How was factor XIII (FXIII) deficiency first recognized?

Updated: Aug 01, 2019
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Perumal Thiagarajan, MD  more...
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The hemostatic system, consisting of blood vessels and blood, plays a crucial role in human survival. The importance of the plasma coagulation system in protecting life and preventing further blood loss following transection of a blood vessel has been understood for a long time. Blood normally is maintained in a fluid state, without evidence of bleeding or clotting. The presence of a bleeding diathesis in families with an X-linked pattern of inheritance of the disorder has been recognized for hundreds of years.

The recognition of factor deficiencies as the cause of hemophilias spurred investigations into the causes of other bleeding disorders and led to progress in understanding normal hemostasis. Knowledge of the fact that blood clots that are formed in the presence of calcium are stronger, insoluble in alkali, and resistant to proteolytic degradation led to the concept of insoluble clots in the earlier part of the last century.

In 1948, Laki and Lorand recognized that a serum factor, termed fibrin stabilizing factor, was responsible for the characteristics of insoluble fibrin clots. [6] In 1960, Duckert et al described the first case of an "undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency," which was a description of the consequences of severe factor XIII (FXIII) deficiency. [7, 8]

The importance of FXIII in the process of coagulation is underscored by symptoms borne by patients who are homozygously deficient in FXIII or who have an antibody that disrupts FXIII function. Paradoxically, alterations in FXIII may predispose patients to thrombosis. Based on all available data, FXIII is clearly involved in the clot preservation side of the delicate balance between clot formation and stability and clot degradation. FXIII participates in other physiologic processes, including wound repair and healing. The many functions of FXIII and the disruptions of those functions by mutations in the genes coding for FXIII are the subjects of on-going investigations. [9, 10, 11]

Gene polymorphisms are being evaluated for their influence on susceptibility to venous and arterial thromboembolism. [12] Variants of coagulation factors, including FXIII Val34Leu, have been implicated in influencing susceptibility to thromboembolic diseases. [13]

There is a question as to whether FXIII Val34Leu polymorphism is protective against idiopathic venous thromboembolism.The substitution of leucine for valine at amino acid position 34 of the FXIII gene, commonly referred to as FXIII Val34Leu polymorphism, has been reported to confer protection against venous thromboembolism. However, the results of a study in a white Canadian population did not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism. [14]

An association may exist between the FXIII Leu allele and a modest protective effect against acute myocardial infarction (MI) and may provide useful information in profiling susceptibility to MI. [15]

FXIII measurement has a variety of uses, potential and confirmed. Plasma levels of FXIII were found to be decreased in children with Henoch-Schönlein purpura having severe abdominal symptoms. Thus, it has been suggested that measurement of FXIII level may be of value to detect the vasculitic process of Henoch-Schönlein purpura before the rash occurs or long after it has disappeared in patients with isolated abdominal or scrotal problems. [16, 17] Immunohistochemistry studies have shown that FXIIIa-positive dermal dendritic cells were increased in a variety of skin tumors, including dermatofibromas. [18]

Severe FXIII deficiency, a rare autosomal recessive coagulation disorder, is associated with a relatively common prevalence of F13B gene defects, at least within the German population. The regions in and around the cysteine disulphide bonds in the FXIII-B protein are the sites of frequent mutations. [19]

FXIIIs aids immobilization and killing of bacteria as well as phagocytosis by macrophages, likely functioning as part of the innate immune system. [20]

Use of relatively new specific FXIII assays are pivotal to avoid missing the diagnosis of FXIII deficiency, a rare but potentially life-threatening disorder. [21]

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