Factor XIII Deficiency

What is Factor XIII Deficiency?

The disease was first described in 1960 by the scientist Duckert and co-authors, who identified 2 brothers with severe hemorrhagic diathesis, characterized by a hereditary deficiency of fibrin-stabilizing factor (factor XIII).

This disease is inherited autosomally by an incomplete recessive type – in homozygotes, the level of factor XIII is usually less than 5% and the disease is severe. In heterozygotes, light and moderate hemorrhagic manifestations are often detected.

There is a similar disease related to the main form of factor XIII deficiency. This pathology is inherited recessively linked to the X chromosome, whereby hemorrhagic diathesis, as in hemophilia, is manifested mainly in males, and the carriers of the disease are women.

Symptoms of Deficit Factor XIII

The most common, as well as the very first sign of a deficiency of the fibrin-stabilizing factor, which is detected in almost all patients, is the slow healing of the umbilical wound and bleeding from it during the first 3 weeks of life.

Umbilical bleeding is often so stubborn and abundant that it requires urgent transfusions. The umbilical syndrome with normal indications of general coagulation tests (clotting time, kaolin-kefalin time, autocoagulogram, prothrombin and thrombin time) directly indicates the need to study factor XIII.

The second most frequent and widespread group is a very dangerous group of hemorrhages in the brain and its membranes at birth or during the first year of life. They are recorded in almost half of the patients, are prone to recurrences and serve as one of

the main causes of death and severe disability of patients. Sometimes cerebral hemorrhages lead to Jackson epilepsy.

At sufficiently early stages of the disease, gastrointestinal bleeding and hemorrhage into the abdominal cavity may develop, however, these bleedings are more rare and less dangerous than intracranial bleeding.

In the future, the number of bleeding increases, and for the deficiency of factor XIII bleeding is characterized by a mixed type. Minor hemorrhages in the skin, bruises, subcutaneous and intermuscular hematomas are frequent, and hemorrhages in the joints are noted in about 20% of cases.

Often, mimicking acute surgical diseases of the abdominal organs, hemorrhages in the peritoneum and retroperitoneal hematomas develop quite rapidly.

In case of insufficiency of the fibrin-stabilizing factor, prolonged and heavy bleeding is observed with cuts, injuries, extraction of teeth and surgical interventions, mild bruising and hematomas, menorrhagia, bleeding during childbirth and abortions.

A description of the patient is found in the literature, in which there were heavy uterine bleeding during 12 pregnancies, due to which all pregnancies ended in spontaneous abortions. At the last 13th pregnancy, factor XIII deficiency was diagnosed and substitution transfusion therapy was carried out (factor XIII was maintained at more than 10%). Under the guise of such regular transfusions, the pregnancy was uneventful and a normal baby was born.

In milder forms of the disease with the level of factor XIII in plasma above 3-5% hematomas, as a rule, no longer occur and predominantly post-traumatic bleeding is observed.

A characteristic feature of the pronounced deficiency of factor XIII is poor healing of wounds and fractures. This defect of reparative regeneration is eliminated immediately after the administration of preparations containing factor XIII. With a milder disease, healing is not significantly impaired.

Diagnosis of Defecit Factor XIII

With a deficit of fibrin-stabilizing factor, all the parameters of the coagulogram remain within the normal range. The study of vascular platelet hemostasis also does not reveal significant violations. Under these conditions, hemorrhagic diathesis requires the determination of factor XIII, since this is the only coagulation factor, with a deficiency in which all tests characterizing different phases of blood coagulation, have normal indicators.

Most laboratory methods for recognizing factor XIII deficiency are based on the determination of the solubility of fibrin clots.

For recognition of mild and latent forms of factor XIII deficiency, qualitative tests are unsuitable, and diagnostics is possible only with the help of quantitative determination. For this purpose, fairly accurate and easily executable Sigg methods are often used.

Factor XIII can also be determined immunologically or immunoradiometrically. The latter group of methods allows differentiation of genetically different groups of fibrin-stabilizing factor deficiency – more frequent antigen-negative and anti-genopositive.

Hereditary fibrin-stabilizing factor deficiency should be distinguished from the many acquired forms of this pathology, starting with transient depressions caused by disseminated intravascular coagulation or multiple and massive blood clots that consume this factor, and ending with forms caused by cirrhosis and liver tumors, uremia, the use of mercury bladders, and urethy, the use of mercury. polymyxin B and streptase, radiation sickness and a number of other diseases.

It was also revealed a decrease in the level of this factor in the plasma in some patients with diseases such as polycythemia, multiple myeloma, Waldenstrom’s disease, but this reduction is especially significant with hemoblastosis.

Treatment of Defetsit Factor XIII

One of the most common and effective methods of treating a disease is factor XIII replacement therapy.

This therapy does not present any technical difficulties, since the above factor is well preserved in hemopreparations in both native and dry plasma, circulating for a long time in the recipient’s blood (half-life period is more than 4 days). Due to the above features of factor XIII, normal hemostasis is ensured with a relatively low final concentration (about 10%).

Bleeding is usually stopped by jet transfusions of plasma in a volume of 10-15 ml / kg, which, if necessary, are repeated every 4-5 days. A lot of factor XIII in cryoprecipitate.

Of the non-specific agents with factor XIII deficiency, aminocaproic acid is more commonly used, since unstabilized fibrin is easily amenable to fibrinolysis, and aminocaproic acid inhibits this enzyme system.

There is little experience of prolonged prophylactic use of plasma and cryoprecipitate in severe forms of factor XIII deficiency. Introduction 1 time in 3-4 weeks with 400 ml of plasma or a single dose of cryoprecipitate prevents hemorrhagic events.