heparitin-sulfate and Cardiovascular-Diseases

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome associated with heparin exposure, a falling platelet count and a high risk of thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use of heparin in this population. Should HIT be suspected, heparin must be avoided in most situations, and anticoagulation with an alternative anticoagulant should be instituted. Preferred agents include the direct thrombin inhibitors argatroban and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors) can be used in some situations. The indirect thrombin inhibitors, danaparoid and fondaparinux, can also be considered at times. These agents and their use in cardiac patients, including patients with acute coronary syndrome, percutaneous coronary interventions, acute ST elevation myocardial infarction or cardiac surgery, will be reviewed.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Drug Administration Schedule; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

Topics: Anticoagulants; Arginine; Cardiac Surgical Procedures; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Factor 4; Polysaccharides; Recombinant Proteins; Sensitivity and Specificity; Sulfonamides; Thrombocytopenia; Thrombosis

Heparin-induced thrombocytopenia/thrombosis is an immunologic reaction to unfractionated heparin characterized by thrombocytopenia, platelet activation and thrombosis. A high index of suspicion is required for timely diagnosis and treatment. Treatment is complex and outcome maybe less then satisfactory.

Topics: Ancrod; Antibodies; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Practice Guidelines as Topic; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Sulfonamides; Thrombin

Heparin-induced thrombocytopenia (HIT) is caused by heparin-dependent, platelet-activating IgG antibodies that increase thrombin generation in vivo, producing a prothrombotic phenotype. In addition to platelet activation, there is in vitro evidence that activation of endothelium and monocytes occurs, perhaps directly by HIT antibodies, but more likely through activated platelet (or microparticle)-endothelial-leukocyte interactions. Patients with cardiac disease receiving heparin present important diagnostic and therapeutic issues when unexpected thrombocytopenia arises. Concomitant vascular disease burden and intravascular catheter use further increase risk of HIT-associated arterial thrombosis in this patient population. Whether arterial thrombosis simply reflects the "hypercoagulability state" of HIT interacting with diseased or injured arteries, or whether arterial "white clots" reflect additional prothrombotic effects of HIT via endothelial and monocyte activation, remains uncertain. Patients with HIT can also develop deep-vein thrombosis, which can progress to limb loss if coumarin (warfarin) leads to severe protein C depletion (coumarin-induced venous limb gangrene). Therapy for patients strongly suspected to have HIT should focus on inhibiting thrombin (or its generation) pharmacologically. Two direct thrombin inhibitors (lepirudin, argatroban) are approved for treating HIT. When using these agents, coumarin anticoagulation should be delayed pending substantial resolution of thrombocytopenia, before cautiously introducing overlapping coumarin therapy.

Topics: Antibodies; Anticoagulants; Cardiovascular Diseases; Coumarins; Heparin; Heparitin Sulfate; Humans; Immunoglobulin G; Models, Biological; Monocytes; Phenotype; Platelet Activation; Platelet Factor 4; Thrombin; Thrombocytopenia; Thrombosis

In summary, the decreased concentration of heparan sulphate within the extracellular matrix of patients with insulin-dependent diabetes mellitus is caused by a combination of genetic factors and poor metabolic control. Decreased concentrations of heparan sulphate are seen in patients with diabetes mellitus and proteinuria and this might be the explanation for the proteinuria as well as the expansion of the mesangium and the intimal dysfunction, including increased permeability of the vessel wall to macromolecules, which is present in such patients. Thus, the effective remodelling of extracellular matrix might explain coincidence of proteinuria, decline in renal function and premature atherosclerosis in patients with diabetes mellitus.

Topics: Albuminuria; Animals; Biomarkers; Cardiovascular Diseases; Diabetic Nephropathies; Heparitin Sulfate; Humans; Models, Biological; Risk Factors

Silicon plays a physiologically essential but mechanistically obscure role in promoting the synthesis of mucopolysaccharides and collagen. In light of reports that increased silicon ingestion impedes cholesterol-induced atherogenesis in rabbits and may be associated epidemiologically with reduced cardiovascular risk, it is reasonable to speculate that supplemental silicon may stimulate endothelial production of heparan sulfate proteoglycans that inhibit intimal hyperplasia.

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; Cholesterol, Dietary; Diet, Atherogenic; Endothelium, Vascular; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Models, Cardiovascular; Proteoglycans; Rabbits; Risk Factors; Silicon