Symptom >> Internal Medicine >> Department of Genetic Diseases

Congenital factor X deficiency

Introduction
Cause
Examine
Diagnosis

Introduction

Introduction Congenital X-factor deficiency: This disease is rare, it is autosomal recessive inheritance, patients parents often marry close relatives, both men and women can be affected. Since Factor X can be involved in the function of the intrinsic and extrinsic coagulation systems, it can also have similar symptoms of Factor VII deficiency, and the degree of bleeding is related to the concentration of Factor X. Homozygous type generally has bleeding symptoms, and the heterozygous factor X concentration is about 20% to 50%, and there is no bleeding tendency. Laboratory tests, prothrombin time (PT), partial thromboplastin time (PTT) and snake venom time were prolonged, the latter can be differentiated from factor VII deficiency. The treatment is based on factor X supplementation, and a concentrated preparation of stored plasma, PPSB or factor X can be used. Infusion of 10-15 ml of plasma per kg of body weight. The effective hemostatic concentration of factor X is about 5% to 10%. The hemostatic concentration of severely bleeding patients is about 15% to 20%.

Cause

Cause

(1) Causes of the disease

The hereditary factor X (FX) deficiency is a vitamin K-dependent coagulation factor synthesized by the liver. The liver first synthesizes a single-stranded molecule consisting of 488 amino acids (including a signal peptide consisting of 40 amino acid residues). FX is activated by FIXa/FVIIIa or FVII TF during coagulation. Once activated, FXa binds to its essential cofactor (FVa) to catalyze the prothrombin to become thrombin. When factor X is deficient, thrombin production is also delayed.

(two) pathogenesis

The hereditary factor X deficiency is an autosomal recessive hereditary disease. The gene encoding FX is located on chromosome 13 and has been successfully cloned and sequenced. The FX gene is 22 kb in length and contains 8 exons. At present, more than 60 mutations have been discovered, the vast majority of which are missense mutations, mainly occurring in exon 8 encoding the catalytic domain. All of these mutations do not result in the production of truncated proteins, nor do they eliminate the expression of FX. This explains from another aspect why mice that do not express FX at all cannot survive in FX knockout mice. of. In clinical practice, although the activity of most patients is reduced, it can still be detected, the antigen level is reduced or normal, and the proportion of very serious mutations such as deletion or cleavage site mutation is extremely small. A very interesting point in the FX gene mutation profile is that no sense mutations have been found, and in other genetic clotting factor deficiencies, this type of mutation accounts for about one-fifth of all mutations. The homozygous FXFruili has severe bleeding, and FX activity is only 6% to 9% normal, but the antigen level is normal. Other similar families have also been reported.

DNA sequencing of all exons and their flanking intron sequences of the FX gene proband and other members of the FX-deficient family found that the FX gene exon 1 missense mutation 11Set(AGT)Arg(AGG), The mutation was first discovered internationally. Figure 1 shows a partial FX gene mutation and its location in the gene.

Examine

an examination

In the absence of clotting factors other than hemophilia A and hemophilia B, patients with factor X deficiency have the most severe clinical bleeding. Hematoma and joint bleeding may occur in 2/3 of patients. When factor X activity is less than 1%, the patient has severe bleeding. When the FX level is 10%, it may only show mild bleeding. Patients with FX activity below 1% have clinical manifestations similar to those of hemophilia A.

Diagnosis is based on clinical bleeding symptoms, genetic type, and laboratory tests. The FXI:C assay or the Biggs thromboplastin assay can determine the diagnosis.

Both prothrombin time (PT) and activated partial thromboplastin time (APTT) are usually prolonged, however, since FX must interact with the F IXa/F VIIIa complex and the FVIIa/TF complex, when FX is deficient It is possible that the effects on the two complexes are not the same. For example, in FX Roma, FX has normal antigen levels, but its effect on exogenous coagulation pathways (3%) is much greater than on endogenous coagulation pathways (30% to 50%). Patients with this mutation have bleeding quality. In other cases, only PT prolongation can be found, while APTT is normal, or APTT is prolonged, while PT is normal. The bleeding time of patients with severe FX deficiency may also be prolonged, but whether the prolongation of bleeding time is related to the barrier of FVa and FXa interaction on platelet surface is not very clear. Python venom can directly lyse and activate FX, so the Russell venom time test is prolonged in most patients. Examination of FX activity and antigen, as well as genetics, is necessary to clarify the diagnosis of hereditary factor X deficiency.

Diagnosis

Differential diagnosis

The disease is mainly differentiated from other hemorrhagic diseases with prothrombin time (PT) normal partial thromboplastin time (PTT), and Biggs thromboplastin test can be differentiated from hemophilia A and hemophilia B. Lupus anticoagulant can prolong PTT, normal PT, and laboratory tests for lupus anticoagulant substances can be identified. The identification of acquired FXI deficiency is the presence of autoantibodies in such patients, which can be identified by antibody screening tests, often in cases of systemic lupus erythematosus.

The diagnosis of hereditary factor X deficiency must be differentiated from the acquired FX reduction secondary to vitamin K deficiency. Liver disease and warfarin can also exhibit symptoms of factor X deficiency, but in both cases, FX The reduction is also secondary, and at the same time there are other vitamin K-deficient clotting factors that can be diagnosed through detailed medical history, physical examination and laboratory tests. Isolated acquired factor X deficiency can be found in patients with amyloidosis, which may be related to the absorption of FX by amyloid. In the absence of clotting factors other than hemophilia A and hemophilia B, patients with factor X deficiency have the most severe clinical bleeding. Hematoma and joint bleeding may occur in 2/3 of patients. When factor X activity is less than 1%, the patient has severe bleeding. When the FX level is 10%, it may only show mild bleeding. Patients with FX activity below 1% have clinical manifestations similar to those of hemophilia A.