see also: [[Stroke]], [[ACS#thrombolysis|thrombolysis for ACS]], [[Pulmonary Embolism#indication for thrombolysis|PE thrombolysis]], [[Stroke#Stroke trials and evidence|Stroke trials and evidence]] > [!References]- > - [Dunn thrombolytic therapy in stroke](x-devonthink-item://717870CB-CCEF-41AE-8E23-EFCC82ECB940) > - [Dunn evidence for hrombolytic therapy in stroke](x-devonthink-item://02755D65-E1D2-45EC-B913-C2EE4B6A68BC) > - [Dunn - thrombolytic therapy in ACS](x-devonthink-item://1667438D-1517-41FD-B7D1-62E76471D349) > - [Rosen thrombolytic therapy for stroke](x-devonthink-item://34BCE5FA-5D8A-4BBE-9655-35F24866FDB1?page=10&start=1847&length=20&search=Thrombolytic%20Therapy) > - [Dunn - Management of PE](x-devonthink-item://8B5017FD-DFF4-479E-888D-AB7B814DAFC5) > - [CHEST guideline antithrombotic therapy for VTE disease](https://journal.chestnet.org/article/S0012-3692(15)00335-9/fulltext) - [bookends pdf](bookends://sonnysoftware.com/ref/DL/248969) > - [Hayes' Tissue Plasminogen Activator](x-devonthink-item://42B5126A-6B76-409F-8195-2D963F236658) > - [Hayes' thrombolysis and heparin reversal](x-devonthink-item://B1217276-B3E7-4AD4-87E5-F5105CDA4546) > - [2017 ESC guideline for management of acute myocardial infarction in pts with ST-segment elevation](https://pubmed.ncbi.nlm.nih.gov/28886621/) # Ultimate thrombolysis table #tables | Condition | Situation | Drug | Dose | comment | | --------- | ------------------------------------------------------------------------ | ------------------ | ------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Stroke | meeting inclusion | alteplase<br>(tPA) | 0.9mg/kg (90mg max)<br>10% bolus , 90% over 60 min<br>- 0.6mg/kg in asian | no anticoaulants after | | Stroke | meeting inclusion | tenecteplase | 0.25mg/kg IV (25mg max) over one min<br>- some still 0.4mg/kg | no anticoagulants or anti-platelet after for 24h. +/- mechanical thrombectomy after. may have a slightly lower risk of ICH. may be superior to tPA in patients who have clot retrieval | | PE | massive PE | alteplase | 10mg IV bolus followed by 40-90mg IV over 2 hours | ETG: 1.5 mg/kg up to 100 mg with 10mg 1 min bolus then remainder by IV over 2 hours <br>(↑ risk bleeding: 10 mg bolus followed by 40mg over 1 h) | | PE | cardiac arrest | alteplase | 25-50mg IV bolus; repeat in 15 min | subsequent give heparin 5000 IU bous | | PE | cardiac arrest | tenecteplase | 0.5 mg/kg up to 50mg IV bolus | withhold heparin during infusion; commence heparin or enoxaparin 1mg/kg when aPTT or thrombin tine is ≤ 2x normal (usually after a few hours) | | STEMI | - STE<br>- CP > 30 m, <12 hours <br>- no PCI available within 90 minutes | *tenecteplase* | 0.5mg/kg | administer *heparin* or *LMWH* in conjunction with all thrombolytic agents . heparin dose:<br>- 60 u/kg bolus<br>- 12 u/kg/h<br>- LMWH likely superior than UFH | | STEMI | above | alteplase | 15mg IV stat<br>then 0.75 mg/kg (to 50 mg) over 30 min<br>then 0.5mg/kg (to 35 mg) Iv over 60 min | | # indications ## stroke thrombolysis indications - clinically measurable stroke NIHSS >4 <25 - clear neurological deficit - within 4.5 hours of symptoms onset - CTB excluded intracerebral haemorrhages and other stroke mimics eg space occupying lesion - older than 18 (?? paeds maybe younger) ; relative contraindication age >80 in 3-4.5 hour window - Risk of intracranial haemorrhage: 2-7% symptomatic haemorrhage. ~1% mortality. asymptomatic ICH more frequent. NNTH is 42 - mortality benefit? : no overall mortality benefit - benefits? : small but significant chance of ↑ neurological outcomes at 90 days (modified rankin). NNT ~10 for functional independence ## PE thrombolysis indications # contraindications ## stroke thrombolysis contraindications See [AHA guidelines 2019](https://www.ahajournals.org/doi/10.1161/STR.0000000000000211), [bookends pdf contraindications](bookends://sonnysoftware.com/annotation/DL/206338/1711733752/25/-51/-491) **Absolute contraindications** - significant pre-morbid disability/comorbidities (==Modified Rankin Score ≥ 4==) - NIHSS > 25 - CT showing signs of early infarction in >1/3 of one MCA territory - *uncontrolled* HTN with ==BP ≥ 180/110== - Can tx with labetalol 10-20mg IV over 1 min/ nicardipine 5mG/h IV increase by 2.5mg/ q5-14 min to 15 /hydralazine - clinical suspicion of ==septic embolism== eg sub-acute bacterial endocarditis - stroke mimic: - ==BGL== <2.8 or > 22mmol/L - ==suspicion of SAH==, even if CT is normal - recent < 10 days ==childbirth==) - Treatment dose of anticoagulation - warfarin with INR ≥ 1.7 - apixaban or LMWH within 12 hours - rivaroxaban within 24 hours (controversial) - dabigatran can be reversed with idracizumab - unfractionaed heparin dose within 12 H if elevated APTT - known ==bleeding diathesis== of any cause (acquired or inhereted) - platelets <100 - ==any prior intracerebral haemorrhage== - ==SAH== if no tx of aneurysm - known intracerebral aneurysm or AVM - stroke secondary to ==aortic dissection== - But not cervical dissection per Dunn - ==CNS neoplasm== - recent ==serious trauma== - major surgery or serious trauma in past 30 days - recent <10 days of prolonged CPR - recent <3 months ulcerative GI disease or oesophageal varices **relative contraindications** - seizures (eg stroke mimic) - minor (eg NIHSS <4) or resolving stroke - very major stroke - MI in last 30 days (risk of myocardial rupture) - pregnancy or parturition within prior 30 days (discuss with obstetrics) - ischaemic stroke in previous 30 days depending on size of infarct - arterial puncture at a non-compressible site or LP in the last week ## STEMI thrombolysis contraindications **Absolute contraindications** Risk of bleeding - active bleeding or bleeding diathesis (excluding menses) - significant closed head or facial trauma within 3 months - suspected aortic dissection (including new neurological symptoms) Risk of intracranial haemorrhage - ==any== prior intracranial haemorrhage - ischaemic stroke within 3 months - known structural cerebral vascular lesion (eg arteriovenous malformation) - known malignant intracranial neoplasm (primary or metastatic) **Relative contraindications** Risk of bleeding - current use of anticoagulants: the higher the international normalised ratio (INR), the higher the risk of bleeding - non-compressible vascular punctures - recent major surgery (within 3 weeks) - traumatic or prolonged (more than 10 minutes) cardiopulmonary resuscitation - recent (within 4 weeks) internal bleeding (eg gastrointestinal or urinary tract haemorrhage) - active peptic ulcer Risk of intracranial haemorrhage - history of chronic, severe, poorly controlled hypertension - severe uncontrolled hypertension on presentation (more than 180 mm Hg systolic or more than 110 mm Hg diastolic) - ischaemic stroke more than 3 months ago, dementia, or known intracranial abnormality not covered in absolute contraindications Other - pregnancy # Tenecteplase dose ## PE - 1/2 standard in age >75 | weight (kg) | IU | mg | mL | | ---- | ---- | ---- | ---- | | <60 | 6,000 | 30 | 6 | | 60-70 | 7,000 | 35 | 7 | | 70-80 | 8,000 | 40 | 8 | | 80-90 | 9,000 | 45 | 9 | | ≥90 | 10,000 | 50 | 10 | ## stroke - 0.25mg/kg (25 mg max) IV over 1 min (some recs still say 0.4mg/kg) # Alteplase tPA dose ## PE - in arrest, give 50mg over 2 min then after 15 min of CPR another 50mg - otherwise: Alteplase is used providing the first 10 mg as a bolus over 2 minutes followed by 90 mg as an infusion over 2 hours. If the patient weighs less than 65 kg then 1.5 mg/kg is provided as an infusion over 2 hours after an initial bolus of 10 mg over 2 minutes ## STEMI see [Dunn - thrombolytic therapy in ACS](x-devonthink-item://1667438D-1517-41FD-B7D1-62E76471D349) - 15mg IV bolus over 1-2 min, followed by infusion of 50mg over 30 min, then 35mg over 1 h - if weight <67 kg, then 15 bolus followed by 0.75mg/kg over 30 min then 0.5mg/kg over 1 h ## stroke - 0.9mg/kg (90mg max) - 0.6 mg/kg in asian may reduce ICH rate - 10% bolus, then 90% over 60 min # complications ## post-thrombolysis bleed See [Rosen - symptomatic intracerebral haemorrhage following thrombolysis](x-devonthink-item://34BCE5FA-5D8A-4BBE-9655-35F24866FDB1?page=14) 2-7% get *symptomatic* ICH; asymptomatic may be higher - stop thrombolysis infusion if ongoing - reverse thrombolysis -- [[TXA]], [[FFP]], [[Prothrombinex]], [[cryoprecipitate]] - **cryo** is the main tx here; 10 units over 10-30 min - send *fibrinogen*; aim ≥ 1.5 - BP control -- target SBP <160, MAP < 110 - control ICP -- head up 30 deg, CO2 35-50, hypertonic fluid as required - manage seizures as required - NSx opinion regarding potential surgical interventions - CVS and resp support as needed ## haemorrhagic transformation ## alteplase angioedema - methylpred 125 mg - Antihistamine - Adrenaline - Icatibent ## re-perfusion injury # controversies ## thrombolysis stroke vs MI ![[Pasted image 20240309033309.png]]