Hereditary factor X deficiency
Introduction
Introduction to hereditary factor X deficiency The lack of hereditary factor X (FX) was first discovered by Hougie in a male patient named Stuart. Therefore, FX is also known as the "Stuart factor." In the absence of clotting factors other than hemophilia A and hemophilia B, patients with factor X deficiency have the most severe clinical bleeding, and hematoma and joint bleeding may occur in 2/3 of patients, with factor X activity below 1%. At the time of the patient, severe bleeding occurred. When the FX level was 10%, it may only show mild bleeding. The clinical manifestations of patients with FX activity below 1% were similar to those of hemophilia A. basic knowledge The proportion of illness: 0.001% - 0.002% Susceptible people: no special people Mode of infection: non-infectious Complications: edema, muscle atrophy
Cause
Hereditary coagulation factor X deficiency etiology
(1) Causes of the disease
FX 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 regulated by FIXa/FVIIIa during coagulation. FVII TF is activated. Once activated, FXa binds to its essential cofactor (FVa) to catalyze prothrombin to become thrombin. When factor X is deficient, thrombin production is delayed.
(two) pathogenesis
Hereditary coagulation 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 species have been found. Mutations, the vast majority of which are missense mutations, occur mainly in exon 8 encoding the catalytic domain, all of which do not result in the production of truncated proteins and do not eliminate the expression of FX, which is another One side explains why mice that do not express FX at all in FX knockout mice are not able to survive. In clinical practice, although most patients have reduced activity, they can still be detected, and antigen levels are reduced or normal. Very serious mutations, such as deletions or cleavage site mutations, account for a very small proportion. It is very interesting in the FX gene mutation spectrum that no nonsense mutations have been found yet, and other genetic clotting factors are lacking. Among them, this type of mutation accounts for about one-fifth of all mutations, and the homozygosity of FXFruili has severe bleeding, and FX activity is only normal 6% to 9%, but anti- The original level is normal, and other similar families have also reported.
Shanghai Ruijin Hospital Shanghai Institute of Hematology performed DNA sequencing on all exons and flank intron sequences of FX gene in a FX-deficient family of probands and other members, and found that FX gene exon 1 missense mutation 11Set (AGT) ) Arg (AGG), this mutation was the first international discovery.
Prevention
Hereditary coagulation factor X deficiency prevention
Establish genetic counseling, strict premarital examination, strengthen prenatal diagnosis, and reduce the birth of children.
Complication
Hereditary coagulation factor X deficiency complications Complications, edema, muscle atrophy
The disease is mainly hemorrhage. For deep tissue hematoma can compress nearby blood vessels to cause tissue necrosis. Compression nerve can cause limb or local pain, numbness and muscle atrophy. Compression of blood vessels can cause ischemic necrosis or congestion and edema of the corresponding blood supply site. Bleeding at the bottom of the mouth, posterior pharyngeal wall, throat and neck can cause difficulty breathing or even suffocation. Patients may be unable to completely absorb blood due to repeated joint cavity hemorrhage, resulting in chronic inflammation, synovial thickening, fibrosis, cartilage degeneration and necrosis, eventually joint stiffness, deformity, peripheral muscle atrophy, resulting in limited normal activities.
Symptom
Hereditary coagulation factor X deficiency symptoms Common symptoms Congenital X factor lack of bleeding tendency Gingival bleeding bleeding after tooth extraction More than nose bleeding Skin freckle muscle bleeding
In the absence of clotting factors other than hemophilia A and hemophilia B, patients with factor X deficiency have the most severe clinical bleeding, and hematoma and joint bleeding may occur in 2/3 of patients, with factor X activity below 1%. At the time of the patient, severe bleeding occurred. When the FX level was 10%, it may only show mild bleeding. The clinical manifestations of patients with FX activity below 1% were similar to those of hemophilia A.
Examine
Examination of hereditary coagulation factor X deficiency
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 may have different effects on the effects of the two complexes. For example, in FX Roma, the antigen level of FX is normal, but its effect on the exogenous coagulation pathway (3%) is better than that on the endogenous coagulation pathway (30). % to 50%) is much larger, 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, and patients with severe FX deficiency have bleeding time. May be prolonged, however, it is not clear whether the prolonged bleeding time is related to the barrier of FVa and FXa interaction on the platelet surface. The viper venom can directly lyse and activate FX. Therefore, the Russell venom time test is prolonged in most patients. FX activity and antigen, as well as genetic testing, are necessary to clarify the diagnosis of hereditary factor X deficiency.
Diagnosis
Diagnosis and identification of hereditary coagulation factor X deficiency
diagnosis
Diagnosis is based on clinical bleeding symptoms, genetic type and laboratory tests, and the FXI:C assay or the Biggs thromboplastin assay can determine the diagnosis.
Differential diagnosis
1. The disease is mainly related to prothrombin time (PT): identification of other hemorrhagic diseases with prolonged thromboplastin time (PTT). The Biggs thromboplastin test can be differentiated from hemophilia A and hemophilia B. Lupus anticoagulant can prolong PTT, normal PT, laboratory examination of lupus anticoagulant can be identified, the identification of acquired FXI deficiency is that there are autoantibodies in such patients, which can be identified by antibody screening test, often occurring in systemic Case of lupus erythematosus.
2. The diagnosis of hereditary coagulation factor X deficiency must be differentiated from the reduction in acquired FX secondary to vitamin K deficiency: Liver disease and warfarin may also exhibit symptoms of factor X deficiency, but in both cases The reduction of FX is also secondary, and there are other vitamin K-deficient clotting factors that can be diagnosed through detailed medical history, physical examination and laboratory tests. Isolated patients can be found in amyloidosis. Acquired coagulation factor X deficiency, which may be caused by amyloid-like absorption of FX.
