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.

Hemophilia A (HA) is the most common severe bleeding disorder in humans, affecting one in 5,000 male births. In severe HA, intron 22 inversion of F8 is the most prevalent mutation, accounting for 40-50% of all mutations; however, little is known about the disease-causing mutations among Egyptian hemophiliacs. We aimed at genotyping all possible known DNA rearrangements of intron 22 of F8 in Egyptian HA patients. Peripheral blood samples were collected from 30 Egyptian HA patients (13 severe, ten moderate, and seven mild cases). Genotyping of F8 intron 22 rearrangements was performed by inverse-shifting PCR (IS-PCR). Our study revealed that seven patients (23.3%) had inversion 22, three patients (10%) had deletion 22, and 20 patients (66.7%) carried the wild-type allele. No intron 22 duplication was detected. The relative proportion of inversion 22-type 1 to inversion 22-type 2 was 85.7% and 14.3%, respectively, whereas the relative proportion of deletion 22-type 1 to deletion 22-type 2 was 33.3% and 66.7%, respectively. A statistically highly significant relation was found between disease severity and F8 intron 22 rearrangements (p = 0.008). Among severe cases, 46.1% had inversion 22, 23.1% had deletion 22, and 30.8% carried the wild-type allele. We conclude that F8 intron 22 inversion/deletion is responsible for about one third of disease-causing mutations among Egyptian hemophiliacs and for nearly 70% in severe cases. In addition, F8 intron 22 inversion/deletion by IS-PCR has proven to be a rapid and robust technique and might be the recommended tool for genetic analysis of HA patients specially with severe cases in developing countries.

In this study, we evaluated the effect of asphyxia on the physiologic inhibition system of coagulation in neonates. Care providers should suspect hypoxia resulting from any obstructed labor and perform the necessary laboratory investigations for coagulation, including antithrombin III, protein C, and protein S levels, to help prevent thromboembolic accidents in asphyxiated neonates, including disseminated intravascular coagulation, necrotizing enterocolitis, and intracranial hemorrhage. Based on the development of antithrombin III and protein C concentrates, which are commercially available, require minimal monitoring, and have very few side effects, the time is ripe for evaluation of optimal treatment for thromboembolic accidents after neonatal asphyxia. This could be even more important if successful neuroprotectant strategies are also developed.

This study provides a relevant contribution to our understanding of the anthropological and historical background of the population in Egypt where Benin haplotype is the commonest β globin gene haplotype and homozygous Benin/Benin is associated with higher stroke risk than other haplotypes.