THSNA 2022 key points

1.  Anemia and Von Willebrand factor levels

Anemia can falsely elevate levels of VWF and factor 8, which can affect diagnosis. This applies only to type 1 disease. So correct anemia and recheck levels in suspected VWD.

2. Prophylaxis with recombinant VWF in severe VWD ( 3 or more spontaneous bleeds in prior 12 months) Vonicog alpha, phase 3 trial

VWF: Ristocetin level < 20, so patients with severe disease were included.

Vonicog alpha was better than on-demand prophylaxis ( previously using plasma product) and reduced the annualized bleeding rate. It was as good as plasma product in those who were on plasma-based routine prophylaxis with no new adverse events.

3.  New guidelines for diagnosis and management of VWD

• In patients with intermediate ( abnl coag studies e.g) and high ( first degree relative with VWD) probability of VWD, do not use a validated BAT. Use BAT if there is a low probability ( ie PCP's office).
• ISTH BAT 4 or higher in men, 6 or higher in women in predictive of bleeding disorder.
• Use VWF binding to GP1B instead of Ristocetin cofactor assay as the preferred functional assay when possible.
• VWF levels pre op:
• minor surgeries: > 0.5, major surgeries and neurosurgery > 1.0
• DDAVP challenge: positive result if the level rises at least 2 fold and is sustained at 1 hr and 4 hr
• Type 1 C VWD increased clearance of VWF --> good level at 1 hr, but drops levels in 4 hr. The VD pro peptide is still elevated at 4 hr.
• Type 1 VWD levels < 30% with or without bleeding
• Type 1 VWD if levels between 30-50% then some abnl bleeding is needed to make the diagnosis.
• Make diagnosis at a steady healthy state esp after correcting anemia.

4. VWD in women

Type 1 VWD: levels increase, factor 8 also, but both fall 2 weeks after delivery, with VWF levels falling more than factor 8 post partum

Type 2: no improvement in activity. 2B worsening thrombocytopenia, 2 No increase in factor 8

type  3 VWD: no increase

vWF must be tested in the 3rd trimester: Ag and or activity

5. Acquired von Willebrand's syndrome:

Causes fall into 4 groups: cardiac, hypothyroidism, malignancy, and autoimmune diseases.

Cardiac: aortic stenosis, VAD, congenital heart disease (  high shear rate with increased clearance)

cancer: MGUS, Waldenstrom's, myeloma, ET and Pvera

Wilm's lung bladder  ( clearance by AB or cell adsorption)

Hypothyroidism: decreased production

MGUS associated VWD may need IVIG and or myeloma rx if bleeding refractory despite factor replacement