Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A prospective study of hemostatic abnormalities in 108 cancer patients was undertken at an oncology clinic in a university teaching hospital. Tests included Quick prothrombin time, activated partial thromboplastin time, thrombin time, platelet count, modified Ivy bleeding time, fibrinogen, fibrin degradation products (FDP), euglobulin lysis time, protamine sulfate test, and factor V, VII, VIII and X assays. Ninety-eight per cent of the patients had one or more abnormal coagulation tests. The commonest abnormalities were elevated fibrin degradation products and prolonged thrombin time. Thrombocytosis occurred in 57% of patients, hyperfibrinogenemia in 46%, thrombocytopenia in 11%, and non had hypofibrinogenmia. It is suggested that platelet count, fibrinogen concentration, and serum FDP assay are the most useful tests in assessing the hemostatic abnormalities in cancer patients, although thrombin time, factor V assay, and bleeding time may also be helpful. The peripheral blood smears of 53 patients were reviewed, and only one showed microangiopathic hemolytic anemia. The data illustrate that subclinical coagulopathy is relatively frequent in patients with malignancy.
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PMID:Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies. 42 Jan 61

Recently, evidence has been reported to suggest that human platelets like several other circulating blood cells may bind insulin. To examine whether human platelets contain specific insulin receptors, washed human platelets suspended in Hepes buffer were incubated at 24 degrees C with 125I-insulin in the presence and absence of unlabeled insulin and specific insulin binding was determined. Insulin binding by platelets increased progressively with time of incubation to reach a maximum at 3 h and was proportional to the number of platelets in the incubation mixture. Maximum insulin binding was observed at pH 8. Insulin degradation by platelets as assessed by TCA precipitability and reincubation studies was minimal. Scatchard analysis of the binding data and dissociation studies revealed evidence of negative cooperativity of the platelet insulin receptor. A high affinity dissociation constant of approximately equal to 3 X 10(9) M-1 was determined and the concentration of platelet insulin receptors was estimated as 25 binding sites/micron2 platelet surface area. Binding of 125I-insulin by platelets was inhibited by unlabeled porcine insulin and to a lesser extent by catfish insulin and porcine proinsulin but not by glucagon, prolactin, growth hormone, and thrombin. The findings indicate that human platelets contain specific insulin receptors. The significance of the platelet insulin receptor, particularly with respect to altered platelet function in diabetes mellitus, remains to be determined.
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PMID:Demonstration and partial characterization of insulin receptors in human platelets. 44 28

Fourteen patients with a documented sudden neurosensory hearing loss and four patients with other diseases causing neurosensory hearing loss were studied. The standardized coagulation workup included hematocrit, activated partial thromboplastin generation time, thrombin generation, prothrombin time, phase platelet count, platelet adhesivity, protamine sulfate, serum antithrombin III activity, fibrinogen, and Factor VIII values. Ony those patients having documented evidence of a neurosensory hearing loss occurring within hours or days were included in this study. Eight of the 14 paitents with a documented sudden neurosensory hearing loss satisfied our laboratory criteria for a diagnosis of in vitro hypercoagulability. Three of these patients had abnormal thrombin generation values, 4 had abnormal serum antithrombin III values, and 1 had an elevated platelet count. Four other patients with other diseases causing neurosensory hearing loss did not show evidence of in vitro hypercoagulability. It would appear from this data that coagulation abnormalities play a role in the pathogenesis of sudden neurosensory hearing loss.
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PMID:Hypercoagulability as a cause of sudden neurosensory hearing loss. 50

This study reports the correlation of the thrombin generation test and the plasma clot impedance test with clinical evidence of hypercoagulability. Thrombin generation is increased and the rate of change of plasma from a liquid to a gel (clot impedance) is increased in situations where the risk of thrombosis is increased. These situations include increasing clinical signs and/or symptoms of thromboembolism, positive lung scans, postoperative total hip replacement, patients over 40 years old, low serum antithrombin III, thrombocytosis, transient cerebral ischemia, and positive isotope venogram for thrombosis. The two tests failed to indicate a significant effect of antiplatelet drugs on the hypercoagulable state. This study shows that the thrombin generation and plasma clot impedance tests are practical, rapid and useful tests for the detection and monitoring of the hypercoagulable state.
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PMID:Evaluation of the in vitro detection of the hypercoagulable state using the thrombin generation test and plasma clot impedance test. 50 79

The effect of prostaglandin E1 (PGE1) on platelets is mediated through the PGE1 receptor and the consequent maintenance of the platelet's discoid shape. The effects of PGE1 and dibutyryl cAMP (dbcAMP) on the deformability of human platelets were studied. Deformability tests based upon the micropipette aspiration on the platelets were performed by using pipettes with radii (Rp) of 0.26-0.36 microns. The time course of the extension length (Dp, in microns) of the platelets in response to aspiration with a negative pressure (delta P) of 5 cm H2 O (delta P x Rp = 0.15 dynes/cm) was analyzed. PGE1 treatment (0.1 microM) resulted in a decrease of platelet deformability as compared with results obtained for apparently non-activated, control platelets. The deformation index, i.e., Dp/Rp (PGE1-treated)/Dp/Rp (control), was significantly reduced to 0.90 +/- 0.04. DbcAMP treatment also significantly decreased the deformability of platelets and this decrease was dbcAMP dose dependent. In contrast, colchicine- or cytochalasin D-treated platelets increased deformability. PGE1-treated platelets had a higher [cAMP]i than controls. Platelets treated with PGE1 or dbcAMP showed a reduced [Ca2+]i increment induced by thrombin as compared to non-treated controls. These results indicate that PGE1 and dbcAMP treatment of platelets is accompanied by an enhancement of platelet resistance to deformation. The increased [cAMP]i and low [Ca2+]i after PGE1 treatment may limit the rearrangement of cytoskeleton and thus enhance platelet resistance to deformation.
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PMID:Prostaglandin E1 and dibutyryl cyclic AMP enhance platelet resistance to deformation. 132 94

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by 14-day cycles of neutropenia, monocytosis, thrombocytosis, and reticulocytosis. Platelets from CH dogs have decreased dense-granule serotonin pools and decreased aggregation responses to collagen, platelet-activating factor (PAF), and thrombin. Recombinant granulocyte colony-stimulating factor (rG-CSF) was administered (5 micrograms/kg, b.i.d.) to four CH and six normal dogs to determine if G-CSF therapy corrected qualitative platelet defects in CH dogs. Neutrophil counts increase to greater than 25,000 cells/microliters within 24 h after starting treatment in all dogs. Treatment with G-CSF blocked neutropenic episodes in the CH dogs. Platelet aggregation, and serotonin content and secretion were significantly (p less than 0.05) decreased in the CH dogs both before and during recombinant human (rh) G-CSF treatment compared to normal dogs. Neutrophil myeloperoxidase, a primary granule enzyme, was significantly (p less than 0.05) decreased in CH dogs and was not corrected by rhG-CSF treatment. Administration of rG-CSF to CH dogs eliminated cell cycles but apparently did not correct cellular defects in CH dogs. Identification of primary biochemical defects in cells from CH dogs may be crucial to investigating the biochemical basis for cyclic hematopoiesis.
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PMID:Effects of recombinant granulocyte colony-stimulating factor treatment on hematopoietic cycles and cellular defects associated with canine cyclic hematopoiesis. 169 76

The dynamics of leukocyte-platelet adhesion and platelet-platelet interaction in whole blood are not well understood. Using different platelet agonists, we have studied the whole blood kinetics of these heterotypic and homotypic interactions, the relative abilities of different leukocyte subsets to participate in platelet adhesion, and the ligands responsible for adhesion. When platelet aggregation was inhibited by the Arg-Gly-Asp-Ser (RGDS) peptide, thrombin stimulation of whole blood resulted in platelet expression of granule membrane protein 140 (GMP-140) and, simultaneously, a marked increase in the percentage of monocytes and neutrophils (PMN) binding platelets, as well as an increase in the number of platelets bound per monocyte and PMN. Lymphocytes were unaffected. Monocytes bound more platelets and at an initially faster rate than PMN. This increase in monocyte and PMN adhesion to platelets was completely inhibited by the blocking monoclonal antibody (MoAb), G1, to GMP-140. When the combination of epinephrine and adenosine diphosphate (epi/ADP) was used as a less potent agonist in the presence of RGDS, GMP-140 expression per platelet was less, and while monocyte-platelet conjugates formed, PMN-platelet conjugates did not. With epi/ADP in the absence of RGDS, there was an immediate, marked decrease in the percentage of all leukocytes with bound platelets, simultaneous with an increase in the percentage of unbound platelet aggregates. As these platelet aggregates dissociated, the percentage of monocytes and PMN with adherent platelets increased, with monocytes again binding at a faster initial rate than PMN. This recovery of monocyte and PMN adhesion to platelets was also inhibited by the G1 MoAb. We conclude that: (1) monocytes and PMN bind activated platelets in whole blood through GMP-140; (2) monocytes have a competitive advantage over PMN in binding activated platelets, particularly when less potent platelet agonists are used; and (3) platelet aggregate formation initially competes unactivated platelets off leukocytes; subsequent aggregate dissociation allows the now activated platelets to readhere to monocytes and PMN through GMP-140. These studies further elucidate the dynamic interaction of blood cells and possible links between coagulative and inflammatory processes.
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PMID:Dynamics of leukocyte-platelet adhesion in whole blood. 171 69

Recent reports have suggested a variation in the density and affinity of fibrinogen binding sites in platelets from patients with myeloproliferative disorders (MPD) which may reflect platelet functional abnormalities in these subjects. We have investigated the binding of 125I-fibrinogen (125I-Fb) to gel-filtered platelets from a large relatively homogeneous group of patients with MPD compared to normal age matched controls. Twenty-two of the patients investigated had polycythaemia vera and four essential thrombocythaemia. The maximal density and affinity (Kd) of 125I-Fb binding was assessed by saturation analysis in gel-filtered platelets (GFP) stimulated with either 10 microM ADP or 150 mU thrombin. In addition the functional significance of the binding sites was studied by evaluating the response of GFP from the two experimental groups by assessing the effects of increasing concentrations of added fibrinogen on the response to 10 microM ADP using standard light transmission aggregometry. In both groups the density of fibrinogen binding sites expressed in response to thrombin stimulation was significantly higher (approximately 2-3 fold) than that found in response to ADP. However, fewer binding sites were detected in the MPD group as compared with the control group in response to both ADP and thrombin. The Kd for 125I-Fb was similar for both agonists in normal controls and was significantly lower than that found in the MPD subjects. Although the 125I-Fb binding study results indicate a significant reduction in both the number and affinity of fibrinogen binding sites in patients with myeloproliferative disorders, the clinical and functional significance of these findings remain uncertain.
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PMID:125I-fibrinogen binding to platelets in myeloproliferative disease. 174 4

A case of thromboembolic pulmonary hypertension associated with long-standing thrombocytosis is presented. In this patient we found a significant local pulmonary platelet activation and thrombin generation as indicated by the existence of a transpulmonary gradient for thromboxane A2, beta thromboglobulin and fibrinopeptide A. Prolonged heparin and acetylsalicylic acid treatment resulted in improvement of clinical and hemodynamic conditions. These findings support the usefulness of anticoagulating and antiaggregating therapy in selected cases of pulmonary hypertension.
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PMID:Pulmonary hypertension associated with long-standing thrombocytosis. 182 75

Platelet aggregation (PA) induced by ADP, collagen and epinephrine, plasma levels of beta-thromboglobulin (beta TG) and thromboxane B2 (TXB2) and serum TXB2 generation were studied in 11 patients with primary thrombocytosis (7 with essential thrombocythaemia and 4 with polycythaemia vera) and compared with 16 healthy subjects. 5 patients suffered from peripheral vascular ischaemia and another 3 had venous thrombosis, but none had bleeding complications. The patients showed an abnormal pattern of platelet function and of thromboxane generation distinct from the healthy subjects in three aspects. a) Shape change was 5-26 times greater, the lag-time of collagen PA was 2.3-2.9 times longer and the extent of epinephrine PA was nil or very low. ADP- or collagen-induced PA was also reduced (p less than 0.02). b) Plasma TXB2 generation (corrected to a normal platelet concentration) stimulated by the three PA inducers was within the range of the healthy subjects in spite of the reduced extent of PA. c) Plasma beta TG level and serum TXB2 generation (both corrected to a normal platelet concentration) were 2.9-7.1 times higher (p less than 0.001) indicating enhanced in vivo platelet activation and possibly increased thrombin generation. These abnormalities were not detected in another 4 patients with secondary thrombocytosis. The abnormal pattern of platelet function and thromboxane generation can be a useful laboratory method in the evaluation of patients with primary thrombocytosis. It might also explain the thrombotic complications which occurred in 8 of the patients in a manner such that increased or normal TXB2 generation overcomes the reduced extent of PA. In this respect, the pronounced serum TXB2 synthesis might be a marker of intravascular thrombosis.
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PMID:An abnormal pattern of multiple platelet function abnormalities and increased thromboxane generation in patients with primary thrombocytosis and thrombotic complications. 183 99


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