OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti–activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

OBJECTIVE To compare humoral insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-β1, and interleukin-1 receptor antagonist (IL-1Ra) concentrations in plasma and 3 types of equine autologous blood-derived preparations (ABPs). SAMPLE Blood and ABP samples from 12 horses. PROCEDURES Blood samples from each horse were processed by use of commercial systems to obtain plasma, platelet concentrate, conditioned serum, and aqueous platelet lysate. Half of the platelet concentrate samples were additionally treated with a detergent to release intracellular mediators. Humoral IGF-1, PDGF-BB, TGF-β1, and IL-1Ra concentrations were measured with ELISAs and compared statistically. RESULTS Median IGF-1 concentration was highest in conditioned serum and detergent-treated platelet concentrate, followed by platelet concentrate and plasma; IGF-1 was not detected in platelet lysate. Mean PDGF-BB concentration was highest in platelet lysate, followed by detergent-treated platelet concentrate and conditioned serum; PDGF-BB was not detected in plasma and platelet concentrate. Median TGF-β1 concentration was highest in detergent-treated platelet concentrate, followed by conditioned serum, platelet lysate, and platelet concentrate; TGF-β1 was not detected in most plasma samples. Median IL-1Ra concentration was highest in platelet lysate, followed by conditioned serum; IL-1Ra was not detected in almost all plasma, detergent-treated platelet concentrate, and platelet concentrate samples. CONCLUSIONS AND CLINICAL RELEVANCE Each ABP had its own cytokine profile, which was determined by the specific processing method. Coagulation and cellular lysis strongly increased humoral concentrations of cell-derived cytokines. No ABP had the highest concentrations for all cytokines. Further studies are needed to assess clinical relevance of these findings.

OBJECTIVE To compare the effects of equivalent volumes of equine plasma and 6% hydroxyethyl starch (600/0.75) solution (hetastarch) administered IV on plasma colloid osmotic pressure (pCOP) and commonly monitored clinicopathologic variables in horses. ANIMALS 6 healthy mares. PROCEDURES In a randomized, crossover study, horses were administered hetastarch or plasma (both 10 mL/kg, IV) 18 months apart. The pCOP and variables of interest were measured before (baseline), immediately after, and at intervals up to 96 or 120 hours after infusion. Prothrombin and activated partial thromboplastin times were measured before and at 2 and 8 hours after each infusion. RESULTS Prior to hetastarch and plasma infusions, mean ± SEM pCOP was 19.4 ± 0.5 mm Hg and 19.4 ± 0.8 mm Hg, respectively. In general, hetastarch and plasma infusions comparably increased pCOP from baseline for 48 hours, with maximum increases of 2.0 and 2.3 mm Hg, respectively. Mean Hct and hemoglobin, total protein, and albumin concentrations were decreased for a period of 72, 96, or 120 hours after hetastarch infusion with maximum decrements of 8.8%, 3.2 g/dL, 1.2 g/dL, and 0.6 g/dL, respectively. Plasma infusion decreased (albeit not always significantly) hemoglobin concentration and Hct for 20 and 24 hours (maximum changes of 1.5 g/dL and 6.6%, respectively) and increased total solids concentration (maximum change of 0.6 g/dL) for 48 hours. Platelet count and coagulation times were minimally affected. CONCLUSIONS AND CLINICAL RELEVANCE Overall, the hetastarch and plasma infusions comparably increased pCOP in healthy horses for up to 48 hours. Hetastarch induced greater, more persistent perturbations in clinicopathologic variables.

OBJECTIVE To measure thrombin generation by high and low tissue factor (TF)–expressing canine cancer cell lines. SAMPLE Canine cell lines CMT25 (high TF–expressing mammary gland tumor cell line) and HMPOS (low TF–expressing osteosarcoma cell line). PROCEDURES Thrombin generation by cancer cells was measured in pooled normal canine plasma by use of calibrated automated thrombography without added trigger reagents. Results were expressed as lag time, time to peak thrombin concentration, peak thrombin concentration, and total thrombin concentration or thrombin generation potential. Corn trypsin inhibitor, hirudin, and annexin V were used to inhibit contact activation, thrombin formation, and phosphatidylserine activity, respectively. Pooled normal human plasma deficient in coagulation factors VII, VIII, IX, X, XI, or XII was used to assess the role of individual coagulation factors on thrombin generation. RESULTS CMT25 generated significantly more thrombin than did HMPOS (mean ± SD, 3,555 ± 604nM thrombin•min and 636 ± 440nM thrombin•min, respectively). Thrombin generation of CMT25 was dependent on factor VII and phosphatidylserine and was independent of contact activation. In contrast, thrombin generation of HMPOS was attributed to contact activation. CONCLUSIONS AND CLINICAL RELEVANCE High TF-expressing canine mammary cancer cells generated thrombin in a plasma milieu in vitro in a factor VII- and phosphatidylserine-dependent manner. These findings support a role for TF in hypercoagulability detected in dogs with mammary gland tumors and potentially for other tumors that strongly express TF.