Study of haemostatic disorders in experimentally induced leishmaniasis in Beagle dogs

Haemostatic alterations in dogs experimentally infected with Leishmania infantumwere studied before and after therapy with meglumine antimonate. Haemostatic function tests including platelet count, collagen-induced platelet aggregation, prothrombin time, activated partial thromboplastin time, thrombin time, plasma fibrinogen determination, and serum fibrinogen/fibrin degradation products concentration were performed. In the course of infection and before treatment, moderate thrombocytopenia (P<0·00001) decreased collagen induced platelet aggregation (P=0·0003), prolonged thrombin time (P=0·0117) and increased fibrinogen/fibrin degradation products were observed. Statistically significant differences of plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time were not encountered. Haemostatic parameters returned to normal values after therapy. The results indicate that Leishmania infection may impair haemostasis suggesting induction of disseminated intravascular coagulation (DIC), and that treating dogs in an early stage of infection may potentially avoid the possibility of developing an uncompensated DIC.     

Effect of carprofen on hemostatic variables in dogs

OBJECTIVE: To evaluate the effect of carprofen on hemostatic variables in clinically normal dogs. ANIMALS: 12 clinically normal Labrador Retrievers. PROCEDURE: 10 dogs (6 females, 4 males) received carprofen (2.2 mg/kg of body weight, PO, q 12 h) for 5 days. Two dogs (untreated control group; 1 female, 1 male) did not receive carprofen. Hemostatic variables (platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, platelet aggregation, and bleeding time) were assessed for all dogs prior to treatment, on day 5 of treatment, and 2 and 7 days after discontinuation of the drug (days 7 and 12). Serum biochemical variables and Hct were assessed prior to treatment and on days 5 and 12. RESULTS: In dogs receiving carprofen, platelet aggregation was significantly decreased, and onset of aggregation was significantly delayed on days 5, 7, and 12, compared with pretreatment values. Activated partial thromboplastin time was significantly increased on days 5, 7, and 12 over pretreatment values in treated dogs, but values remained within reference ranges. Significant differences were not detected in buccal mucosal bleeding time, other serum biochemical and hemostatic variables, or Hct, compared with pretreatment values and the internal control group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of carprofen for 5 days causes minor but not clinically important alterations in hemostatic and serum biochemical variables in clinically normal Labrador Retrievers. Carprofen is commonly used to treat osteoarthritis and chronic pain in dogs, but prior to this study, its effect on platelet aggregation and hemostatic variables was unknown.     

Effects of doxycycline, amoxicillin, cephalexin, and enrofloxacin on hemostasis in healthy dogs

OBJECTIVE: To determine the effects of enteral administration of doxycycline, amoxicillin, cephalexin, and enrofloxacin at therapeutic dosages for a typical duration on hemostatic variables in healthy dogs. ANIMALS: 14 Beagles. PROCEDURE: Doxycycline (10 mg/kg, PO, q 12 h), amoxicillin (30 mg/kg, PO, q 12 h), cephalexin (30 mg/kg, PO, q 12 h), and enrofloxacin (20 mg/kg, PO, q 24 h) were administered in random order to 10 healthy dogs at standard therapeutic dosages for 7 days, with a 7-day washout period between subsequent antimicrobials. In addition, 4 Beagles served as control dogs. Variables were evaluated before and after antimicrobial administration; they included platelet count, Hct, 1-stage prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen concentration, and platelet function. Platelet function was assessed via buccal mucosal bleeding time, aggregation, and a platelet-function analyzer. RESULTS: Administration of all antimicrobials caused a slight prolongation of 1-stage PT and activated PTT and slight decrease in fibrinogen concentration. Cephalexin caused a significant increase in 1-stage PT and activated PTT, amoxicillin caused a significant increase in activated PTT, and enrofloxacin caused a significant decrease in fibrinogen concentration. Platelet count or function did not differ significantly after administration of any antimicrobial. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of commonly used antimicrobials in healthy dogs resulted in minor secondary hemostatic abnormalities, with no change in platelet count or function. Although these changes were clinically irrelevant in healthy dogs, additional studies of the effects of antimicrobial administration on hemostasis in animals with underlying disease processes are warranted.     

An evaluation of activated coagulation time in warfarin-intoxicated dogs

Activated coagulation time, one stage prothrombin time and activated partial thromboplastin time were compared in warfarin-intoxicated dogs. All coagulation tests were significantly prolonged on the third and fourth days following intoxication. Coagulation assays of all dogs except one returned to preintoxication values one day following vitamin K therapy. Significant correlation was found between all coagulation tests in the intoxicated group. Activated coagulation time may provide a useful coagulation screening test to veterinarians with limited laboratory capabilities.     

Platelet function in dogs treated for lymphoma and hemangiosarcoma and supplemented with dietary n-3 fatty acids

A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothrombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.     

Hemostatic abnormalities in dogs with carcinoma: a thromboelastographic characterization of hypercoagulability

Hemostatic abnormalities were investigated in 32 dogs with carcinoma and 19 age-matched healthy dogs. Thromboelastography, hemostasis profile (i.e. prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration), platelet count (PLT), thrombin-antithrombin complexes (TAT), and plasminogen activator inhibitor-1 (PAI-1) activity were evaluated. Dogs with carcinomas had faster thrombus generation (TEG(TG), a mathematic value obtained from the first derivate of the thromboelastographic tracing; 834.8±91.1 vs. 707.8±75.8mm/min; mean±SD), increased fibrinogen concentration (276 vs. 151mg/dL), and PLT (425 vs. 324U×10(9)/L), but had decreased PAI-1 activity (15.7 vs. 26.2IU/mL).The most common hemostatic abnormalities found in carcinoma dogs were hypercoagulability (TEG(TG)>mean+2 SD of healthy dogs) and thrombocytosis (PLT>424×10(9)U/L) in 46% of cases, and hyperfibrinogenemia (fibrinogen >384mg/dL) in 32% of cases. Disseminated intravascular coagulation was uncommon and the extent of disease was not correlated with hypercoagulability. TEG(TG) showed good correlation with fibrinogen (r=0.80) and hyperfibrinogenemia seems to be a main factor of the hypercoagulable state in carcinoma dogs. In conclusion, TEG(TG) is a valid parameter to diagnose hypercoagulability.     

Thrombelastography in dogs admitted to an intensive care unit

Background: Underlying conditions in dogs admitted to an intensive care unit (ICU) can cause hemostatic dysfunction. Thrombelastography (TEG) may be useful in detecting hemostatic alterations as compared with standard coagulation tests. Objectives: The purpose of this study was to compare TEG results and those of standard coagulation tests in identifying hemostatic dysfunction in dogs admitted to an ICU and to investigate associations among the variables measured. Methods: Tissue factor‐activated TEG analysis, d ‐dimer and fibrinogen concentrations, antithrombin (AT) activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count were measured using standard techniques on 27 dogs admitted to ICU with a disease known to be associated with hemostatic dysfunction and in 31 clinically healthy control dogs. Results were compared between groups using nonparametric tests and κ analysis; principal component analysis (PCA) and Spearman rank correlation were used to measure associations among variables. Results: Fourteen of 27 ICU dogs had abnormal TEG tracings, which were used to classify the dogs as hypercoagulable (n=11), hypocoagulable (n=3), or normocoagulable (n=13). Hypercoagulable dogs had significantly increased d ‐dimer (P=.03) and fibrinogen (P=.01) concentrations compared with normocoagulable dogs. In ICU dogs, positive associations were identified between maximum amplitude (MA), α‐angle, fibrinogen concentration, and platelet count, and between PT, aPTT, and reaction time (R). Significant correlations were found between MA and fibrinogen (r_s=.76, P<.001) and between reaction time (R) and PT (r_s=.51, P=.003). Conclusions: TEG was useful in detecting hemostatic dysfunction in dogs in an ICU. Positive associations among variables may provide insight as to how overall coagulation status reflects alterations in clot strength and coagulation time. Dogs with TEG tracings indicative of hypercoagulability are likely in procoagulant states. Future studies of the incidence of thrombotic complications in dogs with hypercoagulable TEG tracings are warranted.     

The utility of plasma D-dimer to identify thromboembolic disease in dogs

This prospective study was designed to investigate D-dimer concentrations in clinically healthy dogs, clinically ill dogs without thromboembolic disease (TE), and dogs with TE. The goals of this study were to determine whether the coagulation cascade is activated in nonembolic metabolic and inflammatory conditions and whether differentiation from TE is possible. Group 1 consisted of 30 clinically healthy dogs presented for routine care. Group 2 consisted of 67 clinically ill dogs without TE. This group was subdivided into the following categories: postoperative surgical procedures, congestive heart failure, renal failure, hepatic disease, and neoplastic disease. Group 3 consisted of 20 dogs diagnosed with TE. A CBC and a measurement of prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen degradation product (FDP) concentration, and plasma D-dimer concentration was performed on dogs in all groups. D-dimer concentrations were highest in dogs with TE; next highest was the hepatic disease group. Only these 2 groups had median D-dimer concentrations markedly different from clinically healthy dogs. The frequency of platelet abnormalities was markedly greater for the TE and neoplastic disease groups. The sensitivity of D-dimer concentrations >500 ng/mL for predicting TE was 100%; however, the specificity of D-dimer for TE at that concentration was 70%. The specificity of D-dimer concentrations >1,000 ng/mL to predict TE was 94% (sensitivity, 80%), and the specificity of D-dimer concentrations >2,000 ng/mL was 98.5% (sensitivity, 36%). FDPs were not high in any TE patient; thus, they may be an insensitive indicator of thromboembolism, with or without overt disseminated intravascular coagulation (DIC).     

Serial assessment of the coagulation status of dogs with immune-mediated haemolytic anaemia using thromboelastography

This study investigated the coagulation status of dogs with immune-mediated haemolytic anaemia (IMHA) over time. Thirty animals with primary IMHA were blood sampled on three occasions over a 5 day period and assays performed included prothrombin time, activated partial thromboplastin time, D-dimer and fibrinogen concentration, antithrombin activity and recalcified unactivated thromboelastography (TEG). Based on TEG, dogs with IMHA were significantly hypercoagulable vs. controls (P<0.001) and over the 5 day period, 3/4 of the TEG parameters reflected increased clotting kinetics (P ≤ 0.02). The 30 day survival of these patients was 80% and, at hospital admission, the TEG maximum amplitude (MA) was significantly higher in survivors than non-survivors (P=0.015). Each unit increase in MA was associated with an increased odds of 30 day survival of 1.13 (95%; CI 1.02-1.25). Based on TEG, most dogs with IMHA were hypercoagulable on admission and their clotting kinetics increased with time. Relative hypocoagulability identified by TEG at initial assessment was found to be a negative prognostic indicator.     

Thrombocytopenia and platelet activity in dogs experimentally infected with Rangelia vitalii

The aim of this study was to evaluate the platelet count, coagulation time and platelet activity in dogs experimentally infected with Rangelia vitalii during the acute phase of the disease. For this study, 12 young dogs (females) were used, separated in two groups. Group A (uninfected control) was composed by healthy dogs (n=5), and group B consisted of R. vitalii-infected animals (n=7). After being inoculated with R. vitalii-infected blood, animals were monitored by blood smear examinations, which showed intra-erythrocytic forms of the parasite five days post-inoculation (PI). Blood samples were collected on days 0, 10, 20 and 30 PI. The material collected was placed in tubes containing EDTA for quantification of platelets, citrate anticoagulant platelet aggregation, and measuring the clotting time. Right after blood collection on days 10 and 20 PI, dogs were anesthetized for collecting bone marrow samples. A significant reduction (P<0.01) of the number of platelets was observed in R. vitalii-infected blood, when compared with uninfected dogs on days 10 and 20 PI. Additionally, macro-platelets were observed only in infected dogs. Prothrombin time and activated partial thromboplastin time did not differ between infected and uninfected dogs. The megakaryocyte count increased (P<0.01) significantly in infected dogs when compared with uninfected ones on days 10 and 20 PI. Platelet aggregation decreased (P<0.01) significantly in infected dogs in comparison to the control on days 10 and 20 PI. Therefore, rangeliosis in dogs causes a severe thrombocytopenia during the acute phase of infection. This platelets reduction probably occurred due to splenic sequestration and/or immune-mediated thrombocytopenia.     

Serum C-reactive protein concentrations in dogs with multicentric lymphoma undergoing chemotherapy

OBJECTIVE: To determine whether serum C-reactive protein (CRP) concentration is high in dogs with multicentric lymphoma, whether CRP concentration changes in response to chemotherapy, and whether CRP concentration can be used as a marker for relapse in dogs with multicentric lymphoma. DESIGN: Cohort study. ANIMALS: 20 dogs with multicentric lymphoma and 8 healthy control dogs undergoing chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) or with vincristine, cyclophosphamide, methotrexate, and L-asparaginase (VCMA) and 20 other healthy dogs. PROCEDURES: Serum CRP concentration was measured weekly during the first month of chemotherapy and then at 3-week intervals until relapse in dogs with multicentric lymphoma, weekly for 16 weeks in healthy dogs undergoing chemotherapy, and once in the healthy dogs not undergoing chemotherapy. RESULTS: For both groups of dogs with lymphoma, mean serum CRP concentration during week 1 (prior to treatment) was significantly higher than mean concentrations following induction of chemotherapy and at the time of relapse. Mean serum CRP concentration in the healthy dogs undergoing chemotherapy was not significantly different at any time from mean concentration for the healthy dogs not undergoing chemotherapy. No significant differences were observed between dogs treated with CVP and dogs treated with VCMA. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that serum CRP concentration is high in dogs with multicentric lymphoma but that serum CRP concentration is not a useful marker for relapse and that chemotherapy itself does not affect serum CRP concentration.     

Effects of L-asparaginase on plasma amino acid profiles and tumor burden in cats with lymphoma

BACKGROUND: L-Asparaginase (Elspar(a)), is an Escherichia coli-derived enzyme that depletes lymphoma cells of asparagine, inhibiting protein synthesis and resulting in cell death. The single agent response rate in cats with lymphoma and impact of L-asparaginase on plasma amino acid concentrations is unknown. HYPOTHESES: L-Asparaginase significantly reduces plasma asparagine concentrations and has demonstrable efficacy against untreated lymphoma in cats. ANIMALS: Thirteen cats with confirmed lymphoma (LSA) of any anatomic site were given 1 dose 400 IU/kg IM) of L-asparaginase for initial LSA treatment. METHODS: Plasma collected at 0, 2, and 7 days after L-asparaginase therapy was assayed for ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. Cats were restaged 7 days later to assess tumor response. Results: Eight cats had T-cell LSA, 4 cats had B-cell LSA, and 1 cat's immunophenotype was unknown. Two complete and 2 partial responses to L-asparaginase were seen. Four cats had stable disease, and 5 cats had progressive disease. Ammonia and aspartic acid concentrations were increased from baseline at 2 and 7 days posttreatment. Asparagine concentrations were decreased from baseline at 2 days but not 7 days posttreatment. Glutamic acid concentrations were increased at day 2 compared to day 7 posttreatment but not compared to baseline. Glutamine concentrations were unchanged. CONCLUSIONS AND CLINICAL IMPORTANCE: L-asparaginase significantly reduced asparagine concentrations within 2 days of treatment, but this effect was lost within 7 days. The apparent overall response rate of feline LSA to L-asparaginase in this study was 30%.     

Evaluation of a bench-top coagulation analyzer for measurement of prothrombin time, activated partial thromboplastin time, and fibrinogen concentrations in healthy dogs

OBJECTIVE: To evaluate a bench-top coagulation analyzer for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen concentration in healthy dogs. ANIMALS: 55 healthy adult dogs. PROCEDURES: PT, APTT, and fibrinogen concentration were determined by use of the coagulation analyzer. Values were compared with results obtained independently by a conventional laboratory. RESULTS: Correlations (with 95% confidence intervals) between the coagulation analyzer and conventional laboratory values were 0.760 (0.610 to 0.857), 0.700 (0.448 to 0.721), and 0.896 (0.878 to 0.918) for PT, APTT, and fibrinogen concentration, respectively. Using linear regression, comparison of data from the coagulation analyzer and the conventional laboratory provided equations relating the coagulation analyzer values with values from the conventional laboratory and suggested that APTT and fibrinogen values from the coagulation analyzer and conventional laboratory were approximately the same within expected random variation. Prothrombin time values for the coagulation analyzer were significantly offset from the PT values for the conventional laboratory but still were correlated reasonably well with the conventional laboratory values. CONCLUSIONS AND CLINICAL RELEVANCE: By use of the mechanical method of analysis, fibrinogen concentrations obtained with a bench-top coagulation analyzer correlated well with results for a conventional laboratory, indicating that the coagulation analyzer is a reliable instrument for determination of this coagulation variable. Coagulation analyzer results for PT and APTT correlated less strongly with those for the conventional laboratory, but they would still be considered clinically reliable.     

Safety of reduced-dosage ketoprofen for long-term oral administration in healthy dogs

OBJECTIVE: To evaluate the safety of reduced-dosage ketoprofen (RDKET) for long-term oral administration in healthy dogs. ANIMALS: 14 healthy Beagles. PROCEDURES: Racemic ketoprofen (0.25 mg/kg, PO) and gelatin capsules, as a drug-free placebo, were each administered to 7 dogs for 30 days. Dogs were periodically monitored via physical examination, blood analyses, endoscopic examinations, fecal occult blood tests (tetramethylbenzidine and guaiac methods), renal function tests (effective renal plasma flow and glomerular filtration rate), urinalyses, urinary enzyme indices (N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transferase), and hemostatic function tests (buccal mucosa bleeding time, cuticle bleeding time, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration). RESULTS: Pyloric antrum lesion grade was significantly higher in the RDKET group on day 28, compared with the pretreatment and control group grades. Fecal occult blood grade measured by use of the tetramethylbenzidine method was significantly higher in the RDKET group on day 30, compared with the pretreatment grade. No other significant differences were detected between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: RDKET induced mild to moderate gastric mucosal injuries especially in the pyloric antrum in healthy Beagles, whereas no adverse effects were observed in renal function or hemostasis. Fecal occult blood tests may be useful as screening tests for adverse gastrointestinal effects induced by RDKET in dogs.     

Coagulation profiles in dogs with congenital portosystemic shunts before and after surgical attenuation

BACKGROUND: Serious postoperative hemorrhage has been reported in dogs after closure of congenital portosystemic shunts (CPS). HYPOTHESIS: In dogs with portosystemic shunting, low coagulation factor activity is responsible for coagulopathy, which can cause complications after surgery. ANIMALS: Thirty-four dogs with CPS and 39 healthy dogs. METHODS: In a prospective study, coagulation times, platelet count, and the activity of 8 coagulation factors were measured in dogs before and after surgical shunt attenuation and in 31 healthy dogs. The effect of abdominal surgery on hemostasis was determined at ovariectomy in 8 healthy dogs. RESULTS: Dogs with CPS had lower platelet counts, lower activity of factors II, V, VII, and X, and increased factor VIII and activated partial thromboplastin time (APTT) compared to healthy dogs. After surgical attenuation, dogs with CPS had decreased platelet counts and activity of factors I, II, V, VII, IX, X, and XI and a prolonged prothrombin time (PT). Ovariectomy resulted in decreased activity of factors VII and X. Six weeks after surgery, portosystemic shunting persisted in 9 of 30 dogs, with no improvement of hemostatic values. CPS dogs without shunting had improved coagulation times and increased activity of factors II, V, VII, and X. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with CPS have lower activity of clotting factors compared to healthy dogs, resulting in a prolonged APTT. Surgical attenuation of the shunt results in increased abnormalities in coagulation times and factors immediately after surgery. Hemostasis is normalized after complete recovery of shunting after attenuation, in contrast to dogs with persistent shunting.     

Combination of CCNU and DTIC chemotherapy for treatment of resistant lymphoma in dogs

BACKGROUND: Pleotropic-glycoprotein (P-gp)-mediated resistance is the usual cause of relapse in dogs with lymphoma. 1-(2-chloroethyl)3-cyclohexyl-1-nitrosurea (CCNU) and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) are alkylating agents that are not affected by P-gp and lack cross-resistance to each other. A combination protocol offers the advantage of improved summation dose and synergistic activity. HYPOTHESIS: A combination of CCNU and DTIC that is well tolerated can be used to treat dogs with lymphoma that developed resistance or failed to respond to previously administered chemotherapy. ANIMALS: Fifty-seven dogs with lymphoma that were resistant to treatment with standard chemotherapy (L-CHOP; L-asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisone). METHODS: Prospective phase I and II trials were performed. CCNU was given PO immediately before a 5-h IV infusion of DTIC. Concurrent antiemetics and prophylactic antibiotics were used. Treatments were administered every 4 weeks. RESULTS: Based on the results of 8 dogs in the phase I study, CCNU at 40 mg/m(2) PO combined with DTIC at 600 mg/m(2) IV was used to treat 57 dogs with resistant lymphoma. Thirteen (23%) dogs had a complete response (CR) for a median of 83 days and 7 (12%) had a partial response for a median of 25 days. The median L-CHOP CR duration of the dogs that did not respond to CCNU-DTIC was significantly longer than that of the dogs that did achieve remission with CCNU-DTIC (225 days versus 92 days, P= .02). The principal toxic event was neutropenia; the median neutrophil count 7 days after treatment was 1,275 cells/microL. Increases in alanine transaminase activity, possibly associated with hepatotoxicity, were detected in 7 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of CCNU and DTIC can be an effective option to rescue dogs with resistant lymphoma.     

Platelet function, antithrombin-III activity, and fibrinogen concentration in heartworm-infected and heartworm-negative dogs treated with thiacetarsamide.

Platelet aggregation and release, platelet number, mean platelet volume, antithrombin-III activity, and fibrinogen concentration were evaluated in heartworm-negative and heartworm-infected dogs at baseline and on days 3, 10, and 21 after treatment with thiacetarsamide. Platelet reactivity was enhanced in a group of dogs naturally infected with Dirofilaria immitis, compared with 2 groups of heartworm-negative dogs, but platelet reactivity was not further enhanced after treatment with thiacetarsamide. A significant decrease in antithrombin-III activity was detected 21 days after treatment. The platelets from a group of laboratory Beagles implanted with 50 adult D immitis displayed enhanced reactivity 6 months after implantation, but by 18 months, platelet reactivity had returned to near, or less than, baseline. Platelet reactivity was enhanced after thiacetarsamide treatment in this group. Thiacetarsamide-associated changes were not observed in platelet number or size; antithrombin-III activity decreased, but the change was not significant. Fibrinogen concentration was increased significantly (P less than 0.05) on day 10. Enhanced adenosine diphosphate (ADP)-induced platelet aggregation was observed on days 3, 10, and 21 after treatment in heartworm-negative dogs. This change was not observed in 6 control Beagles not treated with thiacetarsamide. Although antithrombin-III activity was decreased on day 3 and fibrinogen concentration was increased on day 10, paralleling changes observed in the heartworm-infected dogs, the changes were not statistically significant. In this study, thiacetarsamide was procagulatory in heartworm-negative dogs and may be an important contributing factor to the thromboembolism observed with adulticidal therapy.     

The effect of ticlopidine on canine platelets, fibrinogen, and antithrombin III activity

The effect of ticlopidine on platelet function, platelet number, mean platelet volume, antithrombin III activity, and fibrinogen was evaluated in 10 laboratory beagles. Ticlopidine (62 mg/kg) significantly inhibited ADP- and collagen-induced platelet aggregation within 2 days of the beginning of oral administration. Collagen-induced platelet 14C-serotonin release was not inhibited by day 9 of medication but was inhibited by day 20 in two of three beagles given medication for 32 days. Significant increases in mean platelet number were observed on days 2 and 5. The trend toward increased platelet number continued until day 16, at which time platelet number began to decrease toward baseline in three of three dogs treated for 32 days. Mean platelet volume (MPV) was significantly decreased compared to baseline on days 5 and 9. In three dogs treated for 32 days, the lowest MPV was observed on day 9 in two dogs and on day 12 in one dog. Significant changes were not observed in antithrombin III activity or fibrinogen with ticlopidine treatment.     

Diagnosis of disseminated intravascular coagulation in dogs admitted to an intensive care unit.

OBJECTIVE: To describe and evaluate hemostatic function in critically ill dogs with clinical signs of diseases that predispose to disseminated intravascular coagulation (DIC). DESIGN: Prospective case series. ANIMALS: 59 critically ill dogs (affected dogs) with clinical signs of diseases known to predispose to DIC and 52 clinically normal dogs (control dogs). PROCEDURE: Activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin clotting time (TCT), plasma fibrinogen concentration, serum concentration of fibrin and fibrinogen-related antigens (FRA), and plasma antithrombin III (AT III) activity were determined for all dogs. Results from affected dogs were compared with those of control dogs. In some affected dogs, postmortem tissue specimens were examined for evidence of microvascular thrombosis. A diagnosis of DIC was made by fulfilling at least 3 of the following criteria: 1) abnormal aPTT, PT, or TCT value, 2) low plasma fibrinogen concentration, 3) low plasma AT III activity, 4) high serum FRA concentration, or 5) low platelet count. To evaluate the severity of hemostatic dysfunction, 3 arbitrary categories (mild, moderate, and severe) were proposed. RESULTS: A diagnostic strategy based on moderate hemostatic dysfunction identified DIC in 16 of 59 (27.1%) affected dogs. The AT III activity was < 70% in 15 of 16 dogs with DIC. Microvascular thrombosis was observed in tissue specimens from 7 of 8 affected dogs. Serum FRA and plasma fibrinogen concentrations did not contribute in establishing a diagnosis of DIC. CONCLUSIONS AND CLINICAL RELEVANCE: A diagnosis of DIC can be made when hemostatic dysfunction is moderate in dogs with clinical signs of diseases associated with DIC.     

Effects of 2 concentrations of sodium citrate on coagulation test results, von Willebrand factor concentration, and platelet function in dogs

BACKGROUND: Blood collection tubes containing 3.2% (0.109 M) sodium citrate, instead of 3.8% (0.129 M) sodium citrate, have recently become available in the United States. These tubes are visually indistinguishable from the traditional 3.8% sodium citrate tubes, except for wording on the label. Consequently, samples for hemostatic evaluation are frequently collected in tubes containing the lower concentration of sodium citrate. HYPOTHESIS: Results of hemostasis assays are different in samples collected in 3.2% versus 3.8% sodium citrate. ANIMALS: Twenty healthy dogs. METHODS: This study aimed at determining whether results of standard coagulation tests, von Willebrand factor concentration (vWF:Ag), and platelet function with the platelet function analyzer PFA-100a were affected by the different concentrations of sodium citrate. Blood samples were collected in tubes containing either 3.2% or 3.8% sodium citrate concentrations and processed routinely for coagulation assays (one-stage prothrombin time [OSPT], activated partial thromboplastin time [aPTT], fibrinogen concentration, and platelet count), vWF:Ag, and platelet function assays with a PFA-100. RESULTS: There was no significant difference between samples collected in 3.2% versus those collected in 3.8% sodium citrate for OSPT, aPTT, fibrinogen concentration, platelet count, or vWF:Ag. The closure times with collagen/adenosine diphosphate were significantly shorter (66 +/- 8.1 versus 74.8 +/- 9.7 seconds; P < .0001) with the 3.2% than with 3.8% sodium citrate concentration, and the hematocrit was significantly higher (47.9 +/- 5.6 versus 46.0 +/- 4.7 seconds; P = .03) in samples collected in 3.2% than in those collected in 3.8% sodium citrate. CONCLUSIONS AND CLINICAL IMPORTANCE: There is no clinically relevant effect of collection of blood into 3.2% or 3.8% sodium citrate.