (In Russ)]
  4. Лапин С.В., Тотолян А.А. Иммунологическая диагностика поражений почек при васкулитах. Нефрология. 2003;1:109–19.
    [Lapin SV, Totolyan AA. Immunologic diagnosis of kidney impairment in vasculitis. Nefrologiya. 2003;1:109–19. (In Russ)]
  5. Раимжанов А.Р., Джакыпбаев О.А. Геморрагический васкулит и современная антитромботическая терапия. Бишкек, 2008. 144 с.
    [Raimzhanov AR, Dzhakypbaev OA. Gemorragicheskii vaskulit i sovremennaya antitromboticheskaya terapiya. (Hemorrhagic vasculitis and modern anti-thrombotic therapy.) Bishkek; 2008. 144 p. (In Russ)]
  6. Джакыпбаев О.А., Цопова И.А. Изучение агрегации тромбоцитов у больных геморрагическим васкулитом. Центрально-Азиатский медицинский журнал. 2010; XVI(4):24–6.
    [Dzhakypbaev OA, Tsopova IA. Examination of platelet aggregation in patients with hemorrhagic vasculitis. Tsentral’no-Aziatskii meditsinskii zhurnal. 2010; XVI(4):24–6. (In Russ)]
  7. Емануйлова Н.В. Гемореологические и гемостазиологические показатели при системной красной волчанке, некоторых формах васкулитов и неревматических васкулопатиях: Автореф. дис. ¼ канд. мед. наук. Ярославль, 2011. 20 с.
    [Emanuilova NV. Gemoreologicheskie i gemostaziologicheskie pokazateli pri sistemnoi krasnoi volchanke, nekotorykh formakh vaskulitov i nerevmaticheskikh vaskulopatiyakh. (Hemorheological and hemostatic parameters in systemic lupus erythematosus and non-rheumatic vasulopathies.) [dissertation] Yaroslavl’; 2011. 20 p. (In Russ)]
  8. Kawasaki Y, Suzuki J, Murai M, et al. Plasmapheresis therapy for rapidly progressive Henoch–Schonlein nephritis. Pediatr Nephrol. 2004;19(8):920–3. doi: 10.1007/s00467-004-1514-0.
  9. Wen YK, Yang Y, Chang CC. Cerebral vasculitis and intracerebral hemorrhage in Henoch–Schonlein purpura treated with plasmapheresis. Pediatr Nephrol. 2005;20:223–5. doi: 10.1007/s00467-004-1673-z.
  10. Stephens G, Yan Y, Jandrot-Perrus M, et al. Platelet activation induced metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen. Blood. 2005;105(1):186–91. doi: 10.1182/blood-2004-07-2842.
  11. Vielhauer V, Mayadas TN. Functions of TNF and its receptors in renal disease: distinct roles in inflammatory tissue injury and immune regulation. Semin Nephrol. 2007;3(27):286–308. doi: 10.1016/j.semnephrol.2007.02.004.
  12. Gedalia A. Henoch–Schonlein purpura. Curr Rheumatol Rep. 2004;6(3):195–202. doi: 10.1007/s11926-004-0068-2.
  13. Sabry A, Sheashaa H, El-Husseini A, et al. Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: Its correlation with disease activity. Cytokine. 2006;4:838–42. doi: 10.1016/j.cyto.2006.07.023.
  14. Topaloglu R, Sungur A, Baskin E, et al. Vascular endothelial growth factor in Henoch–Schonlein purpura. J Rheumatol. 2001;28(10):2269–73.
  15. Насонов Е.Л., Шилкина Н.П., Баранов А.А. Васкулиты и васкулопатии. Ярославль: Верхняя Волга, 1999. 616 с.
    [Nasonov EL, Shilkina NP, Baranov AA. Vaskulity i vaskulopatii. (Vasculites and vasculopathies.) Yaroslavl’: Verkhnyaya Volga Publ.; 1999. 616 p. (In Russ)]
  16. Емануйлов В.И. Фактор некроза опухоли a, интерлейкин-4, С-реактивный белок и гемостазиологические показатели у больных системной красной волчанкой и геморрагическим васкулитом: Автореф. дис. ¼ канд. мед. наук. Ярославль, 2007. 19 с.
    [Emanuilov VI. Faktor nekroza opukholi a, interleikin-4, S-reaktivnyi belok i gemostaziologicheskie pokazateli u bol’nykh sistemnoi krasnoi volchankoi i gemorragicheskim vaskulitom. (Tumor necrosis factor alfa, interleukin-4, C-reactive protein and hemostatic parameters in patients with systemic lupus erythematosus and hemorrhagic vasculitis.) [dissertation] Yaroslavl’; 2007. 19 p. (In Russ)]
  17. Jensen T, Kierulf P, Per M. Sandset et al. Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from isolated peripheral blood mononuclear cells. J Thromb Haemost. 2007;97(5):822–9. doi: 10.1160/th07-01-0039.
  18. Баркаган З.С., Костюченко Г.И., Котовщикова Е.Ф. Гипергомоцистеинемия как самостоятельный фактор риска поражения и тромбоза кровеносных сосудов. Патология кровообращения и кардиохирургия. 2002;1:65–71.
    [Barkagan ZS, Kostyuchenko GI, Kotovshchikova EF. Hyperhomocystenemia as an independent risk factor of injury and thrombosis of blood vessels. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2002;1:65–71. (In Russ)]
  19. Тадтаева З.С., Кацадзе Ю.Л. Генетические признаки тромбофилии и уровень гомоцистеина в крови при мигрени и остром нарушении мозгового кровообращения у детей. Тромбоз, гемостаз и реология. 2004;4(20):38–44.
    [Tadtaeva ZS, Katsadze YuL. Genetic signs of thrombophilia and homocystein blood level in migraine and acute cerebrovascular episode in children. Tromboz, gemostaz i reologiya. 2004;4(20):38–44. (In Russ)]
  20. Кузник Б.И., Стуров В.Г., Максимова О.Г. Геморрагические и тромботические заболевания и синдромы у детей. Новосибирск: Наука, 2012. 456 с.
    [Kuznik BI, Sturov VG, Maksimova OG. Gemorragicheskie i tromboticheskie zabolevaniya i sindromy u detei. (Hemorrhagic and thrombotic diseases and syndromes in children.) Novosibirsk: Nauka Publ.; 2012. 456 p. (In Russ)]
  21. Кузник Б.И. Клеточные и молекулярные механизмы регуляции системы гемостаза в норме и патологии. Чита: Экспресс-издательство, 2010. 828 с.
    [Kuznik BI. Kletochnye i molekulyarnye mekhanizmy regulyatsii sistemy gemostaza v norme i patologii. (Cellular and molecular mechanisms of hemostasis system regulation under normal and pathological conditions.) Chita: Ekspress-izdatel’stvo Publ.; 2010. 828 p. (In Russ)]
  22. Smyth SS, Joneckis CC, Parise LV. Regulation of vascular integrins. Blood. 1993;81:2827–43. doi: 10.1042/bj2920749.
  23. Brattstrom L, Wilcken DEL. Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr. 2000;7:315–23. doi: 10.1007/978-94-017-1789-2_2.
  24. Coker A. Heparin-induced thrombocytopenia (HIT) in 2011: An epidemic of overdiagnosis. Thromb Haemost. 2011;106(6):2201–630. doi: 10.1160/th11-09-0677.
  25. McCully KS. Homocysteine, vitamins and prevention of vascular disease. Mil Med. 2004;169(4):325–9. doi: 10.7205/milmed.169.4.325.