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Effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs undergoing elective ovariohysterectomy.

OBJECTIVE: To determine effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs after elective ovariohysterectomy. DESIGN: Randomized, masked clinical trial. ANIMALS: 22 healthy dogs. PROCEDURE: 60 minutes before induction of anesthesia, 11 dogs were given 0.9% NaCl solution (control), and 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], IM). Thirty minutes before induction of anesthesia, glycopyrrolate (0.01mg/kg [0.005 mg/lb]), acepromazine (0.05 mg/kg [0.02 mg/lb]), and butorphanol (0.2 mg/kg 10.09 mg/lb]) were given IM to all dogs. Anesthesia was induced with thiopental (5 to 10 mg/kg [2.3 to 4.5 mg/lb], IV) and maintained with isoflurane (1 to 3%). Ovariohysterectomy was performed and butorphanol (0.1 mg/kg [0.05 mg/lb], IV) was given 15 minutes before completion of surgery. Blood samples for measurement of variables were collected at intervals before and after surgery. RESULTS: In dogs given ketoprofen, platelet aggregation was decreased 95 +/- 10% and 80 +/- 35% (mean +/- SD) immediately after surgery and 24 hours after surgery, respectively, compared with preoperative values. At both times, mean values in dogs given ketoprofen differed significantly from those in control dogs. Significant differences between groups were not observed for mucosal bleeding time or hematologic indices. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of ketoprofen inhibited platelet aggre gation but did not alter bleeding time. Ketoprofen can be given before surgery to healthy dogs undergoing elective ovariohysterectomy, provided that dogs are screened for potential bleeding problems before surgery and monitored closely after surgery.

Animals↗

Bleeding time at altitude.

Disorders of coagulation during ascent to high altitude in the unacclimatized are well recognized. In order to document the sequence of haematological changes, the bleeding time was estimated weekly in six climbers during a six week climb. The median bleeding time was shown to increase by 50% between the first and fourth week, it then plateaued during continued ascent to 5700 m. During the sixth week the bleeding time rapidly reverted to baseline levels whilst still at altitude. The observations might be explained by the compensatory changes in coagulation factors following the initial prothrombotic phase, compounded by increased capillary fragility. Acclimatization to altitude is accompanied by a series of complex haematological changes. The temporal sequence should be considered when devising a strategy to reduce the risk of thrombosis.

Altitude↗

Inhibition of exercise-induced shortening of bleeding time by fish oil in familial hypercholesterolemia (type IIa).

Fourteen patients suffering from familial hypercholesterolemia (type IIa) participated in a double-blind, placebo-controlled trial that evaluated the effects of fish oil ethyl ester (K-85, 5.7 g/day) or a hydroxymethylglutaryl coenzyme A reductase inhibitor (lovastatin, 40 mg/day) alone or in combination on lipid metabolism and bleeding time at rest and after standardized exercise. Lovastatin treatment reduced total cholesterol (-27%), low density lipoprotein cholesterol (-37%), and triglycerides (-18%), whereas high density lipoprotein cholesterol increased significantly (14%). K-85 affected total (-4%), low density lipoprotein (-9%), and high density lipoprotein (+7%) cholesterol insignificantly, whereas the triglyceride level decreased by 24% (p < 0.001). The combined regimen caused an additive decrease in the triglyceride level (41%), which differed significantly (p < 0.01) from that gained by lovastatin alone. Under basal conditions the bleeding time was not influenced by the different interventions. Standardized exercise shortened the bleeding time by 19% (p < 0.001) and 16% (p < 0.001) before intervention and after lovastatin treatment, respectively. After K-85 alone or in combination with lovastatin, the exercise-induced shortening of the bleeding time was totally inhibited, which may reflect a favorable influence of fish oil on the platelet-vessel wall interaction in these high-risk patients.

Adult↗

The gingival bleeding time index.

Recent studies have supported an emphasis on gingival bleeding indices for detection of inflammation. The purposes of the present study were: (1) to evaluate the relationships between the time necessary for stimulated gingival bleeding to occur and both gingival fluid flow and Löe's gingival index, and (2) to develop a clinical index based on gingival bleeding time. In the first part of the study, the elapsed time for gingival bleeding to first occur after sulcular stimulation was correlated with the gingival index and fluid flow on 150 gingival units. A high correlation was found between bleeding time with both the gingival index and exudate flow. A bleeding time index based on a scattergram of the data obtained in part I of the study was then formulated and evaluated in a similar fashion on an additional 172 gingival units. Results indicate a high correlation between the bleeding time index and the other indices. It is concluded that the bleeding time index may be used by itself as an accurate and objective clinical tool to evaluate gingival inflammation.

Gingival Crevicular Fluid↗

The effects of "anti-platelet" drugs on bleeding time and platelet aggregation in normal human subjects.

The effects on hemostasis of several commonly used drugs previously described as inhibiting platelet function were evaluated in a randomized, double-blind study of 54 normal volunteers. The subjects were each given a single dose of aspirin, chlorpromazine, glyceryl guaiacolate, diphenhydramine, indomethacin or lactose placebo. A single dose of aspirin significantly prolonged the template bleeding time and inhibited secondary platelet aggregation two and 24 hours after ingestion. Single doses of indomethacin and chlorpromazine affected aggregation at two hours but had no effect on bleeding time, although multiple doses of indomethacin did prolong bleeding time. Glyceryl guaiacolate inhibited aggregation one hour after ingestion but had no effect on bleeding time. Diphenhydramine did not affect either. These findings suggest that standard doses of many commonly used "anti-platelet" drugs may have little clinical effect on the hemostatic mechanism in normal man. Results of in-vitro platelet-drug incubations may not be directly applicable to in-vivo hemostasis.

Aspirin↗

In vitro testing of platelets using the thromboelastogram, platelet function analyzer, and the clot signature analyzer to predict the bleeding time.

BACKGROUND: Platelet aggregation, thromboxane A2 production and platelet annexin V binding are in vitro tests used to assess platelet function. This study was done to evaluate the clot signature analyzer (CSA), platelet function analyzer (PFA), and thromboelastogram (TE) as in vitro tests to predict the template bleeding time (BT). STUDY DESIGN AND METHODS: Twelve normal volunteers were studied before and after removal of 2 units of RBC. Seven females were reinfused their RBC and 5 males were not. Samples were collected prior to and at 24, 48, and 72 h and 7 days after the RBC removal whether or not reinfusion of RBC was performed for measurement of TE, CSA, PFA and template BT. RESULTS: BT increased significantly following the removal of 2 units of RBC and BT decreased significantly after the reinfusion of the 2 units of RBC in the 7 female volunteers. BT decreased during the 7-day period in the 5 male volunteers not reinfused their RBC. No significant correlations were observed between BT and platelet hemostatic time (PHT) and clotting time (CT) in the CSA and between the bleeding time and the closure time (CT) in the platelet function analyzer (PFA). Significant correlations were observed between BT and K time, the MA, and the angle recorded in the thromboelastogram. CONCLUSION: In this study in vitro testing using the clot signature analyzer, platelet function analyzer and the thromboelastogram could not be used to predict the template bleeding time.

Annexin A5↗

The bleeding time in women: an influence of the sex hormones?

A sex difference in the bleeding time has been reported. To investigate the effects of the different sex hormones, the bleeding time (BT) and hemostatic factors related to it were measured in 209 healthy women: 50 pregnant, 113 menstruating and 46 post-menopausal. The serum levels of estrogens, progesterone and testosterone were distributed as expected for the different groups. There were no significant differences in the BT between any of the groups. No correlations between the BT and female or male sex hormones were found. The findings indicate that although sex hormone mediated effects on platelet/endothelial cell interactions may exist, they do not become evident within the physiological variations in the BT of healthy women.

Adult↗

Low-dose aspirin to pregnant women: single dose pharmacokinetics and influence of short term treatment on bleeding time.

Single dose pharmacokinetics of 75 mg aspirin was investigated in two groups of ten women with clinically normal pregnancies. Eleven non-pregnant subjects in the same age were controls. In group A, gestational age was 27-30 completed weeks, and in group B, 36-39 weeks. Venous blood samples were taken before and up to 240 minutes after the intake of the aspirin. Liquid chromatographic assays for acetylsalicylic acid (ASA) and its metabolite, salicylic acid (SA), was performed. The pharmacokinetics of ASA and SA were similar in group A and B but pregnant subjects had a slower uptake and a lower peak level than controls. The late elimination phase for their compound did not differ between the groups. Nine pregnant women with normal pregnancies had their bleeding time measured by a modified Ivy technique using a Simplate II device before, at the end of, and two weeks after daily administration of 75 mg ASA for two weeks. All had a normal bleeding time before and two weeks after the end of the medication. Eight of the nine subjects had an increased bleeding time by Ivy tests, (p < 0.01) whereas the bleeding time assessed by Duke's method was within normal limits. These studies suggest that during pregnancy changes of the uptake rate and distribution volume modulate the pharmacokinetics of ASA and that this drug given in low dosage to gravidae marginally alters their platelet function.

Aspirin↗

A new thromboxane receptor antagonist, Z-335, ameliorates experimental thrombosis without prolonging the rat tail bleeding time.

We investigated the antithrombotic activity of Z-335, a new thromboxane A2 receptor antagonist, using experimental thrombosis models, and also tested its effect on the rat tail bleeding time. Z-335 (0.1, 0.3, and 1 mg/kg, p.o.) dose-dependently prevented the occurrence of arachidonic acid-induced pulmonary thromboembolism in mice. During photochemically induced thrombosis in the femoral artery of guinea pigs, Z-335 (0.3, 1, and 3 mg/kg, i.v.) dose-dependently prolonged the time required to form thrombi. Moreover, Z-335 (10 mg/kg/day, p.o.) strongly suppressed lauric acid-induced hind limb injury in rats. Z-335 (0.3, 3, 30, and 300 mg/kg, p.o.) did not prolong the tail bleeding time in rats. These results strongly suggest that Z-335 ameliorates experimental thrombosis without prolonging the rat tail bleeding time, and may therefore be a useful antithrombotic drug.

Animals↗

Platelet thromboxane formation and bleeding time is influenced by ethanol withdrawal but not by cigarette smoking.

Platelet count, mean volume, aggregation and associated thromboxane (TXB2) formation, circulating platelet aggregates and bleeding time were examined in 19 noncirrhotic male alcoholic cigarette smokers for four weeks following cessation of prolonged heavy drinking, and in 24 nonalcoholic healthy male volunteers (10 smokers and 14 nonsmokers). The alcoholics showed a 9-fold increase (p less than 0.001) in ADP-stimulated platelet thromboxane formation one to two weeks after ethanol withdrawal. The effect was transient and coincided with a significant (p less than 0.01) shortening of skin bleeding time and a slight increase in circulating platelet aggregates suggesting proneness to thrombosis. No differences were seen between the smoking and nonsmoking healthy volunteers. We conclude that the recovery phase after prolonged heavy drinking is characterized by a transient increase in platelet reactivity which may lead to increased spontaneous formation of circulating platelet aggregates and shortening of bleeding time.

Adult↗

Prolonged bleeding time during nitric oxide inhalation in the rabbit.

During a study on the modulatory effect of inhaled nitric oxide (NO) on the airway, we observed an increased bleeding tendency. Therefore, we studied bleeding time and blood rheology in rabbits during inhalation of 3, 30 and 300 parts per million (ppm) NO. The rabbits were intubated during neurolept anaesthesia and were ventilated mechanically. The bleeding time was significantly increased after 15 min of inhalation of 30 ppm NO, from 51 +/- 5 to 72 +/- 7 s (mean +/- SEM, P < 0.001, n = 7). However, there were no changes in haematocrit, whole blood or plasma viscosity, erythrocyte aggregation tendency, or erythrocyte deformability. Inhalation of 3 ppm NO increased bleeding time from 46 +/- 11 to 59 +/- 8 s (n.s., n = 4) and 300 ppm NO from 48 +/- 12 to 78 +/- 17 s (P < 0.05, n = 4). In another group of rabbits mean arterial pressure (MAP) was monitored using NO inhalation. A non-significant decrease was seen with 3 ppm and 30 ppm NO, from 63 +/- 2 to 59 +/- 3 mmHg (n = 6) and from 65 +/- 2 to 61 +/- 1 mmHg (n = 6) respectively. Inhalation with 300 ppm NO decreased MAP from 62 +/- 3 to 55 +/- 2 mmHg (P < 0.05, n = 6). We conclude from these data that inhalation of NO, 30 ppm or more exerts systemic effects.

Administration, Inhalation↗

[The clinical problem of hereditary hemorrhagic diseases developing prolonged bleeding time].

Thirty-two patients with hereditary hemorrhagic diseases and a platelet functional abnormality were set apart from our group of patients with hereditary hemorrhagic diseases, and their symptoms, signs and hematological examinations were collected; the initial events and the age of the patients when they were obsserved, the main hemorrhagic manifestations during their clinical course, the clinical severity of the disorders, the survival of the patients and the laboratory test for hemostasis useful to make the diagnosis, were evaluated. In reference to bleeding time, thirty patients had abnormal bleeding time, but the other two had normal bleeding time.

Adolescent↗

The effect of inhaled nitric oxide therapy on bleeding time and platelet aggregation in neonates.

The effect of inhaled nitric oxide (iNO) on bleeding time and platelet aggregation was studied in nine newborn infants with resolving pulmonary hypertension. Infants treated with iNO at 40 ppm for 30 minutes had bleeding times that were nearly twofold longer than those obtained 24 hours after iNO was discontinued. iNO had no effect on in vitro platelet aggregation studies.

Administration, Inhalation↗

Discontinuation of the bleeding time test without detectable adverse clinical impact.

BACKGROUND: The bleeding time (BT) test predicts a higher bleeding complication rate in populations at risk for inherited or acquired platelet dysfunction, but it is of limited assistance in evaluating individual patients. There are no reports of clinical outcomes after discontinuation of the BT test. METHODS: Interviews with a subset of the physicians who had ordered the BT test before discontinuation of the test were conducted. The total number of platelet-aggregation tests, the mean number of monthly, unmodified platelet units transfused, the incidence of kidney biopsy complications, and the number of doses of 1-deamino-8-D-arginine vasopressin (DDAVP) administered 5 months before and after discontinuation of the BT test were compared. We recorded the rates of bleeding complications in the Major Surgery Risk Pool during the 12 months before and the 5 months after the discontinuation of the BT test. RESULTS: Clinicians reported they did not significantly change their preprocedural work-ups, postpone an invasive procedure, experience an increase in bleeding complications, or increase their use of blood products after discontinuation of the BT test. Platelet-aggregation tests (n = 9, before and after), platelet transfusions (P = 0.958), and DDAVP administration (before = 24; after = 10) did not increase after discontinuation of the BT test. The rate of postprocedural bleeding complications did not increase significantly in either Major Surgery Risk Pool cases (<3final sigma deviation from the mean rate) or in patients undergoing renal biopsies (P = 0.225 for decrease in hematocrit; P = 1.000 for the percentage of patients transfused) after discontinuation of the BT test. CONCLUSIONS: Our study failed to identify a clinically significant, negative impact of discontinuing the BT test.

Adult↗

[Bleeding times in haemophilia patients treated with lyophilised antihaemophilic globulin (AHG) (author's transl)].

Tests on 16 patients with haemophilia A confirmed earlier studies that bleeding times may be prolonged after treatment with antihaemophilic globulin (AHG). Despite adequate factor VIII substitution by AHG, treatment effect was unsatisfactory in all 16 patients and there were abnormally prolonged bleeding times after several AHG infusions. But determination of bleeding times after single AHG infusion provides no pointer to possible later problems.

Blood Coagulation Tests↗

Whole-blood platelet aggregation, buccal mucosa bleeding time, and serum cephalothin concentration in dogs receiving a presurgical antibiotic protocol.

Whole-blood platelet aggregation (using the impedance method) and adenosine triphosphate (ATP) release, buccal mucosal bleeding time (BT), and serum cephalothin concentration were measured in 21 adult female Beagles before (PRE) and 1 hour (1 HR) after IV administration of cephalothin (22 mg/kg). A second injection of cephalothin (22 mg/kg) was given 3 hours after the first, and blood samples were obtained 1 hour (4 HR, 4 hours after the first injection) and 3 hours (6 HR, 6 hours after the first injection) after the second injection. Samples of jugular blood were obtained from each dog, using citrate as an anticoagulant. A platelet count was obtained for each sample. Platelet aggregation and ATP released from the aggregating platelets were measured within 1 hour of sample collection, using a whole-blood aggregometer. Adenosine diphosphate (ADP) and collagen were used as aggregating agents. Aggregation was measured over 6 minutes for each aggregating agent; ATP release in response to collagen, but not to ADP, was measured over the same period. For 1 HR samples, there was a significant (P < 0.01) reduction from PRE values in the ability of platelets to aggregate in response to ADP. Bleeding time was determined, using a published procedure, with each dog as its own control. Bleeding time during the same period was found to be significantly increased over PRE values for 1 HR (P < 0.01) and 6 HR (P < 0.02) samples. There was no significant difference between BT for 1 HR and 4 HR samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

The bleeding time: current practice in the UK.

A questionnaire survey of current practice in the bleeding time test has been undertaken by the UK External Quality Assessment Scheme in blood coagulation. Completed returns have been received from 358 centres. Most centres (88.5%) perform bleeding times and of these the Ivy test is the most commonly performed. Only 13.6% perform the Duke method. Templates are used to control the procedure by approximately half of the hospitals. There is considerable variability in the type and depth of incision and interpretation of the endpoint. The upper limit of normality not unexpectedly differs considerably between the centres with both Ivy and Duke methods. The use of a commercial template method, 'Simplate', provides a measure of agreement amongst the group of hospitals using this instrument but it remains to be established whether this is the most reliable procedure. In the interim, gross discrepancies in technique or interpretation should be corrected in the light of the findings of the survey.

Bleeding Time↗

[Bleeding time and volume in vitro by THROMBOSTAT].

We tested an in vitro system simulating bleeding time reported by Kratzer et al. Primary hemostasis was studied perfusing an artificial vessel with citrated blood under a constant pressure of 40 mmHg, measuring the blood volume perfused (bleeding volume) and the time until blood flow stopped (bleeding time). The artificial vessel consists of a glass capillary simulating arteriole and a filter covered with collagen type I to provide a surface for the adhesion of platelets. The bleeding volume (mean +/- SD microliters) was 317.7 +/- 93.8 in controls (n = 19), 487.3 +/- 242.1 in idiopathic thrombocytopenic purpura (n = 9), 666.8 +/- 224.1 in aplastic anemia and paroxysmal nocturnal hemoglobinuria (n = 4), greater than 820 in von Willebrand's disease (n = 3), 231.0 +/- 74.5 in hemophilia A (n = 3), 499.0 +/- 269.4 in liver cirrhosis (n = 6), and 457.7 +/- 229.0 in myeloproliferative disorders (n = 11). When citrated blood was applied to this system after incubation with monoclonal antibodies (MoAb) to von Willebrand factor or platelet membrane glycoprotein Ib (GPIb), bleeding volume was significantly increased while no effects were observed after incubation with MoAb to GPIIb/IIIa, factor VIII: CAg and factor XIIIa. These data suggest that in vitro model of primary hemostasis could be used for not only diagnosing bleeding disorders although 'time' is not reliable, but also investigating the mechanisms of hemostasis.

Antibodies, Monoclonal↗