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

Heparin is indispensable anticoagulant for cardiopulmonary bypass, but the dose of heparin is even now under discussion. In this study, hemostatic fluctuation was analyzed during and after the bypass using hemostatic molecular markers. The subjects were 16 adult cases of open heart surgery, 12 males, 4 females. The average age was 55.0 year. Operations were aortocoronary bypass in 12, valvular surgery in 3 and ASD patch closure in one with moderate hypothermic cardiopulmonary bypass. At the beginning of cardiopulmonary bypass, 3 mg/kg heparin was administered and the equivalent amount of protamine sulfate was used for neutralization at the end of the bypass. Platelet count, hematocrit, antithrombin III (ATIII), beta-thromboglobulin, platelet factor 4, fibrinopeptide A, thrombin antithrombin III complex, FDP, D dimer FDP, plasmin alpha 2 plasmin inhibitor complex, tissue plasminogen activator (t-PA), and thrombomodulin (TM) were measured through the operation up to two weeks after surgery. ATIII decreased to 50% of control value all through the bypass. Platelet markers increased immediately, and the activated state continued 3 hours after the bypass. Coagulation markers increased markedly after the aortic declamping, and reached at its peak by three times as control value, immediately after the protamine neutralization and continued for 3 hours. During the bypass, fibrinogenolysis caused by t-PA which was stimulated by non-physiological circulation and stimulating substances, was observed. Fibrinolysis occurred following the hypercoagulability after the neutralization. TM was within normal range before the aortic declamping. But increased gradually after the declamp, and reached twice as much as the base line. It could be concluded that hypercoagulability and high platelet activation might play a role of perioperative thrombosis. Hypercoagulability and increase of serum TM would be related to reperfusion of the lung. The increasing of TM would reflect broad injury of vessel walls after the bypass, because plasma TM increased following the generalized injury of endothelial cells.
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PMID:[A clinical study on hemostatic fluctuation during and after cardiopulmonary bypass using hemostatic molecular markers]. 133 89

Serum amyloid P protein (SAP) is a heparin-binding protein that is found in blood and connective tissues including some types of vascular basement membrane. In this article we present evidence that SAP is capable of blocking the anticoagulant effects of glycosaminoglycans. SAP neutralized the catalytic effect of heparin on the thrombin-antithrombin III reaction more effectively than vitronectin, histidine-rich glycoprotein, fibronectin, and high-molecular-weight kininogen and almost as effectively as platelet factor 4. SAP also blocked the effects of heparin and dermatan sulfate on the inhibition of thrombin by heparin cofactor II. We found evidence for the formation of a high-affinity 1:1 complex between SAP and heparin and for inhibition of binding of both thrombin and antithrombin III to heparin-Sepharose by SAP. We conclude that SAP may account for much of the heparin-neutralizing capacity of plasma under some conditions and that basement-membrane-bound SAP may modulate extravascular coagulation by blocking the anticoagulant effects of basement membrane glycosaminoglycans.
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PMID:Neutralization of the anticoagulant effects of glycosaminoglycans by serum amyloid P component: comparison with other plasma and platelet proteins. 137 16

Mononuclear phagocytes synthesize chondroitin sulfate proteoglycan (CSPG), which is constitutively secreted. Because mononuclear phagocytes are known to interact with blood platelets, the effect of platelets on the release of CSPG in cultured human monocytes was investigated. After 6 days in vitro, the monocytes were supplied with fresh medium with different additions and subsequently exposed to [35S]sulfate for 24 hours before the medium fractions were harvested and analyzed for content of [35S]CSPG. Indirect evidence for the release of stimulatory factors from blood platelets was found when the addition of medium containing 50% serum made from platelet-rich plasma increased the expression of [35S]CSPG almost sevenfold compared with serum-free medium, whereas medium containing 50% serum made from platelet-depleted plasma increased the expression of [35S]CSPG about fourfold. Further, direct evidence for the stimulatory effect of platelets was found as the addition of autologous platelets to serum-free medium increased the expression of [35S]CSPG about threefold, and addition of supernatant from a corresponding number of thrombin-stimulated platelets was almost as efficient. The effect of five different platelet-derived factors (which are all present in serum) was investigated. Both platelet-derived growth factor (PDGF), platelet factor 4 (PF 4), and prostaglandin E2 (PGE2) used in physiologic concentrations were found to stimulate the expression of [35S]CSPG twofold to threefold, whereas transforming growth factor-beta had a slight inhibitory effect. 12-Hydroxyeicosatetraenoic acid had no significant effect on the expression of [35S]CSPG. Further evidence for the stimulatory effect of PDGF, PF 4, and PGE2 was found as serum depleted of these factors had significantly less stimulatory effect than control serum. The increased incorporation of [35S]sulfate into [35S]CSPG in cultures stimulated with serum or platelet-derived factors was not due to differences in molecular size or extent of sulfation of the proteoglycan molecules.
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PMID:Blood platelets stimulate the expression of chondroitin sulfate proteoglycan in human monocytes. 149 23

To maintain a closed system during the preparation of blood components, including the removal of buffy coat, many centers use a quadruple blood bag additive solution system which in this study has been reduced to a cheaper triple bag system. The buffy coat and plasma were after centrifugation transferred to the first satellite bag and, after a second spin, the plasma separated from the buffy coat was transferred to the second satellite bag and stored for a fortnight at 4 degrees C. This resulted in a statistically significant increase in platelet factor 4 and elastase activity levels. No significant changes were found in the levels of C1-esterase inhibitor and kallikrein inhibiting activity, thrombin-antithrombin complexes, soluble fibrin, fibrinopeptide A and spontaneous proteolytic activity. The changes observed must be regarded as clinically insignificant. The platelet count is low enough to meet the requirements for platelet poor plasma. Using this blood component separation technique, one can reduce the CPD/additive solution 4-pack blood bag system to a less expensive 3-pack blood bag system.
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PMID:Blood component processing technique and plasma quality. 149 50

The objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning. In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.
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PMID:Diurnal rhythm in anticoagulant effect of heparin during a low dose constant rate infusion. A study in healthy volunteers. 151 69

The effect of purified human platelet factor 4, a platelet alpha-granule protein, on the growth of the human osteoblastic osteosarcoma cell lines Saos-2 and G-292 was investigated. Platelet factor 4 (20 ng/ml to 2 micrograms/ml) caused a significant, dose-dependent inhibition of human osteoblast-like osteosarcoma cell proliferation. Platelet factor 4 exerted its inhibitory effect under all growth conditions tested: serum-free, serum-stimulated and thrombin-stimulated. The platelet factor 4-induced cell inhibition was not associated with a cytotoxic effect on the cells (assessed by lactate dehydrogenase release). The inhibitory effect of platelet factor 4 was not affected by the presence of indomethacin in the cultures, indicating that the effect was prostaglandin-independent. These results suggest that platelet factor 4 has direct antitumor effects and that it may be important in pathological and physiological processes of bone.
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PMID:Human platelet factor 4 is a direct inhibitor of human osteoblast-like osteosarcoma cell growth. 152 Mar 9

We examined the changes of haemostatic molecular markers after antithrombin III (AT III) administration in a 22-year-old woman with congenital AT III deficiency in the third trimester of pregnancy who did not have thrombosis. Various markers including fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), plasmin-alpha 2antiplasmin, D-dimer, beta-thromboglobulin, and platelet factor 4 were measured before and just after 3,000 U of AT III concentrate, which was given three times per week from the 34 week of pregnancy until delivery. Just after AT III administration, F1 + 2 and FPA levels decreased on most occasions, while TAT sometimes increased. Plasma FPA levels were markedly decreased on all 8 occasions when the plasma FPA levels was above 2.0 ng/ml before AT III administration. Plasma FPA levels were always greater than or equal to 6.4 ng/ml before AT III administration on the 4 occasions when TAT increased to above 115%. The changes of plasma F1 + 2 levels were significantly correlated with the AT III level. These results suggest that prophylactic AT III administration in the third trimester immediately inactivates intravascular thrombin to form TAT and reduce the plasma FPA level. Thus, the transient TAT elevation following AT III administration may not only be due to extraction of thrombin from the fibrin clots of thrombi but also to intravascular thrombin which is not attached to thrombi. FPA is the best molecular marker for thrombin hyperactivity and it should be monitored in AT III-deficient pregnant women in the third trimester.
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PMID:Prophylactic antithrombin III administration during pregnancy immediately reduces the thrombin hyperactivity of congenital antithrombin III deficiency by forming thrombin-antithrombin III complexes. 152 7

Increased plasma fibronectin levels are a highly sensitive and specific predictor of gestational hypertension. Of a total of 105 apparently healthy normotensive primigravid women seen at the outpatient clinic, 10 with increased plasma levels of fibronectin (mean +/- 2 SD), were compared with 14 controls. Parameters of early vascular damage (laminin, preprocollagen III), platelet activation (beta-thromboglobulin, platelet factor 4), and coagulation (thrombin-antithrombin III complexes, fibrinopeptide A) were measured at regular (weekly or monthly) intervals. Abnormal values of laminin (p less than 0.005) and fibronectin (p less than 0.0001) were found up to 4 weeks before the onset of clinical disease. Levels of beta-thromboglobulin (p less than 0.0001) were also elevated at least 4 weeks before the appearance of clinical symptoms. Our results show that increased levels of laminin, fibronectin, and platelet activation, as indicated by beta-thromboglobulin levels, are preclinical features of gestational hypertension and indicate that vascular damage has occurred. Fibrin formation would appear to occur later.
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PMID:Platelet activation and vascular damage in gestational hypertension. 153 75

Circadian variation in hemostatic factors may contribute to a higher frequency of cardiac events observed in the morning and with activity. Diurnal changes in these factors were investigated by measuring in vitro platelet aggregability in response to epinephrine and adenosine diphosphate together with beta-thromboglobulin and platelet factor 4 as indexes of in vivo platelet activation. Activation of coagulation was measured by thrombin-antithrombin III complexes and D-Dimers. Tests were performed in 9 normal healthy subjects. Circadian changes occurred in beta-thromboglobulin (p less than 0.05) and platelet factor 4 (p less than 0.06). Plasma levels of beta-thromboglobulin and platelet factor 4 were lowest with patients supine and resting at 7 and 8 A.M., and increased with activity, with peak levels achieved at 3 P.M. (p less than 0.01). Thrombin-antithrombin III complexes (p = 0.44), D-Dimer (p = 0.36) and in vitro platelet aggregability to adenosine diphosphate (p = 0.20) did not show diurnal variation. There was a trend toward circadian variation in vitro platelet aggregability to epinephrine, but these changes did not achieve statistical significance (p = 0.16). Circadian changes of in vivo release of beta-thromboglobulin and platelet factor 4 correlated to patient activity and not to the morning peaks in ischemic events. These data indicate that changes in platelet function and not in coagulation have a diurnal occurrence.
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PMID:Circadian variation in platelet function in healthy volunteers. 153 87

There is a controversy about whether or not histidine-rich glycoprotein (HRG), the most abundant plasma protein with glycosaminoglycans-neutralizing capacity, is able to prevent the inhibition of human thrombin by heparin cofactor II (HC II) in the presence of dermatan sulfate (DS). The authors studied the interaction of DS and low molecular weight DS, in a purified system with HRG, platelet factor 4 (PF 4), and with HC II. Their results show that HRG, like PF 4, has an affinity, not only for heparin, but also for DS. However, this affinity seems very weak. In fact, HRG is 10 times less effective than PF 4 in neutralizing the 50% antithrombin activity of HC II in the presence of DS.
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PMID:Interaction between histidine-rich glycoprotein and platelet factor 4 with dermatan sulfate and low-molecular-weight dermatan sulfate. 155 54


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