Chapter 41 - Thrombolytics Flashcards
FDA indication for thrombolysis
1) acute MI 2) PE 3) hot stroke 4) arterial thrombosis/embolization 5) DVT 6) CVC occlusion
Thrombolytic agents and indications
TABLE 41.1
Mechanical thrombectomy types
1) hydrodynamic: saline infusion and aspiration using Venturi effect 2) rotational: mascerates thrombus 3) mixing: double balloon to confine space, rotating sinusoidal wire disrupts clot 4) ultrasound: high frequency low power to loosen fibrin strands 5) aspiration: large suction catheter
Fibrinogen level monitoring and management
< 1 g/L or if aPTT > 100 second Reduce or temporarily stop lytic infusion recheck 4-6 hours
Intracranial hemorrhage risk in thrombolysis
higher when used for acute ischemic stroke (6.4-8.8%) PE 0-4.5% AMI 0.3-1.8% PAD 1-2%
Major bleeding with thrombolysis
10-27% for acute limb 5-21% for PE 0.3-5.9% for AMI 4-11% for DVT
Allergy to thrombolysis
mainly to streptokinase since it’s not found in vivo 1-10% of cases < 0.01% life threatening
Emboli after thrombolysis
9-13%
PE after thrombolysis of DVT
< 0-10%
Absolute contraindication to thrombolysis
1) active internal bleeding 2) recent (2 month) CVA, trauma, intracranial or intraspinal surgery 3) known intracranial neoplasm 4) severe uncontrollable HTN 5) uncontrollable clotting disorder 6) previous severe allergic reaction to thrombolytic agent
Relative contraindication to thrombolysis
1) recent (10 days) operative or obstetric procedure, biopsy or procedure in location non-compressible, GI bleed, trauma, cardiopulmonary resus 2) left heart thrombus 3) subacute bacterial endocarditis 4) severe liver or kidney disease 5) diabetic hemorrhagic retinopathy 6) acute pancreatitis 7) pregnancy
Types of thrombolytic agents
1) Plasminogen activators: convert intrinsic plasminogen to plasmin –> cleaves linked fibrin 2) direct acting agent: cleave fibrin linked strands
Approved thrombolytic agents
TABLE 41.2
Streptokinase key points
1) beta-hemolytic streptococci makes it 2) 3 domains: alpha, beta, gamma 3) beta domain formr SK-plasminogen complex 4) half life 20 minutes 5) inactivated by systemic plasmin inhibitor (alpha2 antiplasmin, alpha2 macroglobulin) 6) repeat dosing between 5 days to 1 year not recommended - antibodies
Urokinase key points
1) produced by kidney, originally isolated from urine 2) involved in intracellular signalling, cell proliferation, adhesion, migration 3) plasmin cleaves the precursor in presence of fibrin
Alteplase key points
1) recombinant tPA 2) most commonly used agent 3) half life 5 min 4) terminal half life 72 min 5) cleared by liver
Reteplase key points
1) tPA without the finger, EGF and kringle K1 domain 2) decrease liver clearance 3) half life 15 min 4) terminal half life 1.6 hours 5) cleared by liver and kidney
Tenecteplase key points
1) Threonine103Asparagine, Asparagine 117Glutamine, replace carboxyl-protease domain by 4 alanines 2) decreased fibrin specificity 3) decreased clearance 4) 80 fold higher resistance to PAI1 and enhanced fibrin specificity compared to tPA 5) half life 20-24 min 6) terminal half life 90-130 min
Dosing of thrombolytic agents
TABLE 41.3
Treatment of massive PE
1) IV therapy with shortest infusion time 2) weak recommendation for CDT
PERFECT trial
suggest CDT helps improve pulmonary artery pressure in massive and submassive PE
Dosing of alteplase and reteplase for PE
Alteplase: 100 mg over 2 hr Reteplase: 10U + 10U double bolus injection each 10 U over 2 min period, 30 min apart
Rochester trial on ALI thrombolysis
1) 114 patients UK CDT vs open surgery 2) < 7 days of ALI 3) UK thrombolysis improved 12 months survival 4) limb salvage rate same
STILE trial
Surgery versus thrombolysis for ischemic lower extremity 1) 6 months ischemic symptoms 2) adverse events in CDT therefore terminated study 3) subgroup analysis: if only 14 day ischemia then improve amputation rate than surgery
TOPAS trial
Thrombolysis or peripheral arterial surgery 1) 544 patients 2) < 14 days arterial/bypass occlusion 3) open vs CDT with UK 4) same survival and mortality but avoided surgery with increased major bleed (double)
Recommendation of CDT in ALI
Rutherford class I and IIa
Dosing of alteplase for stroke
Systemic: 0.9 mg/kg (max 90mg): load 10% then infuse over 1 hr CDT: 2 mg bolus/2 min distal to thrombus then 2 mg into thrombus, then 9 mg/hr for 2 hours (max 120 min)
EKOS system
Ekosonic endovascular system - ultrasound + thrombolytic to improve penetration of drug
CaVenT study
CDT vs standart treatment for acute < 21 d iliofemoral DVT 1) 209 patients 2) 6 months IF patency better in CDT 66 vs 47% 3) 24 month PTS lower in CDT 41 vs 55.6% 4) worse major bleeding complication
Drug dosing for ALI thrombolysis
Alteplase: low dose = 0.5-2.5 mg/hr high dose = 0.05 mg/kg/hr (max 100 mg) Reteplase: 2 U bolus then 0.5-1U/hr (max 20 U) Tenecteplase: 0.25-0.5 mg/hr
Dosing for thrombolytic in VTE
Alteplase: 0.25-2 mg/hr Reteplase: 0.75 U/hr Tenecteplase: 0.25-0.5 mg/hr
COOL trial
Cardiovascular thrombolytic to open occluded lines 1) catheter patency better with rtPA vs placebo
Doses for thrombolytic in AVG occlusion
Alteplase 2 mg Reteplase 1U Tenecteplase 1 mg
Doses for thrombolytic in CVC occlusion
Alteplase: 2 mg in 2ml repeat after 120 min Reteplase 0.4U in 2 ml, repeat 30-60 min
CVC occlusion in patients less than 30 kg thrombolysis
Alteplase: 110% of internal lumen volume not to exceed 2 mg in 2 ml repeat in 120 min
