Thrombophilic states

1. Thrombophilic states

2. Thrombophilic state is characterizedby a shift in the coagulationbalancein favour of hypercoagulability – i.e. easier and oftener formation of the blood coagulum • inborn (genetically determined) • acquired

3. Acquired thrombophilic state Thrombophilic reaction is a part of the complex inflammatory and stress response of the organism, and a part of the phylogenetic adaptation in order to deal with presumed damage of the organism.

4. The inflammatory states are accompanied by the following phenomena: • increased expression of selectins (selectin E on endothelial cells, selectin L on leukocytes, selectin P on platelets and endothelial cells) • increased expression of integrins (ICAM-1 and VCAM-1 on endothelial cells, LFA-1 on leukocytes) • mutual interactionsof adhesion molecules induce adhesion and activation of endothelial and inflammatory cells that are stimulated to produce PAF (platelet activating factor) with a subsequent adhesionof plateletsto endothelium,releasing vWf.

5. Virchow`s triad 1/Changes in the pattern of blood flow (flow volume)permanentdilution of coagulation and fibrinolytic factors 2/Changes in the vessel wallintact endothelium has antithrombotic and anticoagulation effects (endothelial dysfunction causes thrombophilia) 3/Changes in the constituents of blood(hypercoagulability) inflammatory reactions, inborn thrombophilic states

6. Clinical situations accompanied by thrombophilia: •infections • tumours, incl. haematological malignancies (often the first sign of the tumour) • operations • hormonal contraception

7. Laboratory diagnostics: * routine examinations: serum levels of CRP, fibrinogen, platelet count, D-dimers * special examinations: serum levels of selectins and integrins – not available in common laboratories

8. Typesof the thrombi white thrombus arterial (platelets – leukocytes – fibrinogen) with small participation of plasma coagulation factors (blood flow washes and dissolves them) • can be also formed on the intact endotheliumat „shear stress“, that leads to its activation(platelets being activated as well) and expression of adhesion moleculeswith a subsequent cascade of thrombophilic reactions

9. Clinical situations caused by the white thrombus: • acute coronary syndromes • arterial thromboses • ischaemic brain strokes

10. red thrombus venous (fibrin – erythrocytes) • often caused by slowing down of the blood flow Clinical situations caused by the red thrombus: • deep venous thrombosis (DVT) of the lower extremities • pulmonary embolization (PE)

11. Clinically important thrombophilic states

12. APC resistance • inborn disease • mutation of the Leiden factor V • Cambridge mutationof the factor V • decreased level of the factor V Examinations: • coagulation –aPTT • PCR – mutation of the Leiden factor

13. Hyperhomocysteinaemia • inborn • acquired Homocysteineis an intermediateproductof the metabolism of the essentialamino acid methionine. • risk factor for the development of arterial and venous thrombosis Therapy:folates +vitamin B

14. Antiphospholipid syndrome (Hughes syndrome) • acquired • multiple different antibodies associated with both arterial and venous thrombosis • primary –three primary classes of antibodies: 1) anticardiolipin antibodies (ACLA) 2) lupus anticoagulant (LA) 3) antibodies directed against specific molecules, incl. a molecule known as beta-2-glycoprotein 1 • secondary – accompanying diseases, such asSLE or other autoimmunediseases, leukaemias, lymphomas

15. Other inborn thrombophilic states • deficit of the protein C • deficit of the protein S  • deficit of antithrombin III • increased levelof prothrombin • deficit of thrombomodulin • increased level of factors VIII, IX, XI, fibrinogen

16. Antithrombogenic mutations • mutation of Annexin V • antithrombogenic mutation may counterbalance thrombophilic mutation in clinical practice and neutralize its thrombophilic effects.