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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.
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PMID:Hemostatic alterations caused by ventricular assist devices for postcardiotomy heart failure. 199 93

The hemostatic response to acute exercise and increased atmospheric pressure was studied in 20 healthy male subjects (18-35 yr of age) exercised to volitional exhaustion on a cycle ergometer in a hyperbaric chamber at 3 atmospheres absolute (ATA). As a means of comparison, 6 of the 20 subjects were exercised in the same manner at 1 ATA. Similar increases in fibrinolytic activity (FA), Factor VIII activity (VIII:C), von Willebrand factor antigen (vWF:Ag) and plasma catecholamine levels were observed following acute exercise at 1 ATA and at 3 ATA. There were no changes in the levels of plasminogen, antithrombin III, Protein C or Fibrinopeptide A (FPA) with exercise either at 1 ATA or at 3 ATA. In addition, there were no changes in plasma catecholamine levels or any of the hemostatic variables measured when atmospheric pressure was increased from 1 ATA to 3ATA without exercise. These findings demonstrate that increasing atmospheric pressure from 1 ATA to 3 ATA does not alter the exercise-induced changes in hemostasis. Therefore, exercise or physical exertion at 3 ATA for a time period not to exceed 30 min does not perturb the hemostatic mechanism and increase the risk of bleeding or thrombosis.
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PMID:The effects of acute exercise and increased atmospheric pressure on the hemostatic mechanism and plasma catecholamine levels. 233 66

Thromboembolic phenomena may occur as humans ascend to high altitude. To investigate the role of the coagulation cascade and its inhibitors in these disorders, venous blood was obtained from eight subjects who participated in the Operation Everest II project. Samples were obtained before and 5 min after completion of a progressive incremental exercise test to exhaustion at sea level and atmospheric pressures of 380 (18,000 ft) and 282 Torr (25,000 ft). Plasma was analyzed for the activity or concentration of factors II, V, VII, VIII complex, IX-XIII, prekallikrein, high-molecular-weight kininogen, fibrinogen, antithrombin III, alpha 2-macroglobulin, alpha 2-antiplasmin, C1-esterase inhibitor, alpha 1-antitrypsin, and protein C. Prolonged exposure to simulated high altitude did not alter the concentration of any of the coagulation factors or inhibitors. Exercise increased the circulating concentrations of the factor VIII complex at sea level, 380, and 282 Torr. However, the increment was less at the simulated high altitudes. The increase in the factor VIII complex was inversely related to arterial O2 saturation and directly related to the work load achieved and blood pH and plasma lactate concentrations. These studies suggest that the gradual development of marked chronic hypoxia does not affect the coagulation cascade.
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PMID:Operation Everest II: coagulation system during prolonged decompression to 282 Torr. 311 52

This review article integrates empirical findings from various scientific disciplines into a proposed psychoneuroimmunological (PNI) model of the acute coronary syndrome (ACS). Our starting point is an existing, mild, atherosclerotic plaque and a dysfunctional endothelium. The ACS is triggered by three stages. (1) Plaque instability: Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and chemoattractants (MCP-1, IL-8) induce leukocyte chemoattraction to the endothelium, and together with other triggers such as the CD40L-CD40 co-stimulation system activate plaque monocytes (macrophages). The macrophages then produce matrix metalloproteinases that disintegrate extra-cellular plaque matrix, causing coronary plaque instability. Acute stress, hostility, depression and vital exhaustion (VE) have been associated with elevated pro-inflammatory cytokines and leukocyte levels and their recruitment. (2) Extra-plaque factors promoting rupture: Neuro-endocrinological factors (norepinephrine) and cytokines induce vasoconstriction and elevated blood pressure (BP), both provoking a vulnerable plaque to rupture. Hostility/anger and acute stress can lead to vasoconstriction and elevated BP via catecholamines. (3) Superimposed thrombosis at a ruptured site: Increases in coagulation factors and reductions in anticoagulation factors (e.g. protein C) induced by inflammatory factors enhance platelet aggregation, a key stage in thrombosis. Hostility, depression and VE have been positively correlated with platelet aggregation. Thrombosis can lead to severe coronary occlusion, clinically manifested as an ACS. Thus, PNI processes might, at least in part, contribute to the pathogenesis of the ACS. This chain of events may endure due to lack of neuroendocrine-to-immune negative feedback stemming from cortisol resistance. This model has implications for the use of psychological interventions in ACS patients.
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PMID:Molecular and cellular interface between behavior and acute coronary syndromes. 1223 62

Hyperthrombinogenesis due to bacterial septicemia may aggravate the risk of irreversible septic shock. In 22 patients with septicemia complicating urinary or alimentary infections, daily assessment of hemostasis was performed throughout 1 week. Standard screening of hemostasis revealed significantly increased mean values of prothrombin time, fibrinogen, and fibrinogen degradation product (FDP) concentration. However, platelet counts, activated partial thromboplastin times (APTT), thrombin times, ethanol gelation tests, and antithrombin activity remained within the normal range. By contrast, except for insignificant changes in protein C activity and activated factor VII content, specific markers of plasma hypercoagulability, that is, thrombin-antithrombin (TAT) complexes, prothrombin activating factor F 1+2, activated factor XII (XIIa), and dimer D were all markedly increased. Pathologic levels of TAT and Xlla were found in 82% and 73% of all plasma samples, respectively. The augmentation of TAT correlated with prolongation of thrombin time and increases in F 1+2 levels. The increase in XIIa correlated with thrombocytopenia, prolongation of APTT, exhaustion of antithrombin, and accumulation of F 1+2 and FDP in the plasma. Moreover, a significant increase in XIIa, stronger positivity of the ethanol gelation test, a greater increase in FDP, and a more pronounced decrease in protein C activity were observed in 8 patients with fatal septic shock. This study suggests the usefulness of TAT and XIIa measurements in the early recognition of plasma hypercoagulation in serious infections.
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PMID:Plasma markers of hypercoagulability in patients with serious infections and risk of septic shock. 1236 Nov 99

Thrombin is an enzyme that is generated in both vascular and non-vascular systems. In blood coagulation, a fundamental process in all species, thrombin induces the formation of a fibrin clot. A dynamical model of thrombin generation in the presence of lipid surfaces is presented. This model also includes the self-regulating thrombin feedback reactions, the thrombomodulin-protein C-protein S inhibitory system, tissue factor pathway inhibitor (TFPI), and the inhibitor, antithrombin (AT). The dynamics of this complex system were found to be highly lipid dependent, as would be expected from experimental studies. Simulations of this model indicate that a threshold lipid level is required to generate physiologically relevant amounts of thrombin. The dependence of the onset, the peak levels, and the duration of thrombin generation on lipid was saturable. The lipid concentration affects the way in which the inhibitors modulate thrombin production. A novel feature of this model is the inclusion of the dynamical protein C pathway, initiated by thrombin feedback. This inhibitory system exerts its effects on the lipid surface, where its substrates are formed. The maximum impact of TFPI occurs at intermediate vesicle concentrations. Inhibition by AT is only indirectly affected by the lipid since AT irreversibly binds only to solution phase proteins. In a system with normal plasma concentrations of the proteins involved in thrombin formation, the combination of these three inhibitors is sufficient both to effectively stop thrombin generation prior to the exhaustion of its precursor, prothrombin, and to inhibit all thrombin formed. This model can be used to predict thrombin generation under extreme lipid conditions that are difficult to implement experimentally and to examine thrombin generation in non-vascular systems.
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PMID:A mathematical model of lipid-mediated thrombin generation. 1297

In the healthy individual intensive physical exercise leads to a minor activation of blood coagulation that appears to be balanced by a concomitant activation of the fibrinolytic system. This study tested the hypothesis that vigorous exercise might give rise to an exaggerated activation of coagulation in subjects with resistance to activated protein C (APC). Molecular markers of thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes) and fibrin formation (fibrinopeptide A), as well as markers of the fibrinolytic activity (plasmin-antiplasmin complexes, D-dimers), were determined in nine asymptomatic male individuals with APC resistance [age, 18 +/- 3 years; maximal oxygen consumption, 56.7 +/- 2.7 ml/kg per min (mean +/- standard deviation)] and in nine male control subjects (age, 19 +/- 4 years; maximal oxygen consumption, 56.2 +/- 3.2 ml/kg per min) after 1 h of running to exhaustion. Baseline levels of prothrombin fragment 1 + 2 were higher in individuals with APC resistance than in controls [0.67 +/- 0.06 nmol/l (mean +/- standard error) versus 0.48 +/- 0.01 nmol/l; P < 0.05]. In response to exercise, hemostatic variables significantly increased in both groups to a similar small extent. Likewise, exercise-induced changes of fibrinolytic variables in subjects with APC resistance paralleled those observed in controls. In summary, exhaustive running in subjects with APC resistance does not provoke an abnormal hemostatic or fibrinolytic response, suggesting that vigorous exercise does not imply an increased risk for thrombosis in young male subjects with APC resistance.
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PMID:Exercise-induced activation of coagulation in subjects with activated protein C resistance. 1516 17

The acronym DIC is commonly interpreted as "death is coming". This pessimistic view emphasizes the deficiency of available treatment options following diagnosis of disseminated intravascular coagulation. Clinically, DIC manifests as a systemic hemorrhagic disorder associated with widespread activation and eventual exhaustion of the coagulation system, although events underlying DIC also involve effectors of inflammation. DIC can be associated with diverse conditions including sepsis and major trauma and, when identified, signifies a significant worsening in prognosis and expected mortality. Although recent clinical studies have shown that activated protein C reduces mortality in patients with severe sepsis, there is a need for further investigation and a better understanding of the underlying mechanisms.
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PMID:Alternative treatments for disseminated intravascular coagulation. 1533 73

The acronym DIC is commonly interpreted as "death is coming." This pessimistic view emphasizes the deficiency of available treatment options following diagnosis of disseminated intravascular coagulation. Clinically, DIC manifests as a systemic hemorrhagic disorder associated with widespread activation and eventual exhaustion of the coagulation system, although events underlying DIC also involve effectors of inflammation. DIC can be associated with diverse conditions including sepsis and major trauma and, when identified, signifies a significant worsening in prognosis and expected mortality. Although recent clinical studies have shown that activated protein C reduces mortality in patients with severe sepsis, there is a need for further investigation and a better understanding of the underlying mechanisms.
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PMID:Alternative treatments for disseminated intravascular coagulation. 1554 51

NK cells have well-established functions in immune defense against virus infections and cancer through their cytolytic activity and production of cytokines. In this study, we examined the frequency of NK cells and their influence on T cell responses in mice given variants of lymphocytic choriomeningitis virus that cause acute or persisting infection. We found increased frequencies of circulating NK cells during disseminating infection compared with uninfected or acutely infected mice. Consistent with recent reports, we observed that the depletion of NK cells in mice with disseminated infection increased peak numbers of virus-specific cytokine producing CD8(+) T cells and resulted in the rapid resolution of disseminated infection. Additionally, we show that NK cell depletion sustained T cell responses across time and protected against T cell exhaustion. The positive effects of NK cell depletion on T cell responses only occurred when NK cells were depleted within the first 2 d of infection. We find that the improved CD8(+) T cell response correlated with an enhanced ability of APCs from NK cell-depleted mice to stimulate T cell proliferation, independently of the effects of NK cells on CD4(+) T cells. These results indicate that NK cells play an integral role in limiting the CD8 T cell response and contribute to T cell exhaustion by diminishing APC function during persisting virus infection.
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PMID:The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection. 2324 78


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