Treatment of von Willebrand Disease with Low Factor VIII Levels

Treatment Algorithm Based on VWD Type

The American Heart Association recommends that the treatment of von Willebrand disease (VWD) with low factor VIII levels should begin with desmopressin (DDAVP) for type 1 and some type 2A VWD patients, followed by VWF/FVIII concentrates if desmopressin is inadequate, while patients with types 2B, 2M, 2N, and 3 VWD should be treated primarily with specific VWF/FVIII concentrates 1, 2, 3
For type 2A VWD, an initial trial of desmopressin is recommended; if inadequate response, switch to VWF/FVIII concentrates, as suggested by the American Society of Anesthesiologists 2, 3
The American Society of Anesthesiologists recommends that VWF/FVIII concentrates are first-line therapy for type 2B, 2M, 2N VWD 3, 4
DDAVP is contraindicated in type 2B due to risk of thrombocytopenia, according to the American Society of Anesthesiologists 4
Human-derived medium-purity FVIII concentrates complexed to VWF are preferred for types 2B, 2M, 2N, as recommended by the American Heart Association 1, 4

For type 3 VWD, DDAVP is ineffective due to virtually complete absence of VWF, and VWF/FVIII concentrates are the only effective treatment option, as stated by the American Journal of Hematology 5
The American Society of Anesthesiologists recommends that dosing of VWF/FVIII concentrates should be calculated to achieve a minimum of 30% of plasma factor concentration for type 3 VWD 2

If VWF/FVIII concentrates are unavailable, cryoprecipitate can be used, as suggested by the American Society of Anesthesiologists 2, 3
Cryoprecipitate is indicated when there is no response to desmopressin, VWF/FVIII concentrates are unavailable, or for patients with congenital fibrinogen deficiencies, according to the American Society of Anesthesiologists 2, 3

For neuraxial anesthesia, VWF activity should be ≥50 IU/dL, as recommended by the Journal of Thrombosis and Haemostasis 6

Prophylactic use of DDAVP in cardiac surgery has shown no benefit in multiple meta-analyses, according to Praxis Medical Insights 7

Administer 0.3 μg/kg IV diluted in 50 mL saline infused over 30 minutes, given 30 minutes prior to scheduled procedures, as recommended by the American Society of Hematology, for type 1 VWD patients 8, 9

Test for von Willebrand activity before starting in patients with bleeding history, and use caution with concurrent antiplatelet agents or anticoagulants due to bleeding risk, as suggested by the National Hemophilia Foundation 10
Hold DDAVP 3-7 days pre- and post-surgery depending on procedure type and bleeding risk, as recommended by the American College of Surgeons 10

The American Heart Association recommends that complete blood count (CBC) with platelet count, prothrombin time (PT), and activated partial thromboplastin time (PTT) be performed to identify thrombocytopenia, coagulation factor deficiencies, and intrinsic pathway abnormalities before initiating DDAVP therapy in patients with von Willebrand disease or hemophilia A 11, 12
The National Heart, Lung, and Blood Institute (NHLBI) guidelines specify that von Willebrand factor antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII) assays be performed before DDAVP use in patients with von Willebrand disease 11, 12

The American Heart Association recommends that patients with Type 2B von Willebrand disease be excluded from DDAVP therapy due to the risk of severe thrombocytopenia, and that VWF/FVIII concentrates be used instead 11
If the VWF:RCo to VWF:Ag ratio is <0.5-0.7, VWF multimer analysis should be performed to exclude Type 2B von Willebrand disease before administering DDAVP 11
Baseline platelet count is essential to identify isolated decreased platelets that may occur in VWD Type 2B 13, 14

Patient-specific factors such as acute or chronic inflammatory illness, pregnancy or estrogen/oral contraceptive use, patient stress, anxiety, or recent exercise, and blood group O individuals can falsely elevate VWF and FVIII levels, potentially masking underlying deficiency 13, 14
African-Americans have higher baseline VWF levels than Caucasians, which should be considered when interpreting laboratory results 11
Blood samples for VWF assays must be transported at room temperature and plasma should be separated promptly at room temperature to prevent cryoprecipitation and ensure accurate results 13, 14

Tranexamic acid (TXA) is recommended as an essential adjunct for surgeries that involve mucosal surfaces, because it reduces bleeding risk in this setting. 15
In minor surgical procedures, TXA is employed in approximately 72 % of cases to support hemostasis. 15
For major operations, TXA is used in about 59 % of cases, frequently in combination with desmopressin (DDAVP) in roughly one‑third of respondents. 15
During obstetric deliveries, TXA is administered in roughly 58 % of cases to limit peri‑delivery bleeding. 15
TXA is inexpensive, widely available, and effective across a broad spectrum of bleeding scenarios, making it a practical choice for peri‑operative management. 15
Clinical algorithms that incorporate TXA alone or together with DDAVP have demonstrated hemostatic efficacy greater than 90 % in small case series; however, the quality of evidence supporting this outcome is low. 15

For minor procedures in patients with type 1 von Willebrand disease, the first‑line regimen is DDAVP combined with TXA. 15
For major surgery, the preferred initial strategy is DDAVP plus TXA when the patient has demonstrated a positive DDAVP response. 15
If bleeding persists despite prophylactic measures, the algorithm advises adding DDAVP (if it has not already been given). 15
In the setting of ongoing hemorrhage, supplementation with platelets and/or fresh‑frozen plasma is recommended as an adjunctive measure. 15
When first‑line therapies fail, escalation to von Willebrand factor/FVIII concentrates or recombinant factor VIIa should be considered. 15