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- Author or Editor: Daniel F. Hogan x
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Abstract
Objective—To determine if clopidogrel enhanced the thrombolytic rate of tissue-plasminogen activator (t-PA) on an in vitro feline whole blood thrombosis model.
Animals—9 purpose-bred cats.
Procedure—Blood obtained from cats before (baseline) and after treatment with clopidogrel (75 mg, PO, q 24 h for 3 days) was anticoagulated with sodium citrate (9:1 volume-to-volume ratio) to which 1 µCi of I125- fibrinogen was added. Thrombi were formed by the addition of calcium chloride and bovine thrombin. Thrombi were placed into autologous plasma to which 0.1 mg of t-PA was added. Plasma samples were collected at different time points to determine the amount of released I125-fibrin split products. Thrombolytic rates were calculated by determining the time to 25%, 50%, and 75% thrombolysis (t25, t50, and t75, respectively). Confidence intervals for t25, t50, and t75 at baseline were compared with those after treatment.
Results—There were no significant differences in thrombolytic rates between values obtained at baseline and after clopidogrel treatment (t25, 18.0 vs 18.5 minutes; t50, 63.3 vs 65.6 minutes; and t75, 163.0 vs 170.1 minutes, respectively).
Conclusions and Clinical Relevance—Clopidogrel did not have an effect on the rate of thrombolysis of feline whole blood thrombi induced by t-PA in this in vitro model. (Am J Vet Res 2004;65:715–719)
Abstract
Objective—To determine whether soybean oil emulsion has an in vitro effect on platelet aggregation and thromboelastography in blood samples obtained from healthy dogs.
Animals—12 healthy adult dogs.
Procedures—Blood samples were collected from each dog into tubes containing EDTA, hirudin, or sodium citrate for a CBC, collagen- and ADP-induced impedance aggregometry, or thromboelastography, respectively. Whole blood platelet aggregation, determined with ADP or collagen agonists, was measured in blood samples containing hirudin and final lipid concentrations of 0, 1, 10, and 30 mg/mL. The thromboelastographic variables R (reaction time), K (clotting time), α angle, and maximum amplitude were evaluated in blood samples containing sodium citrate and final lipid concentrations equivalent to those used for assessment of platelet aggregation.
Results—Median maximum ADP- and collagen-induced platelet aggregation in blood samples containing 1, 10, or 30 mg of lipid/mL did not differ significantly from the value for the respective lipid-free blood sample. Maximum amplitude determined via thromboelastography was significantly reduced in blood samples containing 10 and 30 mg of lipid/mL, compared with findings for lipid-free blood samples. Values of other thromboelastographic variables did not differ, regardless of lipid concentrations.
Conclusions and Clinical Relevance—Maximum amplitude determined via thromboelastography in canine blood samples was significantly affected by the addition of lipid to final concentrations that are several orders of magnitude higher than clinically relevant lipid concentrations in dogs. Lipid treatment appears to have no significant effect on hemostatic variables in dogs, although clinical studies should be performed to confirm these in vitro findings.
Abstract
Case Description—2 horses and 1 pony were evaluated for right-sided (1 horse and the pony) and left-sided (1 horse) acute epistaxis of 1 day's to 1 month's duration.
Clinical Findings—Endoscopic examination of the 3 equids revealed that the hemorrhage originated from the right maxillary artery in 2 equids and from the left internal carotid artery in the third. Mycosis of the auditory tube diverticulum (guttural pouch) was detected in all 3 equids.
Treatment and Outcome—All 3 equids underwent surgery, and transarterial nitinol intravascular plugs were placed to occlude affected blood vessels. All equids survived for a long period (ie, a minimum of 1 to 2 years) and returned to their previous use. All had complete regression of clinical signs of guttural pouch mycosis without additional medical treatment.
Clinical Relevance—The use of transarterial nitinol intravascular plugs appeared to be an effective alternative to other techniques for the treatment of epistaxis secondary to guttural pouch mycosis, including transarterial occlusion devices such as embolization coils.
Abstract
Objective—To determine effects of the glycoprotein IIb/IIIa receptor antagonists abciximab and eptifibatide on in vitro inhibition of cat platelets.
Sample—Venous blood samples from 10 healthy cats.
Procedures—Blood samples were anticoagulated with hirudin. Aliquots of whole blood from each cat were allocated to 5 treatments (baseline, 50 μg of abciximab/mL, abciximab volumetric control treatment, 4μM eptifibatide, and eptifibatide volumetric control treatment). Impedance platelet aggregometry was performed with 6.5μM ADP or 32μM thrombin receptor activator peptide (TRAP). Magnitude of platelet aggregation was determined by measuring the area under the curve 15 minutes after addition of ADP or TRAP.
Results—Eptifibatide caused a significant reduction in platelet aggregation, compared with baseline values, for aggregometry with both ADP (median, 50.0; range, 8 to 122 [baseline median, 306.0; baseline range, 130 to 664]) and TRAP (median, 75.5; range, 3 to 148 [baseline median, 219.0; baseline range, 97 to 578]). There was no significant difference in platelet aggregation with abciximab, the abciximab volumetric control treatment, or the eptifibatide volumetric control treatment for aggregometry with ADP or TRAP.
Conclusions and Clinical Relevance—Eptifibatide caused a significant reduction in platelet aggregation in vitro, but there was no identifiable antiplatelet effect for abciximab. Eptifibatide and abciximab have different binding and inhibitory actions; therefore, it can be hypothesized that abciximab would be ineffective in cats because of a lack of receptor binding, reduced binding kinetics, or lack of downstream signaling. Eptifibatide may be useful in identifying hyperreactive platelets in cats in an in vitro platelet inhibitory assay.
Abstract
Objective—To determine whether ticlopidine exerts an antiplatelet effect, estimate the pharmacodynamics of ticlopidine, and evaluate any acute adverse effects associated with administration of ticlopidine in cats.
Animals—8 domestic purpose-bred sexually intact male cats.
Procedure—Ticlopidine was administered orally (50 mg, q 24 h; 100 mg, q 24 h; 200 mg, q 24 h; and 250 mg, q 12 h). Each treatment period consisted of 10 days of drug administration. Platelet aggregation studies with adenosine diphosphate (ADP) and collagen and evaluation of oral mucosal bleeding times (OMBTs) were performed on days 3, 7, and 10 during each drug administration. Serotonin was measured to evaluate secretion at baseline and on day 10 for cats that received the 250-mg dosage.
Results—A significant reduction in platelet aggregation was detected in response to ADP on days 7 and 10 at 100 mg, on day 3 at 200 mg, and on days 3, 7, and 10 at 250 mg. A significant increase in the OMBT and decrease in serotonin release on day 10 at 250 mg was also detected; however, the cats had anorexia and vomiting at the 250-mg dosage.
Conclusions and Clinical Relevance—Although there was a consistent antiplatelet effect at the 250-mg dosage, there was dose-dependent anorexia and vomiting that we conclude precludes the clinical usefulness of this drug in cats. ( Am J Vet Res 2004;65:327–332)
Abstract
Objective—To establish practical doses and administration frequencies of fondaparinux for cats that would approximate human therapeutic peak and trough plasma anti–factor Xa activities for thromboprophylaxis (TP) and thrombosis treatment (TT) protocols.
Animals—6 healthy adult purpose-bred cats.
Procedures—Dosage protocols for TP and TT were selected on the basis of a single compartment pharmacokinetic model incorporating data from humans but modified to account for the higher body weight–normalized cardiac output of cats. Fondaparinux was administered at 0.06 mg/kg, SC, every 12 hours (TP) for 7 days in one session, and 0.20 mg/kg, SC, every 12 hours (TT) for 7 days in another, with a minimum of 1 week separating the sessions. Plasma anti–factor Xa activity was measured before fondaparinux administration (day 1) and at 2 (peak) and 12 (trough) hours after drug administration on days 1 and 7. Platelet aggregation and thromobelastographic (TEG) parameters were also measured 2 hours after drug administration on day 7.
Results—Peak plasma anti–factor Xa activities on day 7 for TP (median, 0.59 mg/L; range, 0.36 to 0.77 mg/L) and TT (median, 1.66 mg/L; range, 1.52 to 2.00 mg/L) protocols were within therapeutic ranges for humans. However, only the TP protocol achieved trough anti–factor Xa activity considered therapeutic in humans (median, 0.19 mg/L; range, 0.00 to 0.37 mg/L) on day 7. There were significant changes in the TEG parameters at peak for the TT protocol, suggesting a hypocoagulable state. No significant changes in platelet aggregation were evident for either protocol.
Conclusions and Clinical Relevance—A fondaparinux dosage of 0.06 or 0.20 mg/kg, SC, every 12 hours, was sufficient to achieve a peak plasma anti–factor Xa activity in cats that has been deemed therapeutic in humans. This study provided preliminary data necessary to perform fondaparinux dose-determination and clinical efficacy studies.
Abstract
Objective—To determine whether pimobendan has in vitro antithrombotic properties through inhibition of platelets in canine blood samples.
Animals—10 healthy adult dogs.
Procedures—Blood samples were collected from each dog into tubes containing hirudin or sodium citrate. Pimobendan was added to blood samples (final concentration, 0.0, 0.01, 0.1, 1.0, or 10.0μM) containing hirudin prior to undergoing collagen- and ADP-induced whole blood impedance aggregometry. Plasma thromboxane concentrations were measured after platelet aggregation. Pimobendan was also added to blood samples (0.0, 0.01, or 10.0μM) containing sodium citrate prior to thromboelastographic evaluation.
Results—Compared with findings for 0.0μM pimobendan, composite platelet aggregation (area under the curve [AUC]) and maximal platelet aggregation (aggregation units [AUs]) at 10.0μM pimobendan were significantly decreased for collagen-induced aggregation (AUC, 349.7 ± 58.4 vs 285.1 ± 72.2; maximal platelet aggregation, 196.2 ± 25.8 AUs vs 161.5 ± 38.0 AUs), and the AUC and velocity of aggregation at 10.0μM pimobendan were significantly decreased for ADP-induced aggregation (AUC, 268.5 ± 35.1 vs 213.4 ± 77.2; velocity of aggregation, 15.7 ± 2.9 AUs/min vs 11.8 ± 3.5 AUs/min). Pimobendan had no significant effect on plasma thromboxane concentration or thromboelastographic variables, regardless of concentration.
Conclusions and Clinical Relevance—In vitro, pimobendan had an antiplatelet effect in canine blood samples at a concentration 1,000-fold higher than that clinically achievable. These antiplatelet properties do not appear to contribute to the positive clinical profile of the drug in dogs. Pimobendan administration would not appear to confer a risk for bleeding and does not have to be avoided in dogs with thrombocytopenia or those concurrently receiving antiplatelet drugs.
Abstract
Objective—To evaluate antiplatelet effects and pharmacodynamics of clopidogrel in cats.
Design—Original study.
Animals—5 purpose-bred domestic cats.
Procedure—Clopidogrel was administered at dosages of 75 mg, PO, every 24 hours for 10 days; 37.5 mg, PO, every 24 hours for 10 days; and 18.75 mg, PO, every 24 hours for 7 days. In all cats, treatments were administered in this order, with at least 2 weeks between treatments. Platelet aggregation in response to ADP and collagen and oral mucosal bleeding times (OMBTs) were measured before and 3, 7, and 10 days (75 and 37.5 mg) or 7 days (18.75 mg) after initiation of drug administration. Serotonin concentration in plasma following stimulation of platelets with ADP or collagen was measured before and on the last day of drug administration. Platelet aggregation, OMBT, and serotonin concentration were evaluated at various times after drug administration was discontinued to determine when drug effects were lost.
Results—For all 3 dosages, platelet aggregation in response to ADP, platelet aggregation in response to collagen, and serotonin concentration were significantly reduced and OMBT was significantly increased at all measurement times during drug administration periods. All values returned to baseline values by 7 days after drug administration was discontinued. No significant differences were identified between doses. None of the cats developed adverse effects associated with drug administration.
Conclusions and Clinical Relevance—Results suggest that administration of clopidogrel at dosages ranging from 18.75 to 75 mg, PO, every 24 hours, results in significant antiplatelet effects in cats. (J Am Vet Med Assoc 2004;225:1406–1411)
