Comprehensive Pediatric Care of Rare Bleeding Disorders

Muriel Giansily-Blaizot; Jean-François Schved


Pediatr Health. 2010;4(2):209-217. 

In This Article

Abstract and Introduction


Although less common than hemophilia or von Willebrand disease, inherited rare bleeding disorders, comprising afibrinogenemia and deficiencies in factors II, V, VII, X, XI, XIII or V plus VIII combined, or in vitamin K-dependent coagulation factors, may lead to severe bleeding episodes such as recurrent hemarthroses and neonatal intracranial or gastrointestinal hemorrhage. Consanguinity significantly increases the risk of the occurrence of all rare bleeding disorders that are associated with an autosomal recessive pattern of inheritance. Each of the disorders is characterized by a wide interindividual variation in clinical phenotype and a large mutational spectrum with no clear correlation between the phenotype and genotype. Replacement therapy relies on specific molecules or concentrates (afibrinogenemia, factor VII, XI and XIII deficiencies), on a mixture of different concentrates that are otherwise known as a prothrombin complex, which contains factors II, VII, IX and X, or on fresh frozen plasma. International consensus guidelines for treatment modalities are progressing; however, guidelines for prophylaxis, especially in pediatric patients, are lacking.


Inherited rare bleeding disorders (RBD), including afibrinogenemia and deficiencies in factor (F) II, V, VII, X, XI, XIII or V plus VIII combined, or in vitamin K-dependent coagulation factor (VKDC), generally represent 5% of all inherited coagulation disorders[1] with slight variations occurring between countries depending, in particular, on the prevalence of consanguinity in different racial groups. In that way, RBDs differ from hemophilia A and B where the prevalence appears to be similar in all races. The prevalence of RBDs ranges from one in 3,000,000 individuals for the rarest (VKDC or FXIII deficiency) to one in 300,000 individuals for the most common (FVII or FXI deficiencies) homozygous or compound heterozygous forms. All of the above disorders are transmitted in an autosomal recessive manner, implying that the heterozygous carriers are asymptomatic. This is true for the combined FV plus FVIII and VKDC defects where heterozygotes have normal clotting factor levels. Contrary to this, heterozygous carriers for the single deficiency RBDs generally display reduced levels of their respective factor. Those individuals are usually asymptomatic, but symptomatic heterozygous carriers have been widely reported with the FXI deficiency[2] and mild bleeding features might also be observed in FII-, FVII- or FX-deficient heterozygotes.[3–5] Nevertheless, the autosomal recessive trait implies that the risk of presenting with a RBD is increased where consanguineous marriages are common, explaining the aforementioned variable incidences between countries. In addition, there may be no preceding family history to suggest the diagnosis and an affected child may be part of a kindred with very few affected individuals – heterozygous patients usually being asymptomatic. As bleeding symptoms in children manifest in a manner that is distinct to those in adults, pediatricians and neonatalogists need to be aware of these differences and thoroughly investigate every unexpected bleeding event that presents early in life, since it may potentially represent early markers of severe inherited bleeding disorders. Indeed, the most severely affected patients often present with life-threatening hemorrhages within a few days of birth, including intracranial hemorrhages (ICHs) or gastrointestinal hemorrhages. Inadequate or delayed treatment of such neonatal bleeding may increase the risk of mortality or significant long-term disability. Later in life, recurrent joint bleeding may lead to the development of chronic arthropathy. Emphasis should be placed on early diagnosis, replacement treatment and prophylaxis. Two entire issues of the journals Haemophila (2008) and Seminars in Thrombosis and Hemostasis (2009) are devoted to the RBDs and are recommended for supplementary information.


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