Mortality and Morbidities During Long-Term Follow-up After Recovery From Thrombotic Thrombocytopenic Purpura (TTP)

Since recovery from an acute episode of TTP is typically assumed to be complete, subsequent survival has been commonly assumed to be normal except for the risk of death with relapse. However we have observed unexpectedly high mortality among patients in the Oklahoma TTP-HUS Registry who had recovered from their initial episode of TTP. Therefore we documented long-term survival and compared the mortality of our patients to the US population data. To investigate possible risk factors for increased mortality, we documented the frequency of common risk factors for poor health outcomes: abnormal renal function, increased body mass index (BMI), hypertension (HTN) and diabetes (DM).

We included all 68 Oklahoma TTP-HUS Registry patients whose initial episode was associated with severe ADAMTS13 deficiency (<10%), 1995–2010. Health outcome measures for renal function were glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR). BMI and HTN and DM preceding TTP were documented at the time of the initial episode. HTN, DM, GFR, and ACR were documented on patients who survived their initial episode at the time of their last follow-up. HTN and DM were documented by the use of regularly prescribed medication. GFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. ACR was quantified on a random urine sample. Population data were obtained from the National Health and Nutrition Examination Survey (NHANES); we calculated expected proportions based on the age, race, and gender composition of our patient group. We used survival data analysis to compare the mortality of the patients to the U.S. population; we used one way chi-square to compare the relative frequency of BMI, GFR, ACR, HTN and DM of the patients to the expected proportions from the US population.

Fifty-five of the 68 consecutive patients survived their initial episode of TTP. At the time of their initial episode, the median age of the 55 patients was 39 years (range 9–71); 44 (80%) were women; 20 (36%) were black. Median follow-up to August 1, 2012 was 9.5 years (range, 2.3–16.7 years). At the time of their initial episode, BMI was significantly greater than the US population (p<0.001); in 15 (27%) of the 55 patients, BMI was >40 kg/m², indicating morbid obesity. Although the relative frequency of hypertension (16%) and diabetes (9%) was not different from the US population preceding the initial episode of TTP, the relative frequencies were significantly greater than the US population at the time of their last follow-up (hypertension, 47%, p<0.001; diabetes, 22%, p=0.003). The GFR (measured in all 55 patients) and ACR (measured in 37 patients) were not different from the US population (p=0.374 and p=0.053). Nineteen (35%) patients have had 1–4 subsequent episodes of TTP. Eleven (20%) of the 55 patients have died (median age at death, 51 years; range, 41–82), a mortality proportion significantly greater than the age/race/gender matched U.S. population (Table). Two of the 11 patients died during their first relapse. Although relapsed TTP was not an apparent cause of death in the remaining 9 patients, 2 deaths were sudden and unexpected; 7 followed prolonged illnesses: congestive heart failure/myocardial infarction (3), sepsis (2), respiratory failure, ovarian cancer.

Long-term survival after recovery from an acute episode of TTP is significantly less than the age/race/gender-matched US population. Although relapse contributes to increased mortality, the significantly increased relative frequency of hypertension and diabetes are important and previously unrecognized risk factors for poor health outcomes in TTP survivors.

Terrell:Baxter, Inc.: Consultancy; Amgen, Inc.: Consultancy. Kremer Hovinga:Baxter Healthcare: Consultancy, Research Funding. George:Alexion, Inc.: Consultancy; Baxter, Inc.: Consultancy; Amgen, Inc.: Consultancy, PI for clinical trial involving romiplostim, PI for clinical trial involving romiplostim Other, Research Funding.