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Pancytopenia and “B” Symptoms in a Previously Healthy Female Robert J. Hoffman MD December 20, 2006
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Presentation 34 year old female with a history of hypothyroidism presents with abdominal pain, weakness, night sweats, fevers and weight loss. 15 lb unintentional weight loss over 6 weeks Fevers to 101° Recent drenching night sweats Diffuse moderate abdominal pain
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HPI 5-6 weeks of progressive diffuse abdominal pain 5-6 weeks of progressive diffuse abdominal pain Waxes and wanes Better with food Moderate severity New DOE restricting her activity as well New DOE restricting her activity as well Recent diagnosis of Barrett esophagus Recent diagnosis of Barrett esophagus
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PMH Hypothyroidism Hypothyroidism Barrett esophagus based on recent EGD Barrett esophagus based on recent EGD GERD GERD
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Medications Prilosec Prilosec Synthroid Synthroid OCP OCP
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Social History No tobacco, alcohol or illegal drug use No tobacco, alcohol or illegal drug use Single Single Works as an accountant Works as an accountant
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Physical Examination Vitals: T: 98.5 P: 98 RR: 16 BP: 109/41 General: Comfortable appearing, pale, NAD Abd: soft, moderate epigastric and RUQ tenderness. No organomegaly No LAD Otherwise normal exam.
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Labs 1.9 16 5.9 126 140 3.9 103 23 9 0.9 87 MCV: 102 Retic: 2.3% Preg: negative ALT: 36 AST: 27 TBili: 1.8 Alk Phos: 47 LDH: 883 64% PMN 32% Lymph 2% monos 1% eos
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10mm, 8mm, 4mm liver lesions 10mm, 8mm, 4mm liver lesions 5 x 3 cm pelvic mass 5 x 3 cm pelvic mass Small amount of pelvic ascites Small amount of pelvic ascites CT Abdomen
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Initial Hospital Course MRI orderd to f/u pelvic mass. MRI orderd to f/u pelvic mass. Hematology consult obtained, bone marrow biopsy planned for Monday. Hematology consult obtained, bone marrow biopsy planned for Monday. PRBC transfusion PRBC transfusion Haptoglobin < 6, consistent with hemolysis Haptoglobin < 6, consistent with hemolysis LDH elevated LDH elevated
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Hospital Course MRI reveals pelvic “mass” to be an enlarged vaginal vault. MRI reveals pelvic “mass” to be an enlarged vaginal vault. u/s fails to confirm liver nodules u/s fails to confirm liver nodules Decreased bone marrow signal found on MRI c/w marrow replacement Decreased bone marrow signal found on MRI c/w marrow replacement
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Summary Pancytopenia Pancytopenia “B” symptoms “B” symptoms Abdominal pain Abdominal pain Decreased marrow signal Decreased marrow signal Intravascular hemolysis Intravascular hemolysis
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Phew! B12 returns 78 pg/ml B12 returns 78 pg/ml Homocysteine and methylmalonic acid elevated Homocysteine and methylmalonic acid elevated Anti-parietal cell antibody positive. Anti-parietal cell antibody positive. B12 supplements initiated B12 supplements initiated Bone marrow shows hypercellularity and erythroid hyperplasia, consistent with vitamin B12 deficiency Bone marrow shows hypercellularity and erythroid hyperplasia, consistent with vitamin B12 deficiency
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Outcome At one week follow up patient states she “feels better than she has in years” At one week follow up patient states she “feels better than she has in years” Hemoglobin was 9.2 g/dl on d/c and 11.8 g/dl at one week follow up. Hemoglobin was 9.2 g/dl on d/c and 11.8 g/dl at one week follow up. Other cytopenias resolve. Other cytopenias resolve.
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Pernicious Anemia Autoimmune disorder with T-cell mediated immune response to intrinsic factor and gastric parietal cells Autoimmune disorder with T-cell mediated immune response to intrinsic factor and gastric parietal cells Atrophic gastritis Atrophic gastritis Achlorhydria Achlorhydria
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Autoimmune Disorders Hashimoto’s thyroiditis Hashimoto’s thyroiditis DM I DM I Celiac sprue Celiac sprue
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B12 Deficiency Megaloblastic anemia Megaloblastic anemia Leukopenia Leukopenia Thrombocytopenia Thrombocytopenia Peripheral neuropathy Peripheral neuropathy Psychosis, personality changes, memory loss Psychosis, personality changes, memory loss
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Other Findings Ineffective erythropoiesis mild hemolysis Ineffective erythropoiesis mild hemolysis Achlorhydria Achlorhydria Elevated gastrin Adenocarcinoma and carcinoid tumors Adenocarcinoma and carcinoid tumors Atrophic glossitis Atrophic glossitis
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Diagnosis Low B12 OR Low Normal B12 with elevated MMA/homocysteine Low B12 OR Low Normal B12 with elevated MMA/homocysteine Elevated intrinsic factor ab, anti-parietal cell antibody, elevated gastrin Elevated intrinsic factor ab, anti-parietal cell antibody, elevated gastrin Atrophic gastritis on EGD Atrophic gastritis on EGD Schilling test Schilling test
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Treatment Historically treatment is with IM B12 Historically treatment is with IM B12 Recent data suggests po a reasonable alternative Recent data suggests po a reasonable alternative Second pathway for B12 absorption without intrinsic factor
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Treatment Small 1998 study randomized pt’s to cobalomin 1 mg IM at scheduled intervals vs. daily 2mg orally Small 1998 study randomized pt’s to cobalomin 1 mg IM at scheduled intervals vs. daily 2mg orally Higher B12 and lower MMA levels in oral group than IM group at 120 days f/u Only 33 patients Only 7 with clear pernicious anemia Blood, August 1998
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Treatment 60 patients with megaloblastic anemia randomized to 1g IM vs. 1g po daily for 10 days followed by once/wk followed by monthly 60 patients with megaloblastic anemia randomized to 1g IM vs. 1g po daily for 10 days followed by once/wk followed by monthly Hgb, B12, retic, MCV increased in both groups similarly In patients with neurologic deficits, 78% improved in IM vs. 75% in po Small study, etiology of deficiency not fully tested Clinical Therapeutics, 2003
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Treatment PO therapy a reasonable alternative. PO therapy a reasonable alternative. Some experts recommend initial IM therapy, especially in the presence of neurologic symptoms. Some experts recommend initial IM therapy, especially in the presence of neurologic symptoms. PO therapy standard of care in Canada and Sweden. PO therapy standard of care in Canada and Sweden.
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Classic Case? Pancytopenia Pancytopenia Hemolysis Hemolysis Peripheral smear Peripheral smear Glossitis (maybe) Glossitis (maybe)
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Incongruities Barrett esophagus in a patient with achlorhydria? Barrett esophagus in a patient with achlorhydria? “B” symptoms “B” symptoms
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Take Home Points Think of B12 deficiency in patients with cytopenias (not just anemia!), neurologic dysfunction. Think of B12 deficiency in patients with cytopenias (not just anemia!), neurologic dysfunction. Confirm with B12 +/- MMA & homocysteine. Confirm with B12 +/- MMA & homocysteine. Oral therapy is probably preferred. Oral therapy is probably preferred.
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