bluuebunny/crossref_metadata_2025_split huggingface dataset:
von Willebrand Activity and Electrophoretic Mobility of Platelet Factor VIII Related Antigen in Patients with von Willebrand’s Disease
Authors: Sultan Y. , Lamazière J. , Maisonneuve P. 
Published: May 2019

We have previously shown that patients with severe Von Willebrand’s disease (VWd), mainly homozygotes had no factor VIII related antigen (F VIIIRA) in their platelets as well as no Von Willebrand activity (F VIIIVW) as measured by the ristocetin cofactor assay. In all other patients with less severe form of the disease platelet F VIIIRA was detectable. In normal controls electrophoretic mobility of platelet F VIIIRA was found to be identical to the mobility of plasma VIII-RA either on the total platelet lysate or after isolation on sepharose 4B columns.In the present study F VIIIVW and the electrophoretic mobility of F VIIIRA were compared in platelet extracts and the plasma of a number of patients. Seven of the ten patients tested were genetic variants of vwd with very low ratio of F VIIIVW/F VIIIRA suggesting a non functional protein with an increased electrophoretic mobility : one group of patients showed abnormalities of plateletF VIIIRA identical to those found in the plasma. However another group showed a high ratio of F VIIIVW/F VIIIRA suggesting a more active protein than the one in patient’s plasma although the platelet F VIIIRA had an increased electrophoretic mobility. These results are the first example of a F VIIIRA with abnormal electrophoretic mobility associated to high F VIIIVW activity. The loss of F VIIIVW in the patient’s plasma would be a secondary process occuring after F VIIIRA is released in the circulation.
The Action of Immobilized Thrombin on Factor VIII
Authors: Brown J. E. , Carton C. , Hougie C. 
Published: May 2019

The utility of immobilized enzymes in blood coagulation studies is readily apparent. An enzymatic transformation can be stopped by centrifugation and removal of the enzyme beads. This could leave an “activated” factor free of the contaminating “activator”. The further degradation which prolonged exposure to the enzyme often produces can thus easily be stopped. The action of immobilized thrombin on factor VIII warranted testing, since we have observed that hirudin added to a factor VIII solution that has been maximally activated with thrombin prevents the subsequent destruction of “activated” factor VIII. Thrombin was covalently bound to agarose and shown to be active in hydrolyzing a synthetic tripeptide (S-2160) with a pH optimum of 8.5. Tested on human or bovine plasma, immobilized thrombin had no effect on factor VIII activity over 24 hours. Incubated with purified bovine factor VIII (100 units/ml) and tested at various concentrations, no activation of factor VIII activity could be observed. Slow destruction of activity was noted, so that in 16 hours only 20% of factor VIII activity remained compared with glycine-agarose beads as control.It was assumed that a complex of factor VIII and thrombin was necessary for the activated state. To test this, thrombin was labeled with 125I. This iodinated thrombin maintained full factor VIII activating activity. A time dependent binding of factor VIII and thrombin was observed following chromatography on Bio-Gel A 1.5M. This observation, plus the absence of activation of factor VIII by solid phase thrombin, suggests that a factor VIII-thrombin complex rather than limited proteolysis is the mechanism of factor VIII activity enhancement by thrombin.Supported by the National Hemophilia Foundation.
The Heparin Thrombin Clotting Time - A Measure of Platelet Activation?
Authors: O’Brien J. R. , Etherington M. D. , Oamieson Sandra , Shuttleuorth R. 
Published: May 2019

The heparin thrombin clotting time (HTCT) of platelet poor plasma (PPP) measures non-specifically the total heparin neutralizing activity (HNA) of PPP. This HNA must include any platelet factor 4 (PF4) liberated in vivo from “activated” platelets. It is suggested that released PF4 is the main determinant of clinical abnormalities of the HTCT for the folloiijing reasons. (l)There is an inverse relationship between the intra-platelet PF4 determined by a clotting method and the HTCT (Thrombos. Haemostas., 36, 649, 1976). (2)There is minimal activity in plasma from aplasia and I.T.P. (3)There is a mild excess of activity in groups of patients at risk of thrombosis and (4) most activity during thrombosis, operations, acute myocardial infarction and infections, in all of ujhich conditions platelets presumably are involved and “activated”. There is a significant inverse correlation between the HTCT and (5) the plasma “low activity PF4” of Nieuiarouski and (6) the β thromboglobulin (radioimmunoassay).In most healthy people this test is remarkably constant, suggesting a steady state. But there are marked inter-person differences ujhich could indicate different degrees of platelet activation and different thrombotic risks. This test can be routinely carried out in 2 minutes in a hospital laboratory with consistent results over the years. It is already of great clinical use and importance. Since this test can now be normalized therapeutically the question of patient benefit can be raised.
Size and Shape of Human Fibrinogen in Solution
Authors: Hofmann V. , Straub P.W. , Binkert T. , Serrallach E. , Känzig W. , Zulauf M. 
Published: May 2019

In order to obtain information on size and shape of the fibrinogen molecule in solution the translational diffusion coefficient (DT), the rotational diffusion coefficients (DR⊥ and DR//) and the sedimentation coefficients (S) have been measured on human fibrinogen with a clottaoility above 95%. The methods used were dynamic light scattering, nanosecond fluorescence depolarization and analytical ultracentrifugation. Dynamic light scattering yields DT = 2.0 ± 3% x 10-7 cm2sec–1 at a concentration of 7 mg/ml in 0.15 M Tris-NaCl, pH 7.4. DT is strongly dependent on concentration, being 3.4 ± 10% × 10-7 cm2 sec-1 at 0.1 mg/ml. The rotation along the minor axis as measured with the same method is DR = // 1.5 × 106 sec-1 at 0.1 mg/ml. The rotation along the major axis as measured on fibrinogen labeled with dansylchloride is DR// = 1.5 x106 sec–1. S is also strongly dependent on concentration, being 7.9 S at 0.1 mg/ml, 8.1 S at 1 mg/ml and 6.6 S at 10 mg/ml.These results fit with an elongated molecule having an axial ratio of 7. They are compatible with a MW of 340’000 only for concentrations above 2 mg/ml, while at lower concentrations (0.1 mg/ml) they agree with a MW of approximately half the accepted value.
Prospective Study on the Value of a Single Infusion of Dextran 70 During Surgical Operation in the Prevention of Fatal Postoperative Pulmonary Embolism (PE)
Authors: Ljungström Karl-Gösta 
Published: May 2019

At Danderyd’s Hospital a controlled clinical trial of dextran 70 using phlebography in all patients demonstrated a significant reduction in postoperative deep venous thrombosis (DVT) from 52% in the untreated control group to 4% in the dextran group. Johnson et al. 1968. As a consequence, routine prophylaxis of postoperative DVT with dextran 70 was instituted for all patients over 50 years of age undergoing abdominal, orthopedic or urological surgery. A retrospective investigation of. the result of this two-year period of routine prevention with dextran 70, which was preceded and superceded by 2 two-year periods when no dextran was given, revealed the following sequence of fatal PE verified at autopsy over the six-year period:15 (no prophylaxis), 6 (dextran) and 15 (no prophylaxis), Ljungström, 1975.At this stage a prospective study for a new two-year period was started. Infusion of 100 ml of dextran 70 was started during operation in all patients filling one of the following criteria: 1. All patients over 50 years of age undergoing abdominal, orthopedic or urological surgery. 2. All patients undergoing re-operation regardless of age. 3. All patients undergoing major surgery with a history of previous thromboembolic disease regardless of age.During this last two-year period only 3 patients died of fatal postoperative PE. The difference between 15 fatal PE in the non-dextran and 3 in the dextran group was significant, P 0.05. A comparable number of surgical operations were performed during each year of the eight-year period.
Concentrated and Diluted Heparin-Prophylaxis of Postoperative Deep Vein Thrombosis
Authors: Törngren S. , Forsberg K. 
Published: May 2019

Two calcium heparin solutions (Vitrum AB) have been evaluated in a controlled blind study with standard dosage of 5000 IE subcutaneously. The injections were given 2 hours before operation and 12-hourly for 6-8 days after operation. 175 patients undergoing abdominal surgery were included and randomized into 3 groups. 75% of the patients had malignant disease. 66 patients recieved heparin 500 IE/ml (1 ml), 47 patients recieved heparin 25000 IE/ml (0.2 ml) and 62 patients recieved 5% glueos. Deep vein thrombosis (DVT) was diagnosed with the 125I-fibrinogen method. Finally the heparin solutions with different viscocity were compared in an in vitro experiment. The nurses who injected the patients gave injections into weighed bottles with the usual technique.DVT was diagnosed in 32% of the control patients, 15% of those on heparin 5000 IE/ml and 21% of those on heparin 25000 IE/ml. The difference between controls and heparin 5000 IE/ml is statistically significant (p<0.05). In the in vitro experiment the mean dosage of heparin 5000 IE/ml was 5100 IE and the mean dosage of heparin 25000 IE/ml was 4415 IE. The dosage of heparin 25000 IE/ml was significantly less than 5000 IE (p<0.0l).We conclude that the frequency of DVT is reduced with calcium heparin 5000 IE/ml (1 ml) 12-hourly for 6-8 days after operation. The concentrated heparin 25000 IE/ml (0.2 ml) does not significantly reduce postoperative DVT, which probably can be explained from our results in the in vitro study.
Interactions of the ADP Analogs, 2′-0-Methyl ADP and Adenine 9-β-D-Arabinofuranoside 5′-Diphosphate and Catecholamines with Human Platelets
Authors: Ragatz B.H. , Iatridis P.G. , Iatridis S.G. , Markidou S.G. , Asterita M.F. , Gadarowski J. 
Published: May 2019

The two analogs 2'0-methyl ADP (Me'ADP) and adenine 9-β-D-arabinofuranoside 5'-diphosphate (A-Ara-DP) are compounds with stereochemical modification in the pentose moiety of ADP. These compounds have been added individually to citrated platelet rich plasma (PRP) and the concentration dependent interaction of each with platelets has been studied turbidimetrically using a dual channel Payton Aggregometer under the following experimental conditions:variable amounts of compound only; variable amounts of compound challenged at 30" or 5' by an aggregation-stimulating ADP concentration; or variable amounts of compound plus aggregation-stimulating concentrations of epinephrine (EPI) or norepinephrine (NOR) added after 30".Data obtained indicate that both compounds induce reversible aggregation at high concentrations, and that neither compound competes effectively with ADP added after 30". Both compounds delay the secondary wave of aggregation when ADP is added after 5'. Both compounds also exhibit mild dose dependent cooperative effects when epinephrine or norepinephrine are added 30" later.The ADP analogs, Me'ADP and A-Ara-DP, exhibit weak interactions with the platelet ADP receptor, indicating the importance of the ribose conformation in this case. The mild cooperative effects for either of these analogs plus EPI or NOR also suggest that the platelet ADP and catecholamine receptors are independent but interacting. Supported by USPHS HL-15425.
Platelet Factor XI
Authors: Castaldi P.A. , Connellan J. , Smith I. , Michel H. 
Published: May 2019

Contact factors are known to be associated with platelets. There is evidence to suggest that F XI may mediate an enhancement of coagulant activity in response to collagen stimulation of platelets. The aim of this study was to further explore this relationship using fresh platelets and extracts prepared from normals and a F XI deficient subject. Antisera against plasma F XII and F XI were used in tests of collagen induced coagulant activity and the latter antibody in immunoprecipitation studies with platelet extracts. Comparisons were made with antisera to isolated platelet membranes.Collagen induced coagulant activity was inhibited by anti F XI and to a slight degree by anti F XII. F XI-like coagulant activity could be detected in extracts of washed platelets and this activity adsorbed to heparin-sepharose as does plasma F XI. Similar activity could be detected in platelet extracts from the F XI deficient patient. Normal platelets contained an antigen that precipitated with anti F XI.F XI activity and antigen are closely associated with platelets. This may provide a mechanism for enhancement of coagulation.
Aes-, Esca-, Fibrinogen Adsorption and Bioluminescence Studies of Glutardialdehyde-Stabilized Heparin Surfaces
Authors: Larsson Rolf , Eriksson Jan Christer , Lagergren Hans , Olsson Per , Rosengren Åke 
Published: May 2019

The chemical constitution of glutardialdehyde-stabilized cetylamine hydrochloride heparin (CAHG) surfaces was investigated with AES (Auger Electron Spectroscopy) and ESCA (Electron Spectroscopy for Chemical Analysis) before and after plasma exposure.In comparison with a pure heparin film, the CAHG-surface contains a substantial amount of water-insoluble Schiff’s bases and its heparin surface concentration is about a factor of ten lower.On exposure to plasma or blood, proteins are heavily adsorbed onto the CAHG-surface. In contrast to the protein adsorbate on a polyethylene surface, which contains 200 nanograms of fibrinogen/cm2 surface area, the protein adsorbate on CAHG includes no functional fibrinogen. The surface-bound fibrinogen has been measured by radio-immunoassay of fibrino-peptide A split off when the surface is treated with thrombin or Defibrase.The adhesion of ATP-containing cellular material on the surfaces after exposure to blood has been explored with the aid of bioluminescence. These studies show that platelets and some other blood cells adhere to polyethylene surfaces, whereas adsorption of cells does not occur on CAGH-surfaces.It is concluded that the adsence of fibrinogen and cellular material on the CAHG-surface is associated with its non-thrombogenic properties.
Skin Necrosis Complicating Oral Anticoagulant Therapy
Authors: Krzywanek H.J. 
Published: May 2019

Since the first report in 1943 far more than 100 cases of skin necrosis as a complication of oral anticoagulant therapy have been reported, mainly in European countries. Breast, thigh, legs and abdomen are the predominant sites of the lesions, obese women are most frequently affected.10 cases which we observed over the last ten years are presented and the etiology is discussed. The common feature of our patients is a history of fever, probably caused by a bacterial or viral infection, treated with a variety of antibiotics. A complicating or preexisting thrombosis or thrombophlebitis of the leg leads to the initiation of oral anticoagulant therapy. Regularly on the 4th (3.-5.) day of anticoagulant treatment the skin necrosis develops within hours. We suggest that the administration of antibiotics, and perhaps also the infectious process are predisposing factors. The high loading dose at the beginning of coumarin treatment and an abnormal sensitivity of the patient seem to be other important etiologic factors for coumarin necrosis. These points are substantiated by the facts that skin necrosis occurs only in the first days after the start of oral anticoagulant therapy, and by one of our patients who developed another skin necrosis when coumarin therapy was repeated several years later. Oral anticoagulant therapy should not be initiated when antibiotics must be given at the same time. In case anticoagulant treatment is necessary during antibiotic therapy we propose the administration of heparin instead of using coumarin derivatives.
Some Platelet Function Tests Normalized by ICI 55,897 and Clofibrate
Authors: O’Brien J.R. , Etherington M.D. , Jamieson Sandra , Shuttleworth R. 
Published: May 2019

We have shown (Lancet, 2, 995, 1976) that in normal men a diet substituting linoleic acid for most of the normal saturated fat intake is followed by marked changes in some of those platelet function tests which are abnormal in the prothrombotic state. Are these changes due to alterations in the plasma lipids?Clofibrate (Atromid-S) and an analogue, ICI 55,897, were given in double blind cross over studies to respectively 10 and 19 patients with severe peripheral arterial disease and/or a past history of MI. Preliminary analysis indicates that in 3 weeks on 55,897 the mean heparin thrombin clotting time was normalized from 25 seconds pre-treatment to 30 seconds. The fibrinogen decreased from a mean of 371 to 332 mg/%, but this treatment had no effect on the anti-thrombic activity and no effect on the plasma lipids. In the Clofibrate study the lipids and the anti-thrombic activity decreased; the HTCT was probably ameliorated but a marked placebo effect confounded the statistical analysis. However, clinical records of patients to be presented strongly support these conclusions. Thus no simple single mechanism, e.g. a change in lipids, can account for the changes achieved. These observations, however, establish that these tests regularly found to be abnormal in groups of patients at risk of further thrombosis can be changed towards normal in patients by two ICI compounds. It is now vital to find out if these changes are beneficial to the patient.
The Effect of Enhanced Fibrinolytic Activity on the Red Cell Membrane Transport
Authors: Ulutin S.B. , Emekli N. B. , Yardimici T. U. 
Published: May 2019

In dogs and in human subjects, using hepatic vein catheterization before and after the activation of the fibrinolytic system, the blood samples were obtained and the red cell amino acid transport was investigated. The time course accumulation of radioactive histidine in isolated red cells was followed together with the measurements of the fibrinolytic activity.A decrease in the active transport of histidine was observed in the red cells after the stimulation of the fibrinolytic system. Also a correlation between the decrease of active transport and the increase of fibrin-fibrinogen degradation products was seen.
FVIII: A Homologous Series of Covalently Linked Oligomers
Authors: Cockburn C.G. , Reay Diana M.L. 
Published: May 2019

Purified human FVIII was electrophoresed through SDS agarose gels of different concentrations and through SDS Polyacrylamide (PA) gels of exceptionally large pore size (3.75% monomer, 1% cross linking). The gels were calibrated (a) with the FVIII subunit (b) with dimethyl-suberimidate cross-linked human fibrinogen. After Coomassie-blue staining the PA gels were scanned densito-metrically.The results show that freshly purified FVIII at pH 6.5 exists as a homologous series of oligomers and that a linear relationship obtains between the mobility of oligomers 1-6 and log molecular weight. Another linear relationship exists between the higher oligomers due to their significantly raised mobility. This suggests that the higher oligomers have a compact structure which is still partially ordered after SDS denaturation. A plot of log oligomer molarity vs. log subunit number has a gradient of approximately -1, suddenly decreasing to -5.5 after the hexamer, strongly indicating a decrease in the rate of polymerisation after this point. Oligomers 1-6 comprised 88% of the total FVIII, and oligomers 7-9 a further 6%.FVIII left at room temperature for 24 hours associated into extremely large oligomers.
Defibrination Syndrome Developed after Replacement Therapy with PPSB in a Case of Hemophilia B.
Authors: Kazama M. , Iwakura H. , Nakajima M. , Abe M. , Abe T. 
Published: May 2019

A case of Hemophilia B, 20y., had valgus osteotomy of the left femoral neck. The preliminary replacement with PPSB was revealed not to introduce inhibitor and no other abnormal enzyme activity was found except for the slight disturbance of liver function. The operation was gotten ready with injection of 10 vials PPSB and performed smoothly in 2 hours with 340ml of blood loss. PPSB administration was scheduled in a daily dosis of 20 vials divided in twice. But at the third postoperative day, large hematoma concreted in the femoral region with severe pain and was followed by the massive bleeding from the wound. Coagulation tests revealed decreased platelet count, prolonged.PTT and prothrombin time, decreased fibrinogen and increased FDP. The concentration of F.IX was not lifted so high as expected after the injection of 10 vials of PPSB, which, together with the above mentioned changes of coagulation factors, suggested the developement of defibrination syndrome.The replacement of PPSB was continued together with 10,000 U of heparin and 800ml of fresh plasma per day. At the 7th postoperative day, the coagulation findings of defibrination syndrome were gradually improved, bleeding decreased and F. IX level elevated as could be calculated. The administration of PPSB was diminished and discontinued at 29th day and of heparin at 45th day without any bleeding complication thereafter.
Home Care in Germany: Philosophy of Treatment, Results of Intensive Care
Authors: Brackmann H.H. , Hoffmann P. , Etzel F. , Hildenbrand Eqli H. 
Published: May 2019

In the FRG the work of several centers is concerned with introducing a program of self-treatment for hemophi1iacso The general goal of a self-treatment-program is: avoidance of a time lag due to long distances and the expansion of personal freedom and life style possibilities.In respect to the dosage and treatment duration various opinions exist, some of them differing quite noticably from ours. Our conception about the therapy, existing since the beginning of our program (June 1971), is based on an intensive cooperation with the department of orthopedics at the university. Through our teamwork the following results were achieved:- the evaluation of 17.196 acute bleedings registered 93% joint and muscle bleedings- 98% of the patients over 11 years of age with severe and semi-severe hemophilia A or B revealed at least one, in several cases more, arthropathic changes- the pathophysiological process of a joint bleeding leads to an important electromyographic test as well as to new ideas about biomechanic.Based on the general test results a specific dosage plan for each patient resulted, which, together with the orthopedic findings took into consideration the attained biological recovery. Since our goal is the strenghtening and training of muscle in general, every patient receives a specially adopted training program, which largely excludes bleeding. Our results have lead to a 90% improvement of the original orthopedic finding.
Personality Characteristics of Hemophiliac Children
Authors: Ackerman L.L. , Charney D.S. , Verrecchio J. , Eyster M.E. 
Published: May 2019

The personality characteristics of hemophiliac children were assessed in 22 hemophiliacs, mean age of 12.2 years. Twelve had < 1%, 4 had 1-3%, 3 had 4-9%, and 3 had > 10% Factor VIII levels. Eleven boys, 8 to 11 years old were given the Children’s Personality Questionnaire, while the other eleven, ages 12 to 18 years were administered the Junior-Senior High School Questionnaire.Both personality questionnaires measured 14 personality factors, each defining specific personality traits. Means for the 22 hemophiliacs were obtained and compared to values for a control population. Scores for factors B, F, G, M, O, and Q3 were found to differ from the normal range (40.0-60.0) and indicated that, as a group, the hemophiliac children were brighter (B, 72.4), more sober (F, 34.6), more timid (M, 36.8), and their inner feelings and overt behavior poorly integrated (G, 33.4 and Q3, 36.6).The personality profiles of these children are similar to the profiles of children frequently diagnosed as Overly Inhibited Personality Disorder, as defined by the Group for the Advancement of Psychiatry (GAP) classification.