Congenital Thrombophilias: an overview Mohannad Ibn Homaid

General principles We develop thrombosis when we are Deficient in clotting factor inhibitor Producing more coagulation factor either quantitativley or functionally

Group 1 Disorders Group 2 Disorders High Risk Of thrombosis Includes: Protein C and S Deficiency Antithrombin 3 Deficiency Relatively lower risk than group 1 Factor V leiden Prothrombin Mutation Dysfibrinogenemia Increased Cocentration of clotting factors

Group 1 Disorders

Protein C Deficiency Physiology Mutations : 2 Types Dillema Presentation Homozygotes present as neonatal purpura fulminans Heterozygotes develop thrombosis a bit later or when exposed to warfarin Diagnosis Measuring Functional and antigenic levels PCR

Protein S Deficiency Practically the same as Protein C deficiency Physiology. Unbound Levels vs bound Levels Mutation

Anti Thrombin 3 Deficiency Physiology Inactivates factors 2-12-11-10-9 Relationship with heparin Mutations 3 Types Dillema Presentation Severe thrombosis even with functional levels of 70-80% Homozygosity Diagnosis

Group 2 Disorders

Activated protein C resistance and Factor V leiden Physiology Factor V inactivated by Mutations The leiden Allele Found in 90% with APR Presentation Most common Generally Higher risk than normal population but not severe enough to cause purpura fulminanas Diagnosis APR: clotting Assay Factor V leiden :PCR

Prothrombin 201020 A mutation Physiology: Cleaves Fibrinogen to fibrin monomers Mutations Gain of Function Mutation mRNA doesn’t break down so it accumulates produces more prothrombin Presentation Same as all group 2 Disorders Diagnosis PCR

Dysfibrinogenemia Physiology Presentation Diagnosis Cleaved by thrombin into fibrin Aids in stabilizing platelet plugs DYS-fibrinogenemia ? Presentation 50% asymptomatic 50% Symtomatic Oslo 1 Mutation 10% Diagnosis Functional Assays

Other Disorders

Homocystinuria