Written in Blood
vWF activity profiles were generated for each subject and interpreted by linear discriminant analysis
(LDA; a method to determine a
variant vWD diagnostic algorithm).
A jackknife resampling technique
was used to validate LDA estimates
and predict performance in the
general population.
Dr. Roberts and colleagues found
that LDA was able to correctly assign variant vWD phenotype (vWD
type 1C, 2A, 2B, 2M, or 2N) in 124
of 134 patients, or 92.5 percent of
the time. Jackknife analysis applied
to LDA correctly determined variant vWD phenotype in 118 of 134
patients, or 88.1 percent of the time.
“Thus, this assay may correctly assign variant vWD phenotype in a
population of subjects undergoing
evaluation for ‘variant vWD,’” the
authors concluded.
Variability studies conducted on
four different days found that the assay also provided consistent results,
with low intra-plate and inter-plate
variability (coefficient of variation
ranges = 4.7-6.2% [median = 5.2%]
and 11.2-19.2% [median = 14.1%],
respectively). However, the authors
noted, “assay consistency would
need additional evaluation if implemented across various laboratories.”
The researchers noted another
potential limitation of this study:
The results will need to be validated
in a larger population, but implementing this assay on a larger scale
would require batch-production of
pre-coated ELISA plates, rather than
the freshly coated plates that were
used in this study.
“Our findings may prove to
be an improvement in diagnosing
variant vWD. Since it is a screening test, and has potential to lower
costs, it may allow more patients to
be screened for variant vWD,” Dr.
Roberts added. “The method we
used with this assay could potentially be combined with additional
vWF tests, as more vWF physiologic
activities continue to be discovered.
It may change the way in which we
perform laboratory evaluation for
variant vWD.”
REFERENCE
Roberts JC, Morateck PA, Christopherson PA, et al. Rapid
discrimination of the phenotypic variants of von Willebrand
disease. Blood. 2016 February 25. [Epub ahead of print]
34
ASH Clinical News
Defibrotide in Patients with VOD/SOS and
Multi-Organ Failure Following Transplant
Hepatic veno-occlusive disease,
also called sinusoidal obstruction syndrome (VOD/SOS), is
a potentially fatal complication
of allogeneic or autologous hematopoietic cell transplantation
(HCT), and is estimated to occur
in 13.7 percent of patients receiving HCT (range = 0-62.3%). In
cases of severe VOD/SOS, when
patients also experience multiorgan failure, the mortality risk is
greater than 80 percent.
Preclinical data have sug-
gested that defibrotide, a sodium
salt of complex single-stranded
oligodeoxyribonucleotides
derived from porcine mucosal
DNA, can stabilize and protect
endothelial cells – restoring the
balance between the coagulation
NOW FDA
IMPORTANT SAFETY INFORMATION FOR NINLARO® (ixazomib)
WARNINGS AND PRECAUTIONS
• Thrombocytopenia has been reported with NINLARO. During treatment, monitor platelet counts
at least monthly, and consider more frequent monitoring during the first three cycles. Manage
thrombocytopenia with dose modifications and platelet transfusions as per standard medical
guidelines. Adjust dosing as needed. Platelet nadirs occurred between Days 14-21 of each 28-day cycle
and recovered to baseline by the start of the next cyc le.
• Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting, were reported
with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and
supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 1%
of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for
severe symptoms.
• Peripheral Neuropathy (predominantly sensory) was reported with NINLARO. The most commonly
reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo
regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen
(< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of
patients in both regimens. Monitor patients for symptoms of peripheral neuropathy and adjust dosing
as needed.
• Peripheral Edema was reported with NINLARO. Monitor for fluid retention. Investigate for underlying
causes when appropriate and provide supportive care as necessary. Adjust dosing of dexamethasone
per its prescribing information or NINLARO for Grade 3 or 4 symptoms.
• Cutaneous Reactions: Rash, most commonly maculo-papular and macular rash, was reported with
NINLARO. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in
both regimens. Manage rash with supportive care or with dose modification.
• Hepatotoxicity has been reported with NINLARO. Drug-induced liver injury, hepatocellular injury,
hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients
treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen
and 5% in the placebo regimen). Monitor hepatic enzymes regularly during treatment and adjust
dosing as needed.
• Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women should be advised of the potential
risk to a fetus, to avoid becoming pregnant, and to use contraception during treatment and for an
additional 90 days after the final dose of NINLARO.