2009 年一般醫學系臨床病理討論會 Clinical Pathology Conference 討論篇 報告者：第 年住院醫師

Hospital course  PB smear Anisocytosis: 3+ Microcytosis: 1+ Chromic: normochromic Fragmented RBC: found  Hemolytic anemia was confirmed unconjugated hyperbilirubinemia, nucleated red cells, increased RDW, anisocytosis, fragmented RBC

Hospital course  Summary of abnormality 1.Thrombocytopenia 2.Conscious disturbance 3.Hemolytic anemia  Three of the pentad of thrombotic thrombocytopenic purpura (TTP) was matched  No other feasible diagnosis can explain all the abnormality

Hospital course  Plasmaphoresis was arranged  Dexamethasone was given  Empiric antibiotics was prescribed because of fever up to 38.4 ℃ after admission  Two days after admission, an episode of generalized-tonic-clonic seizure occurred. Diazepam and phenytoin were used. The CT of brain was arranged and there was no intracranial hemorrhage

Hospital course  Her conscious level didn’t improve after all this therapeutic management  Bradycardia then asystole occurred at the second hospital day. Cardiopulmonary resuscitation was performed but failure.

Thrombotic thrombocytopenic purpura (TTP)  Potentially fatal disorder characterized by platelet aggregates in microvasculature vessel occlusion tissue ischemia and end-organ damage  Male: female ratio of 1: 2  Prompt diagnosis is mandatory so emergency treatment can be instituted immediately Current Opinion in Neurology. 2003;16:367-73, Hematol Oncol Clin North Am. 2003;17: ,.

Etiology and precipitating factor  Pregnancy  Drugs e.g. ticlopidine, clopidogrel, oral contraception, cyclosporin, mitomycin C and quinine  Autoimmune disorders such as SLE  Infection particularly HIV, toxigenic strains of Shigella and Escherichia coli  Post bone marrow or solid organ transplantation  Post coronary artery bypass graft- 13 cases reported W V Med J.2004; 100(2): 64-6.

Pathophysiology  von Willebrand factor (vWF) endothelial cells and megakaryocytes normally make monomers of vWF that are joined to form larger vWF multimers  Under normal conditions, vWF-cleaving metalloprotease (ADAMTS13) cleaves these multimers

Clinical and laboratory features  Classical pentad (complete pentad< 30%) Thrombocytopenia (platelet count < 20×10 3 ) Microangiopathic hemolytic anemia (MAHA) Neurologic impairment (63-70%) Renal impairment (59%) Fever  Chest pain, abdominal pain

Clinical and laboratory features  RBC fragmentation (schistocytes) ↑ Reticulocyte (increased RBC turnover) ↓ Haptoglobin (binding to free Hb) ↑ LDH (hemolysis, ischemic organs)  Renal or liver impairment (representing ischemic organs)  ↑ Unconjugated (indirect) bilirubin  DAT (direct Coombs test) negative  Normal coagulation studies

Treatment  Plasma exchange (mainstay of therapy ) Superior to plasma infusion Instituted within 24h of presentation plasma volume exchanges qd (40 mL/kg) LDH, usually used as a day-to-day indicator of the severity of hemolysis, along with Hb value and reticulocyte count In the Canadian Apheresis Trial, complete remission is defined as normalization of platelet count for 2 consecutive days with no deterioration in neurological status

Treatment  Cryosupernatant (cryoprecipitate- poor plasma) lacking vWF at least as effective as FFP

Adjunctive therapy  Corticosteroids methylprednisolone 1g IV qd, or prednisolone 1mg/kg PO qd  Antiplatelet agents aspirin and dipyridamole not accepted universally, and might exacerbate the risk of bleeding  RBC transfusion as needed

Contraindications  Platelet transfusions  Desmopressin (DDAVP) releasing vWF from the endothelial cells into blood

Refractory TTP and Immunosuppressive therapies  Vincristine (Immunosupression) case reports or small retrospective studies  Rituximab (anti-CD20 Ab) first use in recent reports  Splenectomy removal of the B cells responsible for the production of autoantibodies inhibiting ADAMTS13