Hereditary dysfibrinogenemia

Introduction to hereditary abnormal fibrinogenemia Hereditary abnormal fibrinogenemia is an autosomal dominant hereditary disease with a high penetrance. Most patients are heterozygous. However, there are also a few homozygous and heterozygous reports in the literature. basic knowledge The proportion of illness: 0.002% Susceptible people: no special people Mode of infection: non-infectious Complications: thrombosis

Causes of hereditary abnormal fibrinogenemia

(1) Causes of the disease

Most of the disease is chromosomal dominant, the main cause is three links of thrombin-fibrinogen reaction: 1 abnormal release of fibrin peptide A or B; 2 abnormal fibrinogen monomer polymerization; 3 fibrinogen monomer cross-linking defect.

(two) pathogenesis

Functional abnormalities of fibrinogen molecules involve all important steps in fibrin formation and stabilization. Converting fibrinogen to insoluble fibrin polypeptide requires first thrombin to cleave fibrinogen, releasing fibrin polypeptide A and fibrin polypeptide. B, the production of fibrin monomer, fibrin monomer and then multimerization, factor XIIa can stabilize the multi-fibrinated fibrin, the process of conversion of soluble fibrinogen to insoluble fibrin in patients with abnormal fibrinemia occurs obstacle.

The most common deficiency is the lack of fibrin multimerization. Abnormal fibrinogenemia can also be caused by a lack of fibrinogen peptide lysis. Fibrin produced by some patients with abnormal fibrinogenemia cannot be fibrinolytic. Dissolved, this part of the patient has a tendency to develop thrombotic disease, therefore, patients with abnormal fibrinogenemia may have bleeding, thrombosis, or no clinical manifestations, abnormal blood clot formation can lead to bleeding and fiber Abnormalities in protein resistance to tissue plasminogen activator (t-PA) or regulation of platelet aggregation can lead to thrombosis.

Many patients with abnormal fibrinogenemia may have poor wound healing at the same time. Patients with heterozygous abnormal fibrinemia usually contain 50% of normal fibrinogen, which is sufficient for the body to coagulate, but abnormal. Fibrinogen may affect the conversion of normal fibrinogen to fibrin. Therefore, in most patients, the bleeding tendency is more serious than estimated. When the abnormality of fibrinogen leads to the decrease of fibrinogen secretion or the acceleration of clearance, it is called Low abnormal fibrinogenemia is currently reported in 23 related cases.

Hereditary abnormal fibrinogenemia prevention

For patients with thrombosis, reasonable anticoagulant therapy can play an effective role in prevention and treatment.

Hereditary abnormal fibrinogen complications Complications thrombosis

A thrombus is a small piece of blood that forms on the surface of the endovascular exfoliation or repair of the cardiovascular system. In variable flow dependent patterns, thrombi consist of insoluble fibrin, deposited platelets, accumulated white blood cells, and trapped red blood cells. Thrombosis is a process of multifactorial changes involving many genetic and environmental factors that interact with each other. Patients with thrombogenic qualities are common in the clinic. The most important features are family history, recurrent, young, the severity of seizures and the unusual location of thrombosis.

Hereditary abnormal fibrinogenemia symptoms Common symptoms Menstrual flow more skin ecchymosis bleeding tendency Microthrombus abortion

About 40% of patients with abnormal fibrinogenemia are asymptomatic, 45% to 50% of cases show hemorrhagic disease, and the remaining 10% to 15% of patients present with thrombotic disease (venous or arterial), or At the same time, there is a tendency to hemorrhage and thrombosis. The abnormal fibrinogenemia has very mild bleeding, which is characterized by soft tissue hemorrhage, prone to ecchymosis and excessive menstrual blood. Although surgery or postoperative bleeding has also been reported, most cases There is no life-threatening risk. Patients with abnormal fibrinemia with a tendency to thrombosis usually have only mild thrombosis and rarely have fatal effects. Other abnormal fibrinogenemia manifestations include spontaneous abortion and wound healing. Bad and so on.

Examination of hereditary abnormal fibrinogenemia

1. The determination result of fibrinogen content varies depending on the method. The results measured by immunoassay, salting out method and heated precipitation method are normal, but the results obtained by thrombin assay are slow due to the slow coagulation of abnormal fibrinogen. Both are low.

2. 125I fibrinogen lifetime assay Rw Mammen assay with the half-life of 125I-labeled abnormal fibrinogen Bethesda I, II, normal results; input of allogeneic normal fibrinogen in patients with abnormal fibrinogen Philadelphia and Bethesda III, Its half-life is normal; however, the patient's own fibrinogen half-life is shortened.

3. Staphylococcal and fibrinogen aggregation experiments SC Jack-Aaweiger reports the presence of abnormal fibrinogen by the aggregation of pathogenic staphylococci and fibrinogen molecules. The principle is: the A chain of fibrinogen and The C-terminus of the B chain can bind to Staphylococcus aureus. If the abnormal fibrinogen is at the C-terminus, this experiment can assist in the examination.

4. Immunoelectrophoresis and immunodiffusion abnormal fibrinogen generally has no abnormal precipitation line, but the precipitation line of abnormal fibrinogen Detroit is broadened; abnormal fibrinogen Los Angeles has two special precipitation lines in immunoelectrophoresis. Abnormal fibrinogens that migrate toward the anode: Baltimore, Detroit, Bethesda I, New York, Nancy, Bethesda II, Buenos Aires, Paris II, Caracas, and Vancouver; etc.; Metz, Amsterdam, and Cleveland I, etc. Other immunoelectrophoresis is normal.

5. Polyacrylamide gel electrophoresis (PAGE) The purified fibrinogen was reduced by SDS-PAGE and showed that most of the abnormal fibrinogen had the same electrophoretic spectrum as normal fibrinogen, but abnormal fibrinogen The electrophoretic bands of Baltimore, Detroit, Metz, and Montreal are more eccentric than the normal distribution. Two B chains are seen in the abnormal fibrinogen Poutoise, one of which is the normal B chain; the abnormal fibrinogen is found in ParisI 2 A chain, one is normal and one is abnormal.

6. DEAE-cellulose chromatography abnormalities Some abnormal fibrinogens exhibit abnormal chromatographic phenomena during DEAE-cellulose chromatography, such as Baltimore, Paris II, Philadelphia, Nancy, etc., abnormal fibrinogens Paris I and Paris. II, Nancy, Philadelphia's elution peak is later than normal.

7. Identification of fibrin clots Abnormal thromboelastograms of some abnormal fibrinogens, such as abnormal fibrinogens Paris I and Paris II, Cleveland I, Detroit, Baltimore, Vienna, Manila, Marburg and Giessen, etc. The gamma value is prolonged and the value of Ma is decreased. Electron microscopy shows some morphological abnormalities of fibrin clots composed of abnormal fibrinogen, such as Giessen, Cleveland II, Baltimore, Montreal, Paris II and Los Angeles.

8. Determination of sugar content The abnormal glycosylation of fibrinogen can be abnormal. The main determinations are hexose, hexose and decanoic acid. The reduction of hexose is: abnormal fibrinogen Cleveland II, Detroit, Manila, Paris E, C1evelandI, etc.; the reduction of aminohexose is: Cleveland I, Manila, Nancy, Cleveland E, etc.; the increase in tannic acid is: Paris II, Nancy, Cleveland I and so on.

According to the condition, clinical manifestations, symptoms, signs, choose to do B-ultrasound, X-ray, CT and hematuria routine, biochemical examination.

Diagnosis and differential diagnosis of hereditary abnormal fibrinogenemia

The diagnosis of this disease should meet the following conditions:

1 has a positive family history of genetics (except for new cases);

2 clinically often manifested as bleeding tendency, thrombosis and wound rupture;

3 laboratory tests are of great value in the diagnosis and differential diagnosis of this disease;

4 Exclude acquired abnormal fibrinogenemia and congenital fibrinogen deficiency.

Differential diagnosis

Abnormal fibrinogenemia should be primarily identified with congenital fibrinogen deficiency and fetal fibrinogen, and all causes of fibrinogen conversion to fibrin delay should be considered:

1. Fibrinogen structure changes.

2. The effect of other plasma proteins or drugs on fibrin formation.

3. Reduced fibrinogen concentration.

Liver disease can cause structural changes in acquired fibrinogen, characterized by elevated levels of sialic acid and shortened fibrinogen life. Acquired abnormal fibrinogenemia can also be seen in acute pancreatitis, malignant tumors, especially primary or secondary Hepatic cancer, renal cell adenocarcinoma and certain lymphomas.

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