Pancytopenia and “B” Symptoms in a Previously Healthy Female

Robert J. Hoffman MDRobert J. Hoffman MDDecember 20, 2006December 20, 2006

Presentation

34 year old female with a history of 34 year old female with a history of hypothyroidism presents with abdominal pain, hypothyroidism presents with abdominal pain, weakness, night sweats, fevers and weight loss.weakness, night sweats, fevers and weight loss.

15 lb unintentional weight loss over 6 15 lb unintentional weight loss over 6 weeksweeks

Fevers to 101°Fevers to 101° Recent drenching night sweatsRecent drenching night sweats Diffuse moderate abdominal painDiffuse moderate abdominal pain

HPI

5-6 weeks of progressive diffuse abdominal 5-6 weeks of progressive diffuse abdominal painpain Waxes and wanesWaxes and wanes Better with foodBetter with food Moderate severityModerate severity

New DOE restricting her activity as wellNew DOE restricting her activity as well Recent diagnosis of Barrett esophagusRecent diagnosis of Barrett esophagus

PMH

HypothyroidismHypothyroidism Barrett esophagus based on recent EGDBarrett esophagus based on recent EGD GERDGERD

Medications

PrilosecPrilosec SynthroidSynthroid OCPOCP

Social History

No tobacco, alcohol or illegal drug useNo tobacco, alcohol or illegal drug use SingleSingle Works as an accountantWorks as an accountant

Physical Examination

Vitals: T: 98.5 P: 98 RR: 16 BP: 109/41Vitals: T: 98.5 P: 98 RR: 16 BP: 109/41

General: Comfortable appearing, pale, NADGeneral: Comfortable appearing, pale, NAD

Abd: soft, moderate epigastric and RUQ Abd: soft, moderate epigastric and RUQ tenderness. No organomegalytenderness. No organomegaly

No LADNo LAD

Otherwise normal exam.Otherwise normal exam.

Labs

1.916

5.9126

140

3.9

103

23

9

0.987

MCV: 102Retic: 2.3%Preg: negativeALT: 36AST: 27TBili: 1.8Alk Phos: 47LDH: 883

64% PMN 32% Lymph2% monos 1% eos

10mm, 8mm, 4mm liver lesions10mm, 8mm, 4mm liver lesions 5 x 3 cm pelvic mass5 x 3 cm pelvic mass Small amount of pelvic ascitesSmall amount of pelvic ascites

CT Abdomen

Initial Hospital Course

MRI orderd to f/u pelvic mass.MRI orderd to f/u pelvic mass. Hematology consult obtained, bone marrow Hematology consult obtained, bone marrow

biopsy planned for Monday.biopsy planned for Monday. PRBC transfusionPRBC transfusion Haptoglobin < 6, consistent with hemolysisHaptoglobin < 6, consistent with hemolysis LDH elevatedLDH elevated

Hospital Course

MRI reveals pelvic “mass” to be an MRI reveals pelvic “mass” to be an enlarged vaginal vault.enlarged vaginal vault.

u/s fails to confirm liver nodulesu/s fails to confirm liver nodules Decreased bone marrow signal found on Decreased bone marrow signal found on

MRI c/w marrow replacementMRI c/w marrow replacement

Summary

PancytopeniaPancytopenia ““B” symptomsB” symptoms Abdominal painAbdominal pain Decreased marrow signalDecreased marrow signal Intravascular hemolysisIntravascular hemolysis

Phew!

B12 returns 78 pg/mlB12 returns 78 pg/ml Homocysteine and methylmalonic acid Homocysteine and methylmalonic acid

elevatedelevated Anti-parietal cell antibody positive.Anti-parietal cell antibody positive. B12 supplements initiatedB12 supplements initiated Bone marrow shows hypercellularity and Bone marrow shows hypercellularity and

erythroid hyperplasia, consistent with erythroid hyperplasia, consistent with vitamin B12 deficiencyvitamin B12 deficiency

Outcome

At one week follow up patient states she At one week follow up patient states she “feels better than she has in years”“feels better than she has in years”

Hemoglobin was 9.2 g/dl on d/c and 11.8 Hemoglobin was 9.2 g/dl on d/c and 11.8 g/dl at one week follow up.g/dl at one week follow up.

Other cytopenias resolve.Other cytopenias resolve.

Pernicious Anemia

Autoimmune disorder with T-cell mediated Autoimmune disorder with T-cell mediated immune response to intrinsic factor and immune response to intrinsic factor and gastric parietal cellsgastric parietal cells

Atrophic gastritisAtrophic gastritis AchlorhydriaAchlorhydria

Autoimmune Disorders

Hashimoto’s thyroiditis Hashimoto’s thyroiditis DM IDM I Celiac sprueCeliac sprue

B12 Deficiency

Megaloblastic anemiaMegaloblastic anemia LeukopeniaLeukopenia ThrombocytopeniaThrombocytopenia Peripheral neuropathyPeripheral neuropathy Psychosis, personality changes, memory Psychosis, personality changes, memory

lossloss

Other Findings

Ineffective erythropoiesis Ineffective erythropoiesis mild mild hemolysishemolysis

AchlorhydriaAchlorhydria Elevated gastrinElevated gastrin

Adenocarcinoma and carcinoid tumorsAdenocarcinoma and carcinoid tumors Atrophic glossitisAtrophic glossitis

Diagnosis

Low B12 Low B12 OR OR Low Normal B12 with Low Normal B12 with elevated MMA/homocysteineelevated MMA/homocysteine

Elevated intrinsic factor ab, anti-parietal Elevated intrinsic factor ab, anti-parietal cell antibody, elevated gastrincell antibody, elevated gastrin

Atrophic gastritis on EGDAtrophic gastritis on EGD Schilling testSchilling test

Treatment

Historically treatment is with IM B12Historically treatment is with IM B12 Recent data suggests po a reasonable Recent data suggests po a reasonable

alternativealternative Second pathway for B12 absorption Second pathway for B12 absorption

without intrinsic factorwithout intrinsic factor

Treatment

Small 1998 study randomized pt’s to Small 1998 study randomized pt’s to cobalomin 1 mg IM at scheduled intervals cobalomin 1 mg IM at scheduled intervals vs. daily 2mg orallyvs. daily 2mg orally Higher B12 and lower MMA levels in Higher B12 and lower MMA levels in

oral group than IM group at 120 days f/uoral group than IM group at 120 days f/u Only 33 patientsOnly 33 patients Only 7 with clear pernicious anemiaOnly 7 with clear pernicious anemia

Blood, August 1998

Treatment

60 patients with megaloblastic anemia randomized 60 patients with megaloblastic anemia randomized to 1g IM vs. 1g po daily for 10 days followed by to 1g IM vs. 1g po daily for 10 days followed by once/wk followed by monthlyonce/wk followed by monthly Hgb, B12, retic, MCV increased in both groups Hgb, B12, retic, MCV increased in both groups

similarlysimilarly In patients with neurologic deficits, 78% In patients with neurologic deficits, 78%

improved in IM vs. 75% in poimproved in IM vs. 75% in po Small study, etiology of deficiency not fully Small study, etiology of deficiency not fully

testedtested

Clinical Therapeutics, 2003

Treatment

PO therapy a reasonable alternative.PO therapy a reasonable alternative. Some experts recommend initial IM Some experts recommend initial IM

therapy, especially in the presence of therapy, especially in the presence of neurologic symptoms.neurologic symptoms.

PO therapy standard of care in Canada and PO therapy standard of care in Canada and Sweden.Sweden.

Classic Case?

PancytopeniaPancytopenia HemolysisHemolysis Peripheral smearPeripheral smear Glossitis (maybe)Glossitis (maybe)

Incongruities

Barrett esophagus in a patient with Barrett esophagus in a patient with achlorhydria?achlorhydria?

““B” symptomsB” symptoms

Take Home Points

Think of B12 deficiency in patients with Think of B12 deficiency in patients with cytopenias (not just anemia!), neurologic cytopenias (not just anemia!), neurologic dysfunction.dysfunction.

Confirm with B12 +/- MMA & Confirm with B12 +/- MMA & homocysteine.homocysteine.

Oral therapy is probably preferred.Oral therapy is probably preferred.