bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified Regimen Of Low Dose Heparin To Improve Prevention Of Venous Thromboembolism (VTE) After Major Surgery
Authors: Cade J F 
Published: July 2018

Low dose heparin, widely used in the prophylaxis of VTE, is incompletely effective in some groups of high-risk patients. For example, after major thoracic surgery for cancer, the incidence of scan-detected deep venous thrombosis (DVT) is reduced from 50-60% to 25-30% by heparin in a dose of 5,000 U bid.The present study compared the use of sodium heparin 7.500 U bid with 5,000 U bid in an attempt to reduce the incidence of DVT further. 71 patients (55 men, 16 women; mean age 61 years, range 40-84) having thoracotomy and resection for cancer were randomized to receive either treatment post-operatively. 125I-fibrinogen leg scanning was performed daily for 10 days.The incidence of DVT was similar in both treatment groups, being 25% with 5,000 U and 20% with 7,500 U (X2 = 0.25, P = NS). Most bilateral or extending DVT (5/6) occurred after 5,000 U and most transient DVT (3/4) after 7.500 U. The highest incidence of DVT was seen following oesophagogastrectomy (35%). No abnormal bleeding occurred in either group.Thus, increasing the dose of heparin did not significantly reduce further the incidence of DVT after major thoracic surgery. It is concluded 1) that further modification of low dose heparin regimens, including even individualization of therapy, is unlikely to be substantially more effective in such patients than present standard regimens, and 2) that, since the thrombogenic stimuli are only partly heparin-responsive, they are likely to be multifactorial and therefore more effectively treated with a combined prophylactic regimen (e.g. low dose heparin and blood flow enhancement) than with a single method.
Venous Stasis - Effect On Release Of Plasminogen Activators
Authors: Risberg B , Bylock A , Kjellström T , Stenberg B 
Published: July 2018

Venous stasis affects the fibrinolytic system. This is clinically utilized in the stasis test. Regional increase in fibrinolytic activity is found in the blood. By what mechanism the fibrinolytic activators are released is not known. It was the purpose of the present investigation to study the morphological and functional changes in the vessel wall after venous stasis.Methods: The infrarenal cavai vein in rats was occluded by a ligature. Biopsies were taken at different intervals from 2 to 8 hours after ligation. Morphological changes were studied with scanning electron microscopy. Tissue fibrinolytic activity was examined histochemically.Results: Stasis was followed by a progressive decrease in plasminogen activator activity in the intimai layer of the vessel wall. At 8 h the decrease was pronounced and the activity significantly lower than control values. The fibrinolytic activity in the adventitial layer was not influenced by stasis. The scanning electron microscopy studies demonstrated a progressive morphological change with destruction of the endothelial cells.Conclusions: Venous stasis was followed by progressive structural deterioration of the endothelial cells with release of plasminogen activators. Cellular degeneration might be responsible for enhanced release of activators during stasis.
The Density Distribution Of Intact Platelets Following Their Isolation From All Other Blood Constituents
Authors: Shaw T , Martin J F , Chesterman C N , Peninqton D G 
Published: July 2018

A method for measuring the buoyant density of platelets which function normally after the procedure, has been developed and critically compared to published methods.Following velocity sedimentation into a gradient of polyvinyl pyrrol 1idone-coated colloidal silica particles (Percoll) at physiological pH and osmolarity, 90% (n=10, SD=10) of the whole blood platelet population was recovered with leukocyte contamination of .002% (n=10, SD=.001); erythrocyte contamination was less.After centrifugation to equilibrium through a second continuous linear Percoll gradient, platelet density showed a Gaussian distribution about a mode of 1.0645 g/ml. (n=13, SD=.0015). Leakage of β thromboglobulin (βTG), lactic dehydrogenase (LDH) and serotonin into the gradients was negligible. Intracellular LDH, serotonin and total protein correlated closely with platelet count, but βTG distribution was skewed towards the denser fractionsPlatelets recovered from the second gradient showed normal aggregation patterns and produced thromboxane B2 and secreted βTG when stimulated by thrombin or arachidonic acid. Addition of plasma was necessary to produce ristocetin-and ADP-induced aggregation, and significant radioactivity was not associated with platelets isolated from blood to which 125I had been addedUnder physiological conditions, arabinogalactan II (Stractan) caused more spontaneous leakage of α-and dense- granule markers than did Percoll. Platelets taken from different interfaces of a discontinuous Stractan gradient were seen to contain platelets of the full density range when they underwent equilibrium centrifugation in linear continuous Stractan or Percoll gradients.True buoyant density of minimally altered platelets has been measured by this new technique.
In Vitro And In Vivo Studies On CP 1415 S A New Platelet Antiaggregating Compound
Authors: Biaqi G , Niebes P , Roba J , Lambelin G 
Published: July 2018

CP 1415 S is a new phenyloxypropanolami ne derivative.In vitro CP 1415 S inhibits aggregation of human platelets inaucedby collagen (EC50 9 μM) or arachidonic acid (EC50 12μM). It also primary and secondary phases of ADP, thrombin and epinephrine induced platelet aggregation. Effective concentrations are in the same range (10 μM) as concerns the secondary aggregation and higher as concerns the primary phase. In presence of 50 μM CP 1415 S, platelet aggregation is fully prevented. Addition of CP 1415 S to platelets maximally aggregated by ADP causes disaggregation in a dose dependent way (EC50 50 μM); similar effect is observed only with prostacyclin (PGI2) and PGE1
Ex-vivo, the antiaggregating properties of CP 1415 S have been demonstrated after single oral administration to rats and Rhesus monkeys (minimal effective dose 10 and 20 mg/kg respectively). After repeated oral administrations, antiaggregating activity was observed from 3 mg/kg/day in rats.In vivo, in rats, using the tail transsection model, bleeding time was significantly (p < 0.01) prolonged by 10 mg/kg P.o. CP 1415 S or ticlopidine. CP 1415 S given orally up to 100 mg/kg had no effect on prothrombin time. CP 1415 S at 1 mg/kg p.o., 2 hours before testing, protected rats (p < 0.001) against acute thrombocytopenia induced by i.v. injection of ADP whereas acetyl salicylic acid and dipiridamole were inactive at 100 mg/kg and ticlopidine was unsignificantly active. Prostacyclin-like substance production by rat vascular tissue, measured by platelet aggregation bioassay, was not affected in rats after 5 or 10 mg/kg i.v.CP 1415 S appears to be a potent inhibitor of platelet aggregation in vitro and ex-vivo. Its ability to disaggregate platelets is currently tested in in vivo models of thrombosis.
Effect Of Prostacyclin (PGI2) On Human Platelet Aggregation And Secretion
Authors: Chesney C M , Pifer D D 
Published: July 2018

PGI2,which increases platelet cAMP(Prostaglandins 13: 389,1977),is a potent inhibitor of aggregation and secretion .We stidued the time course of the same return of platelet function after exposure of platelets to PGI2.Sepharose 2B columns were equilibrated with Tyrode’s albumin buffer, pH7.5 (no Ca2+) containing PGI2 (534nM). Platelet rich plasma was applied and eluted with the same buffer. The filtered platelets(GFP) were then subsampled hourly after elution from the column. Fibrinogen was added to finel concentration of 1.7mg/ml. Platelet aggregation(PA) and release of 14C serotonin (5HT),platelet factor 4(PF4), and factor V (FV) were assayed after stimulation of the platelet by collagen(C), ADP,epinephrine(E), arachidonic acid(AA) and ionophore A23187(I). Data representative of 5 separate studies follow.I(20μg/ml) induced PA was 76%(Ohr),52%(1hr) and 61%(2hr and beyond). Release of 5HT, FV,and PF4 were 60%,1.89u,and 7.97 yg/10 pit, respectively, at time 0 and increased progressively, reaching a plateau at 2 hr. AA(500μg/ml) was 10%(0hr),30%(2hr),68%(3hr) and 8%(4hr). Release of 5HT paralleled PA but release of FV and PF4 remained suppressed for 4 hrs. In contrast α-granule (PF4 and FV)release by C(μg/ml)increased as PA increased while dense granule secretion remained suppressed. PA as well as a and dense granule secretion by ADP (10μM) were minimal during 4 hrs. PA and FV secretion by E (55μM) also remain inhibited for 4 hrs. In spite of this normal dense granule release occurred initially and declined progressively over 4 hours.
The Regulatory Role Of Camp In Induction Of Human Platelet Receptor For Fibrinogen
Authors: Graber S E , Hawiger J 
Published: July 2018

Membrane receptor for fibrinogen plays an essential role in adhesion and aggregation of human platelets by allowing fibrinogen to bridge two or more platelets together. Whereas in normal, unstimulated platelets fibrinogen receptor is not available, it becomes mobilized upon stimulation of platelets with thrombin, ADP, and other stimuli. The mechanism(s) regulating availability of membrane receptor for fibrinogen remains unknown. Following our recent demonstration that prostacyclin (PGI2) prevents mobilization of fibrinogen receptor by thrombin and ADP (Nature 1980, 283,195), we investigated the relationship between cAMP levels and fibrinogen receptor availability. Platelets separated from plasma proteins were briefly exposed to a low thrombin concentration (0.05 U/ml) followed by hirudin to inactivate free thrombin. Binding of 125I-fi- brinogen and cAMP levels were determined in parallel samples. A dose-dependent rise in platelet cAMP levels from 3.3 pM to 10.3 pM/108 platelets in response to PGI2 (3×10-9M - 3×108M) was accompanied by a corresponding inhibition of 125I-fibrinogen binding. The degree of the cAMP increment correlated with binding inhibition (r=0.96). The inhibition of 125I-fibrinogen binding by PGI2 was sustained up to 120 min and was paralleled by a persistent rise in cAMP level. Stimulation of platelet cAMP synthesis “from within” by a ribosylation of the nucleotide regulatory component with subunit A1 of cholera toxin also increased cAMP levels and inhibited fibrinogen receptor mobilization.These results provide evidence that “up and down” regulation of fibrinogen receptor in platelets is linked to changes in cAMP levels induced by different types of adenyl cyclase antagonists and agonists.
Malondialdehyde Formation Induced By Different Collagens
Authors: Balleisen L , Rauterberg J 
Published: July 2018

To get close information about the characteristics of collagen induced MDA formation, platelet aggregation was induced by collagen type I, III a. V in dissolved and fibrillar form and by methylated type I collagen. The MDA formation was measured in the course of aggregation. In case of Meth.c. MDA production is induced also if under certain incubation conditions no aggregation is detectible.During the pl.aggr. induced by dissolved c. some MDA production was seen before the slope of the aggregation curve increased. Parallel to the increasing slope MDA increased fast, and some further increase over a 30 min. period was observed. For fibrillar and meth.c. MDA formation begins just with the increasing slope and reaches a stable plateau. In case of meth.c. the plateau is reached immediately after the maximum of aggregation occurred, in that of fibrillar c. some min. after maximal aggregation. For meth.c. the results obtained in the incubation system were comparable to that in the aggregation system.For meth.c. the kinetics of MDA formation in both systems were further defined. In both systems a concentration dependent saturation kinetic was obtained. In the aggregation system the concentration dependent increase of MDA formation was somewhat faster as in the incubation system and reached its saturation level at a lower collagen concentration.From the increasing and long lasting MDA formation induced by the interstitial collagens we might speculate that in vivo the stimulating activity of the collagens may work for a long time in conditions where the prostacyclin production of the vessel wall is decreased. The characteristics of MDA formation induced by meth.c. suggest that this c. may be a good tool for in vitro studies.
Heparin Resistance In Thrombocytosis And Erythrocytosis
Authors: Wajima T , Maloney T R 
Published: July 2018

Heparin is generally considered to be the drug of choice in the treatment of venous thromboembolism. In most patients an adequate anticoagulant effect can be achieved with doses between 20,000 and 30,000 units/24 hrs. Increased heparin requirement or “resistance to heparin treatment” is seen in patients with massive deep vein thrombosis (DVT), pulmonary emboli, severe AT-III deficiency, or some cancer patients.We encountered heparin resistance in 7 patients, 3 with idiopathic thrombocytosis and 4 with recurrent CVA’s and DVT associated with relative erythrocytosis. In these patients, a therapeutic prolongation of APTT was not achieved by usual doses of heparin, and thromboembolic episodes occurred despite administration of heparin in doses sufficient to prolong APTT to the therapeutic range. The initial PT, PTT, and TT in these patients were normal. Protamine Sulfate test and Ethanol gelation test were negative. Fibrinogen and Factor VIII levels were elevated in all patients.AT-III levels (by immunodiffusion method) were normal.Liver and renal function tests were normal. In the patients with idiopathic thrombocytosis, platelet counts were over 1,500 × 109/l. Platelet aggregation by ADP, epinephrine and collagen was normal or slightly increased. Patients with idiopathic thromocytosis were treated with nitrogen mustard and/or busulfan to reduce the platelet count, then treated with heparin.Patients with relative erythrocytosis had elevated Hct (>55), Hgb (>18 gm%) and whole blood viscosity (>6 with normal <4), but normal red cell mass; plasma volumes were markedly decreased. Platelet counts were normal to slightly increased. Platelet aggregation studies were normal. These patients were treated with hydration and plebotomy to reduce the Hct below 45 and restore normal whole blood viscosity, then with heparin with good clinical results. Correction of thrombocytosis and erythrocytosis is important in optimal anticoagulation.
Hypothesis On The Role Of Platelet Proteins In Atherogenesis
Authors: Farrell R J 
Published: July 2018

Two alternative mechanisms are currently proposed for the development of atheromatous plaques:
(i) accumulation of protein and lipid material from plasma as a result of haemorrheological forces (Copley, 1979);
(ii) proliferation of endothelium in response to a platelet-derived growth factor (PDGF) (Ross, Glomset and Harker, 1977).The former theory implies a continuous process affecting all endothelial cells but varying with anatomical location and other haemorrheological factors. The latter theory proposes the release of PDGF during platelet aggregation and implies an essentially localised process, probably initiated by endothelial injury. Both theories are supported by substantial experimental evidence.This hypothesis aims to reconcile these two theories by emphasising recently discovered properties of platelet proteins:
(i) platelet factor hi having anti-heparin activity, may favour thrombogenesis by inhibiting physiological analogues of heparin;
(ii) β-thromboglobulin, by inhibiting formation of prostacyclin, may predispose to platelet aggregation and mural thrombus formation;
(iii) PDGF, while normally functioning in the response to intimal injury, may when it is inappropriately present lead to intimal hyperplasia and plaque formation.It is proposed that these proteins enter endothelial cells, as governed by haemorrheological factors. The functional (rather than structural) changes so induced then predispose to platelet aggregation and thrombosis with furtner aggregation and ultimately to atherogenesis.
Therapeutic Blood Pressure Reduction Related To Coronary Haemostasis And Acute Myocardial Infarction
Authors: Stewart I McD G 
Published: July 2018

The purpose of this paper is to summarize some clinical observations upon the relation between therapeutically reduced hypertensive blood pressure and acute myocardial infarction (MI) together with sudden cardiac death (SD), and to invite expert advice upon the manner and extent to which the findings may derive from the effects upon the clotting process of impaired blood-flow through coronary arteries partially obstructed by atheroma, a pathogenic development that, I would suggest, owes little or nothing, at this site, to raised blood pressure.In a 6-year study on 169 severe hypertensives under treatment the relative risk of infarction in the patients with final diastolic pressures observed before infarction or its avoidance (FDP) in the range <90mm/Hg (Phase IV) was more than five times greater than in patients with FDP in the range 100-109 (p<0.01), the risk starting to rise again in range 110-114, with similar bimodality in the FDP ranges 76-94, 95-109 and 110-140, the ratios of infarction to numbers being respectively 10/41, 4/52 and 15/70..It is concluded that, in the presence of coronary atheroma hypertension tends to precipitate MI and SD at each extremity of the pressure scale and that hypotensive therapy lowers the incidence of these events at high presure, only for this benefit to be lost if pressure reduction be pressed too far towards “normality”, an imprecise exercise that may from time to time induce severe impairment of coronary perfusion followed by critical myocardial ischemia, arrhythmia and finally MI and SD.How do the recondite, and to most clinicians mysterious, processes of thrombosis and haemostasis respond.to the situation created by this haemodynamic failure? In what ways may blood viscosity, platelet aggregation, and indeed the clotting-factors themselves, contribute to the potentially fatal clinical outcome? And to what extent may the threat posed by these wayward influences be restrained by modern treatment?
A Comparison of Methods for Platelet Lysis and the Isolation of Platelet Membranes
Authors: Barber A. J , Pepper D. S , Jamieson G. A 
Published: July 2018

SummaryFour methods of platelet lysis, namely, sonication, nitrogen cavitation in a high pressure bomb, the use of a “no clearance” tissue homogenizer and simple osmotic lysis have been compared in terms of ease, effectiveness and reproducibility in comparison with a method involving the hypotonic lysis of glycerol-loaded platelets ; the most extensive studies have been carried out using sonication and the tissue homogenizer. In order to reduce the degree of fragmentation of the platelet membrane, the use of surface stabilizing agents such as zinc chloride and fluorescein mercuric acetate have also been investigated. Membranes obtained in these different ways have been isolated by centrifugation on continuous or discontinuous sucrose density gradients and the resulting fractions compared by electron microscopy, enzymatic activity, chemical analysis and hemagglutination inhibition. The glycerol-lysis technique was found to be most effective (85%) in untreated platelets and the degree of lysis was considerably reduced in platelets hardened by the zinc chloride method. Ultrastructural studies showed that the largest membrane fragments (175 nm) were obtained by glycerol lysis of untreated platelets and that smaller vesicles (50-100 nm) were obtained by the other techniques even following membrane stabilization. Double membrane structures were obtained in several of these methods.
The Role of Hageman Factor in Disseminated Intravascular Coagulation Induced by Septicemia, Neoplasia, or Liver Disease
Authors: Mason J. W , Colman R. W 
Published: July 2018

SummaryThe human plasma kallikrein system was assayed in patients with disseminated intravascular coagulation (DIC) induced by gram negative bacteremia, neoplasia and severe liver disease. Only the patients with gram negative septicemia showed activation of plasma kallikrein with concomitant depletion of kallikreinogen and kallikrein inhibition. Since the activation of kallikrein is a function of activated Hageman factor, it is suggested that in DIC associated with gram negative septicemia, Hageman factor activation may be involved in the DIC. In DIC associated with neoplasia or liver disease lack of Hageman factor activation should be considered.
Assessment of Damage to Human Platelets after Aggregation and Other Injuries by Microscopic Observation and Estimation of Serotonin Uptake
Authors: Zbinden G , Mehrishi J. N , Tomlin S 
Published: July 2018

SummaryThe severity of platelet damage induced by hyper- and hypotonic NaCl solutions and freezing and thawing was assessed by microscopic evaluation and measuring inhibition of 5-HT uptake. The same techniques were used to quantitate the effects of aggregating agents. The positively charged macromolecules PS, Poly-L und Poly-O reduced the net negative surface charge as determined by microelectrophoresis, caused platelet aggregation and inhibited 5-HT uptake. The damaging effects of Poly-L and Poly-O were more severe and more closely related to concentration than that of PS. The negatively charged macromolecules Poly-IC and NaPS increased the anodic electrophoretic mobility. Poly-IC and heparin caused a low degree of platelet clumping and no inhibition of 5-HT uptake. NaPS produced severe platelet damage with extensive clumping and complete inhibition of 5-HT uptake. Na laurate had the same effect, but did not alter electrophoretic mobility. ADP caused concentration-dependent platelet aggregation and inhibition of 5-HT uptake. The effects of ADP and NaPS were compared in agitated and non-agitated platelet samples containing identical concentrations of the 2 compounds. Agitation was found to increase the degree of platelet clumping and to reduce 5-HT uptake.
Intestinal Alkaline Phosphatase as a Thrombogenic and Platelet-Altering Factor in Rabbits
Authors: Iatridis S. G , Ferguson J. H , Iatridis P. G 
Published: July 2018

SummaryPurified intestinal alkaline phosphatase (AlPh), 10 mg/kg, was injected intravenously into rabbits. In normal animals, 1 min post-injection, averaged samples showed platelet count decreases to 50% of control values in whole blood and to 20% in centrifuged “platelet-rich” plasma. Small or large platelet aggregates were noted in the counting chambers, and a glass-bead platelet-adhesiveness test gave values at least twice that in the controls. The platelet changes were paralleled by shortening of an ear-lobe bleeding-time test and by an equally temporary shortening of the r and h values in thrombelastograms (TEG) of fresh whole blood. A very significant correlation, in the 1 min data, was with 4 + thrombosis in 30 min occluded test segments of mesenteric veins. Screening tests of coagulation and fibrinolysis were not significantly altered, and the same was true of various clotting factor assays, except perhaps for small changes which might be attributable to limited local clot formation.15 min post-injection, platelet counts had risen again, no aggregates were noted, the TEG normalized, and the thrombosis test was negative.In dicumarolized rabbits, the AlPh injections still elevated the serum alkaline phosphatase and caused the platelet alterations, but now without the thrombophilic changes.Electrophoretic studies of AlPh isoenzyme distribution suggested that the significant post-injection elevations were not those in the total serum or beta-globvlin enzyme levels, but in a specific “gamma” isoenzyme, migrating cathodic to the ß-globulins.The significance of the present experiments to the basic understanding and testings of thrombotic states is briefly discussed.