TRAINING and EDUCATION
How I Treat In Brief
“ Although type 2B von Willebrand disease is defined by [ a gainof-function defect in von Willebrand factor ], it is a clinically heterogeneous disorder that can be difficult to identify and manage .”
— REBECCA KRUSE-JARRES , MD , MPH , and JILL M . JOHNSEN , MD
Fast Facts
✓✓The diagnosis and management of type 2B vWD requires an understanding of the underlying physiology of vWF-platelet interaction .
✓✓Treatment is similar to other types of vWD , but special consideration should be given to situations that can worsen thrombocytopenia , such as pregnancy .
✓✓The mainstays of type 2B vWD treatment remain vWF replacement and vWD adjunct therapies ( including antifibrinolytics and topical hemostatic agents ).
✓✓Treatment with DDAVP is controversial but may be a convenient option for some patients with minor bleeding .
✓✓For patients with type 2B vWD who are pregnant or considering pregnancy , treatment planning requires close monitoring with a multidisciplinary team consisting of representatives from high-risk obstetrics , anesthesia , hematology , neonatology , pharmacy , blood bank , and the coagulation laboratory .
In type 2B vWD , DDAVP is thought to cause release of higher-molecular-weight , hyperfunctional vWF that provokes transient platelet aggregation and thrombocytopenia . The potential to exacerbate bleeding or thrombocytopenia ( which only appears with type 2B vWD ) resulted in the longstanding practice of avoiding the use of DDAVP in type 2B vWD .
Side effects with DDAVP are common , but most are mild and generally subside after 24 hours . To minimize the risks of serious adverse events such as iatrogenic hyponatremia , fluids should be restricted .
DDAVP offers two advantages over other vWD treatments : It is more economical than factor concentrates and can be self-administered intranasally . And , despite the controversies , DDAVP is occasionally used to treat minor bleeding .
Before considering DDAVP for type 2B vWD , we recommend a monitored study demonstrating the platelet nadir and kinetics of platelet recovery , in addition to vWF responsiveness . A pharmacokinetic study is recommended for all types of vWD .
Case # 2 : Management of Type 2B vWD During Pregnancy
A 23-year-old with type 2B vWD was monitored throughout her pregnancy , labor , and delivery , as well as postpartum . During her pregnancy , vWF : Ag , vWF : RCo , and FVIII : C levels increased , but not to normal pregnancy levels . Thrombocytopenia became apparent and progressively worsened , with platelet counts decreasing from 350,000 /µ L before her pregnancy to 31,000 /µ L at 35 weeks .
Because of changes during pregnancy , laboratory testing at 34 to 36 weeks gestation is recommended to assess vWF levels close to delivery , and platelet counts ( and vWF , when possible ) should be monitored weekly thereafter .
At 38 weeks , the patient went into labor . She received vWF replacement at 60 IU / kg , but no platelet transfusion . She had an uncomplicated vaginal delivery without neuraxial anesthesia and without abnormal bleeding . She was maintained on vWF replacement at 30 IU / kg every 12 hours and started on tranexamic acid 1,300 mg orally three times daily .
During the final stages of labor for a vaginal delivery ( or for bleeding at any time ), we recommend an initial vWF replacement dose of 60 IU / kg to a target vWF : RCo greater than 50 percent .
For thrombocytopenic episodes , if platelet count is less than 50,000 /µ L , we request platelet transfusion within 30 minutes of a procedure , then aim for a platelet count greater than 50,000 /µ L and repeat transfusions as needed . For more severe thrombocytopenia ( platelet counts less than 20,000 /µ L ), we recommend platelet transfusion , frequent platelet-count monitoring , and repeat transfusions as needed .
For the duration of labor and delivery , maintenance vWF dosing starts at half the initial bolus dose every eight to 24 hours , adjusting for vWF : RCo peak and trough levels and monitoring FVIII : C levels .
For caesarean section ( C-section ), we aim for a vWF : RCo close to 80 to 100 percent and continue maintenance therapy as described for vaginal delivery . Goals for maintenance treatment after delivery by C-section are a vWF : RCo greater than 50 percent and platelet count greater than 20,000 /µ L for at least five days .
Neuraxial anesthesia is not recommended in patients with type 2 ( and specifically 2B ) vWD because of safety concerns and lack of evidence . We recommend that if neuraxial anesthesia is performed , it be done within one hour of vWF replacement therapy . If an epidural is placed , we request removal as soon as possible after delivery while drug levels are high .
Post-Partum Prophylaxis Four days postpartum , the patient had experienced no excessive bleeding and vWF replacement dosing was reduced to 30 IU / kg every 24 hours for another three days . She completed two weeks of antifibrinolytic treatment . Four weeks after her last dose of vWF , she complained of heavy vaginal bleeding . She was treated with vWF replacement 60 IU / kg , followed by 30 IU / kg daily for two days . Tranexamic acid was restarted and she achieved good control of her bleeding .
Delayed postpartum hemorrhage ( bleeding between 24 hours and 6 weeks postpartum ) is common in women with vWD . For type 2B vWD , we recommend monitoring with vWF replacement for five to seven days , platelet transfusion as needed , and antifibrinolytic therapy for at least two weeks postpartum . If bleeding continues or recurs , additional treatment and other causes of bleeding should be considered .
Diagnosis of Type 2B vWD in the Newborn Laboratory diagnosis in newborns is challenging , but screening may be done on cordblood sampling . Cord blood vWF : Ag and FVIII : C may be normal , but the vWF : RCo can be decreased . Infants with type 2B vWD can have thrombocytopenia and plateletclumping on peripheral smear . Genetic testing for a familial 2B vWD variant also can confirm or exclude the diagnosis .
Infants ’ bleeding risk is not known , but potential causes of hemorrhage should be avoided when possible . In cases of thrombocytopenia with bleeding or for invasive procedures , platelet transfusions should be given . In bleeding patients , both vWF replacement therapy and platelet transfusions should be considered .
Final Considerations
Recently , development and use of bleedingassessment tools have allowed for improved stratification of which patients require further testing and which are most likely to require treatment for their bleeding disorders .
New options for laboratory assessments of vWF activity under investigation include new platelet-binding assays that may offer more stable results than the vWF : RCo assay and provide insight into different functions of vWF . ●
34 ASH Clinical News April 2018