Chapter 34 Vascular Thrombosis Due to Hypercoagulable States

1. Chapter 34Vascular Thrombosis Due to Hypercoagulable States Erika Lu August 22, 2005 Vascular Surgery Conference

2. Epidemiology • Thrombosis is the major cause of death in the world • MI and stroke (arterial thrombosis) are the #1 and #2 killer worldwide • Molecular defects increase a patient’s risk for thrombosis in 18%-30% of all cases of venous thromboembolism • Arterial thrombosis more likely environmental/acquired cause rather than inherited disorder

3. Biochemistry of Thrombosis PK Kallikrein Plasminogen XII XIIa C4bBP PAI-1 XIa Protein S Plasmin IXa APC Insol Fibrin FDP VIIIa VIIa-TF Xa FVL Sol Fibrin Va AT II G20210A Thrombin HCII Fibrinogen

4. Biochemistry of Thrombosis PK Kallikrein Plasminogen XII XIIa C4bBP PAI-1 XIa Protein S Plasmin IXa APC Insol Fibrin FDP VIIIa VIIa-TF Xa FVL Sol Fibrin Va AT II G20210A Thrombin HCII Fibrinogen

5. Arterial Thrombosis • White clot – platelet rich • Rare to see arterial thrombus in a healthy vessel • Usually atherosclerotic change with… • Diabetes • Hyperlipidemia • Tobacco use • Acquired procoagulant states (i.e. HIT and antiphosholipid antibodies

6. Arterial Thrombosis • Manifests in large vessel occlusions • MI and stroke • Peripheral vascular occlusive disease • There are genetic polymorphisms that may increase your risk, but not really predictive of risk of thrombus when you look at large population studies • Elevated factor VII • Elevated fibrinogen • Hyperhomocysteinemia • Elevated lipoprotein a

7. Venous Thromboembolism • Red clot – RBC’s trapped in fibrin strands • Virchow’s Triad: vessel wall change, hypercoagulability and stasis have a major role! • Classic Protein Deficiencies: • Antithrombin III deficiency • Protein C deficiency • Protein S deficiency

8. Venous Thromboembolism • Less common causes for thrombosis • Abnormal fibrinogen • Abnormal plasminogen • Elevated factors XI, IX, and VIII • Hematologic conditions that cause hypercoagulability • TTP • HUS • DIC • Polycythemia vera and essential thrombocythemia

9. Venous Thromboembolism • Acquired Risk Factors: • Immobility • Obesity • Chronic neurologic disease • Cardiac disease • Pregnancy, use of OCP’s • Surgery, particularly thoracoabdominal, ortho, GYN • Trauma • Malignancy • Nephrotic syndrome

10. Venous Thromboembolism • Interesting Factoids on Cancer and VTE • Occult cancer in 0.5 – 5% of VTE pts • 3x more likely to get cancer in next 3 yrs if idiopathic VTE • 19% of cancer pts have a VTE • Chemo increases risk of VTE because it increases tissue factor and expression of E-selectin, thereby increasing thrombus potential

11. Antithrombin Deficiency (1-2%)

12. Protein C and S Deficiencies (2-5%)

13. Heparin-Induced Thrombocytopenia & Thrombosis Syndrome (up to 30%)

14. Lupus Anticoagulant/Antiphospholipid Syndrome

15. Factor V Leiden (resistance to APC)

16. Hyperhomocysteinemia (10%)

17. Prothrombin G20210 Polymorphism (4-6%)

18. Defective Fibrinolysis, Dysfibrinogenemia, and Lipoprotein (a)

19. Abnormal Platelet Aggregation

20. Elevated Procoagulant Factors: VIII, IX, XI

21. What tests do we order? • Antithrombin activity and antigen assay • Protein C activity and antigen assay • Free protein S antigen assau • APC resistance assay • Factor V Leiden by PCR • Homocysteine level • Prothromnin G20210A by PCR • Antiphospholipid or anticardiolipin Ab • Clottable fibrinogen and fibrinogen antigen • Dilute Russell viper venom time • Tissue thromboplastin inhibition time • Β2 glycoprotein I antibodies • PT/PTT • D-dimer

22. Suggested Treatment Algorithm 3-6 months Aggessive ppx anticoag for 2nd VTE Yes VTE Acute Identifiable Therapy Risk/Etiology No Test for Hypercoag ? 6 months State Neg Anticoagulation + Low risk recur Hi-risk recurrence Life-long anticoagulation