Clinical Pathology Conference 討論篇

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. Thrombocytopenia2. Conscious disturbance3. 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 disordercharacterized by platelet aggregates in

microvasculature vessel occlusion tissue ischemia and end-organ damage

Male: female ratio of 1: 2Prompt 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: 177-99, .

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 < 20×103) 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 1.0-1.5 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