bluuebunny/crossref_metadata_2025 huggingface dataset:
Update of 156 Episodes of Central Nervous System Bleeding in Hemophiliacs
Authors: de Tezanos Pinto M. , Fernandez J. , Perez Bianco P.R.
Published: April 2009

Between 1960 and 1991, 156 episodes of central nervous system (CNS) bleeding were documented in 106 patients from a total population of 1,410 hemophiliacs (7.5%). Ninety-one hemophilia A patients presented 131 bleeding episodes; 15 hemophilia B patients had 25 episodes. 32% of these episodes took place in patients less than 5 years of age. 46 % were age 10 or less, and 72% were age 20 or less. The mean age was 14.8 years in hemophilia A and 9 years in hemophilia B patients. A significant increase in the mean age of hemophilia A patients has been observed over the last 10 years; this may be related to HIV infection. A history of recent trauma was documented in 39.7% of the episodes. Spontaneous CNS bleeding was predominant in severe hemophilia (85.2%). One hundred and fifty-four CNS bleeding episodes were intracranial and 2 intraspinal. Of the intracranial episodes, 37.7% were subarach-noid, 29.8 subdural, and 22.7% intracerebral. Factor VIII or IX inhibitors were present in 11.3% of the patients; this figure is slightly lower than that observed in our total hemophilic population. Over 50% of the patients had psychoneurological sequelae; the most frequent were seizure disorders and motor impairment. The overall mortality rate was 29.2%. The mortality was more closely related to the CNS bleeding site than to the severity of hemophilia. Treatment should be based on prompt and prolonged replacement therapy to ensure hemostatic levels of antihemophilia factors.
Management of Factor VIII Inhibitors: Evolution and Current Status
Authors: Bloom A.L.
Published: April 2009

Management of patients with factor VIII (and IX) inhibitors includes management of acute bleeds and methods to induce immune suppression and tolerance and to detect patients at risk of developing inhibitors. The methods used over the years to treat acute bleeding have been more or less successful. The best method is to raise factor VIII levels by human or porcine factor VIII concentrate, but this is not usually possible. Prothrombin complex concentrates, activated or non-activated, have enjoyed some success as factor VIII by passing agents, but the development of recombinant activated factor VII represents a new and promising method of inducing haemoslasis at the site of bleeding whilst minimizing the risk of disseminated intravascular coagulation. Alternatively, the use of tissue factor is under consideration to exploit the extrinsic system. Methods to induce immunological tolerance by use of the ‘Bonn’ regime or by the introduction of immunomodulation with the ‘MalmÖ’ regime of extracorporeal immunodepletion, cyclophosphamide, and intravenous immunoglobulin continue to be attempted with significant but variable success. Gradually the inhibitor problem is being contained, but it is still an important complication of haemophilia therapy.
Desmopressin: A Nontransfusional Treatment of Hemophilia and von Willebrand Disease
Authors: Mannucci P.M. , Cattaneo M.
Published: April 2009

Desmopressin (1-deamino-8-D-arginine vasopressin) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of factor VIII and von Willebrand factor, desmopressin is used for nontransfusional treatment of mild and moderate hemophilia and von Willebrand disease. Desmopressin also shortens the prolonged skin bleeding time in patients suffering from von Willebrand disease and is given to prevent or stop excessive bleeding in such conditions.
AIDS and Hemophilia: Experience in the La Paz Hemophilia Center
Authors: Magallón Martinez M. , Ortega F. , Pinilla J.
Published: April 2009

435 hemophiliacs are usually being attended in the La Paz hemophilia Center (Madrid, Spain). 257 (59%) of these patients have been infected by the human immunodeficiency virus (HIV-1) because of human plasma derivate substitution therapy. The infection has been more frequent among the severely affected patients and among the most treated patients. 82% of the infected patients are between 14 and 40 years old. By December 1991, 95 (37%) of 257 seropositive patients have developed full-blown AIDS. The most frequent opportunistic infection they had suffered was esophageal can-didiasis. Looking for an evolution marker, we can point that the patients older than 35 years with CD4 levels below 200/mm3 had the worst prognosis. There was no difference in the evolution among the patients aged below 17 and those aged between 17 and 35 years. The amount of concentrate used between 1980 and 1984 did not hold any relation to the evolution. 49 patients (51%) of the 95 suffering from AIDS had died by December 1991. The evolution to the death was unrelated to the patient age, CD4 lymphocyte levels, and amount of substitution therapy. In our opinion, the most valuable marker could be the kind of opportunistic infection or tumor the patient suffers from. Finally, Retrovir has demonstrated to be useful in increasing the survival rate of the patients, but after 36 months of treatment, only 33% of those AIDS patients who began taking it remained alive. Retrovir was also used in asymptomatic patients, and during an average period of time of 15 months, a lesser bone marrow toxicity and a stabilization in CD4 lymphocyte levels could be observed, but this was unable to modify the disease progression in those patients who presented circulating p24 antigen.
Financial Assistance for HIV-lnfected Persons with Haemophilia Worldwide
Authors: Schimpf K.
Published: April 2009

In many countries we could note the dramatic developments in regard to financial assistance of HIV-infected haemophiliacs and their families since we distributed the first overview on this to all World Federation of Hemophilia member countries. As a result of the untiring efforts of the National Haemophilia Societies, infected persons and their families receive essential assistance in 15 member countries. It is hoped that this development will sway more and more member countries to consider demands for financial support and provide them with the arguments to succeed.
La Paz Hemophilia Center, 1967-1992: People, Events, and Memories
Authors: Martin-Villar J.
Published: April 2009

In 1967, once urgent blood requirements had been resolved in La Paz Hospital, Madrid, Spain, and adequate supplies of plasma for cryoprecipitation, therefore, being available, a Hemophilia Unit (later Hemophilia Center) was set up to attend to the comprehensive care of hemophilia patients and patients with other coagulopathies. This Center covers a regional area and also a national area for referrals and normally attends 600 patients. In this Center the Spanish Social Security Hemophilia Association was created. In 1983 the first cases of AIDS appeared, occasioning the change from standard factor VIII concentrates to the heat-treated concentrates that had recently appeared on the market. At present the Center is responsible for the medical attention of those hemophilia patients affected by HIV.
Individual and Combined Effects of a Thromboxane Receptor Antagonist and Different Antithrombotic Agents in a Rat Microcirculatory Thrombosis Model
Authors: Giedrojc J. , Fellier H. , Breddin H.K.
Published: April 2009

The antithrombotic effect of a thromboxane A2 receptor antagonist (HN-11501:5-[2-(4-chlorophenylsulfonylamino)-ethyl]-2-thienyloxy-acetic acid) alone and in combination with other antithrombotic agents has been studied in an experimental thrombosis model in which laser lesions are used to induce a defined thrombosis in rat mesenteric venules. The thromboxane receptor antagonist showed a significant and dose-dependent antithrombotic effect if given orally. The strongest additive thrombosis-inhibiting effect was observed after oral administration of HN-11501 at a dose of 2.5 mg/kg together with an intravenous infusion of 1 µg/kg/h of a prostacyclin analogue (cicaprost). An additive antithrombotic effect was also observed after oral application of 2.5 mg/kg of HN-11501 and intravenous injection of 0.2 mg/kg of a low molecular weight heparin (Fraxiparine®). The combination of 2.5 mg/kg of HN-11501 orally with an intravenous injection of 0.1 mg/kg molsidomine also had a significant additive effect. No significant additive effect was observed when 2.5 mg/kg of HN-11501 and 10 mg/kg of acetylsalicylic acid were orally administered simultaneously.
Diagnosis of Glanzmann’s Thrombasthenia and Carrier Detection using Monoclonal Antibodies to Platelet Glycoprotein lIb and IIIa in Immunoblotting
Authors: Perutelli Paolo , Marchese Patrizia , Mori Pier Giorgio
Published: April 2009

Glanzmann’s thrombasthenia is a rare hemorrhagic syndrome, characterized by a quantitative or functional defect of the platelet glycoprotein GPIIb-IIIa complex. The authors describe a method to diagnose thrombasthenic patients and identify carrier subjects by using monoclonal antibodies specific for GPIIb and GPIIIa in an immunoblotting technique. The immunoreaction patterns of two thrombasthenic patients lacking GPIIb or GPIIIa, respectively, are shown. The described method produces further evidence concerning the biochemical heterogeneity of Glanzmann’s thrombasthenia.
Plasma Protein C as a Marker of Hepatocellular Damage in Alcoholic Liver Disease
Authors: Kłoczko J. , Mian M. , Wojtukiewicz M.Z. , Babiuch L. , Bielawiec M. , Galar M.
Published: April 2009

The synthesis of a number of clotting factors takes place in a hepatocyte. Therefore, measurement of these factors in the blood have proved to be of additional value in the diagnosis and follow-up of liver diseases. In the present study we evaluated protein C level in the plasma of patients with liver cell damage due to chronic alcohol consumption. A decrease in plasma protein C concentration which correlated with clinical performance of the patients was found. Significant correlations between the level of protein C and antithrombin III, one-stage prothrombin time, factors VII and X and some biochemical tests reflecting liver cell damage were also stated. The obtained data indicate that plasma protein C level may constitute a useful marker of hepatocellular disease in alcoholics.
Ondansetron (GR 38032F), ein kompetitiver 5-HT3-Rezeptor-Antagonist als Antiemetikum bei Zytostatika-induzierter übelkeit und Erbrechen
Authors: Serve H. , Perker M. , Ertl A. , Reichold M. , Fink U. , Berdel W.E.
Published: April 2009

In einer offenen, substanzorientierten Phase-II/III-Studie wurden 24 Patienten mit dem 5-HT3-Antagonisten Ondansetron als Antiemetikum bei Zytostatika-induziertem Erbrechen behandelt. Patienten mit Cisplatin-haltigen Chemotherapieprotokollen wurden nicht in die Studie aufgenommen. Alle Patienten hatten wÄhrend eines vorangegangen identischen Chemotherapieprotokolls bei konventioneller antiemetischer Therapie unter schwerer Ubelkeit und Erbrechen gelitten . und wurden mit 3 × 8 mg Ondansetron am Tag der Chemotherapie und an den vier folgenden Tagen behandelt. Die Substanz wurde bei insgesamt 90 zytostatischen Therapiezyklen (bei 1 bis 14 Zyklen pro Patient) verabreicht. Lediglich 2 Patienten (8%) erfuhren, gemessen an einer SelbsteinschÄtzung des Schweregrades der Ubelkeit und an der HÄufÍgkeit des Erbrechens im Vergleich zur vorausgegangenen Therapie mit konventionellen Antiemetika, bei keiner Gabe von Ondansetron eine Linderung ihrer Symptome. Bei 11 von 18 mehrfach mit Ondansetron behandelten Patienten (61%) verminderte sich die HÄufigkeit ihres Erbrechens bei jeder Gabe von Ondansetron. Es konnte bei 60 der 90 Anwendungen ein weitgehender (eine bis zwei emetische Episoden in 24 h, 29%) oder kompletter (kein Erbrechen, 37%) Schutz vor Erbrechen durch Gabe von Ondansetron erzielt werden. Als hÄufigste Nebenwirkung trat bei 7 der 24 behandelten Patienten eine Obstipation auf, gefolgt von leichten diffusen abdominellen Schmerzen bei 4 Patienten, wobei hier ein Zusammenhang mit der zytostatischen Therapie nicht auszuschließen ist. Unter Kopfschmerzen litten 3 Patienten. Ein Patient brach deshalb die Therapie ab. Sonstige Nebenwirkungen wurden nicht beobachtet. Somit handelt es sich bei Ondansetron urn ein wirksames und sicheres Antiemetikum bei zytostatischer Therapie.
Double Y-Stent Placement for Tracheobronchial Stenosis
Authors: Oki Masahide , Saka Hideo , Kitagawa Chiyoe , Kogure Yoshihito , Mori Kouki , Kajikawa Shigehisa , Adachi Takashi
Published: April 2009

The silicone stent has been widely used to re-establish airway patency for patients with airway stenosis. The ideal shape of the stent should be well adapted to the tracheobronchial anatomic structures, and its optimal length should cover the entire inner wall of the stenotic airway. Although the silicone Y-stent was developed as a dedicated prosthesis for main carinal stenosis, we often encounter patients with tracheobronchial stenosis that cannot be treated by a single silicone Y-stent. The present study reports 2 cases of malignant disease who underwent double Y-stent placement on the involved carina between the right upper lobe bronchus and the bronchus intermedius as well as on the involved main carina as a unit. The procedure provided successful palliation.
Seasonality of Hair Shedding in Healthy Women Complaining of Hair Loss
Authors: Kunz Michael , Seifert Burkhardt , Trüeb Ralph M.
Published: April 2009

Background: A number of otherwise healthy women with or without clinical alopecia complain of recurrent hair loss, presumably reflecting seasonality in the growth and shedding of hair. Objective: To test the hypothesis that periodicity in hair shedding reflects seasonal changes in human hair growth. Methods: Retrospective case study over a period of 6 years of apparently healthy women with the complaint of hair loss. All underwent biochemical investigations, and trichograms were made. Results: After exclusion of patients with a disease or on drugs known to cause hair loss, 823 women remained. Analysis of trichograms demonstrated annual periodicity in the growth and shedding of hair, manifested by a maximal proportion of telogen hairs in summer. A second peak seems to exist, though it is less pronounced, in spring. The telogen rates were lowest in late winter. Conclusions: These results confirm the findings of former authors who have indicated seasonal changes in human hair growth, though this is the first study performed systematically in a representative number of women.
Pre-Eclampsia Is a Risk Factor of Carotid Artery Atherosclerosis
Authors: Haukkamaa L. , Moilanen L. , Kattainen A. , Luoto R. , Kähönen M. , Leinonen M. , Jula A. , Kesäniemi Y.A. , Kaaja R.
Published: April 2009

Background: A history of pre-eclampsia has been shown to be associated with an increased risk of subsequent coronary artery disease. The intima-media thickness of carotid arteries and the detection of plaques are useful measures as regards preclinical atherosclerosis. The aim of this study was to examine whether women with a history of pre-eclampsia more often show signs of atherosclerosis compared with 2 control groups. Methods: We used data from a large Finnish cross-sectional health examination survey. We had women with previous pre-eclampsia (n = 35) or pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests and physical examination were performed. Information on reproductive and medical history was obtained at the home interview. Carotid atherosclerosis was assessed by ultrasonography. Results: The women with previous pre-eclampsia had significantly (p = 0.008) more atherosclerotic plaques than the healthy parous controls. The intima-media thickness in the women with previous pre-eclampsia also tended to be higher than in the other groups, although the differences did not reach statistical significance. In logistic regression analysis, advanced age (OR: 1.08; 95% CI: 1.04–1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI: 1.50–8.79; p = 0.004) were independent risk factors as regards plaque, and in linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010–0.014; p < 0.001), HDL cholesterol (estimate: –0.049; 95% CI: –0.088 to –0.010; p = 0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000–0.009; p = 0.043) and high-sensitivity C-reactive protein (estimate: –0.003; 95% CI: –0.007 to –0.000; p = 0.048) were independent risk factors with respect to intima-media thickness. Conclusions: Our data suggest that pre-eclampsia is an independent risk factor as regards developing plaque later in life.
Safety and Tolerability of Pardoprunox, a New Partial Dopamine Agonist, in a Randomized, Controlled Study of Patients with Advanced Parkinson’s Disease
Authors: Hauser R.A. , Bronzova J. , Sampaio C. , Lang A.E. , Rascol O. , Theeuwes A. , van de Witte S.V.
Published: April 2009

Aims: To investigate the safety and tolerability of pardoprunox (SLV308), a novel partial dopamine agonist, as an adjunct to levodopa in patients with advanced Parkinson’s disease, using two titration schedules. Methods: Patients were randomized to pardoprunox (n = 51) or placebo (n = 11). Pardoprunox was titrated to the highest tolerated dose (range, 0.3–42 mg/day) over 7 weeks, using a gradual dose escalation without intermediate steps (group 1) or with intermediate steps (group 2). Results: The cumulative drop-out rate was greater in group 1 (without intermediate steps, 56.0%) than in group 2 (with intermediate steps, 34.6%), or with placebo (9.1%). In group 2, doses up to 18 mg/day were well tolerated with a cumulative drop-out rate of 7.7% (2/26) and a drop-out rate due to adverse events of 4.0% (1/26). The most common adverse events reported were nausea, vomiting, headache, and dizziness. There was a trend for reduced OFF time (p = 0.054) in the combined pardoprunox group compared to placebo. Conclusions: The pardoprunox safety and tolerability profile as an adjunct to levodopa was improved using a gradual titration schedule that included intermediate dose steps. Using this titration, doses up to 18 mg/day were well tolerated.
Effects of Aspirin on Embolization in an Arterial Model of Laser-Induced Thrombus Formation
Authors: Vesvres M.H. , Doutremepuich F. , Lalanne M.Cl. , Doutremepuich Ch.
Published: April 2009

This model of arterial thrombosis induced by laser was used to evaluate the effect of aspirin (Aspegic®) on embolization. A partial occlusion was induced in small mesenteric arterioles (diameter 35-40 μm) with an Argon Laser. The laser induced the formation of a vessel wall lesion with damage of endothe-lial cells. Thrombus formed within seconds after the laser lesion and grew rapidly. Embolization began within the minute following the laser flash. Thrombus formation and embolization were repetitive phenomena. The duration of embolization was 6.50 ± 0.84 min in the control group. Then the thrombus became stable and partially obstructed the vessel lumen. The administration of aspirin at three doses (50, 100, 200 mg/kg) by intramuscular injection, 15 min before the laser injury, induced three different phenomena: (1) an increase of the number of laser injuries required for the thrombus formation; (2) a dose-dependent decrease in the duration of embolization, and (3) a dose-dependent decrease in the number of emboli. The highest dose injected induced the strongest reduction in the duration of embolization and the number of emboli.
Which Coagulation Factors Interfere with the One-Stage Prothrombin Time?
Authors: Talstad Ingebrigt
Published: April 2009

Coagulation factors that interfere with the one-stage prothrombin time (PT) were investigated. PT responded with identical activities (adequately) against coagulation factors VII or X, only half as expected against factor IX, less than expected and nonlinearly against factor II. In multiple coagulation factor deficiencies PT did not differ from factor VII, which was the most reduced coagulation factor in warfarin therapy or liver disease. PT may also be influenced by factor VII at high activities.
Development of a Rapid and Sensitive Chromogenic Heparin Assay for Clinical Use
Authors: Wagenvoord R.J. , Hendrix H.H. , Kolde H.J. , Hemker H.C.
Published: April 2009

A new sensitive chromogenic heparin assay is developed, which is well suited for clinical use. For the assay two reaction mixtures are required which can be lyophilized and reconstituted on the day of use. These reagents are stable during at least 6 h. Only two time-dependent pipetting steps are necessary. Any compound that inactivates thrombin, or can potentiate thrombin inactivation by an inhibitor, can be measured with this assay, including standard heparin, low molecular weight heparins, hirudin, α-NAPAP, pentosan polysulphate and dermatan sulphate. It is shown that heparin can be measured accurately in whole blood and in plasma. By addition of dextran sulphate to one of the reagents a platelet factor 4-insensitive assay is developed, so heparin can be measured even in blood that is partially activated and thus contains platelet factor 4 which neutralizes heparin.
Fibrinolytic Imbalance in Essential Thrombocythemia: Role of Platelets
Authors: Bazzan M. , Tamponi G. , Gallo E. , Stella S. , Schinco P.C. , Pannocchia A. , Pileri A.
Published: April 2009

Thrombotic and hemorrhagic complications are frequent in patients with essential thrombocythemia (ET), a myeloproliferative syndrome with an increased number of circulating platelets. Since platelets are a physiological reservoir for the plasminogen activator inhibitor (PAI-1) contained in plasma, we evaluated plasma and platelet tissue plasminogen activator (tPA) and PAI-1 in 20 ET patients with and without thrombotic complications and in 13 control subjects. In ET patients with thrombotic complications there was a significantly greater platelet PAI-1 functional activity than in ET patients without thrombotic complications and in the control group (p < 0.05 and p < 0.025, respectively). Moreover, platelet tPA activity was significantly low in all ET patients (p < 0.001). This fibrinolytic imbalance (increased plasminogen inhibitor and lowered activator) might be a critical cofactor in the thrombotic complications in ET patients.
Prothrombin Fragment 1+2 and Thrombin-Antithrombin Complex Measurements Indicate Continuous and Progressive Intraoperative Thrombin Generation in Liver Transplantation
Authors: Monteagudo Juan , Reverter Juan C. , Pereira Arturo , Pijoan Josefina , Balust Jaime , Escolar Ginés , Mazzara Roberto , Taurá Pilar , Visa José , Ordinas Antonio , Castillo Ricardo
Published: April 2009

Prothrombin fragment 1 + 2 (F1+2) and thrombin-antithrom-bin complex (TAT) have been measured in the different surgical phases in 40 patients undergoing 43 orthotopic liver transplantations (OLT), in order to study thrombin generation throughout the surgical procedure. F1+2 and TAT progressively rose from preoperative values (1.47 ± 0.92 nmol/l and 22.41 ± 19.15 ng/ml, respectively) to the end of anhepatic phase (5.97 ± 2.20 nmol/l, 64.24 ± 11.30 ng/ml), whereas changes in circulating antithrombin III (ATIII) were negligible in this period. Thrombin generation continued to slightly but significantly increase immediately after liver graft reperfusion (F1+2 6.87 ± 1.65 nmol/l, TAT 89.32 ± 7.54 ng/ml), and ATIII levels decreased from 70.61 ± 12.28 to 57.16 ± 9.57%. Higher preoperative values of F1+2 were associated with larger requirements of both packed red blood cells and fresh frozen plasma (FFP) in the host liver explantation phase, whereas the lowest basal levels of ATIII were related to a higher plasma expense in the whole OLT procedure. The activation of circulating prothrombin begins early in OLT, and adequate FFP infusion is capable of maintaining appropriate circulating thrombin-inhibitory activity.
Endothelium Releases More von Willebrand Factor and Tissue-Type Plasminogen Activator upon Venous Occlusion in Patients with Liver Cirrhosis than in Normals
Authors: Tornai I. , Hársfalvi J. , Boda Z. , Udvardy M. , Pfliegler G. , Rak K.
Published: April 2009

Venous occlusion was used in 8 patients with liver cirrhosis and in 10 normals to investigate the pathomechanism of long-term elevation of plasma von Willebrand factor antigen (vWFAg) in liver cirrhosis. The following parameters were determined at baseline, and immediately, 60 min and 24 h after 10 min venous occlusion: vWFAg, ristocetin cofactor (RiCoF), in vitro platelet retention (Adeplat T), and tissue-type plasminogen activator (t-PA). Every baseline value in the liver cirrhosis group was significantly higher than in the controls. In both groups the 10-min values were significantly higher than their corresponding baseline results. Hence, comparing the two groups, in liver cirrhosis a significantly higher release of vWFAg and t-PA could be observed. These findings suggest on the one hand that the increased release contributes substantially to the sustained elevation of plasma vWF level in liver cirrhosis. On the other hand, the results indicate that not only the vascular surface of the diseased liver but most probably the total endothelium plays an important role in this phenomenon.
An Acquired Cryoglobulinemia Which Inhibits Fibrin Polymerization in a Patient with IgG Kappa Myeloma
Authors: Panzer Simon , Thaler Erich
Published: April 2009

A 58-year-old man with multiple myeloma and paraproteinemia (IgGκ) acquired cryoglobulinemia 2 years after the initial diagnosis of the disease. This cryoglobulin interfered specifically with fibrin aggregation. The patient’s fibrinogen was functionally normal; however, clotting times (thrombin clotting time, reptilase clotting time) were prolonged in the untreated plasma and in the supernatant after removal of the cryoglobulins. Untreated patient’s serum, and even more pronounced, the cryoprecipitate inhibited the association of fibrin monomers obtained from healthy controls. The inhibitory activity on fibrin aggregation diminished upon treatment-induced reduction of plasma protein levels.
Controlled Vitamin K Content Diet for Improving the Management of Poorly Controlled Anticoagulated Patients: A Clinical Practice Proposal
Authors: Sorano Gian Gabriele , Biondi Giovanni , Conti Maria , Mameli Giulia , Licheri Donatella , Marongiu Francesco
Published: April 2009

The aim of our study was to investigate the effect of a diet with a known vitamin K content on the monitor test for oral anticoagulant therapy. We studied 10 poorly controlled patients (7 women and 3 men, mean age 48+15 years) in therapy with acenocoumarol for at least 1 year. Another group of 10 poorly controlled patients was considered as a control group. After a baseline period, during which a free diet was allowed, patients were administered a diet with a controlled vitamin K content; in the same period, control subjects were not subjected to any dietary restriction. Thrombotest (Nyegaard, Oslo) was employed for monitoring oral anticoagulant therapy, with a therapeutic range between 2.3 and 4.8 INR. We found a significant difference by thrombotest between the percentages within the therapeutic range obtained before and during dietary treatment (p = 0.0001). The difference in percentages was -0.31 and the 95% CI, of the difference ranged from -0.45 to -0.17. No significant difference was shown in the control group in the same periods. Our data suggest that a diet with a controlled vitamin K content is effective in increasing the percentage of tests within the therapeutic range in patients with poorly controlled anticoagulation.
Fibrinogen and Fibrin Derivatives in Traumatized Patients: Relation to Injury Severity and Posttraumatic Pulmonary Dysfunction
Authors: Sørensen Jens V. , Jensen Hans P. , Rahr Hans B. , Borris Lars C. , Lassen Michael R. , Fedders Ole , Haase Jens P. , Knudsen Flemming
Published: April 2009

In a prospective study including 30 traumatized patients, levels of fibrinogen, fibrinopeptide A (FpA), fibrin monomers (FM) and fibrin degradation products (FbDP) were measured on admission and on days 1 2, 3 and 7 after the incident. High levels of FpA, FM and FbDP were observed immediately after the trauma. Fibrinogen levels increased during the first 7 posttraumatic days whereas FpA and FM decreased. FbDP was significantly higher on day 7 than on day 3. All variables were to some extent correlated to the injury severity score. FbDP were significantly lower on the day after admission in 4 patients who developed pulmonary dysfunction compared with patients without this complication.
Anticoagulation with Nafamostat Mesilate, a Synthetic Protease Inhibitor, in Hemodialysis Patients with a Bleeding Risk
Authors: Matsuo Takefumi , Kario Kazuomi , Nakao Kazukiyo , Yamada Tsutomu , Matsuo Miyako
Published: April 2009

Nafamostat mesilate (FUT) is a synthetic serine protease inhibitor with a short half-life that is used during hemodialysis (HD) in patients with a high risk of bleeding because it does not prolong the systemic coagulation time. To evaluate whether or not FUT is able to effectively prevent clot formation in the extra-corporeal circuit without increasing systemic bleeding, HD using FUT was carried out for 33 sessions in 12 patients with a high risk of bleeding. FUT was continuously infused during HD at 20-40 mg/h to maintain a 2-fold prolongation of activated partial thromboplastin time (APTT) at the dialyzer outlet on the venous side of the circuit. No APTT prolongation was observed on the arterial side of the circuit before FUT infusion, and none of the patients showed increased bleeding during or after HD. However, clots formed in the arterial chamber (30.3%), the dialyzer (36.6%), and the venous chamber (15.1 %). In 2 of the 12 patients, HD was discontinued due to clot formation despite sufficient prolongation of APTT. The mean levels of the thrombin-antithrombin III complex and prothrombin activation fragment 1+2 in the circuit gradually increased on both the arterial and venous sides during HD using FUT, and protein C activity decreased. No significant changes in these parameters occurred during heparin HD in the same patients after the bleeding episode had resolved. Despite sufficient prolongation of APTT in the circuit, FUT was less effective in suppressing thrombin generation when compared to heparin. Therefore, FUT cannot be recommended as an alternative drug to heparin for hemodialysis patients with a bleeding risk.
Decreased High-Molecular Weight Fibrinogen and Impaired Alpha-Chain Polymerization in Full-Term Newborns
Authors: Réganon E. , Vila V. , Laiz B. , Gilabert J. , Aznar J.
Published: April 2009

Some properties of fibrinogen from 30 newborn and 30 normal adult plasmas obtained under the same conditions have been studied. The results show that the high-molecular weight fibrinogen (HMW-Fg) was decreased by nearly 25% in newborn plasma as compared to normal adult values. The kinetics of fibrin gel formation was decreased in newborn as compared with normal adult plasmas (gelation rates 2.2 ± 1 vs. 5.6 ± 0.5 × 10-4 OD/s, lag time 128 ± 25 vs. 72 ± 3 s). The release rates of fibrinopeptide A (FPAp ± FPA) and fibrinopeptide B (FPB) were decreased in newborn fibrinogen (FPAp + FPA 10.8 and FPB 1.2 × 10-3 s–1) as compared to normal adult fibrinogen (FPAp + FPA 11.8 and FPB 1.7 × 10-3 s-1)- Analysis by SDS-PAGE of the reduced, highly cross-linked fibrin from the newborns showed that only 23% of the α-chain participates in the formation of α-chain polymers. The results suggest that the retarded release rate of fibrinopeptides and the decrease in the HMW fibrinogen concentration are causes of the prolonged kinetics of fibrin gel formation in newborns.
Protein S and C4b-Binding Protein Levels in Patients with Stroke: Implications for Protein S Regulation
Authors: Carr, Jr. Marcus E. , Zekert Sheryl L.
Published: April 2009

Protein S circulates either free or bound to C4b-binding protein (C4b-BP). Only free protein S possesses cofactor activity for protein C, a physiologic anticoagulant. Deficiencies of either protein C or protein S are associated with increased thrombotic risk. Over a 23-month period, 40 patients with low free protein S were identified. Eight of these patients were found to have suffered a stroke. This study examined the relationship between total S, free S, and C4b-BP in 15 healthy adult volunteers, in 20 patients with normal protein S levels, in 40 patients with decreased free protein S levels, and in 8 patients with combined low free S levels and stroke. Total and free protein S and C4b-BP levels were determined using the method of Laurell. In healthy adults, free protein S increased with increasing total protein S (r = 0.60). In patients with normal free S, the total S level increased as C4b-BP increased (r = 0.74), and the free S level remained constant. In patients with low free S, total S did not increase with increasing C4b-BP. In stroke patients, the correlation between free S and total S was actually negative (r = -0.449). Evaluation of dissociation constants for the protein S-C4b-BP complex revealed enhanced binding in patients with low levels of free protein S. A non-C4b-BP protein S binding protein, a previously undescribed regulatory factor which modulates S binding to C4b-BP, or shifts in the amount of non-protein S binding C4b-BP are possible explanations of these results.
Evaluation of the Coagulation/Fibrinolysis Balance in Patients with Colorectal Cancer
Authors: van Duijnhoven E.M. , Lustermans F.A.T. , van Wersch J.W.J.
Published: April 2009

The coagulation and fibrinolysis profile was evaluated in 40 patiens with newly diagnosed untreated colorectal carcinoma (24 males, 16 females; 29 patients without and 11 patients with metastases). Fibrinogen, von Willebrand factor antigen, FVIILC, thrombin-antithrombin III complex (TAT III), fibrin monomers (FM), plasminogen activator inhibitor-1 (PAI-1) and I-dimers were tested. None of the patients had clinical or laboratory evidence of serious hemorrhage or thrombosis. The results of global routine coagulation tests (aPTT, PT) were not significantly changed. Significant elevations were found for median fibrinogen, von Willebrand factor antigen, FVIILC, TAT III and D-dimers, compared with a healthy reference group. These results confirm earlier reports of an enhanced level of both coagulation and fibrinolysis markers in carcinoma patients and might be helpful in trying to understand the impact of several relatively new sensitive coagulation and fibrinolysis parameters in colorectal cancer. Moreover the position of the coagulation/fibrinolysis balance might be an explanation for the elevated incidence of thrombotic events in patiens with cancer.
Comparative Study on the Antithrombotic Efficacy of Hirudin, Heparin and a Low-Molecular Weight Heparin in Preventing Experimentally Induced Venous Thrombosis
Authors: Monreal M. , Galego G. , Monreal L. , Angles A.M. , Monasterio J. , Oller B.
Published: April 2009

In a random, blind study, we compared the antithrombotic potential of unfractioned heparin, a low-molecular weight heparin (LMWH) and a recombinant hirudin (r-hirudin) given subcutaneously in a jugular vein thrombosis model in rabbits. All drugs and placebo were injected subcutaneously 2 h before inducing experimental thrombosis. A good thrombo-prophylactic effect was obtained with either LMWH and r-hirudin as compared with placebo. By contrast, no significant differences were found between groups in bleeding time. We also found a small (non-significant) prolongation of the activated partial thromboplastin time in the r-hirudin-treated animals. As for thrombin time, r-hirudin-treated rabbits exhibited too much sensitivity, with noncoagulable end-points. In our study, r-hirudin at the dose used seemed to be as effective as LMWH is in the prophylaxis of venous thrombosis.
Effect of Heparin-lnduced Extracorporeal Low-Density Lipoprotein Precipitation and Bezafibrate on Hemorheology and Clinical Symptoms in Cerebral Multiinfarct Disease
Authors: Walzl M.
Published: April 2009

The effects of heparin-mediated extracorporeal low-density lipoprotein (total cholesterol, lipoprotein (a), triglycerides, fibrinogen) precipitation (HELP) and bezafibrate on fibrinogen, metabolic parameters, hemorheological patterns and clinical symptoms were studied in 40 patients suffering from cerebral multiinfarct disease. After a single HELP application, the patients were randomly assigned to two groups, either receiving sustained-release bezafibrate 400 mg (n = 21) or placebo (n = 19) over a period of 8 weeks. In all cases, HELP led to a statistically significant reduction of fibrinogen (p < 0.0001) and other parameters relevant to hemorheology, this effect, however, only being retained in the bezafibrate group. Parallel to this development, the Mathew scale revealed an improvement after HELP (p < 0.01 in each group) with a further improvement in the bezafibrate group (p < 0.05). The Mini Mental State Examination also showed improved results after HELP ( p < 0.0005 and p < 0.03, respectively), a further improvement being observed in the bezafibrate group (p < 0.05). Comparing the day after HELP treatment to that at the end of the study, the Activities of Daily Living Score showed a statistically significant difference in the fibrate group (p < 0.05). These results support the hypothesis that the improved hemorheologic property of blood is an important factor in clinical recovery as well as basic neurologic function.
Platelet Function in Patients with Chronic Coronary Heart Disease on Long-Term Anticoagulant Therapy: Effect of Anticoagulant Stopping
Authors: Vallés Juana , Aznar Justo , Santos Teresa , Villa Piedad , Fernández Angeles
Published: April 2009

Plasma β-thromboglobulin (βTG), platelet procoagulant activity (PPA) and malondialdehyde were evaluated in a control group and in 59 patients with chronic coronary heart disease (CHD) undergoing long-term anticoagulant therapy (ACT) with acenocoumarol, and within 2 months after its termination. The patients were clinically stabilized after more than 1 year of an acute myocardial infarction. An increase in βTG and PPA was found in the patients, both with or without ACT, when compared to the control group. In addition, PPA was found to be higher in older and hypercholesterolemic patients on ACT. After ACT suppression, PPA activity increased significantly, particularly in younger and normocholesterolemic patients. The results of the present study suggest that CHD patients on ACT have some platelet hyperactivity and that the termination of ACT induces an increase in platelet function, particularly in PPA.
Comparison of a Thromboxane Receptor Antagonist and Aspirin in Experimental Arterial Thrombosis
Authors: Schumacher W.A. , Heran C.L. , Youssef S. , Megill J.R. , Michel I. , Durham S.K.
Published: April 2009

The antithrombotic activities of aspirin, the thromboxane (Tx) A2/prostaglandin endoperoxide-receptor (TP-receptor) antagonist, SQ 30,741, and heparin were determined in anesthetized rats. Heparin (3 doses of 50, 300 U/kg), aspirin (1 and 10 mg/ kg), SQ 30,741 (1 mg/kg + 1 mg/kg/h), or the combination of SQ 30,741 and aspirin (10 mg/kg) was administered intravenously before inducing occlusive thrombosis with 0.1-mA stimulation of the intimal surface of the carotid artery. Light and electron microscopy revealed the thrombi to be composed predominately of platelets enmeshed in a fibrin network. Heparin (300 U/kg), SQ 30,741 and SQ 30,741 + aspirin decreased average thrombus weight by 54, 57 and 39%, respectively. These treatments also reduced the incidence of occlusion and improved carotid blood flow during thrombosis. In contrast, aspirin alone (1 and 10 mg/kg) and the lower heparin dose (50 U/ kg) did not significantly affect thrombus weight or carotid blood flow. To verify adequate drug dosage, pharmacological activities were characterized ex vivo in separate rats. Aspirin (10 mg/kg) inhibited maximum thromboxane (Tx) B2 production in whole blood by 99 ± 1 % and SQ 30,741 blocked 96% of platelet TP-receptors. Heparin increased the activated partial thromboplastin time (APTT) partially at 50 U/kg (∼ 3-fold) and maximally at 300 U/kg ( > 10-fold). These experiments demonstrate the contribution of platelet and coagulation mechanisms to a thrombosis model which is sensitive to a TP-receptor antagonist, but not aspirin.
Haemostasis Unbalance in Pugh-Scored Liver Cirrhosis: Characteristic Changes of Plasma Levels of Protein C versus Protein S
Authors: De Caterina Maurizio , Tarantino Giovanni , Farina Carmela , Arena Amalia , di Maro Giosuè , Esposito Pasquale , Scopacasa Francesco
Published: April 2009

Liver cirrhosis leads to a protido-synthetic impairment that alters the levels of blood clotting factors and haemostasis. The aim of this study was to assess the alterations of haemostatic parameters in the evolution of liver cirrhosis scored according to Child’s classification, with Pugh’s modifications. Thirty-seven patients suffering from alcoholic and non-alcoholic liver cirrhosis, representing stages A5, A6, B7, B8 and C10, were tested for the main blood clotting parameters, i.e. prothrombin time, factor VII, partial activated thromboplastin time, fibrinogen, plasminogen, α2-antiplasmin and physiological inhibitors [antithrombin III (ATIII), protein C (PC), protein S (PS)]. No variations were observed between substages A5 and A6 in any of the parameters, except for coagulation inhibitor levels. Most parameters showed a progressive decrease in stages B and C of the disease. The most significant alterations were found in the physiological coagulation inhibitors, with a sharper decrease in PC and AT III level and a lesser decrease in the level of PS through stages A5 and B8: this evidence could assume an important biological and diagnostic significance.
First Experiences with the Heparin-lnduced Extracorporeal Low-Density Lipoprotein Precipitation in the Treatment of Critical Limb Ischaemia: A New Therapeutical Approach?
Authors: Walzl M. , Lechner P. , Walzl B. , Lechner H. , Cesnik H.
Published: April 2009

The heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) system is based on the fact that besides lipoproteins even fibrinogen, which seems to be a very important factor in pathogenesis of peripheral arterial disease, is precipitated by high-dose heparin at acid pH values. The elimination of excess fibrinogen and lipoproteins, in particular LDL, leads to a markedly improved microcirculation. The restoration of the latter obviously enabled us to perform limb-saving surgical procedures instead of mutilating amputations. 12 patients suffering from peripheral arterial disease were submitted to 18 HELP treatments in each case instead of having their critically ischaemic legs removed. Surgery could be limited to necrosectomy only and the wounds were either primarily sutured or covered with skin grafts. We were able to avoid 13 amputations in these 12 patients who could finally walk out of the hospital. HELP treatment was free of side effects in all of them.
Prevention of Laser Arterial Thrombus Formation with Unfractionated Heparin
Authors: Doutremepuich F. , Aguejouf O. , Azougagh Oualane F.A. , Doutremepuich Ch.
Published: April 2009

A method to induce microthrombi in small mesenteric arteries (30-40 µm) has been developed to study platelet reactions and to investigate antithrombotic drugs. This model was used to evaluate the effect of Ca-heparin. Mesenteric lesions are induced in the vascular system of Wistar rats with an argon laser. The laser induced the formation of vessel wall lesion with damage of endothelial cells. Thrombi formed within seconds after the laser lesion and grew rapidly. Embolization began within a minute following the laser flash. Thrombus formation and embolization were repetitive phenomena. The administration of Ca-heparin at different dosages (0.5,1.0 and 2.0 mg/kg) increases the number of laser injuries required to induce thrombus formation, and dose-dependently decreases the number of emboli and the duration of embolization. The highest dose injected (2.0 mg/kg) induced the strongest reduction in the number of emboli and duration of embolization.
Platelet Count in Acute Pulmonary Embolism: Its Relationship to Recurrences
Authors: Monreal Manuel , Lafoz Elena , Ruiz Joan , Gimenez Georgina
Published: April 2009

We have prospectively studied a large series of patients with acute venous thromboembolism, trying to correlate pulmonary embolism (PE) recurrences to a number of clinical variables, and platelet count behavior. A baseline lung scan was obtained initially in every patient. Repeated chest X-ray and lung scans were obtained routinely 8 days after heparin onset. The primary trial endpoint was confirmed, clinically apparent recurrent PE; in addition, laboratory evidence of subclinical PE at the repeat scan was also considered. PE recurrences were found in 26/180 patients, and 3 out of these patients died because of massive, recurrent PE. No significant differences were found in age and sex distribution, or in the degree of deep vein thrombosis proximity between patients who did or did not develop recurrences. There were, however, differences between groups in platelet count: No differences were found in baseline counts, but mean values were significantly lower by the 8th day when recurrences had appeared (229 ± 86 × 109 liters–1 versus 314 ± 129 × 109 liters–1; p < 0.005). The sensitivity, specificity, positive predictive value and negative predictive value for platelet count decrease were 52, 71, 21 and 91 %, respectively. Thus, platelet count cannot be reliably used for individual cases, but our findings add to the pathophysiological picture of the disease.
Prolonged Physical Conditioning and Blood Platelet Release Markers: A Longitudinal Study
Authors: Ponjee Gabriëlle A.E. , Janssen Eugene M.E. , van Wersch Jan W.J.
Published: April 2009

To study the long-term non-acute effect of endurance physical exercise on blood platelet activation, 20 sedentary males and 14 sedentary females were trained 3 to 4 times a week for 9 months. After 24 weeks all subjects ran a 15-km race; and after 36 weeks a half-marathon (21 km) race. Blood samples were drawn before the training programme and 5 days after both races. Median (interquartile range) platelet factor 4 and β-thromboglobulin pretraining values for the total group were 9 (5-35) and 69 (40-495) IU/ml, respectively. During the course of the training programme, plasma platelet factor 4 concentrations rose steadily and significantly in both the male and female group (p < 0.05), together with a non-significant rise in plasma β-thromboglobulin. At the end of the training procedure, 5 days after the half-marathon run, median (interquartile range) plasma factor 4 and β-thromboglobulin concentrations for the total group were 150 (62-198) and 156 (84-288) IU/ml, respectively. No difference existed in median platelet factor 4 and β-thromboglobulin concentrations of the male and female population before or during the training programme. In summary, the results of this study demonstrate that prolonged physical conditioning of increasing intensity is mainly associated with an elevation of the platelet protein platelet factor 4.