1. Congenital Thrombophilias: an overview
Mohannad Ibn Homaid

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

4. 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

6. Group 1 Disorders

7. 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

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
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 purpura fulminanas
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 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

15. Other Disorders

16. Homocystinuria