WSAVA Nov 2021 Proceedings - Flipbook - Page 27
thrombotic events. One study in veterinary medicine has shown that TXA
induced vomiting can be prevented with maropitant.(2) Another study has
specifically investigated its use as an emetic, and shown that at 60mg/kg
IV TXA reliably induces emesis.(3)
Hyperfibrinolysis – who to treat?
Since the diagnosis of hyperfibrinolysis is difficult in clinical practice
it seems reasonable that antifibrinolytic therapy could be considered
empirically in certain situations. In my opinion, there are 3 scenarios when
I would consider the use of antifibrinolytic drugs.
1. Animals with diseases associated with hyperfibrinolysis that are at risk
of bleeding
This includes dogs with acute liver failure (ALF) and chronic hepatopathies. ALF has been associated with multifactorial coagulation disturbances in dogs, including thrombocytopenia, increased PT/aPTT, DIC,
increased FDPs and increased D dimers.(5) In the same study 25/49
(51%) had evidence of hemorrhage.(5) Another study of TEG in dogs with
ALF identified that 10/21 dogs were hypocoagulable based on the G value,
while 8/21 were hyperfibrinolytic based on LY30, and hyperfibrinolysis was
associated with more severe disease.(6) As such, I use antifibrinolytic
therapy in dogs with ALF with clinical evidence of bleeding.
A proportion of dogs with chronic hepatopathies are also hypocoagulable and/or hyperfibrinolytic on TEG.(7) Additionally, one dog in this case
series had evidence of gastrointestinal bleeding that resolved with EACA
treatment.(7) Based on this study I administer an antifibrinolytic drug to
dogs with chronic hepatopathy that are bleeding, or require an invasive
procedure such as liver biopsy.
2. Animals with diseases / conditions where antifibrinolytic therapy has
been shown to help
This includes greyhounds having surgery and patients with bleeding secondary to severe trauma (based on the human literature).
Approximately ¼ to 1/3 of Greyhounds experience delayed postoperative
hemorrhage after routine procedures such as spay / neuter, compared
to 0-2% in other breeds. This bleeding tends to occur 24-72 hours after
surgery and is thought to be due to a problem with clot maintenance or
fibrinolysis. In a randomized, blinded, placebo controlled clinical trial greyhounds treated with EACA (500mg PO q8h for 3 days after surgery), were
significantly less likely to experience delayed postoperative hemorrhage
(5/50, 10%) than those receiving placebo (15/50, 30%).(8) A retrospective case series from the same group also described the use of EACA to
prevent postamputation bleeding in greyhounds with appendicular bone
tumours.(9) EACA was dosed somewhat differently, in that an IV dose of
500-1000mg of EACA was given immediately post-operatively, followed
by 500-1000mg PO q8h for 5 days.(9) Again, those receiving EACA were
significantly less likely to experience delayed post-op bleeding and no
adverse effects of the drug were noted.(9)
Based on the findings of these studies it is recommended that all greyhound are treated with EACA or TXA in the perioperative period to reduce
the risk of post-operative hemorrhage. It should be noted that a small
proportion (perhaps 10%) of greyhounds may still experience delayed
post-operative hemorrhage, which if severe should be treated with plasma
transfusion.
The use of TXA in human patients with significant hemorrhage after
trauma, has become widely accepted based on the results of the CRASH-2
trial.(10) That study identified that early administration of TXA within 1-3
hours of trauma (1g bolus, followed by 1g CRI over 8h) was associated
with reduced all-cause mortality and reduced deaths from bleeding,
but that there was no benefit of later administration.(10) A case report
in a dog with intra-thoracic hemorrhage after thoracotomy to repair a
diaphragmatic hernia and lung lobe laceration also reported rapid clinical
improvement after commencement of EACA (33mg/kg IV q6h).(11) This
dog also had hyperfibrinolysis document on TEG that resolved with EACA.
(11) My approach is to use antifibrinolytic drugs in trauma patients with
active bleeding severe enough to require blood transfusion. Once the
bleeding has stopped, I then discontinue the antifibrinolytic.
3. When all else fails / you have no other options to stop bleeding
In these cases the perceived benefit of the antifibrinolytic must outweigh
the potential risks of adverse events.
One such patient population are dogs with hemoperitoneum that are
severe enough to require blood transfusion but whose owners decline
surgery. My rationale is that dogs with hemoperitoneum have been shown
to be more hyperfibrinolytic than age and breed matched controls with
the use of tPA-TEG.(12) In contrast, I don’t give antifibrinolytic drugs for
hemoperitoneum in which I am able to rapidly obtain surgical hemostasis.
Part of my rationale is that dogs undergoing splenectomy for splenic
masses (a large proportion of our hemoperitoneum cases) are at risk of
thrombotic complications in the perioperative period.(13) Additionally, a
retrospective study in dogs with surgically treated hemoperitoneum, found
no difference in RBC transfusion requirements or post-operative bleeding
tendency between dogs that received TXA at least 30 minutes prior to
surgery, and those that did not.(14)
The literature documents the use of antifibrinolytic drugs in a wide variety
of other diseases, however at this stage the evidence is minimal.
References:
1. Kelmer E, et al. Effects of intravenous administration of tranexamic
acid on hematological, hemostatic, and thromboelastographic analytes in
healthy adult dogs. J Vet Emerg Crit Care. 2015;25(4):495-501.
2. Kantyka ME, et al. Prospective, controlled, blinded, randomized
crossover trial evaluating the effect of maropitant versus ondansetron
on inhibiting tranexamic acid-evoked emesis. J Vet Emerg Crit Care.
2020;30(4):436-41.
3. Kakiuchi H, et al. Efficacy and safety of tranexamic acid as an emetic in
dogs. Am J Vet Res. 2014;75(12):1099-103.
4. Choi JY, Kim JH, Han HJ. Suspected anaphylactic shock associated with administration of tranexamic acid in a dog. J Vet Med Sci.
2019;81(10):1522-6.
5. Lester C, et al. Retrospective evaluation of acute liver failure in dogs
(1995-2012): 49 cases. J Vet Emerg Crit Care. 2016;26(4):559-67.
6. Kelley D, et al. Thromboelastographic Evaluation of Dogs with Acute
Liver Disease. J Vet Intern Med. 2015;29(4):1053-62.
7. Fry W, et al. Thromboelastography in Dogs with Chronic Hepatopathies.
J Vet Intern Med. 2017;31(2):419-26.
8. Marin LM, et al. Epsilon aminocaproic acid for the prevention of delayed
postoperative bleeding in retired racing greyhounds undergoing gonadectomy. Vet Surg. 2012;41(5):594-603.
9. Marin LM, et al. Retrospective evaluation of the effectiveness of
epsilon aminocaproic acid for the prevention of postamputation bleeding
in retired racing Greyhounds with appendicular bone tumors: 46 cases
(2003-2008). J Vet Emerg Crit Care. 2012;22(3):332-40.
10. CRASH-2 trial collaborators, et al. 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. Lancet. 2010;376(9734):23-32.
11. Yoo SH, et al. Thromboelastographic evidence of inhibition of fibrinolysis after epsilon-aminocaproic acid administration in a dog with suspect-
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