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Thrombolysis
Brandt C. Wible, MD; T. Gregory Walker, MD, FSIR
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KEY FACTS

  • Terminology

    • Preprocedure

      • Procedure

        • Outcomes

          TERMINOLOGY

          • Definitions

            • Thrombolysis: Minimally invasive method for clearing/dissolving intravascular thrombus
              • Intravenous (IV) thrombolysis delivers systemic dose of medication designed to promote fibrinolysis
                • Most commonly used form of thrombolysis
                  • Tissue plasminogen activator (tPA) most frequently used thrombolytic drug
              • Direct intravascular thrombolysis requires placement of catheter/device into thrombosed vessel
                • May place either intraarterially or intravenously
                  • Localized treatment of thrombosed target vessel
            • Thrombolytic agent: Thrombus-dissolving medication
              • tPA
                • Catalyzes plasminogen conversion into plasmin
                • 5 min half-life; high fibrin specificity
                • Recombinant tPA (r-tPA) also available; made using recombinant biotechnology; various proprietary brands
                  • Activase (alteplase) (Genentech)
                  • Retavase (reteplase) (EKR Therapeutics)
                  • TNKase (tenecteplase) (Genentech)
              • Streptokinase
                • Indirect plasminogen activator
                • Unpopular due to antigenicity: Inactivated by antibody formation
              • Urokinase
                • Induces systemic lysis; poor fibrin sensitivity
                • Metabolized in liver; 15 min half-life
            • Catheter-directed thrombolysis (CDT): Infusion of thrombolytic agent via percutaneously placed catheter
              • Also termed pharmacologic thrombolysis
                • May be intraarterial or intravenous
                  • Delivers concentrated dose to thrombosed vessel
            • Mechanical thrombolysis (MT): Fragmentation of thrombus using intravascular medical device
              • Macerates clot into macro-/microscopic debris
            • Pharmacomechanical thrombolysis (PMT): Use of combined mechanical device/thrombolytic agent
              • Increases thrombus surface area in contact with thrombolytic
              • Combined therapy typically more effective
          • Clinical Vascular Thromboembolic Scenarios

            • Acute limb-threatening ischemia (ALI)
              • Sudden decrease in arterial perfusion to limb, potentially threatening its viability
                • Capillary return/pulses/sensation may be compromised/absent
                  • Check for 5 Ps: Pain, pallor, pulselessness, paralysis, paresthesia
                • Causes of acute limb-threatening ischemia
                  • Arterial embolus from proximal source
                  • Arterial disruption/trauma
                  • Acute in situ arterial thrombosis
            • Acute mesenteric ischemia
              • Arterial occlusive form may be embolic or thrombotic; venous form is thrombotic
            • Portal venous thrombosis
              • Primary form: Idiopathic
              • Secondary: Known etiologic factor
                • e.g., prothrombotic state/neoplasm/inflammatory
            • Pulmonary embolism (PE)
              • Massive pulmonary embolism with right heart strain
            • Lower extremity venous thrombosis
              • Phlegmasia cerulea dolens: Severe form of deep venous thrombosis (DVT); thrombotic occlusion of entire venous drainage of extremity
                • Acute, severe pain; cyanosis and edema
                • High risk of fatal pulmonary embolism despite anticoagulation
                • 40-60% result in venous gangrene; 20-50% amputation
                • Underlying malignancy in 50% of cases
              • Postthrombotic syndrome (PTS): DVT sequela
                • Result of chronic venous hypertension
                  • Due to valvular damage, venous reflux, impaired venous return
                • Aggressively treat DVT to limit PTS risk
                  • 20-40% of iliofemoral DVT develop PTS in 2 years
            • Upper extremity venous thrombosis
              • Axillosubclavian vein thrombosis (ASVT)
                • Primary form: Paget-Schroetter syndrome
                • Secondary form: Associated inciting venous injury
                  • Long-term central venous catheters/pacemakers
                  • Malignancy/adenopathy

          PREPROCEDURE

          • Indications

            • Contraindications

              • Preprocedure Imaging

                • Getting Started

                  PROCEDURE

                  • Procedure Steps

                    • Findings and Reporting

                      • Alternative Procedures/Therapies

                        POST PROCEDURE

                        • Things to Do

                          OUTCOMES

                          • Complications

                            • Expected Outcomes

                              Selected References

                              1. Watson L et al: Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev. 11:CD002783, 2016
                              2. Comerota AJ: Thrombolysis for deep venous thrombosis. J Vasc Surg. 55(2):607-11, 2012
                              3. Manninen H et al: Catheter-directed thrombolysis of proximal lower extremity deep vein thrombosis: a prospective trial with venographic and clinical follow-up. Eur J Radiol. 81(6):1197-202, 2012
                              4. Karnabatidis D et al: Quality improvement guidelines for percutaneous catheter-directed intra-arterial thrombolysis and mechanical thrombectomy for acute lower-limb ischemia. Cardiovasc Intervent Radiol. 34(6):1123-36, 2011
                              5. Kühn JP et al: Intraarterial recombinant tissue plasminogen activator thrombolysis of acute and semiacute lower limb arterial occlusion: quality assurance, complication management, and 12-month follow-up reinterventions. AJR Am J Roentgenol. 196(5):1189-93, 2011
                              6. Popuri RK et al: The role of thrombolysis in the clinical management of deep vein thrombosis. Arterioscler Thromb Vasc Biol. 31(3):479-84, 2011
                              7. Schrijver AM et al: Dutch randomized trial comparing standard catheter-directed thrombolysis versus ultrasound-accelerated thrombolysis for thromboembolic infrainguinal disease (DUET): design and rationale. Trials. 12:20, 2011
                              8. Wicky ST: Acute deep vein thrombosis and thrombolysis. Tech Vasc Interv Radiol. 12(2):148-53, 2009
                              9. Semba CP et al: Thrombolysis for lower extremity deep venous thrombosis. Tech Vasc Interv Radiol. 7(2):68-78, 2004
                              10. Semba CP et al: Alteplase as an alternative to urokinase. Advisory Panel on Catheter-Directed Thrombolytic Therapy. J Vasc Interv Radiol. 11(3):279-87, 2000
                              Related Anatomy
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                              Related Differential Diagnoses
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                              References
                              Tables

                              Tables

                              KEY FACTS

                              • Terminology

                                • Preprocedure

                                  • Procedure

                                    • Outcomes

                                      TERMINOLOGY

                                      • Definitions

                                        • Thrombolysis: Minimally invasive method for clearing/dissolving intravascular thrombus
                                          • Intravenous (IV) thrombolysis delivers systemic dose of medication designed to promote fibrinolysis
                                            • Most commonly used form of thrombolysis
                                              • Tissue plasminogen activator (tPA) most frequently used thrombolytic drug
                                          • Direct intravascular thrombolysis requires placement of catheter/device into thrombosed vessel
                                            • May place either intraarterially or intravenously
                                              • Localized treatment of thrombosed target vessel
                                        • Thrombolytic agent: Thrombus-dissolving medication
                                          • tPA
                                            • Catalyzes plasminogen conversion into plasmin
                                            • 5 min half-life; high fibrin specificity
                                            • Recombinant tPA (r-tPA) also available; made using recombinant biotechnology; various proprietary brands
                                              • Activase (alteplase) (Genentech)
                                              • Retavase (reteplase) (EKR Therapeutics)
                                              • TNKase (tenecteplase) (Genentech)
                                          • Streptokinase
                                            • Indirect plasminogen activator
                                            • Unpopular due to antigenicity: Inactivated by antibody formation
                                          • Urokinase
                                            • Induces systemic lysis; poor fibrin sensitivity
                                            • Metabolized in liver; 15 min half-life
                                        • Catheter-directed thrombolysis (CDT): Infusion of thrombolytic agent via percutaneously placed catheter
                                          • Also termed pharmacologic thrombolysis
                                            • May be intraarterial or intravenous
                                              • Delivers concentrated dose to thrombosed vessel
                                        • Mechanical thrombolysis (MT): Fragmentation of thrombus using intravascular medical device
                                          • Macerates clot into macro-/microscopic debris
                                        • Pharmacomechanical thrombolysis (PMT): Use of combined mechanical device/thrombolytic agent
                                          • Increases thrombus surface area in contact with thrombolytic
                                          • Combined therapy typically more effective
                                      • Clinical Vascular Thromboembolic Scenarios

                                        • Acute limb-threatening ischemia (ALI)
                                          • Sudden decrease in arterial perfusion to limb, potentially threatening its viability
                                            • Capillary return/pulses/sensation may be compromised/absent
                                              • Check for 5 Ps: Pain, pallor, pulselessness, paralysis, paresthesia
                                            • Causes of acute limb-threatening ischemia
                                              • Arterial embolus from proximal source
                                              • Arterial disruption/trauma
                                              • Acute in situ arterial thrombosis
                                        • Acute mesenteric ischemia
                                          • Arterial occlusive form may be embolic or thrombotic; venous form is thrombotic
                                        • Portal venous thrombosis
                                          • Primary form: Idiopathic
                                          • Secondary: Known etiologic factor
                                            • e.g., prothrombotic state/neoplasm/inflammatory
                                        • Pulmonary embolism (PE)
                                          • Massive pulmonary embolism with right heart strain
                                        • Lower extremity venous thrombosis
                                          • Phlegmasia cerulea dolens: Severe form of deep venous thrombosis (DVT); thrombotic occlusion of entire venous drainage of extremity
                                            • Acute, severe pain; cyanosis and edema
                                            • High risk of fatal pulmonary embolism despite anticoagulation
                                            • 40-60% result in venous gangrene; 20-50% amputation
                                            • Underlying malignancy in 50% of cases
                                          • Postthrombotic syndrome (PTS): DVT sequela
                                            • Result of chronic venous hypertension
                                              • Due to valvular damage, venous reflux, impaired venous return
                                            • Aggressively treat DVT to limit PTS risk
                                              • 20-40% of iliofemoral DVT develop PTS in 2 years
                                        • Upper extremity venous thrombosis
                                          • Axillosubclavian vein thrombosis (ASVT)
                                            • Primary form: Paget-Schroetter syndrome
                                            • Secondary form: Associated inciting venous injury
                                              • Long-term central venous catheters/pacemakers
                                              • Malignancy/adenopathy

                                      PREPROCEDURE

                                      • Indications

                                        • Contraindications

                                          • Preprocedure Imaging

                                            • Getting Started

                                              PROCEDURE

                                              • Procedure Steps

                                                • Findings and Reporting

                                                  • Alternative Procedures/Therapies

                                                    POST PROCEDURE

                                                    • Things to Do

                                                      OUTCOMES

                                                      • Complications

                                                        • Expected Outcomes

                                                          Selected References

                                                          1. Watson L et al: Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev. 11:CD002783, 2016
                                                          2. Comerota AJ: Thrombolysis for deep venous thrombosis. J Vasc Surg. 55(2):607-11, 2012
                                                          3. Manninen H et al: Catheter-directed thrombolysis of proximal lower extremity deep vein thrombosis: a prospective trial with venographic and clinical follow-up. Eur J Radiol. 81(6):1197-202, 2012
                                                          4. Karnabatidis D et al: Quality improvement guidelines for percutaneous catheter-directed intra-arterial thrombolysis and mechanical thrombectomy for acute lower-limb ischemia. Cardiovasc Intervent Radiol. 34(6):1123-36, 2011
                                                          5. Kühn JP et al: Intraarterial recombinant tissue plasminogen activator thrombolysis of acute and semiacute lower limb arterial occlusion: quality assurance, complication management, and 12-month follow-up reinterventions. AJR Am J Roentgenol. 196(5):1189-93, 2011
                                                          6. Popuri RK et al: The role of thrombolysis in the clinical management of deep vein thrombosis. Arterioscler Thromb Vasc Biol. 31(3):479-84, 2011
                                                          7. Schrijver AM et al: Dutch randomized trial comparing standard catheter-directed thrombolysis versus ultrasound-accelerated thrombolysis for thromboembolic infrainguinal disease (DUET): design and rationale. Trials. 12:20, 2011
                                                          8. Wicky ST: Acute deep vein thrombosis and thrombolysis. Tech Vasc Interv Radiol. 12(2):148-53, 2009
                                                          9. Semba CP et al: Thrombolysis for lower extremity deep venous thrombosis. Tech Vasc Interv Radiol. 7(2):68-78, 2004
                                                          10. Semba CP et al: Alteplase as an alternative to urokinase. Advisory Panel on Catheter-Directed Thrombolytic Therapy. J Vasc Interv Radiol. 11(3):279-87, 2000