Assessment of the Coagulation Profile in Canine Multiple Myeloma: A Cohort Investigation in 234 Dogs

Hypercoagulability in canine multiple myeloma (MM) as described in humans has not been reported and prognostic factors related to hemostasis have not been investigated. Aims of this study were: to describe the haemostatic profile in dogs with MM, to detect a possible hypercoagulable state, and to assess whether coagulation parameters have prognostic value. Haemostatic alteration at the initial visit of dogs affected by MM (Group 1, n = 78) were retrieved from the electronic data- base (P.O.A. System-Plus 9.0®) of the San Marco Veterinary Clinic, between 2002–2015. Dogs with MM met the following criteria: bone marrow plasma cells ≥ 15%, osteolytic lesions, serum mono-biclonal gammopathy and extensive coagulation profile including platelet count, aPTT, PT, fibrinogen, thrombin time (TT), FPDs, D-Dimer and antithrombin (AT). Two groups of dogs individually matched for age, breed, and sex were used as controls: healthy dogs (Group 2, n = 78) and sick dogs without MM (Group 3, n = 78). In addition, the hemostatic profile between clinical bleeding (B-MM, n = 45) (e.g., gum bleeding, epistaxis) and no- clinical bleeding (NB-MM, n = 33) dogs with MM was evaluated. Kruskal-Wallis and Wilcoxon-Mann-Whitney tests were used to compare groups. Risk to death at 90 days after diagnosis within B-MM and NB-MM dogs was evaluated by Pearson's X2 test. ROC curves were used to identify the best analyte to predict death. Prothrombin time and aPTT were increased (p = 0.001) in Group 1 vs groups 2 and 3, TT was increased (p = 0.001) in Group 1 vs 3. The platelet count and AT concentration were decreased in Group 1 vs groups 2 and 3 (p = 0.001). Fibrinogen concentration was decreased in Group 1 vs 3 (p = 0.01). No differences between Groups 1 vs groups 2 and 3 for FDPs and D-dimer were observed. Platelet count and AT concentrations were decreased in B-MM vs NB-MM (p = 0.04; p = 0.026); PT and aPTT and were increased in B-MM vs NB-MM (p = 0.026; p = 0.03). No differences between B-MM and NB-MM were observed for TT, FDPs, D-Dimer. B-MM dogs showed lower mortality rate in respect to NB-MM patient (p < 0.028). The TT resulted the best haemostatic analyte in predicting death in dogs affected with MM (p < 0.04; AUC 64%; 95% CI = 0.48–0.82). Primary and secondary haemostasis are compromised in dogs with MM while tertiary haemostasis appears unaffected. The hypercoagulable state, opposite to humans, is unlikely in dogs with MM. Surprisingly, dogs with MM and clinical bleeding apparently have protective effect against death. The prediction of mortality in canine MM was related to TT

Short report: autistic gastrointestinal and eating symptoms treated with secretin: a subtype of autism

Pervasive Developmental Disorders (PDD) are chronic, lifelong disorders for which there is as yet no effective cure, and medical management remains a challenge for clinicians. The current report describes two patients affected by autistic disorder with associated gastrointestinal symptoms. They received multiple doses of intravenous secretin for a six-month period and were assessed with several specific outcome measures to evaluate drug effect. The administration of secretin led to some significant and lasting improvement in only one case. Gastroesophageal reflux may contribute to some of the behavioural problems and explain the effect of secretin since its suppressive effect on gastric secretion is well known. It is also true that autistic children with gastroesophageal reflux and a higher IQ could constitute a subtype which responds to secretin administration and that could be labelled as a "gastrointestinal subtype"

Bleeding diathesis in canine multiple myeloma and prognostic implications: A cohort study in 156 dogs

Multiple myeloma (MM) is a tumor of plasma cells representing approximately 1% of all canine tumors. Clinical evident bleeding is often referred to as the main finding. The aim of the study was to evaluate the occurrence of clinical bleedings in dogs with MM and its prognostic implications compared to a population of dogs not affected by MM. Two groups of dogs (# 78 each) individually matched for breed, age and gender were considered. Group-1 (exposed) was affected by MM and group-2 (unexposed) was affected by other diseases. They were compared for bleeding and mortality at 90 days after diagnosis (relative risk, RR; attributable risk, AR). Among group-1, bleeding patients (B) were compared with non-bleeding patients (NB) in terms of mortality at 90 days (RR, AR). Incident cases of MM were 78/57,694 (0.13%). Signs of bleeding up to 30 days before the referral presentation were found in 33 (42.3%) group-1 dogs in comparison to 6 (7.7%) group-2 dogs (RR, 5.50, CI 95% 2.55–12.3, p=0.0001; AR, 0.34, CI 95% 0.22–0.47, p=0.0001). Epistaxis was the most frequent sign of bleeding recorded. Nineteen dogs from group-1 (24.3%) and eight from group-2 (10.2%) were non-survivors (RR=2.37, CI 95% 1.14–5.06, p=0.01; AR=0.14, CI 95% 0.02–0.26, p=0.01). Among the group-1, the B dogs, 4/33 (12.1%) were non-survivors, while 15/45 NB dogs (33.3%) were non-survivors (RR=2.75, CI 95% 1.08–7.44, p=0.03; AR=0.21, CI 95% 0.20–0.38, p=0.03). Epistaxis at diagnosis was frequent in MM dogs, and signs of bleeding were associated with a more favorable 90-day prognosis

HAEMOSTATIC PROFILE IN CANINE MULTIPLE MYELOMA: A COHORT STUDY IN 210 DOGS

Human patients with MM have short survival times associated with frequent complications such as throm- bosis.1 Considering their life span, dogs with MM in comparison to humans, have a longer survival times. Hypercoagulable complications in canine MM are not known and prognostic factors linked to haemostasis have been not thoroughly investigated.2 Aim of the study: a) to describe the haemostatic profile in dogs with MM at presentation, b) to assess whether coagulation parameters have a prognostic value, and c) to detect a possible hypercoagulable state. Haemostatic abnormalities in dogs with MM (Group 1, #70) were evaluated via search of the electronic data-base (P.O.A System Plus 9.0 R ) of the San Marco Veterinary Clinic, between 2002-2015. Dogs in- cluded in Group 1 met the criteria: bone marrow plasmacytosis (plasmacells 15%), osteolytic lesions, serum mono-biclonal gammopathy. All groups had a haemostatic panel taken at presentation. Two groups of dogs matched for age, breed, and sex were enrolled as case-control: healthy dogs (Group 2,#70) and dogs affected by various diseases (Group 3,#70). The analytes investigated were: Platelet count (PLT), activated Partial Thromboplastin Time (aPTT), Prothrombin Time (PT), Fibrinogen, Thrombin Time (TT), Fibrin-Fibrinogen Degradation Products (FPDs), D-Dimer and Antithrombin (AT). In addition, within the MM-dogs the haemostatic profile between bleeding (B-MM, #42) and non-bleeding (NB-MM, #28) dogs was evaluated. Statistical differences between groups was evaluated by Kruskal-Wallis test and post-test analysis were performed by Wilcoxon-Mann-Whitney. Risk to death within B-MM and NB-MM dogs was evaluated by Pearson’s X2 test. ROC curves were used to identify the best analyte to predict death. The significance level for all statistical test was set at p<0.05. aPTT, PT and TT were significantly increased in Group 1 compared to Groups 2 and 3. PLT count and AT concentrations were significantly decreased in Group 1 compared to Group 2 and 3. Fibrinogen concentration was significantly decreased in Group 1 compare to Group 3, while no difference was present between Group 1 and 2. No difference were present between Groups 1 versus Group 2 and 3 for FDPs and D-dimer. PLT count and AT concentration were significantly decreased in B-MM compared to NB-MM; aPTT and PT were significantly increased in B-MM compared to NB-MM; finally, no differences between B-MM and NB-MM were present for TT, FDPs, D-Dimer. B-MM dogs showed lower mortality rate in respect to NB-MM patient (p<0.028). AT resulted the best haemostatic analyte in predicting death in dogs affected with MM (p<0.04; AUC 64%; 95% CI 0.50-0.78). Primary and secondary haemostasis are highly compromised in dogs affected by MM while tertiary haemostasis appears to be not altered, suggesting that a hypercoagulable state, opposite to humans, is un- likely in dogs with MM. Surprisingly, in dogs with MM bleeding seems to have a protective effect against death. The best haemostatic assay to predict the mortality in canine MM at 90 days after the diagnosis is the AT. 1) Coppola A, Tufano A, Di Capua M, et al. Bleeding and thrombosis in multiple myeloma and related plasma cell disorders. Semin Thromb Hemost, 2011;37, 929-945. 2) Matus RE, Leifer CE, MacEwen EG, et al. Prognostic factors for multiple myeloma in dog. J Am Vet Med Assoc, 1986;188, 11:1288-1292