ASH News Daily 2012 - Saturday, December 8, 2012 - (Page A-14)
Page A–14
®
RARE DISEASES
TTP/HUS: There’s a Light at the End of the Clogged Arteriole
microangiopathies
BY JOSE A. BUFILL, MD
E
ver since Eli Moschowitz described
the dramatic clinical
course and unusual autopsy
findings of a 16-year-old woman
who experienced fever, rapidly
worsening anemia, petechiae, hemiparesis,
and coma, the first “TTP”
patient, 88 years ago, the story of the
thrombotic microangiopathies has
been a tale of slow but steady success.
Over the next several decades,
other physicians began to recognize
“Moschowitz syndrome” in their
patients and eventually proposed
the “TTP pentad:” five clinical criteria
to help diagnose these rare disorders.
However, the most certain
diagnostic criterion for thrombotic
thrombocytopenic
purpura
(TTP)
was that almost all affected patients
died shortly after the onset of
symptoms. Treatment of the thrombotic
microangiopathies remained
an exercise in frustration until the
1970s, when exchange transfusions
seemed to help some patients. Subsequently,
it was demonstrated that
plasma exchange could reverse the
inevitable decline of many patients
with TTP, and it remains the standard
treatment to this day.
We now have a better understanding
of the basis for the wide
variation of clinical features of these
disorders and how their treatments
work. At the root of the thrombotic
BLEEDING
Will They Bleed … Will They Thrombose? That is the Question
BY ANDREW D. LEAVITT, MD
Program session,
Y
ou know the consult. It goes
something like this: “Hi, I
have an obese 59-year-old
patient with a history of DVT, hypertension,
diabetes, and coronary
artery disease who, and in addition
to his other medications, has been
on dual platelet therapy ever since
placement of two coronary artery
stents 12 weeks ago. He needs to
undergo spinal surgery. Please
tell me how to best manage him
perioperatively to be sure that he
does not bleed, does not have a venous
thromboembolism, and does
not occlude the stent. Oh, and by
the way, his brother had a stroke
two weeks ago, so he is particularly
anxious about an untoward
event.” If that sounds familiar, you
are in luck today.
This morning from 9:30 a.m. to
11:00 a.m. in the Sidney Marcus
Auditorium, Level 4, Building
A in the GWCC, the Education
“Perioperative
Hematology: To Bleed or Not To
Bleed,” will be presented. Experts
will provide insightful and practical
knowledge on the clinical management
of perioperative bleeding and
thrombosis including how to prevent
it and how to treat it. Led by
Sam Schulman, MD, PhD, McMaster
University, the assembled cast
will wax poetic on a very challenging
area in hematology.
Thomas L. Ortel, MD, PhD, Duke
University Medical Center, will
kick off the session by focusing on
“Perioperative Management of Patients
on Chronic Antithrombotic
Therapy.” Dr. Ortel will discuss key
components of preoperative risk
assessment, both thrombotic and
bleeding;
preoperative
manage-
ment of anticoagulants, including
when to discontinue therapy; and
how to incorporate patient-specific
and procedure-specific factors into
clinical recommendations. He will
also
discuss management of pa-
tients on new oral anticoagulants,
both direct thrombin inhibitors and
Factor 10 inhibitors, and those on
anti-platelet therapy.
Next, Jeannie Callum, MD, from
Sunnybrook Health Sciences Centre
in Toronto, ON, will present “Assessing
Perioperative Bleeding.” Attendees
will hear updates on how to
assess bleeding risk prior to surgery
and how the laboratory can best
support clinical management during
assessment and care of the massively
bleeding patient. Dr. Callum
will also present data on the use
of pharmacologic agents as well as
blood products to achieve optimal
outcomes in massive transfusion,
and will provide guidance for others
to establish massive transfusion
protocols at their institutions.
Dr. Schulman will close with a
talk on “Pharmacologic Tools to Reduce
Bleeding in Surgery.” He will
provide updates on how to enhance
coagulation and inhibit fibrinolysis
for safe and improved patient care
are
ultra-large
von Willebrand factor multimers
(ULVWFM). Depending upon the
inciting event, the release of ULVWFMs
may affect the microcirculation
of many tissues, or they may
be more limited, usually confined
to the renal microcirculation. The
systemic versions of the thrombotic
microangiopathies
– TTP with
its various triggers
– may often
be explained
by the impaired
function of ADAMTS-13,
the
enzyme formerly
known as “von
Willebrand factor
cleaving protease.”
On the other
hand, the more
limited thrombotic microangiopathies
– like the hemolytic-uremic
syndromes (HUS) – have been
linked to the Shiga toxin produced
by aggressive strains of E. coli or
to alterations of complement activation.
Both of these events can
cause endothelial injury and trigger
the release of ULVWFMs.
This year, ASH will highlight
We now have a better
understanding of
the basis for the wide
variation of clinical
features of these
disorders and how their
treatments work.
a pioneer of TTP and hemolytic HUS
research on Sunday. James George,
MD, of the University of Oklahoma
Health Sciences Center will receive
the Wallace H. Coulter Award for
Lifetime Achievement in Hematology.
Thanks to the systematic study
of TTP/HUS patients by Dr. George
and his colleagues, clinicians now
benefit from a rigorous
clinical description
of these
difficult-to-diagnose
syndromes,
useful guidelines
for their optimal
treatment, and
long-term followup
data for survivors.
During today’s
Education session,
“The Thrombotic
Thrombocytopenic Purpura and Hemolytic
Uremic Syndromes: New
Insights and New Treatments,” at
4:00 p.m.
(Room B405-B407, Level
the substantial progress made in
our understanding of these rare
disorders, by offering an Education
Program session today and
again on Monday and by honoring
4, Building B, GWCC) Dr. George
will discuss the significant limitations
of the traditional clinical diagnostic
“pentad” in identifying
TTP/HUS patients correctly and
how measurement of ADAMTS-13
levels may or may not contribute to
patient management. The risks of
plasma exchange; the role of prednisone,
rituximab, and platelet transfusions;
and late health problems
ASH NEWS DAILY
Saturday, December 8, 2012
identified in survivors of TTP/HUS
will be reviewed as well.
Key insights into these disorders
have been gleaned from the study
of exceptionally rare families with
inherited versions of TTP and HUS.
Johanna Kremer Hovinga, MD, of
Bern University Hospital, Switzerland,
will describe studies of families
with Upshaw-Schulman syndrome,
an inherited deficiency of
ADAMTS-13. She will discuss important
new insights into the molecular
pathogenesis of TTP, how loss
of immune self-tolerance to ADAMTS-13
accounts for most cases of
acquired TTP, and the potential role
of recombinant ADAMTS-13 in future
treatment.
Carla Nester, MD, from the University
of Iowa will review the eclectic
pathogenesis of HUS, in both its
typical and atypical forms. We now
know that atypical HUS is a disease
of excess complement activation,
and that eculizumab, an inhibitor of
the activation of C5, is highly effective
therapy. So after almost a century
of disappointment, persistence,
and slow success, the story of TTP/
HUS seems to be finally unfolding
toward a favorable outcome.
This session will be presented
again on Monday at 2:45 p.m. in
Room B405-B407.
Dr. Bufill indicated no relevant conflicts
of interest.
and the use of transfusion decision
algorithms based on key
laboratory data. Dr. Schulman
will include critically important
guidance on how to prevent and
manage bleeding in patients on
anticoagulants, including the new
oral agents.
Perioperative management of
patients at risk for bleeding and
clotting requires extensive understanding
of the underlying
biology and therapeutic options
and implementation in a systemsbased
approach. The cast of characters
organized by Dr. Schulman
will not only help optimize your
patient management, but their
presentations will most certainly
make Shakespeare proud.
This Education session will be
presented again tomorrow morning
at 7:30 in Room A411-A412,
Level 4, Building A.
Dr. Leavitt indicated no relevant
conflicts of interest.
Table of Contents for the Digital Edition of ASH News Daily 2012 - Saturday, December 8, 2012
ASH News Daily 2012 - Saturday, December 8, 2012
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