heparitin-sulfate and Coronary-Disease

To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed.. A search of the National Library of Medicine (1992-June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles.. Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included.. HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.

Topics: Animals; Anticoagulants; Arginine; Chondroitin Sulfates; Clinical Trials as Topic; Coronary Disease; Dermatan Sulfate; Drug Combinations; Female; Heparin; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Pipecolic Acids; Pregnancy; Rabbits; Recombinant Proteins; Sulfonamides; Thrombocytopenia

Topics: Aging; Animals; Arteriosclerosis; Ascorbic Acid; Chondroitin; Connective Tissue; Coronary Disease; Diet, Atherogenic; Glycoproteins; Glycosaminoglycans; Heparin; Heparitin Sulfate; Hexosamines; Hexoses; Histamine; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Lipid Metabolism; Lipoproteins, LDL; Mucoproteins; Neuraminic Acids; Rabbits; Rats

The incidence of heparin-induced thrombocytopenia is increasing, and the thrombin inhibitor danaparoid could be a useful alternative. The objective of the present study was to compare danaparoid and heparin in patients undergoing off-pump coronary artery bypass grafting.. In a prospective, randomized, double-blind clinical trial comparing heparin (bolus of 1 mg/kg) with danaparoid (bolus of 40 U/kg), 71 patients underwent off-pump coronary artery bypass grafting with one of the study drugs. The amount of blood lost, the number of homologous blood products transfused, the troponin T levels, and the amount of anti-Xa activity were monitored.. Thirty-four patients underwent 2.6 +/- 0.7 bypasses with danaparoid, and 37 patients underwent 2.5 +/- 0.9 grafts with heparin (P =.8). Postoperative blood losses averaged 1394 +/- 1033 mL in patients receiving danaparoid and 1130 +/- 868 mL in patients receiving heparin (P =.2). The number of homologous blood products transfused averaged 3.6 +/- 7 units in patients receiving danaparoid and 1.9 +/- 4.4 units in patients receiving heparin (P =.2). The number of patients requiring homologous blood transfusion was higher in patients receiving danaparoid (18/34 [53%]) than in patients receiving heparin (10/37 [27%], P =.03). Serum anti-Xa activity averaged 1.6 +/- 0.6 U/mL in patients receiving danaparoid and 1.9 +/- 0.8 U/mL in patients receiving heparin 30 minutes after injection of the drugs (P =.1) and 0.3 +/- 0.1 and 0.04 +/- 0.08 U/mL, respectively, 12 hours after coronary artery bypass grafting (P =.001). Troponin serum levels were similar 48 hours after coronary artery bypass grafting (0.5 +/- 0.6 and 0.4 +/- 0.6 microg/L, respectively).. Although off-pump coronary artery bypass grafting with danaparoid versus heparin increases the number of patients exposed to homologous blood transfusion (relative risk, 2; 95% confidence limits, 1-4), off-pump coronary artery bypass grafting with danaparoid is a valuable alternative to heparin in patients with thrombocytopenia requiring surgical intervention.

Topics: Aged; Analysis of Variance; Anticoagulants; Blood Loss, Surgical; Blood Transfusion; Chondroitin Sulfates; Coronary Artery Bypass; Coronary Disease; Dermatan Sulfate; Double-Blind Method; Drug Combinations; Drug Monitoring; Factor Xa Inhibitors; Female; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Severity of Illness Index; Thrombocytopenia; Troponin T

We examined the vascular expression levels of extracellular superoxide dismutase (EC-SOD), a major antioxidant enzyme in the cardiovascular system, in patients with acute coronary syndromes.. Twenty-one consecutive patients with acute myocardial infarction (AMI), 14 patients with unstable angina, 11 patients with stable angina, and 20 control subjects were studied. The levels of vascular EC-SOD expression were assessed by the difference in plasma EC-SOD concentrations before and after intravenous heparan injection. In the patients with AMI, vascular EC-SOD expression (ng/mL) was significantly higher on day 1 after the onset of AMI (148+/-10) as compared with the control subjects (116+/-6, P<0.05). The vascular EC-SOD expression returned to the normal range on day 7 (104+/-8), and that level persisted thereafter. The vascular EC-SOD expression was also significantly higher in the patients with unstable angina (160+/-13) than in those with stable angina (122+/-10) or in the controls (116+/-6) (P<0.05 each). Moreover, in the patients with AMI, higher levels of vascular EC-SOD expression on day 1 were significantly associated with smaller myocardial infarct size (P<0.05).. This is the first clinical demonstration showing that vascular EC-SOD may be upregulated in acute coronary syndromes in humans in vivo. EC-SOD may play an important protective role against increased oxidative stress during acute ischemic coronary events.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Aging; Coronary Disease; Enzyme Induction; Female; Heparitin Sulfate; Humans; Hypercholesterolemia; Male; Middle Aged; Muscle, Smooth, Vascular; Myocardial Infarction; Oxidative Stress; Oxygen Inhalation Therapy; Prospective Studies; Superoxide Dismutase

Perlecan is one of the three major classes of heparan sulfate proteoglycans (HSPGs) within the cardiovascular system; it interacts with lipid metabolism by binding to lipoprotein lipase (LpL) and apolipoprotein B (apo B) and may be related to vascular disease. We explored interactions between an HSPG2 polymorphism (BamHI marker), and apo B and coronary artery disease (CAD) in patients undergoing coronary angiography. The frequencies of the HSPG2 BamHI +/+, +/-, and -/- genotypes were 4.7, 31.7 and 63.6%, respectively, with a '+' allele frequency of 20.6%. The genotype distribution was in Hardy-Weinberg equilibrium (chi(2)=0.669, P0.05). The +/+homozygotes had the lowest apo B levels (0.74+/-0.06 g/l, n=36) compared to +/- (0.89+/-0.03 g/l, n=241) and -/- (0.93+/-0.02 g/l, n=480) genotypes. Although plasma apo B concentration was the strongest lipid risk factor for significant CAD, the HSPG2 genotypes were not independently associated with the presence of CAD (P=0.640 in males; P=0.224 in females), with significant CAD (P=0.764; P=0.110) or with the number of significantly stenosed coronary arteries (P=0.945; P=0. 335). In Australian Caucasians undergoing coronary angiography the HSPG2 BamHI polymorphism is associated with lower circulating apo B but not with the occurrence or severity of CAD. This may be due to HSPG2-mediated alterations in the HSPG2-apo B-LpL system and requires further exploration.

Topics: Australia; Coronary Disease; Female; Genotype; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Lipids; Male; Middle Aged; Polymorphism, Genetic; Protein Isoforms; Proteoglycans

Topics: Aged; Angina, Unstable; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Coronary Disease; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Male; Reoperation; Thrombocytopenia; Thrombosis; Treatment Failure

Topics: Ancrod; Anticoagulants; Aprotinin; Cardiopulmonary Bypass; Chondroitin Sulfates; Coronary Disease; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Serine Proteinase Inhibitors; Thrombocytopenia; Thrombosis; Treatment Failure

Topics: Adult; Aged; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Coronary Artery Bypass; Coronary Disease; Dermatan Sulfate; Drug Combinations; Female; Heart-Lung Transplantation; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Thrombocytopenia

Orgaran, a heparinoid, has been used successfully in patients with heparin-induced thrombocytopenia. We report three cases in which Orgaran was combined with the glycoprotein IIbIIa receptor antagonist Reopro during coronary angioplasty. Orgaran was given as a single intravenous bolus of 1500 anti-factor Xa units. No ischemic or hemorrhagic complications occurred during or following the procedure.

Topics: Abciximab; Adult; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Chondroitin Sulfates; Coronary Disease; Dermatan Sulfate; Drug Therapy, Combination; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Platelet Aggregation Inhibitors

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Chondroitin Sulfates; Coronary Disease; Dermatan Sulfate; Heparin; Heparinoids; Heparitin Sulfate; Humans; Immunoglobulin Fab Fragments

Two types of heparin-associated thrombopenia can be distinguished. Patients with the type II condition present a particularly difficult management problem when they require full anticoagulation. There is no consensus about the proper anticoagulation management for type II patients who have to undergo cardiopulmonary bypass. The case is reported of a type II heparin-associated thrombopenia patient who underwent successful aortocoronary saphenous vein grafting. Sodium-danaparoid was used for anticoagulation. The anti-factor Xa level was kept below the value reported in the literature for patients undergoing cardiopulmonary bypass. No fibrin formation was observed during the time of cardiopulmonary bypass, nor was any severe postoperative haemorrhage seen, as is frequently described in the literature.

Topics: Aged; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Coronary Artery Bypass; Coronary Disease; Dermatan Sulfate; Drug Combinations; Heparin; Heparinoids; Heparitin Sulfate; Humans; Intraoperative Care; Male; Postoperative Hemorrhage; Saphenous Vein; Thrombocytopenia

Heparin is the standard anticoagulant for patients undergoing cardiopulmonary bypass. There are some patients for whom heparin is unsuitable and ancrod (a defibrinogenating enzyme) has been used as an alternative. We present a patient with heparin-induced thrombocytopenia in whom treatment ancrod was ineffective. The addition of danaparoid sodium (a heparinoid) allowed safe cardiopulmonary bypass. We discuss the reasons for this and suggest that the combination of ancrod and danaparoid sodium is a logical one in such cases.

Topics: Ancrod; Anticoagulants; Aortic Valve Stenosis; Cardiopulmonary Bypass; Chondroitin Sulfates; Coronary Disease; Dermatan Sulfate; Drug Combinations; Drug Therapy, Combination; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Middle Aged; Thrombocytopenia

Heparin is considered necessary during percutaneous coronary interventions; however, heparin is contraindicated in patients with heparin-induced thrombocytopenia and/or heparin antibodies. We describe the successful use of the heparinoid Orgaran (danaparoid sodium) in addition to abciximab (ReoPro) in a patient with heparin antibodies who required rotational atherectomy.

Topics: Abciximab; Antibodies; Antibodies, Monoclonal; Anticoagulants; Atherectomy, Coronary; Blood Coagulation; Chondroitin Sulfates; Coronary Angiography; Coronary Disease; Dermatan Sulfate; Heparin; Heparinoids; Heparitin Sulfate; Humans; Immunoglobulin Fab Fragments; Intraoperative Period; Male; Middle Aged; Thrombocytopenia

Heparan sulfate proteoglycans produced by vascular endothelium may function physiologically to restrain the migration, multiplication, and phenotypic transition of vascular smooth-muscle cells, and to maintain an anticoagulant luminal surface by bonding and activating antithrombin III. Thus, ample production of heparan sulfate proteoglycans may act to prevent atherosclerosis and its thrombotic complications. The ability of exogenous heparin to stimulate synthesis of heparan sulfate proteoglycans by vascular endothelium may be largely responsible for the positive outcomes of most controlled evaluations of low-dose heparin as a long-term therapy for coronary disease. Glucosamine, a biosynthetic precursor of mucopolysaccharides, can substantially enhance mucopolysaccharide production when added to cultured fibroblasts or chondrocytes; the clinical utility of oral glucosamine in osteoarthritis may reflect increased synthesis of cartilage proteoglycans. It is reasonable to speculate that exogenous glucosamine will likewise enhance heparan sulfate proteoglycans production by vascular endothelial cells, and, when administered orally in regimens comparable to those effective in osteoarthritis, will thereby act to retard atherogenesis.

Topics: Animals; Arteriosclerosis; Cartilage; Cells, Cultured; Coronary Disease; Endothelium, Vascular; Fibroblasts; Glucosamine; Glycosaminoglycans; Heparan Sulfate Proteoglycans; Heparin; Heparitin Sulfate; Humans; Models, Cardiovascular; Proteoglycans

An 84-year-old patient with heparin-induced thrombocytopenia (HIT), global cardiac decompensation, and acute renal failure underwent a cardiosurgical intervention using an extracorporeal circuit. For systemic anticoagulation danaparoid (Orgaran) was applied as a heparin substitute preoperatively and maintained for systemic anticoagulation during ECC despite it being eliminated by the kidney. The postoperative recovery was prolonged due to bleeding complications. During cardiopulmonary bypass (216 min) the target level of anti-factor Xa was 1.5 UI/ml. This required continuous infusion and an occasional bolus of danaparoid. Coagulation in the extracorporeal circuit was observed twice at plasma levels below 1.4 IU/ml. There were no thromboembolic or neurologic events. We did not retransfuse blood from the extracorporeal circuit or the cardiotomy reservoir after bypass, but because elimination of danaparoid was impaired in this patient and there is no neutraliser available antifactor Xa postoperatively exceeded 0.6 IU/ml for 30 hours. Diffuse bleeding with tamponade resulted. Weaning the patient from the respirator was achieved 12 hours after the last re-exploration. From the 4th postoperative day 750 IU of danaparoid were administered twice daily subcutaneously for thrombosis prevention. On the 6th postoperative day discharge from the ICU was possible. We conclude that the application of danaparoid for cardiopulmonary bypass in patients suffering from acute renal failure may be complicated by hemorrhage.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Chondroitin Sulfates; Coronary Artery Bypass; Coronary Disease; Dermatan Sulfate; Drug Combinations; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Thrombocytopenia

Glycosaminoglycans (GAGs) were studied in normal and atherosclerotic coronary arteries of 15- to 60-year-old Finnish men who had died accidentally. The GAGs were fractionated and quantified with electrophoretic techniques. The contents of sulfated GAGs (micrograms/cm2 vessel surface area) increased continuously until 20 to 30% of the vessel surface area was covered with fibrous plaques, after which they started to decrease. The largest increases were seen in chondroitin sulfates A and C and dermatan sulfate, the former of which rose earlier with lesion development. In normal coronary arteries the contents of dermatan sulfate and chondroitin sulfates A and C increased significantly with age, but the rises were much smaller than those found in affected vessels. The age-related changes in the percentage composition of GAGs in normal coronaries were qualitatively similar to those found in affected coronaries during lesion development. The alterations in arterial GAGs, therefore, seem to be related to two processes, both of which involve increased formation of connective tissue components by arterial smooth muscle cells: the normal growth and maturation of the vessels with a slow development of diffuse intimal thickening, and atherogenesis, which greatly increases the contents of sulfated GAGs in affected arteries.

Topics: Adolescent; Adult; Aging; Chondroitin Sulfates; Coronary Disease; Coronary Vessels; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Middle Aged