Factor XI deficiency

Gailani D, Lasky NM, Broze GJ (1997) A murine model of factor XI deficiency. Blood Coagul Fibrinolysis 8 134-144... 

Gailani D, Lasky NM, Broze GJ (1997) A murine model of factor XI deficiency. Blood Coagul Fibrinolysis 8 134-144 Healy AM, Rayburn HB, Rosenberg RD, Weiler H (1995) Absence of the blood-clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Proc Natl Acad Sci USA 92 850-854... 

Inhibitor formation has been observed in only a few patients with factor XI deficiency. Like patients with hemophilia A and B, these patients may be treated with prothrombin complex concentrates or recombinant factor Vila (2). 

Bolton-Maggs PH. The management of factor XI deficiency. Haemophilia 1998 4(4) 683-8. 

Plasma thromboplastin antecedent (PTA) XI Factor XI deficiency Rare, primarily in Ashkenazi Jews 4 0.025 Liver 40-80 FA11 HUMAN... 

Another possibility is that some other clotting factor is increased or activated in such a way that the assay system responds fortuitously to it in a way indistinguishable from the usual response to factor VIII, e.g., factors XI and XII factor XII is known to rise on exercise (II). That this might occur over a limited range of the dose-response curve in the thromboplastin generation test system was shown by experiments in which the addition of activation product (Wl) simulated an increased factor VIII concentration (author s unpublished observations, 1960 FI), although statistical invalidity would probably be detectable over a series of experiments if this were the explanation. This also was looked for, but was not found (14). It is interesting that, in a patient with severe factor VIII deficiency and partial factor XI deficiency (SI), adrenaline infusion was followed by a marked rise in factor XI concentration and the appearance of a trace of factor VIII (K. Schulz, personal communication, 1964). Furthermore, the confusion that arose some years ago over factor IX assay now seems to have been due to activation of the contact factors (P4), hence... 

Bolton-Maggs PHB. Factor XI deficiency and its management. Haemophilia 2000 6(Suppl 1) 100-109. 

Congenital deficiency of Factor XI is a relatively rare coagulopathy that has been reported as both an autosomal dominant and autosomal recessive trait. This deficiency state occurs predominantly in the Jewish population. Most patients with this deficiency state remain asymptomatic until trauma or surgery is encountered. Spontaneous hemorrhage is rare in this population. 

Two factor XI products, both containing antithrombin III and heparin, have been associated with evidence of coagulation activation and thrombotic events in patients with pre-existing vascular disease (2). It has been recommended that doses of more than 30 U/kg and factor XI peak concentrations in severely deficient patients of more than 500-700 U/1 should be avoided. In addition, the concurrent use of tranexamic acid or other antifibrinol)4ic drugs should be avoided. 

Hemophilia C occurs at 10% of the frequency of hemophilia A and is the least common form of hemophilia in the United States, where it mainly occurs in Ashkenazi lews. It is caused by a deficiency of factor XI. Unlike hemophilia A and B, there is no bleeding into joints Factor Xlla can apparently activate factor IX directly without first activating factor XI. Nevertheless, afflicted individuals suffer nosebleeds and heavy menstrual bleeding and, like all hemophiliacs, require a clotting agent to prevent excessive bleeding following a tooth extraction (Sect. 11.6.5). 

However, the exercise effect has been demonstrated with assays involving (supposedly maximal) activation of factors XI and XII with kaolin (13), and a system to which activation product was added (VI) duly registered the adrenaline effect. Furthermore, a rise in factor VIII concentration has now been produced by exercise in patients with severe deficiencies of factors XI and XII. Egeberg (E13) tested two patients with gross deficiencies of factor XI, and Goudemand et al. (G2) and A. Parquet-Gemez (personal communication, 1964) tested factor Xll-deficient patients. 

Activated partial thromboplastin time aPTT is performed by adding calcium phospholipids and kaolin to citrated blood and measures the time required for a fibrin clot to form. In this manner, aPTT measures the activity of intrinsic and common pathways. Prolongation of aPTT may be due to a deficiency or inhibitor for factors II, V, VIII, IX, X, XI, and XII. It also may be due to heparin, direct thrombin inhibitors, vitamin K deficiency, liver disease, or lupus anticoagulant. 

Hypercoagulable states include malignancy activated protein C resistance deficiency of protein C, protein S, or antithrombin factor VIII or XI excess antiphospholipid antibodies and other situations. Estrogens and selective estrogen receptor modulators have been linked to venous thrombosis, perhaps due in part to increased serum clotting factor concentrations. Although a thrombus can form in any part of the venous circulation, the majority of thrombi begin in the lower extremities. Once formed, a venous... 

Factor deficiencies include disorders of fibrinogen such as afibrinogenemia and dysfibrinogenemias, prothrombin deficiency, factor V VII, X, XI, XII, and XIII deficiency, prekallikrein and high-molecular-weight kininogen deficiency, combined factor deficiencies, a2 anti-plasmin deficiency, a] antitrypsin Pittsburgh, and protein Z deficiency. 

The most severe cases of human amnesic shellfish poisoning occurred in males of advanced age, which originally suggested that age and sex are predisposing factors (Perl et al. 1990). However, the age-related predisposition is, at least in part, the result of renal impairment (Teitelbaum et al. 1990) and is supported by several experimental studies (Suzuki and Hierlihy 1993 Truelove and Iverson 1994 Xi et al. 1997). Nonetheless, advanced age may enhance snsceptibihty in other ways to domoic acid. Electric field potential analysis of hippocampal slices determined that aged rats differed from younger rats in that they did not exhibit preconditioned tolerance to domoic acid (Kerr et al. 2002). This was interpreted that the older rats may be deficient in neuroprotective mechanisms. 

Vitamin K is necessary for the formation of coagulation factors II, VII, X and XI as well as of proteins C, S and M in addition, it is indispensable for the production of osteocalcin, which stimulates osteoblast activity. It is transported from the liver to the bloodstream in the VLDL. A deficiency is characterized by symptoms similar to those observed in haemorrhagic diathesis. It can be caused by intestinal resorption disturbance or loss of hepatocellular function (reduced carboxyl transfer to specific vitamin K-dependent proteins). 

Fresh frozen plasma contains the components of the coagulation system and is indicated for the replacement of deficient coagulation factors II, V, VII, X, XI, and XIII. Factor VIII and IX deficiencies are treated with specific factor concentrates. Fresh frozen plasma is also used for the rapid reversal of warfarin anticoagulation and in the treatment of disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura is treated by means of therapeutic plasma exchange with fresh frozen plasma as the replacement fluid. Cryo-precipitate, which contains factor VIII, von Willebrand s factor, and fibrinogen, is indicated for the treatment of von Willebrand s disease that does not respond to desmopressin acetate, and for fibrinogen replacement (see Chap. 100). 

Accepting the above limitations of our knowledge of the true in vivo reaction sequence, a series of clot-endpoint tests has been used for many years to determine the hemostatic balance in any patient. The first, known as the thrombin time test, can be used to measure the concentration of fibrinogen (B15). The second assay, the activated partial thromboplastin time test (APTT), measures the components of the intrinsic pathway (M4). These include the serine proteases (Factors XII, XI, X, and II), the cofactors (Factors VIII and V) and again, fibrinogen. Most of the hereditary deficiencies... 

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