Determine a baseline aPTT ratio before starting REFLUDAN; DO NOT START if ratio is >2.5
	Target range for aPTT ratio is 1.5 to 2.5 throughout therapy
	If baseline aPTT ratio is <2.5, administer REFLUDAN bolus and start infusion
	Determine aPTT ratio 4 hours after starting REFLUDAN infusion and at least daily thereafter
	For patients with serious liver injury or an increased risk of bleeding, more frequent aPTT monitoring is highly recommended
	Monitoring the aPTT and creatinine clearance more frequently may prevent a relative overdose in patients at risk of renal impairment during the course of REFLUDAN therapy

	If aPTT ratio is out of target range, confirm at once unless clinical need requires immediate reaction
	For confirmed aPTT ratio >2.5, STOP INFUSION for 2 hours, restart at 50% reduction in infusion rate, redetermine aPTT ratio 4 hours after restart
	If confirmed aPTT ratio is <1.5, increase infusion rate in steps of 20%, redetermine aPTT ratio 4 hours after each dosage change
	In general, an infusion rate of 0.21 mg/kg/h should not be exceeded without checking for coagulation abnormalities, which might be preventive of an appropriate aPTT response

No specific antidote for REFLUDAN is available. If life-threatening bleeding occurs and excessive plasma levels of lepirudin are suspected, the following steps should be followed:

	Immediately STOP REFLUDAN administration
	Determine aPTT and other coagulation levels as appropriate
	Determine hemoglobin and prepare for blood transfusion
	Follow the current guidelines for treating patients with shock

	Individual clinical case reports and in vitro data suggest that either hemofiltration or hemodialysis may be useful in an overdosage situation
	In studies with pigs, the application of von Willebrand Factor markedly reduced bleeding time. The clinical significance of this data is unknown