Table I.

Dosing guidelines followed in the USA and EU VWF/FVIII concentrate studies.

	USA study		EU study
PK infusion	60 IU VWF:RCo/kg		80 IU VWF:RCo/kg
Loading dose	Before amendment	After amendment
Target	1.5 × full dosea	Oral and minor surgery:	VWF:RCo >100%
	VWF:RCo ≥100%	VWF:RCo 50%–60%	FVIII:C >80%
	FVIII:C ≥100%	FVIII:C >40%
		Major surgery:
		VWF:RCo 80%–100%
		FVIII:C 80%–100%
Maintenance dose	Before amendment	After amendment	All: VWF:RCo >50% for ≥6 daysb
Target trough levels	VWF:RCo ≥50%	Oral and minor surgery:	Type 1, minor surgery:
	FVIII:C ≥80% (>50% after day 3)	After day 3: FVIII:C >30%	FVIII:C >50% for ≥4 days
		Major surgery:	Types 2 and 3, minor surgery:
		VWF:RCo and FVIII:C >50% (>30% after day 3)	FVIII:C >50% for ≥7 days
			All major surgery:
			FVIII:C 80%–100% for 7–14 days
Minimum duration	Oral surgery:	Oral surgery:	At least one repeat dose in 24 hours
	At least one dose post-surgery	At least one dose post-surgery
	Minor surgery:	Minor surgery:
	At least 48 hours post-surgery	At least 48 hours post-surgery
	Major surgery:	Major surgery:
	Anticipated for at least 72 hours	Anticipated for at least 72 hours

Legend

^aFull dose: PK-derived dose that would achieve a VWF:RCo level of 100%; in initial protocol, the loading dose was taken as 1.5 times the full dose to compensate for possible extra consumption during surgery.

^bExcluding oral surgery.

FVIII: factor VIII; PK: pharmacokinetic; RCo: ristocetin cofactor; VWF: von Willebrand factor; FVIII:C: coagulation factor VIII activity.