American Journal of Hematology 47:94-99 (1994) z Serum Lactate Dehydrogenase and Platelet Count Predict Survival in Thrombotic Thrombocytopenic Purpura Jeffrey F. Patton, Kenneth R. Manning, Douglas Case, and John Owen Section on Hematology and Oncology, Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina A significant number (some 20%) of patients with thrombotic thrombocytopenic purpura do not respondto standard therapy and die. We reasoned that early identification of those who are likely to fail standard therapy would allow the rational introduction of other treatment modalities. To this end we prospectively evaluated 27 consecutive patients, examining serum LDH levels and platelet counts as markers of disease activity and as predictors of outcome. All patients were treated, accordingto a written protocol, with high volume plasma exchange (35 mllkg), prednisone, aspirin, and persantine. Twenty-one of the 27 patients (78%) are alive following therapy. Initial LDH and platelet values did not distinguish between the survivors and nonsurvivors. However, by day 3 of therapy both LDH levels and platelet counts differed significantly between the two groups. Mean day 3 LDH level for survivors was 364 units/L, and for nonsurvivors, 891 units/L (P < 0.005). Mean day 3 platelet count for survivors was 119,OOO/pL, and for nonsurvivors, 46,OOO/pL (P < 0.005). Receiver Operator Characteristic curves were constructed and assessed by calculating the area under the curve. This analysis showed that LDH is able to discrimi- nate survivorship one day earlier than platelet count. Both LDH level and platelet count are excellent predictors of survival, under standard therapy, after 3 days of treatment. Early identification of those at greatest risk will facilitate the early institution and evalua- tion of alternative methods of treatment, such as splenectomy, intravenous lg, or Vincris- tine. zyxwvutsr o 1994 wiley-Liss, Inc. Key words: TTP, LDH, platelets, prognosis, ROC INTRODUCTION zyxwvutsrq Thrombotic thrombocytopenic purpura (TTP) zyxwvu is an un- common disorder first described by Moschcowitz in 1924 [l]. The disorder is characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic symptoms, renal disease, and fever [2]. The etiology remains undefined. Untreated TTP car- ries a high mortality rate, as high as 95% [3], but recent reports have demonstrated a marked reduction in mortal- ity with rates of 9-22% using high volume plasma ex- change [&]. Rock et al. zyxwvuts [5] demonstrated an improved response with plasma exchange as compared to plasma infusion; however, the role of other agents such as corti- costeroids, aspirin, and dipyridamole in the treatment of ?TP remains unclear. Despite the improvement in mor- tality with the use of plasma exchange, there remains a substantial subset of patients (9-22%) who die from their disease. If these patients could be identified early in the course of their illness, they might benefit from an escala- @ 1994 Wiley-Liss, Inc. tion of standard therapy or a change to alternative ther- apy. Several studies have noted that serum lactate dehydro- genase (LDH) is elevated, often markedly zyx so, in patients with TTP, and that this value returns to normal with successful treatment while remaining elevated with un- successful treatment [6-91. Although the cause of this elevation is uncertain, we decided to examine further the usefulness of LDH as a marker of disease activity and as a prognostic factor in TTP. We report here on all patients treated for acute zyxw TTP at our institution between January 1, 1988 and December 31, 1992, and on our analysis of Received for publication October 25, 1993; accepted April 13, 1994. Address reprint requests to John Owen, M.D., Section on Hematology/ Oncology, Bowman Gray School of Medicine of Wake Forest Univer- sity, Medical Center Boulevard, Winston-Salem, NC 27157-1082.