bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactions of Polylysine with Human Platelets in Plasma and in Suspensions of Washed Platelets
Authors: Guccione M. A , Packham M. A , Kinlough-Rathbone R. L , Perry D. W , Mustard J. F 
Published: July 2018

SummaryThe effects of polylysine on human platelets have been examined in citrated platelet-rich plasma (PRP) and in suspensions of washed platelets in various media. In PRP, polylysine caused aggregation after a lag phase. Heparin inhibited this completely. At certain concentrations of polylysine, two phases of aggregation occurred, the second being associated with release of 14C-serotonin from prelabelled platelets; this phase was inhibitable with prostaglandin E1, acetylsalicylic acid, sulphinpyrazone, adenosine, apyrase, or creatine phos- phate/creatine phosphokinase. Polylysine-induced release also occurred in PRP with EDTA or hirudin as anticoagulant. In suspensions of washed platelets in Tyrode solution containing 0.35% or 4% albumin, or 1% gelatin, polylysine caused immediate platelet-to-platelet adherence and very little release of 14C-serotonin or platelet lysis. Heparin inhibited aggregation, but acetylsalicylic acid, prostaglandin E1, adenosine, apyrase, creatine phosphate/creatine phosphokinase or EDTA did not. In a modified Tyrode-albumin medium containing 1 mM magnesium but no calcium, polylysine-induced aggregation was associated with the release of 14C-serotonin which could be inhibited by acetylsalicylic acid or indomethacin; this is similar to the effect of ADP in this medium. In Tyrode solution without albumin or gelatin, polylysine-induced platelet aggregation was associated with release of a large percentage of 14C-serotonin, together with as much as 18% lysis; indomethacin inhibited this release reaction.
Severe Antithrombin III Deficiency in an Infant Associated with Multiple Arterial and Venous Thromboses
Authors: Mendelsohn Geoffrey , Gomperts Edward D. , Gurwitz Dennis 
Published: July 2018

SummaryInherited antithrombin III (AT-II, heparin cofactor) deficiency is a rare condition, presenting with thrombotic disease in adult life. This paper reports an 8 months old South African Black male infant with multiple large vessel venous and arterial thromboses, and E. coli septicaemia. This was associated with an extremely low plasma AT-II level. Micronodular cirrhosis and intracytoplasmic hyaline globules in the liver cells were present. These globules were eosinophilic, and PAS-positive after diastase. They measured approximately 5 μ to 30 μ in diameter, occurred singly in the liver cells and were located mainly in the periportal areas. The histological findings in the liver are similar to those observed in α1-antitrypsin (AAT) deficiency in which the intracytoplasmic globules represent accumulation of altered AAT. Immunochemical studies carried out on formalin fixed tissue failed to detect cross reaction material with anti-α1 antitrypsin or anti-AT III antiserum. This is the first case report of AT-III deficiency presenting in infancy. It is also the first case associated with distinctive liver pathology.The available data presented are insufficient to distinguish between an inborn defect and acquired causes of the severely depressed AT-III plasma level and the distinctive liver pathology.
The Influence of Ethanol Feeding on the Activities of Factors II, VII, VIII, IX and X in Rats
Authors: Mørland Jørg , Holm Turid , Prydz Hans 
Published: July 2018

SummaryThe effect of chronic administration of ethanol to rats in a controlled regimen upon the activities of the coagulation factors II, VII, VIII, IX and X has been studied.No significant differences were found for factor II, IX and X between the ethanol-treated rats and the control group given an isocaloric diet with carbohydrate replacing ethanol. Factor VII activity was somewhat higher and factor VIII activity decreased significantly in the experimental group when ethanol treatment was combined with an approximately two-fold increase in dietary polyunsaturated fatty acid.
Bleeding Disorder with Abnormal Wound Healing, Acid-Soluble Clots and Normal Factor XIII
Authors: Ragaz Stefan , Kemp Graham , Furlan Miha , Beck Eugene A. 
Published: July 2018

SummaryAn unusual bleeding disorder clinically resembling factor XIII deficiency is presented. The only detectable coagulation abnormality was rapid clot dissolution in 1% monochloroacetic acid. This abnormality was ascribed to the sustained increase of a pepsin-like plasma protease which is activated at low pH. A systematic search for similar phenomena revealed that massive blood transfusion may also enhance plasma-clot solubility in acid, possibly by release of a red cell protease. We conclude that the acid clot solubility test is not a specific indicator of factor XIII deficiency, but this simple assay is recommended for further studies of acid plasma protease activity. The diagnostic relevance and pathophysiologic importance of increased pepsin-like activity in plasma remain to be elucidated.
Parenteral Anticoagulation with the Heparinoid Lomoparan (Org 10172) in Patients with Heparin Induced Thrombocytopenia and Thrombosis
Authors: Ortel Thomas L , Gockerman Jon P , Califf Robert M , McCann Richard L , O’Connor Christopher M , Metzler Diane M , Greenberg Charles S 
Published: July 2018

SummaryProgressive thrombocytopenia may develop in as many as 5% of patients receiving heparin anticoagulation. In these patients, the risk of thromboembolic complications as well as continued thrombocytopenia necessitates discontinuation of heparin and initiation of an alternative anticoagulant when indicated. The heparinoid Lomoparan (Org 10172) is a mixture of several nonheparin low molecular weight glycosaminoglycans with proven anticoagulant efficacy that is generally non-reactive with platelets in the presence of plasma from patients with heparin induced thrombocytopenia, whereas standard heparin will induce platelet aggregation. We evaluated the role of heparinoid as a potential alternative anticoagulant in patients with heparin induced thrombocytopenia. During a 6 month period, we identified six patients with heparin induced thrombocytopenia who required an alternative parenteral anticoagulant, four as primary treatment for specific medical problem, and two as anticoagulation during a necessary surgical procedure. Heparinoid was used successfully in both medical and surgical patients requiring parenteral anticoagulation. In no case was there an exacerbation of the thrombocytopenia nor thromboembolic complications while on heparinoid therapy. Three of our patients sustained hemorrhagic complications, predominantly in the post-surgical setting in association with elevated anti-factor Xa levels and additional anticoagulant agents. We feel that these results confirm the utility of heparinoid anticoagulation in a select subset of patients with heparin induced thrombocytopenia who require continued parenteral anticoagulation.
Immune Status of Asymptomatic HIV-Infected Hemophiliacs: Randomized, Prospective, Two-Year Comparison of Treatment with a High-Purity or an Intermediate-Purity Factor VIII Concentrate
Authors: Mannucci P M , Gringeri A , de Biasi R , Baudo F , Morfini M , Ciavarella N 
Published: July 2018

SummaryIt has been postulated that high-purity factor VIII (FVIII) concentrates, since they contain less alloantigenic proteins than intermediate-purity concentrates, might cause lesser deterioration of the immune systems of hemophilic patients infected with the human immunodeficiency virus (HIV). To evaluate this hypothesis, we have prospectively compared T-lymphocytes subsets and delayed hypersensitivity reactions to skin tests in 17 asymptomatic HIV-positive hemophiliacs randomly assigned to continue treatment with an intermediate-purity concentrate with those of 16 hemophiliacs changed to a high-purity concentrate. For both groups, during the 24-month follow-up period CD4 cell counts showed similar rates of fall from baseline values. There was also no difference in the number of patients anergic to skin tests. Three patients treated with the intermediate purity concentrate and one treated with the high-purity concentrate developed symptoms of HIV infection. On the whole, no striking benefit is conferred to the immune status of asymptomatic HIV-positive hemophiliacs by using this high-purity concentrate for 2 years.
Pharmacological Properties of a Low Molecular Weight Butyryl Heparin Derivative (C4-CY 216) with Long Lasting Effects
Authors: Saivin S , Petitou M , Lormeau J C , Dupouy D , Sié P , Caranobe C , Houin G , Boneu B 
Published: July 2018

SummaryWe have investigated the pharmacological properties of an O-acylated butyryl derivative of the low molecular weight heparin CY 216 (C4-CY 216). In a purified system the ability of C4-CY 216 to catalyze thrombin and factor Xa inhibition was comparable to that of CY 216. The antithrombin and antifactor Xa catalytic efficiencies of C4-CY 216 were reduced 217 and 12 times respectively when albumin (10 mg ml-1) was added to the reagents, while those of CY 216 were essentially unchanged. In plasma, the antifactor Xa specific activity of C4-CY 216 was close to that of CY 216 but the antithrombin specific activity was 2 times lower. After bolus and continuous intravenous injection to rabbits, the clearances of the two activities of C4-CY 216 were on average half the corresponding values of CY 216. After subcutaneous injection, the bioavailability of C4-CY 216 was comparable to that of CY 216. C4-CY 216 was as potent as CY 216 in preventing venous thrombosis in the thromboplastin-Wessler model and the duration of the antithrombotic effect was longer than that of the parent compound. The chemical alteration of CY 216 did not enhance the prohaemorrhagic effect in the rat tail transection model. Therefore, the new concept of heparin derivative having a low clearance and long lasting effects that we have recently reported for unfractionated heparin may also be applied to a low molecular weight heparin.
Anticoagulant Efficacy and Immunogenicity of the Selective Factor Xa Inhibitor Antistasin Following Subcutaneous Administration in the Rhesus Monkey
Authors: Dunwiddie Christopher T , Nutt Elka M , Vlasuk George P , Siegl Peter K S , Schaffer Linda W 
Published: July 2018

SummaryThe antithrombotic efficacy and duration of action of a single subcutaneous administration of the selective factor Xa inhibitor recombinant antistasin (rATS) was evaluated in a rhesus monkey model of mild disseminated intravascular coagulation. rATS (1 mg/kg) was shown to be fully effective and comparable to standard heparin (1,000 U/kg) in the suppression of thromboplastin-induced fibrinopeptide A generation for at least 5 h following a single subcutaneous administration. The absorption rate of rATS, as measured by ex vivo activated partial thromboplastin times (aPTT), mirrored that of standard heparin exhibiting peak anticoagulant activity between 1 and 2 h post administration. The anticoagulant effects of a single rATS dose lasted for longer than 30 h maintaining an aPTT value at least 2-fold higher than baseline. Repeated subcutaneous administrations of rATS resulted in the generation of fully neutralizing antibodies. These results suggest that specific factor Xa inhibition may be as effective as standard heparin in the treatment of venous thrombosis. Due to its antigenicity however, rATS is probably not suitable for chronic subcutaneous anticoagulant therapy.
Transforming Growth Factor β (TGF-β)Inhibits Expression of Fibrinogen and Factor VII in a Hepatoma Cell Line
Authors: Hassan Jane H , Chelucci Cristiana , Peschle Cesare , Sorrentino Vincenzo 
Published: July 2018

SummaryWe have investigated the effect(s) of transforming growth factor (TGF)-β1 and interleukin (IL)-6 on the expression of fibrinogen and blood coagulation factors VII, IX, X mRNAs in a hepatoma cell line (Hep 3B). The results indicate that TGF-β induces a decrease of the basal level of fibrinogen and factor VII mRNAs, but does not affect factor X expression. Furthermore, TGF-β efficiently antagonizes the IL-6 induction of fibrinogen mRNA at late (12-48 h) but not early (6 h) times: this effect is apparently mediated by posttranscriptional mechanism(s). These findings, together with previously reported data on the inhibitory effect of TGF-β on acute phase genes (e.g., ApoAl and albumin), suggest a role for TGF-β in the regulation of liver genes expression. The early stimulatory and late inhibitory effect exerted by IL-6 and TGF-β respectively on fibrinogen mRNA level may play a role in the regulatory mechanism(s) of clot formation in a variety of conditions.
Heparin-Associated Thrombocytopenia: The Antibody Is Not Heparin Specific
Authors: Greinacher A , Michels I , Mueller-Eckhardt C 
Published: July 2018

SummaryIn this study the hypothesis was assessed whether heparin-associated thrombocytopenia (HAT) may be caused by an antibody dependent on polysulfated oligosaccharide epitopes, present not only on heparin but also on different polysulfated substances such as dextran sulfate and pentosan polysulfate. We found that the major factor for eliciting platelet activation with sera of HAT type II patients is neither the structure nor the AT III binding capacity of an oligosaccharide, but rather its grade of sulfation. This was shown by in vitro crossreactivity studies with 40 sera of HAT type II patients using unfractionated heparins, LMW heparins (Fragmin, Fraxiparin), enoxaparin, LMW heparinoid (Org 10172 and its subfractions), de-N-sulfated heparin, dermatan sulfate, dextran sulfate, pentosan polysulfate and dextran. Platelet activation was measured by the heparin induced platelet activation (HIPA) assay and the serotonin release assay (SRA). The platelet activating factor was isolated with the IgG fraction, but did not bind to heparin and dextran sulfate fixed to a solid phase. By isoimmune fixation electrophoresis a monoclonal gammopathy was ruled out in the three sera assessed. The in vivo effect of different LMW heparins and the heparinoid Org 10172 was observed in 10 patients with HAT type II. In a prospective study, a compatible heparin-like anticoagulant was selected for 10 HAT patients for whom further parenteral anticoagulation was required. The only substance that showed no crossreactivity in vitro was the LMW heparinoid Org 10172, which differs from heparin and LMW heparins by its low-grade sulfation. Upon treatment with the heparinoid, all 10 patients had a good clinical outcome, even if they had previously developed thromboembolic complications under LMW heparin administration. As Org 10172 contains a small amount of a LMW heparin-like substance (3%) this heparinoid should not be used in HAT patients without prior in vitro testing. We conclude that heparin-associated thrombocytopenia is not caused by a heparin-specific antibody and that a major factor contributing to the pathomechanism is the high grade of sulfation present in a variety of polysulfated oligosaccharides.
Three Distinct Candidate Point Mutations of the von Willebrand Factor Gene in Four Patients with Type IIA von Willebrand Disease
Authors: Sugiura Isamu , Matsushita Tadashi , Tanimoto Mitsune , Takahashi Isao , Yamazaki Tomio , Yamamoto Koji , Takamatsu Junki , Kamiya Tadashi , Saito Hidehiko 
Published: July 2018

SummaryType IIA von Willebrand disease (vWD) is the most common type II vWD and is characterized by the selective loss of large and intermediate sized multimers. One explanation for this disorder has been postulated to be a qualitative defect in von Willebrand factor (vWF) which results in increased susceptibility to proteolysis at the bond between residues Tyr842 and Met843. Four missense mutations that may cause type IIA vWD have recently been identified near the cleavage site. We analyzed the molecular basis for type IIA vWD in six patients. A 512 bp DNA sequence spanning the proteolytic cleavage site was targeted for PCR amplification and sequencing. We exploited a difference in restriction sites between the vWF gene and the pseudogene and have designed allele-specific oligomer used with PCR to distinguish these two genes. Three candidate missense mutations; Ser743 (TCG) → Leu (TTG), Leu799 (CTG) → Pro (CCG), and Arg834 (CGG) → Trp (TGG) were identified in 4 out of 6 patients. The amino acid substitution at Arg834 has been reported previously, but the other substitutions at Ser743 and Leu799 are novel candidate mutations locating 99 and 43 amino acids to the N-terminal side of the cleavage site, respectively. Our results indicate that amino acid substitutions located relatively distant from the cleavage site may also be involved in type IIA vWD.
Characterization of Three Mutations Causing von Willebrand Disease Type IIA in Five Unrelated Families
Authors: Inbal Aida , Seligsohn Uri , Kornbrot Nurit , Brenner Benjamin , Harrison Paul , Randi Anna , Rabinowitz Ian , Sadler J Evan 
Published: July 2018

SummaryVon Willebrand disease (vWD) type IIA is characterized by decreased ristocetin-induced platelet aggregation, and by the absence from plasma of high molecular weight multimers of von Willebrand factor (vWF). Most mutations causing vWD type IIA are clustered within the A2 domain of the mature vWF subunit that is encoded by exon 28. Using the polymerase chain reaction (PCR), the entire exon 28 from patients with vWD type IIA and normal controls was amplified and sequenced. Three missense mutations were detected that result in the amino acid substitutions Arg(834)→Trp, Gly(742)→Glu, and Ser(743)→Leu. The first mutation occurred independently in three unrelated families; each of the latter mutations was found in one family. By restriction endonuclease analysis and allele-specific oligonucleotide (ASO) hybridization the mutations were confirmed in affected family members and excluded in unaffected members and 50 normal controls. The apparently high frequency of identical independent mutations among patients with vWD type IIA suggests that a precise diagnosis may be possible in a majority of patients using relatively simple recombinant DNA screening assays.
Low Molecular Weight Heparin and Prevention of Postoperative Thrombosis in Abdominal Surgery
Authors: Koppenhagen K , Adolf J , Matthes M , Tröster E , Roder J D , Haas S , Fritsche H M , Wolf H 
Published: July 2018

SummaryIn a prospective, double-blind, randomized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery. Six hundred and seventy-three patients were randomly allocated to the two prophylaxis groups; 20 of these, however, did not undergo surgery and did not receive any prophylaxis. Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day. Treatment was initiated 2 h preoperatively and continued for 7 to 10 days. The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography. Venous thrombosis was diagnosed in 24 of 323 patients (7.4%) treated with low molecular weight heparin and in 26 of 330 patients (7.9%) treated with low-dose heparin. DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group. During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin. No pulmonary embolism was found in patients treated with low molecular weight heparin. Both prophylactic schemes were well tolerated. Intra-and postoperative blood loss, incidence of wound hematoma, frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group. The results of this trial show that the investigated low molecular weight heparin is at least as effective and safe as low-dose heparin in preventing deep vein thrombosis in patients undergoing elective abdominal surgery.
β2-Glycoprotein I Deficiency and the Risk of Thrombosis
Authors: Bancsi László F J M M , van der Linden Irma K , Bertina Rogier M 
Published: July 2018

Summaryβ2-glycoprotein I (β2-GP I) is a plasma protein with a high affinity for negatively charged surfaces. In vitro this protein shows a variety of anticoagulant properties (inhibition of contact activation and platelet dependent prothrombinase activity). Therefore we studied the possibility that a hereditary β2-GP I deficiency is a risk factor for (familial) thrombophilia.Plasma β2-GP I levels were measured in healthy volunteers and four different groups of patients with (familial) thrombophilia. In these 5 groups the prevalence of β2-GP I deficiency (i. e. β2-GP I antigen <77%) was found to be very similar (6.8-12.5%) and statistically not significantly different. This observation suggests that β2-GP I deficiency in itself is not a risk factor for thrombosis.One thrombophilic patient was found to be homozygous deficient of β2-GP I. The transmission of the defect in his family followed autosomal inheritance. One of his brothers was also homozygous deficient and at the age of 35 years still free of thromboembolic complications.The possibility that β2-GP I deficiency could be an additional risk factor for the development of thrombophilia in families with protein C deficiency was evaluated in a panel of 70 unrelated patients with clinically dominant protein C deficiency. The prevalence of β2-GP I deficiency in this group of patients (12.8%) was very similar to that in other groups of normals and patients. Moreover, there was no difference in the frequency of β2-GP I deficiency in symptomatic and asymptomatic protein C deficient patients.
A Soluble Recombinant Factor VIII Fragment Containing the A2 Domain Binds to Some Human Anti-Factor VIII Antibodies that Are not Detected by Immunoblotting
Authors: Scandella Dorothea , Timmons Lisa , Mattingly Mora , Trabold Norma , Hoyer Leon W 
Published: July 2018

SummaryHuman factor VIII (f VIII) inhibitors are pathologic antibodies that inactivate fVIII. A cDNA clone was modified to encode f VIII amino acid residues 373-740 for expression in a baculovirus vector in insect cells. The encoded protein fragment H2 was produced as a soluble, secreted protein, and it was used to test inhibitor plasmas for the presence of antibodies that were not detected by immunoblotting. Seven of 13 inhibitors that bound, only to the fVIII light chain by immunoblotting also bound to fragment H2 in an immunoprecipitation assay. Thus multi-chain inhibitor reactivity of inhibitors is more frequent than previously reported. One of these inhibitors was shown to share the epitope for other inhibitors that bind to H2 within amino acid residues 373-541 in immunoblotting assays. The sensitive immunoprecipitation assay described allows determination of relative H2 binding capacity of the total IgG and epitope localization of inhibitors that cannot be similarly characterized by immunoblotting.