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Öğe Acute myocardial infarction in a patient with essential thrombocythemia treated with glycoprotein IIb/IIIa inhibitor(Sage Publications Inc, 2004) Gül, Ç; Kürüm, T; Demir, M; Özbay, G; Vural, Ö; Iqbal, O; Fareed, JEssential thrombocythemia (ET) rarely causes obstruction of coronary arteries or acute myocardial infarction. Treatment of acute myocardial infarction in patients with ET may be a problem due to the important role of platelets in the pathogenesis of infarction. There is no reported case of acute myocardial infarction with essential thrombocythemia treated with a glycoprotein IIb/IIIa inhibitor. In this report, a 49-year-old woman with essential thrombocythemia, admitted with a diagnosis of acute inferolateral myocardial infarction, was treated with tirofiban, a glycoprotein IIb/IIIa receptor blocker.Öğe Anticoagulant and antiprotease effects of a novel heparinlike compound from shrimp (Penaeus brasiliensis) and its neutralization by heparinase I(Sage Publications Inc, 2001) Demir, M; Iqbal, O; Dietrich, CP; Hoppensteadt, DA; Ahmad, S; Daud, AN; Fareed, JHeparin is usually obtained from mammalian organs, such as beef lung, beef mucosa, porcine mucosa, and sheep intestinal mucosa. Because of the increased use of heparin in the production of low-molecular-weight heparin (LMWH), there is a growing shortage of the raw material needed to produce LMWHs. A previous report described the structural features of a novel LMWH from the shrimp (Penaeus brasiliensis). In order to compare anticoagulant and antiprotease effects of this heparin, global anticoagulant tests, such as the prothrombin time, activated partial thromboplastin time, thrombin time, and Heptest(R), were used. Amidolytic anti-Xa and anti-IIa activities were also measured. The relative susceptibility of this heparin to flavobacterial heparinase was also evaluated. The United States Pharmacopeia (USP) potency of shrimp heparin (SH) was found to be 28 U/mg. SH produced a concentration-dependent prolongation of all of the clotting tests and exhibited marked inhibition of FXa and FIIa. Heparinase treatment resulted in a marked decrease of the anticoagulant effects and neutralized the in vitro anti-IIa actions. However, the anti-Xa activities were only partially neutralized. Protamine sulfate was only partially effective in neutralizing the anticoagulant and antithrombin effects of SH. SH also produced marked prolongation of activated clotting time, which was neutralized by heparinase but not by protamine sulfate. These results suggest that SH is a strong anticoagulant with comparable properties to mammalian heparins and can be used in the development of clinically useful antithrombotic-anticoagulant drugs.Öğe Anticoagulant and antiprotease profiles of a novel natural heparinomimetic mannopentaose phosphate sulfate (PI-88)(Lippincott Williams & Wilkins, 2001) Demir, M; Iqbal, O; Hoppensteadt, DA; Piccolo, P; Ahmad, S; Schultz, CL; Linhardt, RJHeparinomimetic mannopentaose phosphate sulfate (PI-88) (Progen Industries Ltd. Brisbane, Australia), currently developed as an anticoagulant and antiproliferative agent, mainly is composed of a pentomannan. However, tetrasaccharide and disaccharide components are also present. The molecular profile and the anticoagulant potency of PI-88 are investigated in this study. Gel permeation chromatography and polyacrylamide gel electrophoresis analyses were carried out to determine the molecular profile and separation of components of PI-88, respectively. Potentiation of antithrombin III (ATIII) and heparin cofactor-II (HC-LI) activity were measured using chromogenic substrate assay. In order to determine anticoagulant and antiprotease effects of PI-88, various global anticoagulant tests, such as the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Heptest(R) (Haemachem Inc., St. Louis), ecarin clotting time (ECT), activated clotting time (ACT), and thromboelastography (TEG) were used. Anti-Xa and anti-IIa activities also were measured. The effect of PI-88 on the release of tissue factor pathway inhibitor (TFPI) was performed in nonhuman primates who received PI-88 and in endothelial cell culture systems. The relative susceptibility of PI-88 to heparinase I, protamine sulfate (PS), and platelet factor 4 (PF4) also was evaluated. The high-performance liquid chromatography profiles of PI-88 showed that its average molecular weight is approximately 2300 Da. Separation and gradient electrophoretic patterns of PI-88 showed that it is composed of five different fractions. This agent activates HC-II through inhibiting the thrombin generation but not inhibiting ATIII. Although PI-88 produced a concentration-dependent prolongation of all of the clotting tests, ECT gave the best correlation in the dose-response curve (ECT, r(2) = 0.94; TT, r(2) = 0.84; APTT, r(2) = 0.69). Heparinomimetic mannopentaose phosphate sulfate (PI-88) exhibited marked inhibition of FIIa, but not of FXa. Heparinase I failed to produce significant neutralization of PI-88 in all the assays used, whereas PS and PF4 partially neutralized the effects of this compound. Heparinomimetic mannopentaose phosphate sulfate (PI-88) produced fivefold increase in the TFPI levels at 15 minutes after intravenous (IV) injection to primates. The incubation of PI-88 in endothelial cell culture system also showed a strong effect on TFPI release. These results suggest that PI-88 exhibited strong antithrombotic and anticoagulant activity in addition to its known antiproliferative properties. Because of the molecular characteristics and the dual nature of the pharmacologic action of PI-88, this agent represents an attractive pharmacologic agent for the control of thrombotic and proliferative disorders.Öğe Blood levels of nitric oxide and its relevance to C-reactive protein, CD 40L, TF and TNF? in malignancy associated hypercoagulable state.: Pathologic implications.(Amer Soc Hematology, 2003) Fareed, D; Bick, R; Bacher, P; Iqbal, O; Tobu, M; Hoppensteadt, D; Demir, A[Abstract Not Available]Öğe Comparative study on the anticoagulant effects of low molecular weight heparins as measured by whole blood ACT, anti-Xa and a newly developed prothrombinase induced clotting time (PiCT) assay(Amer Soc Hematology, 2005) Hoppensteadt, D; Tobu, M; Wahi, R; Iqbal, O; Walenga, JM; Demir, M; Baltasar, F[Abstract Not Available]Öğe Ecarin clotting time is sensitive to heparinoids: Comparison of two different techniques(Lippincott Williams & Wilkins, 2001) Demir, M; Iqbal, O; Untch, B; Hoppensteadt, DA; Gaikwad, BS; Fareed, JEcarin clotting time (ECT) is currently developed for the specific monitoring of antithrombin drugs, such as hirudin, argatroban, and hirulog. Aqueous reagent and dry chemistry technology have become available for ECT monitoring of antithrombin agents. Currently, many heparinoids and heparinomimetic drugs are being developed. These agents activate heparin cofactor II (HCII) and primarily mediate their effects by inhibiting thrombin. Although the test is specific for antithrombin agents, heparin cofactor II-mediated thrombin inhibitors are capable of prolonging the ECT. In order to study the relative effects of some of these agents, ECT was measured in human plasma supplemented with PI-88 (a sulfated pentomanose; Progen Industries Limited, Sydney, Australia), aprosulate, pentosan polysulfate, dermatan sulfate, unfractionated heparin (UFH), and recombinant hirudin (r-hirudin). All agents were supplemented to the citrated-pooled plasma prepared from 10 healthy volunteers at a graded dosage of 0 to 100 mug/ml. These techniques gave comparable results for all of the agents used (PI-88, r(2) = 0.99; r-hirudin, r(2) = 0.98; UFH, r(2) = 0.98; dermatan sulfate, r(2) = 0.95; aprosulate, r(2) = 0.95; pentosan polysulfate, r(2) = 0.94). The relative anticoagulant effects of various agents used on ECT varied widely, exhibiting their potency in the following order: r-hirudin = pentosan polysulfate > dermatan sulfate > PI-88 > aprosulate > UFH. The sensitivity of ECT was adjusted by varying the concentration of the ecarin reagent. The results suggest that HCII-mediated inhibition of thrombin can be detected by using ECT reagents.Öğe Frequency of anti-erythropoietin antibodies in patients with end stage renal disease treated with recombinant erythropoietin(Amer Soc Hematology, 2005) Hoppensteadt, D; Tobu, M; Fareed, D; Iqbal, O; Baltasar, F; Patel, C; Bansal, V[Abstract Not Available]Öğe Global anticoagulant effects of a novel sulfated pentomanan oligosaccharide mixture(Lippincott Williams & Wilkins, 2001) Piccolo, P; Iqbal, O; Demir, M; Ma, Q; Gerbutavicius, R; Fareed, JPI-88 is a potent antiproliferative agent, which is developed for various indications in cancer. This agent is obtained from yeast fermentation and is primarily composed of pentamannose and tetramannose oligosaccharide units. PI-88 is capable of producing anticoagulant effects, which are mediated by heparin cofactor II. The purpose of this study was to determine the anticoagulant properties of PI-88 in native whole blood, freshly drawn from human volunteers, supplemented with PI-88 at various concentrations (0-100 mug/mL). Whole blood activated clotting time (ACT) was measured using Hemochron instruments. PI-88 produced a strong anticoagulant effect at 100 mug/mL (479.0 +/- 59.5 sec). This anticoagulant effect was comparable to that observed in interventional cardiology and open-heart surgery. At the lower level, PI-88 produced concentration-dependent effects on ACT. Using thromboelastographic techniques (TEG), the effect of PI-88 was measured in terms of various parameters. PI-88 produced potent anticoagulant effects in the TEG studies. At the concentration of 25 mug/mL, it produced a complete anticoagulant effect in whole blood. Whole blood samples supplemented with PI-88 showed a concentration-dependent decrease in the generation of various markers of clotting activation. These results clearly suggest that PI-88 exerts an anticoagulant effect in whole blood. Because of the low-molecular-weight nature and a novel mechanism of action, this new drug may be considered for further development, particularly in cancer patients.Öğe Hyperhomocysteinemia in cancer patients with thrombosis is independent of methylene tetrahydrofolate reductase gene mutation.(Amer Soc Hematology, 2004) Fareed, J; Tobu, M; Hoppensteadt, DA; Cunanan, J; Iqbal, O; Demir, M; Deitcher, S[Abstract Not Available]Öğe Role of PAI-1 and TAFI in the mediation of fibrinolytic deficit in cancer patients.(Amer Soc Clinical Oncology, 2004) Florian-Kujawski, MR; Hoppensteadt, D; Iqbal, O; Demir, M; Tobu, M; Fareed, D; Fareed, J[Abstract Not Available]Öğe Successful use of recombinant hirudin and its monitoring by ecarin clotting time in patients with heparin-induced thrombocytopenia undergoing off-pump coronary artery revascularization(Blackwell Futura Publishing, Inc, 2005) Iqbal, O; Tobu, M; Aziz, S; Gerdisch, M; Da Valle, M; Demir, M; Hoppensteadt, DARefludan (lepirudin-rDNA for injection) is the first direct thrombin inhibitor approved by the United States FDA for anticoagulation to patients with heparin-induced thrombocytopenia (HIT). It was monitored by ecarin clotting time (ECT) assay in patients with HIT. Case histories and clotting parameters for three patients undergoing off-pump coronary artery revascularization procedure are discussed. The first patient received r-hirudin at a dose of 0.2 mg/kg intravenous (IV) bolus followed by 0.15 mg/kg/hour infusion. The second patient received 0.4 mg/kg IV bolus followed by infusion of 0.15 mg/kg/hour infusion. The third patient with renal failure received 0.2 mg/kg IV bolus followed by an infusion of 0.02 mg/kg/hour. Blood samples were drawn at baseline, 5 minutes post bolus and every 15 minutes during the coronary artery revascularization procedure. ECT was performed immediately on the citrated whole blood samples using the ECT cards in conjunction with the point-of-care, the thrombolytic assessment system (TAS) Analyzer (Pharmanetics, Raleigh, NC). The plasma samples were then analyzed for APTT and liquid ECT assay performed on a kinetic centrifugal analyzer (ACL 300 Plus). The ECT by cards was ideally maintained above 600 seconds during the surgical procedure. Additional boluses of Refludan were given as and when necessary (ECT < 600 sec) in order to maintain adequate anticoagulation. The calculated circulating concentrations of Refludan, following a bolus adminstration, based on the ECT cards, liquid ECT and APTT were 3.20 +/- 1.3, 3.51 +/- 1.35 and 2.02 +/- 1.19 mug/mL, respectively.Öğe Upregulation of monocyte chemotactic protein-1 and CD40 ligand in cancer and its modulation by a LMWH enoxaparin: Observations from the Oncenox study.(Amer Soc Hematology, 2003) Fareed, J; Hoppensteadt, D; Iqbal, O; Tobu, M; Demir, A; Cort, S; Deitcher, SR[Abstract Not Available]Öğe Upregulation of monocyte chemotactic protein-1 and CD40 ligand in cancer patients and their modulation by subcutaneous enoxaparin-results from the ONCENOX study(Amer Soc Clinical Oncology, 2004) Iqbal, O; Tobu, M; Demir, MA; Hoppensteadt, D; Fareed, J; Cort, S; Deitcher, S[Abstract Not Available]
