Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to characterize the changes in the quantitative expression of beta 2-integrins and L-selectin detected by means of fluorochrome-conjugated monoclonal antibodies and flow cytometry on leukocytes in the systemic circulation after a major musculoskeletal trauma, i.e. hip replacement surgery, and to relate these changes to parameters of the acute-phase response [plasma acute-phase reactants (C-reactive protein, CRP, and interleukin-6, IL-6) and parameters of coagulation activation (thrombin-antithrombin III complexes, TAT)]. Eight patients with either primary or secondary osteoarthritis of the hip received uncemented total hip prostheses. LFA-1 (CD11a/CD18) was upregulated on granulocytes during the operation. MAC-1 (CD11b/CD18) expression on monocytes increased to peak levels 20 h after surgery, whereas the L-selectin (CD62L) expression on monocytes and granulocytes reached peak values at the end of surgery. The changes in expression of LFA-1 on monocytes, MAC-1 on granulocytes and p150,95 (CD11c/CD18) on monocytes and granulocytes during and after the operation did not reach statistical significance. TAT and IL-6 increased during surgery and reached peak values at the end of the operation and 20 h after surgery, respectively. In contrast, CPR concentrations increased after surgery with peak levels 44 h postoperatively. Significant upregulation of LFA-1 on granulocytes and L-selectin on monocytes and granulocytes preceded the increase in IL-6 which again preceded the increase in CRP. However, the up- or downregulation of leukocyte beta 2-integrins and L-selectin during and after surgery was not significantly correlated with the increase in IL-6. The increases in TAT correlated well with the upregulation of L-selectin on monocytes, but not with the beta 2-integrins known to participate in the coagulation process in vitro. The rise in CRP was inversely correlated with the maximal increase in expression of MAC-1 on monocytes. In conclusion, the changes in leukocyte adhesion molecules during and after surgery indicate changes in critical leukocyte functions. The lack of correlation between quantitative up- and downregulation of leukocyte beta 2-integrins and parameters of the acute phase response suggests that these processes are regulated through independent pathways or that functional up- and downregulation of adhesion molecules, shedding, leukocyte-endothelial adhesion and mobilization of new unactivated cells may result in a net estimate of leukocyte activation not suspected to be positively correlated to acute-phase reactants.
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PMID:Expression of beta-2-integrins and L-selectin by leukocytes and changes in acute-phase reactants in total hip replacement surgery. 873 29

The effects of moderate 30 min cycle ergometer exercise (aerobic metabolism; 0.85-3.71 mmol.1(-1) lactate) followed by short-term exercise at maximal capacity (anaerobic metabolism; 5.09 to 17.75 mmol.1(-1) lactate) on endothelin (ET) and hemostatic variables (tissue plasminogen activator [t-PA] antigen, prothrombin fragments [F1,2], thrombin-antithrombin III complex [TAT], prothrombin time and partial thromboplastin time) were investigated in 15 male healthy subjects of varying fitness levels. Endothelin was measured twice before and immediately after maximal cycle exercise. The results show an increase in endothelin concentration [10.0 pg.ml-1 (baseline) + 6.1 pg.ml-1 (increase post exercise)]. ET did not increase under control conditions. Moderate 30 min exercise caused an increase in t-PA antigen concentration (3.66 + 3.15 ng.ml-1) and short-term maximal exercise produced a markedly higher elevation in this variable (+10.6 ng.ml-1). F1,2 increased (810 + 40 pmol.l-1) under moderate and by 150 pmol.l-1 under anaerobic exercise. TAT increased only at maximal exercise levels (1.01 + 0.32 ng.l-1). No changes were found in any of these variables under control conditions. No correlation of endothelin and the hemostatic variables was found. It is concluded that endothelin and hemostatic markers increase independently during moderate and maximal exercise.
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PMID:Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system. 874 88

Regional limb perfusion with antineoplastic agents stresses the local vasculature in a variety of ways. However, by monitoring the perfusates from limbs treated with melphalan alone or with melphalan plus tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma), we were able to distinguish the effect of the cytokines on the observed coagulant and fibrinolytic responses. We collected samples of effluent from a series of lower extremities that were perfused with the cytokines and/or melphalan as treatment for localized melanoma. Both regimens produced statistically significant evidence of coagulant and fibrinolytic activation. However, limbs receiving cytokines in addition to the melphalan responded with a sharper rise in tissue plasminogen activator (tPA) and plasmin (plasmin-antiplasmin complexes [PAP]) than limbs treated with melphalan alone. Evidence of thrombin formation (prothrombin fragment 1 + 2 [F1 + 2], thrombin-antithrombin complexes [TAT]) was also greater when the cytokines were included, although the response was delayed and less consistent than the fibrinolytic activation.
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PMID:Fibrinolytic and coagulant responses to regional limb perfusions of tumor necrosis factor, interferon-gamma, and/or melphalan. 903 49

The aim of this study was to investigate the hemostatic system in menopausal women before and after three months of treatment with transdermal estradiol (TTS 50, 50 micrograms/die, n = 13) or coniugated equine estrogen (CEE, 0.625 mg/die, n = 9) by evaluating : beta-thromboglobulin, platelet factor 4, factor VIIag, factor VIIc, fibrinopeptide A-FPA-, thrombin-antithrombin-TAT-complexes, antithrombin-AT-activity, protein C, plasma fibrinolytic activity (euglobulin clot lysis time), plasminogen and antiplasmin activity. FPA levels significantly increased during TTS 50 treatment (p < 0.001) while protein C showed a slight but significant decrease in both treatments (TTS 50 p < 0.001, CEE p < 0.05). TAT complexes and AT were found unaltered. Platelet function and fibrinolytic activity did not significantly change. A significant relationship between FPA and estradiol levels, which were significantly increased during. TTS 50 therapy, was found (r = 0.40, p < 0.05). These findings indicate that unopposed estradiol given by transdermal route induces a slight but significant blood clotting activation, which seems strictly related to its biological activity.
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PMID:Effects of estrogen replacement therapy on thrombin generation. 905 93

Malignancy is a risk factor for thromboembolism and anti-cancer chemotherapy can increase this risk. Prophylaxis of thrombosis with very-low-dose warfarin given concurrently with chemotherapy has a significantly reduced rate of thromboembolism in a randomized trial in women with stage IV breast cancer. In a group of 32 patients randomized in one center (16 subjects on warfarin and 16 on placebo), we have prospectively studied the plasma levels of: 1. Markers of 'in vivo' clotting activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2] and D-dimer), 2. Factor VII (FVII), and 3. Natural anticoagulants (protein C [PC] and antithrombin [AT]). The aims of this study were: 1. to examine whether laboratory tests predicted those patients who developed thrombosis, and 2. to evaluate the effect of very-low-dose warfarin on hemostatic variables. The patients' hemostatic parameters were evaluated before entry into the study and after starting chemotherapy +/- prophylaxis, before each course for nine courses. Before-treatment results were compared to those of a sex and age-matched non-cancer control group. There was a significant elevation of plasma levels of TAT (p <0.001), F1+2 (p <0.001), D-dimer (p <0.0001) and FVIIa (p <0.05), as well as an increase of FVII proteolysis (p <0.05), whereas plasma PC and AT concentrations were not different from controls. After starting chemotherapy, markers of clotting activation were progressively lower in the group receiving warfarin prophylaxis compared to the group on placebo. Differences between the groups became statistically significant (p <0.01) after the 4th course of chemotherapy. Deep vein thrombosis occurred in two patients in the placebo arm. The results of this study indicate that before therapy, an hypercoagulable state is present in stage IV breast cancer, and after starting chemotherapy, abnormalities of hypercoagulation markers persist, however they are reduced by very-low-dose-warfarin. None of the laboratory variables could predict thrombosis in the single patient.
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PMID:The effect of very-low-dose warfarin on markers of hypercoagulation in metastatic breast cancer: results from a randomized trial. 945 16

Severely burned patients often present a hypercoagulability situation. However, its magnitude, time course, and relationship with organ failure and outcome remains to be established. Forty-three patients were studied on the first and seventh day after burn for hypercoagulability and fibrinolysis parameters. A hypercoagulability and hyperfibrinolysis state was found the first day after burn demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin-antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA, p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII, p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin plate assay (FA, p<0.01) and high levels of tissue plasminogen activator inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first day. Also, there was a positive correlation of Marshall organ failure score with ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41, p<0.0003). Severely burned patients show a state of transient disseminated intravascular coagulation, related to the development of organ failure and outcome.
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PMID:Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma. 963 Mar 8

Among 379 patients with AML with FAB type M1, 2 and M4-7 diagnosed between 1978 and 1997 in our institution, 19 (5%) had hypofibrinogenemia (HF), ie a fibrinogen level <180 mg/dl. Compared to patients with normal fibrinogen (n = 360) patients with HF had significantly elevated markers of activation of coagulation (TAT, F1.2, FPA) and fibrinolysis (D-dimer, FDP) indicating that disseminated intravascular coagulation/hyperfibrinolysis was the cause of hypofibrinogenemia. Patients with HF had significantly longer prothrombin times, thrombin clotting and reptilase times. Factor X and VIII were significantly lower than in patients without HF. With the exception of M7, HF occurred in all FAB subtypes, but was most common in M5 (12.1%). Patients with HF did not differ from those with normal fibrinogen with regard to age, sex, leukocyte count and other hematological parameters. During induction chemotherapy fibrinogen normalized rapidly (median 5 days) and there was no increased incidence of early hemorrhagic death. The overall and disease-free survival was similar to that of patients without HF.
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PMID:Hypofibrinogenemia in non-M3 acute myeloid leukemia. Incidence, clinical and laboratory characteristics and prognosis. 969 71

A combined hemostatic defect consisting of a reduction in certain procoagulants, anticoagulants (antithrombin III-ATIII-, protein C-PC-) and components of the fibrinolytic system (plasminogen-Plg-) was demonstrated in very-low-birth-weight infants (VLBW <1,500 g) with gestational age 26-32 weeks. Sixteen of them were healthy, 28 were suffering from RDS and 24 from septicemia. The hemostatic defect was more profound in the RDS group, nevertheless increased TAT (thrombin + ATIII complex) and/or PAP values (plasmin + a2-antiplasmin complex) was a more frequent finding in the septicemic group of infants (91.8 vs. 17.9%). Moderate-to-severe thrombocytopenia was detected in a higher percentage in the septicemic (70.8%) than in the RDS group (50%), and increased D-dimers were demonstrated in 34.8 and 28.6% of the infants, respectively. Elevated TAT or PAP values were not always associated with gross coagulation abnormalities, and advanced disseminated intravascular coagulation (DIC) was only documented in 16.7% of the septicemic and 7.1% of the RDS infants. None of the VLBW neonates presented with clinical evidence of thrombosis, although hemorrhagic manifestations were apparent in 34.8 and 14.3% of the neonates with septicemia or RDS, respectively, mainly due to DIC or severe thrombocytopenia. In conclusion, increased TAT and/or PAP values are good indicators of the in vivo activation of the hemostatic system, but still their impact on sick neonates morbidity and mortality remains unknown.
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PMID:Indications of coagulation and/or fibrinolytic system activation in healthy and sick very-low-birth-weight neonates. 974 62

More dialysis treatments have been performed with cellulose based membranes than with any other material. As unmodified cellulose membranes activate the complement system, much effort has been directed toward the development of noncomplement activating cellulose membranes. One successful approach was the substitution of -OH groups in the cellobiose units of the cellulose molecule with tertiary amino groups, which resulted in a membrane called Hemophan. Synthetically modified cellulose (SMC) is a new hemodialysis membrane made by specific chemical modification whereby aromatic benzyl groups are covalently introduced into the cellulosic structure by ether bonds, creating hydrophobic domains within the overall hydrophilic cellulose surface: basic research investigations have shown that a characteristic hydrophobic-hydrophilic balance of surfaces is a prerequisite for improved hemocompatibility. Several cellulose modifications with aliphatic and aromatic groups were performed to achieve a membrane with the desired hemocompatibility profile; SMC, having hydrophobic benzyl groups, causes minimal activation of blood complement, coagulation, and cell activation systems. In vitro experiments with blood showed that C5a generation for SMC was reduced by 94% relative to Cuprophan (compared with 96% for polysulphone, a synthetic hemodialysis membrane). Activation of coagulation (formation of the thrombin-antithrombin III complex [TAT]) in a clinical study showed that SMC caused 16 ng/ml TAT generation compared with 36 ng/ml for polysulphone. SMC, a low-flux cellulosic dialysis membrane, thus combines the typically high diffusive performance characteristics of cellulosic membranes with excellent hemocompatibility, matching synthetic dialysis membranes.
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PMID:Synthetically modified cellulose (SMC): a cellulosic hemodialysis membrane with minimized complement activation. 980 99

The authors studied whether haemostatic abnormalities connected with the development of cerebral circulatory disturbances can be demonstrated in young stroke patients in whom Doppler and angiographic examination failed to reveal deviations indicative of stroke. They determined the in vivo activation of the coagulation system (TAT, F 1 + 2), the degree of secondary fibrinolysis (D-dimer), the plasma levels of the markers of fibrinolysis, with special regard to inhibitors: plasminogen activator inhibitor (PAI-1), alpha 2 antiplasmin (alpha 2 AP), alpha 2 macroglobulin (alpha 2 M), the frequency of pathologic serum lipoprotein (a)-Lp(a)-values and the association of PAI-1 and Lp(a) with the fibrinolytic system. They conclude that in the acute phase of the disease, the TAT and F 1 + 2 values were significantly elevated compared to the control, without change in the D-dimer value. The results suggest that in the tested period increased thrombin generation dominated and it significantly surpassed plasmin activity since the D-dimer values of that period did not indicate substantial increase in secondary fibrinolysis. The results of the study were separately analyzed in acute, chronic TIA and stroke groups. In the TIA and acute group the F 1 + 2 values, while in stroke the TAT values were more elevated. The in vitro fibrinolytic capacity of the patients significantly decreased compared to controls, showing significant correlation with the Lp(a) level, but not with the PAI value. Examination of the marker molecules renders possible to assess the degree of hypercoaguability and of endogenous lysis. Their knowledge is held important for judging the progression of the disease and the therapeutic consequences.
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PMID:[Hemostatic abnormalities in ischemic stroke]. 981 Jan 64


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