Pharmacodynamics, Clinical Indications, and Adverse Effects of Heparin

Abstract

Heparins are a heterogenous group of naturally occurring glycosaminoglycans characterized by anticoagulant activity and a wide range of molecular weights (low molecular weight or fractionated heparins evolving within the past two decades). Cofactors for endogenous inhibitors of coagulation (antithrombin III and heparin cofactor II), heparin administration results in a hypocoagulable state. Various platelet activities, including inhibition of activity induced by platelet-derived growth factors on vascular smooth muscle, also have been noted. Divorced of anticoagulant nature, novel applications may include a role in atherosclerosis prevention, acceleration of collateral coronary as well as peripheral circulation (i.e., angiogenesis), and continued (chronic) post-myocardial infarction therapy. Established indications include treatment of various thrombotic diseases, unstable angina, and thrombosis chemoprophylaxis in medical/surgical patients. The antithrombotic potential of the heparins is used also in thrombosis management related to extracorporeal circulatory assistance or dialysis devices. Heparin's therapeutic potential in the postphlebitic syndrome as well as in acute treatment of myocardial infarction (primarily and adjunctively with various thrombolytic agents) continues to undergo evaluation; however, early data review shows favorable trends for its inclusion in situations that favor thrombus generation (e.g., anterior myocardial infarction). Although associated with thrombocytopenia or hypertransaminasemia, the heparins are relatively well tolerated. In a small subset of patients, a severe thrombocytopenia may ensue, which generally resolves on medication withdrawal. As this class of glycosaminoglycans becomes better characterized, new indications may emerge for both native and the newer fractionated heparins.

Suppression by intradermal administration of heparin of eosinophil accumulation but not oedema formation in inflammatory reactions in guinea‐pig skin

“…With the use of this drug, it has been possible to perform cardiac and orthopaedic surgeries effectively, to anticoagulate properly high risk patients and, more recently, it is being used in the prevention of thrombotic complications following surgery, long term hospitalization and cancer (Hirsh, 1991;Freedman, 1992). Heparin has also received some attention previously as an anti-inflammatory drug but the results of .different trials are conflicting (Boyle et al, 1964;Fine et al, 1968).…”

“…Heparin is a linear anionic polyelectrolyte drug obtained commercially from beef lung or porcine intestinal mucosa and used mainly in the prevention and treatment of thrombotic disorders (Jaques, 1980;Hirsh, 1991;Freedman, 1992). Anti-inflammatory actions of heparin have also been described.…”

Heparin Inhibits Phosphorylation and Autonomous Activity of Ca2+/Calmodulin-Dependent Protein Kinase II in Vascular Smooth Muscle Cells

“…Hyperplasia of vascular smooth muscle cells (VSMC) is the hallmark of early atherogenesis and is considered the major cause of the high failure rate of vascular surgical procedures such as angioplasty, coronary artery bypass grafts, and heart transplants. 1 The severity and prevalence of the problems associated with VSMC hyperplasia have provided the impetus to develop and characterize inhibitors of VSMC proliferation.…”

Highly Sensitive Surface-Enhanced Raman Scattering Sensing of Heparin Based on Antiaggregation of Functionalized Silver Nanoparticles

“…2−5 On the contrary, the overdose of heparin often induces hemorrhage, thrombocytopenia, or other bleeding complication. 6,7 So, the United States, European Union, and China have upgraded inspection standards of heparin after the "heparin incident" in 2008. 8 The therapeutic dosing level of heparin is 2−8 U/mL (17−67 μM) during cardiovascular surgery and 0.2−1.2 U/mL (1.7−10 μM) for postoperative and long-term care.…”