Chapter 41 - Thrombolytics

Question 1

FDA indication for thrombolysis

Answer 1

1) acute MI 2) PE 3) hot stroke 4) arterial thrombosis/embolization 5) DVT 6) CVC occlusion

Question 2

Thrombolytic agents and indications

Answer 2

TABLE 41.1

Question 3

Mechanical thrombectomy types

Answer 3

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

Question 4

Fibrinogen level monitoring and management

Answer 4

< 1 g/L or if aPTT > 100 second Reduce or temporarily stop lytic infusion recheck 4-6 hours

Question 5

Intracranial hemorrhage risk in thrombolysis

Answer 5

higher when used for acute ischemic stroke (6.4-8.8%) PE 0-4.5% AMI 0.3-1.8% PAD 1-2%

Question 6

Major bleeding with thrombolysis

Answer 6

10-27% for acute limb 5-21% for PE 0.3-5.9% for AMI 4-11% for DVT

Question 7

Allergy to thrombolysis

Answer 7

mainly to streptokinase since it’s not found in vivo 1-10% of cases < 0.01% life threatening

Question 8

Emboli after thrombolysis

Answer 8

9-13%

Question 9

PE after thrombolysis of DVT

Answer 9

< 0-10%

Question 10

Absolute contraindication to thrombolysis

Answer 10

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

Question 11

Relative contraindication to thrombolysis

Answer 11

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

Question 12

Types of thrombolytic agents

Answer 12

1) Plasminogen activators: convert intrinsic plasminogen to plasmin –> cleaves linked fibrin 2) direct acting agent: cleave fibrin linked strands

Question 13

Approved thrombolytic agents

Answer 13

TABLE 41.2

Question 14

Streptokinase key points

Answer 14

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

Question 15

Urokinase key points

Answer 15

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

Question 16

Alteplase key points

Answer 16

1) recombinant tPA 2) most commonly used agent 3) half life 5 min 4) terminal half life 72 min 5) cleared by liver

Question 17

Reteplase key points

Answer 17

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

Question 18

Tenecteplase key points

Answer 18

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

Question 19

Dosing of thrombolytic agents

Answer 19

TABLE 41.3

Question 20

Treatment of massive PE

Answer 20

1) IV therapy with shortest infusion time 2) weak recommendation for CDT

Question 21

PERFECT trial

Answer 21

suggest CDT helps improve pulmonary artery pressure in massive and submassive PE

Question 22

Dosing of alteplase and reteplase for PE

Answer 22

Alteplase: 100 mg over 2 hr Reteplase: 10U + 10U double bolus injection each 10 U over 2 min period, 30 min apart

Question 23

Rochester trial on ALI thrombolysis

Answer 23

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

Question 24

STILE trial

Answer 24

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

Question 25

TOPAS trial

Answer 25

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)

Question 26

Recommendation of CDT in ALI

Answer 26

Rutherford class I and IIa

Question 27

Dosing of alteplase for stroke

Answer 27

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)

Question 28

EKOS system

Answer 28

Ekosonic endovascular system - ultrasound + thrombolytic to improve penetration of drug

Question 29

CaVenT study

Answer 29

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

Question 30

Drug dosing for ALI thrombolysis

Answer 30

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

Question 31

Dosing for thrombolytic in VTE

Answer 31

Alteplase: 0.25-2 mg/hr Reteplase: 0.75 U/hr Tenecteplase: 0.25-0.5 mg/hr

Question 32

COOL trial

Answer 32

Cardiovascular thrombolytic to open occluded lines 1) catheter patency better with rtPA vs placebo

Question 33

Doses for thrombolytic in AVG occlusion

Answer 33

Alteplase 2 mg Reteplase 1U Tenecteplase 1 mg

Question 34

Doses for thrombolytic in CVC occlusion

Answer 34

Alteplase: 2 mg in 2ml repeat after 120 min Reteplase 0.4U in 2 ml, repeat 30-60 min

Question 35

CVC occlusion in patients less than 30 kg thrombolysis

Answer 35

Alteplase: 110% of internal lumen volume not to exceed 2 mg in 2 ml repeat in 120 min