Search PubMed⌕ Search

Biomedical subjects

J Fareed

Publications and source records attributed to J Fareed.

At least 37 records · Page 2Linked to original sources
PubMed2001

Ecarin clotting time is sensitive to heparinoids: comparison of two different techniques.

Ecarin 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 Pl-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 microg/ml. These techniques gave comparable results for all of the agents used (PI-88, r2 = 0.99; r-hirudin, r2 = 0.98; UFH, r2 = 0.98; dermatan sulfate, r2 = 0.95; aprosulate, r2 = 0.95; pentosan polysulfate, r2 = 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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Anticoagulant and antiprotease effects of a novel heparinlike compound from shrimp (Penaeus brasiliensis) and its neutralization by heparinase I.

Heparin 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, 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.

Animals↗
PubMed2001

Synthetic heparin pentasaccharide depolymerization by heparinase I: molecular and biological implications.

A synthetic pentasaccharide (SR90107/ ORG31540) representing the antithrombin III (ATIII) binding sequence in heparin is under clinical development for the prophylaxis and management of venous thromboembolism. This pentasaccharide exhibits potent anti-factor Xa (AXa) effects (>750 IU/mg) and does not exhibit any anti-factor IIa (AIIa) activity. Previous reports have suggested that synthetic heparin pentasaccharides are resistant to the digestive effects of heparinase I. To investigate the effect of heparinase I on the AXa activity of pentasaccharide SR90107/ORG31540, graded concentrations (1.25-100 microg/ml) were incubated with a fixed amount of heparinase I (0.1 U/ml). Heparinase I produced a strong neutralizing effect on this pentasaccharide, as measured by AXa activity. This observation led to further studies where high performance liquid chromatography (HPLC) analysis was employed to determine the potential breakdown products of the pentasaccharide. The experiment with the pentasaccharide included incubation (37 degrees C) at 1 mg/ml and exposure to graded concentrations of heparinase I (0.125-1 U/ml). After 30 min of incubation, the enzymatic activity was stopped by heat treatment and the mixture was analyzed using high performance size exclusion chromatography (HPSEC). Heparinase I concentration-dependent cleavage of the pentasaccharide was evident. The breakdown products exhibited a mass of 1,034 d and 743 d, respectively, suggesting the generation of a trisaccharide and a disaccharide moiety. The extinction of a disaccharide moiety in the UV region was high, indicating the presence of a double bond in this molecule. These data clearly suggest that pentasaccharide SR90107/ORG31540 is digestible by heparinase I into its two components. Furthermore, these data support the hypothesis that heparinase I can be used as a neutralizing agent for pentasaccharide overdose. Additionally, a highly methylated analog of the previously mentioned synthetic pentasaccharide. SanOrg34006, which has also been subjected to similar experiments, has shown complete resistance to the depolymerizing function of heparinase I; therefore, its use may be appropriate in chronic situations as a long-acting form of the pentasaccharide.

Antithrombin III↗
PubMed2001

Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa. anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding. Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of > or = 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by >60%, the hemoglobin dropped to >5 g/dL (n = 13). This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 28) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

Anticoagulants↗
PubMed2001

Anticoagulant and antiprotease profiles of a novel natural heparinomimetic mannopentaose phosphate sulfate (PI-88).

Heparinomimetic 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-II) 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), Hep-test (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, r2 = 0.94; TT, r2 = 0.84; APTT, r2 = 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.

Anticoagulants↗
PubMed2001

Global anticoagulant effects of a novel sulfated pentomanan oligosaccharide mixture.

PI-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 microg/mL). Whole blood activated clotting time (ACT) was measured using Hemochron instruments. PI-88 produced a strong anticoagulant effect at 100 microg/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 microg/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.

Anticoagulants↗
PubMed2001

Plasma markers of endothelial dysfunction in chronic obstructive pulmonary disease.

We studied some endothelial cell activity plasma markers, nitric oxide (NO), thrombomodulin (TM), selectins (sP-, sE-, sL-selectin: platelet-P, endothelium-E, leukocyte-L), and tissue factor pathway inhibitor (TFPI) in 14 patients with chronic obstructive pulmonary disease (COPD), matched with 20 normal controls, to evaluate their endothelial cell dysfunction. Both NO (patients: 23.42 +/- 1.67 microg/mL: controls: 40.0 +/- 3.38 microg/mL) and TM levels (patients: 5.46 +/- 1.32 ng/mL; controls: 12.9 +/- 0.51 ng/mL) were significantly decreased in COPD (p < 0.001). sP-selectin levels (patients: 79.42 +/- 18.20 ng/mL, controls: 37.5 +/- 2.84 mg/mL) were significantly higher (p < 0.02), whereas sL-selectin levels (patients: 584.9 +/- 78.98 ng/mL, controls: 1,054.02 +/- 61.28 ng/mL) were significantly decreased in patients with COPD (p < 0.001). In contrast, no differences were seen in sE-selectin. Patients with COPD showed a significantly higher (p < 0.001) TFPI antigen plasma level (mean 112.28 +/- 6 .45 ng/mL; controls 77.68 +/- 0.28 ng/mL) than controls. Our data support the concept of some form of endothelial cell dysfunction, and coagulation abnormalities are present in patients with COPD. However, because the endothelium seems to produce a defense mechanism, the potential usefulness of an antithrombotic therapy in these patients needs further investigation.

Aged↗
PubMed2001

Singlet oxygen inhibits agonist-induced P-selectin expression and formation of platelet aggregates.

Major mediators of activated polymorphonuclear leukocytes (PMN) are the oxidants HOCl and chloramine, which are a source for the nonradical photon-emitting oxidant singlet oxygen (1O2). We were interested in a possible platelet-modulating activity of 1O2. As a stable 1O2 source we chose the mild oxidant chloramine T (CT), which mimics the natural chloramine N-chloro-taurine. Freshly drawn native whole blood from donors (n = 5) was incubated at 0 to 3 mM CT for 1 minute at 37 degrees C. Then saline. 10 microM adenosine diphosphate (ADP), 5 microg/mL collagen, or 6.25 microM thrombin receptor activator peptide (TRAP) were added and the mixtures were allowed to incubate for 3 minutes at 37 degrees C. Aliquots of activated blood were fixed in 1% para-formaldehyde. After removal of the fixative, platelets were labeled with anti-CD61-FITC and anti-CD62P-PE antibodies and analyzed by flow cytometry. An oxidant concentration-dependent decrease in the expression of P-selectin appeared (at 3 mM CT to 39, 23, and 20% of the 100% saline control level for ADP, collagen, and TRAP, respectively). There was also an oxidant concentration-dependent decrease in the formation of platelet aggregates (at 3 mM CT to 8, 12, and 13% of the 100% saline control level for ADP, collagen, and TRAP, respectively; the 50% effective dose was 1.0 to 1.5 mM chloramine). In ADP- and TRAP-stimulated platelets, an oxidant-mediated increase in platelet fragments appeared (at 3 mM CT: three- to fourfold of the initial value). The addition to the blood of 30 mM of the oxyradical scavenger mannitol in contrast to excess methionine did not antagonize these oxidative modulations of platelet activation. The results were confirmed using equimolar concentrations of NaOCI and N-chloro-taurine. This study shows that 1O2 inhibits platelets, decreasing the expression of CD62P and the formation of platelet aggregates. Activated PMN might modulate hemostasis, shifting it into an antithrombotic state. The physiologic signal action and the direct anticoagulant action of 1O2 (released by chloramines such as vancomycin) might be a new principle for pharmacologic intervention in atherothrombosis.

Adenosine Diphosphate↗
PubMed2001

Tissue factor pathway inhibitor release induced by defibrotide and heparins.

We evaluated the release of tissue factor pathway inhibitor (TFPI) induced by defibrotide (DF), a single-stranded, negatively charged polydeoxyribonucleotide extracted from mammalian organ. Ten normal volunteers were injected with an intravenous bolus of 400 mg DF and 2,000 IU unfractionated heparin (UFH). In addition, three volunteers were also injected with an intravenous bolus of 2,000 anti-Xa U of two low-molecular-weight heparins (LMWHs), enoxaparin and nadroparin. UFH caused a 4-fold increase in plasma TFPI at 5 minutes, with a decrease that was parallel to the heparin level measured by the anti-Xa assay. However, at 80 minutes, although the plasma anti-Xa activity of UFH was almost undetectable, the level of TFPI remained 2-fold baseline. DF induced an increase of TFPI that was 2-fold higher than the baseline level, with a steady state achieved between 5 and 20 minutes. At 40 minutes, the TFPI levels returned to basal level. This pattern was not coincident with the clearance of DF and at 40 minutes, the concentration of DF was still one third of the levels at 5 minutes (25.4 +/- 4.04 microg/mL). Both of the LMWHs induced a similar TFPI peak level at 5 minutes (1.5-fold increase) and at 40 minutes the TFPI levels returned to the initial levels. At 5 minutes, both LMWHs showed a higher plasma anti-Xa activity than UFH, which was detectable even at 80 minutes. The current study demonstrated that one of the mechanisms of the antithrombotic activity of DF is mediated via TFPI. Furthermore, the release of TFPI by heparin is mediated by non-antithrombin III binding fragments. Thus, polyanionic electrolytes are capable of releasing TFPI irrespective of their antithrombin III effect.

Adult↗
PubMed2001

Day-night variations in blood levels of nitric oxide, T-TFPI, and E-selectin.

Circadian (8/24 hours) variations in serum nitric oxide (NO), total tissue factor pathway inhibitor (T-TFPI). and E-selectin levels were studied in healthy adults and in subjects with type II diabetes. We postulated a possibility a functional relationship between them because vascular endothelium is the primary site of their synthesis and functions. NO is released by the action of eNO synthase isoform and modulates physiologic responses (e.g., vascular dilation, relaxation, increasing blood flow, inhibition of platelet and white blood cell adhesion); T-TFPI, a coagulation inhibitor, is also released from endothelial cells, and is bound to plasma lipoproteins and to glycosaminoglycans; E-selectin is expressed on endothelial cells after activation by inflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha) and elevated levels have been reported in a variety of pathologic conditions, including diabetes. We found that obese diabetic subjects had greater mean concentrations of NO and E-selectin than healthy men, 39.25 versus 12.71 microM and 81.51 versus 26.03 ng/mL, respectively. The T-TFPI levels were essentially similar in both groups of men, 47.10 versus 48.76 ng/mL. We observed that the time of peak concentrations of T-TFPI and E-selectin was similar to the timing of NO trough levels, suggesting a possible functional relationship. It may be hypothesized, therefore, that the higher concentrations of NO, unbalanced by increases in T-TFPI and E-selectin, may result in increased vascular wall uptake of lipoproteins in diabetic subjects, who are at greater risk than healthy men for developing diffuse atherosclerosis.

Aged↗
PubMed2001

Plasma markers of endothelial dysfunction in pulmonary hypertension.

STUDY OBJECTIVES: To evaluate and to correlate endothelial cell dysfunction, using recently available plasma markers, with the magnitude of pulmonary artery pressure in patients with severe pulmonary hypertension (PH). DESIGN: Selected plasma markers of endothelial cell dysfunction were studied: nitric oxide (NO), thrombomodulin, tissue factor pathway inhibitor, and soluble endothelium, leukocyte, and platelet selectins (sE-, sL-, sP-selectins, respectively). SETTING: Padova University Hospital and Department of Pathology and Pharmacology, Loyola University of Chicago, Chicago, IL. PATIENTS: Fifteen patients had severe PH (four men and 11 women; mean age, 49.7 +/- 2.9 years: seven patients had primary pulmonary hypertension [PPH] and eight patients had secondary pulmonary hypertension [SPH]), and 20 patients were healthy control subjects. MEASUREMENT AND RESULTS: In patients with PH, sP- and sE-selectins were elevated, whereas sL-selectin was lower in comparison with the selectin levels in control subjects. However, the differences between patients with PH and control subjects were significant only for sL-selectin (p < 0.0001) and sE-selectin (p < 0.03). The NO level was significantly lower in patients with PH compared with the NO level in control subjects (p < 0.01). No difference in tissue factor pathway inhibitor level was noted between control subjects and patients with PH. Only a weak correlation was found between thrombomodulin plasma levels and magnitude of systolic pulmonary artery pressure (r = -0.528, p < 0.05). CONCLUSIONS: Our data are in keeping with the evidence for significant endothelial cell dysfunction in patients with PH and the need for chronic anticoagulation believed to increase survival in these patients. In addition, these data seem to suggest a need for newer agents that are able to increase the antithrombotic endothelial function.

Endothelium, Vascular↗
PubMed2001

Tissue factor pathway inhibitor: an update of potential implications in the treatment of cardiovascular disorders.

Tissue factor (TF) plays a crucial role in the pathogenesis of thrombotic, vascular and inflammatory disorders. Thus, the inhibition of this membrane protein provides a unique therapeutic approach for prophylaxis and/or treatment of various diseases. Tissue factor pathway inhibitor (TFPI), the only endogenous inhibitor of the TF/Factor VIIa (FVIIa) complex, has recently been characterised biochemically and pharmacologically. Studies in patients demonstrated that both TF and TFPI may be indicators for the course and the outcome of cardiovascular and other diseases. Based on experimental and clinical data, TFPI might become an important drug for several clinical indications. TFPI is expected to inhibit the development of post-injury intimal hyperplasia and thrombotic occlusion in atherosclerotic vessels as well as to be effective in acute coronary syndromes, such as unstable angina and myocardial infarction. Of special interest is the inhibition of TF-mediated processes in sepsis and disseminated intravascular coagulation (DIC), which are associated with the activation of various inflammatory pathways as well as of the coagulation system. A Phase II trial of the efficacy of TFPI in patients with severe sepsis showed a mortality reduction in TFPI- compared to placebo-treated patients and an improvement of organ dysfunctions. TFPI can be administered exogenously in high doses to suppress TF-mediated effects, alternatively high amounts of TFPI can be released from intravascular stores by other drugs, such as heparin and low molecular weight heparins (LMWH). Using this method high concentrations of the inhibitor are provided at sites of tissue damage and ongoing thrombosis. At present, clinical studies with TFPI are rather limited so that the clinical potential of the drug cannot be assessed properly. However, TFPI and its variants are expected to undergo further development and to find indications in various clinical states.

Animals↗
PubMed2001

Emerging anticoagulant and thrombolytic drugs.

Since its discovery, heparin has been used intensely as an anticoagulant for several medical and surgical indications. However, efforts are in progress to replace heparin because of its serious complications, such as intraoperative and postoperative bleeding, osteoporosis, alopecia, heparin resistance, heparin rebound, heparin-induced thrombocytopenia (HIT) and thrombosis syndrome (HITTS), and other disadvantages. Significant developments in the field of new anticoagulants have resulted in the evaluation and introduction of low molecular weight heparins (LMWHs) and heparinoids, hirudin, ancrod, synthetic peptides and peptidomimetics. However, despite significant progress in the development of these new anticoagulants, a better or an ideal anticoagulant for cardiovascular patients is not yet available and heparin still continues to amaze both basic scientists and the clinicians. To minimise the adverse effects of heparin, newer approaches to optimise its use in combination with the new anticoagulants may provide better clinical outcome. In our experience, the off-label use of argatroban at a dose of 300 microg/kg iv. bolus followed by 10 microg/kg/minute infusion in combination with aggrastat (a glycoprotein [GP] IIb/IIIa inhibitor) at a dose of 10 microg/kg iv. bolus followed by an infusion of 0.15 microg/kg/minute in patients with HIT undergoing percutaneous coronary interventions resulted in elevation of celite activated clotting time (ACT) to 300 seconds followed by a gradual decline and the ACT remained above 200 seconds even after 200 min of drug administration. A bewildering array of newer anticoagulants now exist, such as LMWHs and heparinoids, indirect or direct thrombin inhibitors, oral thrombin inhibitors, such as melagatran (AstraZeneca) and HC-977 (Mitsubishi Pharmaceuticals), Factor IXa inhibitors, indirect or direct Factor Xa inhibitors, Factor VIIa/tissue factor (TF) pathway inhibitor, newer antiplatelet agents, such as GPIIb/IIIa inhibitors, fibrin specific thrombolytic agent, such as tenecteplase and modulation of the endogenous fibrinolytic activity by thrombin activatable fibrinolytic inhibitor (TAFI), Factor XIIIa inhibitors and PAI-1 inhibitors. The quest for newer anticoagulant, antiplatelet and fibrinolytic agents will continue until ideal agents are found.

Journal Article↗
PubMed2001

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.

Abciximab↗
PubMed2001

Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with chronic liver disease.

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a 60 kappaD glycoprotein present in plasma that regulates fibrinolysis by limiting the amount of fibrin available for fibrinolysis by tissue plasminogen activator (t-PA). Chronic liver disease is well-known to be associated with a low-grade fibrinolytic syndrome that under the appropriate stimulus proceeds to an overt disseminated intravascular coagulopathy (DIC) with demonstrable bleeding. In the present study, TAFI activity was measured in the plasma of 74 patients with advanced liver disease, and the levels of TAFI were related to those of other important coagulation and fibrinolytic factors. TAFI levels were very low and essentially undetectable in the plasma of patients with advanced hepatocellular liver disease. No relationship with the degradation products of fibrin was evident.

Adult↗
PubMed2001

A randomized trial of the low-molecular-weight heparin certoparin to prevent restenosis following coronary angioplasty.

OBJECTIVES: The objectives of this study were to evaluate the effectiveness and safety of the low-molecular-weight heparin (LMWH) certoparin in preventing restenosis following balloon coronary angioplasty. BACKGROUND: Restenosis following coronary angioplasty continues to limit the long-term efficacy of this procedure. Animal studies have indicated a potential role for LMWH in reducing restenosis by limiting smooth muscle proliferation. METHODS: This study tested the effects of certoparin, self-administered for 3 months, in reducing restenosis following balloon coronary angioplasty. One hundred and eighteen patients with 158 lesions treated with angioplasty were enrolled in this randomized, placebo-controlled trial. One hundred and two patients completed the study. The endpoint was relative loss measured with quantitative coronary angiography. RESULTS: The relative loss for placebo was 0.19 +/- 0.23 compared to 0.14 +/- 0.21 for LMWH (p = NS). The minimum lumen diameter (MLD) was 1.47 +/- 0.66 for placebo and 1.40 +/- 0.57 for the LMWH (p = NS). There was a reduction (31% for LMWH; 49% for placebo PSDP) in the percent of patients having binary restenosis (MLD < 50% of reference diameter). At the end of the study 77% of the placebo patients and 76% of the LMWH group were asymptomatic (p = NS). There was a low rate of bleeding complications and these were minor. Bone density scans showed that there was no significant occurrence of osteoporosis with 3 months of LMWH. CONCLUSIONS: Administration of certoparin for 3 months is safe, but appears ineffective in reducing post-PTCA restenosis.

Adult↗