瑞典儿童和青少年静脉血栓形成的危险因素

Aim: To identify prothrombotic risk profiles in children and adolescents refer red to a regional coagulation centre in southern Sweden for a first thrombotic e vent. Methods: One hundred and twenty-eight consecutive children and adolescent s (newborn to 20 y) referred for evaluations of a first episode of venous thromb osis were investigated. Clinical data were collected retrospectively, and the fo llowing variables were investigated: protein C, protein S, antithrombin; resista nce to activated protein C; the genotypes FV-G1691A, F II-G20210A,MTHFRC677T, MTHFR-A1298C; coagulation factors VIII and XI. Results: 104/128 subjects (81%) had identifiable acquired risk factors, most often indwelling catheters and hor mone therapy. Predisposing genetic factors related to thromboembolic events were revealed in 53/83 (64%) of subjects who agreed to followup blood sampling, and 17/83 (20%) had two or more inherited risk factors. Combinations of genetic an d acquired risk factors were identified in 45/83 (54%) of the subjects, and 77/ 83 (93%) had at least one such risk factor. Both sexes had one peak in frequenc y at less than 1 y of age and then an increase during adolescence, more in femal es than in males. Plasma values for coagulation factors VIII and XI were age app ropriate and showed a normal Gaussian distribution. Conclusion: This study ident ified prothrombotic risk profiles in almost all children and adolescents with ve nous thrombosis,which underlines the importance of careful evaluation of genetic and acquired risk factors.

Checkmate to liver biopsy in chronic hepatitis C?

Liver biopsy (LB) has traditionally been considered the gold standard for pretreatment evaluation of liver fibrosis in patients with chronic hepatitis C (CHC). However, LB is an invasive procedure with several shortcomings (intra-and interobserver variability of histopathological interpretation, sampling errors, high cost) and the risk of rare but potentially life-threatening complications. In addition, LB is poorly accepted by patients and it is not suitable for repeated evaluation. Further-more, the prevalence of CHC makes LB unrealistic to be performed in all patients with this disease who are candidates for antiviral therapy. The above-mentioned drawbacks of LB have led to the development of non-invasive methods for the assessment of liver fibrosis. Several noninvasive methods, ranging from serum marker assays to advanced imaging techniques, have proved to be excellent tools for the evaluation of liver fibrosis in patients with CHC, whereas the value of LB as a gold standard for staging fibrosis prior to antiviral therapy has become questionable for clinicians. Despite significant resistance from those in favor of LB, noninvasive methods for pretreatment assessment of liver fibrosis in patients with CHC have become part of routine clinical practice. With protease inhibitors-based triple therapy already available and substantial improvement in sustained virological response, the time has come to move forward to noninvasiveness, with no risks for the patient and, thus, no need for LB in the assessment of liver fibrosis in the decision making for antiviral therapy in CHC.

ANTI-HUMAN PLATELET TETRASPANIN(CD9)MONOCLONAL ANTIBODIES INDUCE PLATELET INTEGRIN αbβ3 ACTIVATION IN A Fc RECEPTOR INDEPENDENT FASHION

This study characterized the activation of platelet integrin α bβ3 induced by two anti human platelet tetraspanin monoclonal antibodies(mAbs),HI117 and SJ9A4. Methods.Using 125 I labeled human fibrinogen(Fg),specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured as indication of activation of platelet integrin αbβ3 by the two mAbs. Results.HI117 and SJ9A4(10μg/ml and 20μg/ml) induced evident specific Fg binding to human platelets,suggesting that the two mAbs evoked activation of platelet integrin αbβ3.Further study indicated that HI117 and SJ9A4 induced integrin αⅡbβ3 activation independent of platelet Fc receptors, and that HI117 and SJ9A4 induced integrin αbβ3 activation was inhibited by sphingosing, aspirin, apyrase, and/or PGI2. Conclusion.The anti platelet tetraspanin(CD9)mAbs,HI117 and SJ9A4, can induce platelet integrin αⅡbβ3 activation independent of Fc receptors.Three signaling pathways,i.e.thromboxane,secreted ADP, and cAMP pathways may be involved in the process,with protein kinase C activation presumably being the common step of the three pathways.

Alpha 1-antitrypsin and alpha 1-acid glycoprotein reduce the sensitivity of human dermal fibroblast to endotoxin

Objective: To test the hypothesis that acute phase reactants, such as alpha 1-antitrypsin and alpha 1-acid glycoprotein, could protect mammalian cells from further damage. Methods: Human dermal fibroblasts (5×10 4) were cultured with DMEM plus 10% FBS at 37℃ in a 5% CO 2 incubator. Different doses of LPS (lipopolysaccharide) and/or acute phase reactants were added. After 24 hours, the cultured supernatant was aspirated, the cells were washed, fixed and stained by methylene blue. The unbound stain was washed off. The stained cells were solubilized in 0.1 ml of 1% Triton X-100. The absorbance of each well was measured using an ELISA spectrophotometer. The concentration of LPS which decreased the absorbance to 70% of the control (LPS-free) cultures was defined as LD 30. Results: In order to achieve LD 30 in the presence of acute phase proteins, it was necessary to alter the LPS concentrations. The LD 30 of LPS treated with 0, 0.5, 2, 10 mg/ml antitrypsin and 0, 0.5, 2, 10 mg/ml glycoprotein was 5.4, 6.5, 7.6, 14.2 mg/ml and 5.2, 5.9, 6.9, 10.5 mg/ml, respectively. Statistically, with the treatment of more than 2 mg/ml antitrypsin or glycoprotein, LD 30 increased significantly. Conclusions: Our data show that fibroblasts are susceptible to the direct toxicity of LPS. Alpha 1-antitrypsin and alpha 1-acid glycoprotein can reduce the toxicity and/or increase the tolerance of mammalian cells to LPS.

Comparison of fondaparinux sodium and low molecular weight heparin in the treatment of hypercoagulability secondary to traumatic infection

Purpose： To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods： Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F （18 patients）, the patients were treated with fondaparinux sodium, 2.5 rag, 1/d for 11 d. In group L （18 patients）, the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome （MODS） and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin Ⅲ were measured by the coagulation analyzer. Results： The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L （p 〈 0.05）. Antithrombin Ⅲ got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and llth d （p 〈 0.05）. Fibrinogen levels were gradually increased, and there was no significant difference between two groups （p 〉 0.05）. D-dimer was significantly decreased after anticoagulant therapy for 5 d （p 〈 0.01 ）, and there were significant differences between two groups on the 5th d and 7th d （p 〈 0.05）. It showed no significant difference on the llth d （p 〉 0.05）. Conclusion： Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.