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Chapter 34 Vascular Thrombosis Due to Hypercoagulable States

This chapter discusses the epidemiology, biochemistry, and types of vascular thrombosis, including arterial and venous thromboembolism, and explores the various genetic and acquired risk factors associated with hypercoagulable states.

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Chapter 34 Vascular Thrombosis Due to Hypercoagulable States

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  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

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