von Willebrand disease mechanism: VWF is critical for hemostasis and thrombus formation and plays 2 key roles2:
Binding to collagen and platelets to facilitate platelet plug formation2,3
Binding to factor VIII (FVIII) to protect it from clearance and stabilize plasma FVIII levels2,3
Because VWF protects FVIII in plasma, VWF deficiency or defect leads to increased FVIII clearance, resulting in low FVIII levels in some patients with VWD. Low levels of FVIII (<30-40 IU/dL) may lead to prolonged activated partial thromboplastin time (aPTT)2,4,5,6
VWF is deficient
VWF is defective
VWF is almost absent
An important fact to note about all 3 types of VWD is that they only impact production of functional VWF—VWD itself does not impact patients’ ability to produce FVIII2,9-11
Because VWD patients lack VWF multimer protein, an important protein for clotting, they are prone to bleeds. Patients with VWD Types 1, 2, and 3 have all reported a range of bleeding episodes.
GINGIVAL
MENORRHAGIA
EPISTAXIS
GASTROINTESTINAL
JOINT
In an on-demand clinical trial where VONVENDI was being investigated, 21 adult patients with severe Type 3 VWD (VWF: Ag≤3%) experienced a median (range) of 5.7 (0.0, 36.5) bleeds in a year that required treatment.12
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To treat acute bleeding episodes
To manage bleeding around surgery
To proactively reduce the number of bleeds
2021 ASH/ISTH/NHF/WFH treatment guidelines have provided insight into when prophylaxis may be considered for recommendation in appropriate VWD patients.16
Do not use in patients who have had life-threatening hypersensitivity reactions to VONVENDI or its components (tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, and hamster or mouse proteins).
Thromboembolic reactions, including disseminated intravascular coagulation, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur, particularly in patients with known risk factors for thrombosis, including low ADAMTS13 levels. Monitor for early signs and symptoms of thrombosis such as pain, swelling, discoloration, dyspnea, cough, hemoptysis, and syncope, and institute prophylaxis measures against thromboembolism based on current recommendations.
In patients requiring frequent doses of VONVENDI in combination with recombinant factor VIII, monitor plasma levels for FVIII:C activity because sustained excessive factor VIII plasma levels can increase the risk of thromboembolic events.
One out of 100 subjects treated with VONVENDI in clinical trials developed proximal deep vein thrombosis in perioperative period after total hip replacement surgery.
Hypersensitivity reactions have occurred with VONVENDI. These reactions can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, blurred vision, wheezing and/ or acute respiratory distress. Discontinue VONVENDI if hypersensitivity symptoms occur and administer appropriate emergency treatment.
Inhibitors to VWF and/or factor VIII can occur. If the expected plasma levels of VWF activity (VWF:RCo) are not attained, perform an appropriate assay to determine if anti-VWF or antifactor VIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either VWD or hemophilia A.
In patients with high levels of inhibitors to VWF or factor VIII, VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions. Since inhibitor antibodies can occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.
In clinical trials, the most common adverse reactions observed in ≥2% of subjects (n=100) were headache, vomiting, nausea, dizziness, arthralgia, joint injury, vertigo, ALT increased and generalized pruritus.
One subject treated with VONVENDI in perioperative setting developed deep vein thrombosis after total hip replacement surgery.
Please see VONVENDI full Prescribing Information.VONVENDI [von Willebrand factor (Recombinant)] is a recombinant von Willebrand factor (rVWF) indicated for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for:
Do not use in patients who have had life-threatening hypersensitivity reactions to VONVENDI or its components (tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, and hamster or mouse proteins).
Thromboembolic reactions, including disseminated intravascular coagulation, venous thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur, particularly in patients with known risk factors for thrombosis, including low ADAMTS13 levels. Monitor for early signs and symptoms of thrombosis such as pain, swelling, discoloration, dyspnea, cough, hemoptysis, and syncope, and institute prophylaxis measures against thromboembolism based on current recommendations.
In patients requiring frequent doses of VONVENDI in combination with recombinant factor VIII, monitor plasma levels for FVIII:C activity because sustained excessive factor VIII plasma levels can increase the risk of thromboembolic events.
One out of 100 subjects treated with VONVENDI in clinical trials developed proximal deep vein thrombosis in perioperative period after total hip replacement surgery.
Hypersensitivity reactions have occurred with VONVENDI. These reactions can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, blurred vision, wheezing and/or acute respiratory distress. Discontinue VONVENDI if hypersensitivity symptoms occur and administer appropriate emergency treatment.
Inhibitors to VWF and/or factor VIII can occur. If the expected plasma levels of VWF activity (VWF:RCo) are not attained, perform an appropriate assay to determine if anti-VWF or antifactor VIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either VWD or hemophilia A.
In patients with high levels of inhibitors to VWF or factor VIII, VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions. Since inhibitor antibodies can occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.
In clinical trials, the most common adverse reactions observed in ≥2% of subjects (n=100) were headache, vomiting, nausea, dizziness, arthralgia, joint injury, vertigo, ALT increased and generalized pruritus.
One subject treated with VONVENDI in perioperative setting developed deep vein thrombosis after total hip replacement surgery.
Please see VONVENDI full Prescribing Information.![VONVENDI® [von Willebrand factor (Recombinant)] logo.](/dist/images/vonvendi-logo-white.svg){kind=logo}