Quinine-Induced Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS): Characteristic Clinical Presentation and High Risk for Chronic Kidney Disease (CKD)

Abstract

Abstract▪2216▪This icon denotes a clinically relevant abstract Introduction:Quinine is the most common cause of drug-induced TTP-HUS in the Oklahoma Registry, 1989–2010. In 52 of all 415 clinically diagnosed patients the cause of TTP-HUS was attributed to a drug; in 25 of these 52 patients, quinine was the suspected drug; in the other 27 patients, chemotherapy agents were the suspected cause in 17, cyclosporine in 3, and 6 different drugs in the other 7 patients. Our goal was to describe the presenting clinical features and long term outcomes of patients with quinine-induced TTP-HUS. Methods:We developed an algorithm to define the causal relation between a drug and the occurrence of TTP-HUS that included patient history (precise time interval between drug exposure and onset of symptoms, occurrence of systemic symptoms with previous exposure to the drug) and documentation of drug-dependent antibodies. Presenting clinical features of patients with quinine induced TTP-HUS were compared to patients with TTP and severe ADAMTS13 deficiency. ADAMTS13 activity has been measured in 299 of 321 (93%) patients, 1995–2010. 68 of 299 (23%) had severe ADAMTS13 deficiency. Glomerular filtration rate (GFR) was calculated by the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation (Ann Int Med 2009;150:604). Results:Using this algorithm, 19 of 25 quinine patients had a definite causal relation of quinine to TTP-HUS; among the other 6 quinine patients the causal relation was probable in 1, possible in 2, and unlikely in 3. Among the 27 patients with other suspected drugs, only 1 (gemcitabine) had a definite and 1 (alendronate) had a probable causal relation. In the other 25 patients the causal relationship between the drug and TTP-HUS was only possible or unlikely. The characteristic presenting symptoms of the 19 patients with a definite quinine cause were the sudden onset of fever and chills, gastrointestinal (GI) symptoms, and oliguria. Nine of the 19 patients had had previous systemic symptoms with previous quinine exposure, including two patients with previous episodes of TTP-HUS for which the quinine cause had not been recognized. Sixteen of the 19 patients had ADAMTS13 activity measurements (median, 63%; range 25–100%); their presenting clinical features were significantly different from the 68 patients who had TTP associated with severe ADAMTS13 deficiency, except the frequency of female gender.Clinical featureQuinine (N = 16)ADAMT S13 <10% (N = 68)PAge (median, range)57 (35–77)40 (9–71)<0.001Race (% white)16 (100%)42 (62%)0.002Gender (% women)15 (94%)55 (81%)0.214Fever/chills9 (56%)7 (10%)<0.001GI symptoms16 (100%)47 (69%)0.009Severe neurologic abnormalities1 (6%)35 (52%)<0.001Oliguria/anuria16 (100%)2 (3%)<0.001Hematocrit (%, median, range)23 (19–36)21 (13–33)0.011Platelet count (/uL, median, range)28 (6–54)10 (2–101)<0.001LDH (U/ml, median, range)2762 (339–5878)1372 (256–3909)0.001Creatinine (mg/dL, median, range)8.8 (3.7–15.2)1.5 (0.7–6.6)<0.001Pentad of presenting features4 (25%)4 (6%)0.040Of the 19 patients with a definite quinine cause of TTP-HUS, 1 died and 3 recovered with end-stage renal disease, requiring permanent dialysis and kidney transplantation in two patients. The remaining 15 patients have been followed for a median of 4.8 years (range, 1.2 – 13.8 years). Four have CKD with severely decreased glomerular filtration rate [GFR] (15–29 ml/min/1.73 m2), 7 have CKD with moderately decreased GFR (30–59 ml/min/1.73 m2), and 4 have normal GFR (≥60 ml/min/1.73 m2). Conclusion:Quinine is a common cause of drug-induced TTP-HUS with characteristic clinical features. It is a severe systemic disorder that can cause death and commonly causes CKD. The quinine cause may not be recognized because quinine exposure, from occasional tablets for leg cramps or from tonic water, may be overlooked. Disclosures:No relevant conflicts of interest to declare.