Definition and possible reasons

When a patient has an increased tendency to develop thromboses and/or embolies the patient then has an existing thrombophilia. The formation of the thrombus is then primarily caused by a disorder in the regulation of the coagulation system. A dysbalance in the plasmatic coagulation system primarily seems to influence the venous system. Whether the classic risk parameters for venous thrombosis also are risk parameters for the arterial system is controversially debated. However, it should be considered that the formation of a thrombus is a multifactual event.

Principally the regulation of the plasmatic coagulation system could be due to a disorder e.g.

  • Decreased concentration of coagulation inhibitors
  • Increased activity of pro-coagulating factors
  • Decreased fibrinolytic activity

In these cases a distinction between congenital and acquired disorders should be made.

Risk parameters for venous thrombosis

  • Factor V-Leiden/APC-resistance
  • Prothrombin mutation
  • Persistently high factor VIII levels
  • Protein C-deficiency
  • Protein S-deficiency
  • Antithrombin-deficiency
  • Hyperhomocysteinaemia
  • Lupus Anticoagulants/Antiphospholipid syndrome

Apart from these established risk factors there is a multitude of other possible reasons that still are controversially debated:

  • Heparin cofactor II-deficiency, plasminogen, factor XII, TFPI (tissue factor pathway inhibitor)
  • Increase in histidin rich glycoprotein, fibrinogen, PAI-1, TAFI (thrombin activable fibrinolysis inhibitor),
  • Mutations in the thrombomodulin-gene, PAI-1-gene, factor XIII-gene
  • Release disorders by t-PA.

The formation of a thrombus is a multifactual event and further predisposing thrombophilia factors are identified. Among those:

  • Immobility, trauma, surgery
  • Use of oral contraceptives, hormone substitution (after menopause) pregnancy and bed confinement
  • Malignomes, venous catheter, nephrotic syndrome
  • Myeloproliferative diseases, heparin induced thrombocytopenia
  • High age, high BMI, severe infections
  • Long flights, post thrombotic syndrome

Diagnostic Peculiarities

The Protein C/S-system limits the thrombin formation by irreversibly inactivating the factors Va and VIIIa. Both Protein C and S belong to the vitamin K-dependent factors, i.e. the determination during therapy with phenprocoumon may lead to false values and is therefore only conditionally meaningful.

The antithrombin activity decreases during administration of heparin.

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