bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Malondialdehyde in Cardiovascular Disease: Effect of Prosthetic Heart Valves and Cardioactive Drugs on Production
Authors: Sullivan Jay M , Taylor J Charles , Samaha Joseph K , Lamar Patti , Patrick Darrell R ,   With the technical assistance of
Published: July 2018

SummaryMalondialdehyde (MDA), a product of platelet lipid peroxidation, was measured in human platelet-rich plasma. Levels of 3.19 n moles/109 platelets ± 0.40 S.E. in 11 patients with prosthetic heart valves were elevated (p<0.25) compared to 17 normal subjects (2.09 ± 0.13 n moles/109 platelets). Reduced production (1.44 ± 0.28 n moles/109 platelets, p<0.5) was found in 10 patients with unstable angina. Normal levels were found in patients with mitral stenosis, cardiomyopathy or hypertension. Usual serum levels of drugs used in cardiac treatment reduced MDA levels as follows: acetaminophen, 47% (p<.01); aspirin, 58% (p<.05); furosemide, 32.6% (p<.005), and sulfinpyrazone, 41% (p<.05). Digoxin, dipyridamole, heparin, hydrochlorothiazide, lidocaine, nitroglycerin, procainamide, propranolol, quinidine, or warfarin had no significant effect at therapeutic concentrations. None of the drugs explained the enhanced production in patients with prosthetic valves while analgesic therapy could explain the decreased levels in other cardiacs. The half-time of platelet survival, measured by suppression of malondialdehyde production, was 3.2 ± 0.24 days in 9 normal subjects but could not be measured reliably in most patients because of multiple drug therapies. We conclude that the blood platelets of patients with prosthetic heart valves differ from those of normal subjects in their capacity to release malondialdehyde after stimulation with n-ethylmaleimide. Additionally, we find that inhibition of malondialdehyde production by several pharmacologic agents limits the usefulness of this method for the measurement of platelet survival in cardiac patients.
Reactivity of a Hereditary Abnormal Antithrombin III Fraction in the Inhibition of Thrombin and Factor Xa
Authors: Tran T H , Bondeli C , Marbet G A , Duckert F 
Published: July 2018

SummaryTwo different AT-III fractions were purified from the plasma of a patient with recurrent superficial thrombophlebitis. The abnormal AT-III fraction (A-AT) was compared to the normal AT-III fraction (N-AT) in the inhibition of thrombin and factor Xa. Without heparin, both inactivate proteases in a similar manner and at the same rate. However, at low heparin concentration the thrombin inhibition proceeds more slowly with A-AT than with N-AT. At high heparin concentration the difference between A-AT and N-AT becomes very small. The inhibition of factor Xa follows a similar pattern. It is suggested that the heparin binding site of A-AT differs from that of N-AT resulting in a decreased heparin cofactor activity.
Platelet Function in Acute Myocardial Infarction Patients Compared with Controls
Authors: O'Brien John R , Etherington Michael D , Shuttleworth Robert D , Calwell William H 
Published: July 2018

SummaryA considerable number of tests were carried out comparing 33 patients with acute myocardial infarction (MI), 13 patients with chest pain (CP) and 47 controls. There was some evidence that the plasma platelet factor 4 (PF4) was different in the three groups. The heparin neutralizing activity (HNA) of platelet poor plasma was increased in the MI patients relative to the controls and the intra-platelet HNA was decreased. Malondialdehyde (MDA) formation by platelets maximally stimulated by thrombin was decreased in MI whilst the plasma 5-hydroxyindoles (5HIs) in MI was greatly increased. The acute phase proteins α1 acid glycoprotein and fibrinogen were significantly raised in MI. The results in the CP group were intermediate between the MI and the controls. These findings define more precisely the changes in acute MI and are relevant to the concept of exhausted platelets.
Kinetics and Fate of 111Indium-Oxine Labelled Blood Platelets in Asplenic Subjects
Authors: Heyns Anthon duP , Lötter Matthys G , Badenhorst Philip N , Reenen Otto van , Pieters Henry , Minnaar Phil C 
Published: July 2018

SummaryThe survival, tissue distribution and fate of 111Indium-oxine labelled autologous platelets was studied in four asplenic subjects with serial blood sampling, scintillation camera and computer-assisted imaging. Mean 111In-platelet recovery in the circulation was 89 ± 13% (± 1 SD). Platelet survival curves fitted a linear function best and was 238 ± 41 h. The shape of the survival curves of normal and asplenic subjects differed: in the asplenic subjects the curve was linear whereas that of normal subjects was significantly more curvilinear if analyzed by least squares computer fitting to a gamma function. Early hepatic 111In-activity was significant and transient and ascribed to the "collection injury". As labelled platelets disappeared from the circulation, 111Inactivity in the liver increased progressively and linearly to reach 42.5 ± 14.1 % of whole body activity at 240 h. Radioactivity also accumulated in the bone marrow, but could not be demonstrated in the vasculature of the lower limbs. These results would indicate that in asplenic subjects the major sites of destruction of senescent platelets are the liver and bone marrow.
Soluble Fibrin Complexes and Fibrinogen Heterogeneity in Diabetes mellitus
Authors: Tsianos E B , Stathakis N E 
Published: July 2018

SummaryThe presence of soluble fibrin complexes (SFC) measured by gel filtration of plasma on 4% agarose columns, fibrinogen heterogeneity on 3.5% SDS-polyacrylamide gels and the concentrations of several plasma proteins were evaluated in 39 patients with diabetes mellitus (DM) and 19 matched control subjects. A small but significant increase of SFC was found in DM (p<0.01). On individual basis 51.2% of the patients had increased SFC (>M + 2 SD of the controls). Polyacrylamide gel electrophoresis of the SFC showed no evidence of cross-linking or proteolysis. Plasma clots formed in the presence of EDTA and trasylol were analysed in SDS-polyacrylamide gels in a normal and two lower molecular weight fibrin bands (band I, II, III). The percentage of band I fibrinogen was in diabetics (65.3 ± 4.7%) lower than that of the controls (71.8 ± 4.5%) (p < 0.01). Fibrinogen levels, antithrombin III, α1-antitrypsin, α2-macroglobulin and plasminogen were significantly increased in DM. We suggest that in DM there is an enhancement of intravascular fibrin formation and accelerated fibrinogen degradation to lower molecular weight forms.
Predictive Value of Decreasing Antithrombin III in Deep-Vein Thrombosis
Authors: Andreasen Thorkild Lund 
Published: July 2018

SummaryAntithrombin III (At-III) was measured at the time of admission and two days later in 131 patients laid up in a coronary care unit. The patients were examined for deep-vein thrombosis (DVT) clinically and by means of 125I-fibrinogen scanning. 19 patients developed DVT. In 11 subjects with and 25 without DVT At-III decreased more than 10%. And in 7 with and 17 without DVT At-III decreased more than 15%. One person with DVT had subnormal At-III. By using decrease of At-III or subnormal initial At-III to predict DVT the following predictive value (PV) were found. Decrease ≤ 10%, PV pos.= 0.32 and PV neg. = 0.93. Decrease ≤ 15%, PV pos. = 0.32 and PV neg. = 0.90. The positive predictive values obtained were too low to let decreasing At-III give occasion for prophylactic anticoagulant treatment.
Evaluation of the Effect of Betapropiolactone/Ultraviolet Irradiation (BPL/UV) Treatment of Source Plasma on Hepatitis Transmission by Factor IX Complex in Chimpanzees
Authors: Prince Alfred M , Stephan W , Brotman B , Ende M C van den 
Published: July 2018

SummaryTo evaluate the safety of a β-Propiolactone/Ultraviolet (BPL/UV), irradiated Factor IX complex preparation we inoculated 8 chimpanzees with 25 units Factor IX/Kilo from a pool of 5 production lots which had been treated in this manner. These lots were derived from approximately 1,000 donors. Animals were followed with weekly tests for hepatitis B serologic markers and transaminases, and biweekly liver biopsies, for 6 months. No evidence of transmission of hepatitis B, or non-A, non-B viruses was observed.To further evaluate the BPL/UV procedure a plasma pool was intentionally contaminated with hepatitis B virus and one half of the pool treated with BPL/UV. Factor IX complex was isolated from the treated and untreated pools and each was inoculated into 4 chimpanzees. The Factor IX derived from untreated plasma infected all four animals with an average incubation period of 10.5 weeks, whereas that prepared from BPL/UV treated plasma infected only one of four animals with an incubation period of 21 weeks. These results were interpreted as suggesting that BPL/UV can inactivate approximately 99.9% of hepatitis B virus infectivity.
Effects of Halothane on Platelet Function
Authors: Dalsgaard-Nielsen J , Gormsen J 
Published: July 2018

SummaryHuman platelets in platelet rich plasma (PRP) incubated at 37° C with 0.3–2% halothane for 5–10 min lost the ability to aggregate with ADP, epinephrine and collagen.At the same time uptake and release of 14C-serotonin was inhibited. When halothane supply was removed, platelet functions rapidly returned to normal. However, after high concentrations of halothane, the inhibition of platelet aggregation was irreversible or only partially reversible.The results suggest that halothane anaesthesia produces a transient impairment of platelet function.
Sialic Acid Dependent Polypeptide Chain Heterogeneity of Human Fibrinogen Demonstrated by Two-Dimensional Electrophoresis
Authors: Kuyas Cemal , Haeberli André , Straub P Werner 
Published: July 2018

SummaryHuman fibrinogen was compared with asialofibrinogen by two-dimensional electrophoresis to evaluate the contribution of sialic acid to the heterogeneity of the γ- and Bβ-polypeptide chains.Reduced fibrinogen showed three major variants for both the γ- and Bβ-chains. In addition two minor γ-bands with a more acidic isoelectric point than the normal γ-chains were observed. Electrophoresis in the second dimension (SDS) suggests that these most acidic bands are γ-chain-variants with a higher molecular weight. In asialofibrinogen only two predominant variants with more alkaline isoelectric points were present in each chain type.It is concluded that enzymatic removal of sialic acid partially reduces the heterogeneity of the γ- and Bβ-polypeptide chains of human fibrinogen, but additional sources producing charge heterogeneity must be sought.
An Evaluation of APTT Monitoring of Low-Dose Heparin Dosage in Hip Surgery
Authors: Poller L , Taberner D A , Sandilands D G , Galasko C S B 
Published: July 2018

SummaryThe activated partial thromboplastin time has been used to monitor the effects of low-dose subcutaneous heparin in two groups of patients undergoing hip surgery. The study was performed to determine the degree of anticoagulation required to protect these high-risk patients from post-operative deep vein thrombosis. The patients were randomised to receive a fixed regimen of subcutaneous calcium heparin (5,000 units eight-hourly) or a dose of calcium heparin monitored by maintaining the standardised APTT at 50 secs. In the adjusted group the APTT achieved the target figure in 46% of observations compared to 27% in the fixed group (p μ0.005). Nine patients showed positive 125I-fibrinogen scans and in all, the APTT was below the target value the day before the scan became positive. In contrast, in six of the nine thrombotic patients heparin was detected by antifactor Xa clotting assay. The APTT, therefore, appears to give a better guide to the antithrombotic effect of heparin than the antifactor Xa clotting assay. These preliminary observations suggest that prolonging the standardised APTT method to just above 50 secs improves prophylaxis in high-risk cases. Furthermore, an increased dose of heparin is required than is provided during the conventional low-dose regime of 5,000 units tds. With regular control using the standardised APTT, increasing the dose to the target value does not increase postoperative haemorrhage.Further studies with larger numbers of patients are required in order to show a significant reduction in the incidence of postoperative deep vein thrombosis in hip surgery patients receiving low-dose adjusted heparin.
Plasma Fibrinopeptide A and Beta-Thromboglobulin in Pre-Eclampsia and Pregnancy Hypertension
Authors: Douglas J T , Shah M , Lowe G D O , Belch J J F , Forbes C D , Prentice C R M 
Published: July 2018

SummaryIncreased plasma levels of β-thromboglobulin (βTG) and fibrinopeptide A (FPA), markers of platelet release and thrombin generation respectively, were measured in normal women, women taking oral contraceptives, normal pregnancy and pregnant women with hypertension or pre-eclampsia. No significant increases in βTG or FPA were found in women taking oral contraceptives. Significantly increased concentrations of βTG, but not FPA, were found in normal pregnant women in the second and third trimester of pregnancy when compared with nonpregnant age-matched controls. In eleven women with pregnancy hypertension and thirteen women with pre-eclampsia significantly elevated levels of both βTG and FPA were found when compared with age, parity and gestation-matched pregnant controls. Although the mean value for both βTG and FPA in the group with pre-eclampsia was higher than the group with pregnancy hypertension, the difference was not statistically significant. These findings provide additional evidence that pre-eclampsia and pregnancy hypertension are associated with activation of the coagulation system and the platelet release reaction.
Successive Factor VIII Doses for a Haemophiliac Undergoing Major Surgery Calculated on a Microcomputer
Authors: Duncan Bruce , Lloyd John , Lesnikowski Elizabeth 
Published: July 2018

SummaryDoses of factor VIII to be infused into a haemophiliac undergoing major surgery were calculated on a micro-computer. The degree to which the particular patient responded to infused factor VIII and the rate at which it decayed were estimated by two pre-operative experiments. Plasma levels of factor VIII were predicted over fourteen days during which time the patient was infused with 53,000 iu. A continuous plot of predicted values with time was displayed on a video monitor. The predicted values showed good agreement with assay results.
A Comparison of the Bethesda and New Oxford Methods of Factor VIII Antibody Assay
Authors: Austen D E G , Lechner K , Rizza C R , Rhymes I L 
Published: July 2018

SummaryA collaborative trial has been carried out under the auspices of the International Committee on Thrombosis and Haemostasis to compare the Bethesda and New Oxford methods of antibody assay. It was found that errors between laboratories were much greater than those within laboratories and each laboratory had a bias whereby it always rated samples high or low with respect to the other laboratories. However there was excellent agreement in the order in which laboratories ranked antibody samples and if a standard antibody sample could be provided there would be a significant improvement in numerical agreement between laboratories. On average, for this exercise, a result for a given sample in Bethesda units was 1.21 times the result in New Oxford units although it must be stressed that this ratio could vary from sample to sample.
Biochemical and Metabolic Aspects of Platelet Dysfunction in Chronic Myeloproliferative Disorders
Authors: Pareti F I , Gugliotta L , Mannucci L , Guarini A , Mannucci P M 
Published: July 2018

SummaryFifty-two patients with chronic myeloproliferative disorders (13 with polycythemia vera; 23 with primary thrombocythemia; 6 with myelofibrosis and 10 with chronic granulocytic leukemia) had low platelet levels of adenine nucleotides and serotonin and abnormal uptake and storage of the amine. The storage pool deficiency was confined to the substances contained in the platelet dense bodies, because α-granule and lysosome markers were present in normal amounts. In chronic granulocytic leukemia the storage defect was usually less marked but was accompanied by a decreased formation of thromboxane B2 and normal platelet aggregation in response to arachidonic acid. There was no clearcut relationship of these biochemical abnormalities to prolongation of bleeding time or to thrombotic and hemorrhagic symptoms. The defect was still present in 15 patients after treatment had returned the cell counts to the normal range. Normal levels of 5HT and adenine nucleotides were observed in 8 patients whose platelet counts were high after splenectomy for non-hematological reasons. These findings suggest that biochemical abnormalities are related to the presence in the bone marrow of abnormal clones, resulting in the production of defective platelets.
Effect of cAMP Phosphodiesterase Inhibitors on ADP-Induced Shape Change, cAMP and Nucleoside Diphosphokinase Activity of Rabbit Platelets
Authors: Lam S C-T , Guccione M A , Packham M A , Mustard J F 
Published: July 2018

SummaryThe effects of cAMP phosphodiesterase inhibitors on ADP-induced shape change and cAMP concentrations have been studied. Caffeine (10 mM), theophylline (8 mM), dipyridamole (0.2 mM), or papaverine (0.05 mM) prevented the shape change of washed rabbit platelets induced by 0.4 μM ADP. At these concentrations, none of these cAMP phosphodiesterase inhibitors increased 14C-cAMP in platelets in which the cytoplasmic adenine nucleotides had been labelled with 14C-adenine. By a protein binding assay, only papaverine by itself increased platelet cAMP above its basal level. These results indicate that two pools of cAMP may exist in platelets. Both methods showed that stimulation of platelet adenylate cyclase with PGE1 (1 μM) resulted in an increase in platelet cAMP and all these cAMP phosphodiesterase inhibitors potentiated this increase caused by PGE1. By themselves, some of these compounds may act through mechanisms that do not involve platelet cAMP. The effects of these cAMP phosphodiesterase inhibitors on platelet nucleoside diphosphokinase (NDK) activity were also investigated. At concentrations that prevented ADP-induced shape change, papaverine and dipyridamole had no effect on the formation of 14C-ATP from 14C-ADP by washed rabbit platelets. The methylxanthines partially inhibited NDK activity of washed rabbit platelets and of isolated platelet membranes, probably due to the structural similarity between the adenine ring of ADP and these substances. However, adenine (8 mM) inhibited ADP-induced shape change and platelet NDK activity but was a less effective inhibitor of ADP-induced platelet aggregation. Thus it seems unlikely that interference with platelet NDK or the ADP receptor is the major mechanism by which the methylxanthines inhibit platelet functions.
A Comparison of Pentosan Polysulphate (SP54) and Heparin I: Mechanism of Action on Blood Coagulation
Authors: Fischer A-M , Barrowcliffe T W , Thomas D P 
Published: July 2018

SummaryThe effects of SP54 on inhibition of thrombin, factor Xa and factor IXa, in the presence and absence of antithrombin III (At III), have been examined and compared to those of heparin. SP54 potentiated inhibition of thrombin and Xa by purified At III, but crossed immunoelectrophoresis data indicated that these effects were mediated by binding to the enzyme, rather than to At III. Relatively high concentrations of SP54 were required for inhibition of thrombin and Xa in plasma, but at concentrations less than 2 μg/ml there was a marked suppression of the intrinsic activation of factor X. This effect was shown to be independent of At III, and to be due largely to inhibition of factor IXa. Prothrombin activation by factor Xa and phospholipid was also suppressed by SP54 in the absence of At III, and its effect on the APTT was also shown to be independent of At III. It is concluded that at relatively low concentrations the anticoagulant actions of SP54 are mainly due to these At III-independent pathways.
Thrombin Potentiation of Factor VIII Procoagulant Activity: Assessment by the Two-Stage Assay
Authors: Kopitsky Robert G , Switzer Mary Ellen P , McKee Patrick A 
Published: July 2018

SummaryFactor VIII (FVIII) procoagulant activity is the function of a plasma glycoprotein that is missing or inactive in patients with classic hemophilia. Numerous studies have shown that trace thrombin causes rapid enhancement followed by gradual inactivation of FVIII procoagulant activity. Recent evidence suggests that thrombin activation of the FVIII/von Willebrand factor (vWF) protein is required for inactivation to occur. All of these studies have used the one-stage partial thromboplastin time to assay FVIII activity. Other investigators have used the two-stage assay of FVIII activity and have been unable to demonstrate thrombin-induced enhancement of FVIII activity, although inactivation has consistently occurred. We performed experiments designed to help resolve this disagreement, using the two-stage assay specifically modified to detect thrombin potentiation of FVIII activity. The length of the first-stage incubation time was found to be critical in demonstrating the initial effect of thrombin on FVIII activity. Taking advantage of this finding we were able to show a 4.1 ± 0.5-fold enhancement of FVIII activity upon incubating purified FVin/vWF with 0.04 NIH unit thrombin per ml. The apparent enhancement of FVEQ activity declined with increasing thrombin concentration. Incubation with 0.08, 0.16, and 0.32 NIH unit thrombin per ml resulted in only 3.2 ± 0.5, 2.6 ± 0.5 and 1.5 ± 0.3-fold enhancement, respectively, of FVIII activity. As with results from the one-stage assay, activation was followed by slow inactivation of FVIH/vWF. Using the two-stage assay we also showed 100% inactivation and 100% inhibition of FVIII activity by plasmin and human anti-FVUI IgG, respectively. Plasmin inactivation of FVIII activity showed a dose-response effect. Thrombin was unable to activate plasmin-degraded FVin/vWF. Our results show that thrombin potentiation of FVni activity is easily demonstrable in the two-stage assay. These findings support the contention that activation of FVm activity by thrombin is prerequisite for inactivation and underscore the importance of thrombin activation of FVHI/vWF in the intrinsic clotting system.
Inhibition of Thrombin-Neutralizing Activity of Antithrombin III by Steroid Hormones
Authors: Nagasawa H , Kim B K , Steiner M , Baldini M G 
Published: July 2018

SummaryEstrogens in high doses have been shown to inhibit, in vitro, the thrombin-neutralizing action of antithrombin III (AT III). In this study we investigate the effect of estrogens on AT III in greater detail. To increase the sensitivity of measurement of AT III activity in the absence of heparin, we have developed an assay system utilizing human platelets, AT III and thrombin. The two proteins derived from human plasma were prepared in high purity. Platelet aggregation was induced by approximately 0.02 NIH U of thrombin. AT III was added in amounts that suppressed 95% of the aggregation-inducing effect of thrombin. Estrogens blocked the thrombin-neutralizing effect of AT III in dose-dependent manner. This effect was shown to be specific for AT III. Neither aggregability of platelets nor aggregating effect of thrombin were affected by the steroid hormone. Evidence for binding of estrogen to AT III was obtained from changes in intrinsic fluorescence of AT III. Activity of AT III was also reduced in increasing order of effectiveness by cholesterol, cortisone, testosterone and progesterone. Our studies suggest a direct effect of estrogens and other steroids on AT III, altering its specific neutralization of thrombin.