Intra-operative use of anti-fibrinolytics during neurosurgical procedures


Intra-operative use of anti-fibrinolytics during neurosurgical procedures                                               

Primary brain tumours can contribute to significant haemostatic dysfunction with consequent bleeding complications or thrombo-embolic events, which may have catastrophic impact on a patient’s outcome post surgery.(1,2) The disturbance of haemostasis may not be detectable on routinely performed tests of coagulation, namely activated partial thromboplastin time (APTT), prothrombin time (PT) and platelet count.(2)

Anti-fibrinolytics are agents that interfere with the formation of plasmin from its precursor plasminogen.

Plasmin is a fibrinolytic enzyme and a reduction in plasmin levels causes inhibition of fibrinolysis.   Aprotinin has been shown to reduce blood loss in patients with intra-cranial meningiomas and vestibular schwannomas (3) and tranexamic acid to reduce intracerebral haematoma growth.(4) These benefits have been demonstrated without an increase in thrombo-embolic events.(2) Tranexamic acid is now routinely administered to poly-trauma patients with significant haemorrhage either pre-hospital or in emergency departments to reduce blood loss.(5)

In lieu of national guidance regarding the use of these agents in neurosurgical procedures we seek to understand how anti-fibrinolytics are being used by neuro-anaesthetists/intensivists/surgeons in both elective and emergent neurosurgical procedures.


Dr N. Talbot

Dr H. Church

Dr H. Krovvidi

University Hospitals Birmingham NHS Foundation Trust



  1. Goh KY, Tsoi WC, Feng CS, Wickham N, Poon WS. Haemostatic changes during surgery for primary brain tumours. J Neurol Neurosurg Psychiatry [Internet] 1997;63:334–8 Available from: 2. Gerlach R, Krause M, Seifert V, Goerlinger K. Hemostatic and hemorrhagic problems in neurosurgical patients. Acta Neurochir (Wien) 2009;151:873–900

  1. Palmer JD, Francis JL, Pickard JD, Iannotti F. The efficacy and safety of aprotinin for hemostasis during intracranial surgery. J Neurosurg [Internet] Journal of Neurosurgery Publishing Group; 2003;98:1208–16

Available from:

  1. Sorimachi T, Fujii Y, Morita K, Tanaka R. Rapid administration of antifibrinolytics and strict blood

pressure control for intracerebral hemorrhage. Neurosurgery 2005;57:837–43

  1. Williams-Johnson JA, McDonald AH, Strachan GG, Williams EW. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage

(CRASH-2) a randomised, placebo-controlled trial. West Indian Med J [Internet] Elsevier Ltd; 2010;59:612–24 Available from:





Intra-operative use of anti-fibrinolytics during neurosurgical procedures                                               

Which neurosurgical unit do you currently work in?


                          Answer                                                                                            No Responses                                      Percent

ABERDEEN 1 0.56%
BARTS and THE LONDON 12 6.67%
BELFAST 1 0.56%
BRISTOL 16 8.89%
CORK 1 0.56%
DUNDEE 3 1.67%
GLASGOW 8 4.44%
HULL 1 0.56%
LIVERPOOL 13 7.22%

NATIONAL                                                                                                              8                                         4.44%

OXFORD 1 0.56%
PLYMOUTH 13 7.22%
PRESTON 1 0.56%
SHEFFIELD 12 6.67%
ST GEORGE’S 12 6.67%



180 response(s)

What is your current role within that organisation


                          Answer                                                                                            No Responses                                      Percent

Consultant Neuro-Anaesthetist 158 87.78%
Consultant Anaesthetists 32 17.78%
Consultant Neuro-Intensivist 46 25.56%
Consultant Intensivist 13 7.22%
Trainee (Anaesthesia / ICM) 1 0.56%
other (please specify below) 2 1.11%
Other Answers 2 1.11%



Other Answers:

cons pain          paediatric neuro                                   

180 respondent(s), showing percentage as a maximum of 100% per answer (multiple checkbox selection)


In the last 6 years have you ever used any of the available anti-fibrinolytics to reduce bleeding during neurosurgical procedures?


                          Answer                                                                                            No Responses                                      Percent

Yes 131 72.78%
No 49 27.22%



180 response(s)

In what circumstances have you used anti-fibrinolytics?


                          Answer                                                                                            No Responses                                      Percent

Prophylactically / routinely 54 42.19%
In response to bleeding 99 77.34%
At surgeon’s request 42 32.81%
As part of a clinical trial 10 7.81%
Other – please specify 5 3.91%
Other Answers 7 5.47%



Other Answers:

in accordance with nice guidelines where ebl is expected to exceed 500mls inadequate platelet function on-going treatment of major trauma patient who already received txa loading and was coming to theatre for neuro and other surgery        polytrauma rotem guided trauma

where there is expected major blood loss


128 respondent(s), showing percentage as a maximum of 100% per answer (multiple checkbox selection)               


           Please detail in what types of surgery you have used antifibrinolytics



All neurosurgical operations may benefit if haemostasis inadequate from a haematological cause rather than a          surgical one!

at the start of a crani for excision of a large meningioma, I gave tranexamic acid. I decided against apotinin as I do  not think there is enough evidence that is safe or effective in this circumstance

Complex spine surgery with expected blood loss > 500 ml Intra-operative haemorrhage Haematological advice for  known coagulopathy

Craniotomy for tumours known to be vascular in nature or where patient has been recently anti-coagulated or           where auto-anticoagulation is evident.


Have used prophylactically in meinigiomas / procedures likley to bleed in Jehovah’s Witness patients. In response  to blleding in meningiomas / AVMs / large spinal procedures


Major bleeding in urgent cranioplasty, in response to prolonged “oozing” and in major spinal surgery which may not  be appropriate to this survey

major spinal surgery (i.e. anything more than lumbar disc/decompression) I routinely use tranexamic acid. For           intracranial surgery only when major haemorrhage occurs. Not in neurovascular procedures


multi level lumbar laminectomy (!)

multilevel spinal surgery meningioma surgery


Neurosurgery – craniotomy for tumour and spinal surgery with large resection soft tumour.


Neurovascular-AVM resection Spine-fixation,Adult deformity,tumour Meningiomas


No details. I use in some arthroplastys but have not considered transfer of practice to neuro routine practice


Paediatric brain tumour resection, Malignant Spine decompression.


Patients with high alcohol intake preoperatively, emergency surgery


Pedicle screws fixation,Meningiomas,Spinal tumours


Polytrauma with head injury, bleeding tumours.


Post fossa craniotomy Anterior fossa meningioma surgery major spinal instrumentation


Posterior fosaa tumour surgery with difficult to contol haemorrhage – as part of major transfusion protocol


Posterior fossa bleeding in a child


Posterior fossa craniotomy for microvascular decompression of trigeminal nerve.


Posterior fossa tumour bleeding not cotrolled by surgeon.


primary brain tumours ( usually complex meningioma ) with either excessive bleeding or ROTEM suggestion of         fibrinolysis


Routine use of TXA for paediatric craniofacial surgery. Use of TXA as part of CRASH-3 trial – as this trial is ongoing I would not routinely give TXA for TBI prophylactically. I would use TXA if any neurosurgical patient           (including TBI) lost a significant amount of blood. I have a low threshold for using TXA if the patient has other markers of haemostatic dysfunction, e.g. a history of liver disease, recent antiplatelet usage, thrombocytopaenia.


SAH aneurysm coiling – peri-procedural rupture


Spinal fixation Intracerebral AVM bleeding intraoperatively Intracerebralaneurysm clipping bleeding intraoperatively  Amputation above knee

trans-sphenoidal pituitary sirgery for non-functioning adenoma. Slow but constant ooze – normal coag (INR/APTT  and platelets) Tranexamic acid 1g tried “empirically”

Trauma case with heavy intra cranial bleeding (and extra cranial injuries)


TXA once in tumour surgery. Also used by a colleague for a bleeding aneurysm. NB we are a children’s hospital,      we don’t get many aneurysms!


Use of tranexamic acid in patient bleeding from spinal surgery. Patient went on to have angiogram and         embolisation of bleeding vessel. No sequelae


Where massive blood loss is anticipated. E.G. Major spinal surgery for metastatic tumours and large meninigioma  surgery.



Have you used Tranexamic acid


                          Answer                                                                                            No Responses                                     Percent

Yes 124 96.88%
No 3 2.34%

Other Answers                                                                                                        1                                        0.78%



Other Answers:

more than 6 yrs ago also aprotinine


128 response(s)

When administering tranexamic acid do you usually use


                          Answer                                                                                            No Responses                                     Percent

Bolus only 82 65.60%
Bolus plus infusion 36 28.80%
Infusion only 1 0.80%
Other Answers 5 4.00%
No Answer 1 0.80%



Other Answers:

with additional bolus top up

bolus plus infusion for polytrauma        occasionally with infusion slow bolus

sometimes an infusion too


124 response(s) , 1 No Answer(s)




1g sometimes followed by another 1g (If long procedeure or if major blood loss during major spinal procedures where prophylactic dose given.




Would you usually continue the infusion post operatively? 


                          Answer                                                                                            No Responses                                     Percent

Yes 14 11.57%
No 66 54.55%
N/A 26 21.49%
Other Answers 7 5.79%
No Answer 8 6.61%



Other Answers:

dependent on degree of confidence in haemostasis have on one occassion, but not usually

if bleeding risk continues          if going to critical care

if trauma and within window of trauma infusion only if ongoing haemostatic failure



113 response(s) , 8 No Answer(s)

For how long?





Have you used Aprotinin?


                          Answer                                                                                            No Responses                                     Percent

Yes 17 13.71%
No 94 75.81%
Other Answers 6 4.84%
No Answer 7 5.65%



Other Answers:

not for a while not for years

not in last 6 years         not in the last 5 years not since it was removed from formulary!!

post cardiac surgery not neurosurgery


117 response(s) , 7 No Answer(s)

When administering aprotinin do you usually use


                          Answer                                                                                            No Responses                                     Percent

Bolus only 7 23.33%
Bolus plus infusion 7 23.33%
Infusion only 2 6.67%
Other Answers 7 23.33%
No Answer 7 23.33%



Other Answers: don’t give it.

historical. no longer use it due to thrombotic risk

never given intraoperatively     never use never used it not used recently

this was for accoustic nerve tumours, before there was “evidence” that aprotinine increased mortality


23 response(s) , 7 No Answer(s)



When requested by surgeon – standard intra-op dose (as per cardiac anaesthesia), from memory – 8 vials rapidly  infused.






Would you usually continue the infusion post operatively?


                          Answer                                                                                            No Responses                                     Percent

Yes 1 3.33%
No 15 50.00%
N/A 3 10.00%
Other Answers 1 3.33%
No Answer 10 33.33%



Other Answers:          v v rarely used


20 response(s) , 10 No Answer(s)

For how long?




Have you used Epsilon-aminocaproic acid ?


                          Answer                                                                                            No Responses                                     Percent

Yes                                                                                                                         2                                        1.61%

No 119 95.97%
Other Answers 2 1.61%
No Answer 1 0.81%



Other Answers:

never given intraoperatively     not in uk


123 response(s) , 1 No Answer(s)

When administering epsilon-aminocaproic acid do you usually use


                          Answer                                                                                            No Responses                                     Percent

Bolus only 2 40.00%
Other Answers 1 20.00%
No Answer 2 40.00%



Other Answers:          v v v rarely used


3 response(s) , 2 No Answer(s)

           What bolus dose do you use? (if applicable)




What infusion dose do you use? (if applicable)


Would you usually continue the infusion post operatively?


                        Answer                       No Responses            Percent No                  1          20.00%

N/A 1 20.00%
No Answer 3 60.00%



2 response(s) , 3 No Answer(s)

For how long?


Have you used any other anti-fibrinolytic agent ?


                          Answer                                                                                            No Responses                                     Percent

No 121 98.37%
Other Answers 2 1.63%



Other Answers:

ddavp  iv asa – neuroradiology: coiings


123 response(s)

When using anti-fibrinolytics do you routinely?


                            Yes                                      No                                  No Answer

Perform near patient clotting assays

such as TEG, ROTEM, etc                     





Specifically monitor renal function






Specifically monitor for seizures 19 90 14


116 response(s)

Does your department have a written protocol for administering these agents?


                          Answer                                                                                            No Responses                                     Percent

Yes                                                                                                                         9.36%

No                                                                                                                       125                                      73.10%

Don’t know 18 10.53%
Other Answers 12 7.02%



Other Answers:

apart from nice guidelines, major haemorrhage protocols and trauma guidelines, no as part of massive tranfusion protocol ed protocol for trauma/ major haemorrhage not neurosurgery hopefully hari will write one!

in process        in trauma yes only for major trauma only for trauma patients not neuro only in trauma! protocol only for trauma

yes – within the major trauma and major haemorrhage guidelines. not specifically for management of neuro cases outside of these 2 domains.


171 response(s)

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  1. The use of tranexamic acid ICH is currently being trialled (STOP-AUST)(4) and thus cannot be recommended at present.


I do use these drugs for major spines but I dont clasify that as neurosurgery. If I encountered a large meningioma with likelihood of bleeding then I would use it but fortunately I encounter neurosurgical beeding rarely now. Surgery  has got better.


I have extensive experience of treating major traumatic haemorrhage in the military and have a low threshold for       aggressive early management of haemorrhage. The use of TXA is part of this “bundle”.


I have once given a surgeon dilute TXA solution to put in a bleeding tumour bed (after excision) on cotton wool. Appeared to work well – and substantially reduces systemic effects. I never use TXA without demonstrating a least a little increase in thrombolysis with the rotem. I suspect, that a lot of dilutional coagulopathy is “treated” with TXA I do worry about cerebral microvascular occlusion with TXA. That’s not particularly well known and difficult to demonstrate, especially after craniotomy when minor cognitive dysfunction is overshadowed by the pathology itself and the effects/damage of surgery.But it’s been know for decades. I think, in very big or vascular tumours, preoprative embolizatin of tumour vessels is far more effective that treating a hypothetical hyperfibrinolysis with TXA


I hope that this write up from this survey will take the opportunity to advertise the NICE guidelines for the use of        fibrinolytics in surgery


I use Tranexamic acid in major orthopaedic spinal cases but never in cranial surgery (which I do but I am not            classed as a “neuroanaesthetist”).

Use occasionally for tumour resections or major spinal fixations. Stopped using aprotinin after concerns about           renal impairment post op.




Dr N. Talbot

                         Dr H. Church

Dr H. Krovvidi