Recessively inherited coagulation disorders

Abstract

Deficiencies of coagulation factors other than factor VIII and factor IX that cause bleeding disorders are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500 000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. We investigated more than 1000 patients with recessively inherited coagulation disorders from Italy and Iran, a country with a high rate of recessive diseases due to the custom of consanguineous marriages.Based upon this experience, this article reviews the genetic basis, prevalent clinical manifestations, and management of these disorders. The steps and actions necessary to improve the condition of these often neglected patients are out-

Laboratory testing for fibrinogen abnormalities

“…The function and quantity of plasma fibrinogen can be altered by both inherited and acquired disorders [1,[3][4][5][6][7][8][9][10][11][12][13]. Increased levels of fibrinogen can be seen in pregnancy [3,4], acute or early liver disease [5], and many acute illnesses [6][7][8].…”

“…placental abruption), fibrinolytic therapy [9], hemodilution and severe liver disease [10]. The magnitude of congenital fibrinogen deficiencies range from severe (absent fibrinogen or afibrinogenemia) to moderate and mild (hypofibrinogenemia) [11,12]. In some individuals, the inherited defect in fibrinogen leads to production of a dysfunctional molecule (dysfibrinogenemia), that can be associated with bleeding or thrombosis, or both problems [13].…”

LETTERS TO THE EDITOR: Four cases of hypofibrinogenemia associated with four novel mutations

“…The three different chains are encoded by three genes clustered in a 50 kb region on chromosome 4. Hypofibrinogenemia is defined as a decrease of total plasma fibrinogen concentration and may constitute a risk for bleeding [1]. Heterozygous frameshift mutations, substitutions, and deletions have been identified in 28 cases corresponding to 25 unique mutations (http:// www.geht.org/databaseang/fibrinogen/, release 20).…”

“…In the Framingham study, the heritability of the platelet aggregation response ranged from 44% to 62%, depending on the agonist [1]. This prompted several genetic association studies designed to investigate the impact of platelet receptor gene variations on the platelet response to agonists.…”

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“…Factor VII deficiency is a rare autosomal recessive coagulation disorder [9], and its frequency is higher in countries where consanguineous marriage is more common [10], such as in Lebanon. However, the parents in our case were not consanguineous, and no family history of bleeding disorder could be identified.…”