Heparin and Low-Molecular-Weight Heparin Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety

The text consists of two sections, one for those studying or practicing diagnostic radiology, nuclear medicine and radiation oncology; the other for those engaged in the study or clinical practice of radiation oncology--a new chapter, on radiologic terrorism, is specifically for those in the radiation sciences who would manage exposed individuals in the event of a terrorist event. The 17 chapters in Section I represent a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA. The 11 chapters in Section II address more in-depth topics in radiation oncology, such as cancer biology, retreatment after radiotherapy, chemotherapeutic agents and hyperthermia.

Radiobiology for the Radiologist

Heparin and Low-Molecular-Weight Heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

A tumor-derived growth factor that stimulates the proliferation of capillary endothelial cells has a very strong affinity for heparin. This heparin affinity makes it possible to purify the growth factor to a single-band preparation in a rapid two-step procedure. The purified growth factor is a cationic polypeptide, has a molecular weight of about 18,000, and stimulates capillary endothelial cell proliferation at a concentration of about 1 nanogram per milliliter.

https://science.sciencemag.org/content/sci/223/4642/1296.full.pdf

Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor

https://journal.chestnet.org/article/S0012-3692(12)60118-4/pdf

Parenteral Anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

The observation of heparin on endothelium after injection.

Vascular sequestration of heparin

Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites.

Evidence from endothelium of gastric absorption of heparin and of dextran sulfates 8000.

Plasma levels of the antithrombotic drug heparin, as estimated by coagulation tests, are a poor indicator of antithrombotic effectiveness. The interaction of heparin with endothelium is a poorly studied but important factor in the clinical activity of heparin. This study describes the interaction of heparin with endothelium, following intragastric administration. The concentrations of heparin in endothelium and plasma were determined by gel electrophoresis following administration of heparin to rats by various routes. Heparin concentrations in endothelium versus plasma were approximately 100 times greater following intravenous or ex vivo administration and more than 1000 times greater when administered by intrapulmonary, subcutaneous, intraperitoneal and intragastric routes indicating that the route of administration affects the distribution of the drug. At 2.4 and 6 min after intravenous administration, 88 and 51% respectively of the administered dose was found associated with endothelium. Heparin was rapidly absorbed following intragastric administration and could be detected associated with endothelium at 2.4 min. At 6 min less than 1% of the administered dose was found in plasma, and 45% was associated with endothelium. These results show that endothelium is the main site of heparin distribution. Heparins could also be detected in cellular and pericellular fractions of cultured porcine aortic endothelial cells when 125l-heparin was added to medium. Bound radioactivity was released to medium from both cellular and pericellular fractions suggesting that heparin taken up by endothelium can be released. Intragastric administration of heparin and dextran sulphates significantly prevented thrombus formation in a rat model of thrombosis without significant changes in activated partial thromboplastin times. Administration of heparin by oral or intrapulmonary routes can deliver large amounts to the vasculature for therapeutic effectiveness without incurring high concentrations in plasma which may lead to bleeding.

Linda M. Hiebert

Papers

The observation of heparin on endothelium after injection.

Vascular sequestration of heparin

Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites.

Evidence from endothelium of gastric absorption of heparin and of dextran sulfates 8000.

The heparin target organ--the endothelium. Studies in a rat model.