EFFECT OF MODULATORS OF NITRIC OXIDE SYNTHESIS ON HEMOSTASIS INDICATORS IN EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME
Introduction. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial and venous thrombosis, thrombocytopenia. APS causes habitual miscarriage in 27–42 % of cases.
The aim of the study – to evaluate the effect of L-arginine and aminoguanidine on the blood clotting system and platelet level in experimental antiphospholipid syndrome before and in pregnancy.
Research Methods. The APS was modeled on BALB/c female mice. L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were used for its correction. Platelet counts, fibrinogen concentration and coagulation rates were determined.
Results and Discussion. According to the research results, a decrease in platelet count, an increase in fibrinogen concentration, a shortening of activated partial thromboplastin time (aPTT), a reduction in prothrombin time, an increase of prothrombin correlation index was established in the animals with APS before pregnancy and on the 18th day of pregnancy compare to the control groups. With introduction of L-arginine into the mice with APS before pregnancy and on the 18th day of pregnancy an increase in platelet counts and a decrease in fibrinogen concentration were evidenced relative to the animals with APS. At the same time, in the APS animals the aPTT was further shortened; the pregnant APS mice experienced prolonged aPTT and increased international normalized ratios. With introduction of aminoguanidine into the APS mice, a further shortening of aPTT, a decrease in prothrombin time and international normalized ratio relative to the intact animals were proved. The increase of prothrombin index with introduction of aminoguanidine into the animals with APS before pregnancy and during pregnancy was established.
Conclusions. The tendency to hypercoagulation and the risk of thrombosis in females with APS have been established. It is one of the leading pathobiochemical aspects of pregnancy miscarriage in this disorder. L-arginine contributes to normal hemocoagulation and regulation of platelet counts; aminoguanidine leads to a worsening of the studied parameters of the coagulogram in APS before and during pregnancy.
Klyukvina, G.G. (2007). Antifosfolipidnyy sindrom: klinicheskiye aspekty. [Antiphospholipid syndrome: clinical aspects]. Meditsina neotlozhnykh sostoyaniy – Emergency Medicine, 1 (8), 17-21 [in Russian].
Khalimova, F.T., Gulin, A.V., Malysheva, Ye.V., & Nazirova, A.A. (2012). Kliniko-laboratornyye kharakteristiki antifosfolipidnogo sindroma u zhenshchin s otyagoshchennym akusherskim anamnezom [Clinical and laboratory characteristics of antiphospholipid syndrome in women with a burdened obstetric history]. Vestnik TGU – TSU Bulletin, 17 (4), 1285-1288 [in Russian].
Khalimova, F.T., Gulin, A.V., & Malysheva, Ye.V. (2012). Kharakteristika parametrov svertyvaniya krovi pri antifosfolipidnom syndrome [Characterization of blood coagulation parameters in antiphospholipid syndrome]. Vestnik TGU – TSU Bulletin, 17 (5), 1449-1451 [in Russian].
Demina, T.N., & Firsova, N.A (2016). Pokazateli sistemy gemostaza u beremennykh s preeklampsiyey na fone priobretennoy trombofilii [Indicators of the hemostatic system in pregnant women with preeclampsia against the background of acquired thrombophilia]. Mediko-sotsialnyye problemy semi – Medical and Social Problems of the Family, 21 (1), 5-11 [in Russian].
Ostryakova, Ye.V., Patrushev, L.I., & Reshetnyak, T.M. (2011). Antifosfolipidnyy sindrom i sistema fibrinoliza [Antiphospholipid syndrome and fibrinolysis system]. Nauchno-prakticheskaya revmatologiya – Scientific and Practical Rheumatology, 6, 57-64 [in Russian].
Rudzevich, A.Yu. (2019). Izmeneniya gemostaza u beremennykh s trombofiliyey, vozmozhnost profilaktiki oslozhneniy beremennosti pri priobretennoy trombofilii i antifosfolipidnom sindrome [Changes in hemostasis in pregnant women with thrombophilia, the possibility of preventing pregnancy complications with acquired thrombophilia and antiphospholipid syndrome]. Scientific Review, 1, 48–54. [in Russian].
Granakopoulos, B., & Krilis, S. (2013). The pathogenesis of the antiphospholipid syndrome. The New England Journal of Medicine, 368, 1033–1044.
Krone, K.A., Allen, K.L., & McCrae, K.R. (2010). Impaired fibrinolysis in the antiphospholipid syndrome. Curr. Rheumatol. Rep., 12 (1), 53-57.
Ivanov, A.V. (2014). Narusheniye sistemy gemostaza pri beremennosti: kliniko-diagnosticheskiye aspekty [Violation of the hemostatic system during pregnancy: clinical and diagnostic aspects]. Laboratornaya meditsina – Laboratory Medicine, 4 (11), 60-63 [in Russian].
Madei, P., Piekha, D., & Pluta, D. (2015). Imunolohichni faktory v etiopatohenezi zvychnykh vykydniv [Immunological factors in the etiopathogenesis of habitual miscarriages]. Lvivskyi medychnyi chasopys – Lviv Medical Journal, 3, 89-95 [in Ukrainian].
Makarov, O.H. (2016). Dynamika zmin pokaznykiv systemy zsidannia krovi protiahom vahitnosti u zhinok z trombofilichnymy stanamy [Dynamics of changes in blood clotting during pregnancy in women with thrombophilic conditions]. Svit medytsyny ta biolohii – World of Medicine and Biology, 2 (56), 40-42 [in Ukrainian].
Zaichenko, H.V., Larianovska, Iu.B., & Deieva, T.V. (2011). Morfolohichnyi stan matky ta platsenty pry eksperymentalnomu modeliuvanni hestatsiinoho antyfosfolipidnoho syndromu na myshakh [Morphological state of the uterus and placenta in experimental modeling of gestational antiphospholipid syndrome in mice]. Ukrainskyi medychnyi almanakh – Ukrainian Medical Almanac, 14 (4), 136-141 [in Ukrainian].
Hornytskaya, O.V. (2008). Antyfosfolipydnyy sindrom [Antiphospholipid syndrome]. Eksperymentalna ta klinichna fiziolohiia ta biokhimiia – Experimental and Clinical Physiology and Biochemistry, 1 (4), 61-70 [in Russian].
Kondratiuk, A.S., & Hrynenko, T.V. (2010). Kilkisne vyznachennia fibrynohenu v plazmi krovi turbidymetrychnym metodom z vykorystanniam antsystronu [Quantification of fibrinogen in blood plasma by turbidimetric method using ancistrone]. Fizyka zhyvoho – Physics of the Living, 18 (1), 160-163 [in Ukrainian].
Vovk, T.B., Savchuk, O.M., & Ostapchenko, L.I. (2010). Autoimunni antytila do kliuchovykh komponentiv systemy zsidannia krovi, yaki utvoriuiutsia v krovototsi pry systemnomu chervonomu vovchaku [Autoimmune antibodies to key components of the blood coagulation system that are formed in the bloodstream in systemic lupus erythematosus]. Fizyka zhyvoho – Physics of the Living, 18 (3), 59-63 [in Ukrainian].