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)

The serum levels of thrombopoietin (TPO) were measured in 16 patients with thrombotic thrombocytopenic purpura (TTP), 12 with hemolytic uremic syndrome (HUS), 10 with aplastic anemia (AA), 10 with disseminated intravascular coagulation (DIC), and 71 with idiopathic thrombocytopenic purpura (ITP). The serum TPO levels were measured with a sensitive sandwich enzyme-linked immunosorbent assay. The serum TPO level in the ITP group (1.68 +/- 0.85 fmol/ml) were not significantly increased compared with those of the normal subjects. The TPO levels in the TTP (2.77 +/- 1.38 fmol/ml) and HUS groups (5.77 +/- 4.41 fmol/ml) were higher than those of the normal subjects. The patients with AA (12.7 +/- 8.0 fmol/ml) and those with DIC (13.3 +/- 5.7 mol/ml) had significantly higher serum TPO levels than did the normal subjects and ITP patients. The TPO levels were well correlated with the platelet counts in the TTP patients, and were negatively correlated with the platelet counts in the ITP patients. These results suggest that the serum TPO levels in some thrombocytopenic diseases are regulated not only by the platelet count and the megakaryocyte mass, but also by other factors.
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PMID:Increased serum levels of thrombopoietin in patients with thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or disseminated intravascular coagulation. 935 24

Appropriate laboratory testing for the platelet-type bleeding disorders hinges on an adequate assessment in the history and physical examination. Patients with histories and screening laboratory results consistent with coagulation disorders (hemophilia, disseminated intravascular coagulation) are not appropriate candidates for platelet function testing. In contrast, patients with a lifelong history of platelet-type bleeding symptoms and perhaps a positive family history of bleeding would be appropriate for testing. Figure 6 depicts one strategy to evaluate these patients. Platelet morphology can easily be evaluated to screen for two uncommon qualitative platelet disorders: Bernard-Soulier syndrome (associated with giant platelets) and gray platelet syndrome, a subtype of storage pool disorder in which platelet granulation is morphologically abnormal by light microscopy. If the bleeding disorder occurred later in life (no bleeding with surgery or trauma early in life), the focus should be on acquired disorders of platelet function. For those patients thought to have an inherited disorder, testing for vWD should be done initially because approximately 1% of the population has vWD. The complete vWD panel (factor VIII coagulant activity, vWf antigen, ristocetin cofactor activity) should be performed because many patients will have abnormalities of only one particular panel component. Patients diagnosed with vWD should be classified using multimeric analysis to identify the type 1 vWD patients likely to respond to DDAVP. If vWD studies are normal, platelet aggregation testing should be performed, ensuring that no antiplatelet medications have been ingested at least 1 week before testing. If platelet aggregation tests are normal and if suspicion for an inherited disorder remains high, vWD testing should be repeated. The evaluation of thrombocytopenia may require bone marrow examination to exclude primary hematologic disorders. If future studies with thrombopoietin assays confirm preliminary results, however, the bone marrow examination of certain patients may be replaced by a thrombopoietin level.
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PMID:Overview of platelet physiology and laboratory evaluation of platelet function. 1037 Aug 53

Refractory thrombocytopenia (RTC) is a counter-concept to refractory anemia, which is characterized by isolated thrombocytopenia associated with clonal chromosomal abnormality. The diagnosis of RTC is difficult to establish based on morphologic features alone. And steroid therapy for RTC is often ineffective. We examined 3 patients with RTC to identify its characteristics and measured serum thrombopoietin levels. The mean platelet count was 5.1 x 10(4)/microl and the mean age was 64 years. None of our patients had clinical nor laboratory evidence of liver dysfunction, renal disease or disseminated intravascular coagulation. All patients were negative for antiplatelet antibody, PA-IgG and anticardiolipin-beta2GPI antibody. Leukocyte alkaline phosphatase level was low in two patients. Clonal chromosomal abnormalities of different types were detected in all patients. Bone marrow smears showed micromegakaryocytes. But there were no apparent morphological abnormalities of erythroid and granuloid series. Thrombopoietin levels, as determined by enzyme-linked immunosorbent assay, varied from <0.2 to 1.40 fmol/ml. We could not find the screening tool of RTC. In conclusion, there is a need to identify RTC from isolated thrombocytopenia because the patients with RTC don't have good prognosis as patients with isolated thrombocytopenia. Cytogenetic analysis is necessary to establish the diagnosis of RTC. We recommend that a patient above 50 years of age presenting with isolated thrombocytopenia and a low leukocyte alkaline phosphatase score should be suspected of having RTC.
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PMID:Clinical analysis and TPO levels in three patients with refractory thrombocytopenia. 1050 5

Thrombopoietin (TPO), interleukin (IL)-6, and platelets were measured serially in 9 patients with fulminant meningococcal septicemia and consumption coagulopathy. The results were compared with those of patients with meningococcal meningitis and mild meningococcemia (n=10) and with those of healthy control subjects (n=19). TPO levels in control subjects were below the detection limit (<63 pg/mL). In patients with fulminant meningococcal septicemia, the median TPO level on admission was 193 pg/mL (range, 133-401 pg/mL), and the level peaked within 3-7 days (median, 488 pg/mL; range, 239-1334 pg/mL). Platelet counts remained low, despite the elevated TPO levels. In patients with meningitis or meningococcemia, the median TPO level on admission was 112 pg/mL (range, <63-695 pg/mL), and the TPO level was not detectable within 48 h. Platelet counts for these patients remained within normal limits. Maximum IL-6 levels in patients with septicemia were observed on admission (median, 5317 pg/mL; range, 188-651,000 pg/mL) and increased earlier than TPO levels. In patients with fulminant septicemia, TPO level increases significantly whereas the level of circulating platelets does not.
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PMID:Fulminant meningococcal septicemia: dissociation between plasma thrombopoietin levels and platelet counts. 1077 Jul 23

Thrombopoietin is produced at a constant rate by the liver and kidney and is removed from the circulation upon binding and subsequent uptake via the Tpo receptor, c-Mpl, expressed by platelets and mega-karyocytes. Apart from uptake, this study shows that platelets can also function as a storage pool for Tpo. Upon stimulation with various platelet agonists, full-length biologically active Tpo was released by platelets. Platelet fractionation experiments indicated that this Tpo most likely is contained in the granules. When platelets were preincubated with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three- to fivefold increment in Tpo release was seen. whereas, the release of other granule proteins such as vWF-propeptide or serotonin remained unchanged. Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing Tpo into the platelet supernatant. Intravascular release of Tpo by platelets might occur in patients with massive platelet activation, as occurs in patients with disseminated intravascular coagulation. The Tpo concentration in these patients is elevated (p <0.01) and correlates with markers for thrombin generation, TAT complexes and F1+2(r(p)= 0.8 and 0.9; p <0.01). This suggests that the increment in Tpo concentration was attributed to Tpo release by activated platelets in vivo, which might be instrumental in subsequent stimulation of thrombocytopoiesis.
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PMID:Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis? 1089 50

Several lines of evidence suggest that coagulation may induce the release of thrombopoietin (TPO) into plasma and that TPO levels are higher in disseminated intravascular coagulation. Therefore we set out to illuminate the mechanism of TPO release in the setting of experimental endotoxemia, which induces activation of coagulation and platelets. Endotoxin (lipopolysachharide [LPS], 2 ng/kg) was infused into a total of 54 healthy men in two subsequent studies. Volunteers received infusions of unfractionated heparin, low-molecular-weight heparin, lepirudin, or placebo in a randomized, placebo-controlled fashion after bolus injection of LPS. TPO levels increased on average by 27% to 38% in all groups at 6 hours (P <.05 vs baseline), although all active drugs effectively blocked coagulation. Platelet counts dropped by about 15% at 1 hour after LPS infusion, recovered after 2 days, and exceeded baseline values by 8% to 18% after 7 days (P <.001 vs baseline for all groups). Yet lepirudin blunted the LPS-induced increase in circulating P-selectin by one half (P <.005 vs placebo), whereas both heparins did not diminish the increase in this platelet or endothelial activation marker as compared with placebo. Endotoxemia enhances TPO plasma levels independent of the degree of coagulation induction, which eventually results in increased platelet numbers. Of potential clinical interest is the observation that the direct thrombin inhibitor lepirudin, in contrast to heparins, mitigated LPS-induced platelet activation.
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PMID:Effects of anticoagulation on thrombopoietin release during endotoxemia. 1115 25

We measured Thrombopoietin (Tpo) levels in thrombocytopenic term and preterm babies with infection to investigate the relationship between thrombopietin levels and platelet counts. Sixteen preterm (27-34 weeks' gestational age) and 5 term neonates (38-41 weeks' gestational age) with the diagnosis of neonatal infection and thrombocytopenia (platelets <150 x 10(9)/L) but, without the evidence of disseminated intravascular coagulation, were prospectively enrolled in the study. Fifteen preterm (27-34 weeks' gestational age) and 9 term (38-40 weeks' gestational age) age-matched healthy neonates were enrolled in the study as control. Blood samples were obtained from each subject at the time when infection and thrombocytopenia were detected and stored until assay. Bacterial infection was confirmed by blood cultures in five patients and by tracheal cultures in five. Median Tpo levels of term controls were lower than those of preterm controls (62 pg/mL vs. 87 pg/mL) (p <0.05). Median Tpo levels of thrombocyopenic preterm patients were higher than the levels of healthy preterms (258 pg/mL vs. 87 pg/mL) (p <0.05). Similarly, median Tpo levels of sick terms were significantly higher than those of healthy term controls (209 pg/mL vs. 62 pg/mL) (p <0.001). There was not significant difference between the median Tpo levels of term and preterm babies with infection (258 pg/mL vs. 209 pg/mL) (p >0.05). There was no correlation between platelet counts and Tpo levels in both term and preterm groups. The results of our study show that healthy term and preterm babies have detectable levels of Tpo and preterm babies have higher Tpo levels than term infants. Although thrombocytopenic babies with infection have increased levels of Tpo, these levels are still lower than the levels of thrombocytopenic children/adult patients and there seems to be no correlation between platelet counts and thrombopoietin levels. So our observation of increased Tpo levels may still be inadequate for normal platelet production in this period. and this group of babies may also be candidates for the administration of recombinant human Tpo.
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PMID:Thrombopoietin levels of thrombocytopenic term and preterm newborns with infection. 1155 80

Although a significant minority of patients with cyanotic congenital heart disease (CCHD) are thrombocytopenic, the pathogenesis and prevalence have not been established. This study was designed to address these 2 issues. We included 105 patients with CCHD (60 men and 45 women; aged 21 to 54 years). Systemic arterial oxygen saturations were 69% to 78%. Hematocrits were 62% to 74% with normal iron indexes. In 26 of 105 patients (25%), platelet counts were <100x10(9)/L. The diagnosis was Eisenmenger syndrome in all 26 patients with thrombocytopenia. Platelet production was determined by flow cytometric reticulated platelet counts. Megakaryocyte mass was determined indirectly by thrombopoietin levels. Disseminated intravascular coagulation was based on prothrombin time, activated partial thromboplastin time, and D-dimers. Platelet activation was determined by levels of platelet factor 4 and beta thromboglobulin. Reference ranges were derived from 20 normal acyanotic controls. A reduction in absolute reticulated platelet counts implied decreased platelet production (p<0.001). Normal thrombopoietin levels implied normal megakaryocyte mass. Normal prothrombin time, activated partial thromboplastin time, and D-dimers excluded disseminated intravascular coagulation. Normal platelet factor 4 and beta thromboglobulin indicated absent or minimal platelet activation. Twenty-five percent of the patients with CCHD were thrombocytopenic because platelet production was decreased despite normal megakaryocyte mass. We hypothesized that right-to-left shunts deliver whole megakaryocytes into the system arterial circulation, bypassing the lungs where megakaryocytic cytoplasm is fragmented into platelets, thus reducing platelet production. In conclusion, platelet counts in CCHD appear to represent a continuum beginning with low normal counts and ending with thrombocytopenia.
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PMID:Pathogenesis of thrombocytopenia in cyanotic congenital heart disease. 1682 3

In hematological disorders, thrombocytopenia is frequently observed, and it is sometimes difficult to diagnose the underlying disease. In this symposium, laboratory tests for platelet abnormality were reviewed. Tests for platelet aggregation were reported to be important for the diagnosis of platelet dysfunction. Thrombocytopenia is caused by disseminated intravascular coagulation (DIC), thrombotic microangiopathy (TMA), heparin-induced thrombocytopenia (HIT), antiphospholipid syndrome (APS), idiopathic thrombocytopenic purpura (ITP), etc. As DIC is classified according to the degree of fibrinolysis, it was stated that the measurement of hemostatic molecular markers was further required. TMA is caused by abnormality of ADAMTS13, verotoxin, DIC, etc. HIT is diagnosed by anti-PF4 antibody, but its specificity is not high. Further investigation of TMA and HIT is required. APS is one of the most important diseases which cause thrombosis or abortion, suggesting that a differential diagnosis of APS is important. It was reported that diagnostic criteria of ITP have been established using a new antibody assay for platelets, immature platelet fractions, thrombopoietin, etc. In myeloproliferative disorders such as polycythemia vera and essential thrombocythemia, the mutation of JAK2 V617F was reported to be an important risk factor for thrombosis.
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PMID:[Summary of pathophysiology and diagnosis of patients with platelet abnormality]. 1952 56

Although platelet count is a good parameter for the diagnosis of disseminated intravascular coagulation (DIC), a single measurement of platelet is not enough to reflect the ongoing platelet consumption because of compensatory synthesis of circulating platelet number. Increased thrombopoiesis owing to peripheral destruction is expected in patients with DIC. Reticulated platelet, measured as immature platelet fraction (IPF), and plasma thrombopoietin (TPO) are markers of platelet production. We investigated the potential usefulness of circulating IPF and TPO in 222 patients suspected of having DIC. Both IPF and TPO levels were significantly increased in overt DIC patients and well correlated with DIC score. IPF also correlated with fibrin-related marker such as fibrinogen degradation product and D-dimer. Both IPF and TPO showed better mortality prediction than platelet count with the multivariate logistic regression and Kaplan-Meier survival analysis. These results suggest that IPF and TPO are new potential candidates to detect the severity of DIC and to predict DIC mortality.
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PMID:Prognostic value of immature platelet fraction and plasma thrombopoietin in disseminated intravascular coagulation. 1952 93


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