**5. Rare bleeding disorders**

Rare inherited bleeding disorders (RBDs) include deficiencies of coagulation factors such as fibrinogen, factor II (FII), FV, combined deficiency of FV and FVII, FVIII, FX, FXI, FXIII and vitamin K dependent factors. RBDs are mostly autosomal recessive disorders varying from 1 in 500,000 to 1 in 2–3 million [56]. These disorders are diagnosed by clotting assays such as thrombin time, prothrombin time and activated partial thromboplastin time followed by molecular diagnosis [56].

surprisingly do not show bleeding phenotype. Recent evidences elucidated that platelets endocytose FV from plasma, modify them intracellularly and release it at the site of injury. This platelet released FV is resistant for inhibition. If symptomatic patients usually have umbilical

Understanding the Clotting Cascade, Regulators, and Clinical Modulators of Coagulation

http://dx.doi.org/10.5772/intechopen.75141

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FVII is a 50 Kda single chain polypeptide encoded by F7 gene located on chromosome 13 and FVII levels are influenced by age, sex and health condition such as blood cholesterol and triglyceride levels [73, 74]. FVII deficiency is observed in 1 in 500,000, with variable phenotypes [74]. Some patients do not show bleeding phenotype despite very low FVII levels, whereas others with similar FVII antigen levels show severe bleeding phenotype [74]. The bleeding phenotypes of FVII deficiency include central nervous system hemorrhage, epistatic and menorrhagia [74]. Frozen fresh plasma, prothrombin complex concentrates, plasma derived FVII concentrate, recombinant FVIIa are typically used to treat FVII defi-

Factor X is a single chain polypeptide with a molecular weight of 58,900 kDa and circulates in plasma with a concentration of 10 μg/ml [77]. FX is encoded by FX gene present on chromosome 13 [78]. FX deficiency is characterized by central nervous system and gastro intestinal bleeding [79, 80]. FX deficiency is one of the very rare disorders observed in 1 in 500,000– 1000,000 [79, 80]. Treatments of FX deficiency include highly purified plasma FX, recombinant

FXI is a 80 kDa protein with a plasma concentration of 30 nM, encoded by a 23 kb gene present on chromosome 4 [81–83]. Mutations in the coding region are the major causes for FXI deficiency and the prevalence of FXI deficiency is 1 in 1000,000 [83, 84]. The common symptoms of FXI deficiency are oral and post-operative bleeding. FXI deficient women are prone to menorrhagia. Fresh frozen plasma, FXI concentrate and antifibrinolytic agents are used to

The functional FXIII consist 2 catalytic A subunits (FXIII-A) and 2 carrier subunits (FXIIIB) [85]. FXIII-B is encoded by chromosome 6 and synthesized by the cells derived from bone marrow, whereas FXIIIA is encoded by chromosome 1 and secreted from liver [85, 86]. FXIII crosslinks α and γ subunits of fibrin thereby increases the strength of fibrin clot and increases fibrinolytic resistance [86]. Prevalence of FXIII deficiency is 1 in 2 million, patients with FXIII-A have high tendency of bleeding [87]. 2–5% plasma FXIII is sufficient to prevent bleeding, FXIII concentrates are usually used to treat FXIII deficiency and frozen fresh plasma and

FX, fresh frozen plasma and prothrombin complex concentrates [79, 80].

stump bleeding, skin and mucosal tract hemorrhage [72].

**5.4. FVII deficiency**

ciency [75, 76].

**5.5. FX deficiency**

**5.6. FXI deficiency**

treat FXI deficiency [84].

cryoprecipitate are also recommended [87].

**5.7. FXIII deficiency**
