Self-evaluation Tutorial 2009 Prof Dr Irene Lorand-Metze State University of Campinas SEV 3.2 start Male 34 years old patient. He came to the Emergency Unit of our Hospital referring high fever and cough for 3 days. Sputum was greenish. The patient suffered from schizophrenia and was using clozapine. Physical examination: he was in a bad physical condition. Blood pressure: 105 x 75 mmHg. Heart frequency: 98 beats/min Cefalexine had been instituted. Peripheral blood counts • Hb : 11.1 g/dl • MCV: 85 fl • MCH: 28 pg • Platelets: 133 x 109 /l • Leukocytes: 0.3 x 109 /l neutrophils: 0.1 x 109 /l Avaliação clínica inicial • Dados clínicos sugerem pneunonia lobar • Hemograma: a série mais afetada é a granulocítica • Hb e plaq. Excluem aplasia e leucemia aguda • Até agora parece uma agranulocitose • Nos antecedentes, tem medicação que pode dar agranulocitose (clozapina) Question 1 • According to the clinical data and the peripheral blood counts, which is the most probable diagnosis? 1. Agranulocytosis due to psychotropic agents and infection 2. Acute leukemia and pneumonia 3. Aplastic anemia and pneumonia 4. Myelodysplastic syndrome and infection 5. Fanconi’s anemia and septicemia Question 2 • Which laboratory tests should be collected immediately? 1. 2. 3. 4. 5. Chest radiography Bone marrow cytology and cytogenetics Investigation of PNH Bone marrow cytology and chest radiography Bone marrow histology and DEB test Confirmar a pneumonia neutropenia → mielograma Question 3 - introduction • The chest radiography revealed a pneumonia of the inferior lobe of the left lung. • BM cytology showed: Granulocytic series with blasts and promyelocytes: 11% (Fig 1); erythroblasts: 58% (Fig 2); lymphocytes: 28%; megakaryocytes +++ (Fig 2) Bone marrow cytology Diagnóstico final • Agranulocitose (por clozapina) e pneumonia lobar • Para causas, ainda excluir: • SMD → cariótipo • HPN → pesquisa de deficiência de proteínas ancoradas GPI (CD55, CD59, CD66b, CD14) • Anemia de Fanconi → DEB test Question 3 • And now, which tests are necessary to conclude the diagnosis? 1. 2. 3. 4. 5. Karyotype Investigation for PNH DEB test 1+3 All the above-mentioned tests Question 4 • Karyotype was normal. Expression of CD66b and CD14 on granulocytes or monocytes could not be performed due to the small number of cells in the peripheral blood. DEB test was negative. • What is now the most probable final diagnosis? 1. Aplastic anemia 2. Myelodysplastic syndrome 3. Agranulocytosis due to clozapine 4. Acute leukemia 5. Fanconi’s anemia Question 5 - introduction • After one month, the infection resolved and the patient was discharged. The psychiatrist changed clozapine to risperidone and DZP. • PB counts: Hb : 8.8 g/dl; leukocytes: 5.7 x 109 /l; neutrophils: 3.1 x 109 /l; platelets: 100 x 109 /l Bone marrow cytology BM: erythroblasts: 24%; granulocytes: 63% blasts: 0.5%. Megakaryocytes: +++ Question 5 • What is the cause of the increased granula found in the granulocytic precursors? 1. 2. 3. 4. 5. a sign of persisting infection due to the use of G-CSF indicative of a myelodysplasia due to BM recovery a sign of myelotoxicity (psychotropic drugs) Question 6 • Why does the hemoglobin and the platelet did not fully recover? 1. The patient has aplastic anemia 2. Vitamin deficiency due to the use of parenteral nutrition 3. Myelotoxicity of the antibiotics used 4. the new psychotropic agents are also myelotoxic 5. The patient suffers from PNH. This could not be clarifyed during the infection and low granulocyte counts. • Anemia aplástica excluída: não houve pancitopenia desde o início. Os mielogramas são celulares • HPN: não há dado outro dado clínico que sugere. Mas, se houver dúvida, pode-se repetir • Deficiênica vitamínica: deveria ter sido dosado ácido fólico e B12. Pode ocorrer em pacientes com sepse. Ver a nutrição parenteral e suplementar. A segunda citologia fala contra Agranulocitose - causas • Infecções – Virais: HIV, dengue, hepatite, CMV Bacterianas: Gram – tbc, febre tifoide Fungo: histoplasmose Protozoários: calazar, malária • Autoimunidade – d. Still, LED, etc • Nutricionais - distúrbios alimentares, anemias carenciais Medicamentos e agranulocitose • Analgésicos: dipirona, indometacina, etc • Psicotrópicos: clozapina, risperidona, diazepam, haloperidol • Anticonvulsivantes • Anti-tireoidianos (tiouracil) • Antibióticos, drogas cardiovasculares (captopril, propanolol, nifedipina) • etc SEV conclusion • • • • • • Question 1 - 1 Question 2 - 4 Question 3 - 5 Question 4 - 3 Question 5 - 2 Question 6 - 4