Thrombophilic states

Thrombophilic state is characterized by a shift in the coagulation balance in favour of hypercoagulability – i.e. easier and oftener formation of the blood coagulum is characterized by a shift in the coagulation balance in favour of hypercoagulability – i.e. easier and oftener formation of the blood coagulum inborn (genetically determined) inborn (genetically determined) acquired acquired

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. 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.

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

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

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

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

Types of 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 endothelium at „shear stress“, that leads to its activation (platelets being activated as well) and expression of adhesion molecules with a subsequent cascade of thrombophilic reactions stress“, that leads to its activation (platelets being activated as well) and expression of adhesion molecules with a subsequent cascade of thrombophilic reactions

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

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)

Clinically important thrombophilic states

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

Hyperhomocysteinaemia inborn inborn acquired acquired Homocysteine is an intermediate product of the metabolism of the essential amino acid methionine. - risk factor for the development of arterial and venous thrombosis thrombosis Therapy: folates + vitamin B

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) 1) anticardiolipin antibodies (ACLA) 2) lupus anticoagulant (LA) 2) lupus anticoagulant (LA) 3) antibodies directed against specific molecules, 3) antibodies directed against specific molecules, incl. a molecule known as beta-2-glycoprotein 1 incl. a molecule known as beta-2-glycoprotein 1 - secondary – accompanying diseases, such as SLE or other autoimmune diseases, leukaemias, lymphomas

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

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