Cross-sectional Study on Prevalence of Coagulation Factors Deficiency in Children Attending Assiut University Children Hospital ( a One Year Study)

The most frequent inherited coagulation disorders are haemophilia A and B, due to the deficiency of factor VIII and IX. Haemophilia A and B are clinically indistinguishable from each other and occur in mild, moderate and severe forms (with plasma factor levels of 6-30%, 2-5% and 1% or less respectively). Inherited as X-linked traits, haemophilia A and B are prevalent in the general population of approximately 1 in 10 000 and 1 in 50 000, with no significant racial difference. Other deficiencies of coagulation factors that cause a bleeding disorder, such as afibrinogenaemia, hypoprothrombinaemia, deficiencies of factors V and combined factor V and VIII, VII, X, XI and XIII are inherited as autosomal recessive traits and are generally much rarer than the haemophilias, wich are prevalent in the general population varying between 1 in 500 000 and 1 in 2 000 000. As a consequence of the rarity of these deficiencies, which are expressed clinically only in homozygotes or compound heterozygotes, the type and severity of symptoms, the underlying molecular defects and the actual management of bleeding episodes are not well established as for haemophilia A and B.

Inherited deficiencies are described for all of the known coagulation factors. In addition, there are people with an abnormal bleeding tendency for whom no cause has yet been identified. The concept of overall hemostatic balance is increasingly recognized, that it is not solely the level of a single factor that matters, but the overall control of hemostasis that may determine the bleeding risk. This may explain why the bleeding risk cannot be predicted from a single factor level alone as in, for example, factor VII or factor XI deficiency in particular. The rare factor deficiencies have several common properties: they are inherited in an autosomal manner, although bleeding symptoms have been described in heterozygous partially deficient individuals. These rare deficiencies are more common in populations and countries where cousin marriages are frequent and therefore there is considerable geographic variation in the incidence, in contrast to hemophilia and von Willebrand disease types I or II which occur with the same incidence in different countries.

Clinical manifestations:

In their most severe form, the deficiencies present with serious hemorrhage in the neonatal period; intracranial hemorrhage is a significant presentation of severe deficiency of FXIII, factor VII, factor X or fibrinogen (afibrinogenaemia). Bleeding from the umbilical stump can occur with any of these disorders as it can with severe hemophilia. It is important for caregivers to be aware that any unusual bleeding manifestation must prompt appropriate investigation so that diagnosis is not delayed, and appropriate replacement therapy is given as soon as possible. A history of consanguinity of the parents and their ethnic origin are relevant.

Diagnosis should be straightforward but there are pitfalls in testing. Difficult venepunctures in infants in an emergency may give erroneous results due to tissue factor contamination. Coagulation samples do not travel well, so if plasma samples are sent to another laboratory they must be properly transported, generally frozen and sent on dry ice. It may be helpful to test both parents because, apart from the two truly recessive disorders detailed below, the parents will usually have evidence of partial deficiency. It is important for each laboratory to establish its own normal range, and to ensure that the possibility of genetic carriage of a disorder is fully discussed with parents irrespective of the blood results as the birth of more children with a serious bleeding disorder is a great emotional and social burden especially in countries and communities with poor health resources.