ROLE OF COAGULATION FACTORS IN CORONARY THROMBOSIS IN YOUNG INDIVIDUALS—A HOSPITAL BASED STUDY

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

Download Full-text

Exercise-Induced Fibrinolysis – Fact or Fiction?

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657256 ◽

1982 ◽

Vol 48 (02) ◽

pp. 201-203 ◽

Cited By ~ 26

Author(s):

N A Marsh ◽

P J Gaffney

Keyword(s):

Plasminogen Activator ◽

Degradation Products ◽

Coagulation Factors ◽

Vascular Wall ◽

Strenuous Exercise ◽

Fibrin Degradation Products ◽

Real Increase ◽

Exercise Induced ◽

Male Subjects

SummaryThe effect of strenuous exercise on the fibrinolytic and coagulation mechanisms was examined in six healthy male subjects. Five min bicycle exercise at a work-rate of 800 to 1200 kpm. min−1 produced an abrupt increase in plasma plasminogen activator levels which disappeared after 90 min. However, there was no change in early or late fibrin degradation products nor was there a change in fibrinopeptide A levels or βthromboglobulin levels after exercise although activated partial thromboplastin times were significantly shortened. It is concluded that strenuous exercise does not produce any real increase in fibrinogen-fibrin conversion nor any real increase in the breakdown of these proteins. The role of exercise-induced release of plasminogen activator remains unclear, but probably helps to maintain plasma levels in a discontinuous manner concurrently with the continuous low-level secretion from the vascular wall. The shortening of partial thromboplastin time may be due to the raised levels of plasminogen activator changing the activation state of other coagulation factors.

Download Full-text

The Diagnosis of Lupus Anticoagulants by the Activated Partial Thromboplastin Time - The Central Role of Phosphatidyl Serine

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661166 ◽

1984 ◽

Vol 52 (02) ◽

pp. 172-175 ◽

Cited By ~ 57

Author(s):

P R Kelsey ◽

K J Stevenson ◽

L Poller

Keyword(s):

Screening Method ◽

Coagulation Factors ◽

Phosphatidyl Serine ◽

Test System ◽

Specific Factor ◽

Marginal Effect ◽

Constant Composition ◽

Lupus Anticoagulants ◽

Different Types

SummaryLiposomes of pure phospholipids were used in a modified APTT test system and the role of phosphatidyl serine (PS) in determining the sensitivity of the test system to the presence of lupus anticoagulants was assessed. Six consecutive patients with lupus anticoagulants and seven haemophiliacs with anticoagulants directed at specific coagulation factors, were studied. Increasing the concentration of phospholipid in the test system markedly reduced the sensitivity to lupus anticoagulants but had marginal effect on the specific factor inhibitors. The same effect was achieved when the content of PS alone was increased in a vehicle liposome of constant composition.The results suggest that the lupus anticoagulants can best be detected by a screening method using an APTT test with a reagent of low PS content. The use of a reagent rich in PS will largely abolish the lupus anticoagulant’s effect on the APTT. An approach using the two different types of reagent may facilitate differentiation of lupus inhibitors from other types of anticoagulant.

Download Full-text

Pathophysiology of Thrombosis in Peripheral Artery Disease

Current Vascular Pharmacology ◽

10.2174/1570161117666190206234046 ◽

2020 ◽

Vol 18 (3) ◽

pp. 204-214 ◽

Cited By ~ 1

Author(s):

Aida Habib ◽

Giovanna Petrucci ◽

Bianca Rocca

Keyword(s):

Vascular Tone ◽

Platelet Reactivity ◽

Coagulation Factors ◽

Peripheral Artery ◽

Antithrombotic Agents ◽

Pharmacological Interventions ◽

Physiological Conditions ◽

Vasoactive Mediators ◽

Artery Disease

<P>Under physiological conditions, peripheral arteries release endogenous vascular-protective and antithrombotic agents. Endothelial cells actively synthesize vasoactive mediators, which regulate vascular tone and platelet reactivity thus preventing thrombosis. Atherosclerosis disrupts homeostasis and favours thrombosis by triggering pro-thrombotic responses in the vessels, platelet activation, aggregation as well as vasoconstriction, phenomena that ultimately lead to symptomatic lumen restriction or complete occlusion. <P> In the present review, we will discuss the homeostatic role of arterial vessels in releasing vascular-protective agents, such as nitric oxide and prostacyclin, the role of pro- and anti-thrombotic vascular receptors as well as the contribution of circulating platelets and coagulation factors in triggering the pro-thrombotic response(s). We will discuss the pathological consequences of disrupting the protective pathways in the arteries and the pharmacological interventions along these pathways.</P>

Download Full-text

Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients

Scientific Reports ◽

10.1038/s41598-021-89967-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alberto Polimeni ◽

Isabella Leo ◽

Carmen Spaccarotella ◽

Annalisa Mongiardo ◽

Sabato Sorrentino ◽

...

Keyword(s):

Platelet Count ◽

Meta Analysis ◽

Severe Disease ◽

Coagulation Factors ◽

Primary Analysis ◽

Severe Group ◽

Intravascular Coagulopathy ◽

The Difference ◽

D Dimer

AbstractCoronavirus disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019 and spread rapidly around the world. Several patients with severe COVID-19 infection can develop a coagulopathy according to the ISTH criteria for disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation, resulting in widespread microvascular thrombosis and consumption of coagulation factors. We conducted a meta-analysis in order to explore differences in coagulopathy indices in patients with severe and non-severe COVID-19. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases between December 2019 (first confirmed Covid-19 case) up to April 6th, 2020. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease and Survivors vs Non-Survivors. Furthermore, results on additional coagulation parameters (platelet count, prothrombin time, activated partial thromboplastin time) were also analyzed. The primary analysis showed that mean d-dimer was significantly lower in COVID-19 patients with non-severe disease than in those with severe (SMD − 2.15 [− 2.73 to − 1.56], I2 98%, P < 0.0001). Similarly, we found a lower mean d-dimer in Survivors compared to Non-Survivors (SMD − 2.91 [− 3.87 to − 1.96], I2 98%, P < 0.0001). Additional analysis of platelet count showed higher levels of mean PLT in Non-Severe patients than those observed in the Severe group (SMD 0.77 [0.32 to 1.22], I2 96%, P < 0.001). Of note, a similar result was observed even when Survivors were compared to Non-Survivors (SMD 1.84 [1.16 to 2.53], I2 97%, P < 0.0001). Interestingly, shorter mean PT was found in both Non-Severe (SMD − 1.34 [− 2.06 to − 0.62], I2 98%, P < 0.0002) and Survivors groups (SMD − 1.61 [− 2.69 to − 0.54], I2 98%, P < 0.003) compared to Severe and Non-Survivor patients. In conclusion, the results of the present meta-analysis demonstrate that Severe COVID-19 infection is associated with higher D-dimer values, lower platelet count and prolonged PT. This data suggests a possible role of disseminated intravascular coagulation in the pathogenesis of COVID-19 disease complications.

Download Full-text

The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria

Cells ◽

10.3390/cells10071759 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1759

Author(s):

Yuhki Yanase ◽

Shunsuke Takahagi ◽

Koichiro Ozawa ◽

Michihiro Hide

Keyword(s):

Mast Cells ◽

Cell Activation ◽

Coagulation Factors ◽

Chronic Spontaneous Urticaria ◽

Mast Cell Activation ◽

Coagulation Cascade ◽

Edema Formation ◽

Complement Components ◽

Complement Factors

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by an almost daily recurrence of wheal and flare with itch for more than 6 weeks, in association with the release of stored inflammatory mediators, such as histamine, from skin mast cells and/or peripheral basophils. The involvement of the extrinsic coagulation cascade triggered by tissue factor (TF) and complement factors, such as C3a and C5a, has been implied in the pathogenesis of CSU. However, it has been unclear how the TF-triggered coagulation pathway and complement factors induce the activation of skin mast cells and peripheral basophils in patients with CSU. In this review, we focus on the role of vascular endothelial cells, leukocytes, extrinsic coagulation factors and complement components on TF-induced activation of skin mast cells and peripheral basophils followed by the edema formation clinically recognized as urticaria. These findings suggest that medications targeting activated coagulation factors and/or complement components may represent new and effective treatments for patients with severe and refractory CSU.

Download Full-text

Historical Perspectives on Thrombolytic Therapy

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615940 ◽

1999 ◽

Vol 82 (08) ◽

pp. 971-973

Author(s):

Jürgen van de Loo

Keyword(s):

Thrombolytic Therapy ◽

Acute Coronary Syndromes ◽

Coronary Thrombosis ◽

Basic Research ◽

Medical Field ◽

Pathogenic Role ◽

Missed Opportunities ◽

Historical Perspectives ◽

Coronary Syndromes

IntroductionRetrospectives may result in regret over missed opportunities, in grudging acknowledgment of the success of a scientific rival, anger or bemusement about one’s own mistakes, or just plain pride in achievement. Quite apart from these personal implications, it is fascinating to note how a particular medical field has developed, to identify which forces pushed it ahead or slowed it down, to recognize how political and economic influences affected the outcome, and to reflect on the roles that the personalities of responsible scientists played in the process.I would like to comment on the development of basic research on the fibrinolytic system as a prelude to its clinical application, the role of the pharmaceutical industry in producing acceptable drugs, the debate about the pathogenic role of coronary thrombosis in acute coronary syndromes, and finally, on the acceptance and nonacceptance among cardiologists during the infancy and adolescence of the discipline.

Download Full-text