Here, the bolus is about 60 units/kg (maximum 4,000 units) and the infusion is 1.1.4 Monitoring: The risk of heparin-associated bleeding increases with heparin dose55,56 and with concomitant administration of brinolytic agents57-60 or glycoprotein IIb/IIIa inhibitors.61,62 The risk of bleeding is also increased by recent surgery, trauma, invasive procedures, or concomitant hemo- static defects.63 In hospitalized patients, increasing number of comorbidities, age . 60 y, suprathera- peutic clotting times, and worsening hepatic dysfunc- tion increase the risk of anticoagulant-associated Investigators have reported a relationship between the dose of heparin administered and both its ef - cacy33,47,65 and safety.61,62 Because the anticoagulant response to heparin varies among patients, it is stan- dard practice to monitor heparin and to adjust the dose based on the results of coagulation tests. The evidence for adjusting the dose of heparin to main- tain a therapeutic range is weak and is based on a post hoc subgroup analysis of a descriptive study.66 In contrast, the evidence for maintaining the interna- tional normalized ratio (INR) within a therapeutic range in patients who are treated with vitamin K antagonists is strong because it is based on consistent results of randomized trials and case control studies. assigned to receive identical doses of heparin (an IV bolus of 5,000 units and 30,000 units per day), but one group received 15,000 units of heparin every 12 h by subcutaneous injection and the other 30,000 units of heparin per day by continuous IV infusion. Patients assigned to IV heparin had a signi cantly lower rate of recurrence than those given subcutaneous heparin, presumably as a result of reduced availability of the subcutaneously admin- istered heparin. 