Congenital Thrombophilias: an overview

Mohannad Ibn HomaidCongenital Thrombophilias:an overview

General principlesWe develop thrombosis when we are

Deficient in clotting factor inhibitor

Producing more coagulation factor either quantitativley or functionally

Group 1 DisordersGroup 2 DisordersHigh Risk Of thrombosis

Includes:Protein C and S DeficiencyAntithrombin 3 DeficiencyRelatively lower risk than group 1

Includes:Factor V leidenProthrombin MutationDysfibrinogenemiaIncreased Cocentration of clotting factors

Group 1 DisordersProtein C DeficiencyPhysiologyMutations : 2 TypesDillemaPresentationHomozygotes present as neonatal purpura fulminansHeterozygotes develop thrombosis a bit later or when exposed to warfarinDiagnosisMeasuring Functional and antigenic levelsPCR

Protein S DeficiencyPractically the same as Protein C deficiencyPhysiology. Unbound Levels vs bound LevelsMutationAnti Thrombin 3 DeficiencyPhysiologyInactivates factors 2-12-11-10-9Relationship with heparinMutations 3 TypesDillemaPresentationSevere thrombosis even with functional levels of 70-80%HomozygosityDiagnosis

Group 2 DisordersActivated protein C resistance and Factor V leidenPhysiologyFactor V inactivated by MutationsThe leiden AlleleFound in 90% with APRPresentationMost commonGenerally Higher risk than normal population but not severe enough to cause purpura fulminanasDiagnosisAPR: clotting Assay Factor V leiden :PCR

Prothrombin 201020 A mutation Physiology:Cleaves Fibrinogen to fibrin monomersMutationsGain of Function MutationmRNA doesnt break down so it accumulates produces more prothrombinPresentationSame as all group 2 DisordersDiagnosisPCRDysfibrinogenemiaPhysiologyCleaved by thrombin into fibrinAids in stabilizing platelet plugsDYS-fibrinogenemia ?Presentation50% asymptomatic50% SymtomaticOslo 1 Mutation 10%DiagnosisFunctional Assays

Other DisordersHomocystinuria