Quinine-Induced Immune Thrombocytopenic Purpura Followed by Hemolytic Uremic Syndrome Paul Glynne, MBBS, MRCP (UK), Alan Salama, MA, MBBS, MRCP (UK), Afzal Chaudhry, BSc, MBBS, MRCP (UK), David Swirsky, MD, MRCP (UK), and Liz Lightstone, MA, MBBS, PhD, MRCP (UK) ● Immune thrombocytopenic purpura (ITP) mediated by quinine-dependent platelet reactive antibodies is well recognized. More recently there have been a number of reports of quinine-induced hemolytic-uremic syndrome (HUS). We describe a patient with quinine-induced immune thrombocytopenia who subsequently developed HUS after re-exposure to a single dose of this drug. To our knowledge, this is the first such case reported. Multiple quinine-dependent antibodies have been characterized in the patient’s serum. Initially, quinine-dependent antibod- ies were directed solely against the platelet glycoprotein complex GPIb/IX. After rechallenge with quinine, there was broadening of quinine-dependent antibody specificities, which were now also directed against the platelet glycopro- tein complexes GPIb/IX and GPIIb/IIIa, endothelial cells, and leukocytes. We have shown quinine-dependent antibody-mediated endothelial cell activation, which supports an immunopathogenic role for quinine-dependent antibodies in the causation of this disease.  1999 by the National Kidney Foundation, Inc. INDEX WORDS: Quinine-dependent antibodies; immune thrombocytopenic purpura; hemolytic uremic syndrome; endothelial cells; endothelial cell activation. T HE HEMOLYTIC uremic syndrome (HUS) is an important cause of acute, often irre- versible, renal failure. It is the clinical manifesta- tion of inappropriate endothelial cell (EC) activa- tion that leads to a procoagulant surface on EC, intravascular hemolysis, platelet aggregation, ad- hesion, and activation of white cells. There have been a number of recent reports of HUS after ingestion of quinine. 1-4 Although qui- nine-dependent platelet-reactive antibodies are well recognized in the causation of immune thrombocytopenic purpura (ITP), 5,6 it is now also clear that quinine-induced HUS is associated with quinine-dependent antibodies directed against a number of cell lines, including EC, leukocytes, and erythrocytes. 7,8 The events triggering EC activation in HUS are unknown. There are surface epitopes com- mon to both platelets and EC, suggesting a common immunopathogenic effector pathway in the origin of this condition. However, direct quinine-induced endothelial cell activation has not been shown. We describe a patient with quinine-induced immune thrombocytopenia who subsequently developed HUS after re-exposure to a single dose of this drug. We have investi- gated the patient’s serum for the presence of quinine-dependent antibodies and their ability to activate endothelial cells. CASE REPORT In December 1996, a 62-year-old man presented with a 10-day history of nausea, vomiting, abdominal pain, increas- ing breathlessness, and one episode of diarrhea. Twenty-four hours before admission he developed a purpuric rash, epi- staxis, hemoptysis, and severe dyspnea. He had long- standing hypertension and atrial fibrillation, for which he was taking amlodipine and digoxin. Importantly, he had presented in May 1996 with purpura, epistaxes, and throm- bocytopenia (platelet count, 5  10 9 /L). Blood film examina- tion and a bone marrow aspirate, showing the presence of abundant megakaryocytes, were consistent with a diagnosis of ITP. Other screening investigations at that time, including an auto-antibody profile, were negative. He recovered after treatment with corticosteroids and intravenous immunoglobu- lin. On routine review 3 weeks before the current admission, he had been well, off corticosteroids, with a platelet count of 230  10 9 /L and a serum creatinine of 80 μmol/L. At presentation in December 1996, he was extremely unwell and tachypneic, with a widespread purpuric rash, epistaxis, and gingival and conjunctival hemorrhages. He was in severe pulmonary edema and oligoanuric renal fail- ure. Initial laboratory investigations showed sodium 131 mmol/L, potassium 8.1 mmol/L, bicarbonate 14 mmol/L, urea 51 mmol/L, creatinine 1,376 μmol/L, hemoglobin 7.4 g/dL, white cell count 9.9  10 9 /L, platelets 5  10 9 /L. Lactate dehydrogenase was elevated at 1204 IU/L. Results From the Renal Section, Division of Medicine, and the Department of Hematology, Division of Investigative Sci- ences, Imperial College School of Medicine, Hammersmith Hospital, London, UK. Received March 12, 1998; accepted in revised form June 26, 1998. Address reprint requests to Liz Lightstone, MA, MBBS, PhD, MRCP (UK), Senior Lecturer in Renal Medicine, Renal Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London W12 ONN, United Kingdom. E-mail: llightst@rpms.ac.uk  1999 by the National Kidney Foundation, Inc. 0272-6386/99/3301-0020$3.00/0 American Journal of Kidney Diseases, Vol 33, No 1 (January), 1999: pp 133-137 133