Thromboelastometry for assessment of hemostasis and disease severity in 42 dogs with naturally-occurring heatstroke.

BACKGROUND: Thromboelastometry (TEM) provides a comprehensive overview of the entire coagulation process and has not been evaluated in heatstroke-induced coagulopathies in dogs. OBJECTIVES: To determine the diagnostic and prognostic utility of TEM in dogs with heatstroke. ANIMALS: Forty-two client-owned dogs with heatstroke. METHODS: Prospective observational study. Blood samples for intrinsic and extrinsic TEM (INTEM and EXTEM, respectively) were collected at presentation and every 12 to 24 hours for 48 hours. Coagulation phenotype (hypo-, normo-, or hypercoagulable) was defined based on TEM area under the 1st derivative curve (AUC). RESULTS: Case fatality rate was 31%. Median TEM variables associated with death (P < .05 for all) included longer INTEM clotting time, lower AUC at presentation and at 12 to 24 hours postpresentation (PP), lower INTEM alpha angle, maximum clot firmness, and maximum lysis (ML) at 12 to 24 hours PP, and lower EXTEM ML at 12 to 24 hours PP. Most dogs were normo-coagulable on presentation (66% and 63% on EXTEM and INTEM, respectively), but hypo-coagulable 12 to 24 PP (63% for both EXTEM and INTEM). A hypo-coagulable INTEM phenotype was more frequent at presentation and 12 to 24 PP among nonsurvivors compared to survivors (55% vs 15% and 100% vs 50%, P = .045 and .026, respectively). AKI was more frequent (P = .015) in dogs with hypo-coagulable INTEM tracings at 12 to 24 hours. Disseminated intravascular coagulation was more frequent (P < .05) in dogs with a hypo-coagulable INTEM phenotype and in nonsurvivors at all timepoints. CONCLUSIONS AND CLINICAL RELEVANCE: Hypocoagulability, based on INTEM AUC, is predictive of worse prognosis and occurrence of secondary complications.

Clinical bleeding diathesis, laboratory haemostatic aberrations and survival in dogs infected with Angiostrongylus vasorum: 180 cases (2005-2019).

OBJECTIVES: Bleeding diathesis is a complication in dogs infected with Angiostrongylus vasorum. This retrospective study investigated clinical and laboratory haemostatic differences in A. vasorum-positive dogs with and without signs of bleeding and impact of bleeding on survival. MATERIALS AND METHODS: Demographics, type of clinical bleeding, haematocrit and a range of haemostatic tests, including thromboelastography and derived velocity curves were retrospectively registered from A. vasorum-positive dogs. All parameters were compared between dogs with and without signs of bleeding using univariable analyses. Binomial and multinomial regression models were applied to examine specific indicators in the bleeding dogs. P-values were false discovery rate adjusted, and adjusted P<0.05 was considered significant. RESULTS: One hundred and eighty dogs entered the study, including 65 dogs (36.1%) presenting with bleeding diathesis. Different types of cutaneous and mucosal bleeding were the most common clinical findings. Twenty dogs presented with neurological signs associated with intracranial and intra-spinal bleeding. One hundred and thirty-seven dogs had haematological and/or haemostatic laboratory analyses performed. Haematocrit, platelet count, thromboelastographic angle, maximum amplitude, global clot strength, maximum rate of thrombin generation and total thrombin generation were decreased, while prothrombin time was prolonged in bleeding dogs. Survival rate of bleeding dogs was lower at hospital discharge (76.9%) and 1 month after diagnosis (66.0%) than in dogs without signs of bleeding (94.8% and 90.1% at discharge and at 1 month, respectively). CLINICAL SIGNIFICANCE: Several haemostatic aberrations were detected in A. vasorum-positive dogs with bleeding diathesis. Bleeding was identified as an important negative prognostic indicator in A. vasorum-positive dogs.

Pulmonary hypertension is associated with hypocoagulability in dogs: a retrospective analysis of 66 cases (2013-2021).

OBJECTIVE: To describe coagulation profiles in dogs with echocardiographic evidence of pulmonary hypertension (PH), to compare them to coagulation profiles in dogs without echocardiographic evidence of PH, and to determine the relationship between coagulation profiles and echocardiographic probability of PH. ANIMALS: 66 dogs with PH (cases) and 86 dogs without PH (controls). METHODS: Retrospective evaluation of records between 2013 and 2021 of dogs that had both an echocardiogram and a coagulation panel performed within 7 days. Dogs that received antithrombotics within 7 days of evaluation and dogs diagnosed with congenital or acquired coagulopathy or other severe systemic disease that could lead to coagulopathy were excluded. Dogs with a low echocardiographic probability of PH were also excluded. The dogs were divided into a PH group and non-PH group based on echocardiographic results. Demographic, clinicopathologic, and traditional coagulation parameters and VCM Vet (Entegrion) parameters were compared between the 2 groups. RESULTS: Dogs with PH were significantly older (median, 11 years vs 9.5 years, P = .02) and had a significantly lower body weight (median, 7.3 kg vs 19.3 kg, P < .001) than controls. Dogs with PH also had a significantly greater percent increase in prothrombin time (PT; P = .02), partial thromboplastin time (PTT; P < .0001), and fibrinogen (P = .045); however, their antithrombin concentration was lower (P = .005) compared to controls. Eight of 65 dogs (12.3%) in the PH group and 1/86 (1.2%) dogs in the non-PH group had an elevation of PT and/or PTT greater than 50% above the reference interval (P = .005). Dogs with PH had 11.9 times (95% CI, 1.5 to 97.9; P = .02) greater odds of being hypocoagulable than dogs without PH based on PT and PTT. CLINICAL RELEVANCE: This study demonstrated an association between a moderate to high echocardiographic probability of PH and a hypocoagulable state in dogs as determined by traditional coagulation assays. It underscores the importance of monitoring the coagulation status in canine patients with PH, particularly before initiating antithrombotic medications.

Snake Envenomation.

Snakebite envenomation (SBE) in horses can have devastating outcomes. Tissue damage, cardiotoxicity, coagulopathy, and neurotoxicity can be concerns with SBE. Understanding the actions of venom components is important in developing a successful treatment plan. Antivenom is the mainstay of treatment. Long-term deleterious effects can occur including cardiac dysfunction and lameness.

Prospective evaluation of platelet function and fibrinolysis in 20 dogs with trauma.

OBJECTIVES: To determine platelet function and assess fibrinolysis in dogs following trauma using multiple electrical impedance aggregometry and a modified thromboelastographic (TEG) technique. To determine if the severity of trauma, as assessed by the Animal Trauma Triage (ATT) score and clinicopathological markers of shock, is associated with a greater degree of platelet dysfunction and fibrinolysis. SETTING: University teaching hospital. ANIMALS: Twenty client-owned dogs with trauma (occurring <24 h prior to admission and blood sampling) and ATT score of >4 were prospectively recruited. A control group of 10 healthy dogs was included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Platelet function was measured using multiple electrode platelet aggregometry (MEPA) utilizing arachidonic acid, ADP, and collagen agonists. Fibrinolysis was assessed in citrated whole blood with the addition of tissue plasminogen activator (tPA; 50 U/mL) using kaolin-activated TEG. Conventional statistical analysis was performed to compare coagulation parameters between the groups and assess linear correlations. Median (interquartile range) ATT score was 5 (5-7), and 65% (n = 13) of dogs suffered polytrauma. Mean (± SD) time from trauma to blood sampling was 9 hours (± 6). Median (interquartile range) shock index and plasma lactate concentration were 1.1 (0.7-2.0, n = 16) and 2.9 mmol/L (0.9-16.0, n = 18), respectively. Four dogs did not survive to discharge (20%). There were no differences between the trauma and control group coagulation variables. A moderate negative correlation between ATT score and area under the curve for ADP was found (P = 0.043, r2  = -0.496). CONCLUSIONS: Preliminary evaluation of platelet function measured by MEPA, and fibrinolysis measured by tPA-modified TEG, is not significantly different in this population of dogs with traumatic injury compared to healthy dogs.

Coagulation Disorders, Testing, and Treatment in Exotic Animal Critical Care.

Despite poor recognition in the literature, exotic companion animals are affected by many diseases that can result in disordered coagulation and fibrinolysis. This article outlines current knowledge of hemostasis, common diagnostic tests and reviews reported diseases associated with coagulopathy in small mammals, bird and reptiles. A range of conditions affect platelets and thrombocytes, endothelium and blood vessels, and plasma clotting factors. Improved recognition and monitoring of hemostatic disorders will enable targeted therapy and improved case outcomes.

Rapid resolution of hyperfibrinolysis in dogs with spontaneous hemoperitoneum following surgical control of hemorrhage.

OBJECTIVE: To estimate the point prevalence and duration of hyperfibrinolysis (HF) in dogs undergoing surgical control of spontaneous hemoperitoneum (SHP). DESIGN: Prospective observational study. SETTING: Single veterinary teaching hospital. ANIMALS: Forty-five client-owned dogs with SHP were screened for HF. Eighteen HF dogs treated surgically were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dogs with SHP and evidence of shock admitted for surgical control of hemorrhage were screened for HF. Blood samples were collected for PCV, total plasma protein, platelet count, and thromboelastography with 50 U/mL of tissue plasminogen activator at presentation and every 8 hours postoperatively until 72 hours, discharge, or death. HF was defined as a tissue plasminogen activator-activated thromboelastography lysis percentage measured 30 minutes after maximum amplitude (LY30) of ≥20%. LY30 values were compared to a cohort of samples obtained from healthy dogs (n = 22). The point prevalence of HF in all dogs screened was 40% (18/45 dogs), and the mean LY30 at baseline for HF dogs was 48.9% (±24.2%), which was significantly higher than that of control dogs (4.8% ± 7.1%, P < 0.001) and non-HF dogs (1.9% ± 5.7%, P < 0.001). In HF dogs, there was a significant decrease in LY30 between baseline and 8 hours (P < 0.0001) and between 8 and 16 hours (P = 0.035) but no significant change thereafter. LY30 at 8 hours (4%, range: 0%-23.4%) was not statistically different from control dogs (6.5%, range: 1.2%-32.8%, P = 0.664) suggesting early resolution of HF in this population. Only 2 of 18 dogs were persistently hyperfibrinolytic at 24 hours. Malignancy was diagnosed in 12 of 18 dogs (66.6%), while a benign etiology occurred in 6 of 18 dogs (33.3%). All HF dogs survived to discharge. CONCLUSIONS: HF occurs in some dogs with hypovolemic shock due to hemoperitoneum but resolves rapidly following surgical control of bleeding without antifibrinolytic medications. Routine postoperative use of antifibrinolytics in dogs with hemoperitoneum in dogs undergoing surgical control of bleeding may not be warranted.

Comparison of a viscoelastic point-of-care coagulation monitor with thromboelastography in sick dogs with hemostatic abnormalities.

BACKGROUND: Viscoelastic coagulation monitor (VCM-Vet) is a point-of-care device that has been used to characterize hemostatic abnormalities in sick pets but has not been validated in veterinary patients. OBJECTIVES: We aimed to compare VCM-Vet and thromboelastography (TEG) in sick dogs with suspected disorders of hemostasis. METHODS: Duplicate VCM-Vet tests using untreated native blood performed concurrently on two VCM-Vet machines, and simultaneous TEG tests were performed (one citrated native (CN), and one activated with tissue factor (TF) at a 1:3600 dilution). Each VCM-Vet result was compared with both TF-activated and CN TEG. RESULTS: Fifty-three dogs were enrolled. Eleven cases displayed apparent hyperfibrinolysis. Spearman correlation coefficients for individual VCM-Vet devices and CN and TF TEG were obtained between R and CT values and ranged from 0.21 to 0.27, CFT and K (r = 0.60-0.67), angles (r = 0.51-0.62), and MCF and MA (r = 0.85-0.87). Comparison of the two VCM-Vet devices displayed positive correlations for all clot formation parameters with Lin's concordance correlation coefficients of 0.75-0.95. Variable lysis parameter agreement existed between the VCM-Vet devices and VCM-Vet and TEG. When samples were classified as hypercoagulable or coagulopathic, VCM-Vet had a low positive predictive value (17-33%) for the detection of hypercoagulable states and a moderate negative predictive value (64-74%) for the detection of coagulopathy as defined by TEG. CONCLUSIONS: VCM-Vet and TEG had variable correlations in clot formation values and a strong correlation for final clot strength. More information is needed to make conclusions about the lysis parameters. Artifact in the fibrinolysis portion of the test can confound the interpretation of VCM-Vet results.

Sodium dehydroacetate-induced disorder of coagulation function in broiler chickens and the protective effect afforded by vitamin K.

Sodium dehydroacetate (S-DHA) is used widely as a preservative in several products, including poultry feed. The anticoagulation effect of 200 mg/kg S-DHA in rats has been reported to accompany a reduction in hepatic expression of vitamin K epoxide reductase complex 1 (VKORC1). Poultry and mammals have different physiology and coagulation systems, and species differences in VKORC1 expression have been found. The effect of S-DHA on blood clotting of poultry has not been studies deeply. S-DHA was given to yellow-plumage broilers (YBs) as single and multiple administrations. Vitamin K3 (VK3) was injected into YBs 2 wk after S-DHA administration. Then, the prothrombin time (PT), partial activated prothrombin time (APTT), plasma levels of vitamin K (VK), factor IX (FIX), and S-DHA, and hepatic expression of VKORC1 were obtained. Chicken hepatocellular carcinoma (LMH) cells were also exposed to S-DHA, and the cell activity, VK level, and FIX level were measured. S-DHA prolonged the PT or APTT significantly, decreased levels of VK and FIX in blood, and inhibited hepatic expression of VKORC1. The maximum changes were 1.15-fold in the PT, 1.42-fold in the APTT, 0.8-fold in the VK level, 0.7-fold in the FIX level, and 0.35-fold in VKORC1 expression compared with controls. The cell activity, VK level, FIX level, and VKORC1/VKORC1L1 expression of LMH cells were reduced significantly at S-DHA doses of 2.0 to 10.0 mM. Prolongation of the PT/APTT and lower levels of VK/FIX in YBs or the lower cell activity and VK/FIX levels in LMH cells induced by S-DHA therapy were resisted significantly by VK3 treatment. We demonstrated that S-DHA could induce a disorder in coagulation function in YBs or in LMH cells via reduction of VKORC1/VKORC1L1 expression, and that VK could resist this anticoagulation effect.

Successful treatment of coagulation disorders and hypoalbuminaemia in a puppy with Infectious Canine Hepatitis.

Due to high vaccination coverage of the dog population in Western and Middle Europe, veterinarians are usually not familiar with clinical signs and treatment of Infectious Canine Hepatitis (ICH). This case report describes a 4-month-old female mixed breed dog that was imported from Bulgaria. According to the history, the puppy was presented with lethargy, pyrexia, icterus and melaena. On clinical examination, the dog additionally exhibited a painful abdomen and bleeding tendency at the venous puncture sites. Blood analysis revealed anaemia, left shift without leucocytosis, increased liver enzymes and prolonged coagulation times. Polymerase Chain Reaction (PCR) and subsequently sequence analysis performed out of urine confirmed Canine Adenovirus 1 (CAV-1) as the causative agent of the disease. Peripheral oedema developed on the dog´s head and limbs during the progression of the disease due to severe hypoalbuminaemia. Initial treatment of the puppy included transfusion of whole blood and fresh frozen plasma. Hypoalbuminaemia was treated by transfusion using human albumin. On day eight after starting the treatment, the dog was released from the hospital due to an unremarkable clinically condition. This case report indicates that ICH might become a re-emerging disease by means of rising dog imports. Especially, the severe form of ICH can be associated with several life-threatening complications that require hospitalisation and intensive care treatment.

Coagulation testing in green iguanas (Iguana iguana) with development of prothrombin time assays using reptile and avian thromboplastin.

BACKGROUND: Captive reptiles often present with clinical signs suggestive of a clotting disorder or severe illness that can induce or exacerbate a coagulopathy. However, coagulopathies in reptiles are difficult to characterize due to lack of species-appropriate reagents to perform coagulation tests. The objective of this study was to develop screening tests to evaluate the extrinsic and common pathways of coagulation in green iguanas (Iguana iguana). KEY FINDINGS: Reptile and avian thromboplastin, extracted from reptile and avian brains, respectively, were used to initiate coagulation in prothrombin time (PT) assays and commercially available reagents were used to determine Russell's viper venom time, thrombin time, and fibrinogen using the Clauss method. Coagulation assays were performed on citrate-anticoagulated plasma from 18 healthy green iguanas. Results were summarized as median (minimum-maximum): PT (reptile thromboplastin), 34.8 seconds (27.1-42.1 s), PT (avian thromboplastin), 78.5 seconds (51.6-114.23 s), Russell's viper venom time, 56.15 seconds (18.4-79.7 s), thrombin time, 10 seconds (7.0-36.5 s), and fibrinogen, 258 mg/dl (89-563.0) (2.58 [0.89-5.63 g/L]). SIGNIFICANCE: Commercial reagents can be used to evaluate the common pathway and fibrinogen; however, avian- or reptile-sourced thromboplastin is preferred for a reliable coagulation trigger to perform the PT assay and evaluate the extrinsic pathway.

Characterization of Acute Traumatic Coagulopathy in Cats and Association with Clinicopathological Parameters at Presentation.

OBJECTIVE: This study aimed to document rotational thromboelastometric (ROTEM) characteristics of traumatized cats and to investigate associations between clinicopathological parameters and acute traumatic coagulopathy (ATC). A secondary goal was to determine the relevance of autoheparinization in injured cats. STUDY DESIGN: Cats presenting with acute (<12 hours) trauma were eligible. Cats were allocated to the ATC group (≥2 hypocoagulable parameters) or non-ATC group (≤1 hypocoagulable parameter) based on ROTEM analysis. Clinicopathological parameters were compared between groups and regression was used to find variables associated with ATC. Heparinase-modified ROTEM (HepTEM) was used to assess for heparin effects in a subgroup. RESULTS: Fifty-three cats were included, and the incidence of ATC was 15%. Prolongation of both intrinsic and extrinsic clotting times (CT) was the most frequently altered ROTEM variable in the ATC group, but CTInTEM-prolongation also occurred in 47% of non-ATC cats. The incidence of autoheparinization, defined as concurrent CTInTEM prolongation and CTInTEM:HepTEM ratio >1.1, was 41% and was observed in both cats with and without ATC. None of the evaluated clinicopathological parameters were different between groups or associated with ATC. CONCLUSION: Acute traumatic coagulopathy in cats is mainly characterized by prolonged CT. No relationship between clinicopathological variables and ATC was identified and prediction of ATC based on these variables was not possible. While autoheparinization is important in cats, it is not the sole cause for ATC.

Pathophysiology of hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is a common condition that may lead to hemodynamic instability, decreased oxygen delivery, cellular hypoxia, organ damage, and ultimately death. CLINICAL IMPORTANCE: This review addresses the pathophysiology of hemorrhagic shock. Hemorrhagic shock can be rapidly fatal and is the leading cause of death in human trauma patients. Understanding the pathophysiology of hemorrhagic shock is imperative in understanding the current hemostatic and resuscitative strategies and is foundational to the development of new therapeutic options. KEY POINTS: Shock is a state of inadequate cellular energy production and can be triggered by many causes Both traumatic and non-traumatic causes of hemorrhage can lead to the development of hemorrhagic shock Prompt recognition and attenuation of hemorrhage is paramount in preventing the onset or potentiation of hemorrhagic shock Acute hemorrhage produces distinct physiological responses depending on the magnitude and rate of hemorrhage. Hemorrhagic shock may be directly related to the initial injury but may also be exacerbated and complicated by a post-traumatic coagulopathy, termed acute traumatic coagulopathy.

The pathophysiology of uncontrolled hemorrhage in horses.

BACKGROUND: Hemorrhagic shock in horses may be classified in several ways. Hemorrhage may be considered internal versus external, controlled or uncontrolled, or described based on the severity of hypovolemic shock the patient is experiencing. Regardless of the cause, as the severity of hemorrhage worsens, homeostatic responses are stimulated to ameliorate the systemic and local effects of an oxygen debt. In mild to moderate cases of hemorrhage (<15% blood volume loss), physiological adaptations in the patient may not be clinically apparent. As hemorrhage worsens, often in the uncontrolled situation such as a vascular breach internally, the pathophysiological consequences are numerous. The patient mobilizes fluid and reserve blood volume, notably splenic stored and peripherally circulating erythrocytes, to preferentially supply oxygen to sensitive organs such as the brain and heart. When the global and local delivery of oxygen is insufficient to meet the metabolic needs of the tissues, a cascade of cellular, tissue, and organ dysfunction occurs. If left untreated, the patient dies of hemorrhagic anemic shock. CLINICAL IMPORTANCE: An understanding of the pathophysiological consequences of hemorrhagic shock in horses and their clinical manifestations may help the practitioner understand the severity of blood volume loss, the need for referral, the need for transfusion, and potential outcome. In cases of severe acute uncontrolled hemorrhage, it is essential to recognize the clinical manifestations quickly to best treat the patient, which may include humane euthanasia. KEY POINTS: Uncontrolled hemorrhage may be defined as the development of a vascular breach and hemorrhage that cannot be controlled by interventional hemostasis methods such as external pressure, tourniquet, or ligation. Causes of uncontrolled hemorrhage in horses may be due to non-surgical trauma, surgical trauma, invasive diagnostic procedures including percutaneous organ biopsy, coagulopathy, hypertension, cardiovascular anomaly, vascular damage, neoplasia such as hemangiosarcoma, toxicity, or idiopathic in nature. When a critical volume of blood is lost, the respondent changes in heart rate, splenic blood mobilization, and microcirculatory control can no longer compensate for decreasing oxygen delivery to the tissues In spite of organ-specific microvascular responses (eg, myogenic responses, local mediator modulation of microvasculature, etc), all organs experience decreases in blood flow during severe hypovolemia Acute, fatal hemorrhagic shock is characterized by progressive metabolic acidosis, coagulopathy, and hypothermia, often termed the "triad of death," followed by circulatory collapse.

Evaluation of coagulation parameters in dogs with gallbladder mucoceles.

BACKGROUND: Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Limited information is available on the coagulation status of dogs with GBM. HYPOTHESIS/OBJECTIVES: To determine patterns of coagulation alterations in dogs with GBM and correlate them with clinicopathologic abnormalities and ultrasonographic findings of disease severity. ANIMALS: Twenty-three dogs with GBM identified on ultrasound examination were prospectively enrolled. METHODS: At the time of GBM identification, blood and urine were collected for CBC, serum biochemical panel, urinalysis, prothrombin time, activated partial thromboplastin time (aPTT), factor VIII, protein C (PC), von Willebrand's factor (vWF), antithrombin activity, fibrinogen, D-dimers, and thromboelastrography (TEG). Gallbladder mucoceles were classified into ultrasound types 1 to 5. Medical records were reviewed for clinical presentation, underlying conditions and to determine if systemic inflammatory response syndrome (SIRS) was present. RESULTS: Based on TEG parameters, maximal amplitude, and G, 19/23 (83%) of dogs with GBM had evaluations consistent with hypercoagulability. On plasma-based coagulation testing, dogs with GBM had increased total PC activity (20/23, 87%), fibrinogen (9/23, 39%), platelet count (9/23, 39%), and D-dimers (6/15, 40%) as well as prolongations in aPTT (9/22, 41%) and low vWF activity (5/21, 24%). No correlation was found between TEG G value and any coagulation or clinical pathology variables, ultrasound stage of GBM or disease severity as assessed by the presence of SIRS. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with ultrasonographically identified GBM have changes in whole blood kaolin-activated TEG supporting a hypercoagulable state although traditional plasma-based coagulation testing suggests that a complex state of hemostasis exists.

Utility of the Sonoclot analyzer to assess hyperfibrinolysis in dogs.

BACKGROUND: Coagulation abnormalities, including hyperfibrinolysis, have been documented in sick veterinary patients. Viscoelastic tests, including the Sonoclot Coagulation and Platelet Function Analyzer, are useful in detecting hyperfibrinolysis. Tissue plasminogen activator (tPA) assays have been used to quantify fibrinolysis using thromboelastography. OBJECTIVES: We aimed to document and evaluate changes in the whole blood of healthy dogs exposed to in vitro tPA at varying concentrations using the Sonoclot analyzer. METHODS: Ten milliliters of blood was collected from healthy adult dogs. Sonoclot tests were run in duplicate and included a control sample and five tPA concentrations: 50, 75, 100, 150, and 200 IU/mL of blood. RESULTS: Eleven dogs were enrolled in the study. Based on standard Sonoclot Signature changes, a numeric value fibrinolysis time (FTi) was derived to aid in the quantification of hyperfibrinolysis. Activated clotting time and clot rate Sonoclot values were not significantly affected by any tPA concentration. There was a significant decrease in platelet function (PF) at tPA concentrations equal to and above 75 IU/mL on channel 1 and tPA concentrations of 150 IU/mL and higher on channel 2. There was a progressive decrease in FTi at increasing tPA concentrations. CONCLUSIONS: The Sonoclot analyzer can be used to evaluate hyperfibrinolysis. Predictable changes were seen in the Sonoclot Signature and a decrease in PF and FTi was found with increasing tPA concentrations. The Sonoclot assay with a tPA concentration of 100 IU/mL is suggested a baseline measure of hyperfibrinolysis and has a resultant median FTi of 42 minutes, which is a practical time for clinical applications.

Diagnosis of primary hyperfibrinolysis and in vitro investigation of the inhibitory effects of tranexamic acid in a group of dogs with sarcomas - A pilot study.

Primary hyperfibrinolysis is not well characterised in canine cancer. This prospective case-control pilot study aimed to evaluate tissue plasminogen activator-modified thromboelastography (tPA-TEG) for diagnosis of primary hyperfibrinolysis in dogs with cancer and establish the in vitro therapeutic concentration of tranexamic acid (TXA). Nine dogs with sarcomas and normocoagulable thromboelastograms and 11 healthy dogs were included. For each a whole blood tPA-TEG, and four tPA-TEGs with added TXA in different concentrations were analysed. Lysis percentage at 30/60 min following maximal amplitude (LY30/60), clot lysis index (CL30/60), maximum rate of lysis (MRL), and total lysis (L) were investigated as diagnostic parameters of primary hyperfibrinolysis. In vitro TXA concentrations needed to inhibit 50% (IC50) and 90% (IC90) of the fibrinolytic potential were compared between groups. Significant primary hyperfibrinolysis (LY30 (P = 0.0001), LY60 (P = 0.003), CL30 (P = 0.01), and L (P = 0.02)) was observed in dogs with sarcomas. IC50 and IC90 of in vitro TXA for normalizing LY30 were 13.34 (SE 1.52) and 31.10 (SE 3.01) mg/L for dogs with sarcomas and 4.41 (SE 5.84) and 20.00 (SE 6.18) mg/L for healthy dogs. IC50 and IC90 for normalizing LY60 were 22.18 (SE 1.27) and 58.94 (SE 5.47) mg/L for dogs with sarcomas and 11.25 (SE 2.82) and 56.20 (SE 11.61) mg/L for healthy dogs. The IC50 for LY60 was significantly increased for dogs with sarcomas (P = 0.0003). Primary hyperfibrinolysis was documented by tPA-TEG in dogs with sarcomas. In vitro IC50 and IC90 for TXA were established. Clinical studies are required to establish therapeutic dosages in vivo.

The role of cryoprecipitate in human and canine transfusion medicine.

OBJECTIVE: To evaluate the current role of cryoprecipitate in human and canine transfusion medicine. DATA SOURCES: Human and veterinary scientific reviews and original studies found using PubMed and CAB Abstract search engines were reviewed. HUMAN DATA SYNTHESIS: In the human critical care setting, cryoprecipitate is predominantly used for fibrinogen replenishment in bleeding patients with acute traumatic coagulopathy. Other coagulopathic patient cohorts for whom cryoprecipitate is recommended include those undergoing cardiovascular or obstetric procedures or patients bleeding from advanced liver disease. Preferential selection of cryoprecipitate versus fibrinogen concentrate (when available) is currently being investigated. Also a matter of ongoing debate is whether to administer this product as part of a fixed-dose massive hemorrhage protocol or to incorporate it into a goal-directed transfusion algorithm applied to the individual bleeding patient. VETERINARY DATA SYNTHESIS: Although there are sporadic reports of the use of cryoprecipitate in dogs with heritable coagulopathies, there are few to no data pertaining to its use in acquired hypofibrinogenemic states. Low fibrinogen in dogs (as in people) has been documented with acute traumatic coagulopathy, advanced liver disease, and disseminated intravascular coagulation. Bleeding secondary to these hypocoagulable states may be amenable to cryoprecipitate therapy. Indications for preferential selection of cryoprecipitate (versus fresh frozen plasma) remain to be determined. CONCLUSIONS: In the United States, cryoprecipitate remains the standard of care for fibrinogen replenishment in the bleeding human trauma patient. Its preferential selection for this purpose is the subject of several ongoing human clinical trials. Timely incorporation of cryoprecipitate into the transfusion protocol of the individual bleeding patient with hypofibrinogenemia may conserve blood products, mitigate adverse transfusion-related events, and improve patient outcomes. Cryoprecipitate is readily available, effective, and safe for use in dogs. The role of this blood product in clinical canine patients with acquired coagulopathy remains unknown.

An in vitro study of canine cryopoor plasma to correct vitamin K-dependent coagulopathy in dogs.

OBJECTIVE: To compare the efficacy of fresh frozen plasma (FFP) with cryopoor plasma (CPP) to treat vitamin K-dependent factor deficiency in a canine in vitro setting. DESIGN: In vitro laboratory study. SETTING: University veterinary medical teaching hospital. ANIMALS: Seven units of FFP and 6 units of CPP from unique canine donors from the university veterinary blood bank. INTERVENTIONS: Canine FFP was adsorbed by oral barium sulfate suspension to mimic vitamin K-dependent coagulopathy. A sequential mixing study was completed by adding FPP or CPP to the adsorbed plasma. Measurements of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and factor activities of factors II, VII, and IX (FII, FVII, and FIX) were compared between the 2 treatment groups. MEASUREMENTS AND MAIN RESULTS: When comparing the sequential addition of CPP or FPP to adsorbed plasma, the following had no statistical significance: PT (P = 0.94), aPTT (P = 0.66), FII (P = 0.05), and FIX (P = 0.90). There was a dose-dependent decrease with PT and aPTT and a dose-dependent increase with FII and FIX. In contrast, after the addition of either CPP or FFP, there was a significant difference between the treatment groups for the concentration of fibrinogen (P = 0.005) and activity of FVII (P = 0.044), with FFP resulting in a greater concentration of fibrinogen and CPP resulting in a greater concentration of FVII. Measurements of factor X (FX) were initially included in the study but were later excluded because FX appeared to be continually adsorbed even after the addition of CPP or FFP. CONCLUSIONS: CPP partially corrected the coagulation times and concentration of vitamin K-dependent coagulation factors to the same degree as FFP. CPP, generally less expensive than FFP, may provide an alternative treatment option for vitamin K-dependent coagulopathies, although in vivo testing is needed.

Prevalence of Acute Traumatic Coagulopathy in Acutely Traumatized Dogs and Association with Clinical and Laboratory Parameters at Presentation.

OBJECTIVE: The aim of this study was to determine the prevalence of acute traumatic coagulopathy (ATC) and identify associated clinical and laboratory parameters including rotational thromboelastometry. STUDY DESIGN: Dogs presenting within 6 hours after trauma were allocated to the ATC or non-ATC group based on thromboelastometry analysis (ex-tem S, in-tem S, fib-tem S). ATC was defined as ≥2 hypocoagulable parameters in 1 profile and ≥ 1 hypocoagulable parameter in an additional profile. Parameters used were ex-tem and in-tem clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), maximum lysis and fib-tem MCF. Clinical and laboratory parameters at presentation, animal trauma triage (ATT) score, transfusion requirement and outcome were compared. Logistic regression was used to identify independent factors associated with ATC. RESULTS: Eleven of 33 dogs presented with ATC and showed ex-tem CT and CFT prolongation and reduced MCF amplitude in all profiles (all p < 0.001). pH (p = 0.043) and potassium concentration (p = 0.022) were significantly lower and bleeding (p = 0.027) and plasma transfusions (p = 0.001) more common in dogs with ATC. Time after trauma (p = 0.040) and Animal Trauma Triage score (p = 0.038, including haematocrit as confounding factor) were associated with the presence of ATC. CONCLUSION: Acute traumatic coagulopathy is more common in traumatized dogs than previously reported. Acute traumatic coagulopathy was associated with acidosis, Animal trauma triage score, time after trauma and higher transfusion needs. Coagulation abnormalities include ex-tem CT and CFT prolongations and decreased clot strength.