Choice and discussion of laboratory parameters in thrombophilia.
Thrombophilia
- Hypercoagulation (Thrombophilia) occurs when a patient has a tendency to form a thrombus.
Criteria for thrombophilia
Presence of the ‘risk triad’ – injured vascular endothelium, stasis, hypercoagulation
Data for: Disordered fibrinolysis: 1. defects in t-PA ,2. deficiency of Plg ,3. increased PAI,4. oral contraceptives, 5. Vasculitis
Inherited coagulation disorders
- Inherited hypercoagulable states include deficiencies of protein S, protein C, and antithrombin III.
- Normal amounts of these substances are needed to stop excessive coagulation.
- Each of these three disorders is inherited in an autosomal dominant manner.
- The most common inherited disorder of coagulation inhibitors is protein S deficiency.
- The patient is started on intravenous heparin, which is adjusted to maintain the APTT at 1.5 to 2.5 times the control value.
- Heparin is continued until the prothrombin time is 1.3 to 1.5 times the control value, a process that takes approximately 5 days.
- Increased aggregation of platelets:
- endothelial injury
- activation of the platelets
- stasis
- Decreased capacity of fibrinolysis
- -Decreased level of plasminogen and its activators
- -increased level of the inhibitors of fibrinolysis
Protein C.:is part of the anticoagulant regulatory mechanism
Free Protein S:Protein S is a vitamin K dependent cofactor for the anticoagulant activity of activated protein C (APC).
Antithrombin: (AT) is a major inhibitor of blood coagulation
Antithrombin III deficiency can be of 2 types.
- Type I antithrombin deficiency states in which heterozygous mutations lead to a complete loss of the mutant antithrombin protein result in immunologic and functional levels that are 50% or less than normal.
- Type II antithrombin deficiency states are usually the result of single amino acid changes that result in functional deficits in a molecule that is otherwise synthesized and secreted into the plasma in a normal fashion.
Results from the clinical-laboratory tests
- АТ III, PrC, PrS - deficiency
- НСII
- factor V Leiden, 20210
- factor XII
- fibirnogen
- plasminogen, t-PA, PAI-1
Genetic defect of factor V- Leiden- point mutation The identification of Factor V Leiden mutation is carried out using PCR technology,Resistance to аPrC
- Мethod – chronometric test, based on аPTT and accomplished in the presence or absence of standardized аPrC reagents
- The result is reported as NSR-normalized sensitivity time
- heterozygotes < 2,29 аPrCR
- homozygotes < 1,8 аPrCR
Prothrombin gene mutation: People carrying the mutation have higher levels of factor II than normal and the increased risk of thrombosis is thought to be a function of this.