Arterial thrombosis for the interventional cardiologist: From adhesion molecules and coagulation factors to clinical therapeutics

2003 ◽  
Vol 60 (2) ◽  
pp. 236-246 ◽  
Author(s):  
Ian D. Conde ◽  
Neal S. Kleiman
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer

Blood clotting within the venous circulatory system, in contrast to arterial thrombosis, occurs at a relatively slow pace in response to stagnation of flow (stasis) and activation of coagulation. As with arterial thrombosis, vascular injury, either direct in the setting of trauma or indirect as a diffuse, systemic inflammatory response (that ultimately causes endothelial cell damage), represents an important stimulus. Venous thrombi are intravascular deposits composed predominantly of erythrocytes and fibrin, with a variable contribution of platelets and leukocytes. In a majority of cases, thrombosis begins in areas of slow flow within the venous sinuses of valve cusp pockets either in the deep veins of the calf or upper thigh or at sites of direct injury following trauma (Kakkar et al., 1969; Nicolaides et al., 1971). Stasis predisposes to thrombosis most profoundly in the setting of inflammatory states and activated coagulation factors. Slowed blood flow impairs the clearance of coagulation proteases, which through bioamplification increases the local concentration of thrombin substrate. If local thromboresistance is impaired, as may be the case with inherited or acquired thrombophilias (see Chapter 24), thrombosis occurs. Blood flow velocity is reduced by indwelling catheters, which also causes focal endothelial injury, peripheral edema, pregnancy, and valve cusp damage from prior venous thrombosis and/or chronic venous insufficiency (Trottier et al., 1995). Although venous thrombosis can occur in a variety of sites, the most common encountered in clinical practice is within the deep veins of the lower extremity. Thrombi developing within the veins of the calf or thigh can serve as a nidus for growth (propagation), which may cause complete venous obstruction, or embolize to the lungs (pulmonary embolism).


Author(s):  
Hubert Scharnagl ◽  
Winfried März ◽  
Markus Böhm ◽  
Thomas A. Luger ◽  
Federico Fracassi ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1639-1639
Author(s):  
Debra Hoppensteadt ◽  
Josephine Cunanan ◽  
Anita Sylvester Anderson ◽  
Thomas Bergholt ◽  
Jorgen Berthelsen ◽  
...  

Abstract OBJECTIVE In addition to increased levels of coagulation factors and platelet counts,, microparticles are also found in increased numbers in pregnancy and are generated due to cellular activation and consumption. Microparticles may also be capable of amplifying the procoagulant and inflammatory responses by up regulating the adhesion molecules such as P, E and L selectins. This study will provide newer data on the regulation of microparticles in different trimesters of pregnancy and their relevance to the generation of adhesion molecules and tissue factor (TF). STUDY DESIGN Blood samples from pregnant women at their first prenatal visit and during the second and third trimester (n=50) were collected and citrated plasma samples were profiled for TF (American Diagnostica, Stamford, CT), E, L and P-selection (R &D Systems, Minneapolis, MN) by using commercially available sandwich ELISA methods and microparticles utilizing a functional method from Hyphen Biomed (Neuville-Sur-Oise, France). The results were compiled for each trimester and compared to aged match non-pregnant controls (n=40). RESULTS During the first trimester all of the mediators were increased in comparison to the controls. The relative increase was mediator dependent. L-selectin remained elevated, at a steady level, throughout the pregnancy. E-selectin showed a decrease in the second trimester with a rebound increase in the third trimester. A gradual increase in the TF and microparticles was evident throughout the pregnancy. The P-selectin levels decreased during the second trimester and stayed at this level for the remainder of the pregnancy. CONCLUSION Throughout pregnancy the TF levels directly correlated with an increase in the MP levels indicating that TF cause cellular activation leading to the formation of MPs. However, the levels of the adhesion molecules, which were initially elevated, fluctuate throughout the 2nd and 3rd trimester. These results suggest that increased levels of TF and MPs are progressively generated during pregnancy and may be responsible for the observed thrombotic complications and prothrombotic state in pregnancy.


1991 ◽  
Vol 65 (04) ◽  
pp. 339-343 ◽  
Author(s):  
G D O Lowe ◽  
D A Wood ◽  
J T Douglas ◽  
R A Riemersma ◽  
C C A Macintyre ◽  
...  

SummaryPlasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and Bβ15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide Bβ15-42). Increased viscosity and fibrinogen in smokers were partly reversed in exsmokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.


Medicina ◽  
2010 ◽  
Vol 46 (9) ◽  
pp. 642 ◽  
Author(s):  
Aušra Mongirdienė ◽  
Lolita Kuršvietienė ◽  
Artūras Kašauskas

Though heart failure can mainly be caused by systolic or diastolic dysfunction, the impairments of the neurohormonal, immune, and hemostatic systems are observed too. Therefore, it is not easy to determine etiology of the syndrome. Parameters that can be helpful to predict chronic heart failure, to evaluate its course and the risk of complications are still being searched. The aim of this article is to review the recent studies in order to find the links between the coagulation system and the development of chronic heart failure. Stress is a key factor for the development of most diseases including chronic heart failure too. Signals of emotional and physical stress via particular structures trigger an increase in concentrations of the following hormones: noradrenaline, renin, angiotensin II, aldosterone, vasopressin. It is proved that it causes the disorders of the coagulation system: an increase in the following factors of plasma coagulation (fibrinogen, VII, VIII, fibrinopeptide A, thrombinantithrombin complex), fibrinolysis (D-dimer), endothelium (interleukin 1, endothelin 1, vascular cell adhesion molecules, endothelial growth factor), platelet activity (von Willebrand factor, intercellular adhesion molecules, platelet factor 4, P-selectin, thromboxane A2, thromboglobulin, CD63P) and cytokines (tumor necrosis factor, interleukin 6) and decrease in E-selectin. The role of particular coagulation factors for the development of chronic heart failure has not been understood yet. Thus, it is necessary to carry out further studies.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3852-3852
Author(s):  
Deepa Jayakody Arachchillage ◽  
Simona Deplano ◽  
Eleanor Dunnett ◽  
Steve Owen ◽  
Louise Tillyer ◽  
...  

Abstract Introduction Administration of coagulation factors after major cardiac surgery, with or without cardiopulmonary bypass, may be a strategy for reducing risk of bleeding and requirement for allogeneic blood transfusions. However, transfusion of large volumes of fresh frozen plasma (FFP) is restricted by the competing problem of heart failure, a common complication following cardiac surgery in patients with existing cardiac decompensation. Prothrombin complex concentrate (PCC) has a smaller volume of administration than FFP for a similar amount of coagulation factors, making it an attractive option in this situation. However, patients undergoing complex cardiac surgery may also have prothrombotic conditions and have a high risk of both venous and arterial thrombosis including ischemic neurological complications. We performed a retrospective analysis to investigate whether the use of PCC is safe and effective compared with FFP to treat coagulopathy in patients undergoing isolated coronary artery bypass graft (CABG), valve surgery (with or without concomitant CABG) and major aortic procedures. If the patient was on warfarin, this was stopped at least 5 days before the surgery and appropriate bridging was followed. For patients on dual antiplatelet therapy, P2Y12 receptor inhibitors such as Clopidogrel and Prasugrel were stopped 5-7days before the surgery and Aspirin was allowed to continue. The decision to use PPC or FFP was based on individual patient characteristics such as complexity of the surgery and previous history of increased bleeding during surgery and also ability to tolerate volume. Methods One hundred and seventy consecutive adult patients who underwent major cardiac surgery between January 2015 and December 2015 were studied. Among them, 87 received PCC (male/female = 55/32, mean age= 56 years) and 83 received FFP (male/female = 56/27, mean age = 58 years) to control coagulopathy. The decision on need for coagulation factor treatment and the choice of treatment was made by the treating team of the patient. Those who received both PCC and FFP were excluded. Blood loss within first 12 hours and 24hours from the end of operation, total use of allogeneic blood and platelet transfusion and patient outcomes in terms of thrombotic complications both venous and arterial, incidence of acute kidney injury and 30 day mortality were compared in the two groups. Antiplatelet drug effect on bleeding was also assessed. Results There was no significant difference in the amount of bleeding at the first 12 hours from the end of the operation in the two groups (p=0.25) :median and 95% confidence interval [CI] were 825mL [926-1317] and 787mL [804-1067] patients received PPC or FFP respectively. However, total blood loss within 24hours was significantly higher in patients who received PPC (median [CI] (1575mL [1658-2263]) compared to FFP (median [CI] (1213mL [1244-1641]), P=0.0034. There was no difference in the mean blood loss between patients continued Aspirin at the time of surgery and those who were not on Aspirin in either groups. The use of allogeneic blood (P=.001) and platelets (P=0.03) was significantly higher in patients receiving FFP compared to PPC. A significantly higher number of patients treated with FFP (9.6% vs 3.5%, p=0.002) developed cardiac failure related to circulatory overload. There was no difference in thrombotic events in the two groups: one patient from each group (1.1%) developed venous and arterial thrombosis respectively following surgery. Thirty day mortality rate was similar in the patients receiving FFP or PPC (4%) and none were directly related to surgery. There was no difference in the acute kidney injury in the two groups. Conclusions This retrospective analysis suggests that PCC may be an alternative to FFP in patients undergoing major cardiac surgery. Although there was a higher amount of bleeding within 24hours of surgery in patients treated with PCC, this may reflect the complexity, duration and the individual patient risk of bleeding due to selection bias. The use of PPC may reduce the number of allogeneic blood and platelet transfusion in these patients and reduce risk of circulatory overload. There was no increased risk of thrombosis with use of PCC. However, randomized controlled studies powered to evaluate efficacy and safety in patients receiving PCC versus FFP for coagulopathic bleeding after major cardiac surgery are warranted. Disclosures Laffan: CSL: Other: Travel support; Octapharma: Speakers Bureau.


Author(s):  
D. C. Brindley ◽  
M. McGill

Morphological and cytochemical studies of platelets have reported a surface coat, or glycocalyx, external to the plasma membrane (1). Biochemical analyses have likewise confirmed the highly adsorptive properties of platelets as transporters of coagulation factors (2). However, visualization of the platelet membrane by conventional EM procedures does not reflect this special relationship between the platelet and its plasma environment. By the routine method of alcohol-propylene oxide dehydration for Epon embedding, the lipid bilayer nature of the platelet membrane appears similar to other blood cells (Fig. 1). A new rapid embedding technique using dimethoxypropane (DMP) as dehydrating agent (13) has permitted ultrastructural analyses of the surface features of the platelet-plasma interface.Aliquots of human or rabbit platelet-rich plasma (PRP) were added to equal volumes of 6% glutaraldehyde in Millonig's buffer at 37° for 45 minutes, rinsed in buffer and postfixed in 1% osmium in Millonig's buffer for 45 minutes.


Author(s):  
S.L. Erlandsen

Cells interact with their extracellular environments by means of a variety of cellular adhesion molecules (CAM) and surface ligands. In many instances, CAMs interact in a sequential temporal fashion which suggests that these adhesion molecules may occupy or be polarized to various membrane microdomains on the cell surface. Detection of CAMs can be accomplished by a variety of methods including immunofluorescent microscopy and flow cytometry, and by the use of immunocytochemical markers (i.e. colloidal gold) in electron microscopy. The development of high resolution field emission SEM in the mid 1980's and the Autrata modification of the YAG detector for backscatter electron detection at low voltage has greatly facilitated the recognition of colloidal gold probes for detection of surface CAMs. Low voltage FESEM with Bse imaging provides increased resolution of cell surface topography (~3nm at 3-4 keV) which can be observed in 3-dimensions, and simultaneously permits detection/high spatial resolution of immunogold label by atomic number contrast.


1997 ◽  
Vol 23 (3) ◽  
pp. 83-92 ◽  
Author(s):  
D. Seilhean ◽  
A. Dzia-Lepfoundzou ◽  
V. Sazdovitch ◽  
B. Cannella ◽  
C. S. Raine ◽  
...  

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