In this study we have tried to evaluate the effect of sepsis on the physiologic inhibition system of coagulation in neonates. We should expect the effect of sepsis and its severity and perform the necessary laboratory investigations for coagulation including antithrombin III, protein C and protein S levels to help prevent thromboembolic accidents in neonates with sepsis, including disseminated intravascular coagulation, necrotizing enterocolitis and intracranial hemorrhage. Based on the findings of our study and the results of the other studies, we are in agreement that protein C is a very useful biomarker in severe sepsis, and it is a possible tool for monitoring treatment with activated protein C. We also encourage further placebo-controlled clinical trials to investigate the role of activated protein C and antithrombin III in severe neonatal sepsis and especially in the states before disseminated intravascular coagulation and the disseminated intravascular coagulation states, on the condition that they are guided by the experience and recommendations gained from the PROWESS, ENHANCE, and RESOLVE clinical trials. Protein C might be more effective if dosed according to protein C levels rather according to weight. Furthermore, we encourage future research on activated protein C mutants, which are anticipated to appear very soon because they can reduce some side effects associated with the use of recombinant human activated protein C, such as intracranial hemorrhage and bleeding tendencies, because they have reduced anticoagulant activity while retaining the cytoprotective effects.

The aim of this study was to assess the level of hepcidin in hereditary chronic hemolytic anemias and to correlate the serum hepcidin levels to the need for blood transfusions (frequency of blood transfusions and the serum ferritin level). Seventy pediatric patients with hereditary chronic hemolytic anemias, attending to hematology clinics of Cairo University and Misr University for Science and Technology (MUST) hospitals were the subjects of this study [53 patients with β-thalassemia major (β-TM), 10 patients with β-thalassemia intermedia (β-TI), four patients with congenital spherocytosis and three patients with sickle cell disease) (38 males and 32 females)]; their ages ranged from 1-14 years. Seventy normal children, age- and sex-matched, served as the control group. The results of this study revealed decreased hepcidin levels in patients (all types of congenital chronic hemolytic anemias) [mean ± SD (standard deviation) = 22.9 ± 6.0] compared to controls (mean ± SD = 132.4 ± 16.7) with highly significant statistical difference in between. Hepcidin levels were higher in β-TM patients (mean ± SD = 23.7 ± 6.2) than in β-TI patients (mean ± SD = 21.8 ± 4.0), the hepcidin to ferritin ratio was significantly less than one. In β-TM patients, the mean ± SD was 0.03 ± 0.004, and in β-TI patients the mean ± SD = 0.025 ± 0.002, with highly significant statistical difference with hepcidin-to-ferritin ratios in controls being mean ± SD = 2.3 ± 0.7. Hepcidin and hepcidin/ferritin ratios can be used as good markers of hemolytic anemia and iron overload as they have very high sensitivity (99.0 and 99.0%, respectively) and very high specificity (98.0 and 97.0%, respectively). Our findings highlight the potential usefulness of hepcidin measurement as a diagnostic tool. The use of hepcidin as an adjuvant therapy with iron chelators is important as it has a vital role in combating hemosidrosis.

5168 Background: Thalassemia is the most common genetic disorder in Egypt composes a major health problem with an estimated carrier rate of 5. 3%-9%. Registered cases in large centers in Egypt September 2007 were 9912 cases, and in Cairo University hematology clinic were alone 2597 cases. Patients with thalassemia major requiring regular blood transfusions accumulate iron that is toxic to the heart, liver, and endocrine systems. Hepcidin, is a 25 amino-acid peptide hormone synthesized in the liver is a key regulator of iron homeostasis. Recently, hepcidin was reported to bind to the trans-membrane iron exporter “ferroportin” which is present on macrophages, the basolateral site of entrecotes, and in hepatocytes. Hepcidin induces the internalization and degradation of ferroportin. liver hepcidin controls reduction of iron uptake and release. There is also evidence for local production of hepcidin by macrophages, fat cells and cardiomyocytes. Thus, hepcidin is involved in different regulatory mechanisms that control iron imbalance. Objective: The aim of this study is to assess the level of serum hepcidin in hereditary chronic hemolytic anemias and correlate its level to the need for blood transfusion (frequency of blood transfusion) and the serum ferritin level. Study design: Seventy pediatric patients with hereditary chronic hemolytic anemias were the subjects of this study; 53 thalassemia major (TM), 10 thalassemia intermedia (TI), 4 congenital spherocytosis(CS) and 3 sickle cell disease(SCD) patients, mean age 7. 8+3. 9 years (range 1–14). Seventy normal children age and sex matched were studied as controls. Serum hepcidin was measured in all patients and controls by ELISA technique. Serum Hepcidin was measured in all patients one day pre transfusion and in 20 TM patients 3–4 days post transfusion. Results: Significant decrease in serum hepcidin levels in all patients compared to controls (mean 22. 9 ±6 vs 132. 4±16. 7 ng/ml, P <0. 001). Hepcidin levels were higher in TM (mean 23. 7±6. 2 ng/ml) than in TI patients (mean =21. 8±4 ng/ml) (Fig 1). The median number of blood transfusions in TM was 70/year (range18–120), in TI the median was 7/year (range 6–17). A 280% increase of serum hepcidin levels of pre transfusion levels was found post transfusion in TM patients (n=20). A significant positive correlation was found between serum hepcidin and frequency of blood transfusion (r=0. 4, p<0. 001), serum ferritin (r=0. 28, p <0. 05) and CRP (r=0. 4, p<0. 05). The hepcidin to ferritin ratio a marker of the hepcidin expression relative to the degree of iron burden was significantly less than one in TM and TI patients (0. 03± 0. 004 and 0. 025± 0. 002 respectively) and far from the level in normal controls (mean 2. 3±0. 7, P<0. 001). Hepcidin and hepcidin/ferritin ratio as markers of iron overload in our patients showed high sensitivity and specificity (99% and 98%, 97% respectively) (table 1, fig 2). Discussion and Conclusion: This study examined serum hepcidin and hepcidin/ferritin ratio in hereditary chronic hemolytic anemias, significant low levels were detected. The increase in serum hepcidin level in TM than TI and its marked increase post transfusion in TM patients can be explained by the positive correlation between frequency of blood transfusion and serum hepcidin level in this study. Hepcidin and hepcidin/ferritin ratio can be used as valid markers of iron overload in hereditary chronic hemolytic anemias. Evidence from laboratories around the world have converged on hepcidin as a rational therapeutic agent for treatment of B-thalassemia. Treatment with a hepcidin agonist, at a carefully defined dose, has the potential to ameliorate several aspects of TI due to the specific reduction of iron overload and splenomegaly. Testing this approach provides an exciting opportunity to improve the current management strategies for these diseases, and our study agrees with this approach. Disclosures: No relevant conflicts of interest to declare.