Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is believed that platelets play a key role in the production of pre-eclamptic toxaemia and toxaemia of pregnancy. Toxaemia of pregnancy is described as a condition of chronic DIC where there is thrombocytopenia as well as raised fibrin degradation products. Since fibrinogen receptors are involved in the final stage of the platelet aggregation reaction, we wanted to investigate the platelet receptors for fibrinogen in normal and abnormal pregnancy. Thirty-six normal pregnant women (12 in their 2nd trimester, 24 in their 3rd trimester), 24 pregnant pre-eclamptic toxaemia cases and 16 non-pregnant controls were included in the present study. All patients with pre-eclamptic toxaemia had oedema, proteinuria and hypertension. Flow cytometric study of platelets was undertaken utilizing fluorescein isothiocyanate (FITC)-labelled anti-human fibrinogen antibody in unstimulated and ADP-stimulated (final concentration 0.02 M) platelets. The intensity of platelet fluorescence was classified into three groups and expressed in arbitrary units. The results indicate that there are a higher number of stimulated platelets expressing fibrinogen receptors in the circulation of patients with pre-eclampsia. Thus, it is possible to hypothesize that platelets showing increased fibrinogen receptors aggregate and form microthrombi in smaller vessels in women with pre-eclamptic toxaemia.
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PMID:Functional and fibrinogen receptor studies in platelets in pre-eclamptic toxaemia of pregnancy. 1680 Oct 92

Stromal cell-derived factor-1 (SDF-1) is a CXC chemokine that activates and directs the migration of leukocytes that have CXCR4, which is the unique receptor for SDF-1. Although SDF-1/CXCR4 interaction has been implicated in various inflammatory conditions, its role in modulating coagulation has not been determined. We studied the plasma SDF-1 levels in 90 patients with suspected disseminated intravascular coagulation (DIC) and we found that circulating SDF-1 was significantly increased in the overt DIC patients and was also increased in overt DIC patients who have a poor outcome. We then tested in vitro whether SDF-1 can affect the expression of monocyte tissue factor (TF) and endothelial thrombomodulin (TM), and both of these play important roles in coagulopathy. SDF-1 did not affect the expression of surface TF protein and its function and the TF mRNA level in both monocytes and the monocytic leukemia cell line THP-1. SDF-1 also did not change the surface TM expression of endothelial cells. SDF-1 could enhance low-dose ADP induced platelet aggregation, although it failed by itself to induce aggregation. These findings suggest that plasma SDF-1 might be closely associated with hypercoagulability though its action as a platelet activator.
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PMID:Plasma level of stromal derived factor-1 (SDF-1) is increased in disseminated intravascular coagulation patients who have poor outcomes: in vitro effect of SDF-1 on coagulopathy. 1723 27

Sepsis is a systemic response to an infection that leads to a generalized inflammatory reaction. There is an intimate relationship between procoagulant and proinflammatory activities, and coagulation abnormalities are common in septic patients. Pharmaceutical studies have focused to the development of substances that act on coagulation abnormalities and on the link between coagulation and inflammation. Fructose-1,6-bisphosphate (FBP) is a high-energy glycolitic metabolite that in the past two decades has been shown therapeutic effects in great number of pathological situations, including sepsis. The aims of this study were to assess the effects of FBP on platelet aggregation in vitro and ex vivo in healthy and septic rats and evaluate the use of FBP as a treatment for thrombocytopenia and coagulation abnormalities in abdominal sepsis in rat. FBP inhibited platelet aggregation (P < 0.001) in vitro in healthy rats from the smallest dose tested, 2.5 mM, in a dose-dependent manner. The mean effective dose calculated was 10.6 mM. The highest dose tested, 40 mM, completely inhibited platelet aggregation (P < 0.001) induced by ADP. Platelet aggregation in plasma from septic rats was inhibited only with higher doses of FBP, starting from 20 mM (P < 0.001). The calculated mean effective dose was 19.3 mM. Ex vivo platelet aggregation in septic rats was significantly lower (P < 0.05) than healthy rats and the treatment with FBP, at the dose of 2 g/kg, diminished the platelet aggregation at the extension of 27% (P < 0.001), suggesting that FBP is a potent platelet aggregation inhibitor in vivo. Moreover, treatment with FBP 2 g/kg prevented thrombocytopenia (P < 0.001), prolongation of prothrombin and partial thromboplastin time (P < 0.001), but not fibrinogen, in septic rats. The most important findings in this study are that FBP is a potent platelet aggregation inhibitor, in vitro and ex vivo. It presents protective effects on coagulation abnormalities, which can represent a treatment against DIC. The mechanisms for these effects remain under investigation.
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PMID:Fructose-1,6-bisphosphate inhibits in vitro and ex vivo platelet aggregation induced by ADP and ameliorates coagulation alterations in experimental sepsis in rats. 1970 56

Nucleotides, including ADP, ATP and uridine triphosphate (UTP), are discharged profusely in the circulation during many pathological conditions including sepsis. Sepsis can cause hypotension and systemic activation of the coagulation and fibrinolytic systems in humans, which may cause disseminated intravascular coagulation. We investigated whether nucleotide-induced cardiovascular collapse as provoked by systemic infusion of adenosine, ADP, ATP, UTP and nitric oxide affected the haemostatic system as assessed by whole blood thromboelastography (TEG) analysis. Ten pigs received a randomized infusion of adenosine, ADP, ATP, UTP or nitric oxide until mean arterial pressure was reduced to approximately 40% of baseline simulating sepsis-induced hypotension. The effect of the infusions on the haemostatic system was evaluated by TEG, and endothelial release of tissue plasminogen activator and plasminogen activator inhibitor-1 was measured. In contrast to the other infused substrates, ADP caused a reduction in maximum amplitude (71.4 to 64.2; P < 0.05), and reduced the angle, representing the thrombus formation (75.6 to 66.4; P < 0.05), indicating hypocoagulation. Despite increases in t-PA release (2.1 to 2.7 ng/ml; P < 0.05) and reductions in plasminogen activator inhibitor (33.9 +/- 10.9-17.8 +/- 4.4 ng/ml; P < 0.05) no increased fibrinolysis was found when whole blood was evaluated by TEG. Circulating ADP induces hypocoagulation without signs of increased fibrinolysis as evaluated by TEG. The potential clinical significance of these findings should be investigated further because ADP discharged systemically may possibly contribute to the coagulopathy observed in severe sepsis.
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PMID:Effects of nucleotides and nucleosides on coagulation. 2038 37

Plasmic and platelet components of hemostasis were examined in 50 patients with terminal chronic renal failure (CRF) aged 23 to 67 years and 30 healthy controls of the same age. A plasmic hemostasis component was studied basing on 11 parameters of coagulogram. A platelet hemostasis component was studied by platelet aggregation: spontaneous and induced by ADP (in concentration 1.25, 2.5 and 5.0 mkg/ml), collagen, adrenalin and ristomycin. All CRF patients before hemodialysis had a significant alterations of 6 indices of a plasmic component of hemostasis: activated partial thromboplastic time, content of soluble fibrinmonomeric complexes, thrombine time; of 3 from 7 tests of aggregatogram (ADP, collagen, ristomycin induced aggregation). After hemodialysis severity of the above pathological shifts deteriorated (1.5 to 5 times). Thus, CRF patients on hemodialysis showed aggrevation of impairment of all hemostasis components. They are at risk of hypercoagulation, DIC-syndrome, massive thromboembolism. The above impairment of hemostasis should be considered in prescription of anticoagulant therapy to CRF patients. Monitoring of hemodialysis and adequate correction of the hemostasis system defects may contribute to improvement of quality of life of patients with terminal CRF and lowering of their mortality rate.
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PMID:[Changes in plasmic and platelet hemostasis in patients with chronic renal failure in hemodialysis]. 2264 97

Dengue hemorrhagic fever (DHF) is a more severe manifestation of dengue virus infection. Patients with DHF exhibit abnormal hematological indices, including high hematocrit, low white blood cells, low neutrophils, high lymphocytes, increased atypical lymphocytes, low platelets, slightly prolonged activated partial thromboplastin time, prothrombin time, and thrombin time. Abnormal platelet functions manifest as impaired platelet aggregation to ADP, and concurrent increases in plasma thromboglobulin and platelet factor 4 levels are also seen. Variable reductions in the activities of coagulation factors including prothrombin, V, VII, VIII, IX, and X may be present. The plasma level of antithrombin is typically normal, but protein C and protein S are modestly reduced. Within the fibrinolytic system, slightly increased levels of tissue-plasminogen activator accompanied by slightly increased plasminogen activator inhibitor-1 and decreased thrombin activatable fibrinolysis inhibitor have been demonstrated. These derangements are prominent in patients with DHF grades III and IV, collectively known as dengue shock syndrome. Moreover, patients with excessive depletion of intravascular volume from plasma leakage and/or massive bleeding from endothelial dysfunction, thrombocytopenia, platelet dysfunction, and coagulopathy may exhibit shock, prolonged shock and repeated shock. DIC is also commonly found in these complicated patients. However, most patients recover spontaneously with normalization of abnormal laboratory profiles during the convalescent stage or within one to two weeks after defervescence.
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PMID:Hemostatic derangement in dengue hemorrhagic fever. 2412 Feb 37

Collagen-related peptides, Gly-Pro-Arg and its analogues, were examined for their inhibitory effects on platelet aggregation induced by the addition of ADP. Human platelet aggregation was suppressed by more than 50% with each of Gly-Pro-Arg and such Gly-Pro-Arg-containing peptides as Gly-Pro-Arg-Gly, Gly-Pro-Arg-Gly-Pro, Gly-Pro-Arg-Pro-Pro, and Gly-Pro-Arg-Pro-Pro-Pro at a concentration of 0.3 mm. The inhibitory effects of these peptides were about 10 times higher in human PRP than in rat PRP. Other Gly-Pro-Arg analogues such as Sar-Pro-Arg, Gly-Pro-Lys, Gly-Ala-Arg, and Ala-Gly-Pro-Arg had no inhibitory effect at a concentration from 0.1 to 0.8 mm even in human PRP. Intravenous and oral administrations of Gly-Pro-Arg and enzymatic hydrolysates of collagen suppressed the decrease in platelet count for endotoxin-induced DIC in rats. Collagen itself has been regarded as a potent inducer of platelet aggregation, but these findings suggest that collagen-related peptides and enzymatic hydrolysates of collagen prevent platelet aggregation.
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PMID:In Vitro and in Vivo Anti-platelet Effects of Enzymatic Hydrolysates of Collagen and Collagen-related Peptides. 2886 60


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