The features of the thrombolytics use in the process of the reversal of acute coronary occlusion syndrome

2021 ◽  
pp. 52-57
Author(s):  
Konstantin Robertovich Gulyabin
Keyword(s):  
Thrombus Formation ◽  
Coronary Vessels ◽  
Regulatory System ◽  
Coagulation System ◽  
Internal Factors ◽  
Leading Role ◽  
Treatment And Prevention ◽  
Neurohumoral Regulation ◽  
Acute Coronary Occlusion ◽  
Blood Clots

The mechanism of thrombus formation is a coordinated process that is under the control of neurohumoral regulation and is influenced by a variety of external and internal factors. Any disruption in the regulatory system, activation of some factors and inhibition of others can lead to disruption in the coagulation system, affecting both the plasma and platelet links of hemostasis. The activation of platelets against the background of the existing atherosclerosis of the vessels leads to the formation of blood clots, which clog the lumen of the coronary vessels and can lead to acute myocardial infarction. Today it is well known that increased thrombus formation is not only the cause of the development of acute conditions, but also leads to the progression of the disease. The leading role in the initiation of the thrombus formation process is played by platelets, therefore, the use of antiplatelet drugs is an obligatory link in both the treatment and prevention of thrombosis. In this case, the most important is the need to restore blood flow in the coronary vessels, which provide nutrition to the myocardium. In this regard, correctly selected antithrombotic agents can take a worthy place in the treatment and prevention of cardiovascular pathology, which is based on ischemic thrombosis.

Role of thrombolytic therapy in the modern treatment plan for coronary artery disease and acute coronary artery occlusion

2020 ◽  
pp. 48-54
Author(s):  
Nataliya Sakhno
Keyword(s):  
Coronary Artery ◽  
Treatment Plan ◽  
Coronary Vessels ◽  
Coronary Artery Occlusion ◽  
Coagulation Factors ◽  
Artery Occlusion ◽  
Coagulation System ◽  
Regulation System ◽  
Main Task ◽  
Neurohumoral Regulation

The thrombosis mechanism is a coordinated process under the control of neurohumoral regulation and influenced by various factors. Any violation in the regulation system, activation of some factors and inhibition of others can lead to disorders in the coagulation system, affecting both the plasma and platelet hemostasis. Activation of platelet coagulation factors against the background of vascular sclerosis leads to the formation of blood clots, which clog the lumen of the coronary vessels and can lead to acute myocardial infarction. It was established that thrombosis is the cause of not only acute conditions, but also the progression of the disease. The main task in this case is the restoration of blood flow in the coronary vessels that provide myocardial nutrition. Therefore, correctly selected antithrombotic agents can take rightful place in the treatment and prevention of cardiovascular pathology, which is based on ischemic thrombosis.

Oxidative Stress and Atherosclerosis: Its Relationship to Growth Factors, Thrombus Formation and Therapeutic Approaches

1999 ◽  
Vol 82 (S 01) ◽  
pp. 32-37 ◽  
Author(s):  
Karlheinz Peter ◽  
Wolfgang Kübler ◽  
Johannes Ruef ◽  
Thomas K. Nordt ◽  
Marschall S. Runge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factors ◽  
Vessel Wall ◽  
Inflammatory Responses ◽  
Plaque Rupture ◽  
Thrombus Formation ◽  
Vascular Lesion ◽  
Coagulation System ◽  
Therapeutic Approaches ◽  
Causative Relationship

SummaryThe initiating event of atherogenesis is thought to be an injury to the vessel wall resulting in endothelial dysfunction. This is followed by key features of atherosclerotic plaque formation such as inflammatory responses, cell proliferation and remodeling of the vasculature, finally leading to vascular lesion formation, plaque rupture, thrombosis and tissue infarction. A causative relationship exists between these events and oxidative stress in the vessel wall. Besides leukocytes, vascular cells are a potent source of oxygen-derived free radicals. Oxidants exert mitogenic effects that are partially mediated through generation of growth factors. Mitogens, on the other hand, are potent stimulators of oxidant generation, indicating a putative self-perpetuating mechanism of atherogenesis. Oxidants influence the balance of the coagulation system towards platelet aggregation and thrombus formation. Therapeutic approaches by means of antioxidants are promising in both experimental and clinical designs. However, additional clinical trials are necessary to assess the role of antioxidants in cardiovascular disease.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

scholarly journals MicroRNA as Biomarkers for Platelet Function and Maturity in Patients with Cardiovascular Disease

2021 ◽  
Author(s):  
Oliver Buchhave Pedersen ◽  
Erik Lerkevang Grove ◽  
Steen Dalby Kristensen ◽  
Peter H. Nissen ◽  
Anne-Mette Hvas
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Function ◽  
Assessment Tool ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Quality Assessment Tool ◽  
Treatment And Prevention ◽  
Increased Risk ◽  
Meta Analyses ◽  
Potential Use

AbstractPatients with cardiovascular disease (CVD) are at increased risk of suffering myocardial infarction. Platelets are key players in thrombus formation and, therefore, antiplatelet therapy is crucial in the treatment and prevention of CVD. MicroRNAs (miRs) may hold the potential as biomarkers for platelet function and maturity. This systematic review was conducted using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To identify studies investigating the association between miRs and platelet function and maturity in patients with CVD, PubMed and Embase were searched on October 13 and December 13, 2020 without time boundaries. Risk of bias was evaluated using a standardized quality assessment tool. Of the 16 included studies, 6 studies were rated “good” and 10 studies were rated “fair.” In total, 45 miRs correlated significantly with platelet function or maturity (rho ranging from –0.68 to 0.38, all p < 0.05) or differed significantly between patients with high platelet reactivity and patients with low platelet reactivity (p-values ranging from 0.0001 to 0.05). Only four miRs were investigated in more than two studies, namely miR-223, miR-126, miR-21 and miR-150. Only one study reported on the association between miRs and platelet maturity. In conclusion, a total of 45 miRs were associated with platelet function or maturity in patients with CVD, with miR-223 and miR-126 being the most frequently investigated. However, the majority of the miRs were only investigated in one study. More data are needed on the potential use of miRs as biomarkers for platelet function and maturity in CVD patients.

Biochemical and Pharmacological Properties of SANORG 34006, a Potent and Long-Acting Synthetic Pentasaccharide

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4197-4205 ◽  
Author(s):  
J.M. Herbert ◽  
J.P. Hérault ◽  
A. Bernat ◽  
R.G.M. van Amsterdam ◽  
J.C. Lormeau ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Therapeutic Index ◽  
Inhibitory Effect ◽  
Experimental Models ◽  
Treatment And Prevention ◽  
Long Acting

Abstract SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It is an analog of the “synthetic pentasaccharide” (SR 90107/ ORG 31540) which represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 ± 0.3 v 48 ± 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 ± 15 anti–factor Xa U/mg v850 ± 27 anti-factor Xa U/mg for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long-lasting anti–factor Xa activity and inhibition of thrombin generation (TG) ex vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats, rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%. SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of the anti–factor Xa activity of AT. It strongly inhibited thrombus formation in experimental models of thromboplastin/stasis-induced venous thrombosis in rats (IV) and rabbits (SC) (ED50values = 40.0 ± 3.4 and 105.0 ± 9.4 nmol/kg, respectively). The duration of its antithrombotic effects closely paralleled the ex vivo anti–factor Xa activity. SANORG 34006 enhanced rt-PA–induced thrombolysis and inhibited accretion of125I-fibrinogen onto a preformed thrombus in the rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA therapy might be helpful in facilitating thrombolysis and preventing fibrin accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG 34006 did not enhance bleeding in a rabbit ear incision model at a dose that equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited a favorable therapeutic index. We suggest that SANORG 34006 is a promising compound in the treatment and prevention of various thrombotic diseases.

Abstract P707: Trends, Predictors and Outcomes of Cerebrovascular Disease Amongst Patients With Thrombotic Microangiopathy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Priyadarshee Patel ◽  
Urvish K Patel ◽  
Graca Vanessa ◽  
Abhinav Patel ◽  
Davis Chacko ◽  
...  
Keyword(s):  
Thrombotic Microangiopathy ◽  
Thrombus Formation ◽  
Cerebral Arteries ◽  
Temporal Trends ◽  
Cross Sectional Study ◽  
Coagulation System ◽  
Trend Test ◽  
Cross Sectional ◽  
Logistic Regression Models ◽  
The Usa

Background: Thrombotic Microangiopathy (TMA) is a rare disorder affecting the coagulation system causing microangiopathic thrombus formation within various blood vessels including the cerebral arteries. It may be seen in association with thrombocytopenia, anemia, purpura and kidney failure as well as complications of various systemic viral illnesses. We sought to estimate the trends, predictors, and outcomes of CeVD in patients having ™ from a nationally representative database of the USA. Methods: In this cross-sectional study, we identified hospitalization with TM using ICD-9/10-CM from the National Inpatient Sample (NIS) for the years 2008-2017. Prevalence of CeVD was identified by validated ICD-9/10-CM codes. We utilized Cochran Armitage trend test and multivariable survey logistic regression models to analyze temporal trends, outcomes and predictors of any CeVD in TM patients. Results: Out of a total 58,850 hospitalizations among TMA patients, 4,668 (7.9%) developed CeVD. Prevalence of CeVD increased from 6.2% in 2008 to 8.2% in 2017 (pTrend<0.001). Patients who developed CeVD were older and more likely to be female. In multivariable regression analysis, increasing age (OR 1.2; 95%CI 1.1-1.2; p<0.0001); females (OR 1.3; 95%CI 1.1-1.6;p<0.0004); African American (OR 1.4; 95%CI 1.2-1.7;p<0.001) and hypertension (OR 1.3; 95%CI 1.1-1.6; p<0.0001). CeVD was also associated with higher length of stay (18 vs 12 days; p<0.001). Additionally, CeVD was associated with higher in-hospital mortality (aOR 2.1; 95%CI 1.7-2.5; p<0.001) and discharge to facility (aOR 3.0; 95%CI 2.4-3.5; p<0.001) after adjusting with confounders. Conclusion: We observed the mildly incremental prevalence of CeVD among TMA patients. We were able to identify the TMA patient population susceptible to CeVD, most commonly occurring in older, females and African Americans. CeVD was also associated with significantly poor outcomes in TM. These findings may pose similarities to other systemic viral illness-induced thrombotic microangiopathy such as COVID-19. Further studies are required to improve the outcomes of these susceptible patient populations.

Circulating platelet-derived microparticles in systemic lupus erythematosus

2006 ◽  
Vol 95 (01) ◽  
pp. 94-99 ◽  
Author(s):  
Gino Alfaro ◽  
Manuela Goycoolea ◽  
Teresa Quiroga ◽  
Mauricio Ocqueteau ◽  
Loreto Massardo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Thrombus Formation ◽  
Annexin V ◽  
Coagulation System ◽  
Systemic Lupus ◽  
Double Labeling ◽  
Cellular Source ◽  
Risk For Thrombosis

SummaryThe risk for thrombosis is significantly increased in systemic lupus erythematosus (SLE), affecting both venous and arterial vessels. Activated platelets are known to participate in thrombus formation and growth. A general feature of activated cells is the shedding of microparticles (MP) which support coagulation by exposure of negatively charged phospholipids and possibly tissue factor (TF). In this work we characterized circulating MP in patients with SLE and their relationship with a procoagulant state. Thirty patients with SLE (aged 15–72 years, mean age 38 years) and 20 healthy controls (aged 22–54 years, mean age 34 years) were studied; patients fulfilled 4 revised criteria for SLE. The number and cellular source of circulating MP were determined by flow cytometry using double labeling with specific monoclonal antibodies and annexin V. Thrombin generation was measured as the endogenous thrombin potential (ETP) without the addition of exogenous phospholipids and TF; under these conditions the generation of thrombin depended directly on the number of MP present in plasma. Thrombin anti-thrombin (TAT) and plasmin-antiplasmin (PAP) complexes were measured by ELISA. Compared to the controls, circulating MP were significantly elevated in the patient group (1218 ± 136 vs 653 ± 74 x103/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927± 131 vs 517 ± 72 x103/ml plasma, p:0.009 ). ETP was higher among patients as compared to the controls (804± 64 vs 631 ± 37 nM thrombin, p: 0.025). Plasma levels of TAT in patients and controls were 3.4 ± 0.8 and 1.4 ± 0.5 µg/L, respectively (p:0.04), and of PAP complexes were 62.5 ± 14 and 24.05± 2.5 µg/ml, respectively (p: 0.014).The number of platelet-derived MP correlated significantly with thrombin generation (r: 0.42; p: 0.038) and TAT levels (r: 0.40; p: 0.035).We did not find an association of circulating MP with disease activity nor with the presence of antiphospholipid antibodies. The increased number of circulating platelet-derived microparticles and their association with high ETP and activation of the coagulation system suggest that these microparticles play an important role in the pathogenesis of the prothrombotic state in SLE patients.

Comparative Studies of an Orally-active Factor Xa Inhibitor, YM-60828, with other Antithrombotic Agents in a Rat Model of Arterial Thrombosis

1998 ◽  
Vol 79 (02) ◽  
pp. 410-416 ◽  
Author(s):  
Kazuo Sato ◽  
Yumiko Sakai ◽  
Fukushi Hirayama ◽  
Hiroyuki Koshio ◽  
Yuta Taniuchi ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Test Drug ◽  
Antithrombotic Agent ◽  
Antithrombotic Activity ◽  
Thrombosis Model ◽  
Treatment And Prevention ◽  
Orally Active

SummaryWe examined the antithrombotic activity of a novel synthetic inhibitor of factor Xa, YM-60828, in an electrically-induced carotid artery thrombosis model in rats. In the first experiment, the antithrombotic activity of YM-60828 after i.v. infusion was compared with those of heparin, darteparin and argatroban. Test drug was administered by i.v. infusion from 30 min before electrical stimulation to the end of the experiment. YM-60828 at 1 mg/kg/h significantly improved patency status, prolonged the time to occlusive thrombus formation and duration of patency. Heparin at 300 U/kg/h also improved these parameters, but were accompanied by a marked increase in systemic coagulation time. In the second experiment, the antithrombotic activity of YM-60828 after oral administration was compared with those of ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate and warfarin. Test drug was orally administered to fasted rats 60 min before electrical stimulation. YM-60828 at 30 mg/kg p.o., but not ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate or warfarin, significantly reduced the incidence of occlusion and improved carotid arterial patency. These results suggest that YM-60828 may be a promising antithrombotic agent for the treatment and prevention of arterial thrombosis which can be given by oral as well as intravenous administration.

Coagulation (Hemostasis and Thrombosis)

2012 ◽  
Author(s):  
Rajiv K. Pruthi
Keyword(s):  
Risk Factors ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Fibrin Clot ◽  
Coagulation System ◽  
Bleeding Disorders ◽  
Hemostatic System ◽  
Blood Clots ◽  
Anticoagulant System ◽  
Plug Formation

The coagulation system has 2 essential functions: to maintain hemostasis and to prevent and limit thrombosis. The procoagulant component of the hemostatic system prevents and controls hemorrhage. Vascular injury results in activation of hemostasis, which consists of vasospasm, platelet plug formation (platelet activation, adhesion, and aggregation), and fibrin clot formation (by activation of coagulation factors in the procoagulant system). The anticoagulant system prevents excessive formation of blood clots, and the fibrinolytic system breaks down and remodels blood clots. Quantitative abnormalities (deficiencies) and qualitative abnormalities of platelets and coagulation factors lead to bleeding disorders, whereas deficiencies of the anticoagulant system are risk factors for thrombosis. Common disorders of hemostasis and thrombosis are reviewed.

In Vitro Thrombogenicity Testing of Artificial Organs

1998 ◽  
Vol 21 (9) ◽  
pp. 548-552 ◽  
Author(s):  
R. Paul ◽  
O. Marseille ◽  
E. Hintze ◽  
L. Huber ◽  
H. Schima ◽  
...  
Keyword(s):  
Heart Valves ◽  
Early Stage ◽  
Thrombus Formation ◽  
Testing Procedure ◽  
Artificial Organs ◽  
Coagulation System ◽  
In Vitro Testing ◽  
Animal Testing ◽  
Thrombogenic Potential

Thromboembolic complications remain as one of the main problems for blood contacting artificial organs such as heart valves, bloodpumps and others. In vitro evaluation of thrombogenesis in prototypes has not previously been part of the standard evaluation of these devices. In comparison to hemolysis testing, evaluation of the thrombogenic potential is more difficult to perform because of the complexity of the blood coagulation system. We present an in vitro testing procedure that allows the accelerated examination of the thrombogenic potential of different types of blood pumps. Additionally, first results are presented that indicate the reliability of the accelerated clotting test for mechanical heart valves. Results for the centrifugal pump BioMedicus and two microaxial pumps have shown typical thrombus formation at locations such as bearings. The results indicate that the accelerated clotting test is an excellent addition to the much more expensive animal testing of artificial organs or assist devices. In vitro testing permits studies of thrombus formation to be performed at an early stage and at low costs and also facilitates a more precise investigation of device areas known to be potential hot spots for thrombus formation.

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