Thrombocytopenic thrombotic purpura (TTP) and hemolytic uremic syndrome (HUS) form a group of diseases distinguishable by the development of thrombotic microangiopathy. Both are life-threatening disorders classically described by a pentad of symptoms: microangiopathic hemolytic anemia, thrombocytopenia, fever, renal failure and altered mental status. Early initiation of plasma exchange (PEX) is vital when TTP/HUS is suspected. However, diagnostic criteria are imprecise and clinical judgment remains the primary impetus for initiation of treatment. ADAMTS13 levels have not proven to be highly specific or sensitive for diagnosis of outcomes in TTP/HUS, and the delay in laboratory reporting limits its use in the acute setting. There may be other data available that more closely correlates with prognosis. The goal of this single institution retrospective study is to assess (i) the association of easily available clinical and laboratory factors with early death in patients with clinically diagnosed TTP/HUS, and (ii) the association of these factors among survivors with the length of stay (LOS) during the initial hospitalization with TTP/HUS.
After IRB approval, medical record review of adult patients at a single tertiary medical center treated with plasma exchange (PEX) for presumed TTP/HUS between 1999 and May 2013 was performed. For the 62 discrete cases identified, demographic and clinical data was obtained from the medical center and pertinent information was collected. Descriptive analysis was used to evaluate clinical symptoms and laboratory biomarkers with respect to their associations with survival. Episodes of TTP/HUS in the same patient were considered discrete if they occurred greater than 3 months apart. Survival was defined by hospital discharge without readmission for TTP/HUS or their sequelae for 3 months following discharge. The association of demographic factors (age, gender), symptoms (fever, neurologic changes, abdominal pain), and laboratory factors (hemoglobin [Hb], white blood cell count [WBC], platelet count, acute kidney injury [AKI] based on creatinine, AST, ALT, lactate dehydrogenase (LDH), indirect bilirubin, prothrombin time (PT), partial thromboplastin time (PTT), reticulocyte count) with survival during the first 3 months was studied using univariate analysis. ADAMTS13 levels were not included in analysis as the decision to treat with PEX was made in all cases prior to knowledge of any deficiency. All factors that attained a p value of, <= 0.1 were analyzed collectively using logistic regression with backward model selection. For survivors (n=49), the association with length of stay was compared with each of the above factors and was similarly studied using univariate analysis and multiple linear regression.
In our sample (n=62), median age was 48 years and 26 (42%) were male. Of these, 79% (n=49) survived to discharge and did not have relapse or known death until 3 months afterwards. Thirteen (21%) died during hospitalization or within 3 months after discharge. There were 55 TTP and 7 HUS patients included in this retrospective cohort. Acute kidney injury (AKI) was diagnosed in 44 (71%) patients. On univariate analysis, factors associated with death included: AST (p=0.009) and AKI (p=0.045) with trends noted for hemoglobin (p=0.080) and PT (p=0.078). On multiple logistic regression, association with death was observed with AKI (OR: 0.093, 95% CI 0.009 – 0.950, p= 0.04) and hemoglobin (OR: 0.65, 95% CI 0.434 – 0.975, p=0.037). Among the 49 survivors (median age 45.1, range 12-81 years; 28 (57%) were female), correlation of the LOS in hospital with all variables was assessed. On linear regression analysis, elevated white blood cell count (WBC) (p=0.027) and prolonged prothrombin time (PT) (p=0.035) were independently associated with prolonged hospitalization.
Clinical and laboratory markers found to have an independent association with death are AKI and low hemoglobin. It may be possible to risk stratify patients more accurately with clinical algorithms based on this evidence even before ADAMTS13 levels are available. Increased WBC count and prolonged PT are independently associated with increased length of stay. The application of our results could therefore be used for further risk stratification in prospective studies of outcomes in patients diagnosed with TTP/HUS.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.