allopurinol and Pancytopenia

A previously healthy 74-year-old patient without a prior history of hematological disease presented with an acute respiratory infection. Peripheral pancytopenia led us to perform a bone marrow biopsy, and the diagnosis of undifferentiated acute myelogenous leukemia (AML, 61% blasts) was made. Following antibiotic treatment and resolution of the infection, the blast count in the bone marrow fell to 2%, leaving a clinicopathologic picture consistent with myelodysplastic syndrome (MDS, French-American-British type refractory anemia), and the patient survived for a total of 16.5 months following the initial presentation with cytokine support. A preterminal blast proliferation occurred during a bacterial ear infection and rapidly responded to a withdrawal of cytokine support, antibiotic therapy, and hydroxyurea. The patient succumbed ultimately to an apparent myocardial infarct. Clinicians should consider transient acceleration of MDS in their differential diagnosis when confronted with apparent AML and acute infection.

Topics: Acute Disease; Aged; Allopurinol; Anemia, Refractory; Anti-Bacterial Agents; Biopsy; Blood Cell Count; Bone Marrow; Death, Sudden, Cardiac; Diagnosis, Differential; Diagnostic Errors; Drug Therapy, Combination; Fatal Outcome; Granulocyte Colony-Stimulating Factor; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Male; Otitis Media; Pancytopenia; Respiratory Tract Infections

Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited.. A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study.. Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups.. Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns.

Topics: Administration, Oral; Adult; Alanine Transaminase; Arginine; Aspartate Aminotransferases; C-Reactive Protein; Cardiovascular Diseases; Double-Blind Method; Endothelium, Vascular; Enzyme Inhibitors; Febuxostat; Female; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Pancytopenia; Placebos; Prospective Studies; Renal Dialysis; Risk Factors; Treatment Outcome; Uric Acid; Xanthine Oxidase

BACKGROUND Pancytopenia is a hematological condition which is characterized by decreases in all three cellular elements: RBC, WBC, and platelets. As a result, patients with pancytopenia are more prone to anemia, infections, and excessive bleeding. Pancytopenia can be caused by medications or drug interactions that suppress the bone marrow. This case report highlights a drug interaction between allopurinol and mercaptopurine which led to pancytopenia and septic infection, resulting in the patient's death. This could easily have been avoided if a clinical pharmacist had been consulted. CASE REPORT A 55-year-old female patient with a past medical history of gout, depression, back pain, and type 2 diabetes was recently diagnosed with ulcerative colitis and was discharged with a new prescription of mercaptopurine. After 2 months of concurrent use of allopurinol and mercaptopurine, she developed infected foot ulcers, which progressed rabidly to sepsis. At the time, her laboratory findings confirmed pancytopenia. Despite treatment, the patient died. CONCLUSIONS This case illustrates the importance of consulting a clinical pharmacist in order to avoid such medical error. The dose of mercaptopurine should be reduced to 25% of the recommended dose when it is given concurrently with allopurinol to reduce the risk of pancytopenia. Health care providers should think about the significant role of clinical pharmacy services. In our case, there were no clinical pharmacist involved in the care of this patient, and as a result of such negligence, the patient lost her life.

Topics: Allopurinol; Colitis, Ulcerative; Diabetic Foot; Drug Interactions; Fatal Outcome; Female; Gout; Gout Suppressants; Humans; Immunosuppressive Agents; Mercaptopurine; Middle Aged; Pancytopenia; Pharmacists; Pharmacy Service, Hospital; Referral and Consultation; Sepsis

To investigate the clinical and pathologic features of patients with drug reaction with eosinophilia and systemic symptoms (DRESS) in Taiwan.. Case series and retrospective analysis.. A medical referral center in Northern Taiwan.. Sixty cases of DRESS occurring from June 1998 to May 2008.. Clinical characteristics for specific drugs and important prognostic factors in DRESS.. Patients ranged in age from 6 to 90 years (mean age, 51 years). The female to male ratio was 1.3 to 1. The most common culprit drugs were allopurinol, phenytoin, and dapsone. Exanthematous eruption was the most common skin manifestation, but purpurae and blisters were also observed. Hepatic (80%), renal (40%), and pulmonary (33%) involvement were also common. The overall mortality rate was 10%. Allopurinol-induced DRESS was characterized by preceding chronic renal insufficiency and frequent renal involvement. Pancytopenia indicated a poor prognosis.. Drug reaction with eosinophilia and systemic symptoms has a variable clinical presentation, and its definition requires clarification. It may be a heterogeneous syndrome with some particular patterns related to different drugs. Early diagnosis and prompt discontinuation of offending drug regimens are essential.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Infective Agents; Anticonvulsants; Child; Dapsone; Drug Eruptions; Eosinophilia; Female; Gout Suppressants; Humans; Male; Middle Aged; Pancytopenia; Phenytoin; Prognosis; Retrospective Studies; Risk Factors; Taiwan; Young Adult

Azathioprine has been used in rheumatology for more than twenty years. Indications are collagen diseases with multiorgan involvement, where co-medications are frequently necessary. We describe a patient suffering from pancytopenia following a combination therapy of azathioprine and allopurinol because of lupus erythematodes and diabetic nephropathy with hyperuricemia.

Topics: Aged; Allopurinol; Antirheumatic Agents; Autoantibodies; Azathioprine; Blood Cell Count; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Erythrocyte Count; Female; Gout Suppressants; Hematopoiesis; Humans; Hyperuricemia; Lupus Erythematosus, Systemic; Pancytopenia

To study the clinical impact of gout treatment following cardiac transplantation.. We performed an audit of all cardiac transplant recipients of the Alfred Hospital before August 1998 who lived in Victoria.. We studied 225 patients (81% men), with a mean post-transplant follow-up of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring post-transplantation. Twenty-three patients developed gout de novo. Of the 24 patients who received allopurinol, 6 developed pancytopenia and required hospitalization. Fourteen received a change in immunosuppression: in 5 patients following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two patients received colchicine; 5 developed neuromyopathy. Impaired renal function, diuretic use, and hypertension were more common in this sub-group. Non-steroidal anti-inflammatory agents, used in 16 patients, caused serious complications in 1 patient (life-threatening peptic ulceration and hemorrhage, precipitating dialysis-dependent chronic renal failure).. Cardiac transplant recipients, when treated for gout, are at high risk of therapeutic complications. Thus, gout treatment significantly affects care, health, and immunosuppression of these patients.

Topics: Adolescent; Adult; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Female; Gout; Heart Transplantation; Humans; Male; Middle Aged; Pancytopenia

(1) Allopurinol increases the haematological toxicity of azathioprine and mercaptopurine, with a risk of pancytopenia. (2) Combination of allopurinol with azathioprine or mercaptopurine should be avoided.

Topics: Allopurinol; Antimetabolites; Contraindications; Drug Interactions; Humans; Mercaptopurine; Pancytopenia; Treatment Outcome

We reported a rare case of pancytopenia caused by allopurinol. A 61-year-old man was first admitted in May 1993, because of thrombocytosis. He had suffered from chronic glomerulonephritis. He was administered allopurinol for hyperuricemia from March 1993. On first admission the laboratory findings revealed leukocytosis (10,100/microliter) and thrombocytosis (971 x 10(3)/microliter) in the peripheral blood. Myelofibrosis was strongly suspected due to increased number of MgK and reticular fiber in the bone marrow. Two months later, he readmitted due to pancytopenia (WBC 1,300/microliter, Hb 6.2g/dl, Plt 10 x 10(3)/microliter). His bone marrow showed markedly hypocellular. Because we suspected that pancytopenia was induced by allopurinol, we discontinued allopurinol and administered oxymetholone, G-CSF, and EPO, WBC, RBC, and platelet count had been recovered about one and half months later. In vitro co-culture indicated that CFU-G, E, and Meg in the bone marrow cells after recovery from pancytopenia were markedly suppressed in the presence of patient's serum and oxipurinol. Pancytopenia due to allopurinol was reported to be rare, and some authors showed that it will sometimes be fatal. Because pancytopenia of this case had been recovered in a relatively short time with cytokine therapy, it was thought to be effective for pancytopenia due to drug like this case.

Topics: Allopurinol; Antimetabolites; Drug Therapy, Combination; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Myeloproliferative Disorders; Oxymetholone; Pancytopenia; Recombinant Proteins

To report the price of a drug interaction between azathioprine and allopurinol that resulted in pancytopenia in a patient who had undergone a heart transplant.. A 63-year-old white man who received an orthotopic heart transplant in 1987 was hospitalized in June 1991 with a diagnosis of pancytopenia. His immunosuppressive medications on admission included cyclosporine 125 mg bid, azathioprine (AZA) 200 mg/d, and prednisone 2.5 mg/5 mg every other day. Six weeks prior to admission, the patient's local physician prescribed allopurinol for left wrist pain suspected to be gout. It was determined that the pancytopenia was caused by the drug interaction between AZA and allopurinol, both of which were withheld on admission. During hospitalization, the patient's white blood cell count dropped to 1.1 x 10(3)/mm3 with an absolute neutrophil count of less than 0.5 x 10(3)/mm3, a platelet count of less than 20 x 10(3)/mm3, and a hemoglobin of 3.7 g/dL. Four units of packed red blood cells were transfused and regramostim (GM-CSF) therapy was begun on hospital day 3 to speed the marrow recovery process. The patient was discharged on hospital day 8 and AZA, which had been withheld since admission, was restarted. The dosage was titrated to 200 mg/d over the following 2 weeks. The price of this patient's hospital stay was $13,042.. Not included in this price was the effect this drug interaction had on the patient's quality of life. Even after discharge from the hospital, it was estimated that it would take up to 3 months for the patient to fully recover his previous level of strength and functional capability. This interaction between AZA and allopurinol could easily have been avoided. Both the physician and the pharmacist missed this well-documented and potentially life-threatening drug interaction. Also, the patient failed to notify the transplant team when allopurinol was prescribed by his local physician. The importance of patient responsibility for medication therapy must be stressed to help avoid unnecessary drug interactions.. Undetected drug interactions can be life-threatening to patients as well as costly to the healthcare system. Drug interactions also can have a profound negative effect on the patients' quality of life, the price of which cannot be measured in dollars alone. It is vital that the physician, pharmacist, and patient work together to optimize therapeutic outcomes and avoid unnecessary drug interactions.

Topics: Allopurinol; Azathioprine; Cost of Illness; Drug Interactions; Gout Suppressants; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Pancytopenia; Quality of Life

Topics: Allopurinol; Azathioprine; Chemical and Drug Induced Liver Injury; Drug Synergism; Drug Therapy, Combination; Graft Rejection; Hemolysis; Humans; Kidney Transplantation; Male; Middle Aged; Pancreatitis; Pancytopenia; Postoperative Complications; Uric Acid

Topics: Allopurinol; Azathioprine; Drug Therapy, Combination; Humans; Male; Middle Aged; Pancytopenia

A leukaemic child is described who presented with renal failure and gout attributable to hyperuricaemia before the leukaemia could be diagnosed.

Topics: Acute Kidney Injury; Allopurinol; Child, Preschool; Female; Gout; Humans; Leukemia, Lymphoid; Pancytopenia; Prednisolone; Uric Acid; Vincristine