anti-activated protein C disease
Introduction
Introduction to anti-activated protein C In the APTT, if APC is added during the test, the APV is prolonged due to the inactivation of the factors Va and VIIIa by APC. If the APTT is not prolonged or prolonged after the addition of APC, it is called anti-activated protein C (APCD). basic knowledge The proportion of illness: the incidence rate is about 0.0001% - 0.0002% Susceptible people: no specific population Mode of infection: non-infectious complication:
Cause
Anti-activated protein C disease etiology
(1) Causes of the disease
Factor V Leiden mutations in APCD are autosomal dominant.
(two) pathogenesis
There are racial and regional differences in the occurrence and mechanism of APC-R. In addition to the factor V Leiden mutation, there may be different mechanisms such as mutation of other gene sites of Factor V or mutation of factor VIII gene and acquired factors. APCD has congenital and acquired scores. The former is mostly caused by hereditary defects of coagulation factors. The most common is the factor VLeiden mutation. Under normal circumstances, APC cleaves factor Va at Arg506, which causes the latter to lose its procoagulant activity. Factor V Leiden mutation refers to a missense mutation (GA) of the nucleotide 1691 of the factor V gene, which causes the amino acid at position 506 of the factor V molecule to change from Arg to Gln, thereby being free from the cleavage of APC. V still has normal procoagulant activity, and can resist the cleavage of APC, causing the body to be in a hypercoagulable state. Other genetic defects include factor V306 site mutation, factor VIII mutation, etc. Acquired APCD is common in antiphospholipid antibody. Patient.
Prevention
Anti-activated protein C prevention
Can take warfarin prevention.
Complication
Anti-activated protein C complications Complication
There is no complication of this disease.
Symptom
Anti-activated protein C symptoms common symptoms venous thrombosis
Mainly manifested as deep vein thrombosis.
Examine
Anti-activated protein C examination
1APC-APTT test;
2 chromogenic substrate method;
3 DNA analysis, the most used is the APC-APTT test, which includes two APTT tests, one sample added APC; the other without APC, the results are expressed by APC-SR:
APC-SR=(APTT without APC)/(APTT with APC)
Under normal circumstances, APC-SR 2.
The patient APC-SR can also be divided by the normal human APC-SR to obtain the corrected APC-SR, ie, n-APC-SR. Under normal circumstances, n-APC-SR>0.84, <0.84 can be diagnosed as APC resistance. For the factor V Leiden mutation, the heterozygous patient has an n-APC-SR of 0.45 to 0.70, and a homozygous patient of <0.45, but whether the APC resistance is caused by FV Leiden can only be determined by genetic analysis.
The chromogenic substrate method is based on the principle that APC can inactivate the factor FVIIIa to limit the formation of FXa. By detecting the activity of FXa to hydrolyze phenolamine and indirectly reacting to APC resistance, the APC-SR and APC-APTT measured by this method are basically Consistent.
DNA analysis uses PCR techniques and nucleotide sequence analysis to determine gene mutations in Factor V and to determine whether the patient is heterozygous or homozygous.
According to the condition, clinical manifestations, symptoms, signs, choose to do B-ultrasound, CT, X-ray, electrocardiogram, biochemistry, hematuria and other tests.
Diagnosis
Diagnostic identification of anti-activated protein C
Diagnostic criteria
1. Diagnostic criteria and basis
The domestic diagnostic criteria developed in Zhang Zhinan's book "Diagnostic and Efficacy Standards for Blood Diseases".
(1) There is venous thrombosis or asymptomatic.
(2) Anti-activated protein C sensitive ratio (APC-SR) < 2 or corrected anti-activated protein C sensitive ratio (n-APC-SR) < 0.84.
2. Foreign diagnostic criteria
(1) There is venous thrombosis or asymptomatic.
(2) Autosomal dominant inheritance.
(3) There are homozygotes and heterozygotes: the homozygous n-APC-SR value is <0.4, and the heterozygous n-APC-SR is 0.4 to 0.7.
(4) Factor V gene analysis mostly has FV Leiden.
3. Diagnostic evaluation
(1) Although APCD is closely related to venous thrombosis, it is not determined that APCD has thrombosis. The survey in Europe and the United States shows that the incidence of APCD in normal Caucasians can be as high as 15%, but a considerable number of patients can have no history of thrombosis for life. Patients with APCD have a significantly increased risk of thrombosis during pregnancy, surgery, oral contraceptives, and other risk factors such as protein C, protein S, and antithrombin deficiency. Therefore, there is a significant increase in the risk of thrombosis. In patients with thrombotic episodes of APCD, care should be taken to exclude congenital or acquired deficiency of combined protein C, protein S and antithrombin, and to exclude other high risk factors for thrombosis, including whether antiphospholipid antibodies are positive.
(2) Although APCD is mostly autosomal dominant, for the above reasons, other members of the family may not have a thrombus attack, so family history does not help the diagnosis.
(3) Although the reference values of APC-SR and n-APC-SR are given in the diagnostic criteria, the results obtained by using reagents from different sources are different. Therefore, each laboratory should establish its own normal reference value.
(4) In addition to reagents, APC-APTT, the test is also affected by other factors, such as protein S and factor II, V, VIII, IX, X levels are reduced, oral warfarin treatment, anti-phospholipid antibodies can affect Therefore, many APC-R heterozygotes are missed or misdiagnosed. Therefore, a modified trial is used to dilute the plasma to be tested with the deficiency factor V plasma, which can effectively correct the effects of other anticoagulant deficiency or anticoagulant drugs. And the sensitivity is greatly improved, especially for the APC-R caused by the factor VLeiden mutation, the specificity is up to 98.8%, and the sensitivity is almost 100%. In addition, the main advantage of the chromogenic substrate method is that it is not resistant to anticoagulation. The influence of drugs or other coagulation factors, such as APC-APTT, is helpful to improve the diagnostic rate. Antiphospholipid antibodies, including lupus-like anticoagulants and anti-cardiolipin antibodies, can interfere with APC-APTT, and the test results in low APC-SR. The use of platelet extracts can rule out the effects of antiphospholipid antibodies.
(5) The processing of the specimen to be inspected is very important. APC-SR is the ratio of the measured result of the patient to the normal person. Therefore, if the patient's plasma to be tested is cryopreserved, the normal control plasma should also be frozen accordingly. Platelets after freezing and thawing can affect the test and significantly reduce APC-SR. Therefore, platelets in plasma should be removed as much as possible when separating specimens.
Differential diagnosis
The main need to exclude the congenital or acquired deficiency of the combined protein C, protein S and antithrombin, as well as other acquired factors, such as the presence of antiphospholipid antibodies.
