Congenital Thrombophilias : an overview

1. Congenital Thrombophilias:an overview MohannadIbnHomaid

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

6. Group 1 Disorders

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

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

10. 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

11. Group 2 Disorders

12. 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 purpurafulminanas • Diagnosis • APR: clotting Assay • Factor V leiden :PCR

13. 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

14. 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

15. Other Disorders

16. Homocystinuria