Congenital Thrombophilia: Pathogenesis and Complications
Authors: Brian Yu Chieh Cheng, Yan Yu* Reviewers: Mehul Gupta, Hannah Yaphe, Tejeswin (Jovey) Sharma, Man-Chiu Poon* *MD at time of publication
Group I
Hereditary deficiencies of coagulation inhibitors
Group II
Hereditary disorders with ↑ levels or function of coagulation factors
Antithrombin (AT) deficiency
AT inhibits thrombin & activated coagulation e.g. factor X (FXa)
Autosomal dominant mutation of the
SERPINC1 gene causes ↓ production of AT
↓ AT concentrations allows thrombin & FXa to promote secondary hemostasis
Protein C (PC) deficiency
Protein S (PS) deficiency
Factor V Leiden
Autosomal dominant point mutation of the Factor V gene
Single nucleotide substitution (G1691A) results in mutated form of FVa protein
FVa becomes resistant to aPC & PS inactivation
FVa is broken down at ↓ rate
Prothrombin mutation
Autosomal dominant point mutation of the Prothrombin gene
Single nucleotide substitution (G20210A) of the gene’s 3’ untranslated region
Accumulation of prothrombin mRNA & protein copies of prothrombin
↑ concentration of prothrombinà ↑ conversion to thrombin
↑ clotting factor quantity or function due to mutations intrinsic to these clotting factors
Activated Protein C (aPC) & PS combine to inhibit
activated clotting Factors V & VIII (FVa & FVIIIa)
Autosomal dominant mutation of the PROC & or PROS1 gene ↓ production of PC and/or PS
↓ aPC & PS concentrationsà less breakdown of FVa & FVIIIa, ↑ blood’s clotting ability
↑ clotting factor function due to ↓ inhibition or breakdown of clotting factors
Congenital Thrombophilia
An inherited abnormality / imbalance of blood coagulation factors that increases the risk of thrombus formation
↑ generation of thrombin
↑ clotting tendency, especially in veins where blood flow is slower/prone to stasis (see Calgary Guide slide on Virchow’s Triad)
Venous Thromboembolism
Deep Vein Thrombosis Pulmonary Embolism
Sign/Symptom/Lab Finding
Published August 15, 2021 on