bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors and Long-term Follow-up of Patients with the Immune Type of Heparin-Induced Thrombocytopenia
Authors: Lindhoff-Last Edelgard , Wenning Britta , Stein Martina , Gerdsen Frank , Bauersachs Rupert , Wagnert Roland
Published: June 2007

Dispositional risk factors for developing the immune-type of heparin-induced thrombocytopenia (HIT) are yet unclear. This article presents a long-term follow-up of patients with HIT to define possible risk factors that may increase the risk of HIT. The clinical course of acute HIT was analyzed retrospectively in 52 patients with HIT. Thirteen patients died;8 due to HIT. A follow-up investigation was performed in 28 of the remaining 39 patients 29 ± 12 months after the onset of HIT, including genotyping for the factor V G1691A- and the prothrombin G20210A-mutation, measurement of antithrombin, protein C, protein S, factor VIII, and factor XII activity as well as the concentration of antiphospholipid antibodies. The results were compared to an age- and sex-matched control group. New thromboembolic events and re-exposure to heparin were also documented. No difference between patients and controls was observed concerning the factor V Leiden mutation, the prothrombin mutation, factor XII, antithrombin, protein S, or protein C deficiency and antiphospholipid antibodies. Increased factor VIII activity was found in 16 of 21 HIT patients compared to 4 of 21 controls (p=0.0005). New thromboembolic events developed in 5 patients within 9 months after HIT. One patient had been re-exposed to heparin 9 months after acute HIT without any complications. Increased factor VIII activity was frequently observed in patients in whom HIT developed. Thromboembolic complications within the first months after onset of HIT occurred often.
Global Anticoagulant Effects of a Synthetic Anti-Factor Xa Inhibitor (DX-9065a): Implications for Interventional Use
Authors: Tobu Mahmut , Iqbal Omer , Ma Qing , Schultz Christopher , Jeske Walter , Hoppensteadt Debra , Lewis Bruce , Fareed Daniel , Fareed Jawed
Published: June 2007

Heparin has been conventionally used as an anticoagulant for medical and surgical indications. Because factor Xa is an essential component of the prothrombinase complex and leads to the generation of thrombin, its inhibition has become a focus of newer antithrombotic drug development. The in vitro anticoagulant profile of DX-9065a, a synthetic direct factor Xa inhibitor, was studied using activated clotting time assay, thrombelastography, and global clotting tests, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), diluted aPTT, Heptest, Heptest-HI, dilute Russell's viper venom time (dRVVIT), thrombin time, ecarin clotting time, and amidolytic anti-Xa assay. In addition, the effect of DX-9065a on platelet aggregation and inhibition of thrombin generation markers (FPA, Fl + 2, and TAT) were studied. The pharmacokinetic and pharmacodynamic profiles of DX-9065a were also studied in a non-human primate (Macaca mulatta) model. DX-9065a produced a concentration-dependent increase in the Hemochron celite ACT and HemoTec ACT. Clotting times of 538 ± 19 and 401 ± 12, respectively, were reached at a concentration of 25 μg/mL signifying that DX-9065a may be useful in interventional cardiological procedures. DX-9065a prolonged the r-time on thrombelastography. DX-9065a did not show any effect on adenosine diphosphate (ADP)-, collagen-, epinephrine-, and arachidonic acid-induced platelet aggregation at concentrations up to 10 μg/mL. DX-9065a exhibited a concentration-dependent prolongation of the PT, aPTT, diluted aPTT, Heptest, dRVVT, and reached the clotting times of 51.6, 132, 193, 47.9, 129.9 seconds, respectively, at a final concentration of 12.5,tg/mL; compared to a control value of 10.6, 30.2, 41.9, 14, 32.2 seconds, respectively. DX9065a did not affect the ecarin clotting time and thrombin time at concentrations up to 12.5 μg/mL. Because DX-9065a prolonged the dRVVT, this may impact diagnostic screening of patients with systemic lupus erythematosus.
Good or Poor Responses of Hemostatic Molecular Markers in Patients with Hematopoietic Disorders After Treatment of Disseminated Intravascular Coagulation
Authors: Watanabe Rika , Wada Hideo , Yamamuro Miho , Inoue Akiko , Watanabe Masato , Kumeda Kousuke , Sakakura Miho , Okugawa Yoshinaga , Nakasaki Takahiro , Deguchi Hiroshi , Gabazza Esteban C. , Mori Yoshitaka , Nishikawa Masakatsu , Nobori Tutomu , Shiku Hiroshi
Published: June 2007

Changes of hemostatic markers in 226 patients with disseminated intravascular coagulation (DIC) and hematopoietic disorders were examined after treatment of DIC. The changes in prothrombin time (PT) ratio, fibrinogen, fibrin and fibrinogen degradation products (FDP), antithrombin, and protein C, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), and soluble fibrin monomer complex (SFMC) in all patients with DIC were significant during the clinical course of DIC, but those of D-dimer, thrombomodulin (TM), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) were not. Activated partial thromboplastin time (aPTT) and PT were significantly longer in the poor response group than in good response group. Plasma levels of FDP, TAT, PPIC, SFMC, TM, and DIC score were significantly higher in poor response group than in good response. Protein C and antithrombin levels were significantly lower in poor response group than in good response group. The changes of PT ratio, fibrinogen, FDP, DIC score, antithrombin, plasmin inhibitor, and protein C were significant in the good response group, but these levels were not significant in the poor response group. The changes in plasma TAT and SFMC levels were significant in the good response group but were not in poor response group. The changes in D-dimer, TM, TF, or TFPI were not significant in both groups. These findings suggest that anticoagulant agents should be administered at levels below TAT 40 ng/mL or SFMC 300 μg/mL in patients with DIC and hematopoietic disorders.
Mechanical Prosthetic Heart Valve Thrombosis Despite Optimal Anticoagulation in a Patient with Congenital Thrombophilia (Factor V Leiden)
Authors: Pegoraro Cinzia , Biasiolo Alessandra , Iliceto Sabino , Pengo Vittorio
Published: June 2007

Failure of anticoagulant therapy in a patient with a St. Jude heart valve in the mitral position is reported. After 8 years of optimal anticoagulation at an International Normalized Ratio between 2.5 and 3.5, a floating thrombus was discovered by chance during transthoracic echocardiography and then surgically removed. A study for congenital or acquired thrombophilia disclosed a positivity for activated protein C resistance, due to the presence of factor V Leiden. The intensity of warfarin anticoagulation was increased to provide more protection for the patient.
The Effect of a Loading Dose (300 mg) of Clopidogrel on Platelet Function in Patients with Peripheral Arterial Disease
Authors: Matsagas Miltiadis , Jagroop I. Anita , Geroulakos George , Mikhailidis Dimitri P.
Published: June 2007

Clopidogrel acts on the P2Y12 adenosine diphosphate (ADP) purinergic receptors on human platelets. The aim of this study was to establish if a loading dose of clopidogrel inhibits platelet activation in patients with peripheral arterial disease (PAD). Two indices of platelet activation were considered: platelet shape change (PSC) and aggregation. Citrated blood was collected from ten PAD patients who were not on aspirin, at baseline (0 hours) and 2 and 4 hours after these patients ingested a loading dose (300 mg) of clopidogrel. ADP (5,mol/L)-induced platelet aggregation in whole blood was inhibited after 2 hours (free platelet count, 47% ± 19% vs. 68% ± 15%; p < 0.001) and 4 hours (47% ± 19% vs. 66% ± 16%; p 5 0.001). There was also a significant inhibition of 5-hydroxytrypta-mine (5HT, 5.0 Amol/L)-induced platelet aggregation at 2 hours. This trend was also observed for 10-,umol/L ADP-induced aggregation. ADP (0.3-0.4 /imol/L)-induced PSC was significantly inhibited at 4 hours (increase in median platelet volume, 6.3%, 1.8-10.7 vs. 1.2%, 0-5.3; p = 0.01). 5HT (0.5 /Lmol/L)-induced PSC at 4 hours was also significantly inhibited (8.1, 5.3-10.6 vs. 3.0, 0-8.2; p = 0.03). A loading dose of clopidogrel (300 mg) inhibits platelet activation in PAD patients, as early as 2 hours. To the authors' knowledge, no other study considered the effect of a loading dose of clopidogrel in PAD.
A Model for Clinical Estimation of Perioperative Hemorrhage
Authors: Howe Christopher , Paschall Christopher , Panwalkar Amit , Beal James , Potti Anil
Published: June 2007

The purpose of this study was to assess the accuracy of estimated blood loss (EBL) as a reliable predictor of actual blood loss during orthopedic procedures. Between 1999 and 2002, 198 orthopedic cases were reviewed. A retrospective review compiled preoperative and postoperative demographic and laboratory data from the surgical patients. Estimated blood loss data was-collected from the perioperative and anesthesia reports. Statistical nalysis of EBL vs. change in hemoglobin yielded a correlation e6efficient of 0.189 and a p value of 0.008. We used multiple linear regression to obtain a model to predict change in hemoglobin based on EBL and the intravenous fluids received. The model is as follows: predicted change in hemoglobin = 1.001 x estimated blood loss (in liters) + 0.441 x intravenous fluids received (in liters) + 2.334. The study population included 198 patients, 126 males and 72 females, who met our inclusion criteria. The mean age was 68.1 years (range: SD 12.5), induding 126 males (64%) and 72 females (37%). The mean amount of perioperative intravenous fluids given was 1,732 mL (SD: 773). The mean surgical time was 64.8 minutes (SD: 23.1). The mean preoperative hematocrit and hemoglobin levels were 40.9 g/dL (SD: 4.3) and 13.9 g/dL (SD: 1.6), respectively. The mean postoperative hematocrit and hemoglobin levels were 32.0 g/dL (SD: 6.0) and 10.7 g/dL (SD: 1.6), respectively. The mean difference of preoperative hemoglobin vs. postoperative hemoglobin was 3.3 g/dL (SD 2.1). In this retrospective study, clinical estimation of blood loss was closely correlated with actual change in perioperative hemoglobin. Accurately predicting the postoperative hemoglobin level may prevent many unnecessary blood transfusions and related complications.
Point of Care: Diagnostics in Hemostasisthe Wrong Direction?
Authors: Stief Thomas W. , Fareed Jawed
Published: June 2007

Point-of-care-testing (POCT) is performance of a laboratory assay outside the laboratory by nontrained personnel. The advantages of POCT are: more rapid medical decisions, avoidance of long sample transports, and small samples. The disadvantages of POCT are: no laboratory personnel, insufficient calibration, quality control and maintenance, poor documentation, high costs, difficult comparability POCT/central laboratory. Therefore, disposing of a 24-hour central laboratory, the POCT spectrum should be limited to the vital parameters: K+, Ca++, Na+, glucose, creatinine, blood gases, hemoglobin or hematocrit, NH3, lactate. POCT offers no advantages, if the hospital has a rapid transport system such as a pneumatic delivery to the central laboratory. The rapid diagnosis of the acute hemostasis state of a patient should be performed in the 24-hour central laboratory that is connected to all hospital wards via a good pneumatic delivery.
Effects of Lipid Abnormalities on Arteriosclerosis and Hemostatic Markers in Patients under Hemodialysis
Authors: Kushiya Fumihiko , Wada Hideo , Sakakura Miho , Mori Yoshitaka , Gabazza Esteban C. , Nishikawa Masakatsu , Nobori Tsutomu , Noguchi Mitsuya , Izumi Kazuo , Nakasaki Takahiro , Takagi Mikio , Shiku Hirosi
Published: June 2007

Vascular events caused by arteriosclerosis are the major cause of death in patients under hemodialysis (HD). Arteriosclerosis is associated with lipoprotein abnormalities such as increased serum levels of low-density lipoprotein (LDL), especially of modified LDL (M-LDL) and oxidized LDL (Ox-LDL). We examined the relationship between markers of arteriosclerosis, hemostasis, and lipid metabolism in patients with chronic renal failure, hyperlipidemia, and healthy volunteers. In patients under HD, the serum levels of total cholesterol, LDL, and triglyceride (TG) were decreased, but the serum levels of M-LDL were increased compared to HL and healthy volunteers. In patients with CRF, the serum levels of OxLDL in patients under HD were lower than in those under continuous ambulatory peritoneal dialysis or conservative therapy. The plasma levels of antithrombin and protein C were significantly lower and the plasma levels of thrombomodulin were significantly higher in patients under HD compared to those under conservative therapy. These data show that patients under HD were more in hypercoagulable state than those under conservative therapy. Among patients under HD, only the plasma levels of von Willebrand factor were significantly increased in patients with more than 30 U/L of Ox-LDL compared to those with less than 30 U/L of Ox-LDL. There was no significant difference in the tests of arteriosclerosis among M-LDL values and OxLDL values. These findings suggest that abnormalities of lipid are not the main risk factor for arteriosclerosis disease in patients under HD.
Pretreatment Determination of the Serum Urokinase Plasminogen Activator and its Soluble Receptor in Advanced Small-Cell Lung Cancer or Non-Small-Cell Lung Cancer
Authors: Cobos Everardo , Jumper Cynthia , Lox Charles
Published: June 2007

This study was undertaken to evaluate the circulating urokinase plasminogen activator (uPA), and its soluble receptor (suPAR) in patients with either small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Thirty-one male and female patients with stage III or IV NSCLC and 17 with stage III or IV SCLC were compared to 138 age-matched non-smoking controls of both sexes. Before any treatment was undertaken, serum was obtained and evaluated for its content of uPA and suPAR with enzyme-linked immunosorbent assay. The results indicated a wide variation in serum uPA content that was not significant, while extremely significant increases in suPAR were found. The natural physiologic relationship between uPA and its receptor was lost in both SCLC and NSCLC, which could indicate abnormal alterations of uPA suPAR, suggesting these factors aid in the process of invasion and metastasis of lung cancer.
Influence of Different Anticoagulant Agents on Fibrinopeptide A Generation
Authors: Tobu M. , Iqbal O. , Messmore H. L. , Ma Q. , Hoppensteadt D. A. , Fareed J.
Published: June 2007

The purpose of this study was to determine the in vitro effects of different anticoagulant drugs on fibrinopeptide A (FPA) generation inhibition and to identify whether there is any correlation between FPA generation, Hemochron ACT, global clotting as says, and chromogenic assays. Unfractionated heparin is a conventionally used anticoagulant. New anticoagulant drugs such as low molecular weight heparins (LMWHs), pentasaccharide, and antithrombin drugs are now approved for various indications. Anti-Xa drugs are in various phases of clinical development. The influence of different anticoagulant agents has been studied on fibrinopeptide A generation, Hemochron celite ACT, global clotting assays, and chromogenic anti-Xa and anti-Ila assays. Different LMWHs (Clivarin, Dalteparin, Enoxaparin, and Tinzaparin), anti-Xa agents (Pentasaccharide, DX-9065a and unfractionated heparin), and anti-Ila agents (PEG-Hirudin, Hirudin, Efegatran and Argatroban) were studied. The blood from healthy volunteers (n=4) was drawn for each drug. Imuclone FPA enzyme-linked immunosorbent kit assay, Hemochron celite ACT assay, global clotting assays (PT, APTT, Heptest-HI, thrombin time), and Loyola chromogenic anti-Xa and anti-Ila assays were studied. Pentasaccharide demonstrated minimal effects on the whole blood clotting time such as ACT and on inhibition of FPA generation (IC50 > 25 /g/mL). DX-9065a exhibited a significant prolongation of ACT and marked inhibition of FPA generation (IC50 = 4.12 Ag/mL). Unfractionated heparin showed a marked inhibition of FPA generation (IC,, = 5.16 Aog/mL). Pentasaccharide, DX-9065a and UFH showed a marked correlation between ACT and inhibition of FPA generation. LMWHs demonstrated concentrationdependent inhibition of FPA generation. LMWHs studied showed good correlation between FPA generation inhibition and ACT test. Similar correlation was seen between FPA generation inhibition and the APTT, anti Xa (heptest-HI assay) and anti-IIa activity. Anti-IIa drugs demonstrated concentration-dependent inhibition of FPA generation. Their FPA generation inhibition potency is correlated with the ACT assay. A strong correlation between Hemochron ACT and FPA generation inhibition was observed. Based on this significant correlation, the FPA generation inhibition can be predicted by point-of-care ACT assay.
Acute Myocardial Infarction Caused by Delayed Heparin-Induced Thrombocytopenia and Acute Immunoreaction due to Re-exposure to Heparin in a Systemic Lupus Erythematosus Patient with HIT Antibodies
Authors: Suzuki Shunji , Sakamoto Susumu , Okada Takeaki , Matsuo Miyako , Saitoh Atsushi , Matsuo Takefumi
Published: June 2007

A patient with systemic lupus erythematosus and anticardiolipin antibodies and antibodies to platelet factor 4/heparin complexes suffered an acute myocardial infarction caused by delayed heparin-induced thrombocytopenia after heparin administration given to treat pulmonary hypertension. Furthermore, additional heparin administration for emergency coronary angiography appeared to have led to an acute immunoreaction, which might have resulted in acute coronary occlusion during coronary angiography and to a decreased platelet count. The present findings suggest that one must suspect delayed-type HIT in rare cases of induction of thrombosis after the cessation of heparin treatment, and avoid re-exposure to heparin in such cases.
Molecular and Pharmacologic Profile of Tinzaparin and A Comparable Low-Molecular-Weight Bacterial Sulfaminoheparosan
Authors: Maddineni Jyothi , Ma Qing , Hoppensteadt Debra A. , Demir Muzaffer , Manoni Marco , Cornelli Umberto , Fareed Jawed
Published: June 2007

Low-molecular-weight heparins (LMWH) represent depolymerized porcine mucosal heparin derivatives, which are commonly used for the management of thrombotic disorders. Because of their widespread usage, the supplies of the raw material namely unfractionated heparin are nearly exhausted. Porcine mucosal tissue is almost exclusively used for the preparation of these agents. Thus, there is a timely need for the production of heparin like drugs from other sources. Fermentation techniques have been used to produce carbohydrates such as dextran and innulin for therapeutic purposes. Bacterial cell wall polysaccharide mimics the linear hexose units, which constitute heparin. Utilizing Escherichia coli cell membranes produced by fermentation technology, chemical sulfation and enzymatic epimerization, sulfaminoheparosan type of polymer mimick LMWHs. Using this technique, a novel LMW sulfaminoheparosan derivative (Q93C/239) was produced by Inalco, Milan, Italy. To compare this heparin analogue, a LMWH, namely tinzaparin, was used to determine the relative anticoagulant, antiprotease, and molecular profile. Additional studies were carried out to determine the susceptibility of this agent to heparinase-I. These comparative studies exhibited both antiprotease and anticoagulant properties similar to those of tinzaparin. However LMW sulfaminoheparosan resisted heparinase-I digestion at low heparinase-I concentrations. These studies demonstrate that the sulfaminoheparosan derived LMW components exhibit similar molecular and anticoagulant profile as tinzaparin and warrant additional preclinical and clinical development to determine their potential usefulness as antithrombotic agents.
Can Hematocrit and Platelet Determination on Admission Predict Shock in Hospitalized Children with Dengue Hemorrhagic Fever? A Clinical Observation from a Small Outbreak
Authors: Wiwanitkit Viroj , Manusvanich Pornake
Published: June 2007

Dengue infection is a major public health problem, affecting children in the Southeast Asia region. In Thailand, the dengue hemorrhagic fever is still a major infectious disease among the children with up to two to three epidemics per year. Hemoconcentration accompanied by platelet depletion are the predominant laboratory signs of dengue hemorrhagic fever. Findings from 23 hospitalized patients with dengue hemorrhafic fever in a small outbreak in a provincial hospital in Thailand are reported. The question if hematocrit and platelet determination on admission can predict shock in hospitalized children with dengue hemorrhagic fever was studied. The data from the discharge summary of these patients were studied, focusing on the admission hematology laboratory data. Regression analysis was used to test the correlation between the admission hematology laboratory data (hematocrit, white blood cell count, and platelet) and the focused outcome (shock or no shock). Of these 23 patients, shock did not develop in 19, and shock developed in four. There was no significant difference in admission hematology laboratory data between both groups (p < 0.05). The regression analysis revealed no significant correlation between the studied hematology laboratory data and the focused outcome (p > 0.05). It means that the three studied investigations on admission cannot predict shock in our hospitalized dengue hemorrhagic cases. From this study, it can imply that closed monitoring of dengue hemorrhagic patients is necessary. The general practitioner cannot rely on the admission hematology laboratory data to predict shock in these patients. Additionally, it might confirm that, although dengue infection can be fatal, with proper supportive treatment, especially hospitalization and hydration for severe cases, the outcome is very good.
Thrombin Generation by Exposure of Blood to Endotoxin: A Simple Model to Study Disseminated Intravascular Coagulation
Authors: Stief T. W.
Published: June 2007

Pathologic disseminated intravascular coagulation (PDIC) is a serious complication in sepsis. In an in-vitro system consisting of incubation of fresh citrated blood with lipopolysaccharides (LPS) or glucans and subsequent plasma recalcification plasmatic thrombin was quantified. Five hundred microliters of freshly drawn citrated blood of healthy donors were incubated with up to 800 ng/mL LPS ( Escherichia coli) or up to 80 μg/mL Zymosan A (ZyA; Candida albicans) for 30 minutes at room temperature (RT). The samples were centrifuged, and 30 μL plasma were recalcified with 1 volume or less of CaCl2 (25 μmoles Ca2+/mL plasma). After 0 to 12 minutes (37°C), 20 μL 2.5 M arginine, pH 8.6, were added. Thirty microliters 0.9 m M HD-CHG-Ala-Arg-pNA in 2.3 M arginine were added, and the absorbance increase at 405 nm was determined. Fifty microliters plasma were also incubated with 5 μL 250 m M CaCl2 for 5, 10, or 15 minutes (37°C). Fifty microliters 2.5 M arginine stops coagulation, and 50 μL 0.77 m M HD-CHG-Ala-Arg-pNA in 2.3 M arginine starts the thrombin detection. The standard was 1 IU/mL thrombin in 7% human albumin instead of plasma. Arginine was also added in the endotoxin exposure time (EET) or in the plasma coagulation reaction time (CRT). Tissue factor (TF)-antigen and soluble CD14 were determined. LPS at blood concentrations greater than 10 ng/mL or ZyA at greater than 1 μg/mL severalfold enhance thrombin generation, when the respective plasmas are recalcified. After 30 minutes EET at RT, the thrombin activity at 12 minutes CRT generated by the addition of 200 ng/mL LPS or 20 μg/mL ZyA is approximately 200 mIU/mL compared to approximately 20 mIU/mL without addition of endotoxin, or compared to about 7 mIU/mL thrombin at 0 minutes CRT. Arginine added to blood or to plasma inhibits thrombin generation; the inhibitory concentration 50% (IC 50) is approximately 15 m M plasma concentration. Endotoxin incubation of blood increases neither TF nor sCD14. This assay allows the study of the hemostasis alteration in PDIC, particularly in PDIC by sepsis. The thrombin generated by blood plus endotoxin incubation and plasma recalcification suggests that the contact phase of coagulation; e.g., triggered by cell components of (phospholipase-) lysed cells such as monocyte or endothelium DNA or phospholipid-vesicles (microparticles), is of primary pathologic importance in sepsis-PDIC. Arginine at plasma concentrations of 10 to 50 m M might be a new therapeutic for sepsis-PDIC.
Vitamin E and a-Lipoic Acid Supplementation Increase Bleeding Tendency via an Intrinsic Coagulation Pathway
Authors: Marsh Susan A. , Coombes Jeff S.
Published: June 2007

Vitamin E and a-lipoic acid are potent nutritional antioxidants, and when used together, their antioxidant capabilities are improved as a-lipoic acid recycles vitamin E. Supplementation of vitamin E has been shown to prolong platelet aggregation but the effects of vitamin E and a-lipoic acid supplementation on bleeding tendency have yet to be reported. Young, male rats consumed either control diet (n=5) or vitamin E and a-lipoic acid-supplemented diet (n=5) for 14 weeks. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured as markers of intrinsic and extrinsic coagulation pathways respectively in addition to lipid peroxidation (malondialdehyde). Supplementation significantly prolonged APTT (23.8±1.5 vs 31.4±1.2s, p<0.05) compared to the control diet; however, there was no significant difference in PT (27.8±1.5 vs 26.6±0.9s, p>0.05). While vitamin E was increased (p<0.05), there was no significant difference in plasma levels of malondialdehyde (p>0.05). Dietary supplementation of vitamin E and a-lipoic acid increases bleeding tendency via inhibition of the intrinsic coagulation pathway with no change in markers of lipid peroxidation. Such supplementation could benefit patients with cardiovascular disease who exhibit elevated levels of coagulation and oxidative stress.
Hemorrhagic Complications in Patients Treated with Anticoagulant Doses of a Low Molecular Weight Heparin (Enoxaparin) in Routine Hospital Practice
Authors: Ellis Martin H. , Hadari Ruth , Tchuvrero Noa , Shapira Shirley , Kovlenko Irena , Kozmiakova Mariana , Zissin Rivka , Elis Avishay
Published: June 2007

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5±15.5 years and the mean duration of enoxaparin therapy was 3.8±1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5±10.4 versus 66.8±15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14±3.8 days) than those with minor (4±2.5 days) or no hemorrhage (2.9±2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.
Diabetic Ulcers: Microcirculatory Improvement and Faster Healing With Pycnogenol
Authors: Belcaro G. , Cesarone M. R. , Errichi B. M. , Ledda A. , Di Renzo A. , Stuard S. , Dugall M. , Pellegrini L. , Gizzi G. , Rohdewald P. , Ippolito E. , Ricci A. , Cacchio M. , Cipollone G. , Ruffini I. , Fano F. , Hosoi M.
Published: June 2007

Diabetic microangiopathy leads to lower limb ulcers that are very slow to heal. Pycnogenol was evaluated on diabetic ulcers in a controlled trial. Ulcer medications were used in 4 groups (30 patients): (1) systemic Pycnogenol and local application; (2) local Pycnogenol only; (3) oral Pycnogenol; and (4) medications only (control group). Ulcerated areas and symptom scores were more reduced with the combined oral and local treatment ( P < .05). Oral and local treatment were less effective, but still improved compared with the controls. Combined treatment produced 89% complete healing at 6 weeks versus 84% with local treatment and 85% with oral treatment; healing in controls was 61%. The combined treatment group and oral only group had better microcirculation after the combined treatment. Combined local and systemic application of Pycnogenol may offer a new treatment of diabetic ulcers. Local treatment also speeds ulcer healing.
Spontaneous Thrombolysis: A Forgotten Determinant of Life or Death
Authors: Kovacs Iren B. , Yamamoto Junichiro
Published: June 2007

Substantial evidence suggests that spontaneous thrombolytic activity of blood is an effective mechanism for protection against tissue damage that is the consequence of lasting arterial occlusion. Despite the generally held belief that coronary artery disease and stroke are preventable, a promising avenue of prevention, namely the identification and prophylactic treatment of those at risk of inefficient spontaneous thrombolysis, has been neglected. This is mainly due to the lack of physiologically relevant test. A recently described technique allows the measurement of spontaneous thrombolysis, that is, lysis of an autologous platelet-rich thrombus in the absence of added plasminogen activators. Early results suggest that this test may have significant clinical potential both in identifying those at risk from fatal thrombotic event and in finding new therapeutic avenues of improving spontaneous thrombolytic activity.
Secondary Prevention of Venous Thromboembolic Events in Patients With Active Cancer: Enoxaparin Alone Versus Initial Enoxaparin Followed by Warfarin for a 180-Day Period
Authors: Deitcher Steven R. , Kessler Craig M. , Merli Geno , Rigas James R. , Lyons Roger M. , Fareed Jawed
Published: June 2007

This study evaluated enoxaparin alone versus initial enoxaparin followed by warfarin in secondary prevention of venous thromboembolic events in adults with active malignancy. Cancer patients (n = 122) with acute symptomatic venous thromboembolic events were randomly allocated to receive subcutaneous enoxaparin 1.0 mg/kg every 12 hours for 5 days, followed by 1.0 mg/kg daily (group 1a) or 1.5 mg/kg daily (group 1b) for 175 days, or subcutaneous enoxaparin 1.0 mg/kg every 12 hours for at least 5 days and until a stable international normalized ratio of 2 to 3 was achieved on oral warfarin begun on day 2 and continued to day 180 (group 2). There were no significant differences in major and minor bleeding rates between treatment groups. No bleeding events were intracranial or fatal. Enoxaparin treatment was feasible, generally well tolerated, and effective for a 180-day period in the secondary prevention of venous thromboembolic events in patients with active malignancy.
Relative Neutralization of the Biological Actions of Sulfaminoheparosans (K5 Derivatives) and Heparins by Protamine Sulfate
Authors: Maddineni Jyothi , Hoppensteadt Debra A. , Cornelli Umberto , Manoni Marco , Fareed Jawed
Published: June 2007

Biosynthetic, semisynthetic, and synthetic analogues of heparins are currently developed as substitute antithrombotic agents for heparin. Sulfaminoheparosan (SAH) represents a bacterial polysaccharide (K5)-derived antithrombotic polymer from which pharmacologically active products with varying molecular weights (5-25 kDa) can be derived. These agents have been shown to exhibit pharmacologic effects comparable to heparins. The objective of this investigation is to determine the relative neutralization profile of various SAH derivatives, also called as bioheparins, by protamine sulfate. Four SAH fractions with varying molecular weights (20, 9, 7, and 6 kDa), a low molecular weight heparin (LMWH), tinzaparin, and unfractionated heparin (UFH) were supplemented to normal human pool plasma over a concentration range of 6.2 to 100 μg/mL. A fixed amount of protamine sulfate at 25 μg/mL (final concentration) was supplemented to determine the neutralization profile by performing tests such as prothrombin time (PT), activated partial thromboplastin time (APTT), Heptest, prothrombin-induced clotting time (PiCT), and amidolytic anti-Xa and anti-IIa assays. Protamine sulfate produced varying degrees of neutralization of all bioheparin fractions in the clotting assays. In the amidolytic anti-IIa assay relatively stronger inhibition was noted for all agents than inhibition of FXa. On a cumulative basis the neutralization profile of SAHs was comparable with heparins. These results suggest that the anticoagulant activities of SAH derivatives can be antagonized by protamine sulfate. These studies warrant further in vivo investigation to validate the relative neutralization profile of sulfaminoheparosans.
Significance of Factor V, Prothrombin, MTHFR, and PAI-1 Genotypes in Childhood Cerebral Thrombosis
Authors: Ozyurek Emel , Balta Gunay , Degerliyurt Aydan , Parlak Hülya , Aysun Sabiha , Gürgey Aytemiz
Published: June 2007

The aim of this study was to evaluate the significance of factor V (FV) G1691A, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G genotypes in development of childhood cerebral thrombosis (CT). A total of 113 Turkish children with CT were studied and compared with the control group. The carrier frequency of the factor V G1691A mutation was found to be significantly higher in the patient group (17.7%) than controls (7.4%). The presence of this genotype was associated with a 2.7-fold increased risk of developing CT (95% confidence interval [CI], 1.0—7.0). The prevalence of prothrombin G20210A mutation in 110 patients (4.5%) was insignificantly higher than controls (2.3%) (odds ratio, 2.0; 95% CI, 0.4—10.7). A statistically significant increase in the frequency of homozygous MTHFR C677T genotype was observed in 62 patients (11.3%) compared to controls (4.3%), and this genotype was associated with 2.8-fold increased CT risk (95% CI, 1.0—8.0). The incidence of PAI-1 4G/4G genotype in 65 patients (21.5%) was slightly lower than that of controls (26.0%), but the differences did not reach statistical significance (odds ratio, 0.8; 95% CI, 0.4—1.5). The results of this study suggested that factor V G1691A and MTHFR C677T genotypes may be associated with an increased risk of developing CT in Turkish children.
The Frequency of Factor V Leiden and Concomitance of Factor V Leiden With Prothrombin G20210A Mutation and Methylene Tetrahydrofolate Reductase C677T Gene Mutation in Healthy Population of Denizli, Aegean Region of Turkey
Authors: Kabukcu Sibel , Keskin Nazan , Keskin Ali , Atalay Erol
Published: June 2007

Factor V Leiden causing activated protein C resistance is the most common inherited form of thrombophilia leading to thrombosis. Its frequency shows great ethnic and geographic variations. The aim of this study was to determine the frequency of FV Leiden and coinheritance of FV Leiden with two other frequent hereditary thrombophilia causes, namely, prothrombin G20210A and methylene-tetrahydrofolate reductase ( MTHFR) C677T mutation in the Aegean region of Turkey. The study population consisted of 1030 (500 men and 530 women) apparently healthy subjects. Functional resistance to activated protein C (APC) was measured by using the test kit STA staclot APC-R ((Diagnostica Stago, Asnieres, France, Cat. No. 00721). In subjects with APC resistance, molecular analyses of FV Leiden and of prothrombin G20210A and MTHFR C677T mutation were performed by using FV-PTH-MTHFR StripA (Vienna Lab, Labordiagnostika GmbH, Austria) kit, which was based on hybridization of polymerase chain reaction (PCR) amplified DNA products with mutation-specific oligonucleotide probes. Functional APC resistance was present in 93 subjects (9%). FV Leiden mutation was found in 87 of 93 subjects with APC resistance by PCR method. The FV Leiden carrier frequency was found to be 8.4% (87/1030). Seventy-six individuals were heterozygous (7.3%), and 11 were homozygous (1.06%). Among the 87 subjects with FV Leiden mutation, 45 subjects had MTHFR C677T gene mutation (7 homozygous, 38 heterozygous) and 4 subjects had heterozygote prothrombin G20210A gene mutation. A combination of FV Leiden and prothrombin G20210A and MTHFR C677T gene mutation was detected in 3 subjects. The results indicate that FV Leiden prevalence is quite high and coexistence of FV Leiden with other hereditary causes of thrombosis such as prothrombin G20210A mutation and MTHFR enzyme defect is not rare in healthy population of Aegean region of Turkey.
Lower Contribution of Factor V Leiden or G202104 Mutations to Ischemic Stroke in Patients With Clinical Risk Factors
Authors: Eterović Davor , Titlić Marina , Čulić Viktor , Zadro Renata , Primorac Dragan
Published: June 2007

It was suggested that factor V Leiden and prothrombin G20210A mutations increase the risk of ischemic stroke only in combination with clinical risk factors of arterial ischemic disease. In these studies the controls were derived from the general population, with fewer clinical risk factors, which might have produced biased results. The factor V Leiden and prothrombin G20210A mutations were examined by polymerase chain reaction technique in 120 ischemic stroke patients and 120 controls younger than 65 years of age. Each patient had his own control, tightly matched in clinical risk factors. The prevalences of factor V Leiden and prothrombin G20210A mutations in patients were 8.3% (P = 0.02) and 7.5% (P = 0.04), respectively, and 2.5% for controls for both mutations. All carriers were single heterozygotes. In patients, but not in controls, the carriers of either mutation were mostly women and with fewer clinical risk factors for arterial ischemic events. In particular, considering both mutations as a single coagulation deficit, their presence increased the likelihood of ischemic stroke (odds ratio [OR] = 3.6; 95% confidence interval [CI] 1.4—9.3), especially among women (OR = 4.6; 95% CI: 1.2—17.8), normotensive persons (OR = 9.2; 95% CI: 1.1—17.8) and those having normal cholesterol (OR = 5.9; 95% CI: 1.6—21.2) and triglyceride serum concentrations (OR = 4.3; 95% CI: 1.5—12.8). In the studied sample of adult North Mediterranean population younger than 65 years the prevalences of factor V Leiden and prothrombin G20210A mutations were greater in patients with ischemic stroke than in matched controls. Unlike in studies with unmatched controls, we observed an apparently negative interaction of these mutations with clinical risk factors.
Increased Concentration of Soluble CD40 Ligand in Preeclampsia
Authors: Alacacioglu Inci , Ozcan Mehmet Ali , Piskin Ozden , Yuksel Faize , Alacacioglu Ahmet , Demirkan Fatih , Ozsan Hayri Guner , Polat Mesut , Ozgenc Yigit , Undar Bulent
Published: June 2007

Preeclampsia has been associated with increased platelet activation detected before disease onset. Platelets are involved in hemostasis and also directly initiate an inflammatory response of the vessel wall. Inappropriate activation of platelets may be involved in pathogenesis in preeclampsia by promoting coagulation and thrombosis, and also as a mediator of inflammation. Platelets may release inflammatory mediators such as soluble CD40 ligand. The plasma level of soluble CD40 ligand was investigated during preeclamptic (n =20) and normal pregnancies (n = 20) to emphasize inflammatory response in preeclampsia. The mean soluble CD40 ligand levels were 1.08 ± 0.43 ng/mL in patients with preeclampsia and 0.76 ± 0.24 ng/mL in healthy pregnant women, which was statistically significant ( P = .01). To clarify whether inflammation may cause inappropriate endothelial cell activation or inappropriate endothelial cell activation may start this inflammatory response, future studies are needed in a larger study population.
A Prospective Comparison of New Japanese Criteria for Disseminated Intravascular Coagulation
Authors: Hayakawa Mineji , Gando Satoshi , Hoshino Hirokatsu
Published: June 2007

In Japan, early diagnosis and early treatment of disseminated intravascular coagulation (DIC) based on the old Japanese criteria have greatly improved the outcomes of DIC patients with hematopoietic malignancy. However, the prognoses of critically ill patients with DIC have remained poor. To overcome this situation, new Japanese DIC criteria for critically ill patients were established in 2002. The new Japanese DIC criteria adopted a concept of coagulopathy associated with systemic inflammatory response syndrome. In the present study, we prospectively investigated the relationships between the new criteria and organ failure, prognosis, and other sets of DIC criteria. This study included 74 patients whose platelet counts were below 150 × 109/L. Daily DIC scores and sequential organ failure assessment scores were recorded from days 0 to 4 once the patient was included
Optimal Input Shaper Design For High-Speed Robotic Workcells
Authors: Chan Timothy , Godbole Kedar , Hou Edwin
Published: June 2007

This paper deals with the feedforward control of a high-speed robotic workcell used by the NIST-ATP Precision Optoelectronics Assembly Consortium as a coarse stage to achieve micrometer-level placement accuracy. To maximize the speed of response under different load conditions, robust feedforward algorithms are considered. An optimal shaper is synthesized to trade off performance and robustness according to assembly specifications of the workcell. The optimal shaper along with standard shaper designs such as zero vibration, zero vibration and derivative, and extra insensitive are applied to conduct cycle time testing on the robotic workcell. The performance of each shaper is evaluated with respect to residual vibration, robustness, and speed. Specifically, the workcell performance for various unknown loading conditions is observed. It is shown that the optimal shaper produces the best overall results.
Vibration Absorbers: A Review of Applications in Interior Noise Control of Propeller Aircraft
Authors: Wright R. I. , Kidner M. R. F.
Published: June 2007

Control of interior noise levels in aircraft has been a significant research area over the last two decades. Vibration absorbers have often been researched as more efficacious solutions to this problem than absorbent blankets or fully active systems. In this paper we review the large body of work performed in this field and we offer an indication of the remaining areas for fruitful research. Surprisingly few installations of vibration absorbers for interior noise control have been realized, and we believe this is due to the pervasive belief in industry that vibration absorbers can only be applied to control resonant, not forced behavior in a structure. The potential of adaptive passive control using vibration absorbers has been shown by many researchers, and we believe that this direction may yield several practical solutions to the problem of interior noise in aircraft.
An Integral Equation Approach for Shape Optimization of Plate Piezoelectric Patch
Authors: Zhang J. , Bruch J. C. , Sloss J. M.
Published: June 2007

In this paper, we consider a vibrating system with piezoelectric patches whose minimum vibration frequency is to be maximized subject to some constraint on the patch geometry. A numerical scheme is constructed based on the integral equation approach for the computation of the corresponding eigenvalue problem and the boundary parametrization optimization technique. Various numerical results are provided for the case of a Plexiglas plate with PVDF sensor and actuator patches.
Fuzzy Sliding Mode Controller for a Flexible Single-Link Robotic Manipulator
Authors: Bazzi B. A. , Chalhoub N. G.
Published: June 2007

Two robust non-linear controllers have been developed in this study to control the rigid and flexible motions of a single-link robotic manipulator. The controllers consist of a conventional sliding mode controller (CSMC) and a fuzzy sliding mode controller (FSMC). The effects of fuzzy-tuning some of the CSMC control parameters on the overall performance of the arm have been investigated in this study. Furthermore, the proposed FSMC, whose parameters are determined by fuzzy inference systems, has been designed herein based on two Lyapunov functions. The rationale is to considerably reduce the momentum of the system before entering the boundary layer neighboring the sliding surface. This will significantly attenuate the structural deformations of the arm. The digital simulations have demonstrated that the structural deformations, incurred by the beam at the onset of its movement, can be significantly reduced by fuzzy-tuning some of the control parameters. Furthermore, the results have illustrated the superiority of the FSMC over the CSMC in producing a less oscillatory and more accurate response of the angular displacement at the base joint, in damping out the unwanted vibrations of the beam, and in requiring significantly smaller control torques.
Study of the Vibration Control of a Rotor System Using a Magnetorheological Fluid Damper
Authors: Wang J. , Meng G.
Published: June 2007

A shear mode magnetorheological (MR) fluid damper used for rotor vibration control is designed and manufactured, and the theoretical model of a cantilevered rotor system with the MR fluid damper is established. The response properties of the rotor system are studied theoretically and experimentally. It is found from the study that the Coulomb friction of the damper is increased as the magnetic field strength applied to the MR fluid increases. As a result, the vibration amplitude of the rotor system supported by the MR damper is decreased near the undamped critical speeds, but is increased in a rotating speed range between the first and the second undamped critical speeds. At the same time, the damped critical speed of the rotor system is increased with the increase of the applied magnetic field. Based on these characteristics, a simple on-off control method is used to suppress the rotor vibration across the critical speeds, and the results show that the method is very effective.
Impact of Pay-for-Performance Contracts and Network Registry on Diabetes and Asthma HEDIS® Measures in an Integrated Delivery Network
Authors: Levin-Scherz Jeffrey , DeVita Nicole , Timbie Justin
Published: June 2007

This article reviews the experience of a large, heterogeneous integrated delivery network that incorporated physician quality metrics into pay-for-performance contracts. The authors present criteria for including measures in pay-for-performance contracts and offer a practical approach to determining withhold return or bonus distribution based on improvement and performance. They demonstrate interventions undertaken to improve performance, including the development of a claims-based registry. Empirical data show that the network performance improved more than the comparable state and national performance during the period of this observational study. The authors conclude that pay for-performance contracts led to development of medical management programs including a claims-based registry and nonphysician interventions, which helped significantly improve selected HEDIS scores.