bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Characterization of NH2-Terminal Fibrinogen Bβ Fragments from N-DSK of Human Fibrinogen
Authors: Birken S , Agosto G , Lahiri B , Canfield R
Published: July 2018

In order to investigate the early release of NH2-terminal plasmic fragments from the Bβ chain of fibrinogen, substantial quantities of Bβ 1-42 and Bβ 1-21 are required as immunogens, as radioimmunoassay standards and for infusion into human volunteers to determine the half-lives of these peptides. Towards this end methods that employ selective proteolytic cleavage of these fragments from fibrinogen have been developed. Both the N-DSK fragment, produced by CNBr cleavage of fibrinogen, and Bβ 1-118 were employed as substrates for plasmin with the finding of higher yields from N-DSK. Bβ 1-42 and Bβ 1-21 were purified by gel filtration and ion-exchange chromatography on SP-Sephadex using volatile buffers. When the purified preparation of Bβ 1-42 was chromatographed on reverse-phase high performance liquid chromatography, two peaks of identical amino acid composition were separated, presumably due either to pyroglutamate or to amide differences.
Influence of Noise on Blood Coagulation
Authors: Chohan I S , Singh I , Rai R M
Published: July 2018

A study conducted in rats exposed to a continuous noise of 110 decibels over a period of 3 weeks revealed development of significantly prolonged bleeding time, higher plasma fibrinogen content, and progressively shorter activated partial thromboplastin time in test animals. These changes suggest a coagulopathy induced by noise stress.
The Effect of Albumin Bound Polyunsaturated Fatty Acids on Human Platelets
Authors: Holme Stein , Brox Jan H , Krane Hedvig , Nordøy Arne
Published: July 2018

Platelet rich plasma (PRP) was incubated at 22–24° C for 24 hr with various polyunsaturated fatty acids (PUFA), bound to albumin, to determine whether changes in the FA composition of the platelet phospholipids might induce changes in platelet behavior and in platelet structural integrity. The PUFA tested were linoleic (18:2 w6)*, linolenic (18:3 w3), dihomo-gamma linolenic (20:3 w6), arachidonic (20:4 w6) and eicosapentaenoic acids (20:5 w3). Only PRP incubated with 20:3 w6 and 20:5 w3 incorporated significant amounts of these FA into the platelet phospholipids and showed inhibition of aggregation and TxB2 production with collagen. However, the inhibition was not due to the incorporation of these FA’s into the phospholipids as observed by washing and resuspension of the FA incorporated platelets in control plasma, or to any change in structural integrity. It is suggested that the effect of 20:3 w6 and 20:5 w3 on aggregation is due to metabolites of these FA’s released from the platelets.
The Effect of Collagen Mediated Platelet Release on Plasma Prekallikrein Activation
Authors: Weerasinghe K M , Scully M F , Kakkar V V
Published: July 2018

Collagen mediated platelet aggregation caused -5.6 ± 6.7% inhibition and +39.1 ± 15.2% potentiation of prekallikrein activation in plasma from normal healthy volunteers between 20–40 and 50–65 years of age, respectively (n = 15, p <0.01). The amouns of platelet factor-four (PF4) released in the two groups were not significantly different. Collagen treatment in the presence of indomethacin caused +11.5 ± 3.6% and +59.6 ± 19.5% potentiation in the 20–40 and 50–65 age groups respectively (p <0.02). Adrenaline mediated platelet aggregation caused -55.2 ± 7.1% and -35.2 ± 8.3% inhibition in the 20–40 and 50–65 age groups, respectively. Collagen treatment of platelet-deficient-plasma and platelet-rich-plasma in EDTA also caused potentiation of prekallikrein activation.

The results indicate that the observed degree of prekallikrein activation after platelet aggregation is a net result of the inhibitory effect of PF4 and the potentiatory effect of activated platelets. The potentiatory effect was greater after collagen treatment as compared to adrenaline treatment, and in the 50–65 age group as compared to the 20–40 age group.
The Inability of Propranolol and Aspirin to Inhibit the Response of Fibrinolytic Activity and Factor VIII-Antigen to Infusion of DDAVP
Authors: Brommer E J P , Derkx F H M , Barrett-Bergshoeff M M , Schalekamp M A D H
Published: July 2018

We tested the response of the fibrinolytic activity and factor VIII-antigen levels to infusion of DDAVP in healthy volunteers and we studied the influence of propranolol and aspirin on this response. After DDAVP, 0.4 μg/kg in 10 min i. v., the fibrinolytic activity of redissolved euglobulins rose from 179 to 452 mm2 (lysis area of fibrin plates); after pretreatment with propranolol, 320 mg per day during 7 days, DDAVP induced a similar rise (from 166 to 471 mm2) and after pretreatment with a single dose of aspirin, 600 mg, ingested 5 hr before the DDAVP infusion, the lysis area increased from 159 to 455 mm2

Factor VIII-antigen level increased within 60 min after DDAVP from 104 to 208%; after pretreatment with propranolol from 111 to 230% and after a single dose of aspirin, DDAVP induced a rise from 107 to 206%.

From these data we conclude that neither baseline levels nor the release of plasminogen activator or factor VIII after DDAVP infusion are influenced by β-blockade or by interference with prostaglandin synthesis.
Drugs Effect on Platelet Survival Time: Comparison of Two Pyrimido-Pyrimidine Derivatives in Patients with Aortic or Mitral Replacement
Authors: Schbath J , Boissel J P , Mathy B , Ville D , Benveniste E , Sanchini B , Leizorovicz A , Belleville J , Dechavanne M , Maitre P , Gillet J , Bentamar A
Published: July 2018

A prospective randomized trial of the effects of 2 antiplatelet aggregating drugs, dipyridamole (375 mg/d), a related substance RA 233 (1500 mg/d) and placebo, concomitantly with oral anticoagulants, was carried out in patients with prior valvular replacement. The study was aimed to determine effect on platelet survival time (PST) of these 2 agents. The trial sample consisted of 40 males and 15 females aged 40–70 years (average 53 years). 32 received Björk-Shiley valve in aortic position; 23 underwent mitral valve replacement: 3 with Cooley-Cutter, 11 with Lillehei- Kaster 500 and 9 with Starr-Edwards 6120 prostheses; 28 patients had aortic stenosis, 21 aortic insufficiency. All the PST measured after 3 months of treatment were within normal ranges and not different between placebo, dipyridamole or RA 233 treated subjects: averages in days were, respectively, 7.49, 7.11 and 6.88. The present study did not support the claim that modem valve prosthesis could lead to a shortened PST.
An Antiplatelet Monoclonal Antibody That Inhibits ADP and Epinephrine-Induced Aggregation
Authors: Vilella R , Lozano T , Mila J , Borche L , Ercilla G , Ordinas T , Vives J
Published: July 2018

A monoclonal antibody (Mab) named EDU-3, was produced by fusing splenocytes from one Balb/c mouse, immunized with a mixture of platelets and non-T cells from heparinized human peripheral blood, with the HAT-sensitive myeloma line P3-NS1/ l.Ag4.1. By indirect immunofluorescence (IF) it was seen that this Mab reacted with all normal human platelets and bone marrow megakaryocytes, but did not react with lymphoid cells from normal donors, or platelets from Glanzmann’s thrombasthenia (GT) patients. Immunoprecipitation and SDS-PAGE experiments demonstrated that this Mab recognizes an epitope on the IIb-IIIa glycoprotein complex (GPC). EDU-3 inhibited platelet aggregation and release of ATP induced by ADP and epinephrine. Aggregation induced by arachidonic acid, ristocetin and bovine factor VIII were not inhibited by EDU-3. The difference between EDU-3 and other Mab directed against the IIb-IIIa GPC is discussed.
Response of Femoral Venous Oxygen Tension to Graduated Pressure Stockings - Possible Relationship to Deep Vein Thrombosis
Authors: Okoye G C , Evans J H , Beattie J , Lowe G D O , Lorimer A R , Forbes C D
Published: July 2018

Venous oxygen tension (pO2) was measured in discrete samples of blood obtained through the femoral vein of cardiac catheterisation patients before, during and after application of sustained external graduated pressure in the form of compression stockings (T. E. D. Kendall). There was a significant reduction (p <0.05) of pO2 from the baseline value both 30 sec and one minute after the application of the pressure stockings. Thereafter, the pO2 rose to baseline values. Two minutes after the stockings were removed there was again a significant reduction (p <0.05) of pO2 from the baseline value. We suggest that the decrease in ivenous pO2 on application of external pressure may be a reflection of washing out of stagnant hypoxic blood from the venous valve pockets, which may be related to the formation of deep vein thrombosis (DVT).
A Quick Method for Screening Platelet Dysfunctions Using the Whole Blood Lumi-Aggregometer
Authors: Ingerman-Wojenski Carol M , Silver Melvin J
Published: July 2018

Patients who present with a clinical history suggesting a bleeding disorder are often tested initially for a clotting defect rather than for platelet dysfunction, due to the length of time necessary to complete a platelet function study in platelet-rich plasma. We have developed a sensitive method for measuring platelet aggregation and release of ATP employing the Whole Blood Lumi-Aggregometer. This method makes it possible to quickly detect patients who require further study for possible platelet function disorders such as cyclooxygenase deficiency, storage-pool defect, thrombasthenia, and von Willebrand’s disease. The results obtained with this electrical impedance instrument do not differ from those obtained with the conventional optical method. However, it is now possible to recognize a platelet function defect within 30 min of obtaining a 5 ml sample of citrated whole blood. Further, platelets of unusual size or density are not lost to testing through centrifugation.
A Cooperative Clinical Trial of High-Dose Immunoglobulin Therapy in 177 Cases of Idiopathic Thrombocytopenic Purpura
Authors: Uchino Haruto , Yasunaga Kojiro , Akatsuka Jun-lchi
Published: July 2018

A study was conducted with the cooperation of 31 university hospitals and 44 general hospitals in Japan on high-dose immunoglobulin therapy for idiopathic thrombocytopenic purpura (ITP).

Sulfonated immunoglobulins were administered to 177 patients, comprising 102 children and 75 adults for two to seven days, and a favorable rise of platelet count was found in 114 (64.4%) of these patients.

In particular, of the 107 patients who had not responded favorably to adrenocortico-steroids therapy, 63 cases showed a favorable rise of platelet count. And of the 14 patients who had not responded favorably to splenectomy, 6 cases showed a favorable rise of platelet count.

In the majority of cases the platelet count fell to its pretreatment level within one month after the start of sequence of administration.

Although a dosage of 400 mg/kg/day was suitable for most patients, the wide range of individual responses suggested the desirability of determining an optimal dose for each patients.
Observations on the Heparin Neutralizing Activity of Outdated Platelet Concentrates
Authors: Griffiths B L , Collins J R , Huntsman R G
Published: July 2018

A crude extract of outdated, washed, frozen and thawed, platelet concentrates was prepared and optimally diluted for use in the A. P. T. T. test as a source of platelet phospholipid (P. F. 3). The extract contained, in addition to P.F. 3, active heparin neutralizing activity (P. F. 4), which was able to neutralize plasma heparin up to a concentration of approximately 0.8 units/ml plasma. Although these observations are of a preliminary nature, it is felt that the extract can be used to follow the “intrinsic” coagulability of plasma samples from patients receiving therapeutic heparin. Utilizing the A. P. T. T. test system, the determination of coagulability and the neturalization of heparin result from the use of this extract in a single test.
Further Characterization of Human Platelet Activation in the Absence of Aggregation: Phosphorylations of Specific Proteins and Relationship with Platelet Secretion
Authors: Nunez Danièle , Levy-Toledano Sylviane
Published: July 2018

Platelet aggregation and secretion have been described to be associated with phosphorylation reactions. Thrombasthénie and EDTA-treated control platelets undergo a normal serotonin release in the absence of aggregation. We now studied the phosphorylation of specific proteins associated with platelet secretion. In the presence of ionophore, significant increases occurred in the phosphorylation of two polypeptides of 43,000 and 20,000 molecular weight (P43 and P20) in a concentration dependent manner, and this was accompanied by an increase in the 14C-5HT release. The 32P-labelling of P43 and P20 reaches a peak within 1 min of platelet activation and is followed by a rapid dephosphorylation over the next 2-10 min. While the P20 is identified as the myosin light chain, the identity and the function of the P43 remain unknown.

Isoelectric focusing separates 4 proteins from P43 during two dimensional electrophoresis, but only one of them is phosphorylated by A 23187. Chlorpromazine (CPZ) and trifluoperazine (TFP) inhibit the P43 and P20 phosphorylation as well as the 14C- 5HT release in a dose dependent manner. The inhibitory action of the drugs is more pronounced for P43 than for P20, especially when the reactions are carried out at 20° C instead of at 37° C, while the release reaction is still inhibited under these conditions. These results allow different hypotheses for the relationship of phosphorylation-secretion and indicate the importance of one of these proteins (P43) for the release reaction.
Immunological Alterations in Haemophiliacs Treated with Lyophilized Factor VIII Cryoprecipitate from Volunteer Donors
Authors: Ceuppens J L , Vermylen J D , Colaert J , Desmyter J , Gautama K , Stevens E , The A L , Vanham G , Vermylen C , Verstraete M
Published: July 2018

We studied immune function in Belgian haemophiliacs treated with Factor VIII from volunteer donors. No patient had clinical evidence of immune deficiency. We found a decrease in T-helper cells (p <0.0005), in the ratio of T-helper over T-cytotoxic/ suppressor cells (1.72 ± 0.47 versus 2.24 ± 0.82 in controls, p <0.005) and in lymphocyte responsiveness to mitogens (p <0.05).

These findings could not be linked to the amount of F VIII received over the last year, the time since last F VIII administration, circulating immune complexes (54% positive patients, 7% positive controls, p <0.005), increased ALT levels, antibodies to cytomegalo-virus (85% of the patients, 45% of the controls, p <0.005), antibodies to Epstein-Barr virus, nor to the presence of HLA-DR 5 which was found in 56% of the haemophiliacs (20% of the overall Belgian population, p <0.005).

Either F VIII induces long lasting immunological alterations unrelated to AIDS, or haemophilia is itself associated with such changes.
The Anticoagulant Effects of the Hookworm, Ancylostoma ceylanicum: Observations on Human and Dog Blood In Vitro and Infected Dogs In Vivo
Authors: Carroll S M , Howse D J , Grove D I
Published: July 2018

Extracts of adult Ancylostoma ceylanicum prolonged the prothrombin time (PT) and partial thromboplastin time with kaolin (PPTK) of both human and dog plasmas in vitro. Excret-ory/secretory (E/S) products of these worms had similar effects while larval extract prolonged the PTTK only. Thus, the anticoagulant activities of this parasite are dependent upon the stage of the worm’s life cycle. Collagen- and ADP-induced platelet aggregation were inhibited by adult and larval extracts. When the peripheral blood and bleeding times of dogs with varying worm burdens were examined, the only abnormality was shortening of the PTTK in the most heavily infected animals. Homogenates of dog small bowel subjacent to adult hookworms prolonged the PT of dog plasma and electron microscopical examination of this tissue revealed aggregation of platelets in blood venules without fibrin deposition. Thus, this study provides evidence that the anticoagulant properties of hookworms may have biological significance in infected animals.
Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism
Authors: Dupe R J , English P D , Smith R A G , Green J
Published: July 2018

A quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.
High and Low Affinity Heparin Compared with Unfractionated Heparin as Antithrombotic Drugs
Authors: Merton R E , Thomas D P , Havercroft S J , Barrowcliffe T W , Lindahl U
Published: July 2018

A preparation of heparin was separated by affinity chromatography into two fractions: one of high (HAH) and the other of low (LAH) affinity to antithrombin III. These two fractions were compared with unfractionated heparin (UFH) by in vitro assay and their ability to impair experimental stasis thrombosis was also examined. Although the in vitro activity of HAH was double that of UFH, HAH was less effective than UFH as an antithrombotic drug; LAH was virtually inactive, both in vitro and in vivo. A mixture of 30 μg/kg of HAH and 50 μg/kg of LAH was as effective in preventing thrombosis as 80 μg/kg of UFH, and was more effective than 40 μg/kg of HAH alone, demonstrating that LAH potentiates the action of HAH in vivo.
Histidine-Rich Glycoprotein Modulates the Anticoagulant Activity of Heparin in Human Plasma
Authors: Lijnen H R , Van Hoef B , Collen D
Published: July 2018

Addition of 0.05 IU of heparin per ml normal plasma prolongs its thrombin time from 20 to 27s, but that of plasma specifically depleted in histidine-rich glycoprotein (by immunoadsorption) from 20 to 180s. Reconstitution of the depleted plasma with normal plasma or with purified histidine-rich glycoprotein normalizes its thrombin time.

In 54 plasma samples from hospitalized patients a significant negative correlation was found between the anticoagulant activity of heparin measured by thrombin inhibition and the plasma level of histidine-rich glycoprotein (r = 0.69). It is concluded that the level of histidine-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma to an extent which appears to be pharmacologically and possibly clinically relevant.
Effects of Acetylsalicylic Acid on Human Platelet Function In Vivo at Salicylate Steady State
Authors: Simrock R , Missalla A , Schwidtal P , Lischke V , Breddin H K
Published: July 2018

The results of clinical trials concerning the use of acetylsalicylic acid (ASA) as antithrombotic drug are contradictory. Inhibition by ASA of platelet prostaglandin synthesis and aggregation is prevented by its metabolite salicylic acid (SA) in animals and in human platelets in vitro. It was suggested that ASA might produce its own inhibitor, thereby diminishing its efficiency in thromboembolic disease.

In four healthy male subjects there was no difference in inhibition of collagen-induced platelet aggregation after the administration of 500 mg ASA alone or at salicylate steady state (3 g SA daily). But the inhibition of tissue-extract-induced platelet shape change was diminished and shortened by pretreatment with SA. We conclude that SA does not inhibit the effects of ASA on human platelet aggregation in vivo in therapeutic dose ranges. The clinical importance of the SA/ASA-interaction on tissue-extract-induced platelet shape change remains to be clarified.
A Study of a Caucasian Family with Variant von Willebrand’s Disease in Association with Vascular Telangiectasia and Haemoglobinopathy
Authors: Hanna W , McCarroll D , Lin D , Chua W , McDonald T P , Chen J , Congdon C , Lange R D
Published: July 2018

A family was identified which carries multi-haematological disorders including Type IIA von Willebrand’s disease, vascular telangiectasia, and a haemoglobinopathy (haemoglobin S trait). In the affected individuals, the von Willebrand’s disease varies in its expression from an asymptomatic form to a severe form especially in those patients with telangiectasia. Some patients have vascular telangiectasia in the mucous membranes of the mouth and lips. In two patients endoscopy disclosed telangiectasia in the mucous membranes of the gastrointestinal tract. All of the patients who had telangiectasia also had von Willebrand’s disease. An incidental finding was the presence of an abnormal haemoglobin (haemoglobin S) in some family members. The pattern of inheritance of the haemoglobinopathy was unrelated to the inheritance pattern of von Willebrand’s disease. The presence of haemoglobin S did not interfere with the aggregation of platelets in response to ristocetin.
Platelet Survival in Streptozotocin-Induced Diabetic Rats
Authors: Winocour P D , Laimins M , Colwell J A
Published: July 2018

Platelet 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.
Metabolism of Sodium Pentosan Polysulphate in Man – Catabolism of Iodinated Derivatives
Authors: MacGregor I R , Dawes J , Paton L , Pepper D S , Prowse C V , Smith M
Published: July 2018

An iodinated derivative of the heparin analogue SP54 has been prepared and used in conjunction with unlabelled SP54 to study the catabolism and organ distribution of this potential antithrombotic agent in healthy human volunteers. As observed previously with 125I-heparin, we found that the 125I-SP54 was rapidly cleared from the circulation, returning later in a desulphated form. Organ distribution studies with 123I-SP54 suggested that the liver and spleen were major sites of desulphation. Gel filtration and Polybrene binding showed the presence of sulphated macromolecular SP54 and desulphated macromolecular and depolymerised SP54 in post-injection urines. No depolymerised material was present in plasma suggesting depolymerisation occurs in the kidney.
Effect of Plasma Dilution on Adsorption of Fibrinogen to Solid Surfaces
Authors: Brash J L , ten Hove P
Published: July 2018

The adsorption of various plasma proteins to three solid surfaces has been studied as a function of plasma concentration. Albumin adsorption on glass showed no dependence on plasma concentration and increased to a plateau value on both polyethylene and siliconized glass. Immunoglobulin G (IgG) adsorption showed no dependence on plasma concentration on any surface. Fibrinogen adsorption increased with plasma concentration and then decreased, the maximum occurring at about 1% normal plasma concentration and varying somewhat with the surface. On glass the kinetics of fibrinogen adsorption was dependent on plasma concentration: at concentrations less than the adsorption maximum, the kinetics was conventional, with adsorption increasing onto a plateau; at concentrations greater than the adsorption maximum, kinetics curves also showed maxima the position of which shifted to longer times as plasma concentration decreased. These data are interpreted in terms of competitive adsorption between fibrinogen and other, as yet unidentified species in plasma. The data reported are in general agreement with the model of Vroman (12) for plasma-surface interactions which holds that initially adsorbed fibrinogen is later replaced by high molecular weight kininogen (HMWK), the rate of replacement depending on the relative activity of the surface in promoting coagulation.
Abnormal Platelet Serotonin Uptake and Binding Sites in Myeloproliferative Disorders
Authors: Caranobe C , Sié P , Fernandez F , Pris J , Moatti S , Boneu B
Published: July 2018

A simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient’s platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient’s platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.
Blood Changes and Enhanced Thromboxane and 6-Keto Prostaglandin F1α Production in Experimental Acute Plasmodium Bergei Infection in Hamsters
Authors: Essien E M , Arnout J , Deckmyn H , Vermylen J , Verstraete M
Published: July 2018

Golden hamsters inoculated intraperitoneally with Plasmodium bergei infected mouse blood regularly developed P. bergei parasitaemia. This was associated with progressive thrombocytopenia and leucocytosis as the degree of parasitaemia increased with time. When infected whole blood was stimulated with collagen, significantly enhanced thromboxane B2 (TXB2) production per platelet was seen. 6-keto prostaglandin (PG) F1α formation in the same system increased from the sixth infection day onwards and correlated with the relative leukocytosis. The production of 6-keto PGF1α by aorta rings was significantly higher during the 4-7th days postinoculation. The increase in thromboxane production however was much more important than that of 6-keto PGF1α and it therefore is concluded that P. bergei parasitaemia in hamsters tilts the haemostatic balance towards the platelet hyperaggregability that has also been described in P. falciparum infection in man.
Inhibition by Heparin of Platelet Accumulation In Vivo
Authors: Barrett P A , Butler K D , Morley J , Page C P , Paul W , White A M
Published: July 2018

In vivo platelet aggregation has been studied using a novel, minimally invasive technique. No aggregatory effects of heparin were observed on normal circulating platelets nor was there enhancement of aggregation of platelets during activation by fhtravenous injection of ADP, collagen, PAF acether or thrombin. On the contrary, high doses of heparin were found to inhibit platelet accumulation induced by ADP, collagen or PAF-acether. Inhibition of these responses necessitated doses of heparin in excess of those required for anti-coagulant effects. The present experiments do not establish a mechanism for such inhibition. Extension to other species, including man, is needed before attributing clinical relevance to the present observations.
Acquired Factor XI Inhibitors in Two Patients with Hereditary Factor XI Deficiency
Authors: Morgan Kangathevy , Schiffman Sandra , Feinstein Donald
Published: July 2018

Two patients with hereditary factor XI deficiency developed inhibitors following plasma transfusions. Neither had severe spontaneous bleeding. The patients’ plasmas neutralized both factor XI in plasma, purified factor XI, and purified factor XIa. The inhibitor in both patients’ plasmas adsorbed to Protein A- Sepharose. The inhibitors eluted from Protein A-Sepharose were partially neutralized by kappa and lambda light chain antisera indicating that they were polyclonal IgG antibodies. Both inhibitors markedly decreased adsorption of factor XI to glass surfaces. The cleavage of factor XI by trypsin was unaffected by the inhibitors. The lack of severe spontaneous bleeding in both of these patients strongly suggests that an alternate coagulation mechanism bypassing factor XI must compensate for this severe defect.
Biological and Thrombolytic Properties of Proenzyme and Active Forms of Human Urokinase – II. Turnover of Natural and Recombinant Urokinase in Rabbits and Squirrel Monkeys
Authors: Collen D , De Cock F , Lijnen H R
Published: July 2018

The turnover of recombinant pro-urokinase (Rec-pro-UK), recombinant urokinase (Rec-UK) and natural urinary urokinase (Nat-UK) was studied in rabbits and in squirrel monkeys (Samiri sciureus). Following intravenous injection, urokinase activity disappeared rapidly from the blood. The initial disappearance rate could be described by a single exponential term with a t½ of 3 to 6 min for each molecular form of urokinase in both species. Urokinase related antigen, measured with a radioimmunoassay in the plasma of the squirrel monkeys disappeared with a t½ of 3.5 min for Rec-pro-UK, 6.0 min for Rec-UK and 8.0 min for Nat-UK.

The clearance and organ distribution of Rec-pro-UK, Rec-UK and Nat-UK was studied with the use of 125I-labeled preparations. In each case the radioactivity initially disappeared rapidly from the plasma, also with a t½ of a few min, but then the disappearance rate slowed down. Labeled Rec-UK in which the active site histidine was irreversibly blocked by alkylation, disappeared equally rapidly from the plasma. Measurement of the organ distribution of 125I at different time intervals revealed that all three types of urokinase were rapidly accumulated in the liver, which was followed by release of degradation products in the blood. Experimental hepatectomy prolonged the t½ of each type of urokinase very markedly (t½ >30 min).

These findings indicate that urokinase is rapidly removed from the blood by clearance and degradation in the liver. Recognition by the liver does not require a functional active site and is not mediated via carbohydrate side chains. Inactivation by plasma protease inhibitors does not represent a significant pathway of urokinase inhibition in vivo.
Preoperative AT-III Values and Clinical Postoperative Thrombosis: A Comparison of Three Antithrombin-III Assays
Authors: Lynch Dona M , Leff Linda K , Howe Stephen E
Published: July 2018

Three antithrombin-III assays (Sigma functional plasma, von Kaulla functional serum, and Calbiochem-Behring radial immunodiffusion) are compared using preoperative serum and plasma from 48 patients admitted for cardiovascular or other major vascular surgery. Medical records were reviewed for evidence of thrombotic complications. Eight patients (17%) in this selected population had clinical evidence of postoperative thrombotic complications. The sensitivity and specificity for each AT-III assay were calculated, and the positive and negative predictive values in this population were determined. Sigma’s plasma AT-III had the highest positive predictive value (67%) and negative predictive value (100%). The functional serum and RID assays had significantly lower positive predictive values (23% and 38% respectively) and negative predictive values of 86%. Using the Two Sample t-Test to evaluate differences in AT- III values between the two patient groups, i.e., those who experienced thrombotic complications and those who did not, only the functional plasma AT-III method was statistically significant at a 95% confidence interval.
Platelet Survival and Function in Animals with Prosthetic Mitral Valve: The Effect of Nafazatrom
Authors: Al-Mondhiry H , Pierce W S , Richenbacher W
Published: July 2018

Thromboembolism remains a serious problem in patients with prosthetic heart valves. Previous studies documented a number of platelet abnormalities in such patients and correlated the occurrence of thromboembolic complications with short platelet survival. We have studied platelet survival and platelet aggregation in eight goats fitted with prosthetic mitral valves and repeated the studies following treatment with nafazatrom, a potent antithrombotic agent. Eleven survival studies in eight animals showed a platelet survival not significantly different from control (6.52 ± 0.72 vs. 6.94 ± 0.81 days). Following seven to ten days of oral drug administration, platelet survival in the test animals was 7.34 ± 0.96 days, significantly longer than pretreatment results (p <0.01). Animals with the shortest pretreatment platelet survival achieved substantial prolongation of platelet life span following drug treatment. The drug caused no change in ex vivo platelet aggregation.
Venous Thrombosis Following Diagnostic Transvenous Catheterization by Percutaneous Catheter Insertion: An Evaluation of Desmopressin as a Thromboprophylactic Agent
Authors: Nilsen D W T , Haerem J , Westheim A , Skjennald A , Grendahl H , Godal H C
Published: July 2018

The preventive effect of desmopressin with respect to catheter induced thrombosis was studied in a randomized double-blind trial, consisting of 30 patients undergoing percutaneous transcubital right heart catheterization. Phlebography of the catheterized arm was performed after five days. The frequency of postcatheterization thrombosis was reduced by 33 per cent, from 86 per cent in the treatment group to 53 per cent in the control group (0.1 <p <0.2). This effect was restricted to minor thrombi, whereas major thrombosis could not be prevented.

Patient materials such as that of the present study, may become useful in preliminary investigations of thromboprophylactic agents.
Clearance and In Vivo Release by Heparin of Human Platelet Factor 4 (PF4) in the Rabbit
Authors: Prosdocimi M , Scattolo N , Zatta A , Fabris F , Stevanato F , Girolami A , Cella G
Published: July 2018

13 male New Zealand rabbits were injected with two different doses (25 μg/Kg and 100 μg/Kg) of human platelet factor 4 antigen (PF4). The disappearance of the protein was extremely fast with an half-life for the fast component of 1.07 ± 0.16 and 1.76 ± 0.11 min respectively. The half-life for the slow component, detectable only with the highest dosage, was 18.8 min.

The administration of 2500 I.U. of heparin 30 min after PF4 administration induced a partial release of the injected protein and its clearance from plasma was slow, with half-life of 23.3 ± 5.9 min and 30.9 ± 2.19 min respectively.
The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy
Authors: Christe M , Gattlen P , Fritschi J , Lämmle B , Berger W , Marbet G A , Duckert F
Published: July 2018

The contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).

Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.
Indium-111-Labelled Human Platelets: A Method for Use in Severe Thrombocytopenia
Authors: Heyns A du P , Badenhorst P N , Wessels P , Pieters H , Kotzè H F , Lötter M G
Published: July 2018

We describe and evaluate a simple method for labelling autologous human platelets with Indium-111-oxine in patients with severe thrombocytopenia. Twenty patients with immune thrombocytopenia and platelet counts ranging from 5 to 119 × 109/1 were investigated. Platelets were isolated from blood by differential centrifugation, residual platelets were repeatedly washed from the red cell layer and buffy coat and labelled with In 111 in saline. A mean of 55% ± 21 of platelets were harvesteo from the blood, labelled with 49% ± 24 efficiency and 15.8 × 108 labelled platelets reinjected to the patients. Contamination of the platelets with red cells and plasma was low. The labelled platelets were viable as assessed by in vitro aggregation, recovery in the circulation and mean survival time. This method permits quantitative platelet imaging with autologous labelled platelets in patients with severe thrombocytopenia.
The Use of Functional and Quantitative Assays to Study Glycoprotein Ib in Platelets Stored Under Various In Vitro Conditions
Authors: Taylor M Ann , Anstee D J
Published: July 2018

There is much evidence to suggest that platelet membrane glycoprotein Ib is involved in the haemostatic function of platelets and it has been suggested that loss of this glycoprotein may occur during in vitro storage of platelet concentrates. In this study two quantitative radioimmunoassays were developed to measure the content of glycoprotein lb in platelets stored under a range of conditions used in blood banks. One assay involved the use of iodinated Maclura pomifera lectin and the other the binding of a monoclonal antibody (AN51) specific for glycoprotein lb. The results showed that there was no significant reduction in the glycoprotein Ib content of platelets under the storage conditions used. These results suggest that any loss of haemostatic effectiveness which occurs on in vitro storage of platelet concentrates is not attributable to a selective loss of glycoprotein Ib from the platelet surface.
High Fibrinopeptide A (FPA) Levels in Acute Non-Lymphocytic Leukemia Are Reduced by Heparin Administration
Authors: Gugliotta L , Viganò Silvana , D’Angelo A , Guarini Anna , Tura S , Mannucci P M
Published: July 2018

Plasma levels of fibrinopeptide A (FPA) in 30 untreated patients with acute non-lymphocytic leukemia (ANLL) were significantly higher than in 30 healthy controls (p <0.001). Patients without laboratory signs of disseminated intravascular coagulation (DIC) had levels of FPA higher than controls (p <0.02) but markedly lower than patients with DIC (p <0.001). Five patients with M3 leukemia had a higher mean FPA level (p <0.02) and a lower peripheral blast cell count (p <0.05) than patients with other cytological subtypes of ANLL. When patients with M3 were excluded, a significant correlation was observed between the peripheral blast cell counts and the FPA levels (r = 0.66, p <0.001). FPA levels were similar with body temperature either above or below 38° C. After intravenous bolus of heparin FPA dropped to normal levels in 14 out of 17 patients who had high baseline values. These findings indicate that intravascular thrombin formation, which probably result from the expression of procoagulant activities of blast cells, is the main cause of high FPA in the majority of patients with acute non-lymphocytic leukemia.
Fibrinolytic Activators and Inhibitors in Terminal Renal Insufficiency and in Anephric Patients
Authors: Brommer E J P , Schicht I , Wijngaards G , Verheijen J H , Rijken D C
Published: July 2018

Fibrinolytic factors were measured before and after DDAVP- infusion in 18 patients on chronic, regular haemodialysis, 11 of whom underwent bilateral nephrectomy, and in 7 patients in whom non-functioning kidneys were still present. Baseline fibrinolytic activity was normal or high in all but two cases. Before haemodialysis, the response to DDAVP-infusion was greatly reduced in the majority of patients as compared with healthy controls, irrespective of the baseline level. This was in accordance with mean t-PA-antigen levels which increased only slightly after DDAVP. When DDAVP was given after haemodialysis, previous non-responders showed a normal increase in fibrinolytic activity. The level of free t-PA-inhibitors was normal in most cases as were levels of α2-antiplasmin. and α2-macroglobulin.
Intra-Operative Activation of Coagulation - A Stimulus to Thrombosis Mediated by Vasopressin?
Authors: Grant P J , Tate G M , Davies J A , Williams N S , Prentice C R M
Published: July 2018

Vasopressin infusions in normal volunteers that produce concentrations in plasma comparable to those seen during stress, cause an increase in plasma factor VIII and shortening of the euglobulin clot lysis time (ECLT). We have investigated the relationship between endogenous vasopressin (aVP) release and haemostatic function in 7 patients undergoing major abdominal surgery. Blood samples were taken at nine intervals during the operative procedure. Plasma aVP levels peaked at median values of 51 pg/ml during bowel manipulation and remained elevated on the first post-operative day. Following, and in close temporal relationship with the rise in aVP there were increases in factor VIII coagulant activity, the ristocetin co-factor, von Willebrand antigen, plasminogen activator activity (106/ECLT2) and fibrinopeptide A concentrations with shortening of the activated partial thromboplastin time. The relationship was similar to that seen following infusion of a VP in human volunteers. The results are consistent with the hypothesis that aVP is an important mediator of changes in haemostatic function which accompany stress and might contribute to the thrombotic risk associated with surgical operations.
Fibrinogen Milano II: A Congenital Dysfibrinogenaemia Associated with Juvenile Arterial and Venous Thrombosis
Authors: Haverkate F , Koopman J , Kluft C , D’Angelo A , Cattaneo M , Mannucci P M
Published: July 2018

A congenitally abnormal fibrinogen was isolated from blood of a young man with deep-vein thrombosis. Two other affected members of his family had three episodes of severe arterial thrombosis. The fibrinogen showed a delayed clotting by thrombin, but a normal clotting by Arvin®, Reptilase®, and prothrom-bin-staphylocoagulase complex. Analysis of the fibrinopeptides A and B by High Performance Liquid Chromatography did not reveal an abnormal peptide structure. The rate of release of A and B peptides by thrombin was strongly delayed, whereas the rate of release of fibrinopeptide A by Arvin® appeared to be normal. The fibrin polymerization rate was normal. Interactions between the abnormal fibrinogen, platelets and the fibrinolytic system were also normal. Evidence is presented that the defective interaction between fibrinogen Milano II and thrombin is associated with a defective binding of thrombin to the fibrin moiety of the abnormal fibrinogen.
Functional Involvement of Thrombospondin in Platelet Aggregation Induced by Low Versus High Concentrations of Thrombin
Authors: Kao K J , Shaut David M , Klein Paul A
Published: July 2018

Thrombospondin (TSP) is a major platelet secretory glycoprotein. Earlier studies of various investigators demonstrated that TSP is the endogenous platelet lectin and is responsible for the hemagglutinating activity expressed on formaldehyde-fixed thrombin-treated platelets. The direct effect of highly purified TSP on thrombin-induced platelet aggregation was studied. It was observed that aggregation of gel-filtered platelets induced by low concentrations of thrombin (≤0.05 U/ml) was progressively inhibited by increasing concentrations of exogenous TSP (≥60 μg/ml). However, inhibition of platelet aggregation by TSP was not observed when higher than 0.1 U/ml thrombin was used to activate platelets. To exclude the possibility that TSP inhibits platelet aggregation by affecting thrombin activation of platelets, three different approaches were utilized. First, by using a chromogenic substrate assay it was shown that TSP does not inhibit the proteolytic activity of thrombin. Second, thromboxane B2 synthesis by thrombin-stimulated platelets was not affected by exogenous TSP. Finally, electron microscopy of thrombin-induced platelet aggregates showed that platelets were activated by thrombin regardless of the presence or absence of exogenous TSP. The results indicate that high concentrations of exogenous TSP (≥60 μg/ml) directly interfere with interplatelet recognition among thrombin-activated platelets. This inhibitory effect of TSP can be neutralized by anti-TSP Fab. In addition, anti-TSP Fab directly inhibits platelet aggregation induced by a low (0.02 U/ml) but not by a high (0.1 U/ml) concentration of thrombin. In conclusion, our findings demonstrate that TSP is functionally important for platelet aggregation induced by low (≤0.05 U/ml) but not high (≥0.1 U/ml) concentrations of thrombin. High concentrations of exogenous TSP may univalently saturate all its platelet binding sites consequently interfering with TSP-crosslinking of thrombin-activated platelets.
Partial Thromboplastin Time Test - Proposed Performance Guidelines
Authors: Koepke J A
Published: July 2018

The partial thromboplastin time (PTT) test is widely used as a screening test for the detection of hemophilia. It is also used to monitor patients on heparin anticoagulation. This proposal from a ICSH Panel proposes guidelines for the performance of this test, including comparable reference ranges, precision and sensitivity requirements.
Evaluation of Blood Glucose before and after Bariatric Surgery
Authors: Martins Ana , Oliveira Alexandre
Published: July 2018

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