1. Surgical Grand Rounds 03/10/2013 Thrombolysis never too late

2. Case presentation Mr X Background Hx:
EVAR (AUI + R-L fem-fem crossover)
Intermittent claudication L>R for the last 18 months

3. 2013
Admitted with a 10 day hx of acute deterioration of left foot pain progressing to rest pain

4. Past Medical History Hypertension Dyslipidaemia Medications
- Pravastatin
- Amlodipine
Aspirin
Bisoprolol
NKDA
Social Hx: smoker
Fam Hx : PVD

5. Examination Left cold, pale foot Pulses not palpable ABIS:
Right : Normal
Left :
Underwent full investigation for embolus source (Holter, Echo)

6. CT angio 2013
Thrombus in distal popliteal. Non occluding

7. CT angiogram 2013
Right Iliac limb. Left occluder

8. Fem – Fem Crossover
Fem – fem crossover

9. Distal SFA patent

10. Occlusion in left distal popliteal artery

11. Angiogram prior to thrombolysis
Distal SFA occlusion

12. Angiogram Post thrombolysis
Highlight of this case: Even though a thrombus has been present since april 2013, thrombolysis was successful in clearing out the thrombus.

13. Thrombolysis
Catheter-directed thrombolysis performed by vascular surgeons/interventional radiologists
Plan
Mechanism
Indications/contraindications
Technique
Peri-procedural protocol/complications
Evidence

14. MECHANISM OF ACTION ACTIVATION Prothrombin (II) Thrombin (IIa)
(Converts)
Platelets
Fibrinogen (I)
Fibrin (Ia)
Clot
(Binds)
tPA
(Converts)
DEGRADATION
Plasminogen
Plasmin
FDPs 14 14

15. Indications Acute limb iscahemia Acute embolus
Thrombosis of a stenosis in a native artery
Thrombosed arterial bypass graft 15

16. Relative Contra-indications
Haemorrhagic diathesis
Recent GI bleed
Hx stroke, intracranial tumour/aneurysm, spinal surgery
Pancreatitis
Bacterial endocarditis
Documented GI neoplasm, varices
Recent surgery 16

17. Thrombolysis - Technique
Contralateral access via common femoral artery
Guidewire traversal test / Catheter tip into thrombus.
Single vs multi side hole
Low-Dose Infusion:
0.5-1mg tPA per hour
Heparin – pericatheter thrombosis
Sequential angiograms
Advance catheter tip / co-axial system
? Treatable critical stenosis
Accelerated Infusion
Pulse Spray, Hi-dose bolus 17 17

18. tPA Protocol (Acute Limb Ischaemia)
Overnight continuous infusion techniques using multislit catheter
Surgeon/Radiologist initiating tPA to inject 5mg bolus into clot through infusion catheter
Infuse via pump at 5ml/hr (1mg tPA/ hr) to cont. until rpt angiogram 18

19. tPA Protocol (Acute Limb Ischaemia) Cont.
Sub-therapeutic heparin given through side port of the sheath in the groin (2500 IU bolus then 500 IU/hr as maintenance)
Monitor aPTT to ensure < 60secs
Monitor Fibrinogen levels 6 hourly to maintain > 100mg/dL
Repeat angiogram the next morning
Remove sheaths after waiting 1 hr post tPA termination & Activated Clotting Time < 175
Continue therapeutic heparin arm if indicated with 6 hourly monitoring of APTT between 60-90 19

20. MANAGEMENT OF PATIENTS ON TPA
Baseline obs & Dopplers
Check tPA and Heparin are correctly connected and running
Infusion running
Infusion NOT running
CALL SURGICAL TEAM
Check 1/2 hourly obs:
T°, HR, BP
Inspect access site of thrombolysis catheter
Dopplers
Causes for concern:
Bleeding from site
Persistant tachycardia post thrombolysis initiation
Increasing groin pain
Hypotension
Headache
Altered motor function(?TIA/CVA)
Altered mental state
No Change 20

21. Patient Guidelines on tPA
Strict bed rest
Urinary Catheter in situ
Normal diet
Bloods: FBC, U&E, Coags, Fibrinogen levels, Group & Crossmatch (2 units)
Check angiogram day post procedure
Infusion can only be stopped upon instructions by Surgeon/Radiology team and the team is to remove infusion catheter 21

22. TPA vs. Surgery 3 randomized, clinical trials in 1990’s
Rochester series – urokinase vs surgery, 114 pts
Limb salvage rate similar in both - 82% at 12 months
Survival rate thrombolysis group (84%) vs 58% (more cardiopulmonary complications)
STILE trial – rt-PA, urokinase vs surgery, 234 pts
Patients with acute ischemia (0-14 days) who were treated with thrombolysis had improved amputation-free survival and shorter hospital stays, but those with chronic ischemia (> 14 days), surgical revascularisation was more effective and safer
TOPAS trial - urokinase
Amputation free survival
Thromb: 71.8% (6/12), 65% at 1 yr
Surgery: 74.8% (6/12), 69.9%
Major Haemorrhage 12.5% Vs 5.5%
Open procedures 315 Vs 551 at 6 months
There are 3 randomized clinical trials related to TPA vs. Surgery – rocehster series, stile trial and topas 22

23. To summarise
Rochester – Mortality Surgery > Thrombolysis, similar outcome limb
STILE – acute cases better with lysis
TOPAS – Similar outcome with decreased need for open surgery
All showed higher risk bleeding with thrombolysis 23

24. Cochrane review Five trials with a total of 1283 participants
Berridge C et al - Surgery versus thrombolysis for initial management of acute limb ischaemia – updated 2013
All RCTs comparing thrombolysis and surgery for the initial treatment of acute limb ischaemia
Five trials with a total of 1283 participants

25. Results
No significant difference in limb salvage or death at 30 days, six months or one year for initial surgery vs thrombolysis.
At 30 days, thrombolysis patients had higher rate of
stroke (1.3%) vs (0%)
major haemorrhage (8.8%) vs (3.3%)
distal embolisation (12.4%) vs (0%) (OR 8.35; 95% CI 4.47 to ).
Participants treated by initial thrombolysis underwent a less severe degree of intervention (OR 5.37; 95% CI 3.99 to 7.22) and displayed equivalent overall survival (OR 0.87; 95% CI 0.61 to 1.25).

26. National Audit of Thrombolysis for Acute Leg Ischemia (NATALI)
Data collected over 10 years
11 centres in UK, thrombolysis
Major haemorrhage rate 7.85%
Stroke rate 2.3% - ½ haemorrhagic
Earnshaw et al JVS 2004 26

27. NATALI Adverse Predictors of Amputation free survival
Age, DM, Duration + Severity of Ischemia, Neurosensory deficit
Poor Predictors of Patient Survival
Female, Age, IHD, Native vessel occlusion and embolic etiology 27