Background One of the leading causes of maternal death is Post Partum Haemorrhage (PPH),

which is on the rise (Leonardsen et al., 2021). Shakur et al. (2010) report in The Woman Trial Study
Protocol that approximately 530,000 women will die from complications of pregnancy or childbirth,
and 2 percent of the 14 million women who experience Post Partum Haemorrhage (PPH) will die
within 2 to 4 hours of the onset of haemorrhage. Since the results of the trial were published in
2017, it has been widely accepted that the administration of intravenous (IV) tranexamic acid (TXA)
reduces mortality from PPH and has become part of clinical guidelines for health providers within
pre-hospital and in-hospital settings, such as the Canterbury District Health Board (CDHB) Maternity
Guidelines (GLM0021-Postpartum-Haemorrhage.Pdf, 2022) and Emergency Ambulance Guideline
(EAS CGPs, 2022). If administered within 3 hours from the onset of bleeding TXA has the potential to
reduce mortality by up to one-third. Following this time frame there is little benefit from its
administration (GLM0021-Postpartum-Haemorrhage.Pdf, 2022). Because of this window of
therapeutic benefit, women experiencing PPH in rural sectors may be at an unnecessarily higher risk
of death by PPH as they may have no early access to TXA before reaching a hospital (Kane et al.,
2021). In the prehospital setting, TXA is the only antifibrinolytic by EAS responders in New Zealand
NZ) and its use is limited as only those with an Authority to Practice (ATP) at Paramedic and above
can administer TXA which is stored in their drug module, unable to be accessed by anyone with an
ATP below this skill level. Secondly, it is limited by way of administration, it may be given IV only.

The aim of this report is to discover if the use of TXA administered via the IM route will offer the
same benefits to reducing PPH mortality as administration via the IV route, thereby circumventing
limitations of use within the Emergency Ambulance Services (EAS) sector. EAS providers could then
solve this health discrepancy by including TXA in vehicle manifests, enabling Emergency Medical
Technicians (EMT) and First Responders (FR) in all regions to provide TXA in the setting of PPH. This
would also ensure EAS providers met The World Health Organization’s (WHO) recommendation that
TXA should be freely accessible for the treatment of TXA wherever emergency obstetrics is
practiced (Shakur‐Still et al., 2022).

Pharmacology – what is TXA and how does it Work TXA is a synthetic analogue of an amino acid
(bears resemblance to)– lysine and a member of the antifibrinolytic class of drugs used to inhibit the
breakdown of blood clots (fibrinolysis) as well as stabilising clot formation. Blood clots are formed
via a complex process known as the clotting cascade, one of the steps within this process is where
fibrinogen (a glycoprotein produced by the liver) is converted to fibrin by thrombin. Fibrin then
works with platelets to form blood clots. Fibrinolysis, (the breakdown of clots), occurs as the
appearance of fibrin causes plasminogen activation and conversion to plasmin by tissue plasminogen
activator (tPA). Degradation of the blood clot occurs. The process of fibrinolysis is reliant on lysine
binding sites on plasminogen and t-PA binding with the lysine residues found on the surface of fibrin,
local plasmin forms and clots are broken down. TXA, as an analogue of lysine, has high affinity for
and competes with plasminogen and t-PA for the lysine residues on fibrin, and so, when enough TXA
is present in plasma, TXA has the ability to block plasminogen and t-PA binding and plasmin is not
able to form. Fibrinolysis is prevented, preserving the formed clot (Kane et al., 2021; Nishida et al.,
2017; Shakur‐Still et al., 2022).

Medicines given via the IV route have a 100% bioavailability meaning the entire dose of medicine is
available for uptake by cells. This is true for TXA, and it has a half-life (time taken for active drug
concentration to lessen by half) of 2-11 hours, with a duration of action 3 hours after first dose
(Chauncey & Wieters, 2022). In healthy subjects the therapeutic blood concentration of TXA, >10
mg/L, can be reached very quickly via the IM route. Kane et al. (2021) and Shakur‐Still et al. (2022)
describe therapeutic levels being reached within ≤ 15 minutes with a bioavailability predicted to be
100%. A 2020 study involving swine shows IM availability to be 97% (Spruce et al., 2020). TXA is
eliminated via the kidneys (Shakur‐Still et al., 2022)

TXA in PPH Consideration needs to be given to differing pharmacokinetics in pregnant women

due to the physiologic changes that take place during pregnancy. Coupled with this is when referring
to a major PPH, shock is likely to be present, with both conditions possibly affecting absorption,
metabolism, distribution, and excretion of medicines. Of note the glomerular filtration rate (GFR) is
markedly increased during pregnancy and plasma volumes increase. This means there is an
increased volume of distribution (Vd) and increased clearance of medicines (Shakur et al., 2018;
Shakur‐Still et al., 2022). Shocked states reduce tissue perfusion which can affect absorption and
distribution of medicines (De Paepe et al., 2002; Grassin-Delyle et al., 2021). Following birth the
plasma concentration of t-PA doubles and brings with it a early increase in D-Dimer levels. D-Dimer is
a fibrinolysis protein produced to break down blood clots and is indicative of the amount of clot
breakdown (Olson, 2015).

A D-dimer test is a blood test that checks for blood-clotting

problems. It measures the amount of D-dimer, a protein your
body makes to break down blood clots. A positive test means
the D-dimer level in your body is higher than normal. It
suggests you might have a blood clot or blood clotting
problems.
In hospital, all had received a loading dose of 1 gm first ivgender and GFR no apparent effect on
pharmkinetice. Blood lactate and signs of shock had no apparent impact on rate of absorption
results consistent with those of healthy vounteers. Results cannot be generalised to women with
pph due to physiologic changes GRASSIN

What level of D-dimer indicates clot?

D-dimer is a protein the body releases when blood clots break down. Its presence in
the blood or urine may indicate that a person has developed a clot. D-dimer levels
of 0.50 mg/L or higher may indicate blood clots somewhere in the body. HIGHER D
DIMER MORE CLOST BROKEN DOWN BY PLASMIN

WOMAN ETAC

Tmax

Tembolism risk

Prophylactic use

Pre vs in hospital available interventions

Demographics
Statistic values

Culture

demograpics

Chauncey, J. M., & Wieters, J. S. (2022). Tranexamic Acid. In StatPearls [Internet]. StatPearls
Publishing. https://www.ncbi.nlm.nih.gov/books/NBK532909/

De Paepe, P., Belpaire, F. M., & Buylaert, W. A. (2002). Pharmacokinetic and pharmacodynamic
considerations when treating patients with sepsis and septic shock. Clinical Pharmacokinetics,
41(14), 1135–1151. https://doi.org/10.2165/00003088-200241140-00002

Emergency Ambulance Service, Clinical Procedures and Guidelines,. (2022).

GLM0021-Postpartum-Haemorrhage.pdf. (n.d.). Retrieved March 14, 2023, from

https://edu.cdhb.health.nz/Hospitals-Services/Health-Professionals/maternity-care-guidelines/
Documents/GLM0021-Postpartum-Haemorrhage.pdf

Grassin-Delyle, S., Shakur-Still, H., Picetti, R., Frimley, L., Jarman, H., Davenport, R., McGuinness, W.,
Moss, P., Pott, J., Tai, N., Lamy, E., Urien, S., Prowse, D., Thayne, A., Gilliam, C., Pynn, H., & Roberts, I.
(2021). Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: A clinical
trial. British Journal of Anaesthesia, 126(1), 201–209. https://doi.org/10.1016/j.bja.2020.07.058

Kane, Z., Picetti, R., Wilby, A., Standing, J. F., Grassin-Delyle, S., Roberts, I., & Shakur-Still, H. (2021).
Physiologically based modelling of tranexamic acid pharmacokinetics following intravenous,
intramuscular, sub-cutaneous and oral administration in healthy volunteers. European Journal of
Pharmaceutical Sciences, 164, 105893. https://doi.org/10.1016/j.ejps.2021.105893

Leonardsen, A.-C. L., Helgesen, A. K., Ulvøy, L., & Grøndahl, V. A. (2021). Prehospital assessment and
management of postpartum haemorrhage- healthcare personnel’s experiences and perspectives.
BMC Emergency Medicine, 21(1), 98. https://doi.org/10.1186/s12873-021-00490-8

Nishida, T., Kinoshita, T., & Yamakawa, K. (2017). Tranexamic acid and trauma-induced
coagulopathy. Journal of Intensive Care, 5, 5. https://doi.org/10.1186/s40560-016-0201-0

Olson, J. D. (2015). D-dimer: An Overview of Hemostasis and Fibrinolysis, Assays, and Clinical
Applications. Advances in Clinical Chemistry, 69, 1–46. https://doi.org/10.1016/bs.acc.2014.12.001

Shakur, H., Beaumont, D., Pavord, S., Gayet‐Ageron, A., Ker, K., & Mousa, H. A. (2018).
Antifibrinolytic drugs for treating primary postpartum haemorrhage. Cochrane Database of
Systematic Reviews, 2. https://doi.org/10.1002/14651858.CD012964

Shakur, H., Elbourne, D., Gülmezoglu, M., Alfirevic, Z., Ronsmans, C., Allen, E., & Roberts, I. (2010).
The WOMAN Trial (World Maternal Antifibrinolytic Trial): Tranexamic acid for the treatment of
postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials,
11, 40. https://doi.org/10.1186/1745-6215-11-40

Shakur‐Still, H., Grassin‐Delyle, S., Muhunthan, K., Ahmadzia, H. K., Faraoni, D., Arribas, M., &
Roberts, I. (2022). Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A
systematic search and narrative review. International Journal of Gynaecology and Obstetrics,
158(Suppl 1), 40. https://doi.org/10.1002/ijgo.14201
Spruce, M. W., Beyer, C. A., Caples, C. M., DeSoucy, E. S., Kashtan, H. W., Hoareau, G. L., Grayson, J.
K., & Johnson, M. A. (2020). Pharmacokinetics of Tranexamic Acid Given as an Intramuscular
Injection Compared to Intravenous Infusion in a Swine Model of Ongoing Hemorrhage. Shock
(Augusta, Ga.), 53(6), 754–760. https://doi.org/10.1097/SHK.0000000000001427