Short report
BMJ Support Palliat Care: first published as 10.1136/bmjspcare-2021-003427 on 4 February 2022. Downloaded from http://spcare.bmj.com/ on February 11, 2022 at USP - Universidade de
1
Mountbatten Hospice, Newport,
Isle of Wight, UK
2 Objectives To investigate the efficacy and safety
Palliative Care Team, Isle of
Wight NHS Trust, Newport, UK
Correspondence to
Dr Paul Howard, Mountbatten
Hospice, Newport, Isle of Wight,
UK; ​paul.​howard1@​nhs.​net
Received 19 October 2021
Accepted 24 January 2022
© Author(s) (or their
employer(s)) 2022. No
commercial re-­use. See rights
and permissions. Published by
BMJ.
To cite: Howard P, Curtin J.
BMJ Supportive & Palliative
Care Epub ahead of
print: [please include Day
Month Year]. doi:10.1136/
bmjspcare-2021-003427
Howard P, Curtin J. BMJ Supportive & Palliative Care 2022;0:1–5. doi:10.1136/bmjspcare-2021-003427
Bleeding management in palliative
medicine: subcutaneous tranexamic
acid - retrospective chart review
Paul Howard ‍ ‍,1,2 John Curtin1,2
ABSTRACT
of subcutaneously (SC) administered tranexamic
acid.
Methods A retrospective chart review of the
use of SC tranexamic acid in a single palliative
care centre. We reviewed the use of this
approach since it was introduced in our locality
2 years ago. All clinical notes, medication
administration records and infusion monitoring
documentation were examined to ascertain
therapeutic aim, efficacy and tolerability.
Results SC tranexamic acid was administered
to 22 patients. The most common causes of
bleeding were coagulopathy (5), bleeding
tumours (9) and thrombocytopaenia (5). The
therapeutic aim was either to prevent (6)
or treat (16) bleeding and was achieved in
17/22 patients. During this 2-­year period, our
experience evolved resulting in a greater use
of short bolus infusions to achieve more rapid
control of bleeding events. Both short and
continuous SC infusions were well tolerated with
no instances of SC site reactions. One patient
developed a suspected arterial thrombus in the
last hours of life around the time of converting
from oral (PO) to SC tranexamic acid.
Conclusions SC administration of tranexamic
acid appears to be an effective and well tolerated
alternative option for the palliative management
of bleeding when the PO and intravenous routes
are not available. Further research is needed
to clarify tranexamic acid’s safety in palliative
populations.
INTRODUCTION
Bleeding in palliative care can be
distressing for patients, their families
and healthcare professionals. Further, it
can precipitate unwanted admissions to
hospital, cause symptomatic anaemia and
shorten life. Causes include thrombocy-
topaenia, anticoagulation, coagulopathy
(deranged INR [International Normalised
Ratio] and/or APTR [Activated Partial
Key messages
What was already known?
► Tranexamic acid is an important palliative
treatment for bleeding.
► Continuous subcutaneous infusion of
tranexamic acid is reported.
What are the new findings?
► Tranexamic acid boluses can be given by
short subcutaneous infusion.
► Both continuous and short subcutaneous
infusions are well tolerated and appear
Sao Paulo. Protected by copyright.
effective.
What is their clinical significance?
► Subcutaneous tranexamic acid is a
straightforward palliative intervention for
bleeding.
Thromboplastin Ratio]) and bleeding
(eg, fungating) tumours. In advanced
cancer, the reported incidence of signifi-
cant bleeding is 6%–14% and of terminal
haemorrhage is 3%–12%.1
Effective treatments for bleeding could
alleviate such distress and help maintain
quality of life. Adapting such treatments
where necessary, to enable their delivery
in the community, could facilitate end
of life choices such as a preference to
remain at home. Where treatments aimed
at the underlying cause are inappropriate
or ineffective, bleeding is often treated
palliatively with haemostatic dressings,
tranexamic acid or topical epinephrine
(epinephrine).2 3
Tranexamic acid is a lysine-­ analogue
that interferes with the plasmin cascade
responsible for dissolving fibrin clots.
It is mostly renally excreted unchanged
and, thus, a dose reduction is required
in those with renal impairment. It can be
used topically, orally and intravenously.4 5
Nebulised administration for haemoptysis
is also reported.6 However, the onset of
action of oral tranexamic acid is delayed
1
 Short report
and may be further impaired by gastric stasis or upper
gastrointestinal haemorrhage. Recurrent intravenous
cannulation can be problematic, particularly in the
community. Subcutaneously (SC) administration is
well tolerated in the postsurgical setting.7 8 In pallia-
tive care, Hall, Gibbs et al successfully treated bleeding
in the home setting using both continuous SC infusion
(CSCI) (SC syringe driver) and SC bolus administra-
tion once the oral route was lost because intravenously
administration wasn’t possible.9 Sutherland prevented
bleeding recurring when the intravenous route was
lost by converting to CSCI in the last 18 days of life.10
Two years ago, we encountered a patient who had
responded well to oral tranexamic acid, and wished to
die at home, but was frightened of bleeding once too
weak to swallow oral medication. Our colleagues in
St Christopher’s, London, shared their experience of
SC use, enabling us to care for our patient in her own
home. Because it appeared to be a potentially valuable
option for selected patients, we set out to collate our
experience.
METHOD
We undertook a retrospective chart review of the use
of SC tranexamic acid in a single palliative care centre.
The Squire Quality Improvement Checklist was used
as a framework for collating our experience and iden-
tifying learning from this newly introduced practice.
Patients receiving parenteral tranexamic acid
ampoules in our community palliative care service
and inpatient hospice were identified using both the
electronic patient record and pharmacy dispensary
systems. Their electronic records were then reviewed
to identify those receiving one or more SC doses either
as a SC bolus, short SC infusion (SSCI) or CSCI. Those
who were pre-­ emptively prescribed SC tranexamic
acid because they were at risk of bleeding, but who
did not require any SC doses were excluded. Similarly,
those receiving only PO, topical or intravenous doses
were excluded.
We reviewed the clinical notes, medication admin-
istration records, and infusion monitoring documen-
tation for all included patients. The therapeutic aim
of the SC tranexamic acid, whether that aim was
achieved and the dose used, were ascertained along
with details of tolerability and place of care. Effi-
cacy was measured by the number of patients where
bleeding ceased throughout the treatment period. The
tolerability of SC tranexamic acid was measured by
the number of patients reported to have experienced
any adverse event or SC site reaction. SC sites were
routinely examined four times daily in our inpatient
hospice or once daily for patients in their own homes.
Where necessary, the health professionals involved
in prescribing, supplying, administering or monitoring
the SC tranexamic acid were asked for additional
details about the patients identified. Further, they were
2 Howard P, Curtin J. BMJ Supportive & Palliative Care 2022;0:1–5. doi:10.1136/bmjspcare-2021-003427
BMJ Support Palliat Care: first published as 10.1136/bmjspcare-2021-003427 on 4 February 2022. Downloaded from http://spcare.bmj.com/ on February 11, 2022 at USP - Universidade de
asked about their experience and views of using SC
tranexamic acid.
RESULTS
Data were collected from October 2019 to September
2021. We identified 22 patients receiving SC
tranexamic acid by either CSCI (10), SSCI (6), or both
(6). Most (19) had an underlying malignancy. The most
common causes of bleeding were thrombocytopaenia
(5), coagulopathy (5) and bleeding tumours (9). The
majority (15) were cared for in our 16 bedded inpa-
tient hospice; the remainder were in their own homes.
Those receiving SC tranexamic acid to prevent
bleeding (6) were at risk of bleeding but unable to
receive oral tranexamic acid. Of these, none experi-
enced bleeding. The remainder (16) received it to treat
bleeding. Of these, bleeding either ceased or reduced
to a level that was not bothersome in 11. Thus, overall,
the therapeutic aim was achieved in 17/22 patients.
Table 1 chronologically describes our evolving expe-
rience. Initially, only the CSCI method was used. We
then encountered a patient with intermittent bleeding
who declined our suggested CSCI but agreed to our
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alternative recommendation of a SSCI (patient 9).
Because this controlled bleeding quickly, we used it
increasingly to manage active bleeding. Since it was
well tolerated, we subsequently reduced the infusion
volume to 50 mL to enable boluses to be administered
more quickly.
Both SSCI and CSCI were well tolerated with no
instances of SC site reactions. None of those with
haematuria (3) experienced clot retention, although
in patient 12, frequent bladder washouts were used to
prevent this until the bleeding stopped. One patient
developed a suspected arterial thrombus in the last
hours of life around the time of converting from PO to
SC tranexamic acid.
For CSCI, tranexamic acid 1500–2000 mg was
diluted with water for injection to a total volume
of either 17 mL (1500 mg) or 22 mL (2000 mg) and
administered over 24 hours using a McKinley T34
pump. We have not combined it with any other medi-
cation and are not aware of compatibility data relevant
to doing so. Its alkaline pH might be expected to cause
precipitation with many commonly used (acidic) end-­
of-­life care medicines.
For SSCI, tranexamic acid 500–1000 mg is added
to 50 mL of sodium chloride 0.9% and infused SC
under gravity over approximately 15–30 min. This
is repeated if required and/or followed by a CSCI.
Although 10%–20% of the intended SSCI dose can
remain in the giving set, efficacy appeared unaffected
by the residual dose.
Health professionals involved in administering SC
tranexamic acid reported it to be a welcome additional
option for a distressing symptom and noted that it was
a straightforward process using techniques that are
 Short report

BMJ Support Palliat Care: first published as 10.1136/bmjspcare-2021-003427 on 4 February 2022. Downloaded from http://spcare.bmj.com/ on February 11, 2022 at USP - Universidade de
Table 1 Characteristics of patients receiving subcutaneous tranexamic acid
Cause of bleeding Medication
(relevant blood results, (dose, duration, method) Safety and Efficacy and
Patient Age underlying diagnosis) Care setting (SSCI=given over 30 mins) tolerability comments
1 78 Thrombocytopaenia* (platelets 10, Community 1500 mg/24 hours CSCI for 2 days No site problems Converted from PO
acute transformation of chronic when oral route lost; no
myeloid leukaemia) bleeding recurrence
2 77 Fungating facial tumour Inpatient 2000 mg/24 hours CSCI† for No site problems Converted from PO
(malignant melanoma) hospice 2 days when oral route lost; no
bleeding recurrence
3 58 Thrombocytopaenia* (platelets 12, Community 1500 mg/24 hours CSCI for No site problems Converted from PO
acute lymphoid leukaemia) 14 hours when oral route lost; no
bleeding recurrence
4 66 Fungating mouth tumour Inpatient 1500 mg/24 hours CSCI for 2 days No site problems Converted from use of
(squamous cell carcinoma) hospice mouthwashes when oral
route lost and bleeding
developed; bleeding
stopped with CSCI
5 87 Fungating scalp tumour Inpatient 1500 mg/24 hours CSCI for 2 days No site problems Converted from PO
(squamous cell carcinoma) hospice when oral route lost; no
bleeding recurrence
6 40 Vomiting due to suspected Community 1000 mg/24 hours CSCI for 1 day; No site problems Dose reduced due to
haematemesis then reduced to renal failure. No benefit:
(end stage renal failure) 500 mg/24 hours CSCI for 2 days stopped after 72 hours.
7 70 Haematemesis Community 1500 mg/24 hours CSCI for 1 day No site problems Bleeding stopped
(pancreatic cancer)
8 94 Haematemesis Community 1500 mg/24 hours CSCI for 1 day No site problems Bleeding stopped

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(bowel cancer)
9 55 Fungating nasal sinus tumour Community 500 mg SSCI 3 times in 2 months. No site problems The PRNs were effective
(squamous cell carcinoma) Then 1000 mg SSCI followed by The higher dose
2000mg CSCI† for 2 days until controlled more severe
death bleeding for the last
48 hours of life
10 79 Malaena Inpatient 1500 mg/24 hours CSCI for 6 days No site problems Converted from PO
(stomach cancer, multiple myeloma) hospice when oral route lost; no
bleeding recurrence
11 72 Coagulopathy Inpatient 500 mg SSCI followed by No site problems Bleeding largely stopped;
(INR 1.7, liver cirrhosis) hospice 1500 mg CSCI† for 48 hours some minor bleeding
after mouthcare but not
enough to need PRN
12 76 Haematuria Inpatient 1000 mg SSCI (2 doses in 1 day); No site problems Bleeding stopped with
(cancer of the bladder) hospice died 6 days later the second dose; renal
impairment may have
resulted in a prolonged
benefit from the 2 SSCI
doses; no clot retention
occurred.
13 72 Haematuria due to Inpatient 1000 mg SSCI (2 doses, 4 days No site problems No clot retention
thrombocytopaenia* hospice apart); second SSCI dose occurred but bleeding did
(platelets 12, multiple myeloma) followed by 1500 mg/24 hours not fully resolve despite
CSCI (1 day), increased to further PRN SSCI doses
2000 mg/24 hours CSCI (for and titration of CSCI
1 day) dose.
14 89 Fungating scalp tumour Inpatient 1000 mg SSCI‡ (2 doses, 1 month No site problems Given SSCI initially for
(squamous cell carcinoma) hospice apart; 1000–1500 mg three times faster onset of action.
a day PO in the interim) Bleeding stopped and
was controlled with PO
for 1 month. Second SSCI
given with good effect
for bleeding despite PO
tranexamic acid
15 60 Use of apixaban; possible concurrent Inpatient 1000 mg SSCI (one dose) No site problems Bleeding stopped
coagulopathy (APTR 2.33, INR 1.1, hospice
hepatic metastases; pancreatic
cancer)

Continued

Howard P, Curtin J. BMJ Supportive & Palliative Care 2022;0:1–5. doi:10.1136/bmjspcare-2021-003427 3

 Short report

BMJ Support Palliat Care: first published as 10.1136/bmjspcare-2021-003427 on 4 February 2022. Downloaded from http://spcare.bmj.com/ on February 11, 2022 at USP - Universidade de
Table 1 Continued
Cause of bleeding Medication
(relevant blood results, (dose, duration, method) Safety and Efficacy and
Patient Age underlying diagnosis) Care setting (SSCI=given over 30 mins) tolerability comments
16 84 Haemoptysis (squamous cell lung Inpatient 1000 mg SSCI‡, followed by No site problems Given SSCI initially for
carcinoma) hospice 500 mg three times a day PO faster onset of action.
Bleeding reduced and no
longer bothersome
17 88 Haematemesis and malaena Inpatient 1000 mg SSCI‡, followed by No site problems Haematemesis lessened
(bowel obstruction; diverticular hospice 1500 mg CSCI for <24 hours to small single episode at
disease; advanced dementia) (until death) death. Melaena and fresh
PR bleeding continued
18 76 Melaena and fresh rectal bleeding Inpatient 1000 mg SSCI‡, followed by No site problems Given SSCI initially for
due to coagulopathy hospice 1000 mg two times a day PO. faster onset of action.
(INR 1.6, metastatic Once oral route lost, switched Bleeding stopped.
cholangiocarcinoma; radiation to 1500 mg CSCI until death
proctitis) (2 days)
19 68 Haematemesis and melaena Inpatient 1500 mg CSCI for <24 hours Suspected lower Converted from PO when
(oesophageal cancer) hospice (infusion stopped; see comment) limb thrombosis oral route lost.
(causality unclear) Lower limb thrombosis
clinically diagnosed but
imaging not arranged
because the dying
process had started
. Patient died within
36 hours of CSCI starting
20 74 Rectal bleeding due to suspected Inpatient 500 mg SCCI‡ No site problems Previously treated with

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coagulopathy§ hospice intravenously tranexamic
(obstructive jaundice; pancreatic acid and vitamin K in an
cancer) acute hospital
Melaena recurred
14hours later
21 51 Haematuria due to coagulopathy Inpatient 1000 mg SCCI‡ and repeated No site problems Frank haematuria
(INR 1.9, metastatic colorectal hospice 7 hours later resolved to blood stained
cancer; bilateral ureteric stents) urine
22 74 Spontaneous subdural haematoma Community 1000 mg SSCI‡, followed by No site problems Subsequently admitted
due to thrombocytopaenia* 1500 mg CSCI (given for 10 days to the inpatient hospice.
(platelets 39, myelodysplasia) and then converted to PO) Condition improved with
return of oral route
*In our locality, platelet transfusions are not generally undertaken outside of the hospital setting; platelet counts are expressed as 109/L.
†Diluted to 22 mL, rather than 17 mL.
‡With increasing experience of tolerability, SSCIs were diluted in 50 mL, rather than 100 mL, to allow more rapid administration.
§No confirmatory blood results because they would not have affected management, but coagulopathy suspected due to worsening jaundice.
APTR, Activated Partial Thromboplastin Ratio; CSCI, continuous SC infusions; INR, International Normalised Ratio; PRN, When required ('pro re nata'); SCI,
subcutaneously infusion; SSCI, short SC infusion.

already familiar to those administering other palliative
care medications SC.
DISCUSSION
Although we cannot be certain about efficacy in this
open-­ label retrospective chart review, we conclude
that SC tranexamic acid is a well tolerated and straight-
forward palliative intervention for both treating and
preventing bleeding in patients with bleeding tumours,
coagulopathies and thrombocytopaenia. We thank our
colleagues in St Christopher’s for supporting the intro-
duction and evolution of this valuable practice in our
locality.
Although thrombotic events after intravenous
tranexamic acid in the trauma and peri-­ operative
setting are no more common than with placebo,11 12 it
is unclear whether these findings can be extrapolated
to palliative care populations, where prothrombotic
predispositions are common.13 Patient 19 reported
leg symptoms the day before his tranexamic acid
was converted from PO to CSCI, although signs of
acute ischaemia were not present until the day after
commencing tranexamic acid CSCI. Further, their
underlying cancer was, itself, prothrombotic. Thus,
we were unable to determine whether the SC and/
or PO tranexamic acid contributed. Further research
could usefully characterise whether tranexamic acid in
the palliative setting is associated with this potentially
serious adverse effect.
Seizures are described with high-­ dose intrave-
nous tranexamic acid boluses (50–100 mg/kg/30 min)
during cardiac surgery,14 but not with lower doses used
in other contexts.11 We used lower doses and did not
see any seizures. A study comparing different dose

4 Howard P, Curtin J. BMJ Supportive & Palliative Care 2022;0:1–5. doi:10.1136/bmjspcare-2021-003427


regimens for cardiac surgery found no advantage to
loading doses greater than 10 mg/kg/30 min.15
This retrospective analysis represents low quality
evidence because there are several sources of potential
bias. Although community patients were identified by
electronic searches, inpatients were partly identified by
clinician’s recollection resulting in a risk of selection
bias. Further, where oral tranexamic acid was switched
to SC, it is possible that the effect of previous oral
treatment persisted, for example as a result of renal
impairment. In those receiving SC tranexamic acid for
bleeding, it is possible that bleeding might have ceased
spontaneously without treatment.
This analysis illustrates how palliative care profes-
sionals and their patients must often make decisions
with incomplete information. Thus, we believe it
highlights the need to better collaborate, collate and
share our experiences to strengthen our evidence
base. Despite its draw backs, this series highlights
a promising attempt to take a hospital intervention
and deliver it in the community, enabling patients to
remain in their chosen place of care.
CONCLUSION
Subcutaneous administration of tranexamic acid
appears to be a well-­tolerated alternative option for
the palliative management of bleeding when the oral
and intravenous routes are not available. SSCI of bolus
doses may achieve rapid control of bleeding events.
Further bleeding might be prevented by CSCI. Further
research is required to better characterise the risks of
tranexamic acid in the palliative care setting.
Acknowledgements We would like to thank Dr Emma Hall,
Consultant in Palliative Medicine, St Christopher’s Hospice,
London, for sharing her clinical experience with the use of SC
tranexamic acid and Sandra Clawson, our clinical pharmacist,
for supporting the introduction of this new practice into our
locality.
Contributors PH and JC jointly conceived and conducted the
audit; PH and JC jointly wrote the manuscript.
Funding The authors have not declared a specific grant for this
research from any funding agency in the public, commercial or
not-­for-­profit sectors.
Competing interests None declared.
Patient consent for publication Not applicable.
Provenance and peer review Not commissioned; externally
peer reviewed.
Twitter Paul Howard @Paul_Howard_IoW
Howard P, Curtin J. BMJ Supportive & Palliative Care 2022;0:1–5. doi:10.1136/bmjspcare-2021-003427
Short report
BMJ Support Palliat Care: first published as 10.1136/bmjspcare-2021-003427 on 4 February 2022. Downloaded from http://spcare.bmj.com/ on February 11, 2022 at USP - Universidade de
ORCID iD
Paul Howard http://orcid.org/0000-0002-4521-6310
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