The Effect of Sulfinpyrazone and Aspirin on the IVY Template Bleeding Time

The Canadian Stroke Study has afforded us an opportunity to study the effect of sulfinpyrazone 800 mg daily, aspirin 1200 mg daily, both drugs together, and a placebo on the Ivy template bleeding time. Patients with transient cerebral ischemic attacks were randomized to one of the treatment groups and studied before and during treatment.In 352 patients studied pre-drug, the mean bleeding time was 5.02 ± 2.38 (± 1 SD) minutes. Aspirin significantly prolonged the bleeding time (p=.001). Sulfinpyrazone alone had no effect on the bleeding time. In patients receiving both drugs, the effect was no greater than that of aspirin alone. 51Cr platelet survival studies have been completed in 47 patients during treatment. The mean of 8.4 days was similar to the mean in 17 normal controls(8.3 days). However, analysis by treatment groups remains to be done.

Non-Occlusive Bleeding Times May Improve the Value of Ivy Bleeding Times

10.1055/s-0038-1645049 ◽

1990 ◽

Vol 63 (03) ◽

pp. 371-374 ◽

Cited By ~ 4

Author(s):

Zella R Zeigler

Keyword(s):

Blood Loss ◽

Clinical Evidence ◽

Bleeding Time ◽

Bone Marrow Failure ◽

Venous Occlusion ◽

Spontaneous Bleeding ◽

Heterogeneous Behavior ◽

The Mean ◽

Aspirin Ingestion ◽

SummaryThe present studies measured bleeding times, without venous occlusion, in a series of patients, whose bleeding times (+ venostasis) consistently exceeded 20 min. During these tests, the amount of blood loss (expressed as mg/min) was also quantitated. To allow comparison, normal controls were studied before and following aspirin ingestion. In normal controls, the mean standard Ivy bleeding time was 5.0 with a range of 2.5 to 7.5 min. Two hours after aspirin (650 mg), this increased to 7.3 min (range 4.0−12.0). For comparison, the non-occlusive bleeding time averaged 3.8 min (1.0−6.5) and after aspirin 5.3 min (2.5−11.5). The measured amount of blood loss was 5.0 mg/min (0−10.5 mg/ min) under all of the above conditions. At the other extreme, patients with severe bone marrow failure had occluded and nonoccluded bleeding times in excess of 20 min. Moreover, these were often associated with excess blood loss. By contrast, patients with “Ivy” values >20 min in association with platelet counts >10,000/μl had unpredictable bleeding parameters. In the latter group, the non-occluded values ranged from 1 to >20 min. Of particular note, the non-occlusive times appeared to correlate with spontaneous bleeding manifestations. Only a rare patient (1/37), whose non-occluded value was <20 min, had worrisome bleeding. By contrast, serious bleeding manifestations were observed in 39% whose non-occluded value exceeded 20 min. This was even higher (64%) in those with a non-occluded value >20 min and excess blood loss. These studies provide laboratory and clinical evidence for the heterogeneous behavior of patients with venostasis bleeding times >20 min. These additional laboratory measurements may be helpful in defining risk of spontaneous bleeding and in evaluating therapeutic strategies in such patients. However, studies will need to be performed to correlate this type of information with bleeding associated with invasive diagnostic or surgical procedures.

A Comparison Between Low Molecular Weight Heparin (KABI 2165) and Standard Heparin in the Intravenous Treatment of Deep Venous Thrombosis

10.1055/s-0038-1660139 ◽

1985 ◽

Vol 54 (04) ◽

pp. 813-817 ◽

Cited By ~ 107

Author(s):

Göran Bratt ◽

Eva Törnebohm ◽

Staffan Granqvist ◽

Wiveca Åberg ◽

Dieter Lockner

Keyword(s):

Molecular Weight ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Low Molecular Weight Heparin ◽

Bleeding Time ◽

Low Molecular Weight ◽

Treatment Groups ◽

Intravenous Treatment ◽

Heparin Activity ◽

The Mean

SummaryIn order to study whether a low molecular weight heparin (LMWH) of mw 4000 D is effective in the treatment of deep venous thrombosis (DVT), patients with DVT verified by phlebography were randomized to treatment by continuous intravenous infusion of either unfractionated heparin (UFH) or LMWH. The initial dose was 240 U (anti F Xa)/kg/12 h. TTiis study (study I) was stopped because of major bleeding in 2 newly operated patients in the LMWH group after 27 patients had been treated. The heparin activity measured as F Xa inhibition assayed in retrospect, was found to be much higher in the LMWH group (mean 1.6-2.0 anti F Xa U/ml) than in the UFH group (mean 0.5-0.8 anti F Xa U/ml).A second study was therefore initiated in which the DVT patients were randomly given UFH (240 U/kg/12 h) or LMWH only 120 U (anti F Xa)/kg/12 h, as initial doses (study II). In this study 27 patients could be evaluated, the mean heparin activity still being higher in the LMWH group (0.9-1.2 anti F Xa U/ml) than in the UFH group (0.5-0.7 anti F Xa U/ml).A second phlebographic investigation showed progression of thrombus size in 3 (11%) of the UFH patients of studies I and II (n = 29) and improvement in 14 (48%). There was no progression in any LMWH patient, 6 (50%) had improved in study I and 10 (77%) in study II. The mean decrease of thrombus size score (according to Marder) during treatment did not differ between the 3 groups.Antithrombin III decreased significantly in the UFH group but not in the LMWH groups. Aminotransferases increased in all 3 groups. There was no difference in mean capillary bleeding time between the 3 treatment groups.Although this material is relatively small, our findings suggest that LMWH seems to be of similar effectivity as UFH.

Accuracy of Weighted Platelet Mean Life Span in 4-Day Platelet Survival Studies

10.1055/s-0039-1687275 ◽

1979 ◽

Author(s):

F.J. Casals ◽

J. M. Paulus

Keyword(s):

Measurement Errors ◽

Survival Curve ◽

Simulated Data ◽

Normal Subjects ◽

Weighted Mean ◽

Platelet Survival ◽

The Mean ◽

Survival Test ◽

Survival Studies ◽

Sampling Times

A platelet survival test of short duration, if available, would prove useful in clinical trials which evaluate the effects of antithrombotic agents. To determine the accuracy of a 4-day survival test the weighted mean of the linear and logarithmic estimates of mean longevity was computed from simulated data based on gamma (GA) or logistic-exponential (LE) functions of known mean longevities. Seventeen different sets of parameters were used for GA and 11 for LE. For each set the % circulating activity was calculated at 12 sampling times from 0.02 to 3.8 days and 30 simulated tests were created by introducing measurement errors having the same distribution as that experimentally determined in 28 normal subjects. The mean square error ranged from 3 .7 to 12.6 % for LE functions and 8.5 to 12.6 % for GA (except one value of 17.6 %). Eliminating all samples prior to 8hrs did not affect the mean error. By relying on the most significant part of the survival curve, the 4-day test appears as accurate as the 10-day one while promising to be easier to repeat and better accepted by patients

Isopycnicyty and Relations Between Platelet Volume, Density and Age

10.1055/s-0039-1680649 ◽

1977 ◽

Author(s):

B. Boneu ◽

C. Caranobe ◽

F. Vigoni ◽

A. Blasco ◽

R. Bierme

Keyword(s):

Mathematical Analysis ◽

Significant Variation ◽

Volume Density ◽

Volume Distribution ◽

Platelet Volume ◽

Platelet Survival ◽

The Mean ◽

Survival Studies ◽

Log Normal ◽

Evident Relationship

The conflicting results, published in literature, concerning the correlation and significance of platelet volume, density and age are possibly due to the different experimental procedures utilized : medium, densities or centrifugation. We present here the results obtained in man with two methods of centrifugation (I : 800g/60mn ; II : 7000g/20mn) and three different linear isoosmolar gradients (a : Ludox-PVP ; b : Albumin ; c : Metrizamide).With the methods I a, b, c we obtain only one gaussian platelet population. There is an evident relationship between apparent platelet densities and their volumes : the denser the platelets the larger they are. The platelets of each fraction present a log normal volume distribution. The platelet survival studies (51 Cr) demonstrate that platelet volume and age are independent. With the methods II a, b, c we also obtain only one gaussian platelet population but no significant variation of volume between dense and light platelets (except for Ludox-PVP). The mathematical analysis of platelet kinetics (75 Se - 51 Cr) indicates : (1) that young platelets (age < 48h) present the same heterogeneity as the whole platelet population, but the mean density is lower ; (2) the potential survival of platelets of various densities is identical ; (3) the young platelets increase slightly their density during the first four days of their survival. Thus there is continuously some sort of exchange between platelet populations, (peripheral maturation phenomenon).In conclusion ours are conflicting results too. We demonstrate in fact that the second method achieves an isopycnic separation but not the first one.

Platelet Survival in Streptozotocin-Induced Diabetic Rats

10.1055/s-0038-1661089 ◽

1984 ◽

Vol 51 (03) ◽

pp. 307-312 ◽

Cited By ~ 13

Author(s):

P D Winocour ◽

M Laimins ◽

J A Colwell

Keyword(s):

Diabetes Mellitus ◽

Diabetic Rats ◽

Diabetic Rat ◽

Platelet Survival ◽

Survival Studies ◽

SummaryPlatelet survival in diabetes mellitus may be decreased or normal, and it is not clear whether altered platelet survival is due to a platelet or to a non-platelet defect. Therefore, platelet survival studies were performed at intervals up to 28 days in streptozotocin-induced diabetic and normal rats, using washed platelets from diabetic or normal animals.When compared to platelets from control rats, there was a significant decrease in platelet survival when platelets from 7 and 14 day diabetic rats were injected into normal controls or into diabetic rats.After 28 days of diabetes, platelet survival in diabetic rats was significantly lengthened, whether the platelets came from control or diabetic rats. Conclusions. (1) Shortened platelet survival in the diabetic rat is caused initially by a platelet defect. Later, non-platelet factors become dominant. (2) These findings may help explain reported discrepancies in results of platelet survival in diabetes mellitus.

The Clinical Usefulness of the Platelet Aggregation Test for the Diagnosis of Heparin-Induced Thrombocytopenia

10.1055/s-0038-1651610 ◽

1993 ◽

Vol 69 (04) ◽

pp. 344-350 ◽

Cited By ~ 175

Author(s):

B H Chong ◽

J Burgess ◽

F Ismail

Keyword(s):

Platelet Aggregation ◽

Heparin Therapy ◽

Serotonin Release ◽

Point System ◽

Control Groups ◽

Heparin Induced Thrombocytopenia ◽

Heparin Concentration ◽

Release Test ◽

The Mean ◽

SummaryThe platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.

The Influence of Ascorbic Acid on Platelet Structure and Function

10.1055/s-0038-1651445 ◽

1975 ◽

Vol 34 (01) ◽

pp. 050-062

Author(s):

Dale H Cowan ◽

Richard C Graham ◽

Patricia Shook ◽

Ronda Griffin

Keyword(s):

Ascorbic Acid ◽

Open Channel ◽

Channel System ◽

Short Intervals ◽

Platelet Survival ◽

Artifactual Changes ◽

Survival Studies ◽

And Function ◽

Induced Aggregation ◽

Platelet Structure

SummaryTo determine the effect on platelet behavior of transient exposure of platelets to ascorbic acid, studies of platelet function and ultrastructure were done before exposure to ascorbic acid at pH 6.5, during exposure to pH 6.5, and after restoration of pH to pre-acidifìcation levels. The effect of ascorbic acid (A. A.) was compared to that of HCl and citric acid (C. A.). ADP- and collagen-induced aggregation of normal platelets were significantly impaired by both A. A. and C. A. but were less affected by HCl. The release of 14C-serotonin was significantly reduced by each agent. The ultra-structure of normal platelets brought to pH 6.5 by A.A. was normal. After neutralization, there was marked dilatation of the open channel system and loss of the disc shape. When platelets were brought to pH 6.5 by A. A., then neutralized, the aggregates which formed after stimulation by ADP or collagen were smaller than normal, the platelets were less closely approximated, and degranulation was less complete. The data show that exposure of platelets to ascorbic acid for short intervals impairs their function when measured after restoration of pH to levels compatible with maximal responses. Platelet survival studies using autologous platelets labelled with 51Cr in the presence or absence of ascorbic acid showed that the recovery of normal platelets was unaffected by ascorbic acid, whereas recovery of platelets from patients with idiopathic thrombocytopenic purpura, idiopathic thrombocythemia, and alcohol-related thrombocytopenia was markedly reduced. The injury resulting from the use of ascorbic acid in preparing platelets for studies of platelet survival in patients with disorders affecting platelets may impair the recovery of the cells, resulting in artifactual changes in the survival studies.

The Estimation of Blood Platelet Survival

10.1055/s-0038-1649028 ◽

1972 ◽

Vol 28 (03) ◽

pp. 447-456 ◽

Cited By ~ 3

Author(s):

E. A Murphy ◽

M. E Francis ◽

J. F Mustard

Keyword(s):

Standard Deviation ◽

Least Squares ◽

Experimental Error ◽

Blood Platelet ◽

Least Squares Estimation ◽

Systematic Relationship ◽

Platelet Survival ◽

The Mean ◽

Normally Distributed

SummaryThe characteristics of experimental error in measurement of platelet radioactivity have been explored by blind replicate determinations on specimens taken on several days on each of three Walker hounds.Analysis suggests that it is not unreasonable to suppose that error for each sample is normally distributed ; and while there is evidence that the variance is heterogeneous, no systematic relationship has been discovered between the mean and the standard deviation of the determinations on individual samples. Thus, since it would be impracticable for investigators to do replicate determinations as a routine, no improvement over simple unweighted least squares estimation on untransformed data suggests itself.

Functional Monitoring after Trabeculectomy or XEN Microstent Implantation Using Spectral Domain Optical Coherence Tomography and Visual Field Indices—A Retrospective Comparative Cohort Study

Biology ◽

10.3390/biology10040273 ◽

2021 ◽

Vol 10 (4) ◽

pp. 273

Author(s):

Marc Schargus ◽

Catharina Busch ◽

Matus Rehak ◽

Jie Meng ◽

Manuela Schmidt ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Cohort Study ◽

Visual Field ◽

Spectral Domain ◽

Optical Coherence ◽

Treatment Groups ◽

Rnfl Thickness ◽

Comparative Cohort Study ◽

The Mean ◽

All Treatment

The aim of this study was to compare the efficacy of trabeculectomy (TE), single XEN microstent implantation (solo XEN) or combined XEN implantation and cataract surgery (combined XEN) in primary open-angle glaucoma cases, naïve to prior surgical treatment, using a monocentric retrospective comparative cohort study. Intraocular pressure (IOP) and the number of IOP-lowering drugs (Meds) were monitored during the first 24 months after surgery. Further disease progression was monitored using peripapillary retinal nerve fiber layer (RNFL) thickness examinations using spectral domain optical coherence tomography (OCT) as well as visual acuity (VA) and visual field (VF) tests. In the TE group (52 eyes), the mean IOP decreased from 24.9 ± 5.9 to 13.9 ± 4.2 mmHg (p < 0.001) and Meds decreased from 3.2 ± 1.2 to 0.5 ± 1.1 (p < 0.001). In the solo XEN (38 eyes) and the combined XEN groups, the mean IOP decreased from 24.1 ± 4.7 to 15.7 ± 3.0 mmHg (p < 0.001) and 25.4 ± 5.6 to 14.7 ± 3.2 mmHg (p < 0.001), while Meds decreased from 3.3 ± 0.8 to 0.8 ± 1.2 (p < 0.001) and 2.7 ± 1.2 to 0.4 ± 1.0 (p < 0.001), respectively. The VF and VA indices showed no sign of further deterioration, the RNFL thickness further decreased in all treatment groups after surgery. TE and XEN led to comparable reductions in IOP and Meds. Although the VA and VF indices remained unaltered, the RNFL thickness continuously decreased in all treatment groups during the 24-month follow-up.

Filociclovir Is an Active Antiviral Agent against Ocular Adenovirus Isolates In Vitro and in the Ad5/NZW Rabbit Ocular Model

Pharmaceuticals ◽

10.3390/ph14040294 ◽

2021 ◽

Vol 14 (4) ◽

pp. 294

Author(s):

Eric G. Romanowski ◽

Islam T. M. Hussein ◽

Steven C. Cardinale ◽

Michelle M. Butler ◽

Lucas R. Morin ◽

...

Keyword(s):

Antiviral Activity ◽

Topical Treatment ◽

Antiviral Agent ◽

Human Adenovirus ◽

Treatment Groups ◽

Ocular Infections ◽

The Mean ◽

Eye Infection

Presently, there is no FDA- or EMA-approved antiviral for the treatment of human adenovirus (HAdV) ocular infections. This study determined the antiviral activity of filociclovir (FCV) against ocular HAdV isolates in vitro and in the Ad5/NZW rabbit ocular model. The 50% effective concentrations (EC50) of FCV and cidofovir (CDV) were determined for several ocular HAdV types using standard plaque reduction assays. Rabbits were topically inoculated in both eyes with HAdV5. On day 1, the rabbits were divided into four topical treatment groups: (1) 0.5% FCV 4x/day × 10 d; (2) 0.1% FCV 4x/day × 10 d; (3) 0.5% CDV 2x/day × 7 d; (4) vehicle 4x/day × 10 d. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. The resulting viral eye titers were determined using standard plaque assays. The mean in vitro EC50 for FCV against tested HAdV types ranged from 0.50 to 4.68 µM, whereas those treated with CDV ranged from 0.49 to 30.3 µM. In vivo, compared to vehicle, 0.5% FCV, 0.1% FCV, and 0.5% CDV produced lower eye titers, fewer numbers of positive eye cultures, and shorter durations of eye infection. FCV demonstrated anti-adenovirus activity in vitro and in vivo.