Teaching Pearls:
- Hypercoagulable etiologies: Acquired vs inherited causes.
- Inherited Hypercoagulable work-up: Protein C, Protein S, Factor V Leiden, Antithrombin 3, Prothrombin G2021A
- Acquired causes: prolonged rest, high risk surgery, hospitalization, medications, age
- In acute infection/acute clot, the Protein C, protein S and Antithrombin 3 levels may be decreased, giving a false positive result. The Factor 5 Leiden and Prothrombin Gene mutation are gene studies so they are not affected by acute illness.
- You can see both arterial and venous clots in Anti-phospholipid syndrome and Paroxysmal Nocturnal Hematuria (think myelosuppression and thrombosis, intravascular hemolysis)
- Thrombosis plus thrombocytopenia –> Think HIT, APS, PNH
- Clinical Diagnosis of APS: Unexplained thrombocytopenia, spontaneous miscarriages, arterial/venous thrombosis
- Laboratory Diagnosis of APS: aCL, B2GP, LA, timing requires positivity of markers even after three months due to false positive serologic studies
Inherited Thrombophilia
| Conditions | Epidemiology | MOA | Severity of Hypercoagulability |
| Factor V Leiden | Most common cause, 5% of Caucasians | Point mutation in one active site of protein C, decreased ability to inactivate factor V | Moderate |
| Prothrombin Gene Mutation | Second most common cause | More stabilized prothrombin (harder to inactivate) | Moderate |
| Protein C | Less Common | Protein C inactivates factors Va and VIIIa. | Severe |
| Protein S | Less Common | Protein S is a cofactor for protein C | Severe |
| AT Deficiency | Less Common | Antithrombotic protein that inhibits factor II and X | Severe |
SCVMC IM Chief Resident Blog 