Blood Fluidity Research Articles

Kruppel-Like Factor 2 (KLF2) Regulates Endothelial Thrombotic Function

The vascular endothelium maintains blood fluidity by inhibiting blood coagulation, inhibiting platelet aggregation, and promoting fibrinolysis. Endothelial cells lose these nonthrombogenic properties on exposure to proinflammatory stimuli. We recently identified the Kruppel-like factor KLF2 as a novel regulator of endothelial proinflammatory activation. Here it is found that KLF2 differentially regulates key factors involved in maintaining an antithrombotic endothelial surface. Overexpression of KLF2 strongly induced thrombomodulin (TM) and endothelial nitric oxide synthase (eNOS) expression and reduced plasminogen activator inhibitor-1 (PAI-1) expression. Furthermore, overexpression of KLF2 inhibited the cytokine-mediated induction of tissue factor (TF). In contrast, siRNA mediated knockdown of KLF2 reduced antithrombotic gene expression while inducing the expression of pro-coagulant factors. The functional importance of KLF2 was verified by in vitro clotting assays. By comparison to control infected cells, KLF2 overexpression increased blood clotting time as well as flow rates under basal and inflammatory conditions. In contrast, siRNA-mediated knockdown of KLF2 reduced blood clotting time and flow rates. These observations identify KLF2 as a novel transcriptional regulator of endothelial thrombotic function. The full text of this article is available online at http://circres.ahajournals.org.

Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction

The objective of this study was to evaluate the long-term predictive value of the haemostatic, inflammatory and haemorheologic disturbances in transmural myocardial infarction (MI). Sixty-four (59 male) consecutive survivors of a MI, with a mean age of 58.3 +/- 12.0 years, were followed over a period of 36 months. Eighteen patients had a cardiovascular event defined as the composite of death, non-fatal MI, unstable angina and stroke. The haemostatic (protein C activity-PtC, antithrombin III, plasminogen activator inhibitor-1), haemorheologic (blood fluidity and components, erythrocyte membrane fluidity) and inflammatory (polymorphonuclear elastase, leukocyte count) profiles were determined at hospital discharge, using standard methodology. Our results can be summarized as follow: (i) at hospital discharge, the subgroup of patients with events had higher leukoactivity, leukocyte count, membrane fluidity, prognosis cyte count (7833.0 +/- 1696.0 vs. 10294.0 +/- 3129.0; p = 0.011), lower PtC (100.65 +/- 19.08 vs.81.25 +/- 19.95; p = 0.002), and lower erythrocyte aggregation (14.26 +/- 5.94 vs. 11.47 +/- 3.45; p = 0.031) in relation to the ones without events; (ii) By Cox regression the protein C activity lower tertile (OR 0.169; 0.045-0.628; p = 0.008); erythrocyte membrane outer layer fluidity upper tertile (OR 0.067; 95% CI 0.011 - 0.393; p = 0.003); and erythrocyte aggregation lower tertile (OR 0.182; 0.038 - 0.876; p = 0.034) were independent predictors of the composite endpoint. We can conclude that some haemostatic, haemorheologic and inflammatory disturbances, at hospital discharge, are long-term independent predictors of recurrent cardiovascular events in transmural myocardial infarction survivors.

Haemorheology in Exercise and Training

Disruption of the normal rheological properties of blood is considered an independent risk factor for cardiovascular disease and plays a significant role in the aetiology of atherothrombogenesis. The acute increase in whole blood viscosity may unfavourably affect the microcirculatory blood flow and oxygen delivery to the tissues. It is universally accepted that exercise and physical activity performed on a regular basis has health benefits. However, the effects of exercise on the rheological properties of blood have not received much research attention. Recent, limited evidence indicates that the viscosities of whole blood and plasma increase in response to a variety of exercise protocols. The increase in whole blood viscosity is mainly attributed to an increase in haematocrit and plasma viscosity, whereas the deformability and aggregability of red blood cells remain unaltered. The increases in plasma viscosity and haematocrit have been ascribed to exercise-induced haemoconcentration as a result of fluid transfer from the blood to the interstitial spaces. The haemorheological changes associated with strenuous exercise appear to be linked with enhanced oxidative stress and depletion of antioxidant capacity, and that may affect oxygen delivery and availability to the tissues. Although significant advances have been made in many areas of exercise haematology, the long-term effects of endurance training on blood rheology have been very briefly examined and the exact effect of training has not as yet been determined. Available cross-sectional and longitudinal studies indicate that the blood of endurance athletes is more dilute and this has been attributed to an expansion of blood volume, particularly plasma volume as a result of training. The low haematocrit values in trained athletes represent a hydration condition rather than iron stores deficiency. It has been suggested that this hypervolaemia and blood dilutional effect of endurance training may be advantageous for heat dissipation and greater cardiac stroke volume and lower heart rates during exercise. Enhanced blood fluidity also facilitates oxygen delivery to the exercising muscles because of a reduced resistance to blood flow within the microcirculation. Furthermore, the increase in plasma volume may contribute to the body water pool and help offset dehydration. The influence of strength and power training on blood rheology is not known. The physiological mechanisms responsible for and the functional consequences of the haemorheological changes associated with exercise to a large extent remain speculative. The paradox of haematocrit and blood rheology in exercise and training warrants additional studies. Likewise, further investigations are necessary to determine the possible link between overtraining and blood rheological profiles.

S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors

The defining characteristic of a tumor cell is its ability to escape the constraints imposed by neighboring cells, invade the surrounding tissue and metastasize to distant sites. This invasive property of tumor cells is dependent on activation of proteinases at the cell surface. The serine proteinase plasmin is one of the key proteinases that participate in the pericellular proteolysis associated with the invasive program of tumor cells. The assembly of plasminogen and tissue plasminogen activator at the endothelial cell surface or on the fibrin clot provides a focal point for plasmin generation and therefore plays an important role in maintaining blood fluidity and promoting fibrinolysis. S100A10, a member of the S100 family of Ca2+-binding proteins, is a dimeric protein composed of two 11 kDa subunits. Typically, S100A10 is found in most cells bound to its annexin A2 ligand as the heterotetrameric (S100A10)2(annexin A2)2 complex, AIIt. In addition to an intracellular distribution, S100A10 is present on the extracellular surface of many cells. The carboxyl-terminal lysines of S100A10 bind tPA and plasminogen resulting in the stimulation of tPA-dependent plasmin production. Carboxypeptidases cleave the carboxyl-terminal lysines of S100A10, resulting in a loss of binding and activity. Plasmin binds to S100A10 at a distinct site and the formation of the S100A10-plasmin complex stimulates plasmin autoproteolysis thereby providing a highly localized transient pulse of plasmin activity at the cell surface. The binding of tPA and plasmin to S100A10 also protects against inhibition by physiological inhibitors, PAI-1 and alpha2-antiplasmin, respectively. S100A10 also colocalizes plasminogen with the uPA-uPAR complex thereby localizing and stimulating uPA-dependent plasmin formation to the surface of cancer cells. The loss of S100A10 from the extracellular surface of cancer cells results in a significant loss in plasmin generation. In addition, S100A10 knock-down cells demonstrate a dramatic loss in extracellular matrix degradation and invasiveness as well as reduced metastasis. Annexin A2 plays an important role in plasminogen regulation by controlling the levels of extracellular S100A10 and by acting as a plasmin reductase. The mechanism by which annexin A2 regulates the extracellular levels of S100A10 is unknown. This review highlights the important part that S100A10 plays in plasmin regulation and the role this protein plays in cancer cell invasiveness and metastasis.

Antihypertensive Potential and Mechanism of Action of Astaxanthin: II. Vascular Reactivity and Hemorheology in Spontaneously Hypertensive Rats

The current study was designed to determine the effects of a dietary astaxanthin (ASX-O) on vascular reactivity in spontaneously hypertensive rats (SHR), in order to verify its antihypertensive action mechanism. We evaluated contractions induced by phenylephrine (Phe), angiotensin II (Ang II) and the xanthine/xanthine oxidase (Xan/XOD) system, and relaxations induced by sodium nitroprusside (SNP) as well as endothelium-dependent relaxations mediated by acetylcholine (ACh) in thoracic aorta of the SHR, with and without ASX-O intervention. We also investigated the effects of ASX-O on blood rheology using a microchannel array system. In this study, ASX-O showed a significant modulatory effect on nitric oxide (NO)-induced vasorelaxation by the NO-donor SNP (p<0.05). However, it did not show significant effects in restoring the impaired endothelium-dependent relaxation to ACh in the SHR. On the other hand, the constrictive effects by Phe, Ang II and Xan/XOD were ameliorated by ASX-O (p<0.05). ASX-O also demonstrated significant hemorheological effect by decreasing the microchannel transit time of whole blood. In conclusion, the results suggest that ASX-O may act in modulating the blood fluidity in hypertension, and that the antihypertensive effects of ASX-O may be exerted through mechanisms including normalization of the sensitivity of the adrenoceptor sympathetic pathway, particularly [alpha]-adrenoceptors, and by restoration of the vascular tone through attenuation of the Ang II- and reactive oxygen species (ROS)-induced vasoconstriction.

The effects of herbal medicine on the reduced blood fluidity by collagen-induced arthritis (CIA) in mice

The effects of herbal medicine on the reduced blood fluidity by collagen-induced arthritis (CIA) in mice

Blood Rheology, Sex Hormones, and Cortisol in Athletes

The interrelations of blood rheology, plasma proteins and lipids, and steroid hormones (total testosterone, estradiol, and cortisol) were studied in athletes (N = 14). Blood (BV), plasma (PV), and erythrocyte suspension (ESV) viscosities; fibrinogen; total cholesterol (Ch); low density lipoprotein (LDL) Ch; and plasminogen activity were lower in the athletes than in control subjects (N = 10). The specific peripheral vascular resistance (SPVR) to BV ratio and PWC170 were lower in the athletes. All these parameters correlated with decreased estradiol. Discriminant analysis indicated PWC170, estradiol, and ESV to be the main parameters discriminating the groups. Decreased estradiol seemed to be associated with an increased physical activity in the athletes, as evident from its correlation with PWC170 and differences in the body composition (a correlation with the body mass index). No significant difference was found in total Ch and cortisol. However, in the combined sample, decreased testosterone was associated with decreased BV, which was explained by direct correlations of the hormone with hematocrit (Ht) and PV through relationships with Ch and triglycerides (TG). Increased cortisol correlated with the higher plasma fluidity in the athletes as a result of inverse correlations of the hormone with TG and the increased suspension stability of the blood. Training-induced changes in hormonal and metabolic parameters were assumed to play an important role in the regulation of blood fluidity in athletes.

Co-localization of P2Y1 receptor and NTPDase1/CD39 within caveolae in human placenta.

Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) is the dominant ecto-nucleotidase of vascular and placental trophoblastic tissues and appears to modulate the functional expression of type-2 purinergic (P2) G-protein coupled receptors (GPCRs). Hence, this ectoenzyme could regulate nucleotide-mediated signalling events in placental tissue. This immunohistochemical and immuno-electron microscopic study demonstrates the expression of NTPDase1/CD39, P2Y1 and P2Y2 receptors in different cell types of human placenta. Specifically P2Y1 has an exclusive vascular distribution whereas P2Y2 is localized on trophoblastic villi. Co-localization of P2Y1 and NTPDase1/CD39 are observed in caveolae, membrane microdomains of endothelial cells. The differential localization of these P2 receptors might indicate their unique roles in the regulation of extracellular nucleotide concentrations in human placental tissues and consequent effects on vascular tone and blood fluidity.

Critical role of the vascular endothelial cell in health and disease: a review article

AbstractObjective: To review the human and veterinary literature on the role of the vascular endothelial cell in health, as well as during hypoxic and inflammatory disease states.Data sources: Data from human and veterinary literature were reviewed through a Pubmed search and a manual search of the references listed in articles covering some aspect of vascular endothelial cell function.Human data synthesis: The development of techniques that allow the maintenance and growth of endothelial cells in culture has produced an explosion of new research in the area of endothelial cell physiology. This plethora of data has revealed the critical role that vascular endothelial cells play in both health and disease states. Interspecies variations can occur with respect to the vascular endothelial cell physiology and its response to pathologic conditions.Veterinary data synthesis: There is a paucity of information regarding the role of the vascular endothelial cell in health or disease of small animals. Many human studies use species cared for by veterinarians, providing information that may be applied to small animals and that may be used to construct future studies.Conclusion: An organ system itself, the vascular endothelium is an essential component of all organs in the body. The endothelial cell lining functions to maintain selective permeability between the blood and the tissue it supplies, regulate vascular tone, sustain blood fluidity through regulation of coagulation, and modulate interaction of leukocytes with the interstitium and inflammatory reactions. During disease states, the endothelial cell functions locally to limit the boundaries of the disease process. If these functions are not controlled, they can become a part of the pathogenic process, contributing to blood stasis and thrombosis, potentiation of local inflammation and interstitial edema formation, subsequent tissue hypoxia, and multiple organ dysfunction. Pharmacological investigations targeting the modulation of endothelial function during disease states have not yet advanced treatment protocols. Since all critically ill animals are at risk for some degree of endothelial cell dysfunction, treatment regimens should focus on promoting capillary blood flow and tissue oxygen delivery.

Effect of the over intake of foods on the fluidity of whole blood through Capillaries

Effect of the over intake of foods on the fluidity of whole blood through Capillaries

Endothelium as an organ system.

The endothelium is a highly dynamic cell layer that is involved in a multitude of physiologic functions, including the control of vasomotor tone, the trafficking of cells and nutrients, the maintenance of blood fluidity, and the growth of new blood vessels. Over the past several decades, advances in basic research of the endothelium have far outstripped those in the clinic. One explanation for this growing bench-to-bedside chasm relates to the inflexible and largely outdated nature of the present-day medical infrastructure. The constraints of medical subspecialization have created a conceptual blind spot, namely, the inability to appreciate the endothelium for what it is: a cell layer that is teeming with life, every bit as active as any other organ in the body. The overall goal of this review is to bring the endothelium "to life" and to argue that future breakthroughs in biomedicine are contingent on acceptance of the endothelium as a bona fide organ system.

T lymphocyte-endothelial cell interactions.

Human vascular endothelial cells (EC) basally display class I and II MHC-peptide complexes on their surface and come in regular contact with circulating T cells. We propose that EC present microbial antigens to memory T cells as a mechanism of immune surveillance. Activated T cells, in turn, provide both soluble and contact-dependent signals to modulate normal EC functions, including formation and remodeling of blood vessels, regulation of blood flow, regulation of blood fluidity, maintenance of permselectivity, recruitment of inflammatory leukocytes, and antigen presentation leading to activation of T cells. T cell interactions with vascular EC are thus bidirectional and link the immune and circulatory systems.

Endothelial function, inflammation, and prognosis in cardiovascular disease

The vascular endothelium is an active, dynamic tissue that controls many important functions, including regulation of vascular tone and maintenance of blood circulation, fluidity, coagulation, and inflammatory responses. Cardiovascular risk factors affect many of the normal functions of the endothelium. In particular, oxidized low-density lipoprotein cholesterol initiates a series of events that begin with cell activation, endothelial dysfunction, local inflammation, and a procoagulant vascular surface. These conspire to result in plaque formation and ultimately plaque rupture and cardiovascular events. Endothelial dysfunction may be evaluated by means of invasive techniques, such as coronary artery reactivity to acetylcholine, or noninvasive techniques, such as brachial artery ultrasonography. Loss of endothelium-dependent vasodilation is a characteristic feature throughout the development of atherosclerosis, and it is independently related to future adverse cardiovascular risk. Therefore, measurement of endothelial function can possibly be used to determine risk, to triage management, and to improve outcomes. At the same time, inflammation is a crucial factor in the atherosclerotic disease process. To identify and monitor the ongoing inflammatory process, markers of inflammation such as C-reactive protein (CRP) have been studied. Scientific evidence shows that elevated plasma CRP values add to the predictive ability of other established risk factors; moreover, elevated values appear to augment the Framingham Coronary Risk Score in identifying individuals who should be considered for cardioprotective treatment programs. Interestingly, thiazolidinediones (TZDs), peroxisome proliferator-activated receptor–γ agonists that are effective in the treatment of type 2 diabetes mellitus, not only increase insulin sensitivity but can benefit endothelial function because they exhibit anti-inflammatory effects. For many individuals, including those with the metabolic syndrome and/or type 2 diabetes, endothelial dysfunction and elevated plasma CRP levels indicate increased risk of cardiovascular disease. Notably, the TZDs have been shown to reduce CRP levels and may improve endothelial function.

Haemostasis in inflammatory bowel diseases: clinical relevance.

In inflammatory bowel disease (IBD), many alterations of haemostasis have been reported. Furthermore. IBD is associated with thromboembolic disease. Literature on new insights into the physiology of haemostasis. the interaction between haemostasis and inflammation, plasmatic and mucosal changes in haemostasis in IBD, and haemostasis-interfering therapy in patients with IBD are reviewed. Haemostasis is a vascular-bed-specific, locally regulated, physiological phenomenon aimed at the maintenance of fluidity of blood, and not a simple cascade-shaped chain of reactions. Coagulation activation is part of the inflammatory response, but coagulation activation induces pro-inflammatory effects at the same time. Coagulation and fibrinolysis are activated in the course of IBD. but sometimes in a misbalanced way. Overall, this may induce a state of plasmatic hypercoagulation, irrespective of disease activity. Thromboembolic disease is a common extra-intestinal manifestation of IBD. Established treatment of thromboembolism is similarly useful in IBD patients: concurrent aggressive treatment of exacerbations is recommended. Intractable gastrointestinal bleeding seldom occurs, and has mainly been reported in patients with untreated active IBD. Thrombophilic genetic background does not seem to be responsible for either the increased risk of thromboembolism, or the prevalence of IBD. Haemostasis-interfering therapy to alter the course of IBD is experimental. Thromboembolism is an extraintestinal manifestation of IBD, partly because of the associated state of plasmatic hypercoagulation. Thrombophilic genetic background does not contribute to prevalence or course of IBD: genetic investigations may be restricted to patients with clinically proven thrombophilia. Anticoagulant therapy can normally be given to patients. but not as an established therapy against IBD.

Lysophosphatidylcholine Acts as an Anti-hemostatic Molecule in the Saliva of the Blood-sucking Bug Rhodnius prolixus

Blood-sucking arthropods possess a variety of anti-hemostatic factors in their salivary glands to maintain blood fluidity during feeding. In this work we demonstrate the anti-hemostatic properties of lysophosphatidylcholine (lysoPC) isolated from the salivary glands of Rhodnius prolixus. First, we examined salivary glands of fourth and fifth instar nymphs for their phospholipid composition. The lumen displayed an accumulation of its phospholipid content, mainly phosphatidylcholine and lysoPC, with a 6-fold increase for the latter. To determine the presence of phospholipids in the saliva, fourth instar nymphs were fed with a32P-enriched blood meal. After 28 days their saliva was collected and subjected to lipid extraction, thin-layer chromatography, and autoradiography. The results showed the presence in the saliva of the same phospholipids present in the lumen. We then examined possible biological roles of these phospholipids when compared with other known effects of lysoPC. The luminal lipid extract and purified lysoPC from the lumen and saliva were tested for inhibition of washed rabbit platelets' aggregation induced by alpha-thrombin and platelet-activating factor. Both the luminal lipid extract and salivary lysoPC showed an increasing inhibition of aggregation, which correlated with the response of the platelets to standard lysoPC (up to 13 microg/ml). Next, salivary lysoPC was incubated with porcine arterial endothelial cells for 24 h. After incubation, culture medium was assayed for nitric oxide and showed increased nitric oxide production, similar to control cells exposed to standard lysoPC (up to 20 microg/ml). Together these data demonstrate the presence of lysoPC in the saliva of Rhodnius prolixus and its potential anti-hemostatic activities.

Favorable Impact of a Vegan Diet with Exercise on Hemorheology: Implications for Control of Diabetic Neuropathy

A little‐noticed clinical report indicates that a low‐fat, whole‐food vegan diet, coupled with daily walking exercise, leads to rapid remission of neuropathic pain in the majority of type 2 diabetics expressing this complication. Concurrent marked improvements in glycemic control presumably contribute to this benefit, but are unlikely to be solely responsible. Consideration should be given to the possibility that improved blood rheology – decreased blood viscosity and increased blood filterability – plays a prominent role in mediating this effect. There is considerable evidence that neural hypoxia, secondary to impaired endoneurial microcirculatory perfusion, is a crucial etiologic factor in diabetic neuropathy; the unfavorable impact of diabetes on hemorheology would be expected to exacerbate endoneurial ischemia. Conversely, measures which improve blood fluidity would likely have a beneficial impact on diabetic neuropathy. There is indeed evidence that vegan diets, as well as exercise training, tend to decrease the viscosity of both whole blood and plasma; reductions in hematocrit and in fibrinogen may contribute to this effect. The fact that vegan diets decrease the white cell count is suggestive of an improvement in blood filterability as well; filterability improves with exercise training owing to an increase in erythrocyte deformability. Whether these measures influence the activation of leukocytes in diabetics – an important determinant of blood filterability – remains to be determined. There are various reasons for suspecting that a vegan diet can reduce risk for other major complications of diabetes – retinopathy, nephropathy, and macrovascular disease – independent of its tendency to improve glycemic control in type 2 patients. The vegan diet/exercise strategy represents a safe, ‘low‐tech’ approach to managing diabetes that deserves far greater attention from medical researchers and practitioners.

3P-0851 Characterization of the relationship between blood fluidity and coagulation activation using microchannel array flow system analysis

3P-0851 Characterization of the relationship between blood fluidity and coagulation activation using microchannel array flow system analysis

Evidence of prolonged disturbances in the haemostatic, hemorheologic and inflammatory profiles in transmural myocardial infarction survivors

SummaryHaemostatic, hemorheologic and inflammatory disturbances have been associated with acute coronary syndromes. Most knowledge is reported in cross sectional studies and are without time dependent evolution of these profiles.The aim of this study was to evaluate, during the first year, the evolution of the haemostatic, hemorheologic and inflammatory profiles determined at hospital discharge in survivors with transmural myocardial infarction (MI).Eighty eight (79 male; 9 female) mean age of 58 ± 11 years, survivors of a transmural MI were prospectively studied at discharge, 6 months and one year after the event. Haemostatic (protein C, antithrombin III and plasminogen activator inhibitor 1), hemorheologic (blood fluidity and components) and inflammatory profiles (polymorphonuclear elastase and leukocyte count) were determined using standard methodology.The results of the study can be summarized as follows: (1) Protein C decreased (p &lt; 0.05) over time while PAI-1 only varied significantly until 6th month. (2) Plasma viscosity and fibrinogen (p &lt; 0.001) decrease over time, while erythrocyte aggregation (p &lt; 0.001) and haematocrit increased. Whole blood viscosity did not vary. (3) Leukocyte decreased (p &lt; 0.001) and elastase did not (4). Those patients with cardiovascular events (n = 7) had higher PAI-1 concentration (p&lt;0.05) and leukocyte count (p &lt; 0.01), at discharge (5) Left ventricle ejection fraction correlated significantly with plasma viscosity (r = 0.35 p &lt; 0.05). The results of this longitudinal study show dynamic modifications of the haemostatic, hemorheologic and inflammatory profiles during the first year of a transmural myocardial infarction. In addition, there are interrelations between them and the clinical profile that could help to explain the clinical evolution of this group of patients.

グルコサミンの血小板機能に及ぼす影響

Glucosamine, an amino monosaccharide naturally occurring in the connective and cartilage tissues, contributes to maintaining the strength, flexibility and elasticity of these tissues. In recent years, glucosamine has been widely used to treat osteoarthritis in humans, because glucosamine increases proteoglycan synthesis and prevents cartilage degradation. Recently, we have revealed that glucosamine suppresses neutrophil functions, thereby possibly exhibiting anti-inflammatory actions in arthritis. Alternatively, we have found that glucosamine improves the fluidity of blood (hemorheology) analyzed by microchannel array. Therefore, in this study, we evaluated the effects of glucosamine on the functions of platelets, which play an essential role in thrombosis. Glucosamine suppressed platelet aggregation in response to ADP-stimulation, but not collagen-and thrombin-stimulation. Furthermore, glucosamine inhibited the extracellular release of granular constituents (ATP and platelet factor 4), and the production of thromboxane from ADP-stimulated platelets. In addition, glucosamine significantly inhibited the mobilization of intracellular calcium and the phosphorylation of Syk associated with platelet activation. Together these observations suggest that glucosamine suppresses platelet aggregation via the inhibition of calcium mobilization, Syk phosphorylation, granular content release and thromboxane production. Thus, glucosamine may have preventive effects on thrombosis by its suppressive actions on platelet functions.

Basic mechanisms of hemostasis.

Hemostasis governs two essential processes of human life in that it maintains the fluidity of blood under physiological conditions and prevents excessive blood loss after injury. Hemostasis is regulated by components of the vessel wall and blood cells and by humoral coagulation factors. Under normal conditions, these components are involved in an active equilibrium through activation, propagation, and termination of the hemostatic pathways. This equilibrium is disturbed upon vascular injury, leading to a procoagulant response when needed. Unfortunately, pathological disturbances can occur as a result of inherited or acquired coagulation factor deficiencies that may lead to bleeding or thrombotic disorders.