Effect of early administration of tranexamic acid on ongoing haemorrhage in dogs with non-surgically treated haemoabdomen.

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic drug used for the prophylaxis and treatment of haemorrhage of various origin. This retrospective study investigated the effect of TXA on ongoing bleeding in dogs with nonsurgically treated haemoabdomen. The study population consisted of 48 dogs treated in the period 2009-2020 at the Small Animal Clinic of the Vetsuisse Faculty of Zurich. Twenty-eight of 48 dogs were treated with 20 mg/kg TXA IV within 3h of diagnosis of haemoabdomen. Dogs treated with and without TXA were monitored over 48 hours for signs of ongoing haemorrhage. Ongoing haemorrhage was defined as an increase in abdominal fluid accumulation, a decrease in haematocrit of >5% over time or need for surgical exploration after at least 12 hours of medical treatment. Transfusion requirements, cumulative amount of fluid therapy, heart rate, respiratory rate, temperature, systolic and mean arterial pressure, estimate of abdominal fluid identified by FAST analysis, venous haematocrit, abdominal haematocrit, serum albumin, serum lactate and thrombocyte count were extracted from patient records at 6, 12, 24 and 48 hours after diagnosis of haemoabdomen. Groups were comparable at presentation, however dogs of the TXA group showed a significantly lower abdominal haematocrit at presentation (37 vs 45%, P=0,034) and a higher fluid accumulation (P=0,019), both persisting over time. None of the outcome parameters for ongoing haemorrhage was significantly different between groups. Transfusion requirement was low and similar in both groups. Of interest, none of the 16 dogs undergoing thromboelastometry showed hyperfibrinolysis at presentation. We conclude that other mechanisms than antifibrinolytic therapy was responsible for cessation of bleeding in the majority of patients.

INTRODUCTION: L'acide tranexamique (TXA) est un médicament anti fibrinolytique utilisé pour la prophylaxie et le traitement des hémorragies d'origines diverses. Cette étude rétrospective a examiné l'effet du TXA sur les saignements en cours chez les chiens présentant un hémoabdomen traité sans chirurgie. La population étudiée était composée de 48 chiens traités entre 2009 et 2020 à la clinique pour petits animaux de la faculté Vetsuisse de Zurich. Vingt-huit des 48 chiens ont été traités avec 20 mg/kg de TXA IV dans les 3 heures suivant le diagnostic de l'hémoabdomen. Les chiens traités avec et sans TXA ont été surveillés pendant 48 heures pour détecter les signes d'hémorragie en cours. L'hémorragie en cours a été définie comme une augmentation de l'accumulation de liquide abdominal, une diminution de l'hématocrite de >5% dans le temps ou la nécessité d'une exploration chirurgicale après au moins 12 heures de traitement médical. Les besoins transfusionnels, la quantité cumulative de traitement liquidien, la fréquence cardiaque, la fréquence respiratoire, la température, la pression artérielle systolique et moyenne, l'estimation du liquide abdominal identifié par l'analyse FAST, l'hématocrite veineux, l'hématocrite abdominal, l'albumine sérique, le lactate sérique et la numération des thrombocytes ont été extraits des dossiers des patients à 6, 12, 24 et 48 heures après le diagnostic d'hémoabdomen. Les groupes étaient comparables à la présentation, mais les chiens du groupe TXA présentaient un hématocrite abdominal significativement plus faible à la présentation (37 vs 45 %, P=0,034) et une accumulation de liquide plus importante (P=0,019), ces deux phénomènes persistant dans le temps. Aucun des paramètres de résultat pour l'hémorragie en cours n'était significativement différent entre les groupes. Les besoins en transfusion étaient faibles et similaires dans les deux groupes. Il est intéressant de noter qu'aucun des 16 chiens soumis à la thromboélastométrie ne montrait d'hyperfibrinolyse à la présentation. Nous concluons que d'autres mécanismes que le traitement anti fibrinolytique étaient responsables de l'arrêt des saignements chez la majorité des patients.

Characteristics of hyperfibrinolysis in dogs and cats demonstrated by rotational thromboelastometry (ROTEM).

Hyperfibrinolysis (HFL) is a pathophysiological mechanism that has not been described in dogs or cats extensively. The aim of this study was to describe rotational thromboelastometry (ROTEM) parameters and underlying diagnosis in dogs and cats with HFL and evaluate association with bleeding diathesis. The ROTEM database was retrospectively searched for EXTEM (ROTEM activated with proprietary tissue factor) tracings with maximum lysis at 60min ≥15%. Concurrent ROTEM and plasma coagulation tests, thrombocyte number, diagnosis and survival to hospital discharge were extracted from medical records. Analysis of differences between dogs and cats and of factors associated with bleeding, fulminant HFL (clot breakdown within 30min) and survival to hospital discharge were performed. Hyperfibrinolysis was detected in eight cats presenting with haemoabdomen or haemothorax (n=4/8, 50%) and trauma (n=3/8, 38%) and in 36 dogs with angiostrongylosis (n=12, 33%), neoplasia (n=7, 19%), liver disease (n=4, 11%) and others including apparently healthy dogs (n=3, 8%). Hyperfibrinolysis was associated with prolonged EXTEM and APTEM (EXTEM with added apoprotein for inhibition of HFL) clotting time and decreased FIBTEM (EXTEM with added cytochalasin D for inhibition of thrombocytes) maximum clot firmness (MCF) in dogs and cats and with decreased EXTEM MCF in dogs. Bleeding dogs had significantly hypocoagulable EXTEM tracings. Fulminant HFL was associated with severe hypofibrinogenaemia in dogs (P=0.005) and was not associated with survival to hospital discharge. Evidence of HFL was demonstrated in dogs and cats with bleeding, trauma, parasitic and neoplastic disease. HFL is associated with late and weak clot formation.

Effects of Hydroxyethyl Starch 130/0.4 on Serum Creatinine Concentration and Development of Acute Kidney Injury in Nonazotemic Cats.

BACKGROUND: Hydroxyethyl-starch (HES) solutions might have renal adverse effects in humans and dogs. OBJECTIVE: To determine if administration of 6% HES-130/0.4 is associated with an increase in serum creatinine concentration and development of acute kidney injury (AKI) in nonazotemic cats. ANIMALS: A total of 62 critically ill cats; 26 HES exposed and 36 unexposed. METHODS: Retrospective cohort study (2012-2015). Serum creatinine concentrations were recorded and changes in serum creatinine concentrations before exposure (baseline) and 2-10 and 11-90 days, respectively, were determined. Development of AKI was defined as a > 150% increase or >26 µmol/L increase in serum creatinine concentration from baseline. Risk factors, such as HES administration, cumulative volume of HES (mL/kg) and number of days of HES administration leading to development of AKI, and change in serum creatinine were analyzed. RESULTS: Cats in the HES cohort received a mean volume of 98.5 ± 76.2 mL/kg (range, 8-278 mL/kg) HES over a median of 4 (range, 1-11) days, resulting in a median dose of 20.1 (range, 8-40.5) mL/kg per day. Short-term %change in serum creatinine concentration (P = 0.40) and development of AKI (P = 0.32) were not significantly different between cohorts. Multivariable logistic regression did not identify HES dose in mL/kg (P = 0.33) and number of days of HES application (P = 0.49) as a risk factor for development of AKI. CONCLUSION AND CLINICAL IMPORTANCE: Hydroxyethyl-starch administration to critically ill nonazotemic cats seems to be safe. A larger prospective study is required to determine the effect of HES administration at higher dosages and for prolonged time periods.

Hyperfibrinolysis and Hypofibrinogenemia Diagnosed With Rotational Thromboelastometry in Dogs Naturally Infected With Angiostrongylus vasorum.

BACKGROUND: The pathomechanism of Angiostrongylus vasorum infection-associated bleeding diathesis in dogs is not fully understood. OBJECTIVE: To describe rotational thromboelastometry (ROTEM) parameters in dogs naturally infected with A. vasorum and to compare ROTEM parameters between infected dogs with and without clinical signs of bleeding. ANIMALS: A total of 21 dogs presented between 2013 and 2016. METHODS: Dogs with A. vasorum infection and ROTEM evaluation were retrospectively identified. Thrombocyte counts, ROTEM parameters, clinical signs of bleeding, therapy, and survival to discharge were retrospectively retrieved from patient records and compared between dogs with and without clinical signs of bleeding. RESULTS: Evaluation by ROTEM showed hyperfibrinolysis in 8 of 12 (67%; 95% CI, 40-86%) dogs with and 1 of 9 (11%; 95% CI, 2-44%) dogs without clinical signs of bleeding (P = .016). Hyperfibrinolysis was associated with severe hypofibrinogenemia in 6 of 10 (60%; 95% CI, 31-83%) of the cases. Hyperfibrinolysis decreased or resolved after treatment with 10-80 mg/kg tranexamic acid. Fresh frozen plasma (range, 14-60 mL/kg) normalized follow-up fibrinogen function ROTEM (FIBTEM) maximal clot firmness in 6 of 8 dogs (75%; 95% CI, 41-93%). Survival to discharge was 67% (14/21 dogs; 95% CI, 46-83%) and was not different between dogs with and without clinical signs of bleeding (P = .379). CONCLUSION AND CLINICAL IMPORTANCE: Hyperfibrinolysis and hypofibrinogenemia were identified as an important pathomechanism in angiostrongylosis-associated bleeding in dogs. Hyperfibrinolysis and hypofibrinogenemia were normalized by treatment with tranexamic acid and plasma transfusions, respectively.

Changes in Serum Creatinine Concentration and Acute Kidney Injury (AKI) Grade in Dogs Treated with Hydroxyethyl Starch 130/0.4 From 2013 to 2015.

BACKGROUND: Hydroxyethyl starch (HES) solutions may cause acute kidney injury (AKI) in humans. OBJECTIVE: To compare AKI grades in 94 dogs exposed and 90 dogs that were unexposed to 6% HES-130/0.4. ANIMALS: Dogs receiving 6% HES-130/0.4 (HES cohort) or crystalloids (unexposed cohort) between 2013 and 2015. METHODS: Historical cohort study. Diagnosis, total cumulative dose and total mL/kg of HES administered, time frame of HES administration and serum creatinine concentrations up to 90 days after initiation of HES treatment were retrospectively reviewed. The AKI grades were retrospectively determined by IRIS guidelines. RESULTS: Exposed dogs received a median cumulative dose of 69.4 mL/kg (range, 2-429 mL/kg) HES over a median of 4 (range, 1-16) days, resulting in a median dose of 20.7 (range, 2-87) mL/kg/d. Although the cohorts differed in terms of age and diagnosis, AKI grades were not significantly different at the evaluated short- and long-term time points. Results of ordinal logistic regression identified the number of days of HES administration as significantly associated with an increase in AKI grade within 10 days (P = .038), whereas there was no significant association among HES exposure, HES mL/kg/d, and an increase in AKI grade. CONCLUSIONS AND CLINICAL IMPORTANCE: HES-130/0.4-treated dogs were not more prone to develop AKI than HES-untreated, but the number of HES days was significantly associated with an increase in AKI grade within 10 days post-HES administration. The time frame of HES treatment should be kept short. Prospective, randomized clinical trials are required to assess the effect of HES on renal function in dogs.