bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Integration of Government Funding and Family Support for Musculoskeletal Tumor Care in a Resource-Constrained Country
Authors: Adegbehingbe O.O. , Akinyoola A.L. , Ariyibi A.L. , Oginni L.M.
Published: May 2009

Background: Malignant musculoskeletal tumor (MMST) outcome reflects the level of supportive care provided. In Nigeria, the supportive care available to patients with MMST is limited by a lack of funding. Patients often present late, and receive only orthodox care as psychosocial care is not available. We evaluated the effect of direct incorporation of government funding and family support on MMST patient acceptance and completion of treatment. Methods: A 3-year prospective multicenter intention-to-treat study was undertaken in a tertiary care setting. The first step was a nonselective randomization of MMST patients into 2 groups, Wesley Guilds Hospital Firm A (WGHFA) and Wesley Guilds Hospital Firm B (WGHFB) using the computer software Excel. The control group was WGHFA, which consisted of patients who self-financed their oncology care. The WGHFB patients’ governments (local or state) provided funds according to medical reports and the patients had relatives who offered psychosocial support. The second step entailed treatment (surgery, chemotherapy and radiotherapy) and follow-up. Outcome measures were the interval between presentation at hospital and surgical intervention, acceptability of limb amputation, completeness of treatment courses, duration of hospital stay and mortality. The reproducibility of the methodology was reappraised at the Federal Medical Center. Kruskal-Wallis analysis was used, and an alpha error of <0.05 at a CI of 95% was taken to be significant. Results: A total of 112 cases of MMST were managed during the study period. Seventy-one (63.4%; 37 WGHFA; 34 WGHFB) met the inclusion criteria. Age, sex, tribe, religion, comorbid factors and mean weekly income were not significant factors influencing improved MMST care among the WGHFB patients. 32 WGHFB versus 7 WGHFA patients accepted the treatment plan. The mean duration of hospital stay before surgery (p < 0.001), discharge against medical advice (p < 0.000), limb salvage (21 vs. 2, p < 0.001), limb amputation (3 vs. 12, p < 0.05, 95% CI 8.3–37.9), completeness of treatment (33 vs. 7, p < 0.05), mean duration of hospital stay, in days (23 vs. 39, p < 0.05) and mortality at 1-year follow-up (13 vs. 28, p < 0.02) were significant. Conclusion: The cost of cancer care is a challenge for patients with MMST in a resource-constrained country such as Nigeria. Direct integration of the government and family into MMST care will serve as a link between the cancer patient and the source of funds. It raises the possibility of an effective psychosocial approach to improve patient outcome through enhanced treatment acceptability and completion, and so reduce morbidity and short-term mortality.
Neoadjuvant 5 Fluorouracil-Cisplatin Chemoradiation Effect on Survival in Patients with Resectable Pancreatic Head Adenocarcinoma: A Ten-Year Single Institution Experience
Authors: Turrini Olivier , Viret Frédéric , Moureau-Zabotto Laurence , Guiramand Jérome , Moutardier Vincent , Lelong Bernard , de Chaisemartin Cécile , Giovannini Marc , Delpero Jean-Robert
Published: May 2009

Objectives: It is the aim of this study to assess the outcome of patients who received neoadjuvant 5-fluorouracil-cisplatin chemoradiation (CRT) for stage I/III pancreatic adenocarcinoma. Methods: Eligible patients (n = 101) received radiation therapy (45 Gy) associated with continuous infusion of 5-fluorouracil accompanied by a cisplatin bolus. Results: Of the 102 patients enrolled in the study, 26 patients had progression of cancer during treatment and were deemed unresectable; 1 patient died during CRT of septic shock. Sixty-two of 75 remaining patients underwent pancreaticoduodenectomy. The overall median survival of all 102 patients in the study was 17 months, with a 5-year survival of 10%. For patients who underwent resection, the median survival was 23 months. Correspondingly, the median survival was 11 months for the 40 unresected patients (p = 0.002). The 5-year survivals for resected and unresected patients were 18 and 0% (p = 0.01), respectively. A complete pathological response to neoadjuvant CRT was noted for 8 patients (13%). Margin and lymph node positivity was present in 5 (8%) and 15 (24%) patients, respectively. There was documented local recurrence in 8 (13%) and distant recurrence in 36 (58%) patients, with the liver being the most common site. Conclusion: Neoadjuvant 5-fluorouracil-based CRT had a limited impact on survival but appeared to be associated with improved local control.
Cardiac Surgery with Extracorporeal Circulation in Severe Factor VII Deficiency
Authors: Ferster A. , Capouet V. , Deville A. , Fondu P. , Corazza F.
Published: May 2009

We describe here successful open heart surgery with extarcor-poreal circulation and haemodilution in a child with severe congenital factor VII deficiency. Substitution therapy was realized with factor VII concentrate (SD proconvertin concentrate, Bio-Transfusion). This is the first report case of successful cardiac surgery in severe congenital factor VII deficiency.
Characterization of a Novel Activation-Specific Antiplatelet Monoclonal Antibody
Authors: Fukuroi T. , Kawakatsu T. , Nomura S. , Hamamoto K. , Kido H. , Yamaguchi K. , Suzuki M. , Yanabu M. , Soga T. , Kokawa T. , Yasunaga K.
Published: May 2009

We developed a murine monoclonal antibody (KmT-50) which binds to a protein expressed on the surface of human platelets after activation. KmT-50 is an immunoglobulin G1 monoclonal antibody that recognizes a 50-kD antigen localized in intracellular organelles and the open canalicular system of unstimulated platelets. After platelets were stimulated, the antigen was secreted via the surface-connected canalicular system and exposed on the platelet membrane. KmT-50 bound not only to human platelets, but also to rabbit and monkey platelets. This new antibody may be useful for experimental studies on thrombosis and hemostasis.
Heparin Infusion Facilitates ex vivo Spontaneous Platelet Aggregation in Patients with Acute Myocardial Infarction Who Have Undergone Thrombolytic Therapy
Authors: Noris Patrizia , Bertolino Giampiera , Previtali Mario , Ferrario Maurizio , Balduini Carlo L.
Published: May 2009

We investigated ex vivo spontaneous platelet aggregation (SPA) in platelet-rich plasma in 37 patients with acute myocardial infarction. It occurred in about 50% of subjects receiving heparin after streptokinase treatment, while it rarely took place in patients who did not receive either streptokinase or heparin and in those treated with streptokinase alone. The study of patients receiving heparin for deep vein thrombosis suggested that SPA may derive from adenosine diphosphate released from platelets during sample handling. We suggest that heparin infusion may facilitate ex vivo platelet activation and that this mechanism is operative in patients with acute myocardial infarction who have undergone thrombolytic therapy.
Is Tissue Factor Pathway Inhibitor Involved in the Antithrombotic Effect of Heparins?
Authors: Østergaard P. , Nordfang O. , Petersen L.C. , Valentin S. , Kristensen H.
Published: May 2009

Tissue factor pathway inhibitor (TFPI) is released into the circulation after intravenous or subcutaneous injection of heparin or low-molecular-weight heparin (Logiparin®) in humans. The plasma concentration of TFPI is increased 2- to 4-fold by a prophylactic dose of Logiparin, and this excess TFPI remains in the circulation only in the presence of the heparin. TFPI and heparin show strong synergism in clotting assays at concentrations obtained after heparin injection in humans. Animal studies have demonstrated that TFPI by itself has antithrombotic properties. It is concluded that the release of TFPI may contribute significantly to the antithrombotic effect of heparin.
Antithrombotic Properties of a Truncated Recombinant Tissue Factor Pathway Inhibitor in an Experimental Venous Thrombosis Model
Authors: Holst Jan , Lindblad Bengt , Bergqvist David , Nordfang Ole , Østergaard Per B. , Petersen Jens L. , Nielsen Gert , Hedner Ulla
Published: May 2009

The aim of this study was to investigate whether a truncated recombinant tissue factor pathway inhibitor (rTFPI1-161) had an antithrombotic effect comparable to low-molecular-weight (LMW) heparin. A randomized double-dummy study was conducted with 40 rabbits in 6 groups. An experimental thrombosis was induced in the jugular veins by a combination of destroyed endothelium and restricted blood flow. Group 1 was given placebo; group 2, LMW heparin 60 anti-factor Xa units/kg; group 3, rTFPI1-161 0.1 mg/kg; group 4, rTFPI1-161 1.0 mg/kg and group 5, rTFPI1-161 10.0 mg/kg. rTFPI1-161 reduced the thrombus weights in all treated groups, with a significant effect in doses between 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis was significantly reduced in all treated groups. No hemorrhagic side effects were noted. In conclusion, rTFPI1-161 (1.0-10.0 mg/kg) has an antithrombotic effect comparable to that of LMW heparin.
Simplified Prothrombin Time Standardization
Authors: Talstad Ingebrigt , Korsbrekke Knut
Published: May 2009

An analysis of prothrombin time (PT) standardization methods is presented. The present recommended ratio method demonstrated complex calibration and wide therapeutic ranges. Standardization by coagulation activities resulted in different therapeutic ranges due to the different sensitivity of assays for the protein induced by vitamin K absence (Pivka) inhibitor. A new method – the modified coagulation activity method – applied a reference assay against which any PT assay can be calibrated by clotting times, and the results were expressed in coagulation activities by the reference assay. This method was preferable due to simple calibration, narrow therapeutic ranges and identical results by any PT assay.
Simplified Calibration of Prothrombin Time Assays
Authors: Talstad Ingebrigt
Published: May 2009

The calibration of prothrombin time (PT) assays was studied. A simple calibration between pooled normal plasma and pooled stable plasma was as satisfactory as more complex calibration methods based on linear or orthogonal regression between log clotting times of abnormal and/or normal plasmas.
Factor VIII in Blood Plasma of Haemophilic Sheep: Analysis of Clotting Time-Plasma Dilution Curves
Authors: Neuenschwander Stefan , Pliška Vladimir
Published: May 2009

The sheep haemophilia A, recently described in a flock of White Alpine sheep, is probably caused by the production of a less potent mutant of factor VIII (F-VIII). Other potential mechanisms, such as drastic reduction (or lack) of F-VIII production, or occurrence of an F-VIII inhibitor, are less likely. This conclusion was based on the analysis of plasma dilution-clotting effect relationships in normal female (anestrous, non-pregnant) sheep, female carriers of haemophilia A, and afflicted male sheep. A response model underlying the analysis was suggested, its validity tested, and a mathematical analysis suitable for routine evaluation procedure recommended.
Plasminogen Activator Inhibitor 1 Activity and Lipoprotein(a) in Nephropathic Patients with Non-lnsulin-Dependent Diabetes mellitus versus Patients with Nondiabetic Nephropathy
Authors: Schleiffer Thomas , Hellstern Peter , Freitag Markus , Brass Horst
Published: May 2009

Increased plasma activity of plasminogen activator inhibitor 1 (PAI-1) is considered as a risk factor for thrombosis associated with atherosclerosis by reduction of fíbrinolysis. Since nephropathic patients with non-insulin-dependent diabetes mellitus (NIDDM) are a cardiovascular high-risk group, which has yielded only controversial results as to the regulation of PAI-1, we compared 19 overt nephropathic NIDDM patients (mean age 63 years, serum creatinine 1.9 mg/dl, proteinuria 4.2 g/ day) to 17 nondiabetic nephropathic patients with various causes of renal insufficiency (mean age 63 years, serum creatinine 2.8 mg/dl, proteinuria 3.9 g/day). We found normal PAI-1 levels for patients with diabetic nephropathy and significantly elevated PAI-1 levels within the upper normal range for nondiabetic nephropathic patients. Common risk factors in both groups were very high levels of fibrinogen, lipoprotein(a), serum cholesterol, and LDL cholesterol.
Standardization of Immunoassays for Antiphospholipid Antibodies with β2GPI and Role of Other Phospholipid Cofactors
Authors: Amiral J. , Larrivaz I. , Cluzeau D. , Adam M.
Published: May 2009

Presence of β2 Glycoprotein I (β2GPI), in addition to phos-pholipids, is an absolute requirement for binding APA. This binding is frequently observed with β2GPI coated alone, however many APA react only with β2GPI complexed to phospholipids, but not with phospholipids alone. We demonstrate that a subgroup of rabbit polyclonal antibodies to human β2GPI binds to this protein only when it is coated on a solid surface, but not if it is in solution. In addition, β2GPI present in goat serum is strongly fixed by the coated phospholipids and the complexes formed bind as well APA as the rabbit antibodies to β2GPI. The diluent used for testing APA, has a strong incidence on APA’s reactivity as it can be a source of β2GPI. Antibody binding to β2GPI, Proth-rombin, Protein S, and Annexin V, coated in the presence or in the absence of phospholipids, was tested in 55 patients with the antiphospholipid syndrome. The strongest binding of antibodies was observed in 39 plasma to a mixture of phospholipids and purified human β2GPI, however 17 samples also presented a significant reactivity to β2GPI alone. Nine plasmas contained antibodies to Prothrombin, 4 to Protein S, 3 to Annexin V, and 1 to Protein C. We conclude that most of the APA are directed to a complex of β2GPI and phospholipids although in some patients antibodies to β2GPI alone or to other phosphoslipid binding proteins are present.
Digital Image Analysis of Platelet-Extracellular Matrix Interactions: Studies in von Willebrand Disease Patients and Aspirin-Treated Donors
Authors: Díaz-Ricart Maribel , Carretero Marta , Castillo Ricardo , Ordinas Antonio , Escolar Ginés
Published: May 2009

We have developed an automated image analysis method which provides en face morphometric evaluation of platelet interactions with coverslips coated with extracellular matrices. This procedure gives also additional information on the intensity of platelet-surface interactions in the same specimens. To standardize the method, anticoagulated human blood was flowed at 800 s-1 during 10 min at 37°C through a parallel perfusion chamber in which extracellular matrix (ECM)-coated coverslips were placed. The sensitivity of the new method was tested in similar studies performed in patients with von Willebrand disease or treated with aspirin (500 mg/ day). The extent of platelet deposition on the ECMs was evaluated by both standard and new morphometric procedures. Coverslips were successively embedded in resin and processed for cross-sectional analysis and results were compared with those provided by the new automated procedure. A good correlation was found between results of covered surface obtained by both methods (r = 0.86; p < 0.005). Results from perfusions performed with blood from patients with platelet defects confirmed the correspondence of grey levels in the digitized images with the heights of groups of interacting platelets calculated from cross sections. The new automated method, in only one stage, allows a reliable evaluation of the global interaction of platelets with the ECM and effectively detected qualitative modifications in platelet-platelet interactions in patients with known platelet defects. The method described could be applied to the evaluation of the interactions of platelets with purified components of the subendothelium.
Single-Donor Platelet Concentrates: Changes of Surface Glycoproteins during Storage
Authors: Böck M. , Gawaz M.P. , Dietzler A. , Heim M.U. , Mempel W.
Published: May 2009

Storage of single-donor platelet concentrates is currently limited to 5 days. During this period, however, numerous morphologic and biochemical changes have been observed. These changes result in functional impairment of stored platelets. The present study describes increased binding of a monoclonal antibody against GMP 140 on the surface of stored single-donor platelets revealing an activation process. In contrast, binding of monoclonal antibodies directed against glycoprotein complex (GP) IIb-IIIa and ligand-induced binding site (LIBS1) is slightly diminished during storage. When platelets are stimulated with ADP GMP 140, GP IIb-IIIa, and LIBS1 are expressed to a higher extent than on the surface on non-stimulated platelets. The quantity exposed, however, depends upon the storage time. It is significantly reduced when platelets are stored for longer than 1-2 days. The present data indicate that storage of single-donor platelet concentrates affects fibrinogen binding, cell to cell cohesion, and release reaction. The results are in good agreement with conventional aggregation and in vitro bleeding time measurements.
D-Dimer and Thrombin/Antithrombin III Complex – Diagnostic Tools in Deep Venous Thrombosis?
Authors: Tengborn Lilian , Palmblad Suzanne , Wojciechowski Josef , Peterson Lars-Erik , Stigendal Lennart
Published: May 2009

In order to evaluate the usefulness of determining D-dimer and thrombin-antithrombin III complex (TAT) in the diagnosis of deep venous thrombosis (DVT), three D-dimer assays were tried: one ELISA and one latex test from Diagnostica Sta-go and one new latex method from Biopool. TAT was assessed using an ELISA (Behringwerke). We studied 96 consecutive outpatients with suspected DVT, of whom 36 had phlebographically confirmed DVT. Statistical calculations showed high sensitivity and a negative predictive value for the D-dimer ELISA (97% for both), confirming the results obtained by others. The new latex method (Biopool) showed similar figures (96% for both). The latex method from Diagnostica Stago and TAT showed lower sensitivity and negative predictive values. No differences in the D-dimer results were found with or without antifibrinolytics in the tubes for blood sampling. Our data suggest that negative results when using the new simple and cheap latex method (Biopool) may reduce the number of phlebographic examinations.
Differences in Plasminogen Activator Inhibitor 1 Activity between Blacks and Whites May Be Diet Related
Authors: Jerling Johann C. , Vorster Hester H. , Oosthuizen Welma , Silvis Nelly , Venter Christine S.
Published: May 2009

Two matched groups of healthy non-smoking male volunteers between 18 and 23 years old and with a body mass index of 19-24 kg/m2 were selected from urban whites (n = 15) and from rural Vendas (blacks; n = 17). Fasting venous blood samples were collected between 07.00 and 10.00 h, and a validated food frequency questionnaire was administered. The results showed highly significant differences in dietary patterns. Significant differences were observed with regard to serum cholesterol (p < 0.02), percentage high-density lipoprotein cholesterol (p < 0.02), calculated insulin sensitivity index (p < 0.04), and plasma fibrinogen levels (p < 0.03). Tissue plasminogen activator antigen did not differ significantly. The plasminogen activator inhibitor 1 activity was significantly lower (p < 0.0001) in the Vendas than in the whites. It is concluded that diet may be an important determinant of plasminogen activator inhibitor 1 activity.
Are Low-Molecular-Weight Heparins Useful for the Prophylaxis and Treatment of Arterial Thrombi?
Authors: Samama Charles Marc , Combe Sophie , Ill Patrick , Barre Eric , Dreux Sophie , Viars Pierre
Published: May 2009

The pharmacologic specificity of low-molecular-weight heparins (LMWHs) has enabled multiple attractive developments in the prophylaxis and treatment of arterial thrombosis. Their high antithrombotic potency associated with a potentially lower induced bleeding risk, the lack of platelet interaction, the prevention of myointimal hyperplasia, and the lower incidence of heparin-induced thrombocytopenia, are major advantages. New studies in cardiology and vascular surgery demonstrate a high efficacy for LMWHs associated with a low risk.
Tissue Factor Pathway Inhibitor (Tfpi) – An Update
Authors: Sandset Per Morten
Published: May 2009

There is compelling experimental evidence that tissue factor pathway inhibitor (TFPI) exerts important role(s) as a natural anticoagulant. Iinmunodepletion of TFPI lowers the treshold by which tissue factor (TF) can induce disseminated intravascular coagulation. Conversely, infusion of recombinant TFPI protects against thrombosis and disseminated intravascular coagulation in numerous experimental models. Since TFPI mutants associated with thrombosis have not yet been identified, a definite role of TFPI in coagulation is yet to be assigned. Current research on TFPI is mainly focused on the cell biology of TFPI, on the contribution of TFPI to the anticoagulant action of heparins, and on the role of lipoprotein-associated TFPI. TFPI is produced constitutively in endothelial cells, and is to a great extent bound to its surface. The binding molecule(s) have not yet been characterized, but TFPI is rapidly released by heparin and other negatively charged ions. In other cell lines degradation of TFPI is mediated by the low density lipoprotein receptor-related protein, which may be important for its clearance. In plasma, TFPI contributes strongly to the postheparin anticoagulant effect seen in dilute prothrombin time assays. The effect is probably mediated by redistribution of TFPI. Moreover, in the presence of heparin, antithrombin and TFPI cooperate to inhibit activation of coagulation. Antithrombin abrogates activation of factor VII bound to TF, whereas TFPI inhibits factor VIIa/TF complexes formed. The role of lipoprotein associated TFPI is still essentially unknown, but may play an important role in atherosclerosis.
Management Of Venous Thromboembolism: Optimization By Clinical Trials
Authors: Turpie Alexander G.G.
Published: May 2009

Antithrombotic therapy is mandatory in most patients with venous thrombosis. The results of randomized trials have established the requirement for initial treatment with heparin and have determined the optimal anticoagulant regimen for secondary prophylaxis. Recent studies have demonstrated that low molecular weight heparins, that have improved pharmacologic and pharmacokinetic properties over standard heparin, are effective and safe in the treatment of deep vein thrombosis. Two large randomized clinical trials have shown the feasibility of the outpatient treatment of patients with acute deep vein thrombosis with low molecular weight heparins. Home therapy will result in improved clinical utility of anticoagulant treatment and in cost savings.
Plaque Rupture, Thrombosis, and Therapeutic Implications
Authors: Fuster Valentin , Badimon JuanJose , Chesebro James H. , Fallon John T.
Published: May 2009

The basic mechanisms of atherosclerotic progression leading to the acute coronary syndromes (ACS) have been elucidated during the few years. In this brief presentation, we outline 1) Definition of Atherosclerotic Lesions: eight morphologically different lesions are defined (Type I to VI) in various phases of disease. 2) Vulnerable Lipid-Rich Plaques and the ACS: The type Va lesions tend to be relatively small in size, but soft or vulnerable to a &lquo;passive&rquo; phenomenon of plaque disruption; in addition, an &lquo;active&rquo; macrophage-dependent enzymatic (genesis of metalloproteinase) phenomenon of plaque disruption is evolving. 3) Thrombosis: we have shown that monocytes/macrophages in lipid-rich plaques may play a detrimental role after plaque disruption, promoting thrombin generation and thrombosis through the tissue factor pathway that can be prevented by tissue factor pathway inhibition; such pathway of thrombosis appears to be critical in teh development of the ACS. 4) Effect of Lipid-Modifying Strategies and other Risk Factors on the Vulnerable Lipid-Rich Plaques: when high LDL-cholesterol is reduced therapeutically, efflux from the plaques of the liquid or sterified cholesterol, and also its hydrolysis into cholesterol crystals depositing in the vessel wall, predominate over the influx of LDL-cholesterol; consequently, there is a decrease in the softness of the plaque and so, presumably in the “passive” phenomenon of plaque disruption; modification of other risk factors presumably also favorably effect LDL-cholesterol influx and efflux. 5) Antithrombotic Strategies: the evolving antithrombotic approaches under investigation are briefly outlined.
Pathogenic Role Of Antiprotein-Phospholipid Antibodies
Authors: Carreras L.O. , Forastiero R.R.
Published: May 2009

Antiphospholipid antibodies (aPL) are a heterogeneous family of antibodies, including those specific for a variety of phospholipid (PL)-binding proteins and also those reacting with PL molecules. The former seem to be associated with the antiphospholipid syndrome (APS). At present, the main proteins proposed as antigens are β2 glycoprotein I, prothrombin, protein C, protein S, kininogens and annexin V. Anionic PL might play a key role “in vivo” in the binding of aPL to PL-bound proteins. Different mechanisms may be involved in the pathogenesis of the APS, including effects of aPL on the protein C system and antithrombin III and also on platelets, endothelial cells and monocytes. Recent data on experimental animal models have provided support for a causative role of aPL in the clinical complications of the APS.
Antiphospholipid-Protein Antibodies: Clinical Use Of Laboratory Test Results (Identification, Predictive Value, Treatment)
Authors: Triplett Douglas A.
Published: May 2009

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which recognize protein-phospholipid complexes. Among the proteins implicated are: β2 Glycoprotein I, prothrombin, Annexin V, protein C, and protein S. Laboratory tests are used to identify, predict potential clinical complications, and manage patients with the antiphospholipid-protein syndrome (APS). Emerging evidence suggests laboratory tests can be used to stratify relative risk of patients with APA.
Low Prevalence of the Factor V Leiden among Patients with Ischemic Stroke
Authors: Sánchez Joaquín , Román José , de la Torre Maria J. , Velasco Francisco , Torres Antonio
Published: May 2009

The aim of the study is to determine if a novel thrombophilia mechanism (factor V Leiden) that is associated with resistance to activated protein C (APC) is in itself a risk factor for the development of ischemic stroke (IS). Sixty-six controls and 66 patients with IS were included in an unmatched case-control study. In the group of patients selected for this study, other causes of IS were ruled out. APC resistance was considered if activated partial thromboplastin time (aPTT) measured in the presence of APC was less than 2.2 times prolonged when compared to aPTT in the absence of APC (APC ratio < 2.2). Digestion with a restriction enzyme of a previously amplified exon 10 of the gene that encodes for factor V was used to detect the presence of the factor V mutation. We identified 5 patients (prevalence: 7.5%) with APC resistance (mean age: 31 years, range: 6-52 years). Mutation in factor V gene was confirmed in three of them. In the control group we detected 3 (4.5%) low APC ratios, all of them carrying specific factor V mutation. We cannot conclude a significant association between APC resistance and IS [odds ratio: 1.72; χ2 Mantel and Haenszel was 0.53 (p = 0.4673) and exact Fisher’s test p = 0.3589] but these 5 young adults suffered an episode of IS having APC resistance as the only prothrombotic condition. In conclusion, these results cannot prove a statistical association between APC resistance and IS. Further studies must be done in order to confirm that there is no relationship between APC resistance and IS in young adults when major risk factors are excluded.
Effects of Prostacyclin Substitution on Systemic Procoagulant Turnover and Cardiorespiratory Variables in Experimental Hypercoagulability
Authors: Scherer Ralf , Schmidt Ulrich , Kox Wolfgang , Paar Dietrich
Published: May 2009

Endotoxin infusion (lipopolysaccharide from Escherichia coli 120 μg kg–1 i.v.) was titrated to produce hypercoagulability in rabbits and the effects of prostacyclin (PGI2) treatment (continuous infusion of 6 ng kg–1 min–1 i.v.) on coagulation variables, cardiorespiratory variables, and fibrin deposition in the microcirculation of vital organs were studied. PGI2 infusion did not influence the concentration of soluble fibrin, throm-belastographic variables, or systemic platelet aggregability. Fibrin deposition in the microcirculation of the liver and the lungs was reduced to 50% of that observed in untreated animals (p < 0.01). The antiplatelet properties of PGI2 were unable to reduce experimental endotoxin-induced systemic procoagulant turnover but improved organ perfusion during the initial phase of disseminated intravascular coagulation.
Modulation of C4b-Binding Protein Isoforms during the Acute Phase Response Caused by Orthopedic Surgery
Authors: Criado-García Olga , González-Rubio Carolina , Lôpez-Trascasa Margarita , Pascual-Salcedo Dora , Munuera Luis , Rodriguez de Córdoba Santiago
Published: May 2009

Orthopedic surgery is described as an event with a high risk of thromboembolic diseases. This is probably a consequence of a synergistic combination of different risk factors in the patients subjected to this type of surgery, including age, immobilization, anesthesia and different hypercoagulable states. After surgery patients develop an acute-phase response that leads to changes in several plasma proteins. One of these proteins is the complement regulator C4b-binding protein (C4BP). We have recently shown that in some acute-phase patients C4BP is incorrectly controlled (with elevation of the C4BPΒ-containing isoforms), leading to a potential hypercoagulable state by decreasing the plasma levels of free (active) protein S. Here we have studied whether patients subjected to orthopedic surgery have an appropriate modulation of the C4BP isoforms during their postoperative acute-phase responses. We have analyzed the evolution of the C4BP isoforms in serial samples from 11 patients who have undergone knee (or hip) prosthesis surgery (mean age 70 years), or scoliosis surgery (mean age 18 years). Our data suggest a similar evolution of C4BP isoforms in all these patients, with an almost exclusive increase of C4BP isoforms lacking C4BPΒ polypeptides and steady levels of free protein S.
Effects of Medium-Term Antihypertensive Therapy on Haemostatic Parameters in Patients with Essential Hypertension
Authors: Trifiletti A. , Barbera N. , Scamardi R. , Bagnato L. , Pizzoleo M.A. , Nevoso A. , Lasco A. , Pedullà M. , Frisina N.
Published: May 2009

This study assessed the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the main haemostatic variables in 22 patients, of either sex, with newly diagnosed uncomplicated essential hypertension. In the patients and in 10 control subjects, plasma levels of thrombomodulin, β-thromboglobulin, D-dimer, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) had previously been measured. Only the levels of t-PA and PAI-1 were found to be higher than in controls. All these haemostatic evaluations were carried out after 6 and 12 months of treatment with an ACE inhibitor, cilazapril, 5 mg/day. This treatment significantly lowered the mean arterial pressure in the whole group from 133 to 106 mm Hg (after 6 months) and to 105 mm Hg (after 12 months), p < 0.05. No significant difference in any haemostatic parameters was observed after 6 and 12 months of treatment. The present study confirmed that treatment with cilazapril for 12 months lowers daytime ambulatory mean arterial pressure in patients with essential hypertension, without any significant increase in the tendency of blood to clot.
Fibronectin, Platelet Factor 4 and Beta-Thromboglobulin in Endemic Hepatosplenic Schistosomiasis: Relation to Acute Hematemesis
Authors: El-Bassiouni N.E. , El Bassiouny A.E. , Akl M.M. , El-Khayat H.R.
Published: May 2009

Some platelet Α-granule contents were assessed in parallel with other markers of hemostatic imbalance in 50 patients with hepatosplenic schistosomiasis (15 patients with compensated hepatosplenomegaly, 15 patients with advanced hepatic fibrosis and ascites and 20 patients during an acute attack of hematemesis from ruptured esophageal varices). Platelet factor 4 (PF4), Β-thromboglobulin (Β-TG), fibronectin (FN), prothrombin fragment 1 + 2, thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP) and D-dimer were assessed in schistosomal patients compared to controls (15 healthy subjects). A significant increase in both thrombin (high TAT and prothrombin fragment 1 + 2 levels) and plasmin (high FbDP and D-dimer levels) generation was detected in decompensated patients establishing the presence of a steady state of low-grade disseminated intravascular coagulation, with and without overt bleeding, in these patients. A decrease in plasma FN concentration was found in diseased groups compared to controls. The reduction in plasma levels of FN paralleled the defective liver function and matched the relative decrease in tissue FN in liver specimens of decompensated patients suggesting that FN levels can be used to evaluate the pathological staging of the disease. A significant increase in Β-TG and PF4 levels was noted in decompensated patients with ascites and/or acute hematemesis compared both to controls and compensated patients reflecting platelet Α-granule release and consequently increased in vivo platelet activation which may initiate and/or perpetuate the pathophysiological mechanisms of the hemostatic imbalance underlying the hemorrhagic diathesis in hepatosplenic schistosomiasis.
Acquired Isolated Factor VII Deficiency during Sepsis
Authors: Biron C. , Bengler C. , Gris J.C. , Schved J.F.
Published: May 2009

Isolated acquired factor VII deficiency is uncommon. We report 11 cases of acquired factor VII deficiency associated with severe systemic sepsis. All patients initially displayed a heterozygous-like factor VII deficiency confirmed by both clotting and amidolytic assays, associated with low factor VII antigen levels, and increased haemostasis markers (D-dimers, prothrombin fragments 1.2, thrombin-antithrombin complexes). After sepsis recovery, normal factor VII levels were evidenced. Isolated factor VII consumption or proteolytic degradation by leucocyte proteases can be evoked, but the mechanism of acquired factor VII deficiency during sepsis remains to be elucidated. The knowledge of this syndrome should avoid false diagnosis of congenital factor VII deficiency.
Efficacy and Safety of Low Molecular Weight Heparin, Unfractionated Heparin and Warfarin for Thrombo-Embolism Prophylaxis in Orthopaedic Surgery: A Meta-Analysis of Randomised Clinical Trials
Authors: Palmer A.J. , Koppenhagen K. , Kirchhof B. , Weber U. , Bergemann R.
Published: May 2009

The efficacy and safety of low molecular weight heparin (LMWH), unfractionated heparin (UFH) and warfarin for prophylaxis of thrombo-embolism in orthopaedic surgery were compared using meta-analysis techniques. Twenty-two studies were included, 2 of which compared LMWH to warfarin. The mean probabilities to develop deep-vein thrombosis (DVT), pulmonary embolism and major and minor bleeding using UFH were: 0.21 (95% confidence interval, CI: 0.18-0.24); 0.01 (95% CI: 0.01-0.02); 0.05 (95% CI: 0.03-0.07), and 0.19 (95 % CI: 0.17-0.22), respectively. The relative risk (RR) of DVT for LMWH vs. UFH was 0.76 (95% CI: 0.60-0.91), p < 0.05 and for LMWH vs. warfarin 0.78 (95% CI: 0.69-0.87), p < 0.05. The RR of minor bleeding for LMWH vs. UFH was 0.76 (95% CI: 0.64-0.92), p < 0.05. The RR of minor bleeding for LMWH vs. warfarin was 3.28 (95% CI: 2.21-4.70), p < 0.05. Conclusion: in orthopaedic surgery, LMWH is significantly superior to both UFH and warfarin in the prevention of DVT and results in significantly less minor bleeding complications when compared to UFH, but significantly more minor bleeding when compared to warfarin.
Effect of Dermatan Sulphate on Activated Partial Thromboplastin Time Determined with Different Reagents
Authors: Iorio Alfonso , Nucciarelli Fabio , Renga Cinzia , Nenci Giuseppe G. , Gianese Francesco , Agnelli Giancarlo
Published: May 2009

Five widely used activated partial thromboplastin time (APTT) reagents (Actin-FS, Actin-FSL, Hemolab Silimat, IL-Test APTT Ellagic Acid and Thrombofax Activated) were compared for their sensitivity and precision in measuring the effect of dermatan sulphate on blood coagulation. On each of 4 days, aliquots of the same normal human plasma pool were mixed with dermatan sulphate (MF701) at concentrations ranging from 10 to 100 μg/ml, and APTT was measured in duplicate with all the reagents by a photo-optical coagulometer. The order of testing between and within reagents was changed every day. The relationship of APTT ratio to dermatan sulphate concentration was linear with all the reagents. There were statistically significant differences between reagents in their sensitivity to DS, as reflected by linear regression slopes. IL-Test was the most sensitive reagent. At dermatan sulphate concentrations of 20, 50 and 80 μg/ml APTT ratio ranged from 1.5 to 1.7, 1.9 to 2.3 and 2.3 to 2.9, respectively, according to the reagent. The lambda coefficient and coefficient of variation derived from regression analysis, both reflecting assay precision, ranged from 0.57 to 0.71 and from 4.6 to 5.1 %, respectively, with all but the least precise reagent. The best sensitivity/precision balance was displayed by IL-Test. The APTT reagent should therefore be standardized, with special regard to sensitivity to DS, when testing the relationship of dermatan sulphate clinical effects to APTT response.
Prediction of the Transfusion Effect of Platelet Concentrates as Measured by a Model of Primary Hemostasis ex vivo
Authors: Kratzer M.A.A. , Storck K. , Groh J.
Published: May 2009

A method to determine primary hemostasis ex vivo (Thrombostat) was modified to monitor the transfusion effect of platelet concentrates (PC) in 12 patients with thrombocytopenia following bone marrow transplantation. It was possible to measure platelet function in patients with a platelet count lower than 2 × 1010/1. In addition, the platelet aggregometer (Born) was adapted to determine cell function in PC anti-coagulated with acid citrate dextrose of citrate phosphate dextrose. It was possible to make a prediction (r = 0.89) of the effect of a given PC on a patient’s ex vivo primary hemostasis parameters. Platelet aggregation following addition of 20 μM ADP to PC, obtained from 12 single donors, resulted in an average maximal light transmission (light transmission/age of concentrate in days) of 61 %/1 day and 37%/5 days, respectively. The same experiment gave only 39%/1 day and 13%/4 days for pooled platelets. To avoid possible immunization and bleeding complications, a reliable monitoring of platelet transfusion seems highly desirable.
Activated-Protein-C Resistance in Cancer Patients
Authors: Green David , Maliekel Kochurani , Sushko Elena , Akhtar Rasheed , Soff Gerald A.
Published: May 2009

Background: Resistance to activated protein C (aPC) is usually linked to factor V Leiden, but may occur in other disorders associated with hypercoagulability. In this study, we investigated the frequency of resistance to aPC in patients with advanced cancer and examined the relationship of aPC resistance to other markers of coagulation activation. Methods: Patients (n = 39) had an established diagnosis of advanced cancer; controls (n = 20) were healthy persons. aPC resistance was measured as the ratio of activated partial thromboplastin times with and without aPC (aPC-sensitivity ratio, aPC-SR). The factor V Leiden mutation was detected by a polymerase-chain-reaction based technique. Other assays were performed by standard laboratory methods. Data were analyzed using t tests and the Pearson correlation. Results: aPC-SR was below 2 SD for 5 of the cancer patients (13%), but none of the controls; only 1 of the 5 had the factor V Leiden mutation. aPC-SR was inversely correlated (p < 0.01) with factor VIII and fibrinogen in patients and with prothrombin activation fragment 1.2 (F1.2) in controls. Patient factor VIII, von Willebrand factor, (vWF), fibrinogen, F1.2 and D dimer were all significantly increased (p < 0.01); antithrombin III, protein C and proteins were similar to controls. Factor VIII correlated with vWF (p < 0.001) and F1.2 with d-dimer (p < 0.001). Other associations (p < 0.05) were observed between factor V and protein C, fibrinogen and protein C, factor V and antithrombin III and protein C and antithrombin III. Four cancer patients had a history of thromboembolism; their aPC-SR was similar to that of patients without thrombosis. Of the several coagulation measures examined, only vWF was higher in the patients with thrombosis (p = 0.01). Interpretation: Cancer patients have evidence of intravascular coagulation and increases in procoagulants and may have aPC resistance. The aPC resistance is not due to factor V Leiden, but is rather associated with elevated levels of factor VIII and fibrinogen, and in itself does not predict thrombosis.
Vitamin K Metabolism in a Patient Resistant to Vitamin K Antagonists
Authors: Keréveur A. , Leclercq M. , Trossaërt M. , Dupeyron J.P. , Parent F. , Horellou M.H. , Conard J. , Bachmann F. , Samama M.M.
Published: May 2009

We investigated various pharmacokinetic and pharmacody-namic parameters in a 63-year-old man, resistant to warfarin, fluindione, acenocoumarol and phenprocoumon. Daily doses of up to 30 mg of the long-acting phenprocoumon yielded a drug concentration of 85 mg/1 (usual range 1-5 mg/1) but the international normalized ratio remained around 1. The plasma half-life of phenprocoumon was approximately 350 h (normal 120-150 h). Thus, the resistance was not due to malabsorption or to an accelerated metabolism of the drug. The level of vitamin K1 (1,202 ng/1) was insufficient to induce resistance. De-carboxyprothrombin concentrations were low, demonstrating that the γ-carboxylation of the precursors of the vitamin Independent coagulation factors was not effectively reduced. The concentration of vitamin K epoxide, normally increased under oral anticoagulation, correlated to the vitamin K concentration (r2 = 0.77) but the quotient epoxide/vitamin K remained 4-fold lower than that of 22 warfarin-sensitive patients, suggesting an absence of blockade of the vitamin K reductase by phenprocoumon. This resistance to all the molecular forms of the vitamin K antagonists is most likely due to a reduced affinity of the drugs to a mutant vitamin K reductase.
Role of Oxygen Radicals in Tissue Factor Induction by Endotoxin in Blood Monocytes
Authors: Polack Benoît , Pernod Gilles , Barro Claire , Doussière Jacques
Published: May 2009

In response to bacterial endotoxin (lipopolysaccharide, LPS) monocytes synthesize and express on their surface tissue factor (TF) which triggers the blood coagulation cascade. Since LPS stimulates active oxygen species production by these cells, we investigated the roles of superoxide anion and nitric oxide in the induction of TF in human blood monocytes. Scavengers of reactive oxygen intermediates such as N-acetyl cys-teine or pyrrolidine dithiocarbamate were able to block TF induction. In addition, inhibition of NADPH oxidase and/or NO synthase which are major sources of active oxygen species in phagocytes also blocked TF induction. The restoration of TF expression, in monocytes treated with inhibitors of reactive oxygen production, by NN’-dimethyl-γγ‘-dipyridylium dichloride and/or sodium nitrosylpentacyanoferrate (III), which generate respectively O-2 and NO, suggests that these two radicals participate in the induction of TF at the surface of blood monocytes stimulated by LPS.
Structural Alterations in Erythrocytes from Patients with Chronic Obstructive Pulmonary Disease
Authors: Santini Maria Teresa , Straface Elisabetta , Cipri Antonio , Peverini Mario , Santulli Maria , Malorni Walter
Published: May 2009

Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of deep lung and pulmonary hypoxemia. In order to investigate if the clinical manifestations of this disease can be correlated to specific alterations in red blood cell (RBC) morphology, the erythrocytes from 12 COPD patients and 12 control subjects were obtained and examined by scanning electron microscopy (SEM), fluorescence microscopy and electron paramagnetic resonance (EPR) spectroscopy. The results demonstrate that the RBCs from COPD patients are greatly altered with respect to control erythrocytes. Specifically, SEM analysis revealed important shape changes while light fluorescence microscopy demonstrated microfilament network (actin and spectrin) redistribution. Finally, EPR spectroscopy, using the paramagnetic spin label 5-nitroxystearate, revealed an increase in membrane order (rigidity) in the erythrocytes of COPD patients with respect to controls. When taken together and when compared to the morphological variations present in the RBCs of other ill patients (i.e., diabetics), the data presented in this report seem to suggest that changes in erythrocyte shape and rheological properties play a key role in RBC dysfunction in the course of COPD.
Identification of Two Different Mutations Causing Protein S Deficiency in Two Unrelated Belgian Families Using a Nonisotopic Scanning and Sequencing Method
Authors: Messiaen Ludwine , Callens Tom , Baele Gaston
Published: May 2009

Hereditary protein S deficiency is a risk factor for developing recurrent venous thromboembolic disease and is caused by a defect in the protein S 1 (PROSl) gene. Identification of the mutation in the PROSl gene can overcome diagnostic uncertainty in family members with borderline protein S levels. We describe a novel nonisotopic method for molecular diagnosis of protein S deficiency, using fluorescein-labeled amplification and sequencing primers. As a first step, all exons of the PROS 1 gene are selectively amplified, and heteroduplex analysis is performed. As a second step, all exons are analyzed by direct sequencing. Using this method, we have characterized the molecular defect in two Belgian families with hereditary protein S deficiency type I: a frameshift mutation in exon XIV (1881insTC) and a missense mutation caused by a T-to-C transition, resulting in substitution of Leu405 by Pro (L405P).