Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

VWD type unknown with bleeding

1st line – resuscitation + von Willebrand factor (VWF)-containing concentrate

Back
INITIAL
|
VWD type unknown with bleeding
1st line – 

resuscitation + von Willebrand factor (VWF)-containing concentrate

Patients with bleeding require resuscitation as appropriate, along with treatments specific for VWD.

Patients with bleeding and unknown VWD type should be treated with VWF-containing concentrate until historical and/or laboratory information allows identification of the specific type of VWD.

Most VWF concentrates are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF concentrate is also available. VWF concentrates may differ in the amount of FVIII, the VWF:FVIII ratio, and the multimeric composition of VWF. Plasma-derived VWF concentrates that contain both VWF and FVIII are effective immediately.[66] Recombinant VWF concentrate contains only VWF and following infusion, it takes approximately 6 hours for the endogenous levels of FVIII to reach haemostatic levels if they are low beforehand.[67] Thus, an initial loading dose of FVIII concentrate must be given when serious or life-threatening bleeding is treated with recombinant VWF concentrate. The FVIII infusion should not need repeating. In some countries, a high-purity plasma-derived VWF concentrate with very low levels of FVIII is available; an initial loading dose of FVIII may also be required if this is used for serious or life-threatening bleeding.[61][68]

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

Pregnant women with bleeding should generally receive the same treatment as non-pregnant women. Antenatal care should be provided in a specialist centre by a multidisciplinary team, including haematologists and obstetricians with expertise in this field.

Consider – antifibrinolytic therapy

Back
INITIAL
|
VWD type unknown with bleeding
Consider – 

antifibrinolytic therapy

Additional treatment recommended for SOME patients in selected patient group

Tranexamic acid and aminocaproic acid are most effective for mucous membrane bleeding (i.e., involving oral mucosa, gastrointestinal or genitourinary tract). Antifibrinolytics should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice between the two routes depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Pregnant women with bleeding should generally receive the same treatment as non-pregnant women. There are no data on the long-term administration of tranexamic acid in pregnancy, but it is known to cross the placenta. Antenatal care should be provided in a specialist centre by a multidisciplinary team, including haematologists and obstetricians with expertise in this field.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose.

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

2nd line – resuscitation + cryoprecipitate

Back
INITIAL
|
VWD type unknown with bleeding
2nd line – 

resuscitation + cryoprecipitate

Patients with bleeding require resuscitation as appropriate, along with treatments specific for VWD.

Cryoprecipitate is an alternative option to von Willebrand factor (VWF)-containing concentrate. Except in an emergency situation where virally inactivated VWF-containing concentrate is unavailable, cryoprecipitate should be avoided because it does not undergo viral inactivation.[60]

Consider – antifibrinolytic therapy

Back
INITIAL
|
VWD type unknown with bleeding
Consider – 

antifibrinolytic therapy

Additional treatment recommended for SOME patients in selected patient group

Tranexamic acid and aminocaproic acid are most effective for mucous membrane bleeding (i.e., involving oral mucosa, gastrointestinal or genitourinary tract). Antifibrinolytics should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice between the two routes depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Pregnant women with bleeding should generally receive the same treatment as non-pregnant women. There are no data on the long-term administration of tranexamic acid in pregnancy, but it is known to cross the placenta. Antenatal care should be provided in a specialist centre by a multidisciplinary team, including haematologists and obstetricians with expertise in this field.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose.

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

all types VWD with severe bleeding uncontrolled by other VWD-specific therapies

1st line – platelet transfusion

Back
INITIAL
|
all types VWD with severe bleeding uncontrolled by other VWD-specific therapies
1st line – 

platelet transfusion

In patients with bleeding refractory to all other VWD-specific therapies, platelets are a useful source of von Willebrand factor (VWF), which is released at the site of injury. Platelet VWF is absent in patients with type 3 VWD.

Pregnant women with severe bleeding should generally receive the same treatment as non-pregnant women. Antenatal care should be provided in a specialist centre by a multidisciplinary team, including haematologists and obstetricians with expertise in this field

ACUTE

all types VWD with severe bleeding or before invasive procedures where sustained elevation of VWF levels is necessary: non-pregnant

1st line – von Willebrand factor (VWF)-containing concentrate

Back
ACUTE
|
all types VWD with severe bleeding or before invasive procedures where sustained elevation of VWF levels is necessary: non-pregnant
1st line – 

von Willebrand factor (VWF)-containing concentrate

VWF-containing concentrate should be administered for severe bleeding and major surgeries when more prolonged therapy is necessary.

Most VWF concentrates are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF concentrate is also available. VWF concentrates may differ in the amount of FVIII, the VWF:FVIII ratio, and the multimeric composition of VWF. Plasma-derived VWF concentrates that contain both VWF and FVIII are effective immediately.[66] Recombinant VWF concentrate contains only VWF and following infusion, it takes approximately 6 hours for the endogenous levels of FVIII to reach haemostatic levels if they are low beforehand.[67] Thus, an initial loading dose of FVIII concentrate must be given when serious or life-threatening bleeding is treated with recombinant VWF concentrate. The FVIII infusion should not need repeating. In some countries, a high-purity plasma-derived VWF concentrate with very low levels of FVIII is available; an initial loading dose of FVIII may also be required if this is used for serious or life-threatening bleeding.[61][68]

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

Consider – antifibrinolytic therapy

Back
ACUTE
|
all types VWD with severe bleeding or before invasive procedures where sustained elevation of VWF levels is necessary: non-pregnant
Consider – 

antifibrinolytic therapy

Additional treatment recommended for SOME patients in selected patient group

Antifibrinolytic therapy can be used prophylactically or therapeutically in patients who are bleeding or undergoing invasive procedures, in conjunction with VWF-containing concentrate.[20][61]

Antifibrinolytics are most effective for mucous membrane bleeding (i.e., involving oral mucosa, gastrointestinal or genitourinary tract). Antifibrinolytics should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

2nd line – cryoprecipitate

Back
ACUTE
|
all types VWD with severe bleeding or before invasive procedures where sustained elevation of VWF levels is necessary: non-pregnant
2nd line – 

cryoprecipitate

Cryoprecipitate is an alternative option to von Willebrand factor (VWF)-containing concentrate. Except in an emergency situation where virally inactivated VWF-containing concentrate is unavailable, cryoprecipitate should be avoided because it does not undergo viral inactivation.[60]

Consider – antifibrinolytic therapy

Back
ACUTE
|
all types VWD with severe bleeding or before invasive procedures where sustained elevation of VWF levels is necessary: non-pregnant
Consider – 

antifibrinolytic therapy

Additional treatment recommended for SOME patients in selected patient group

Antifibrinolytic therapy may be used as an adjunct to cryoprecipitate. Antifibrinolytic therapy can be used prophylactically or therapeutically in patients who are bleeding or undergoing invasive procedures.[20][61]

Antifibrinolytics are most effective for mucous membrane bleeding (i.e., involving oral mucosa, gastrointestinal or genitourinary tract). Antifibrinolytics should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice between the two routes depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

minor bleeding or minor invasive procedures involving mucous membranes: non-pregnant

1st line – antifibrinolytic therapy

Back
ACUTE
|
minor bleeding or minor invasive procedures involving mucous membranes: non-pregnant
|
type 1 VWD
1st line – 

antifibrinolytic therapy

Antifibrinolytic therapy may be used for mucous membrane bleeding or procedures (i.e., involving oral mucosa, gastrointestinal or genitourinary tract). It may also be used in combination with desmopressin or VWF-containing concentrate for this indication.[20][61]

In patients with type 1 VWD with baseline VWF activity levels >0.30 IU/mL and a mild bleeding phenotype undergoing minor mucosal procedures, the 2021 ASH ISTH NHF WFH (American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and World Federation of Hemophilia) guidelines suggest using tranexamic acid alone as monotherapy.[61]

Evidence comparing different haemostatic therapy options is limited, and the treatment plan should be individualised according to the bleeding risk associated with the specific procedure and the patient’s bleeding history and phenotype.[60][61]​​

One dose before dental cleanings may be effective to prevent oozing. Repeat dosing may be effective alone to treat bleeding from mucosal surfaces.

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice between the two routes depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

Consider – desmopressin or von Willebrand factor (VWF)-containing concentrate

Back
ACUTE
|
minor bleeding or minor invasive procedures involving mucous membranes: non-pregnant
|
type 1 VWD
Consider – 

desmopressin or von Willebrand factor (VWF)-containing concentrate

Additional treatment recommended for SOME patients in selected patient group

Desmopressin may be used in combination with antifibrinolytic therapy in patients known to respond to this drug. VWF-containing concentrate may be used in combination with antifibrinolytic therapy in patients who do not respond to desmopressin or who have contraindications to its use (e.g., patients with atherosclerosis, cardiac insufficiency or other conditions that are treated with diuretics, polydipsia, or seizure disorders).

Patients with type 1 VWD and von Willebrand factor (VWF) levels <0.30 IU/mL should be tested to see whether they respond to desmopressin, unless its use is contraindicated.[61] Adults with VWF levels ≥0.30 IU/mL can be presumed desmopressin responsive.[61][63] Desmopressin use results in release of VWF and factor VIII (FVIII) from endothelial stores.[64] Patients should have at least a twofold increase in VWF levels 30 minutes to 1 hour after administration, with resulting values >0.50 IU/mL.[61] Some patients with type 1 VWD have accelerated clearance of VWF, and so a measurement should also be obtained 4 hours after administration.[61]

Fluid retention may occur as a result of the action of desmopressin in the kidneys; thus, it is important to practice fluid restriction following desmopressin administration to reduce the risk of hyponatraemia. Because of this, desmopressin is usually avoided in older adults and young children (<2 years old) for whom hyponatraemia is a particular danger. Use in children aged ≥2 years is possible with careful monitoring.[20]

The intravenous route is preferred for inpatient treatment and surgery, while the intranasal route is used to allow patients to self-treat at home. Due to tachyphylaxis and the risk of hyponatraemia, desmopressin should not be administered for more than three consecutive days.[61][65]

Most VWF-containing concentrates are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF concentrate is also available. VWF-containing concentrates may differ in the amount of FVIII, the VWF:FVIII ratio, and the multimeric composition of VWF. Plasma-derived VWF concentrates that contain both VWF and FVIII are effective immediately.[66] Recombinant VWF concentrate contains only VWF and following infusion, it takes approximately 6 hours for the endogenous levels of FVIII to reach haemostatic levels if they are low beforehand.[67] Thus, an initial loading dose of FVIII concentrate must be given when serious or life-threatening bleeding is treated with recombinant VWF concentrate. The FVIII infusion should not need repeating. In some countries, a high-purity plasma-derived VWF concentrate with very low levels of FVIII is available; an initial loading dose of FVIII may also be required if this is used for serious or life-threatening bleeding.[61][68]

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

Primary options

desmopressin: children <2 years of age: consult specialist for guidance on dose; children ≥2 years of age and adults: 0.3 micrograms/kg intravenously/subcutaneously as a single dose, may repeat after 8-12 hours and then every 24 hours if needed according to response and laboratory studies, maximum 20 micrograms/dose

More

OR

desmopressin nasal: children <2 years of age: consult specialist for guidance on dose; children ≥2 years of age and adults <50 kg body weight: (1.5 mg/mL) 150 micrograms in one nostril, may repeat if needed according to response and laboratory studies; children ≥2 years of age and adults ≥50 kg body weight: (1.5 mg/mL) 150 micrograms in each nostril (total dose 300 micrograms), may repeat if needed according to response and laboratory studies

More

1st line – antifibrinolytic therapy

Back
ACUTE
|
minor bleeding or minor invasive procedures involving mucous membranes: non-pregnant
|
type 2 or 3 VWD
1st line – 

antifibrinolytic therapy

​Antifibrinolytic therapy may be used in combination with desmopressin or von Willebrand factor (VWF)-containing concentrate for mucous membrane bleeding or procedures (i.e., involving oral mucosa, gastrointestinal or genitourinary tract).[20][61]

Evidence comparing different haemostatic therapy options is limited, and the treatment plan should be individualised according to the bleeding risk associated with the specific procedure and the patient’s bleeding history and phenotype.[60][61]

One dose before dental cleanings may be effective to prevent oozing. Repeated dosing may be effective to treat bleeding from mucosal surfaces.

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice between the two routes depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

Plus – desmopressin or von Willebrand factor (VWF)-containing concentrate

Back
ACUTE
|
minor bleeding or minor invasive procedures involving mucous membranes: non-pregnant
|
type 2 or 3 VWD
Plus – 

desmopressin or von Willebrand factor (VWF)-containing concentrate

Treatment recommended for ALL patients in selected patient group

Desmopressin is used in combination with antifibrinolytic therapy in patients known to respond to this drug. VWF-containing concentrate should be used in combination with antifibrinolytic therapy in patients who do not respond to desmopressin or who have contraindications to its use (e.g., patients with atherosclerosis, cardiac insufficiency or other conditions that are treated with diuretics, polydipsia, or seizure disorders).

Some patients with types 2A and 2M WD may have a response to desmopressin, allowing its use for minor bleeding or minor procedures, particularly in combination with antifibrinolytic therapy. These patients should be tested to assess desmopressin response before any planned treatment.[61] Desmopressin is generally ineffective in type 2N VWD, but some patients may have a response.[20][60]​ Desmopressin is generally ineffective and contraindicated in type 2B VWD (although its use in this setting has been reported), and it may worsen thrombocytopenia.[20][61]​​ Patients with type 3 VWD do not respond to desmopressin and require treatment with VWF concentrate.[60][61]​​

Desmopressin use results in release of VWF and factor VIII (FVIII) from endothelial stores.[64] Patients should have at least a twofold increase in VWF levels 30 minutes to 1 hour after administration, with resulting values >0.50 IU/mL.[61] Some patients with type 1 VWD have accelerated clearance of VWF, and so a measurement should also be obtained 4 hours after administration.[61]

Fluid retention may occur as a result of the action of desmopressin in the kidneys; thus, it is important to practice fluid restriction following desmopressin administration to reduce the risk of hyponatraemia. Because of this, desmopressin is usually avoided in older adults and young children (<2 years old) for whom hyponatraemia is a particular danger. Use in children aged ≥2 years is possible with careful monitoring.[20]

The intravenous route is preferred for inpatient treatment and surgery, while the intranasal route is used to allow patients to self-treat at home. Due to tachyphylaxis and the risk of hyponatraemia, desmopressin should not be administered for more than three consecutive days.[61][65]

Most VWF-containing concentrates are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF concentrate is also available. VWF-containing concentrates may differ in the amount of FVIII, the VWF:FVIII ratio, and the multimeric composition of VWF. Plasma-derived VWF concentrates that contain both VWF and FVIII are effective immediately.[66] Recombinant VWF concentrate contains only VWF and following infusion, it takes approximately 6 hours for the endogenous levels of FVIII to reach haemostatic levels if they are low beforehand.[67] Thus, an initial loading dose of FVIII concentrate must be given when serious or life-threatening bleeding is treated with recombinant VWF concentrate. The FVIII infusion should not need repeating. In some countries, a high-purity plasma-derived VWF concentrate with very low levels of FVIII is available; an initial loading dose of FVIII may also be required if this is used for serious or life-threatening bleeding.[61][68]

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

Primary options

desmopressin: children <2 years of age: consult specialist for guidance on dose; children ≥2 years of age and adults: 0.3 micrograms/kg intravenously/subcutaneously as a single dose, may repeat after 8-12 hours and then every 24 hours if needed according to response and laboratory studies, maximum 20 micrograms/dose

More

OR

desmopressin nasal: children <2 years of age: consult specialist for guidance on dose; children ≥2 years of age and adults <50 kg body weight: (1.5 mg/mL) 150 micrograms in one nostril, may repeat if needed according to response and laboratory studies; children ≥2 years of age and adults ≥50 kg body weight: (1.5 mg/mL) 150 micrograms in each nostril (total dose 300 micrograms), may repeat if needed according to response and laboratory studies

More

minor bleeding or minor invasive procedures not involving mucous membranes: non-pregnant

1st line – desmopressin

Back
ACUTE
|
minor bleeding or minor invasive procedures not involving mucous membranes: non-pregnant
|
type 1, 2A, 2N, or 2M VWD and known desmopressin responder
1st line – 

desmopressin

Desmopressin may be used in patients with types 1, 2A, 2N, or 2M VWD who are known to respond to this drug.

Patients with type 1 (and VWF levels <0.30 IU/mL), 2A, or 2M VWD should be tested to see whether they respond to desmopressin, unless its use is contraindicated.[61] Adults with type 1 VWD and VWF levels ≥0.30 IU/mL can be presumed desmopressin responsive.[61][63] Desmopressin is generally ineffective in type 2N VWD, but some patients may have a response.[20][60] Patients should have at least a twofold increase in VWF levels 30 minutes to 1 hour after administration, with resulting values >0.50 IU/mL.[61] Some patients with type 1 VWD have accelerated clearance of VWF, and so a measurement should also be obtained at 4 hours after administration.

Fluid retention may occur as a result of the action of desmopressin in the kidneys; thus, it is important to practice fluid restriction following desmopressin administration to reduce the risk of hyponatraemia. Because of this, desmopressin is usually avoided in older adults and young children (<2 years old) for whom hyponatraemia is a particular danger. Use in children age ≥2 years is possible with careful monitoring.[20]

The intravenous route is preferred for inpatient treatment and surgery, while the intranasal route is used to allow patients to self-treat at home. Due to tachyphylaxis and the risk of hyponatraemia, desmopressin should not be administered for more than three consecutive days.[61][65]

Primary options

desmopressin: children <2 years of age: consult specialist for guidance on dose; children ≥2 years of age and adults: 0.3 micrograms/kg intravenously/subcutaneously as a single dose, may repeat after 8-12 hours and then every 24 hours if needed according to response and laboratory studies, maximum 20 micrograms/dose

More

OR

desmopressin nasal: children <2 years of age: consult specialist for guidance on dose; children ≥2 years of age and adults <50 kg body weight: (1.5 mg/mL) 150 micrograms in one nostril, may repeat if needed according to response and laboratory studies; children ≥2 years of age and adults ≥50 kg body weight: (1.5 mg/mL) 150 micrograms in each nostril (total dose 300 micrograms), may repeat if needed according to response and laboratory studies

More

Consider – antifibrinolytic therapy

Back
ACUTE
|
minor bleeding or minor invasive procedures not involving mucous membranes: non-pregnant
|
type 1, 2A, 2N, or 2M VWD and known desmopressin responder
Consider – 

antifibrinolytic therapy

Additional treatment recommended for SOME patients in selected patient group

​Antifibrinolytic therapy may be used as an adjunct to desmopressin in patients who are bleeding or undergoing surgical or invasive procedures.[20][61]

For minor surgery or invasive procedures, the 2021 ASH ISTH NHF WFH (American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and World Federation of Hemophilia) guidelines suggest using desmopressin with adjunctive tranexamic acid over using desmopressin.[61] However, this recommendation was based on very low certainty evidence with a focus on patients with severe bleeding phenotypes, and there is some concern for overtreatment or increased adverse effects.[61]

Evidence comparing different haemostatic therapy options is limited, and the treatment plan should be individualised according to the bleeding risk associated with the specific procedure and the patient’s bleeding history and phenotype.[60][61]

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

1st line – von Willebrand factor (VWF)-containing concentrate

Back
ACUTE
|
minor bleeding or minor invasive procedures not involving mucous membranes: non-pregnant
|
type 1, 2A, 2N, or 2M VWD and known desmopressin non-responder or contraindications to desmopressin use; type 2B or 3 VWD
1st line – 

von Willebrand factor (VWF)-containing concentrate

​VWF-containing concentrate can be used in patients with types 1, 2A, 2N, or 2M VWD who do not respond to desmopressin or have a contraindication to its use (e.g., patients with atherosclerosis, cardiac insufficiency, or other conditions that are treated with diuretics, polydipsia, or seizure disorders).[61]

VWF-containing concentrate is the preferred option in patients with type 2B or 3 VWD. Desmopressin is generally ineffective and contraindicated in type 2B VWD (although its use in this setting has been reported), and it may worsen thrombocytopenia.[20][61]​ Patients with type 3 VWD do not respond to desmopressin.[60][61]​​

Most VWF-containing concentrates are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF concentrate is also available. VWF-containing concentrates may differ in the amount of FVIII, the VWF:FVIII ratio, and the multimeric composition of VWF. Plasma-derived VWF concentrates that contain both VWF and FVIII are effective immediately.[66] Recombinant VWF concentrate contains only VWF and following infusion, it takes approximately 6 hours for the endogenous levels of FVIII to reach haemostatic levels if they are low beforehand.[67] Thus, an initial loading dose of FVIII concentrate must be given when serious or life-threatening bleeding is treated with recombinant VWF concentrate. The FVIII infusion should not need repeating. In some countries, a high-purity plasma-derived VWF concentrate with very low levels of FVIII is available; an initial loading dose of FVIII may also be required if this is used for serious or life-threatening bleeding.[61][68]

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

Consider – antifibrinolytic therapy

Back
ACUTE
|
minor bleeding or minor invasive procedures not involving mucous membranes: non-pregnant
|
type 1, 2A, 2N, or 2M VWD and known desmopressin non-responder or contraindications to desmopressin use; type 2B or 3 VWD
Consider – 

antifibrinolytic therapy

Additional treatment recommended for SOME patients in selected patient group

​Antifibrinolytic therapy may be used as an adjunct to VWF-containing concentrate in patients who are bleeding or undergoing surgical or invasive procedures.[20][61]

For minor surgery or invasive procedures, the 2021 ASH ISTH NHF WFH (American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and World Federation of Hemophilia) guidelines suggest using VWF-containing concentrate with adjunctive tranexamic acid over using VWF-containing concentrate alone.[61] However, this recommendation was based on very low certainty evidence with a focus on patients with severe bleeding phenotypes, and there is some concern for overtreatment or increased adverse effects.[61] 

Evidence comparing different haemostatic therapy options is limited, and the treatment plan should be individualised according to the bleeding risk associated with the specific procedure and the patient’s bleeding history and phenotype.[60][61]

Tranexamic acid and aminocaproic acid may be given orally or intravenously. The choice depends on patient factors and convenience. For example, the intravenous route will mostly be used for patients undergoing surgery.

If available, tranexamic acid mouthwash is also extremely useful for bleeding in the oral cavity. It can be swallowed or not, as preferred. The mouthwash may need to be prepared by a pharmacist.

Tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

all types VWD: pregnant

1st line – specialist referral

Back
ACUTE
|
all types VWD: pregnant
1st line – 

specialist referral

Antenatal care should be provided in a specialist centre by a multidisciplinary team, including haematologists and obstetricians with expertise in this field.[14][71]

During pregnancy, patients with type 1 VWD, especially if mild, may experience a significant rise in VWF levels. This may result in VWF levels that are within the normal range at term, so that no treatment or special measures are required. In type 2 VWD, the VWF levels may rise during pregnancy; however, the functional activity will rarely enter the normal range, necessitating VWD-specific treatment.[14][72][73] In type 3 VWD, there is no rise in VWF levels during pregnancy, so treatment is required for delivery.

VWD-specific treatment during gestation is not usually necessary, unless there is bleeding or an additional risk factor.[14] If treatment during gestation is necessary, pregnant women should generally receive the same treatment as non-pregnant women.

Consider – desmopressin or von Willebrand factor (VWF)-containing concentrate

Back
ACUTE
|
all types VWD: pregnant
Consider – 

desmopressin or von Willebrand factor (VWF)-containing concentrate

Additional treatment recommended for SOME patients in selected patient group

VWF levels and factor VIII activity should be assessed in the third trimester to determine plan for delivery.[61] If VWF levels do not rise to target, as in other circumstances, desmopressin or VWF-containing concentrate should be used.[14] It is recommended to target VWF levels 0.50 to 1.50 IU/mL prior to neuraxial anaesthesia. There is uncertainty regarding the target VWF level postpartum, but targeting higher VWF levels >1.50 IU/mL, often achieved in pregnant women without VWD, may reduce the risk of postpartum haemorrhage.[61][73]

Responsiveness to desmopressin should ideally be established prior to pregnancy.[14][74] Desmopressin is safe to administer during pregnancy but should not be used in the presence of pre-eclampsia or cardiovascular disease.[61][75]

Fluid retention may occur as a result of the action of desmopressin in the kidneys; thus, it is important to practice fluid restriction following desmopressin administration to reduce the risk of hyponatraemia.[20]

The intravenous route is preferred for inpatient treatment and surgery, while the intranasal route is used to allow patients to self-treat at home. Due to tachyphylaxis and the risk of hyponatraemia, desmopressin should not be administered for more than three consecutive days.[61][65]

VWF-containing concentrate should be used in patients who do not respond to desmopressin or who have contraindications to its use. Most VWF concentrates are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF concentrate is also available. VWF concentrates may differ in the amount of FVIII, the VWF:FVIII ratio, and the multimeric composition of VWF. Plasma-derived VWF concentrates that contain both VWF and FVIII are effective immediately.[66] Recombinant VWF concentrate contains only VWF and following infusion, it takes approximately 6 hours for the endogenous levels of FVIII to reach haemostatic levels if they are low beforehand.[67] Thus, an initial loading dose of FVIII concentrate must be given when serious or life-threatening bleeding is treated with recombinant VWF concentrate. The FVIII infusion should not need repeating. In some countries, a high-purity plasma-derived VWF concentrate with very low levels of FVIII is available; an initial loading dose of FVIII may also be required if this is used for serious or life-threatening bleeding.[61][68]​

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

Primary options

desmopressin: adults: 0.3 micrograms/kg intravenously/subcutaneously as a single dose, may repeat after 8-12 hours and then every 24 hours if needed according to response and laboratory studies, maximum 20 micrograms/dose

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OR

desmopressin nasal: adults <50 kg body weight: (1.5 mg/mL) 150 micrograms in one nostril, may repeat if needed according to response and laboratory studies; adults ≥50 kg body weight: (1.5 mg/mL) 150 micrograms in each nostril (total dose 300 micrograms), may repeat if needed according to response and laboratory studies

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Consider – antifibrinolytic therapy

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ACUTE
|
all types VWD: pregnant
Consider – 

antifibrinolytic therapy

Additional treatment recommended for SOME patients in selected patient group

​All women with VWD are at increased risk of postpartum haemorrhage, especially delayed. Tranexamic acid should be considered in the postpartum period, and patients should be reassured that it is safe to use if breastfeeding.[14][61]

VWD-specific treatment during gestation is not usually necessary, unless there is bleeding or an additional risk factor.[14]​ If treatment during gestation is necessary, pregnant women should generally receive the same treatment as non-pregnant women. There are no data on the long-term administration of tranexamic acid in pregnancy, but it is known to cross the placenta. Antenatal care should be provided in a specialist centre by a multidisciplinary team, including haematologists and obstetricians with expertise in this field.[14][71]

Primary options

tranexamic acid: adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

Plus – platelet transfusion

Back
ACUTE
|
all types VWD: pregnant
|
with thrombocytopenia
Plus – 

platelet transfusion

Treatment recommended for ALL patients in selected patient group

In type 2B VWD, thrombocytopenia can worsen with pregnancy, and platelet transfusion may be needed for delivery.[14][73]

ONGOING

all types VWD with heavy menstrual bleeding

1st line – hormonal therapy

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ONGOING
|
all types VWD with heavy menstrual bleeding
1st line – 

hormonal therapy

Patients with heavy menstrual bleeding (HMB) should be managed jointly by haematologists and gynaecologists in the context of multidisciplinary clinics when feasible.[61][62][76] Haematologists may not be familiar with aspects of gynaecology or hormonal therapy, and similarly gynaecologists may be unfamiliar with haemostasis.

Hormonal therapy may be used as a first-line option to treat HMB in those who do not wish to conceive, and where benefits of treatment outweigh any risks.[61][62] For HMB, combined oral contraceptives and progestin-only contraceptives usually decrease menstrual blood flow.[20][77] Although evidence in women with VWD is sparse, a progestin-releasing intrauterine device (IUD) has been shown to be effective for the treatment of HMB in women without bleeding disorders.[62][76]

There are many different contraceptive products and regimens available. Consult your local drug information source for more information.

1st line – antifibrinolytic therapy

Back
ONGOING
|
all types VWD with heavy menstrual bleeding
1st line – 

antifibrinolytic therapy

Patients with heavy menstrual bleeding (HMB) should be managed jointly by haematologists and gynaecologists in the context of multidisciplinary clinics when feasible.[61][62][76] Hematologists may not be familiar with aspects of gynaecology or hormonal therapy, and similarly gynaecologists may be unfamiliar with haemostasis.

Antifibrinolytic therapy may be used as a first-line option to treat HMB in those who wish to conceive and those who do not wish to conceive.[61][62] Antifibrinolytic therapy has been documented to be effective in treatment of HMB in women without bleeding disorders. The efficacy of aminocaproic acid in treating HMB is assumed from studies using tranexamic acid.[54]

Tranexamic acid and aminocaproic acid should not be used in upper renal tract bleeding or in the presence of disseminated intravascular coagulation.

Primary options

tranexamic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

OR

aminocaproic acid: children and adults: dose depends on route of administration and type of procedure; consult specialist for guidance on dose

2nd line – desmopressin or von Willebrand factor (VWF)-containing concentrate

Back
ONGOING
|
all types VWD with heavy menstrual bleeding
2nd line – 

desmopressin or von Willebrand factor (VWF)-containing concentrate

Desmopressin is an alternative therapy for HMB for those who do not respond to, or cannot tolerate, other measures, but evidence for benefit is inconclusive.​[61]​​[62][78] Similarly, VWF concentrate-containing may be used.[62][66]

Desmopressin may be used in patients known to respond to this drug. VWF-containing concentrate should be used in patients who do not respond to desmopressin or who have contraindications to its use (e.g., patients with atherosclerosis, cardiac insufficiency, or other conditions that are treated with diuretics, polydipsia, or seizure disorders).

For home therapy, desmopressin is most readily given as an intranasal spray. Fluid retention may occur as a result of the action of desmopressin in the kidneys; thus, it is important to practice fluid restriction following desmopressin administration to reduce the risk of hyponatraemia.[20] Due to tachyphylaxis and the risk of hyponatraemia, desmopressin should not be administered for more than three consecutive days.[61][65]

Most VWF-containing concentrates are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF concentrate is also available. VWF-containing concentrates may differ in the amount of FVIII, the VWF:FVIII ratio, and the multimeric composition of VWF. Plasma-derived VWF concentrates that contain both VWF and FVIII are effective immediately.[66] Recombinant VWF concentrate contains only VWF and following infusion, it takes approximately 6 hours for the endogenous levels of FVIII to reach haemostatic levels if they are low beforehand.[67] Thus, an initial loading dose of FVIII concentrate must be given when serious or life-threatening bleeding is treated with recombinant VWF concentrate. The FVIII infusion should not need repeating. In some countries, a high-purity plasma-derived VWF concentrate with very low levels of FVIII is available; an initial loading dose of FVIII may also be required if this is used for serious or life-threatening bleeding.[61][68]​

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

Primary options

desmopressin nasal: children and adults <50 kg body weight: (1.5 mg/mL) 150 micrograms in one nostril, may repeat if needed according to response and laboratory studies; children ≥2 years of age and adults ≥50 kg body weight: (1.5 mg/mL) 150 micrograms in each nostril (total dose 300 micrograms), may repeat if needed according to response and laboratory studies

OR

desmopressin: children and adults: 0.3 micrograms/kg intravenously/subcutaneously as a single dose, may repeat after 8-12 hours and then every 24 hours if needed according to response and laboratory studies, maximum 20 micrograms/dose

2nd line – combination therapy

Back
ONGOING
|
all types VWD with heavy menstrual bleeding
2nd line – 

combination therapy

Combination therapy (e.g., tranexamic acid combined with either hormonal therapy or desmopressin) may be another option if first-line treatment is ineffective, but there is a lack of data on its efficacy, impact on quality of life, and adverse effects.[62][79]

all types VWD with significant chronic or recurrent bleeding

1st line – prophylaxis with von Willebrand factor (VWF)-containing concentrate

Back
ONGOING
|
all types VWD with significant chronic or recurrent bleeding
1st line – 

prophylaxis with von Willebrand factor (VWF)-containing concentrate

Prevents bleeding in patients with significant chronic or recurrent bleeding, typically due to haemarthrosis, gastrointestinal bleeding, or heavy menstrual bleeding.[61] Prophylaxis is most often necessary in patients with more severe VWD, such as types 2 and 3 VWD.

Patients and/or family members can be instructed in home infusion. Patients with type 3 VWD can occasionally develop antibodies to VWF after treatment with VWF-containing concentrate.

VWF-containing concentrates may differ in the amount of factor VIII, the VWF:factor VIII ratio, and the multimeric composition of VWF. At present, most available products are plasma-derived and undergo treatment to minimise the risk of viral transmission. Recombinant VWF is also available.

VWF and factor VIII levels should be monitored if VWF-containing concentrate is administered repeatedly. Dosing should be adjusted such that factor VIII levels are not excessively elevated because of a potential risk of thrombosis.[69]

VWD-specific treatment during gestation is not usually necessary, unless there is bleeding or an additional risk factor.[14] If treatment during gestation is necessary, pregnant women should generally receive the same treatment as non-pregnant women. Antenatal care should be provided in a specialist centre by a multidisciplinary team, including haematologists and obstetricians with expertise in this field.

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