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.

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ASH News Daily 2012 - Saturday, December 8, 2012

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