bluuebunny/crossref_metadata_2025_split huggingface dataset:
INVESTIGATIONS ON MULTIMERIC STRUCTURE OF PLATELET VON WILLE-BRAND FACTOR IN PATIENTS WITH HEREDITARY DISORDERS OF PLATELET FUNCTION
Authors: Vigh Zs , Scharrer I 
Published: June 2019

Von Willebrand factor (vWF), a multimeric glycoprotein, plays an essential and multifunctional role in the hemostatic process. It is well known that platelet glycoproteins IB, IIB and IIIA contain receptors for vWF. Von Willebrand factor was also found in alpha granules of platelets. Therefore we investigated the multimeric structure of platelet vWF in 12 patients with different inherited disorders of platelet function. The patients had the following diagnosis: Hermansky Pudlak syndrome, Thrombasthenia and up to new undefined hereditary disorders of platelet function. The method is based upon:1) washing of platelets 2) release of platelet vWF 3) separation of vWF multimers by SDS-agarose electrophoresis 4) subsequent blotting of vWF mul timers onto nitrocellulose 5) staining by peroxidase conjugated antibodies.The investigations were repeated 3 times and compared to those of normal platelets. In 2 patients with Hermansky-Pudlak syndrane no multimeric structure could be detected in platelets whereas the multimeric pattern of plasma of these patients was normal. Also in one patient with the tentative diagnosis: thrombasthenia we couldn't find any multimeric structure in platelets compared to the normal multimeric composition of plasma. In 2 patients with giant platelets the multimeric distribution was normal. In the remaining 6 patients we observed multimeric structure which was different from that seen in vWd variants and in healthy volunteers. In 1 patient we found normal multimeric pattern in plasma and platelets.Based on our findings it can be assumed that the analysis of multimeric structure of platelet vWF can be helpful for the diagnostic approach and for the insight in pathogenesis of inherited disorders of platelet function.
FURTHER STUDIES ON TYPE IID VON WILLEBRAND'S DISEASE (vWD) VARIANTS
Authors: Hill F G H , Enayat M S , Williams C W , Short P E 
Published: June 2019

Five individuals from a single kindred and 3 other unrelated patients with type IID vWD have been studied. Multimeric analysis patterns obtained using discontinuous gel electrophoresis were identical both in major and minor band positions and distribution. In 2 where lysed platelets were studied, platelet and plasma multimeric analysis patterns were identical. EDTA plasma when compared with citrate plasma had more intense bands but there was no increase in intermediate or high molecular weight multimers. When fresh, frozen and thawed plasma or plasma left at 4°C for 24 hours were studied using multimeric analysis with autoradiography using 2 monoclonals (ESVWF 2 and 10) against vWF epitopes, significantly more intense autoradiographs were obtained with non-fresh rather than fresh plasma. These results suggest that freezing and thawing or storing plasma initiate a conformational change with the exposure of more epitope sites in these variants.Despite bleeding times in excess of 20 minutes ristocetin and botrocetin induced platelet aggregation and ristocetin and botrocetin cofactor assays were normal on fresh plasma. Both cofactor activities fell by 25-30% when fresh plasma was frozen and thawed once, whereas vWF:Ag fell by 20%.These results suggest that in IID vWD vWF:Ag is unstable and easily undergoes conformational change with loss of ristocetin and botrocetin cofactor activities and exposure of increased numbers of some epitopes.
NEW VARIANT FORMS OF von WILLEBRAND'S DISEASE
Authors: Matthews K B , Kernoff P A , Tuddenham E G D , Goodall A H 
Published: June 2019

Two unusual variants of von Willebrand's Disease (vWD) have been observed; one resembling Type Ic vWD and one an unclassified variant form of the disease. Both are associated with a history of mild bleeding and with a prolonged bleeding time.Two related patients (father and daughter) presented with reduced vWF activity (RiCoF) and vWF:Ag. Multimer analysis showed the presence of all molecular weight multimers but with a lack of triplet structure. This was confirmed in 3% agarose gels and resembled the pattern of multimers previously described as Type Ic vWD. Both patients responded well to DDAVP.In the second case the patient had a lowered vWF activity (RiCoF) but normal vWF:Ag, analogous to a Type Ila vWD pattern. Mutimer analysis however demonstrated the presence of all MW multimers with a normal triplet structure. This defect was not detected with two monoclonal antibodies that recognise the GPIb binding site on vWF and is thought to represent a minor abnormality in the vWF molecule in this patient.
EFFECT OF DDAVP ON PRIMARY HEMOSTASIS WITH CONGENITAL AFIBRINOGENEMIA
Authors: Taki M , Inagaki M , Miura T , Saito N , Meguro T , Yamada K 
Published: June 2019

It has been reported recently that DDAVP might be an useful tool in the therapy and prevention of bleeding in patients with congenital afibrinogenemia (CA).To study the mechanism of its efficacy, changes in the platelet functions of a patient with CA were examined prior to, and one hour after, the infusion of DDAVP (0.4 μg/Kg). A patient with Glanzmann's thrombasthenia (GT) was also examined, to allow a study of the role of platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa), a deficient platelet in GT, in the resulting effects of the drug. When both patients were infused with DDAVP, the level of plasma von Willebrand factor (vWF) increased two- to fourfold, accompanied by an enhancement of ristocetin-induced platelet agglutination. The level of plasma fibrinogen was never changed.The prolonged bleeding time observed was markedly improved only in the CA patient, remaining unchanged in the GT patient, after the infusion of DDAVP. This indicates that DDAVP is effective in diminishing the bleeding tendency in CA, but not in GT. Among the platelet functions tested, only the platelet retention rate on glass beads, ADP-induced platelet aggregation and collagen-induced platelet aggregation improved in CA, each remaining unchanged in GT. In particular, collagen-induced platelet aggregation was markedly improved in the CA patient. However, the platelet adhesion to collagen (50 μg/ml)-Sepharose remained normal, both before and after the infusion of DDAVP in CA.These results suggest that an increase in the plasma vWF level and the existence of platelet membrane GPIIb/IIIa may be necessary for the improvement of primary hemostasis, after the infusion of DDAVP. The vWF-mediated platelet aggregation by collagen or ADP may produce this effect in the CA patient.
SUCCESSFUL SURGICAL MANAGEMENT OF A PATIENT WITH COMBINED FACTOR V AND VIII DEFICIENCY WITH DDAVP + FFP
Authors: McKenna R , Cole E R , DOOLAS A 
Published: June 2019

A 59 year-old white male with a life long history of severe bleeding following trauma or surgical procedures was documented to have a combined factor V and factor Vlll-C deficiency. His baseline factor V ranged between 16% - 30% and factor VIII-C was between 20% - 30%. His APTT ranged between 50 - 56 seconds (21-31 N) with a prothrombin time activity between 33% - 40% of normal ( ≥ 70% N). Factor II, Vll/X, X, IX, XI, XII, template bleeding time and platelet function studies were normal. There was no severe factor XIII deficiency.
Since the response of these patients to DDAVP is unknown and the patient was admitted with a large hematoma in the subolecranon bursa, DDAVP was infused in a dose of 0.5 μ g/kg body weight over 15 minutes. The baseline factor VIIl-C of 20% rose to 55% at 5 minutes after termination of DDAVP and to 62% and 66% at 3 and 6 hours respectively. The factor VIII-C level dropped to 45% and 36% at 12 and 24 hours respectively after a single dose of DDAVP. As measured by a sensitive 125I-fibrin assay, this dose of DDAVP caused a net rise in plasminogen activator activity of 2.43 CTA U/ml.The patient had worn an inguinal truss for approximately 20 years for two large oblique inguinal hernias, one of which entended to the level of the mid-thigh. Pre and peri-operative management of the right inguinal herniorrhaphy consisted of DDAVP in a dose of 0.5 μg/kg Q 12 hourly for two doses, FFP at 9 ml/kg Q 12 hourly for three doses, and Amicar for 48 hours starting post-operatively. This regimen maintained the factor VIIl-C at ∼ 50% with factor V between 44% - 50% for a period of three days. On the 4th postoperative day a left inguinal herniorrhaphy was accomplished with DDAVP and FFP (dosage similar to previous) administered Q 12 hourly for three doses, then once in the next 24 hours, and Amicar for three days. A 4 cm wound hematoma noted on the first day of the second surgical procedure was evacuated, and was due to the presence of a bleeder since Vlll-C and V levels were higher than the values indicated on the first procedure. No red cell transfusions were given; fluids were restricted to 600 ml per day for 24 hours after the last dose of DDAVP. Successful bilateral inguinal herniorrhaphies without significant hemorrhages was achieved with exposure to a minimal volume of blood products.
HEMOPHILIAC MENINGITIS WITH PARTICULAR MANIFESTATION AND HIV ANTIBODIY IN SPINAL FLUID
Authors: Abe T , Terao T , Nakayama Y , Kato Y , Kazama M , Takahashi I 
Published: June 2019

A 25-year-old patient with hemophilia A, who had had thrombocytopenia since 1985, was admitted to a hospital in August 1986 because of headache and slight disturbance of consciousness. Diagnosis of cerebral bleeding was made based on brain CT scan. Lymphadanopathy was noted then, and after relief of the symptoms S. aureus sepsis developed. Examination of serum for HIV antibody performed at this time gave a positive result. He was transferred to our hospital for evaluation of AIDS-relatedimmunologic disorder. The ratio of T4/T8 was 0.16, but no definitive opportunistic infections were found. Soon later, he developed headache and fever. There were no other neurological signs. Spinal fluid examination revealedlymphocytic pleocytosis without bacilli, fungi or antibodiesto viruses commonly causing encephalomeningitis. However, antibodyto HIV was detected in the spinalfluid. By a supportive care with useof antibacterial agents thesymptoms were alleviated with diminishing of the pleocytosis in spinal fluid. Lentinan, an antitumor polysaccharide, was administered with some effect on his immunologic functions. Three months later, meningitis recurred which wasalsorelieved by a supportive care.HIV is known to cause meningeal and CNS diseases. In this case the presence of HIV antibody in the spinal fluid was interpreted to be due to HIV invasion of nervous system. Furthermore, this casehas some particular feature in consideration of the common pictureof neurological involvements of AIDS, indicating that HIV induced a variety of meningeal and CNS manifestations.
HTLV III/LAV ANTIBODY STATUS, AND IMMUNOLOGICAL ABNORMALITIES IN A HEMOPHILIC POPULATION FROM PORTUGAL Campos
Authors: Campos M , Santos L , Lobato J , Melo C , Justica B 
Published: June 2019

An immunological study in a population of 46 hemophiliacs (A and B)under replacement therapy mainly with cryo, plasma and eventually withccmercial concentrates was carried out to detect changes related to HTLV III infection and those due totreatment. We followed the patients during 85-87 and we evaluate the abnormalities over a period of 2 years . Methods. Ig's (nephelometry): total lymphocytes, T3, T4, T8 subsets and B cells (IF microcopy):delayed hypersensivity skin tests (DHST) ,7 antigens: serology for HTLV III (ELISA and WB) (β 2 microglobulin (ELISA) Results. In 85,10 patients had anti HTLV III(28%) and all these received concentrates.9 out 46 had never been treated with concentrates and all were negative for HTLV III . Most of the HTLV III +ve patients showed lymphopenia, low T4 and total B cells, anergy or depressed DHST,increase Ig levels, mainly IgG and IgM. Among the HILV -ve patients there were no significant diferences between tose treated withconcentrates and most showed only an increased Ig's levels (IgG and IgM During 85 and 86 all the patients were treated with plasma, cryo and heat-treated concentrates. In the end of 86 none of the seronegative showed seroconversion. Among the 10 seropositives in 85,1 died (AIDS) ,1 is in ARC and 8 are ssymptomatic . All theseroposi tive patients shows high levels of β2 microglobulin.Conclusions . The low incidence of seropositivity for HTLV III,is probably due to the scarce use of comercial concentrates before 85. The absence of seroconversion despite the use of heat-treated concentrates is probably due to the safe of the product s. We must emphazise the absence of clinical symptoms in 8 seropositive patientsduring two years. There is a positive correlation between the level of (β2 microgldbulin and the seropositivity. Theimmunological profile observed is related more to the parenteraladministration of blood products thanto the specific composition and/or method of preparation of the therapeutic products. The serological profile from the HTLV III +ve patients isprobably a result of the administration in the past of comercial concentrates virus infected.
HEMOSTATIC PARAMETERS DURING PREPARATION OF LEUKOCYTE-POOR BLOOD
Authors: Losito R , Sternbach M , Masson A , Paguin M , Boyer A , Trepanier A 
Published: June 2019

Non-hemolytic febrile transfusion reactions are believed to be due to sensitization to granulocytes. Leukocyte removal can diminish or prevent the reaction. Use of the Pall filter (Pall Bio Medical Prod. Corp.) has resulted in some patient reactions. The purpose was to re-investigate this filter in vitro and compare it to the Imugard (Terumo) and the Erypur (Organon Teknika) filters and study their influence on hemostatic activation pathways. Method: RBC cones., aged 5 or 10 days, were centrifuged (5,200 R. P. M., 4°C, 15 m.). Cells were leftundisturbed for 6-24 hours before filtration. Hematological parameters analysed included: leukocyte, red cell and platelet counts, differential and scanning electron microscopy. Activation studies related to clotting, fibrinolysis, kinin and complement pathways including both biological and immuno-assays; they consisted of the recal time, PTT, pro time, Factors I, VIII, XII, HMW kininogen, kallikrein, F. D. P., AT-III, alpha 2-macroglobulin, alpha 1-antitrypsin, plasminogen, Cl inactivator, C3, C4 and C5. Over 75 filtrations have been performed. Results of cell recovery are illustrated in table below. Changes in tests related to activation were minimal with the Pall filter while a wide spectrum of derangements were common with the other twofilters.Conclusion: it appears the Erypur filter gives optimal results in the removal of leukocytes and platelets, whereas there is good recoveryof red cells by the Pall and Imugard filters. Secondly, the Pall filter (nylon) does not appear to be involved with the contact pathways whereas Erypur (cellulose acetate) and Imugard (cotton) have an influenceon these pathways.
FIBRINOLYTIC POTENCY OF NON ANTICOAGULANT, OXI-EEDUCED SLOW AND FAST MOVING HEPARINS
Authors: Porta R , Pescador R , Niada R , Mantovani M , Prino G 
Published: June 2019

It is well known that heparin is able to induce an increase of fibrinolytic activity when i.v. administered in man and in several animal species. Nevertheless, its anticoagulant properties can cause serious problems of bleeding and this restricts the therapeutic use of heparin. An oxi-reductive process applied to heparin leads to a conpound with reduced anticoagulant activity. Moreover, heparin can be separated into slow moving (SM) and fast moving (FM) components on the basis of electrcphoretic properties. The SM and FM components display quantitatively different biological activities. The aim of this paper was to verify if the oxi-reduction could affect or not the fibrinolytic activities of SM and FM. SM and FM, prepared by ethanolic precipitation from parent heparin, were oxidized by periodate and stabilized by reduction (RO-SM and RO-FM). The USP, APTT and anti Xa titres were determined in vitro using sheep plasma and kits from Boehrirger Biochemia (APTT) and Sigpia (Anti Xa). Fibrinolytic activities were assessed ex vivo after i.v. injection into rabbits at different doses to find out the effective dose hundred (ED100). The euglobulin fraction obtained from plasma was applied on human fibrin plates and the lysis areas were measured. The Table gives the resultsThe oxi-reduction decreased dramatically the anticoagulant activities of SM and FM heparins while their fibrinolytic activities were practically unaffected. Tne oxi-reduced heparins could be helpful therapeutic agents in pathological conditions characterized by a diminished fibrinolytic activity. They could represent an effective alternative to heparin; the very lew anticoagulant activities reduce the risk of bleeding, specially in the high risk patients, while the good fibrinolytic activity, comparable to heparin, could allow the dissolution of fibrin clots.
PRODUCTION AND CHARACTERISATION OF MONOCLONAL ANTIBODIES AGAINST HEPARIN Deborah
Authors: Rathjen A , Geczy Carolyn L 
Published: June 2019

To complement the studies using MAbs to AT III and because of the reported ability of heparin to modulate several aspects of the cell-mediated immune response, we have prepared two mouse monoclonal antibodies (MAbs) to porcine mucosal heparin.MAb 25/15 is an IgGl and MAb 26/7 is an IgM. Both MAbs have iso-electric points between pH5.85 and 6.55. The MAbs recognise porcine and bovine mucosal heparin and rat mast cell heparin. Heparins with both high and low affinitiesfor antithrombin III (ATIII) bound both MAbs but neither MAb altered the binding of heparin to AT III. These antibodies did not recognise other proteoglycans (chondroitin sulphate types A, B and C, keratan sulphate and hyaluronic acid) with the exception of heparan sulphate, (the cellular equivalent of heparin) and Arte- paron (Luitpold-Werk, Munchen; a synthetically poly- sulphated chondriotin sulphate), in competition and solid-phasebinding assays. Dextransulphate(Pharmacia) was also recognised by these MAbs. Cross-reactivity with Arteparon and dextran sulphate indicate that charged sulphate goups on the mucopolysaccharides may be importantBfor MAb binding. The Mabs described may beuseful probes for endogenous heparin at the cellular and tissue level and may allow further investigation of the many biological activitiesof heparin
PROPHYLAXIS AGAINST POSTOPERATIVE DEEP VEIN THROMBOSIS (DVT)- A DOUBLE-BLIND MULTICENTER TRIAL COMPARING A HEPARIN FRAGMENT GIVEN ON THE EVENING BEFORE SURGERY WITH CONVENTIONAL LOW DOSE HEPARIN
Authors: Bergqvist D , Frisel J , Hallböök T , Horn A , Lindhagen A , Ljungndér H , Ljungström K G , Mätzsch T , Onarheim H , Risberg B , Törngren S , Örtenwall P , Burmark U S 
Published: June 2019

Bergen, Halmstad, Goteborg and KabiVitrum AB Stockholm, Sweden and Norway. At the Xth Int. Congress on Thrombosis and Haemostasis in San Diego results from a multicenter trial on 432 patients were presented, comparing a low molecular weight heparin (LMWH) fragment (Fragmin, Kabi) once daily with low dose heparin twice daily. Prophylaxis started 2 hours preoperatively. The frequency of postoperative DVT did notdiffer (6.4 % v. 4.3 %) but the onset of thrombosis was delayed in the LMWH group. Haemorrhagic complications occurred significantly more often in the LMWH group (11.6 % v. 4.6 ?o). The results were similar independent whether the analysis was made according to the intention to	treat principle or based on patients with correct prophylaxis. On the basis of these data and newer knowledge regarding the pharmacokinetics of LMWH a second prospective randomized double-blind multicenter trial on patients.older than 40 years undergoing elective abdominal surgery was started. The only difference was that the first dose of 5000 ariti-factor Xa units of LMWH was given on the evening before surgery. Only conventional low dose heparin was given 2 h before surgery. The study is designed to include 1000patients, a number which will be obtained during the spring 1987. At the time of abstract deadline 799 patients have been included. The over-all frequency of DVT (fibrinogen uptake test) is 6.8 %, the frequency of haemorrhagic complications 3.6 % and mortality 1.8 % (one fatal pulmonary embolism). These frequencies remained unaltered after inclusion of 336, 576, 655 and 799 patients. Although the code has not been broken yet, it can be concluded that the new regimen with start of prophylaxis the evening before surgery has not altered the frequency of DVT or mortality whereas the frequency of haemorrhagic side effects has decreased considerably.
PROTEIN C, FIBRINOGEN KINETICS AND PLATELET SURVIVAL IN PATIENTS WITH RECURRENT VENOUS THROMBOSIS
Authors: Crow M J , Learoyd P A , Warrington R , Rajah S M 
Published: June 2019

Recurrent venous thrombosis though uncommon leads to post phlebitic limb syndrome. The pathogenesis is not readily definable in all cases. We have examined the platelet, coagulation and fibrinolytic systems of a small group of patients with venographically proven recurrent thromboses. Currently 14 patients have been studied. Besides routine investigations all patients had the following: 111 In labelled platelet survival, 125 I fibrinogen kinetics, Protein C (functional and antigenic), a full fibrinolytic screen, antithrombin 111 and plasma B-Tg. With the exception of isotopic studies all investigations were performed on two occasions. No patient was suffering a thrombotic event at the time of inclusion into the study. Protein C levels, fibrinolytic screens and antithrombin 111 levels were within normal limits for all patients, while plasma B-Tg was raised. Platelet and fibrinogen kinetic data is shown in the table (mean+/−SEM):Mean fibrinogen kinetics were normal with only 2 patients displaying increased turnover. Mean platelet survival was reduced and turnover raised, although a further 2 patients had normal values. These results indicate that this group of patients requires extensive investigation including isotopic studies. The shortened platelet survival time found appears to indicate platelet activation and consequently a possible therapeutic role for antiplatelet drugs combined with anticoagulants
PLASMA DEHYDROEPIANDROSTERONE SULPHATE CONCENTRATIONS AND DEEP VEIN THROMBOSIS AFTER MAJOR ABDOMINAL SURGERY
Authors: Mellbring G , Chotai J , Nilsson T K 
Published: June 2019

Dehydroepiandrosterone sulphate (DHEAS) is a major secretory product of the human adrenal gland. Its precise functions are uncertain, but it has been postulated as a discriminator of life expectancy and aging. We have previously reported significantly lower plasma levels of DHEAS pre- and postoperatively in men developing DVT after major abdominal surgery, as compared to patients who remained free of DVT. Recent data suggest that the DHEAS concentration is also independently and inversely related to death from cardiovascular disease in men over 50 years of age. We here report data on preoperative plasma concentrations of DHEAS (measured with RIA) in 96 patients over 40 years of age, who underwent major abdominal surgery, and correlated the result to the development of postoperative DVT as diagnosed by the 125I-fibrinogen uptake test.Thirty patients (31%) developed postoperative DVT during the first ten postoperative days. The plasma levels of DHEAS were significantly lower in the patients with postoperative DVT compared to those without (median 1.95 umol/1; Q1−Q3, 1.30−3.00 vs. median 3.35 umol/1; Q1−Q3 1.60−4.70; p < 0.02). Ninety per cent of the patients who developed postoperative DVT had a DHEAS value lower than 3.9 umol/1, while 45 % of the patients who remained free of DVT had a DHEAS value higher than 3.9 umol/1.In conclusion, the data suggest that a low preoperative value of DHEAS predisposes the development of postoperative DVT in patients undergoing major abdominal surgery. It seems like the DHEAS concentration in plasma can be a valuable factor in a predictive index for postoperative DVT in those patients.