Effect of new chalcone analogues on hemostasis in animals with experimental «сytokine storm»

2021 ◽  
Author(s):  
Д.И. Поздняков ◽  
В.М. Руковицина ◽  
А.В. Сосновская ◽  
Е.А. Олохова
Keyword(s):  
Platelet Aggregation ◽  
Antithrombin Iii ◽  
Serum Levels ◽  
Thrombin Time ◽  
Cytokine Storm ◽  
Reference Drug ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Antithrombin Iii Activity ◽  
D Dimer

Введение. «Цитокиновый шторм» представляет собой расстройство иммунной системы с выраженной гиперцитокинемией, характеризующееся развитием коагуляционных нарушений с высоким уровнем летальности. Цель исследования: оценить влияние новых аналогов халкона на изменение реакций гемостаза у крыс в условиях экспериментального «цитокинового шторма». Материалы и методы. Исследование было выполнено на 80 крысах- самцах линии Wistar, разделенных на 8 равных групп по 10 особей. «Цитокиновый шторм» моделировали путем внутрибрюшинного введения липополисахарида в дозе 10 мг/кг. Исследуемые соединения в дозе 20 мг/кг интраперитонеально и препарат сравнения — гепарин (20 ЕД/кг, подкожно) вводили через 60 мин после моделирования патологии. Через 24 ч в сыворотке крови у крыс оценивали содержание фибриногена, D-димера, растворимых фибрин-мономерных комплексов (РФМК), активность антитромбина III (АТ-III), тромбиновое время (ТВ) и степень АДФ-стимулированной агрегации тромбоцитов. Результаты. Применение аналогов халкона способствовало восстановлению гемостатических реакций, что выражалось в снижении концентраций фибриногена, D-димера, РФМК, степени агрегации тромбоцитов и повышении активности АТ-III и ТВ. При этом в ряду изучаемых веществ соединение, содержащее гидроксил во 2-м положении и метильную группу в 5-м положении, проявляло несколько больший уровень фармакологической активности, нежели остальные исследуемые соединения. Заключение. На основании полученных данных можно предположить актуальность дальнейшего изучения аналогов халкона как средств, нормализующих гемостаз при гиперцитокиновых расстройствах. Background. «Cytokine storm» is a disorder of the immune system with severe hypecytokinemia, characterized by the development of coagulation disorders with a high level of mortality. Objectives: to evaluate the effect of new chalcone analogues on changes of hemostasis reactions in rats under the conditions of an experimental «cytokine storm». Materials/Methods. The study was performed on 80 male Wistar rats divided into 8 equal groups of 10 individuals. The «cytokine storm» was modeled in animals by intraperitoneal injection of lipopolysaccharide at a dose of 10 mg/kg. The test-compounds at a dose of 20 mg/kg intraperitoneally and the reference drug — heparin (20 U/kg, subcutaneously) were administered 60 minutes after the pathology simulation. After 24 hours, the serum levels of fi brinogen, D-dimer, soluble fibrin-monomer complexes, antithrombin III activity, thrombin time, and the degree of ADP-stimulated platelet aggregation were evaluated in rats. Results. The study showed that the use of chalcone analogues contributed to the restoration of hemostasis reactions, which was expressed in a decrease in theconcentration of fibrinogen, D-dimer, soluble fibrin-monomer complexes, the degree of platelet aggregation, and an increase in antithrombin III activity and thrombin time. At the same time, among the studied substances, the compound containing hydroxyl in the 2nd position and the methyl group in the 5th position showed a slightly higher level of pharmacological activity than the other test compounds. Conclusions. Based on the obtained data, it is actuality to assume the relevance of further study of chalcone analogues as agents that normalize hemostasis in hypercytokine disorders.

Bleeding in Uremic Patients after Carbenicillin

1976 ◽  
Vol 36 (01) ◽  
pp. 115-126 ◽  
Author(s):  
K Andrassy ◽  
E Weischedel ◽  
E Ritz ◽  
T Andrassy
Keyword(s):  
Platelet Function ◽  
Antithrombin Iii ◽  
Serum Levels ◽  
Coagulation Factors ◽  
Coagulation System ◽  
Hemorrhagic Diathesis ◽  
Thrombin Time ◽  
Antithrombin Iii Activity

SummaryHemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels > 300 μg/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal fibrinogen-fibrin conversion and a modified electrophoretic mobility of antithrombin III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives.This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity.Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenave et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels “only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function”.

Influence of means of prevention of adverse effects of space flight on the plasma component of the system of regulation of the aggregate state of human blood

2020 ◽  
Vol 60 (11) ◽  
pp. 818-820
Author(s):  
Dmitry S. Kuzichkin ◽  
Aleksey Yu. Kochergin
Keyword(s):  
Adverse Effects ◽  
Human Blood ◽  
Space Flight ◽  
Physical Activities ◽  
Thrombin Time ◽  
Soluble Fibrin ◽  
Antiorthostatic Hypokinesia ◽  
Fibrin Monomer ◽  
The Impact ◽  
D Dimer

Introduction. It is known that the factors of space flight shift the coagulation balance of blood in the direction of procoagulant. The effect of space flight factors on the hemostatic potential of human blood with the simultaneous effect of preventive measures and compensation for their adverse effects has not been practically studied. The aim of study was to study the effect of physical exertion, electromyostimulation, mechanical stimulation of the foot, and blood-substituting solutions on the main indicators of the human hemostasis system in experiments with 21-hour antiorthostatic hypokinesia, 7-day "dry" water immersion, and 120-day isolation in a hermetic volume. Materials and methods. Concentrations of fibrinogen, plasminogen, soluble fibrin-monomer complexes, D-dimer, antithrombin III, protein C, and α2-antiplasmin were determined in citrate plasma; values of thrombin time, activated partial thromboplastin time, and prothrombin time. Results. It was found that the infusion of blood-substituting colloidal solution "venofundin" prevents the tendency to increase the level of soluble fibrin-monomer complexes observed during 21-hour antiorthostatic hypokinesia. Electromyostimulation leads to increased levels of fibrinogen and D-dimer during 7-day immersion. The complex of physical activities used in the experiment with 120-day isolation helps to reduce the level of D-dimer. Conclusions. The results indicate that when modeling the impact of space flight factors, a favorable hypocoagulation effect is provided by an infusion of venofundin, as well as a complex of balanced physical activities.

scholarly journals Evaluation of Soluble Fibrin Monomer Complex in Patients with Sars-Cov-2 COVID-19 Infection

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Meera Sridharan ◽  
Aneel A. Ashrani ◽  
Dong Chen ◽  
Nahla M. Heikal ◽  
Ariela L. Marshall ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Mayo Clinic ◽  
Onset Time ◽  
The Other ◽  
Onset Date ◽  
Thrombin Time ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Prolonged Aptt ◽  
D Dimer

Introduction: In patients with SARS-CoV-2 COVID-19 infection elevated D-dimers are associated with a poor prognosis. Although suggestive of DIC, the majority of patients do not fulfil ISTH criteria for DIC. Studies have demonstrated that when compared to D-dimer, fibrin monomers are more sensitive and specific when differentiating overt DIC from non-overt DIC. Our special coagulation laboratory (SCL) routinely measures soluble fibrin monomer complex (SFMC) as part of our DIC profile in samples with elevated D-dimers. Here we aimed to investigate the percentage of patients with COVID-19 infection with elevated SFMC as performed as part of the DIC profile. Methods: Between April 1st 2020 and July 26, 2020 inpatients at the Mayo Clinic Rochester, MN campus with COVID-19 infection who underwent DIC testing in SCL were identified through SCL database. Patients were excluded if SARS-CoV2 PCR results were not available in the Mayo Clinic electronic medical record (EMR). DIC profile components include prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen and D-dimer. Reflex SFMC is performed if D-dimer is elevated. Data abstracted from EMR included results of laboratory tests, date of COVID-19 symptom onset, date of SARS-CoV2 PCR positivity, and death within 30 days of hospital admission. The ISTH DIC score was calculated and patients were labeled as overt DIC or non-overt DIC based off of ISTH DIC score ≥5. Results: 35 patients (19 female), median age 59 years (28-91) met our study criteria DIC profiles were obtained 6.5 (1-37) days after COVID-19 symptom onset (n=33) with 28 obtained within 14 days of symptom onset. Time to DIC profile from SARS-CoV2 PCR testing was 4 (0-37) days (n=35) with 31 having testing completed within 14 days of PCR positivity. 8 patients were intubated during hospitalization and of the remaining 27, 67% required supplemental oxygen. 21/35 (60%) patients had an elevated fibrinogen (526.5 mg/dL (201-800)) while 19/35 (54%) had a prolonged PT (12.8 seconds (10.1-99.6) and 5/35 (14%) had a prolonged APTT (31 seconds (24-68)). 17 patients with prolonged PT and 3 patients with prolonged APTT had factor activity assays performed (Figure 1A). 9/35 (25%) had thrombocytopenia (230 x 109/L (12-709) and 27/35 (77%) patients had an elevated D-dimer (895 ng/ml FEU (220- >100,000). D-dimer was higher in males than in females (p: 0.049). Of those with elevated D-dimer only 5/27 (18.5%) had an elevated SFMC (5 mcg/ml (5- >1100) (Figure 1B). 4/35 (11%) patients had ISTH DIC scores ≥ 5 and all had score of 5. All of these patients had D-dimer > 2000 ng/ml while only 2 had elevated SFMC however SFMC in both of these patients was < 15 mcg/ml. Of these, one patient with SFMC of 12 mcg/ml had known cirrhosis and the other with an SFMC of 11 mcg/ml had acute decompensation and associated shock liver. This patient also had venous thrombosis 3 days prior to DIC profile and died from complications related to COVID-19 infection. Of the two other patients with high ISTH score and normal SFMC, one had previous chronic thrombocytopenia of < 50 x109/L while the other had concomitant admission for acute and recurrent pancreatitis in the setting of alcoholism with acute intoxication. Six patients died within 30 days of admission and in 2/5 performed SFMC was elevated (Figure1C). Conclusion: Compared to 77% of patients with elevated D-dimers, of those tested only 18.5 % of patients had elevated SFMC. It has been hypothesized that the elevated D-dimer noted in COVID-19 pulmonary infection is a direct consequence of acute lung injury and not overt DIC. Although preliminary, the small percentage of patients with overt DIC by ISTH criteria and normal SFMC in the majority of the current cohort support this hypothesis; however studies in a larger more controlled cohort are needed to confirm these findings. Disclosures Sridharan: Alexion: Honoraria. Pruthi:Merck: Honoraria; Instrumentation Laboratory: Honoraria; HEMA Biologics: Honoraria; Bayer Healthcare: Honoraria; Genentech Inc.: Honoraria; CSL Behring: Honoraria.

scholarly journals Some features of the hemostasis system in pregnant women at risk of developing preeclampsia

2021 ◽  
Vol 6 ◽  
pp. 61-65
Author(s):  
V.І. Chermak
Keyword(s):  
Platelet Aggregation ◽  
Pregnant Women ◽  
Antithrombin Iii ◽  
Main Group ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Soluble Fibrin ◽  
Hemostasis System ◽  
Healthy Women ◽  
Risk Of Preeclampsia

The objective: a study of the hemostasis system in pregnant women with a risk of preeclampsia development.Materials and methods. 100 pregnant women with the risk for preeclampsia (main group) were examined. The risk factors were determined according to the Guideline “Hypertensive Disorders During Pregnancy”, Order No. 676 of the Ministry of Health of Ukraine. The control group contained of 50 healthy women with physiological pregnancy. The groups were representative in age and reproductive history.The following indicators of hemostasis were studied: the platelet system (the number of platelets, their aggregation ability and the total platelet aggregation index (TPAI), the coagulation system (autocoagulation test, thrombin time, prothrombin index, fibrinogen concentration) and the state of the fibrinolysis system which was determined by such indicators: plasma level of free heparin, activity of antithrombin III, indicators of ethanol and protamine sulfate tests, concentration of soluble fibrin in blood plasma.Results. In pregnant women with a risk of preeclampsia, there are changes in platelet hemostasis indicators: a significant decrease in the number of platelets and a significant (p<0.05) increase in platelet aggregation ability, there is a tendency to an increase in TPAI indicators. In the main group a significant increase in the fibrinogen concentration, plasma lysis indicators and a tendency to an increase of the free heparin concentration, a decrease of antithrombin III and, in comparison with the indicators in healthy women, a 3-fold increase in the content of soluble fibrin (p<0.05) were found.Conclusions. In pregnant women with a risk of preeclampsia development, there are disorders in the vascular-platelet hemostasis, coagulation and fibrinolytic blood systems, namely, a significant tension in the platelet link of the system, an increase in thrombogenic potential, and a sharp inhibition of the fibrinolytic link of hemostasis.

Prevention of massive intraoperative bleedings associated with heparin with the systemic use of fibrin monomer in the experiment

2019 ◽  
pp. 48-55
Author(s):  
А.П. Момот ◽  
В.М. Вдовин ◽  
Д.А. Орехов ◽  
Н.А. Лычёва ◽  
И.Г. Толстокоров ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Unfractionated Heparin ◽  
Loss Rate ◽  
Antithrombin Iii ◽  
Fibrinogen Level ◽  
Circulating Blood Volume ◽  
Intraoperative Bleeding ◽  
Fibrin Monomer ◽  
Antithrombin Iii Activity

Цель исследования - изучение способности фибрин-мономера предупреждать тяжелую интраоперационную кровопотерю, ассоциированную с введением нефракционированного гепарина, при дозированной травме печени. Методика. На кроликах «Шиншилла» индуцировали гипокоагуляцию нефракционированным гепарином (150 ед/кг). Профилактику интраоперационных кровотечений осуществляли внутривенным введением фибрин-мономера (0,25 мг/кг) за 1 ч до травмы или протамина сульфата (1,5 мг/кг) за 10 мин до травмы. После нанесения стандартной травмы печени оценивали объем (в % ОЦК) и темп (мг/с) кровопотери. Анализировали число тромбоцитов, активированное парциальное тромбопластиновое время, протромбиновое и тромбиновое время свертывания, уровень фибриногена и активность антитромбина III, параметры ротационной тромбоэластометрии крови. Результаты. Объем кровопотери в группах животных после в/в введения фибрин-мономера и протамина сульфата на фоне гепаринизации был, соответственно, в 5,1 и 4,0 раза меньше по сравнению с группой плацебо, получавшей тот же антикоагулянт. Вместе с тем, фибрин-мономер не влиял на параметры коагулограммы (отсутствие видимого гемостазиологического эффекта) и тромбоэластограммы, тогда как применение протамина сульфата в качестве антидота гепарина сопровождалось нормализацией данных тромбоэластометрии и коррекцией гипокоагуляционного сдвига по активированному парциальному тромбопластиновому времени, протромбиновому и тромбиновому времени. Заключение. Установлено, что фибрин-мономер (0,25 мг/кг) снижает посттравматическое кровотечение в условиях блокады свертывания крови гепарином без видимых признаков восстановления гемостатического равновесия. The research objective was to study the ability of fibrin monomer to prevent severe intraoperative blood loss associated with administration of unfractionated heparin in controlled liver injury. Methods. Hypocoagulation was induced in chinchilla rabbits with unfractionated heparin (150 U/kg). Intraoperative bleeding was prevented by administration of fibrin monomer (FM, 0.25 mg/kg, i.v.) one hour prior to the injury and of protamine sulfate (PS, 1.5 mg/kg, i.v.) 10 min prior to the injury. Following the liver injury, blood loss was assessed as percentage of circulating blood volume and the blood loss rate (mg/s). Platelet counts, aPTT, PT, TT, fibrinogen level, antithrombin III activity, and parameters of blood rotation thromboelastometry were analyzed. Results. The volume of blood loss was 5.1 times and 4.0 times less, respectively, after the FM and PS administration during heparinization compared to the placebo group treated with the same anticoagulant. However, FM affected neither coagulogram indexes (no visible hemostasiological effect) nor thromboelastogram while the use of PS as an antidote for heparin was associated with normalization of thromboelastometric data and correction of hypercoagulative changes in aPTT, PT, TT. Conclusion. FM at a dose of 0.25 mg/kg reduced severity of posttraumatic bleeding induced by heparin inhibition of coagulation with no visible signs of hemostatic balance recovery.

scholarly journals Azolo[1,5-a]pyrimidines and Their Condensed Analogs with Anticoagulant Activity

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 274
Author(s):  
Konstantin V. Savateev ◽  
Victor V. Fedotov ◽  
Vladimir L. Rusinov ◽  
Svetlana K. Kotovskaya ◽  
Alexandr A. Spasov ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Anticoagulant Activity ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antiviral Agents ◽  
Multiple Organ ◽  
Thrombin Time ◽  
Cytokine Storm ◽  
Reference Drug

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

Recombinant Human Transgenic Antithrombin in Cardiac Surgery

2002 ◽  
Vol 96 (5) ◽  
pp. 1095-1102 ◽  
Author(s):  
Jerrold H. Levy ◽  
George J. Despotis ◽  
Fania Szlam ◽  
Peter Olson ◽  
David Meeker ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Coronary Artery ◽  
Coronary Artery Bypass Grafting ◽  
Coronary Artery Bypass ◽  
Antithrombin Iii ◽  
Artery Bypass ◽  
Bypass Grafting ◽  
Artery Bypass Grafting ◽  
Fibrin Monomer ◽  
D Dimer

Background Acquired antithrombin III (AT) deficiency may render heparin less effective during cardiac surgery and cardiopulmonary bypass (CPB). The authors examined the pharmacodynamics and optimal dose of recombinant human AT (rh-AT) needed to maintain normal AT activity during CPB, optimize the anticoagulant response to heparin, and attenuate excessive activation of the hemostatic system in patients undergoing coronary artery bypass grafting. Methods Thirty-six patients scheduled to undergo elective primary coronary artery bypass grafting and who had received heparin for 12 h or more before surgery were enrolled in the study. Ten cohorts of three patients each received rh-AT in doses of 10, 25, 50, 75, 100, 125, 175, or 200 U/kg, a cohort of six patients received 150 U/kg of rh-AT, and a control group of six patients received placebo. Results Antithrombin III activity exceeded 600 U/dl before CPB at the highest dose (200 U/kg). Doses of 75 U/kg rh-AT normalized AT activity to 100 U/dl during CPB. Activated clotting times during CPB were significantly (P &lt; 0.0001) greater in patients who received rh-AT (844 +/- 191 s) compared with placebo patients (531 +/- 180 s). Significant (P = 0.001) inverse relations were observed between rh-AT dose and both fibrin monomer (r = -0.51) and D-dimer (r = -0.51) concentrations. No appreciable adverse events were observed with any rh-AT doses used in the study. Conclusions Supplementation of native AT with transgenically produced protein (rh-AT) in cardiac surgical patients was well tolerated and resulted in higher activated clotting times during CPB and decreased levels of fibrin monomer and D-dimer.

scholarly journals Thrombin antithrombin complex and IL-18 serum levels in stroke patients

2010 ◽  
Vol 2 (1) ◽  
pp. 1 ◽  
Author(s):  
Ornella Piazza ◽  
Giuliana Scarpati ◽  
Simona Cotena ◽  
Maria Lonardo ◽  
Rosalba Tufano
Keyword(s):  
Antithrombin Iii ◽  
Degradation Products ◽  
Focal Cerebral Ischemia ◽  
Serum Levels ◽  
High Serum ◽  
Fibrin Degradation Products ◽  
Markers Of Inflammation ◽  
Complex Picture ◽  
Thrombin Antithrombin Iii Complex ◽  
D Dimer

The complex picture of inflammation and coagulation alterations comes to life in acute stroke phases. Increasing evidence points to a strong interaction and extensive crosstalk between the inflammation and coagulation systems: the interest towards this relationship has increased since recent experimental research showed that the early administration of antithrombin III (ATIII) decreases the volume of ischemia in mice and might be neuroprotective, playing an antiinflammatory role. We aimed to establish the extent of the relationship among markers of inflammation (S100B and IL-18) and procoagulant and fibrinolytic markers (ATIII, thrombin-antithrombin III complex (TAT), Fibrin Degradation Products (FDP), D-dimer) in 13 comatose patients affected by focal cerebral ischemia. Plasma levels of TAT, D-dimer and FDP, IL18 and S100B were increased. IL-18 and S100B high serum levels in ischemic patients suggest an early activation of the inflammatory cascade in acute ischemic injury. The basic principles of the interaction between inflammatory and coagulation systems are revised, from the perspective that simultaneous modulation of both coagulation and inflammation, rather than specific therapies aimed at one of these systems could be more successful in stroke therapy.

scholarly journals General casual hypothermia as a threat of thrombosis in rats

2014 ◽  
Vol 95 (3) ◽  
pp. 385-388
Author(s):  
N A Lycheva ◽  
I I Shakhmatov
Keyword(s):  
Platelet Aggregation ◽  
Peripheral Blood ◽  
Adenosine Diphosphate ◽  
Cold Injury ◽  
Clotting Factor ◽  
Fibrinogen Concentration ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Third Stage ◽  
Aggregation Activity

Aim. To study the hemostasis at the pre-reactive period of cold injury occurred at the third stage of the decompensated phase of general casual hypothermia. Methods. Experiments were performed on on 23 Wistar rats. General casual hypothermia was simulated by placing the animals in individual cages in a freezer with in-temperature of -25 °C. Animals were kept in the freezer until the rectal body temperature of +30 °С. Blood samples of 10 animals, kept at 22°C during the same exposure time, were used as a control. Hemostasis parameters, including platelets and coagulation panel, as well as blood serum anticoagulant and fibrinolytic activity, were assessed in peripheral blood. Induced platelet aggregation was measured by aggregometer, with 10 μg/ml adenosine diphosphate solution as the inductor. Results. General casual hypothermia was not associates with changes in the peripheral blood. At the same time, increased platelet count by 19% (р 0.05) and reduced platelet aggregation activity by 9 times (р 0.05) was observed. The coagulation panel at the pre-reactive period of cold injury was associated with Echitox coagulation time increase by 42% (р 0.05), together with fibrinogen concentration drop by 25% (р 0.05). Increased polymerization time of circulating soluble fibrin monomer complexes by 36% (р 0.05) was suggestive of reduced I clotting factor serum concentrations. In the same animals, the serum concentration of soluble fibrin monomer complexes was increased by 96% (р 0.05), suggesting the increased clotting activity. Conclusion. Decompensated phase of general casual hypothermia was associated with significant changes of on the hemostasis. The set of observed changes was suggestive of increased clotting activity as the response to the cold trauma and predisposition to clotting in experimental animals.

scholarly journals A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives: its application to the measurement of soluble fibrin in plasma

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 2109-2117 ◽  
Author(s):  
G Soe ◽  
I Kohno ◽  
K Inuzuka ◽  
Y Itoh ◽  
M Matsuda
Keyword(s):  
Monoclonal Antibody ◽  
Beta Chain ◽  
Aggregation Assay ◽  
Soluble Fibrin ◽  
Amino Terminal ◽  
Conformation Changes ◽  
Fibrin Monomer ◽  
Latex Beads ◽  
Thrombotic Diseases ◽  
D Dimer

Using urea-solubilized human fibrin monomer as an immunogen, we raised in mice a battery of monoclonal antibodies that reacted with the immunogen but not with urea-treated or native fibrinogen. Although they all failed to react with acid-solubilized fibrin monomer (acid-FM) alone, an antibody designated as IF-43 was found to recognize acid-FM, which was bound with fibrinogen or its derivatives to form a 1:2 complex of soluble fibrin. The epitope for this antibody, thus, appears to be exposed most probably by conformation changes induced in the acid- FM molecule upon formation of the complex. Because IF-43 was able to recognize fibrin-derived plasmic fragment E treated with urea but not the thrombin- and urea-treated amino-terminal disulfide knot of fibrinogen, the presence of the A alpha (52–78) residue segment seems to be prerequiste for the epitope expression. The antibody was found to react with soluble fibrin monomer spiked to normal plasma dose- dependently up to 200 micrograms/mL. By an aggregation assay using latex beads coated with IF-43, we found that concentrations of soluble fibrin monomer in plasma derived from patients with thrombotic diseases were mostly elevated, but not necessarily correlated with those of the D-dimer, reflecting another aspects of the disease. Furthermore, the soluble fibrin monomer in plasma derived from patients with thrombotic diseases was found to be depleted solely of the A peptides, but not the B peptides, based on its subunit polypeptide compositions lacking the beta-chain on immunoblotting.

Sign in / Sign up

Export Citation Format

Share Document