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Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment

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A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Animal Physiology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 20894

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Dr. Nadja E. Sigrist

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Vetsuisse Faculty of Zürich and VET ECC CE (Veterinary Emergency and Critical Care Consulting & Education), University of Zurich, Zurich, Switzerland
Interests: Coagulopathies in Dogs and Cats

Special Issue Information

Dear Colleagues,

Coagulation disorders in dogs and cats are associated with high morbidity and mortality. Identification of some coagulation abnormalities such as hyperfibrinolysis or thromboembolism is challenging despite the availability of viscoelastic coagulation testing, and the pathophysiology of many coagulopathies is still mainly unknown or extrapolated from studies in people.

Further research for straightforward diagnosis, identification of pathomechanisms, and appropriate treatment is needed for the successful management of coagulopathies in dogs and cats. Interaction with each other, sharing of experiences, and publication in a timely manner play a crucial role in achieving these goals. With the Special Issue “Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms, and Treatment”, we invite you to submit studies prospectively or retrospectively investigating any objective regarding coagulopathies in dogs and cats. The aim of this Special Issue is to collate a body of work on the subject of coagulopathies in companion animals and to demonstrate and share current standards and new insights as well as future solutions of this important hemostatic abnormality.

I look forward to your submissions!

Thank you,

Dr. Nadja E. Sigrist
Guest Editor

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Keywords

coagulation
coagulopathy
ROTEM
TEG
rotational thromboelastometry
thromboelastography
platelet
coagulation factor
coagulation time
fibrinogen
PT
aPTT
fibrinogen
CT
MCF
MA
hemophilia
DIC
hemostasis

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Published Papers (9 papers)

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Research

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20 pages, 3188 KiB

Open AccessArticle

Evaluation of the Effect of Induced Endotoxemia on ROTEM S^® and Platelet Parameters in Beagle Dogs Anaesthetized with Sevoflurane

by Annette P. N. Kutter, Fabiola B. Joerger, Barbara Riond and Barbara Steblaj

Animals 2023, 13(19), 2997; https://doi.org/10.3390/ani13192997 - 22 Sep 2023

Viewed by 1239

Abstract

Endotoxemia is thought to induce severe changes in coagulation status. In this study, blood samples from six beagle dogs receiving 1 mg/kg E. coli lipopolysaccharide (LPS) intravenously were analyzed to describe the concurrent changes in platelet count, platelet function assessed with impedance thromboaggregometry, thromboelastometry and d-dimers during artificially induced endotoxemia and its therapy with fluids and vasopressors at five timepoints (baseline, after LPS and 30 mL/kg Ringer’s acetate, during noradrenaline ± dexmedetomidine infusion, after a second fluid bolus and a second time after vasopressors). Results were analyzed for changes over time with the Friedman test, and statistical significance was set at p < 0.05. We found decreased platelet count and function and changes in all platelet-associated rotational thromboelastometry (ROTEM) variables indicating hypocoagulability, as well as increases in d-dimers indicating fibrinolysis within one hour of intravenous administration of LPS, with partial recovery of values after treatment and over time. The fast changes in platelet count, platelet function and ROTEM variables reflect the large impact of endotoxemia on the coagulation system and support repeated evaluation during the progress of endotoxemic diseases. The partial recovery of the variables after initiation of fluid and vasopressor therapy may reflect the positive impact of the currently suggested therapeutic interventions during septic shock in dogs. Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

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12 pages, 248 KiB

Open AccessArticle

Clinical Use of Canine Thawed Refrigerated Plasma: A Historical Case Series

by Weiqin Chee, Claire R. Sharp and Corrin J. Boyd

Animals 2023, 13(12), 2040; https://doi.org/10.3390/ani13122040 - 20 Jun 2023

Cited by 1 | Viewed by 1797

Abstract

Thawed plasma (TP) refers to defrosted fresh frozen plasma stored refrigerated. TP is used in human medicine for the rapid provision of coagulation factors and resuscitation of haemorrhagic shock, but its use in dogs is poorly described. The objectives of this historical case series were to describe the reasons for TP transfusion, treatment outcomes, and adverse events associated with canine TP transfusions in a veterinary teaching hospital. We hypothesised that TP would be used most commonly for the treatment of haemorrhage secondary to anticoagulant rodenticide intoxication and trauma. Blood bank plasma transfusion logs were searched to identify dogs that received at least one unit of TP between December 2015 and June 2021. Briefly, 166 dogs received a total of 262 units of TP. Anticoagulant rodenticide intoxication (37/166, 22.3%) was the most common reason for transfusion, followed by traumatic haemorrhage (23, 13.9%) and spontaneous haemoperitoneum (22, 13.2%). The majority of dogs received one unit of TP (111/166, 67.1%) and pRBCs were commonly simultaneously transfused with TP (65, 39.2%). Severe prolongations of prothrombin time and activated partial thromboplastin time were reduced following TP transfusions. Allergic reactions were the most common transfusion reaction (19/166, 11.4%). Most dogs survived to discharge (101/166, 60.8%). Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

12 pages, 290 KiB

Open AccessArticle

Evaluation of a Viscoelastic Coagulation Monitoring System (VCM Vet^®) and Its Correlation with Thromboelastometry (ROTEM^®) in Diseased and Healthy Dogs

by Imke Hennink, Laureen Peters, Geert van Geest and Katja-Nicole Adamik

Animals 2023, 13(3), 405; https://doi.org/10.3390/ani13030405 - 25 Jan 2023

Cited by 6 | Viewed by 2477

Abstract

Thromboelastometry provides a real-time assessment of global coagulation in whole blood. A novel bed-side viscoelastic coagulation monitor (VCM) has been developed for use in small animals. The aims of the study were to determine inter-device agreement of two VCM devices, to evaluate the correlation between VCM and rotational thromboelastometry as a reference method (ROTEM), and to determine the sensitivity and specificity of VCM to diagnose hypo-, normo-, and hypercoagulability. ROTEM (extrinsic and intrinsic activation) analysis was performed using citrated blood and VCM analysis using native blood. Twenty healthy and forty diseased dogs with and without coagulopathies were enrolled. The VCM inter-device agreement was moderate to strong for most of the parameters, depending on the grading scale. Correlation between VCM and ROTEM was moderate to strong for parameters of clotting time and clot strength. The VCM most likely detects true hypocoagulability and reliably rules out hypocoagulability. The VCM has a high sensitivity in diagnosing normocoagulability, but incorrectly classified dogs with abnormal coagulation as normocoagulable. The VCM was not able to detect hypercoagulability. ROTEM and VCM cannot be used interchangeably. Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

14 pages, 742 KiB

Open AccessArticle

Evaluation of Haemostasis in Dogs Affected by Resectable Malignancy

by Barbara Bruno, Cristiana Maurella, Paola Gianella, Giulio Mengozzi, Erica Ferraris and Antonio Borrelli

Animals 2023, 13(1), 164; https://doi.org/10.3390/ani13010164 - 31 Dec 2022

Viewed by 1718

Abstract

Dogs with neoplasm are at risk of thrombosis, yet there is no information on the haemostatic alterations that may result from the surgeries performed to remove neoplastic masses. The aim of this study was to observe the characteristics of haemostasis in dogs undergoing surgery to remove a malignancy by means of rotational thromboelastometry and thrombin generation. Haemostasis was assessed immediately before surgery (T0), 24 h after surgery (T1), and two weeks after surgery (T2). Statistically significant differences were found between the thromboelastometric parameters at T0 vs. T1, with increases observed in MCF, the α angle, and G parameters in the ex-TEM and in-TEM profiles. In the thromboelastometric analysis performed after surgery differences were identified between T1 and T2, with a decrease observed in parameters such as CFT, MCF, the α angle, and G. Between T0 and T2, only a significant decrease in CT was detected in the fib-TEM profile. No differences were found in the comparison among the results obtained via thrombin generation. In dogs with resectable malignancies, the surgeries performed to remove cancer affected coagulation, causing a tendency towards hypercoagulability. The interference with coagulation was transient, and 2 weeks after surgery, the thromboelatometric results returned to those obtained before surgery (T0). Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

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11 pages, 1028 KiB

Open AccessArticle

Biomarkers of Coagulation and Inflammation in Dogs after Randomized Administration of 6% Hydroxyethyl Starch 130/0.4 or Hartmann’s Solution

by Corrin J. Boyd, Anthea L. Raisis, Claire R. Sharp, Melissa A. Claus, Giselle Hosgood and Lisa Smart

Animals 2022, 12(19), 2691; https://doi.org/10.3390/ani12192691 - 6 Oct 2022

Viewed by 2071

Abstract

Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES. Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

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12 pages, 275 KiB

Open AccessArticle

Comparison of Jugular vs. Saphenous Blood Samples, Intrarater and In-Between Device Reliability of Clinically Used ROTEM S Parameters in Dogs

by Johanna Vuille-dit-Bille, Nicole Weingand, Rahel Jud Schefer, Martina Stirn, Katja-Nicole Adamik, Justus M. K. Rathmann and Nadja E. Sigrist

Animals 2022, 12(16), 2101; https://doi.org/10.3390/ani12162101 - 17 Aug 2022

Cited by 3 | Viewed by 1673

Abstract

Rotational Thromboelastometry (ROTEM) allows for the global assessment of hemostasis in whole blood samples. Preanalytical and analytical factors may influence test results, and data about the reliability and reproducibility of lyophilized ROTEM tests are scarce. Therefore, the objective of this study was to evaluate the influence of blood collection site on ROTEM S parameters and to assess intrarater and in-between device variability. A total of thirty, healthy, staff-owned dogs were included. Blood collection and ROTEM analysis were performed by trained staff according to a standardized protocol. Extrinsically activated (tissue factor; Ex-TEM S), with the addition of cytochalasin for platelet inhibition (Fib-TEM S), and intrinsically activated (In-TEM) analyses were performed. Analysis of our data showed significant variability for various Ex-TEM S and Fib-TEM S parameters from different collection sites and intrarater and in-between device measurements. We conclude that serial monitoring with ROTEM should be performed on the same device, with blood always taken from the same collection site using a standardized blood sampling technique. While In-TEM S, apart from maximum lysis, showed very stable and reliable results, we suggest interpreting especially clotting and clot formation parameters from Ex-TEM S and Fib-TEM S tests with caution and using duplicate measurements to detect outliers and to prevent initiation of incorrect therapies. Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

15 pages, 467 KiB

Open AccessArticle

Evaluation of the Effect of Storage Time on ROTEM S^® Parameters in Healthy and Ill Dogs

by Nicole Weingand, Johanna Vuille-dit-Bille, Rahel Jud Schefer, Annette P. N. Kutter, Martina Stirn, Katja-Nicole Adamik and Nadja E. Sigrist

Animals 2022, 12(15), 1996; https://doi.org/10.3390/ani12151996 - 7 Aug 2022

Cited by 2 | Viewed by 1881

Abstract

Viscoelastic testing as a bedside test to assess global haemostasis has gained popularity in the past decade, with rotational thromboelastometry (ROTEM) and thromboelastography (TEG) being the two commonly used devices. TEG studies suggest analysis 30 min after blood sampling. However, the reproducibility of results over time for ROTEM analysis using lyophilized samples in dogs has not been established. In this study, we investigated the influence of time on viscoelastic testing, using 33 healthy staff-/client-owned dogs for blood sampling and repeated measurements of ROTEM tracings at three different time points after blood collection. Additionally, a group of 21 hospitalized patients with suspected coagulation disorders were included to investigate whether stability over time was comparable between healthy and ill dogs. We demonstrated a significant difference of ROTEM tracings over time, with a tendency towards hypocoagulability over time. These changes do have a clinical relevance as they exceed reference intervals and could therefore lead to erroneous conclusions about a patient’s coagulation status. Therefore, time-specific reference intervals are proposed and presented in this publication. Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

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14 pages, 600 KiB

Open AccessArticle

Retrospective Evaluation of Intravenous Enoxaparin Administration in Feline Arterial Thromboembolism

by Athanasia Mitropoulou, Esther Hassdenteufel, Joanna Lin, Natali Bauer, Gabriel Wurtinger, Claudia Vollmar, Estelle Henrich, Nicolai Hildebrandt and Matthias Schneider

Animals 2022, 12(15), 1977; https://doi.org/10.3390/ani12151977 - 4 Aug 2022

Cited by 4 | Viewed by 3841

Abstract

Induction of a hypocoagulable state is imperative in the treatment of feline arterial thromboembolism. Publications in human medicine report the use of enoxaparin intravenously in selected cases. The aim of our retrospective study was to report the regain of perfusion, short-term outcome, and complications of cats treated with a novel intravenous enoxaparin protocol (1 mg/kg bolus injection followed by 3 mg/kg/day continuous infusion) combined with oral clopidogrel administration. The secondary aim was to report the monitoring of enoxaparin with anti-Xa activity. There were 36 cats included. The probability of reaching limb reperfusion was significantly (p = 0.0148) higher with anti-Xa activity within or above the target range compared to results below the target range (19/21, 90% versus 11/20, 55%). The complications observed were acute kidney injury (15/36, 42%), hemorrhage (2/36, 6%), and neurological signs (6/36, 17%). The most common causes of death/euthanasia were cardiac instability, acute kidney injury, neurological abnormalities, and limb necrosis. The hospital discharge rate was 83% (10/12) for single limb and 29% (7/24) for dual limb thrombosis; the difference was significant (p = 0.0039). The median hospitalization time for the survivors was 119.5 (95–480) h. Our study supports the use of intravenous continuous rate infusion of enoxaparin in combination with oral clopidogrel for cats with aortic thromboembolism. We report similar discharge rates and lower hemorrhage rates than previously reported with thrombolytic treatment. Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

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Review

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14 pages, 560 KiB

Open AccessReview

Fibrinolysis in Dogs with Intracavitary Effusion: A Review

by Andrea Zoia, Michele Drigo, Marco Caldin, Paolo Simioni and Christine J. Piek

Animals 2022, 12(19), 2487; https://doi.org/10.3390/ani12192487 - 20 Sep 2022

Cited by 4 | Viewed by 2599

Abstract

Physiologic fibrinolysis is a localized process in which stable fibrin strands are broken down by plasmin in response to thrombosis. Plasmin activation can also take place separately from the coagulation process, resulting in pathologic fibrinolysis. When plasmin activation exceeds the neutralizing capacity of plasmin inhibitors, severe bleeding can potentially take place. Although the processes which regulate coagulation and fibrinolysis in the blood are well known, it is less clear as to what extent the same processes take place in the body cavities and whether they influence systemic hemostasis. The results of the studies herein cited demonstrate that coagulation followed by fibrinogenolytic/fibrinolytic activity takes place in all kinds of canine ascitic and pleural fluids. Moreover, systemic clotting abnormalities suggesting primary fibrinolysis/primary hyperfibrinolysis (i.e., elevated plasma fibrin/fibrinogen degradation products [FDPs] and normal D-dimer concentrations with fibrinogen concentrations ≤ 100 mg/dL or above this cut-off, respectively) occur in dogs with intracavitary effusion. Enhanced fibrinolytic activity in dogs with intracavitary effusion can also be detected using rotational thromboelastometry (ROTEM), although the degree of agreement between ROTEM and FDPs, D-dimer and fibrinogen concentrations is poor. Finally, contrary to the thrombotic events commonly documented in some humans and cats with cardiac diseases, bleeding tendencies due to primary fibrinolysis/primary hyperfibrinolysis have been documented in dogs with cardiogenic ascites. Full article

(This article belongs to the Special Issue Coagulopathies in Dogs and Cats: Diagnosis, Pathomechanisms and Treatment)

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