Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII-X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K-deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two-stage (TGT) method than by the one-stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K-deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.
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PMID:The multiple coagulopathies of biliary atresia. 669 16

Solute transport and alterations in complement and clotting induced by a new high-flux cellulose acetate membrane (CA-HF800-E, Diaphan) were compared with those for cellulose triacetate (CTA) and polysulphone in a cross-over clinical study. The membranes are similar in their small-molecule removal. Serum beta 2-microglobulin decreased with all membranes but the decrease was independent of membrane type. Associated with beta 2-microglobulin removal was a protein loss which averaged 2636 mg for Diaphan, 4937 mg for CTA, and 2500 mg for polysulphone. Albumin presence in the dialysate was less than the limit of detection (5 mg/l) but for each of the membranes, occasional readings above the limit of detection were noted. C3a generation for Diaphan is comparable with that for CTA and polysulphone, but differed for C5a and neutropenia. A highly significant correlation of the area under the concentration time curve of the two complement components was noted for the cellulose based membranes (r = 0.875, P = 0.0002 for Diaphan, r = 0.823, P = 0.006 for CTA) this relationship was less marked for polysulphone (r = 0.396, P = 0.29). Induction of clotting characterized by the thrombin-antithrombin III (TAT) complex were similar for the three membranes, as were changes in platelet counts. Our findings indicate that while it is possible to modify cellulose to produce a membrane whose solute transport and biocompatibility is similar to synthetic membranes such as polysulphone, the structural modifications induce considerable differences in the amount of protein lost.
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PMID:Clinical comparison of high-flux cellulose acetate and synthetic membranes. 817 78

Septic shock and multiple organ failure may be associated with coagulation activation, disseminated fibrin formation, and consumption of coagulation inhibitors such as antithrombin III. We have evaluated prospectively coagulation measurements in patients with severe chemotherapy-induced neutropenia. This group of patients was chosen because of their high risk of developing severe septic complications, thus allowing serial prospective coagulation testing before and during evolving sepsis or septic shock. Sixty-two patients with febrile infectious events were accrued to the study. Of these, 13 patients progressed to severe sepsis and 13 additional patients to septic shock as defined according to standard diagnostic criteria. At the onset of fever, factor (F) VIIa activity, FVII antigen and antithrombin III (AT III) activity decreased from normal baseline levels and were significantly lower in the group of patients who progressed to septic shock compared with those that developed severe sepsis (medians: 0.3 v 1.4 ng/mL, 21 v 86 U/dL and 45% v 95%; P < .001). The decrease of these measurements in septic shock was accompanied by an increase in prothrombin fragment 1+2 (median: 3.6 v 1.4 nmol/L; P = .05), a marker of thrombin generation. These differences were sustained throughout the septic episode (P < .0001). FVIIa and AT III levels of < 0.8 ng/mL and < 70%, respectively, at onset of fever predicted a lethal outcome with a sensitivity of 100% and 85%, and a specificity of 75% and 85%, respectively. In contrast, FXIIa-alpha antigen levels were not different between groups at onset of fever but increased modestly during the course of septic shock (P = .001). Thus, septic shock in neutropenic patients is associated with increased thrombin generation. Furthermore, both FVIIa and AT III measurements are sensitive markers of an unfavorable prognosis.
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PMID:Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. 916 Jul 2

Haematological changes in the septic patient are, primarily, neutropenia or neutrophilia, thrombocytopenia and disseminated intravascular coagulation (DIC). Thrombocytopenia frequently arises from DIC although inhibition of thrombopoiesis or immunological platelet damage also occur. DIC contributes to bleeding and microvascular thrombosis, leading to multiple organ failure. Tissue factor release, primarily mediated by tumour necrosis factor, activates the clotting system; fibrinolysis is initially activated, but later becomes inhibited by the release of plasminogen-activator inhibitor (PAI-1), further fostering multiple organ failure. Most septic patients have compensated, chronic DIC, detectable by assays of molecular markers; the earliest signs are already found during the systemic inflammatory response syndrome. Compensated DIC later becomes decompensated with rapid consumption of factors including inhibitors such as antithrombin III (AT III) and proteins C and S. AT III concentrations of < 60-70% of the normal values predict outcome. Management of DIC must address the underlying disease, interrupt the activated haemostasis system and replace consumed coagulation constituents. Interruption of haemostasis with heparin may be attempted, but bleeding may worsen. Administration of a natural anticoagulant, such as AT III, may arrest clotting without concomitant risk of bleeding. In several animal models of DIC, AT III concentrates shortened the duration of DIC and reduced multiple organ failure and mortality. Similar benefits have been reported in early studies of patients with DIC, especially in the absence of sepsis. Studies are under way to determine whether outcome will improve if patients with sepsis are treated before the development of shock and plasma AT III concentrations are maintained at 100-150% of normal.
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PMID:The haematological manifestations of sepsis. 951 Oct 82

A prospective crossover clinical study evaluated solute removal and biocompatibility of a tailored, hydrophobic-hydrophilic microdomain structure produced from a blend of polyamide, polyarylethersulfone, and polyvinylpyrrolidone (Polyflux) compared with Fresenius Polysulfone in dialyzers of similar surface area. The clearance of small molecules (urea, creatinine, and phosphate) for both membranes was comparable. Plasma levels of beta2 microglobulin were reduced at the end of treatment with both membranes (49.8% of pretreatment values for Polyflux; 45.9%, Fresenius Polysulfone) and was associated with the recovery of 207 +/- 84 mg of beta2 microglobulin from the dialyzing fluid for Polyflux compared with 147 +/- 29 for Fresenius Polysulfone (p = 0.12). The dialyzing fluid also contained 7,758 mg of protein when using Polyflux compared with 7,793 mg using Fresenius Polysulfone (standard error of difference for any pair was 511 mg). No albumin was present in the dialysis fluid for either membrane. Neutropenia, platelet adhesion to the membrane, and complement activation characterized by C3a, C5a, and SC5b-9 generation were slight and independent of membrane type. Membrane thrombus generating potential measured by thrombin:antithrombin III were also similar. These results indicate that the tailored, hydrophobic-hydrophilic microdomain structure of the membrane results in a favorable biocompatibility profile and clinically acceptable solute removal similar to the widely used Fresenius Polysulfone membrane.
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PMID:A microdomain-structured synthetic high-flux hollow-fiber membrane for renal replacement therapy. 1066 21