Armelle M. deLaforcade

Identification of hypercoagulability in dogs with primary immune-mediated hemolytic anemia by means of thromboelastography

OBJECTIVE To evaluate whole blood hemostasis by means of thromboelastography in dogs with primary immune-mediated hemolytic anemia (IMHA) to determine whether these dogs had evidence of hypercoagulability prior to the administration of immunosuppressant medications, blood transfusion products, or anticoagulant agents. DESIGN Evaluation study. ANIMALS 11 client-owned dogs admitted to a teaching hospital for management of primary IMHA and 20 clinically normal dogs. PROCEDURES Citrated whole blood samples were obtained from all dogs for performance of kaolin-activated thromboelastography. Citrated plasma was harvested from blood samples of dogs with IMHA for plasma-based coagulation testing, including activated partial thromboplastin time, prothrombin time, D-dimer concentration, fibrinogen concentration, and antithrombin activity. RESULTS Compared with control dogs, dogs with primary IMHA had evidence of hypercoagulability as indicated by a significantly lower median (range) clot formation time (0.8 seconds [0.8 to 2.0 seconds] vs 1.9 seconds [1.3 to 3.8 seconds]), higher median angle (76.1° [59.2° to 84.6°] vs 64.0° [45.4° to 71.0°]), higher median maximum amplitude (75.9 mm [66.3 to 86.3 mm] vs 55.7 mm [49.9 to 63.6 mm]), and higher median clot strength (15,000 dyne/cm(2) [9,900 to 31,400 dyne/cm(2)] vs 6,100 dyne/cm(2) [4,900 to 8,700 dyne/cm(2)]). CONCLUSIONS AND CLINICAL RELEVANCE Dogs with primary IMHA had hypercoagulability as demonstrated by thromboelastography at the time of initial diagnosis and prior to treatment. Such hypercoagulability may be a precursor to clinically evident thrombosis as a complication of the disease process.

Evaluation of use of human albumin in critically ill dogs: 73 cases (2003–2006)

OBJECTIVES To evaluate the use of human albumin in critically ill dogs. Design-Retrospective case series. ANIMALS 73 client-owned hospitalized dogs. PROCEDURES Medical records of dogs that received human albumin were reviewed to assess effects of the use of human albumin on serum albumin concentration, colloid osmotic pressure, and total protein concentration; determine the relationships between these variables and outcome; and assess its safety. Data for signalment, diagnoses, physiologic variables, dosage, amount of crystalloid fluid administered prior to human albumin administration, complications, and outcome were reviewed. Additionally, pre- and postadministration values for serum albumin, colloid osmotic pressure, and total protein were recorded. RESULTS Administration of human albumin resulted in significant changes in serum albumin, colloid osmotic pressure, and total protein. The serum albumin, total protein, degree of improvement in serum albumin, colloid osmotic pressure, and dosage of human albumin were significantly greater in survivors. Seventeen of 73 (23%) dogs had at least 1 complication that could be potentially associated with the administration of human albumin that occurred during or immediately following administration of human albumin. Three of 73 (4%) dogs had severe delayed complications. CONCLUSIONS AND CLINICAL RELEVANCE Administration of human albumin significantly increased serum albumin, and total protein concentrations and colloid osmotic pressure, especially in survivors. Because of the high mortality rate of the study population and other confounding factors, it was uncertain whether complications were associated with the underlying disease or with human albumin administration. Acute and delayed complications may have been under-recognized.

Use of human immunoglobulin in addition to glucocorticoids for the initial treatment of dogs with immune-mediated hemolytic anemia

OBJECTIVE To determine the utility of human intravenous immunoglobulin (hIVIG) for the initial treatment of canine immune-mediated hemolytic anemia (IMHA). DESIGN Blinded, randomized, clinical trial. SETTING Veterinary teaching hospital. ANIMALS Twenty-eight, client-owned dogs with primary IMHA. INTERVENTIONS At enrollment, after diagnosis of IMHA, dogs were randomly assigned to receive either hIVIG or placebo, in a blinded fashion. For the next 14 days, all dogs received glucocorticoids as the sole immunosuppressant agent. All dogs received low-molecular-weight heparin as an anticoagulant. D-dimer concentrations were evaluated at the beginning and end of the study protocol to monitor for thromboembolic complications. MEASUREMENTS AND MAIN RESULTS Twenty-five of 28 dogs (89%) were discharged from the hospital. Thirteen of those received hIVIG and 12 received placebo. Twenty-four dogs (86%) were alive 14 days after enrollment, and of these 13 received hIVIG and 11 received placebo. D-dimer concentrations were elevated in 86% of all dogs at the time of diagnosis. CONCLUSIONS For initial treatment of dogs with IMHA, the addition of hIVIG to corticosteroid treatment did not improve initial response, nor did it shorten hospitalization.

Treatment and predictors of outcome in dogs with immune-mediated thrombocytopenia

OBJECTIVE To characterize the clinical course of disease and identify prognostic indicators for immune-mediated thrombocytopenia in dogs. DESIGN Retrospective cohort study. ANIMALS 73 dogs treated for immune-mediated thrombocytopenia at the Foster Hospital for Small Animals at the Tufts Cummings School of Veterinary Medicine and the Tufts Veterinary Emergency Treatment and Specialties Hospital. PROCEDURES Medical records from the period of January 2002 through June 2008 were reviewed to identify dogs with a diagnosis of immune-mediated thrombocytopenia. Data collected included signalment, clinical signs, results of initial diagnostic tests, treatment, complications, and survival duration. RESULTS Dog ages ranged from 5 months to 15 years (median, 8.1 years). Cocker Spaniels were overrepresented, compared with their distribution in the entire hospital population during the same period. Sixty-one of the 73 (84%) dogs survived to discharge. Seven (11 %) of those dogs were lost to follow-up. Five of the remaining 54 (9%) dogs had a relapse of the disease. The presence of melena or high BUN concentration at admission to the hospital was significantly correlated with a decreased probability of survival. CONCLUSIONS AND CLINICAL RELEVANCE Immune-mediated thrombocytopenia is a serious yet treatable disease, which may have a lower rate of recurrence than previously reported. The presence of melena or high BUN concentration in the study suggested a poor prognosis for affected dogs.

Investigating hypercoagulability during treatment for immune-mediated thrombocytopenia: a pilot study.

BACKGROUND Thromboembolism has recently been described as a complication following treatment for idiopathic thrombocytopenic purpura (ITP). This pilot study was undertaken to determine whether dogs suffering from ITP experience hypercoagulability during treatment and recovery. STUDY DESIGN Thromboelastograms (TEG) were performed on dogs with ITP within 24 hours of admission to the hospital, the first day the platelet count exceeded 40 × 10(9) /L (Day 1), and on Days 4, 7, and 14. KEY FINDINGS All dogs had hypocoagulable TEG tracings on initial admission to the hospital, but developed TEG tracings suggestive of hypercoagulability during the study period as indicated by increased maximum amplitude. SIGNIFICANCE Dogs with ITP developed changes on TEG consistent with hypercoagulability during the study period. Many factors are likely to contribute to these changes. The clinical risk of thrombosis in these patients is unknown.Background Thromboembolism has recently been described as a complication following treatment for idiopathic thrombocytopenic purpura (ITP). This pilot study was undertaken to determine whether dogs suffering from ITP experience hypercoagulability during treatment and recovery. Study design Thromboelastograms (TEG) were performed on dogs with ITP within 24 hours of admission to the hospital, the first day the platelet count exceeded 40 × 109/L (Day 1), and on Days 4, 7, and 14. Key findings All dogs had hypocoagulable TEG tracings on initial admission to the hospital, but developed TEG tracings suggestive of hypercoagulability during the study period as indicated by increased maximum amplitude. Significance Dogs with ITP developed changes on TEG consistent with hypercoagulability during the study period. Many factors are likely to contribute to these changes. The clinical risk of thrombosis in these patients is unknown.

Thromboelastographic Evaluation of Dogs with Congenital Portosystemic Shunts

BACKGROUND On plasma-based assays, dogs with congenital portosystemic shunts (CPSS) have changes in serum concentrations of both pro- and anticoagulant proteins, but how these abnormalities affect whole blood coagulation assays (eg, thromboelastography) are unknown. OBJECTIVES To conduct kaolin-activated thromboelastography (TEG) analysis in dogs with CPSS and to compare TEG coagulation status with clinical presentation, routine serum biochemistry, and plasma-based coagulation tests. ANIMALS Twenty-one client-owned dogs with CPSS confirmed by ultrasound examination or nuclear scintigraphy. METHODS In a prospective study, signalment, clinical presentation, TEG analysis, CBC, serum biochemistry, and hemostatic tests (platelet count, prothrombin time [PT], activated partial thromboplastin time [aPTT], quantitative fibrinogen, antithrombin [AT] activity, protein C [PC] activity, d-dimers, and factor VIII activity) were analyzed in dogs with CPSS. RESULTS Dogs with CPSS had significantly shorter K values and increased angle, maximum amplitude (MA), and G values compared with the reference population. On plasma-based coagulation testing, dogs with CPSS had significantly prolonged PT, lower platelet counts, lower AT and PC activities, and increased d-dimers and factor VIII activity. Evaluation of G value defined 9/21 dogs with CPSS as hypercoagulable. These dogs were more likely to have hepatic encephalopathy (HE) than CPSS dogs that had normal coagulation. CONCLUSIONS AND CLINICAL IMPORTANCE TEG analysis detected hemostatic abnormalities consistent with a hypercoagulable state in some dogs with CPSS. The presence of a hypercoagulable state was 40 times more likely in dogs with symptomatic HE.

Kaolin-activated thromboelastography in echocardiographically normal cats

OBJECTIVE To determine reference values for kaolin-activated thromboelastography in echocardiographically normal cats. ANIMALS 30 healthy cats without evidence of cardiomyopathy on echocardiographic examination. PROCEDURES All cats underwent echocardiographic examination, the findings of which were reviewed by a board-certified cardiologist. Cats that struggled (n = 10) received mild sedation with butorphanol and midazolam IM to permit phlebotomy without interruption in jugular venous blood flow. Blood samples were collected for analysis of thromboelastography variables, PCV, total solids concentration, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin concentration. RESULTS All 4 thromboelastography variables had < 5% mean intra-assay variability. Mean values were as follows: reaction time, 4.3 minutes; clotting time, 1.6 minutes; α angle, 66.5°; and maximum amplitude, 56.4 mm. Compared with nonsedated cats, cats that required sedation had a significantly shorter clotting time and greater α angle, whereas reaction time and maximum amplitude were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE Kaolin-activated thromboelastography was a reliable test with unremarkable intra-assay variability in echocardiographically normal cats. Sedation may affect certain thromboelastography variables, but the effect is unlikely to be clinically important. It remains unknown whether subclinical cardiomyopathy has a significant effect on thromboelastography variables in cats.

Iatrogenic water intoxication in two cats.

OBJECTIVE To describe 2 cats that developed acute iatrogenic water intoxication, one associated with a continuous infusion of water provided via an esophagostomy tube and one following SC administration of 5% dextrose in water (D5W). CASE OR SERIES SUMMARY A 10-year-old cat with squamous cell carcinoma was hospitalized for treatment of dehydration. Rehydration was provided with water via an esophagostomy tube at 5.7 mL/kg/h. After 30 hours of therapy, the cat was found dull and weak. Serum sodium was markedly decreased at 116 mmol/L (116 mEq/L). Supplemental water was stopped, and IV furosemide and mannitol were provided to eliminate free water. Hypertonic saline (1.5%) was administered IV to rapidly restore the sodium concentration. The serum sodium concentration corrected over 17 hours, and the cat was discharged without neurological complications. The second cat had previously received 300 mL D5W subcutaneously and represented 8 hours later with lethargy and paresis with a serum sodium level of 126 mmol/L (126 mEq/L). Intravenous fluid therapy was provided using 0.9% NaCl. Over the following day, the cats mentation and paresis resolved and sodium concentrations normalized. NEW OR UNIQUE INFORMATION PROVIDED These 2 cases describe a presumed uncommon iatrogenic complication of severe hyponatremia due to water provided either via an esophagostomy tube or subcutaneously. While oral rehydration is often considered ideal, it may result in signs of water intoxication if not carefully monitored; additionally, D5W is never considered an acceptable fluid choice as a SC bolus. If promptly recognized, acute hyponatremia may be corrected rapidly with no lasting consequences.

Effects of in vitro hemodilution with crystalloids, colloids, and plasma on canine whole blood coagulation as determined by kaolin‐activated thromboelastography

OBJECTIVE To investigate the effects of in vitro hemodilution with lactated Ringers solution (LRS), hetastarch (HES), and fresh frozen plasma (FFP) on whole blood coagulation in dogs as assessed by kaolin-activated thromboelastography. DESIGN In vitro experimental study. SETTING University teaching hospital. ANIMALS Six healthy client-owned dogs. INTERVENTIONS Whole blood was collected and diluted in vitro at a 33% and 67% dilution with either LRS, HES, or FFP. MEASUREMENTS AND MAIN RESULTS Kaolin-activated thromboelastography was performed on each sample as well as a control. Thromboelastographic parameters R (min), alpha (deg), K (min), and MA (mm) were measured and compared to the sample control for each dilution using mixed model methodology. Prolongation in coagulation times were seen at both dilutions with LRS and HES. There was no significant difference in R times at the 33% dilution, but R time was significantly prolonged at the 67% dilution with HES (P = 0.004). MA was significantly decreased for LRS at both dilutions (P = 0.013, P < 0.001) and more profoundly decreased for HES (P < 0.001, P = 0.006). No significant difference in any parameter was found for FFP. CONCLUSIONS In vitro hemodilution of whole blood with both LRS and HES but not FFP resulted in significant effects on coagulation with HES having a more profound effect. In vivo evaluation of changes in coagulation with various resuscitation fluids is warranted and may be clinically relevant.

Veterinary trauma centers.

In this issue of the Journal, Abelson et al1 report the results of a prospective single-centered investigation on the incidence of coagulopathy following severe acute trauma in dogs. The mere fact that the study was a prospective investigation of trauma in dogs already puts the study in a select category and serves as a reminder that focused investigations related to veterinary trauma are needed. Much of the existing studies relating to veterinary trauma are retrospective in nature. Evidence based protocols for the approach to treating animals sustaining severe trauma are lacking and some commonly employed practices are directly extrapolated from the human literature on trauma despite the recognition that key differences exist in the types of trauma sustained, the availability of pre-hospital care, and in the medical and surgical approaches to certain types of injuries. The ability to conduct large scale studies of animals sustaining severe trauma could lead to evidence based treatment recommendations and the development of protocols that that would greatly impact the outcome of this population of patients. A multi-institutional collaborative approach to gathering data on a large number of veterinary trauma patients would provide a foundation for veterinary trauma research. Such an undertaking requires organization, structure and funding in order to ensure that the information is adequately collected and managed. This undertaking was fortunately achieved in people with the formation of a Committee on Trauma, and we are happy to report that a similar effort in veterinary medicine is underway. Veterinary trauma patients account for 11–13% of admissions to small animal veterinary tertiary centers.2, 3 Although the reported survival to discharge rate in dogs with traumatic injury is very good (85–91%),3–5 trauma is the second leading cause of death behind infectious disease for dogs under 1 year of age and neoplasia for dogs >1 year of age.6 A multidisciplinary, multiinstitutional group (Spontaneous Trauma in Animals Team [STAT]) was created in 2009 with a vision to improve trauma patient outcome through comparative and translational medicine. The team’s ultimate goal is to establish naturally occurring trauma in dogs as a pre-clinical model to improve human and veterinary trauma patient care, much in the same way veterinary oncologists and neurologists have done.7, 8 During the ACVECC Multidisciplinary/Post Graduate Review meeting in January 2010, representatives from the STAT team gathered to discuss the idea of creating a network of veterinary trauma centers (VTC) that would collaborate to provide exceptional patient care as well as develop a method to enhance multi-institutional clinical research and education. As a result of this discussion and early efforts by the group, the American College of Veterinary Emergency and Critical Care (ACVECC) established the Veterinary Committee on Trauma (VetCOT) as an ad hoc committee in 2011. In people, trauma is the leading cause of death in people <34 years of age.9 In an effort to improve trauma patient care, the American College of Surgeons (ACS) established the Committee on Trauma (ACS-COT) in 1922.10 The first trauma centers were established in Chicago (Cook County Hospital) and San Francisco (General Hospital) in 1966.11 Ten years later (1976) the first “Resource” document was published regarding resource requirements for trauma centers. The goal of creating requirements for trauma centers is to ensure that all of the specialties required for definitive treatment of trauma patients are available with minimal delay, and to avoid the need to transfer patients with multi-system injuries to other facilities. It was hoped that “by virtue of the expertise contained within, training and research will be facilitated and there will be reciprocal improvements in trauma related services.”11 In 1987, the ACS-COT formalized their Consultation and Verification process. Trauma centers then seeded the development of trauma systems which allowed for coordinated trauma care within communities, ensuring patients received the right resources for the right care at the right time. There is extensive literature documenting the improvement in trauma patient outcome in people cared at established trauma centers.9 The newly established VetCOT is striving to adapt the successes and modify the struggles encountered during the creation of human trauma networks in order to achieve measurable improvements in veterinary trauma patient care. The VetCOT is composed of 5 subcommittees populated by representatives from across the United States, Canada, and Australia. Drs. Kelly Hall and Claire Sharp spearheaded the effort to create the first document (“Guidelines”) outlining proposed resources required for Level I, II and III VTCs. The Guidelines and Verification subcommittee, led by Drs. Claire Sharp and Armelle deLaforcade, worked to modify the document and generate a consensus on requirements for VTCs (https://sites.google.com/a/umn.edu/vetcot/). This committee also generated an electronic survey distributed to all Diplomates of the ACVECC to ascertain interest in trauma center participation and identify, in a blinded fashion, the first wave of provisional VTCs based on likelihood that they would be able to verify