Preliminary Findings from the Prospective Multicenter Surveillance, Epidemiology and Risk Factors for Thrombotic Thrombocytopenic Purpura (SERF-TTP) Study

Background: Due to the rarity of TTP (approximately 4 cases per million), epidemiologic data and correlative laboratory samples from a prospectively identified incident cohort of TTP patients are needed. Methods: SERF TTP is a NHLBI-funded 15-site study targeted to identify 300 incident TTP patients and 600 age-/gender-matched community controls. Results: From nine IRB-approved collaborating sites, 22 incident TTP cases and 17 controls have been interviewed. Data and plasma (acute and convalescent samples) are available for 19 TTP patients (Table 1). Their mean age is 42.5 years (range, 20 – 80 years), and 90% are female. Using the Rose-Eldor TTP Scoring system based on platelets, creatinine, hemoglobin, and neurologic function, 37% would be classified as severely ill (score > 4 of a maximum 8 points). Mean time from symptom onset to diagnosis was 9.2 days, median 5.5 days (range, 0 to 33 days). Severity of TTP was poorer for the 5 patients whose treatment did not begin for at least 16 days (16–33 days) versus the other 14 patients (mean Rose-Eldor score of 4.6 versus 4). Medications which had been prescribed to the patients prior to TTP onset included herbal supplements (n= 5) and hormone replacement therapy or oral contraceptives (n= 6). All patients received at least daily therapeutic plasma exchange (TPE). A platelet count >150,000 was reached at a mean of 9.4 days following TPE initiation. At 30-days follow-up, all patients were alive, although 3 had an exacerbation requiring daily TPE reinstitution. Fourteen patients (78%) experienced an adverse event, including allergic reactions to plasma (n=9), citrate-related toxicity (n=9) and venous access complications (n=2) including one with major hemorrhage requiring transfer to the intensive care unit. Conclusion: The clinical characteristics of the SERF-TTP cohort are similar to those reported from large single-site studies, although the survival rate (100% versus 71% and 83%) is higher. Only a minority of incident TTP cases in the modern era present with renal insufficiency or neurologic findings - highlighting the importance of developing reliable diagnostic laboratory testing. Clinical Characteristics at Presentation Study Platelets 2mg/dl Fever Neurologic symptoms Mortality (1) Zheng XL, Kaufman RM et al. Blood.2004; 103: 4043; (2)Vesely SK, George JN et al. Blood.2003; 102: 60. HSCT: Hematopoetic stem cell transplantation, FK-506: Tacrolimus. SERF-TTP n=19 95% 79% 32% 11% 47% 0% Washington University (1) (excluding HSCT/FK506 cases) n= 28 96% 82% 29% 32% 50% 29% Oklahoma TTP-HUS Registry (2) (ADAMTS13 < 5%) n=18 100% 100% 22% NA (Not Available) 56% 17%