Hereditary factor V deficiency
Introduction
Introduction to hereditary coagulation factor V deficiency Hereditary coagulation factor V (FV) deficiency, the patient is a woman, with mild to moderate bleeding throughout her life. This disease is autosomal recessive, rarely seen, and the incidence rate does not exceed 11 million. A small number of parents are married to close relatives. Some patients may be associated with other congenital anomalies, such as ureteral malformations, patent ductus arteriosus. basic knowledge The proportion of illness: 0.02% Susceptible people: no special people Mode of infection: non-infectious Complications: hematuria
Cause
Causes of hereditary coagulation factor V deficiency
(1) Causes of the disease
The disease is autosomal recessive, but there are also several reports of dominant inheritance types.
(two) pathogenesis
FV is a single-chain glycoprotein synthesized by liver and megakaryocytes. The plasma concentration is 7g/ml, and the half-life is about 12-15h. Except in plasma, megakaryocytes and platelet -granules are also present. Platelet FV accounts for blood FV. 20%, mature FV is a single-chain glycoprotein composed of 2196 amino acid residues, with a molecular weight of 330,000. Its structure is similar to that of factor VIII. The arrangement is also A1-A2-B-A3-C1-C2, amino acids in regions A and C. The sequence is about 40% homologous to the corresponding region of FVIII, and the B region is different from the B region of FVIII. During the activation of FV, the B region is lost, and the FV gene is located in the long arm of the first pair of chromosomes (1q21~25), and the gene is long. 80kb, mRNA is 6.8kb, there are 24 introns and 25 exons. During coagulation, FVa, together with calcium ions and phospholipids as cofactors, greatly accelerates the enzymatic action of FXa on prothrombin to produce thrombin. As a cofactor, FV needs to be cleaved by thrombin into a double-stranded molecule FVa linked by calcium bridge. The cleavage site is arginine 709-serine 710, spermine 1018-serine 1019, and arginine 1545-serine 1546. 3 sites, light chain (A3-C1-C2) with phospholipids, prothrombin and APC binding Point; heavy chain (A1-A2) and light chain are required to link FXa, FVa is inactivated by APC (when S, Ca2 and phospholipids are stored), FV antigen determination indicates that most homozygotes lack FV, only a few have FV with dysfunction, some mutations cause FV deficiency, and the missense mutation C-221- reduces FV activity. The substitution of C1779-Sue produced by nt5509GA in exon 16 leads to partial deficiency of FV, and the other mutation is external. Deletion of 4 bases in neutron 13 resulted in the appearance of a stop codon, resulting in the deletion of part of the F region of the synthetic FV, the A3, C1 and C2 regions, the FV Leiden mutation, and the majority of hereditary APC resistance. A heterozygous molecular defect is associated with a double heterozygote, although the FV activity is reduced, but hemostasis is normal, and thrombosis may occur due to the phenotype of APC resistance.
Prevention
Prevention of hereditary coagulation factor V deficiency
Establish genetic counseling, strict premarital screening, and strengthen prenatal diagnosis to reduce the birth of children.
Complication
Hereditary coagulation factor V deficiency complications Complications
hematuria.
Symptom
Hereditary Coagulation Factor V Deficiency Symptoms Common Symptoms Gum bleeding Bleeding Bleeding Skin Frecking After tooth extraction Hemorrhage Intra-articular hemorrhage Congenital X-factor deficiency
This disease is only homozygous patients with bleeding symptoms, its FV: C often less than 10%, manifested as skin ecchymosis, nose bleeding, bleeding gums, menorrhagia, trauma or bleeding after tooth extraction, severe bleeding after surgery, hematuria and Gastrointestinal hemorrhage also occurs, muscle and joint bleeding is rare, but it also occurs, cerebral hemorrhage is rare, due to platelet FV deficiency, platelet coagulation function is weakened, some patients have low plasma FV, only mild bleeding symptoms, bleeding symptoms and platelet FV The correlation of content is better than the correlation with plasma FV level. FV Quebec autosomal inheritance, severe bleeding symptoms, platelet FV activity is normal 2% to 4%, is a defect in FV activity secondary to platelet defects, FV level is Venous or arterial thrombosis has been reported in 2% to 14% of normal patients, and FV activity in heterozygous cases is 26% to 60% of normal, with no bleeding symptoms.
Examine
Examination of hereditary coagulation factor V deficiency
1. Both patients with homozygous PT and PTT were prolonged, and all of them could be corrected by adsorption plasma. The time of thrombin was normal. A few patients may have prolonged bleeding time, which may be related to platelet FV deficiency.
2 The heterozygotes were normal except for the quantitative determination of FV:C.
3. The diagnosis needs to determine its procoagulant activity (FV: C), the homozygous for severe bleeding is often lower than 1% of normal people, the bleeding symptoms are often less than 10%, and the homozygous FV: C can reach 20%. The zygote FV: C is usually 30% to 60%, and cases with abnormal FV:Ag have also been reported, suggesting that similar to other genetic clotting factor diseases, FV deficiency also has heterogeneity.
Diagnosis
Diagnosis and identification of hereditary coagulation factor V deficiency
The medical history, clinical manifestations and laboratory tests can diagnose the disease, and the FV:C measurement has diagnostic significance.
The hereditary factor V deficiency must be differentiated from the combined deficiency of hereditary factor V and hereditary factor VIII. The combination of the two lacks a specific syndrome, and the activity of both factors is only normal 15%-20 %, in cases of mild deficiency of FV or FVIII should consider the possibility of a combined deficiency of the two, specific inhibitors of FV can be found in patients after surgery, but few patients treated with antibiotics It has been found that although the acquired coagulation factor V deficiency due to the above reasons is transient, it can cause bleeding, and FV reduction can also occur in DIC and severe liver diseases.
