suggested algorithm for using serum biomarkers for the diagnosis of liver fibrosis in chronic hepatitis C infection

Hepatitis C virus infection [HCV] is endemic in Egypt. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in chronic hepatitis C patients. However, it is invasive, associated with sampling error and poses potential complications. A non-invasive alternative is needed. This assessed the accuracy of certain biochemical markers and ultaronography in predicting the stage of fibrosis in chronic hepatitis C patients. Sixty five patients with chronic HCV were enrolled. Ultrasonographic examination, complete blood count and liver function tests were done. Serum levels of hyaluronic acid [HA] and YKL-40 [a 40-kDa glycoprotein produced by stellate cells] were determined. Liver biopsy was done. Fibrosis was correlated with biochemical markers and ultrasonographic findings. Histopathological examination showed that 39 patients [60%] had F1, nine [14%] had F2, 17 [26%] had F3 and none had F0 or F4 scores. A value of alanine aminotransferase [ALT] index <0.38, HA <9.7 ng - ml[-1] or portal vein [PV] cross-sectional area <25.8 mm[2] excluded significant fibroses [>/= F2]. A value of aspartate aminotransferase [AST] + ALT<39.5 or ratio of AST index to the platelet count [APRI] <0.235 or HA x 100 per platelet [Plt] < 9.534 excluded the presence of advanced fibrosis with 100% negative predictive value [NPV]. Using these values, advanced fibrosis could be excluded in 72% of our patients. An APRI value of >/= 1.1 can diagnose advanced fibrosis with 100% positive predictive value [PPV] in 10%of our patients. Hence, only 18% of our patients in whom liver biopsy was recommended were not classified by these parameters. YKL-40 did not help in the diagnosis of advanced fibrosis. Applying a simple algorithm based on ALT, AST, platelet count, PV cross-sectional area, in addition to HA level may eliminate the need for liver biopsies in more than 80% of chronic HCV patients

Hemostatic markers of coagulopathy in acute promyelocytic leukemia

Hemostatic disorders are leading causes of death in patients with acute myeloid leukemia [AML] and particularly those with acute prom yelocytic leukemia [APL]. A contribution of fibrinolytic mechanisms has been claimed in the patho genesis of APL coagulopathy but investigations of the fibrinolytic activity of prom yelocytes have yielded conflicting results, sometimes based on reports of scattered [single] cases. The aim of this work is to study the changes of the different markers of thrombin generation and fibrinolysis in patients with APL and those with other AML subtypes [non APL-A ML], and to clarify the patho genesis of coagulopathy in patients with APL compard with those with non APL -A ML. The study included blood samples of 15 patients with APL and 25 patients with non APL-A ML, as well as 20 apparently healthy children with matched age and sex as a control group. Cases and controls were all subjected to the following investigations: pro thrombin concentration [PC], activated partial thromboplastin time [APTT], thrombin-anti thrombin complex [TAT], prothrombin fragment 1+2 [PF1+2], fibrinopeptide A [FPA], D-dimer, fibrinogen level, plasminogen activator inhibitor [PAI] and alpha 2-antiplasmin [alpha 2-AP]. As regards the markers of thrombosis PC was significantly lower in APL and AML in comparison to controls and in the same time it was significantly lower in APL in comparison to AML. PT, APTT, TAT, PF1+2, FPA and D-dimer levels in plasma of both APL and AML were significantly higher than controls and also it was found that these markers were significantly higher in APL than AML. About the fibrinolytic markers, fibrinogen was significantly lower in the cases of APL and AML than controls and it was found to be significantly lower in APL than AML. PAI and alpha 2-AP were significantly lower in APL and AML than controls but there was no significant difference between APL and AML. In the APL group a positive correlation was found between bone marrow promyelocyte% and D-dimer [r= 0.718, P< 0.003**] and between TAT and prepheral absolute promyelocyte [x10/L] [r=0.677, P< 0.006**]. In conclusion, acute myeloid leukemia in children, either APL or non-APL causes some changes in hemostatic mechanisms leading to acute DIC which was proved by the following tests: * Procoagulant activation which is proved by prolongation of APTT, PT, increased TAT, prothrombin fragment 1+2, fibrinopeptide A plasma levels as well as decreased prothrombin concentration and fibrinogen levels. * Fibrinolytic activation proved by decreased plasminogen activator inhibitor, alpha 2-antiplasmin plasma levels as well as increased plasma level of D-dimer which is a marker of plasmin activation. * Inhibitor consumption, proved by the study showed that the aforementioned laboratorial abnormalities were aggravated among cases with APL than those with non-APL-AML So DIC can be detected before bleeding