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)

A 63-year-old woman was diagnosed as having blue rubber bleb nevus syndrome (BRBNS) with disseminated intravascular coagulation (DIC). Hematological data showed typical DIC: PT 13.2 sec, activated PTT 55.3 sec, fibrinogen 20 mg/100 ml, FDP-E 928 ng/ml, D-dimer 3,477 ng/ml, platelet count 25 x 10(3)/microliters. Although hypofibrinogenemia was successfully controlled by the continuous infusion of heparin, 10,000 units/day, thrombocytopenia has continued. Based on shortened platelet life span, high level of platelet associated IgG, and increased number of megakaryocyte in the bone marrow, the thrombocytopenia was thought to be due to antiplatelet antibody. Her platelet count returned to normal after intravenous infusion of high-dose gamma globulin (IVIg, Sandoz) at the dose of 400 mg/kg for 2-5 days, while corticosteroid, Gabexate mesilate, synthetic thrombin inhibitor MD-805, urinastatin and warfarin had no effect. Thus, DIC or thrombocytopenia may become a serious complication in some patients with BRBNS and IVIg may be useful for correcting thrombocytopenia in the patient.
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PMID:Blue rubber bleb nevus syndrome with disseminated intravascular coagulation and thrombocytopenia: successful treatment with high-dose intravenous gammaglobulin. 204 21

To assess immune responses to malaria-induced thrombocytopenia, an haematologic and immunologic study was performed on 25 patients with imported malaria upon admission and 8 days after treatment. Thrombocytopenia (150 x 10(9)/litre) was detected in 19 cases (P. falciparum: 11 cases, P. ovale: 6 cases, P. vivax: 2 cases). No laboratory evidence of disseminated intravascular coagulation impairment was found in any of the patients. Bone marrow examination performed in 9 cases showed no abnormality in the megakaryocyte series. Platelet count was independent of circulating parasite levels (r = 0.27) and inversely related to the number of antibody binding sites (ABS) on platelets (r = -0.6, p. less than 0.01). The indirect Coombs test (r = -0.54; p less than 0.01) and IgG and IgE levels (p less than 0.02) gave similar findings. A statistical correlation was observed between the level of circulating immune complex and the number of ABS (r = 0.525, p less than 0.01). Thus malaria-induced thrombocytopenia seems to mainly involve IgG type antiplatelet antibody activity. Although they may be implicated in the binding of antibodies to platelets, circulating immune complexes do not appear to mediate thrombocytopenia.
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PMID:[Platelet antibody activity in malaria thrombocytopenia]. 223 82

We performed a 1-year prospective study of 807 consecutive infants admitted to a regional neonatal intensive care unit to determine the frequency, natural history, mechanism(s), and cause of thrombocytopenia. Thrombocytopenia developed in 22% of the infants. The platelet count nadir usually occurred by day 4 and resolved by day 10. Possible mechanisms responsible for the thrombocytopenia were assessed by comparing mean platelet volume, platelet-associated IgG (PAIgG), and coagulation test results in those infants whose platelet count fell below 100 X 10(9)/L (n = 97) with values in age-, weight-, and disease-matched control infants without thrombocytopenia (n = 80). In some thrombocytopenic infants, 111In-labeled-platelet survival, an estimate of megakaryocyte number in bone marrow biopsy specimens obtained at autopsy, and response to platelet infusions were also assessed. The thrombocytopenia was caused by increased platelet destruction, as shown by short 111In-labeled-platelet survival (12 to 128 hours), a rising mean platelet volume during the first week of life, normal numbers of megakaryocytes, and a poorer than predicted response to platelet infusions. A potential cause for the thrombocytopenia could be found in the majority of infants: 52% had elevated levels of PAIgG, 21% had laboratory evidence of disseminated intravascular coagulation, and 12% had had exchange transfusions. In contrast, the control infants had normal coagulation assay results, and only 15% had elevated levels of PAIgG. Birth asphyxia was identified as an associated risk factor for thrombocytopenia. This study demonstrates that transient, destructive thrombocytopenia develops in a large proportion (22%) of infants admitted to a neonatal intensive care unit, and that birth asphyxia is an important risk factor.
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PMID:Frequency and mechanism of neonatal thrombocytopenia. 370 23

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

The recent advances in the psychoneuroimmunology have suggested that the hematopoiesis may be under a neuroendocrine regulation, mainly exerted by the pineal gland. In particular, melatonin (MLT), which is the main pineal hormone, has appeared to stimulate platelet generation, probably by promoting the megakaryocyte fragmentation and modulating the cytokine network involved in platelet production. On this basis, we have evaluated the effect of pharmacological doses of MLT on platelet number in patients with persistent thrombocytopenia due to different causes. The study included 200 patients, who were randomized to receive supportive care alone or MLT at 20 mg/day orally in the evening, for al least 1 month. No MLT-related toxicity occured. Platelet mean number rapidly and significantly increased in response to MLT, and a normalization of platelet number was achieved on MLT therapy in 71/98 (72%) patients. The least responsive form of thrombocytopenia was DIC. This study shows that the pineal hormone MLT may represent a well tolerable and effective therapy of thrombocytopenia due to different pathogenetic mechanisms.
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PMID:Growth Factors: Thrombopoietic Property of the Pineal Hormone Melatonin. 1139 74

Platelets are anucleate cells that fragment from mature megakaryocytes and play an essential role in thrombosis and hemostasis. Platelets are among the first cell types to be recruited to an injured blood vessel, assisting in endothelial repair. Platelet hyperactivation contributes to the development of atherosclerosis, myocardial infarction, and ischemia of peripheral limbs. A fall in platelet counts, due to a variety of conditions, including disseminated intravascular coagulation, chemotherapy or genetic disorders, may lead, in most severe cases, to death from hemorrhage. This review focuses on the late stages of megakaryocyte differentiation and platelet fragmentation, including associated cytoskeletal changes, and on the importance of apoptotic events for these processes. Studies point to a unique biological system in which programmed cell death may be linked with biogenesis of new cells.
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PMID:Role of apoptotic processes in platelet biogenesis. 1464 46

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

Triggering receptor expressed on myeloid cells-like (TREM-like) transcript-1 (TLT-1), a type 1 single Ig domain orphan receptor specific to platelet and megakaryocyte alpha-granules, relocates to the platelet surface upon platelet stimulation. We found here that patients diagnosed with sepsis, in contrast to healthy individuals, had substantial levels of soluble TLT-1 (sTLT-1) in their plasma that correlated with the presence of disseminated intravascular coagulation. sTLT-1 bound to fibrinogen and augmented platelet aggregation in vitro. Furthermore, the cytoplasmic domain of TLT-1 could also bind ezrin/radixin/moesin family proteins, suggesting its ability to link fibrinogen to the platelet cytoskeleton. Accordingly, platelets of Treml1-/- mice failed to aggregate efficiently, extending tail-bleeding times. Lipopolysaccharide-treated Treml1-/- mice developed higher plasma levels of TNF and D-dimers than wild-type mice and were more likely to succumb during challenge. Finally, Treml1-/- mice were predisposed to hemorrhage associated with localized inflammatory lesions. Taken together, our findings suggest that TLT-1 plays a protective role during inflammation by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. Therefore, therapeutic modulation of TLT-1-mediated effects may provide clinical benefit to patients with hypercoagulatory conditions, including those associated with inflammation.
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PMID:TREM-like transcript-1 protects against inflammation-associated hemorrhage by facilitating platelet aggregation in mice and humans. 1943 12