Congenital Thrombophilias an overview Mohannad Ibn Homaid General

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 Relatively lower risk than group 1 Includes: • Protein C and S Deficiency • Antithrombin 3 Deficiency Includes: • 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 �m. RNA doesn’t break down so it accumulates produces more prothrombin �Presentation �Same as all group 2 Disorders �Diagnosis �PCR

Dysfibrinogenemia �Physiology �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