bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence Of Anticoagulants Upon The Results Of Platelet Function Tests: Aggregation (PA) And Release Reaction(RR)
Authors: Wurzinger J L , Blasberg P 
Published: July 2018

Citrate (11 mM) is generally used as anticoagulant when platelet functions are tested. In contrast to heparin anticoagulation, citrate drastically lowers calcium levels creating a milieu, incompatible with life in an organism. However, the effects of heparin on platelet function are still a matter of debate, studies on this subject employing variable protocols of heparin administration and thus probably being responsible for the existing conflict of results. The present study attempts a systematic comparison of spontaneous as well as ADP and adrenaline induced PA and the RR under influence of either heparin or citrate used as anticoagulant. Spontaneous and ADP or adrenaline induced (each 5×10-7 M) PA were tested in a 2-channel rheoaggregometer simultaneously on platelet rich plasma (PRP) samples prepared from blood anticoagulated with 5 U heparin/ml or 11 mM citrate. ADP and adrenaline induced PA were tested 90 and 60 min after blood withdrawal respectively. Spontaneous PA was tested 30, 60, 90, 120 and 180 min after blood withdrawal.RR was assessed by measuring β-thromboglobulin (β-TG) release from gel filtered platelets, incubated for 30 min with varying doses of heparin (1,5,50 U/ml) or citrate (5,11,22 mM). Strict isothermia of 37°C was kept during all steps of the experimental procedure.We found that:
1. Adrenaline and ADP induced aggregation were significantly higher in heparinized than in citrated PRP.
2. Spontaneous PA in heparinized PRP too was higher than in citrated PRP during the interval looked upon.
3. Heparin added to gel filtered platelets enhanced, whereas citrate lowered β-TG release as compared to controls.
From our results we conclude that the differences in the behaviour of heparinized and citrated PRP are not only due to an effect of heparin itself, but also to the difference in calcium levels
Hairy Cell Leukemia: Report Of A Case With A Plasma Mediated Defect In Platelet Function And Platelet Morphology
Authors: Mattson J C , Sanal S 
Published: July 2018

A 60-year-old male with hairy cell leukemia developed purpura. Studies performed prior to splenectomy and at a time when purpuric lesions were present demonstrated a severe platelet functional defect characterized by absent primary and secondary wave aggregation with ADP and Ristocetin, absent Collagen aggregation, and diminished Epinephrine aggregation. In addition PF3 was decreased and the bleeding time prolonged. EM demonstrated a mixed population of degranulated, enlarged platelets and normal platelets. Following splenectomy PF3 levels and the bleeding time returned to normal. Repeat aggregation studied performed post-splenectomy showed return of primary wave aggregation but persistent absence of secondary wave aggregation in response to ADP, and virtually absent response to Collagen. Ristocetin aggregation returned to normal, but Epinephrine failed to produce any response. EM performed post-splenectomy demonstrated normal platelets. Tests performed on the patient’s pre-splenectomy plasma indicated the presence of an inhibitor which was capable of inhibiting primary aggregation, nucleotide release and secondary wave aggregation in normal platelets with all agents tested.This inhibitor had no effect on adhesion in a collagen adhesion assay. Full inhibitory effect was present after incubation of inhibitor plasma and normal platelets for 5 min. but with longer incubation times inhibition of aggregation was less pronounced suggesting either dissociation or destruction of the platelet bound inhibitor. Partial characterization of the inhibitor demonstrated that it was dialyzable, stable at 56 C for 30 min. and at 4 C for 72 hrs., and present in a 50% ammonium sulfate fraction of plasma. These studies suggest that the inhibitor is a globulin which appears to exert its inhibitory effect by nonspecific, easily dissociable binding to the platelet surface.
Inhibition Of Thromboxane Synthesis And Of Arachidonate- Induced Platelet Behaviour In Platelets From Different Individuals
Authors: Heptinstall S , Bevan J , Cockbill S R , Fox S C , Hanley S P , Luqmani R 
Published: July 2018

Several agents inhibit thromboxane synthesis in platelets so might be expected to modulate the arachidonate- induced platelet release reaction and the platelet aggregation that accompanies it. Such agents include the nonsteroidal anti-inflammatory agents (NSAIAs) that inhibit cyclo-oxygenase activity, the selective inhibitor of thromboxane synthetase UK-34787, and dipyridamole. We have assessed their influence on the ability of platelets to convert arachidonate to malondialdehyde (MDA, a marker of thromboxane synthesis) and on the arachidonate-induced release reaction (release of 14C-serotonin from labelled platelets.Platelets from different individuals respond differently to some of these agents. Whereas similar concentrations of each of acetylsalicylic acid, indomethacin, flurbiprofen and tolmetin were required to inhibit MDA production in platelets from different donors, higher concentrations of these NSAIAs were sometimes required to inhibit the arachidonate-induced release reaction in platelets from some donors than were required in platelets from others. UK-34787 inhibited both MDA production and the release reaction in platelets from some donors, but in platelets from others it had little effect on release despite inhibiting MDA generation. Dipyridamole was more effective as an inhibitor of the platelet release reaction in platelets that were responsive to UK-34787 than in platelets that were not.These different effects of agents on platelets from different individuals might be relevant to their effectiveness in thromboembolic disease. Perhaps participants in clinical trials should be stratified according to the responsiveness of their platelets to the particular drugs under scrutiny.
In Vivo Inhibition Of Thromboxane A2-Synthetase : Protective Effect Against Collagen And Arachidonate Infusion
Authors: Sincholle D , Fontaine C , Martin B , Bonne C , Regnault P 
Published: July 2018

Rabbits and rats anaesthetised with thiopental were infused intravenously either with sodium arachidonate or collagen. Blood pressure and pneumogram were recorded and Thromboxane B2 (T×B2) plasma level was measured prior and after infusion. The aggregating agents elicited hypotension, respiratory break down and killed the animals. These events were associated with an increase in plasma T×B2 concentration. Intraperitoneal pretreatment of animals with derivatives of imidazole (1 -(3-hydroxy-1-oct enyl)-imidazole , chlorhydrat e (CBS6l2) and its nicotinic ester (CBS634) delayed toxic effects and death. In the standard conditions used in this study, the lethal dose of arachidonate in the rabbit was 8.4 t 1.0 mg/kg. This dose was increased to 21.6 ± 4.3 and 50.4 ± 8.0 when the animals were pretreated with CBS6l2 at the dose of respectively 12.5 mg/kg and 25 mg/kg. In the same way, the lethal dose of collagen in the rat was 0.5 ± 0.1 mg/kg in controls and 1.2 t 0.1 mg/kg after treatment with thromboxane-synthetase inhibitor (CBS634 = 25 mg/kg). The lethal dose of collagen was correlated to the concentration of T×B2 formed in the blood (controls : 4.4 ± 0.3 ; treated : 1.7 ± 0.2 ng/ml).Potential interest of these antithrombotic drugs could be strengthened by further pharmacokinetic studies after oral treatment actually in progress.
Normal Prostacyclin-Like Activity In A Patient With Thrombotic Thrombocytopenic Purpura
Authors: Pini M , Manotti C , Quintavalla R , Dettori A G 
Published: July 2018

Deficiency of prostacyclin (PGI2) has been related to the pathogenesis of thrombotic thrombocytopenic purpura (TTP), and reduced PGI2 activity is thought to be secondary to a lack of plasma factor(s) which normally stimulates PGI2 production. We measured PGI2 production by means of the method of Moncada et al (Lancet 1:18, 1977), as platelet aggregation inhibitory activity released by venous specimen removed surgically in a 52 year-old woman with TTP in the acute phase of the disease. The patient was subsequently cured by plasma exchange.Platelet aggregation inhibitory activity released from venous tissues of the patient was normally detectable and comparable to that of a healthy control. Moreover, patient plasma was able to induce release of prostacyclin-like activity from exhausted veins (both from patient and normal control) as well as normal plasma. Hence release of PGI2 like activity from venous tissues and ability of plasma to stimulate prostacyclin synthesis in normal vascular tissues were not impaired in our patient with TTP in the acute phase of the disease.Our findings demonstrate that PGl2 deficiency is not implicated in the pathogenesis of all cases of TTP.
Effect Of Prednisone On Platelet Function In Patients With Bleeding Disorders
Authors: McKenna R , Bachmann F , Pichairut O , Whittaker B 
Published: July 2018

There is considerable controversy regarding the effect of Prednisone on the hemostatic mechanism of normal people versus patients with bleeding diatheses. We administered Prednisone 15 mg TID to patients with a positive history of a bleeding disorder, and evaluated the bleeding time and other in-vitrc tests of platelet function prior to and between the 5th and 7th day after Prednisone.Eleven patients were admitted into this study over a one year period. All patients had a history of excessive bruising, epistaxis, bleeding after dental extractions, and gastrointestinal or other bleeding in various combinations. Two out of the eleven had template bleeding times of greater than 15 minutes both before and after the Prednisone. These two patients were subsequently proven to have von Willebrand’s disease by the washed platelet ristocetin assay. In the remaining 9 patients, the pre-Prednisone bleeding time was 9.3 ±3.7 minutes (x ± 1 S.D.) whereas the post-Prednisone bleeding time was 5.8 ±3.6 minutes (x ±1 S.D.). These results were significant(td=3.83;df:7;p=0.007).Platelet aggregation in response to exogenous ADP (1 μM, 3 μM) Sigma bovine tendon collagen (1.8 mg/ml F) and epinephrine (5.5 × 104M), platelet retention in a glass bead column or platelet factor 3 availability did not improve or worsen after Prednisone therapy. The mean platelet count of 328,000±94,000 (x ±1 S.D.) was significantly (p=0.05) higher than the mean pre-Prednisone platelet count of 268,000±77,000 (x ±1 S.D.).In conclusion, we have shown that large doses of Prednisone appear to shorten the bleeding time in patients with significant defects in the primary hemostatic mechanism. However the bleeding time improvement is not evident in patients with von Willebrand’s disease.
Hemodynamic Effects And Changes Of Blood Flow Distribution By Dextran 70, Dihydroergotamin (DHE) And Their Combination
Authors: Lindblad B , Bergqviat D 
Published: July 2018

Dextran 70 and DHE are both effective in reducing the risk for postoperative thromboembolic complications. As they at least in part have different mechanisms of action it is important to analyse if their combination potentiates the prophylactic effect. Therefore it is necessary to study the effect on hemodynamics and tissue blood flow, a problem which is delt with in this report.MATERIAL AND METHODS: In 18 dogs the following parameters were followed: cardiac output, heart rate, arterial blood pressure, central venous pressure, pulmonary artery pressure, left atrium pressure and volume blood flow in the femoral vein. Blood flow distribution was determined by the radioactive microsphere technique.RESULTS: Dextran 70 gave an increase of cardiac output and femoral vein flow. Other hemodynamic parameters were mainly unaffected. Total peripheral resistance decreased. DHE increased arterial blood pressure, central venous pressure and pulmonary arterial pressure. Cardiac output and femoral vein flow were unchanged.Tissue blood flow increased in general slightly after infusion of dextran 70. No significant change in blood flow distribution was seen. DHE reduced pancreatic and thyroid blood flow and increased tissue blood flow to the central nervous system. The blood flow to other organs including the heart was unaffected. The combination of dextran 70 and DHE influenced hemodynamic parameters and flow distribution in an additative way.CONCLUSIONS: From this experimental study it is concluded that it is possible to combine dextran and DHE without inducing a circulatory overload. DHE increased tissue blood flow to the central nervous system.
Nonocclusive Coronary Thrombosis In Acute Myocardial Infarction
Authors: Frink R J 
Published: July 2018

TIn depth histologic study was performed on 23 patients who died during the acute phase or within the first three months following acute myocardial infarction. Six died suddenly and unexpectedly out of the hospital, five of these with the acute myocardial infarction unrecognized.The remainder were hospital deaths, five within the first 48 hours, 8 between 2-14 days, and 4 between 14 and 94 days. Five cases showed subendocardial infarction (SI). Four of these occuring out of hospital. The remaining 18 cases were transmural infarctions (TI). Sixteen of 17 hospital deaths exhibited TI.Special emphasis was given to a histologic search for coronary artery thrombosis, particularly nonocclusive thrombosis (NT), and fibrin fragments in the microcirculation. An acute coronary thrombus (ACT) was found in 22 of 23 (96%) cases. The ACT was totally occlusive in 12 of 23 (52%), and NT in 17 of 23 (74%). TI was associated with an acute occlusive thrombus (OT) in 11 of 18 (61%) , and with NT in 12 (67%). All five cases with SI had a NT. Seven (30%) exhibited both an OT and NT located in different coronary arteries. Six of these had TI.Fibrin fragments were located in the microcirculation of the myocardium in 15 of 23 (65%). These were associated with the fresh OT in 8 of 15 (53%) and with a NT in 12 of 15 (80%).Conclude:
1. NT is more common than OT in deaths associated with acute myocardial ’infarction
2. Fibrin fragments are present in the majority of patients with ACT, particularly NT.
3. SI was consistently asscoiated with NT.
4. OT and NT are frequently present in different arteries in the same heart.
5. NT are common in patients with TI.
Digital Capillary Pressure In Diabetics With Retinopathy
Authors: Tooke J E 
Published: July 2018

Patients with diabetes mellitus have an impaired capacity to di late their digital circulation. This impairment may contribute to the pathogenesis of digital ischaemia. In this study the capacity to di late digita l capillary circulation was assessed in diabetics with established microvascular disease (retinopathy) and compared with that found in diabetics who were clinically free of complications. Ten non-insulin-dependent diabetics (NIDDS) with severe retinopathy and 10 newly diagnosed NIDDS were studied in a constant temperature room maintained at 24°C following 30 minutes acclimatization. Nailfold capillary pressure (CP) was determined using a modified Landis microinjection technique. Mean ar ter ial limb CP was significantly (p<0.05) lower at 38.0 cm H2O in the patients with retinopathy compared to 47.2 cm H2 0 in the uncomplicated diabetics. Mean transcapilla ry pressure gradient in the patients with retinopathy was 6 cm H2O compared to 17 cm H2O in the uncomplicated group. There was no signif icant difference in the mean blood glucose level of the 2 groups at the time of pressure measurement. In the patients with retinopathy a r ter ial limb CP showed a negative correlation with blood glucose level (r = -0.6, p<0.05), but no correlation with duration of diabetes (r = +0.26, N.S.). These results support the contention that diabetic digital capillary perfusion is dependent on the level of blood glucose.The lower mean capillary perfusion pressure observed in the patients with retinopathy despite a similar blood glucose level to the uncomplicated patients suggests that the diabetic who develops retinopathy has a propensity for digital ischaemia that is independent of diabetic control.
Platelet Function Parameters In Diabetic Patients
Authors: Woods A I , Meschengieser S S , Sutton N M , Lazzari M A 
Published: July 2018

Abnormalities in platelet function tests have already been described in diabetic patients reflecting platelet hyperreactivity. An attempt to determine which of the tests seemed to be more affected in the diabetic population was done in a group of 34 diabetic patients (20 men and 14 women, age range 15-76). The tests performed included assay of Ristocetin Cofactor (McFarlane et al.) circulating
platelet aggregates (CPA) (Wu-Hoak) and platelet
aggregation induced by ADP in low concentration
(0.6 x 10-6M) and Bovine Factor VIII (0.001 U/ml). In matched controls only 3.5% had a positive aggregation induced by Bovine F VIII and with ADP (0.6 x 10-6M% ) the extent of maximum aggregation was 30%.In 15 of the 34 patients (44%) aggregation induced by ADP in high dilution was greater than 50% and this was the test more frequently affected. The level of Ristocetin Cofactor was increased (>160%) in 12 of 34 patients (35%) and aggregation induced by BF VIII was positive also in 12 patients (35%). The detection of CPA was positive in 9 patients (26%). Two patients had spontaneous platelet aggregation and in them all the other tests performed were also positive. Three patients had 3 of the tests altered, and 11 patients only had 2 affected tests.The assay more affected was the ADP induced aggregation followed by the Ristocetin Cofactor levels and BF VIII induced aggregation. The test less affected was the CPA. A correlation with clinical data will be mentioned.
Interest Of The Study Of Prekallikrein And Fibrinolysis In Diabetic Patients
Authors: Adjizian J C , Janody D , Droulle C , Jeunehomme G , Leutenegger M , Potron G 
Published: July 2018

For the comprehension of macro and microangiopathy diabetes physiopathology, it appeared to us interesting to study the contact factors and plasmatic fibrinolysis. The study covered 144 patients with all types of diabetes. Measurement of prekallikrein, plasminogen and fast α2 antiplasmin were carried out on chromogen substrates (S 2302 and 2251 - Kabi) using an automatic apparatus (Kern 0 Mat 2 Coultronics).At the same time, we studied the glycemia response, A1C hemoglobin and Willebrand factor.A dynamic and evolutive study was made on patients with an artificial pancreas. Results showed variations due to age, diabetes equilibration and in particular low rates of prekallikrein with a decrease of the fibrinolytic system in diabetic patients with macroangiopathy.
Partial Purification and Characterization of an ADP Phosphohydrolase from Human Plasma
Authors: Holmsen I , Holmsen H 
Published: July 2018

SummaryPlasma contains enzymes capable of dephosphorylating ADP, ATP and AMP (adenosine di-, tri- and monophosphate). In platelet-rich plasma these enzymes are important for the regulation of the levels of (platelet-aggregating) ADP and (aggregation-inhibitory) adenosine.Plasma ADPase and ATPase were studied at 1 (µM substrate concentration using an isotope technique. Both enzymes were precipitated from plasma at 45-65% saturation with (NH4)2S04 and emerged together by gel filtration on Sephadex G-200 and from DEAE-Sephadex (0.12-0.20 M Cl-, pH 8.2). In combination these procedures gave 1,500-1,800 times purification of ADPase relative to plasma. The purest fraction contained ATPase, ADPase and AMPase in a 0.17:1.00:2.92 proportion, quite different from their 5.34:1.00:5.34 proportion in plasma. Adenosine deaminase and adenylate kinase were not present in the purest fraction, whereas nucleoside diphosphokinase appeared to be present.The purified ADPase was stimulated by low concentrations of Mg2+ and Mn2+, whereas high concentrations were inhibitory. This inhibition could not be explained by an increase in the ionic strength. Ca2+ and Zn2+ were inhibitory at all concentrations used (0-3 mM). Lineweaver-Burke plots were linear for both ADPase and ATPase in the 0−4 x 10-5 M substrate range, and both enzymes had Km = 1.1 x 10−5 M. Increase of the substrate concentration above 4 x 10−5M gave deviation from MichaelisMenten kinetics, and Eadie-Hofstee plots indicated the presence of “high-Km” ADPase and ATPase. The latter enzymes were not studied.Déphosphorylation of 3H-ADP by purified “low-Km” ADPase was reduced by nonradioactive diphosphates of guanosine, inosine, cytidine and uridine in the same way as when nonradioactive ADP was used. Nonradioactive AMP also reduced dephosphorylation of 3H-ADP, whereas nonradioactive ATP did not.Cyanide, cysteine and tartrate inhibited “low-Km” ADPase whereas p-chloromercuribenzoate, p-chloromercuribenzoesulphonate and N-ethylmaleimide had no effect. EDTA inhibited the enzyme activity in a way that could not be abolished by excess Mg2+. Purified plasma “low-Km” ADPase thus appears to be an unspecific enzyme, as one and the same active site does not seem to distinguish between the base moiety of nucleoside diphosphates, and catalyzes hydrolysis of phosphate esters as well as pyrophosphate bonds. The relation between plasma ADPase and ATPase remains unclear.
Effects of Lead Acetate on Platelet Aggregation, Ultrastructure and Serotonin Release
Authors: Davis R. B , Holtz G. C 
Published: July 2018

SummaryThe effects of lead on blood platelet function and ultrastructure have been investigated. Lead acetate was injected intravenously in 27 rats and was added to rat and human platelet rich plasma in vitro. In vitro studies showed that concentrations of 2.5 × 10-3 M lead acetate reduced or blocked aggregation of rat and human platelets by adenosine diphosphate, collagen, and thrombin. Radioactive serotonin release from human platelets was inhibited by 10-4 M lead acetate. One hour after the injection of lead, platelet aggregation by thrombin was reduced, but platelet aggregation by adenosine diphosphate and collagen showed little change. Three days after lead, aggregation of platelets by collagen and thrombin was blocked and aggregation by adenosine diphosphate reduced. Thrombocytopenia was present 4 days after intravenous lead acetate. Electron micrographs of platelets showed that the mean number of mitochondria per platelet was increased, whereas alpha granules were reduced. Dense bodies were not significantly changed. Lead acetate affects platelet function in concentrations reported in human bone marrow in lead poisoning, and may relate to the binding of free sulfhydryl groups by lead.
Gel Filtration
Authors: Tangen O , Berman H. J , Marfey P 
Published: July 2018

SummaryHamster platelets have been separated from their plasmatic enviroment by means of gel filtration. This method of separation gave an excellent yield of platelets free of non-adsorbed plasma proteins.Gel filtered platelets (GFP), and platelets washed by repeated centrifugations and resuspensions (CP) were compared to each other and to platelets left undisturbed in their native plasma (PRP). Only slight morphological differences between the three platelet preparations could be detected by phase microscopy. In the concentration range of .28–.71 μM ADP, GFP, resuspended in PPP, showed the same degree of aggregation as did PRP. At lower concentrations of ADP, GFP aggregated to a lesser degree than did PRP. CP exhibited aggregation comparable to PRP only at higher concentrations of ADP (.71–1.42 (μM ADP). GFP also supported clot retraction to the same extent as did PRP.It would appear that gel filtration provides a new, gentle and rapid method for separation, from plasma, of platelets with activity very similar to that of platelets in PRP.