Management of Bleeds or Invasive Procedures with FVIII/VWF or VWF Concentrates

Recommendations on the management of acute bleeds or invasive procedures with FVIII/VWF or VWF concentrates

Product Type of bleed or surgery Loading dose IU VWF:RCo/kg BW Maintenance dose IU VWF:RCo/kg BW Therapeutic goal VWF and FVIII trough activity levels
Haemate*
FVIII/VWF 1:2
Minor/moderate 40-50 IU/kg 40-50 IU/kg 12-24 h until bleed controlled > 30-50 IU/dL
Major 60-80 IU/kg

40-50 IU/kg every 8-12 h for at least 3 days

Then 40-60 IU/kg daily for at least 7 days

> 50 IU/dL
then
> 30 IU/dL
Wilate*
FVIII/VWF 1:1
Minor/moderate 20-40 IU/kg 20-30 IU/kg 12-24 h until bleed controlled > 30-50 IU/dL
Major 40-60 IU/kg

40-60 IU/kg 12-24 h for at least 3 days

Then 20-40 IU/kg daily for at least 5-7 days

> 50 IU/dL
then
> 30 IU/dL
Wilfactin**
FVIII/VWF 0:1
Minor/moderate 40-50 IU/kg 40-50 IU/kg 12-24 h until bleed controlled > 30-50 IU/dL
Major 40-80 IU/kg

40-60 IU/kg 12-24 h for at least 3 days

Then 20-40 IU/kg daily for at least 7 days

> 50 IU/dl
then
> 30 IU/dL
Veyondi**
FVIII/VWF 0:1
Minor/moderate 40-50 IU/kg 40–50 IU/kg 12–24 h until bleed controlled > 30-50 IU/dL
Major 50-80 IU/kg

40-60 IU/kg 8-24h for 2-3 days

Then 20-40 IU/kg daily for at least 7 days

> 50 IU/dL
then
> 30 IU/dL

For levels with repeat dosing, adjust dose on VWF/FVIII activity levels.
* Continued treatment using a FVIII-containing VWF product may cause an excessive rise in FVIII activity, which may increase the risk of thromboembolic events.
In Wilate, each unit of VWF activity comes with more FVIII activity than in Haemate and there is need for fewer VWF units to get both VWF and FVIII targets into range.
** First dose should be started on the preoperative day or rFVIII should also be administered if patient FVIII < 40 IU/dL. A concentrate devoid of FVIII is suitable for patients having risk of thrombosis.

  • Minor/moderate bleeds: nose, mouth, mucocutaneous, muscle, soft tissue, heavy menstrual bleeds.

  • Major bleeds: severe or refractory epistaxis, CNS trauma, hemarthrosis, traumatic hemorrhage.

  • Dosage depends also on the VWD type and baseline VWF/FVIII activity levels: type 1 moderate or severe (VWF:Act typically <30 IU/dL), type 2 and type 3 VWD.

  • Preoperative target plasma VWF/FVIII activity levels >80-100 IU/dL in major surgery and >50 IU/dL in minor surgery.

  • Prophylactic maintenance treatment may be required up to 3-6 months in GI bleeds.

Recommendations on the management of acute bleeds and therapeutic targets

Management of specific bleeds Patient’s body weight (kg)*
Loading dose (IU/kg) < 20 20-40 40-60 60-80 80-95 95-115
Minor bleed (nose, mouth, mucocutaneous 30-50 500 500-2000 1000-3000 2000-4000 2500-4500 3000-5500
Muscle, soft tissue 30-50 500 500-2000 1000-3000 2000-4000 2500-4500 3000-5500
Menorrhagia 20-40 - 500-1000 1000-2000 2000-2500 2500-3000 2500-4000
GI-bleed 40-60 500 1000-2000 1500-3000 2500-3500 3500-5500 4000-6500
Major bleed (severe or refractory epistaxis, CNS trauma, hearmathrosis, traumatic hemorrhage) 40-60 1000 1500-3000 2500-4500 3500-6000 4500-7000 5000-8000

In addition to VWF/FVIII or VWF concentrated, the patient is given tranexamic acid.
* Dosage depends also on the VWD type and baseline VWF/FVIII activity levels.

  • Treatment is continued until the bleeding stops, for several days in major bleeds.

  • Prophylactic maintenance treatment may be required up to 3-6 months in GI bleeds.

Recommendations on the management of surgeries and other invasive procedures for patients with VWD

Surgery and other invasive procedures Patient’s body weight (kg)*

Loading dose (IU/kg)

<15

15-25

25-35

35-45

45-55

55-65

65-75

75-85

85-95

95-105

Major surgery

VWF:Act >50 IU/dL or higher

50-80

500-1000

500-2000

1000-2500

2000-3500

2000-4500

2500-5000

3000-6000

3500-6500

4000-7000

5000-8000

Maintenance dose every 12-24 h

20-40

500

500-1000

500-1500

1000-1500

1000-2000

1500-2500

1500-3000

2000-3500

2000-4000

2500-4000

Minor surgery

VWF:Act >30-50 IU/dL

30-50

500

500-1000

500-1500

1000-2000

1500-2500

1500-3000

2000-3500

2000-4000

2500-4500

3000-5000

Maintenance dose every 12-24 h

20-30

500

500

500-1000

1000-1500

1500

1500-2000

2000

2000-2500

2000-3000

2500-3000

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* Dosage depends also on the VWD type and baseline VWF/FVIII activity levels.

  • The initial dose is given 30-60 minutes before the procedure.

  • The duration of treatment is determined by the VWD type and the nature of the invasive procedure by closely monitoring the patient’s clinical and laboratory status.

  • In case of major surgery, in patients with severe VWD, treatment should be given for at least 1-2 weeks post surgery.

Key Adjustments by Product

  • Haemate®: Higher VWF:FVIII ratio (~2.4:1), often need more IU/kg VWF, but FVIII rises slower.

  • Wilate®: Balanced 1:1 ratio, lower IU/kg doses suffice, monitor FVIII closely (risk of overshoot).

  • Wilfactin® / Veyvondi® (VWF-only): Always consider adding FVIII with first dose if baseline FVIII < 40 IU/dL. Advantage: less FVIII accumulation long-term.