3.4.21.27	malfunction	a deficiency in FXI (hemophilia C) results in a more benign bleeding phenotype compared with a deficiency in either FVIII (hemophilia A) or FIX (hemophilia B). Most hemophilia C cases involve Ashkenazi Jews and result from either of 2 mutations in the FXI gene (E117X and F283L). Greater than 180 mutations are present but in lesser frequency. FXI deficiency also arises from acquired inhibitors that neutralize its activity, these patients may not respond well to FXI replacement therapy. Bleeding in those with hemophilia C is rarely spontaneous, it tends to occur in response to surgery or trauma, and especially in tissue prone to fibrinolysis (the urinary track or oral cavity). Prolonged activated partial thromboplastin time due to FXI deficiency	707308	
3.4.21.27	malfunction	activated partial thromboplastin time is abnormal in all cases with severe or moderate FXI deficiency. FXI deficiency is not an absolute contraindication to neuraxial anesthesia	707134	
3.4.21.27	malfunction	addition of murine FXI to human FXI deficient plasma rescues the prolonged activated partial thromboplastin time, but with a slightly reduced activity compared with the human protein. FXI-/- mice are healthy, fertile, and phenotypically indistinguishable from wild-type animals. Mating between heterozygous FXI+/- mice follows the expected Mendelian ratio arguing against an association of FXI deficiency and increased risk of abortion. Plasma from FXI null mice show a severely prolonged activated partial thromboplastin time compared with wild-type animals. Bleeding times in adult FXI-/- mice are indistinguishable from wild-type animals, suggesting that FXI does not significantly contribute to fibrin formation. Formation of thrombi is severely defective in FXI-/- mice. Both fibrin deposition and platelet accumulation are reduced in FXI null mice compared with wild-type. FXI deficiency increases survival and reduces leukocyte infiltration and coagulopathy	709722	
3.4.21.27	malfunction	congenital FXI deficiency is associated with a variable, mild to moderate bleeding disorder. Severe deficiency is prevalent in people of Jewish ancestry. The severe mutation Glu117Stop encodes a truncated protein, and homozygotes lack plasma FXI antigen. The more subtle missense mutation Phe283Leu causes a defect in FXI dimer formation. Most cases of FXI deficiency are associated with low plasma levels of FXI protein. Deficiency or inhibition of FXI interferes with platelet accumulation in growing thrombi. A4 domain mutations associated with FXI deficiency interfere with dimerization. FXI-deficient plasma exhibits a prolonged activated partial thromboplastin clotting time	707856	
3.4.21.27	malfunction	enzyme deficiency results in bleeding diathesis referred to as hemophilia C	732897	
3.4.21.27	malfunction	factor XI deficiency can lead to delayed clot formation and decreased thrombin generation	731773	
3.4.21.27	malfunction	FXI deficiency is a rare inherited coagulation disorder characterized by infrequent spontaneous bleeding, but increased risk of hemorrhagic complications especially after trauma or surgery	707148	
3.4.21.27	malfunction	FXI deficient humans suffer from mild hemorrhage (hemophilia C), which is characterized by trauma or soft tissue-related hemorrhage, primarily involving tissues with high fibrinolytic activity. Bleeding severity in FXI deficiency is not associated with FXI plasma levels. Addition of murine FXI to human FXI deficient plasma rescues the prolonged activated partial thromboplastin time, but with a slightly reduced activity compared with the human protein	709722	
3.4.21.27	malfunction	FXI-null mice are healthy, and their reproduction follows the expected mendelian ratios without impaired fecundity. FXI-null mice are protected against oxidative iron chloride-induced carotid artery thrombosis and infusion of human FXI reverses this protection. Thrombus formation in FXI-null mice is also reduced in response to laser injury of arterioles in the cremaster muscle. FXI deletion is also effective in preserving carotid artery blood flow in response to compression injury	707308	
3.4.21.27	malfunction	mice lacking FIX, FXI, or FXII on a background of low tissue factor expression have a severe bleeding disorder but are viable. Superimposing FIX or FXI deficiency on the low tissue factor background results in death in utero from bleeding	707856	
3.4.21.27	malfunction	patients who have a very severe FXI deficiency are prone to development of inhibitor antibodies. During major surgeries, a single low dose of recombinant activated factor VII and tranexamic acid secure normal haemostasis in patients with severe FXI deficiency who can not receive blood products	710600	
3.4.21.27	malfunction	probably due to inbreeding, presence of FXI deficiency	709722	
3.4.21.27	physiological function	78% homology to human FXI at the protein level. FXI is critical for fibrin formation in vivo. FXI may have additional functions in regulation of inflammation or tissue repair distinct from its role in coagulation	709722	
3.4.21.27	physiological function	activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor	731538	
3.4.21.27	physiological function	activated factor XI inhibits chemotaxis of polymorphonuclear leukocytes. Coagulation factor XI participates in the intrinsic coagulation pathway upon its activation, contributing to hemostasis and thrombosis. Factor XIa attenuates N-formylmethionyl-leucyl-phenylalanine-induced Ca2+mobilization	717958	
3.4.21.27	physiological function	coagulation factor XI induces Ca2+ response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1	752439	
3.4.21.27	physiological function	factor XI is important in the tissue factor-independent propagation phase of clot formation, not in the initiation process	731773	
3.4.21.27	physiological function	factor XIa plays its major role in promoting late thrombin formation (i.e. the thrombin required for thrombin activatable fibrinolysis inhibitor-mediated inhibition of fibrinolysis)	718045	
3.4.21.27	physiological function	FXI is a biomarker with increased levels reported as a risk factor for venous thromboembolism and myocardial ischemia or stroke	707308	
3.4.21.27	physiological function	FXI is the zymogen of a blood coagulation protease, factor XIa (activated factor IX), that contributes to hemostasis through activation of factor IX. Almost all FXI circulate in a complex with kininogen	707856	
3.4.21.27	physiological function	FXI is the zymogen of a plasma protease that contributes to fibrin formation and stability by activating factor IX. Circulates in plasma in complex with high molecular weight kininogen	709721	
3.4.21.27	physiological function	involvment of FXI in thrombosis, role for activated factor FXI in tissue infammation	707308	
3.4.21.27	physiological function	low concentrations of tissue factor and exogenous factor XIa, each too low to elicit a burst in thrombin production alone, act synergistically when in combination to cause substantial thrombin production	752615	
3.4.21.27	physiological function	presence of a single precursor of FXI and plasma kallikrein, appearance of FXI among early tetrapods	709722	
3.4.21.27	physiological function	the enzyme is involved in the coagulation cascade	732897	
3.4.21.27	physiological function	the enzyme plays a pivotal role in regulation of chemerin bioactivity in plasma	753068	
3.4.21.27	physiological function	the opossum genome has two distinct genes for both FXI and plasma kallikrein, indicating that the gene duplication event leading to separate factors occurred early in mammalian evolution	709722