hematology cpc bao le, do internal medicine october 9, 2007
TRANSCRIPT
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Hematology CPC
Bao Le, DO
Internal Medicine
October 9 , 2007
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Objectives
Presenting a case Bariatric surgery Neurologic complications of Bariatric surgery Peripheral neuropathy Macrocytic anemia Myelodysplastic syndrome Conclusion
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Case
CC: Sore throat.
HPI: A 43 y/o man presents to the ER with: A 3-day history of mouth and throat pain associated with a white
coating. Temperature of 102 F at home with chills. Progressively fatigued over past 5 months. Overt dyspnea on exertion with walking 10 yards. Progressive numbness of his fingers and toes ascending to mid shin
and mid forearm over one year.
He denies: Changes in mentation or tongue soreness. Bright red blood per rectum or black tarry stools.
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Case (Cont’)
● PMH: Bariatric surgery at the
age of 25, in 1987. Weighed 541 lbs prior to
the surgery.
PSH: Bariatric surgery.
Family hx: No blood dyscrasias. Positive for obesity.
Social hx: Worked as a laborer. No heavy metal exposure. 10 pack/year tobac history. Less than 1 drink EtOH/day.
Medications: B12 injections. Iron 325 mg BID. MVI.
ROS: Pertinent per HPI.
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Case (Cont’)
Physical Exam: VS: 110/75, 105, 97% RA, 101.2 F, 240 lbs, 6’1” GEN: toxic, uncomfortable, no dyspnea with
conversation. HEENT: oral mucosa coated with thrush, tongue
appears normal, non-icteric sclera, conjuctiva was pale. NECK: prominent carotid pulse, no thrill or bruit, no
lymphadenopathy. CV: tachycardic, S1 S2, no m/g/rubs. RESP: clear. ABD: mod obese, no TTP, no organomegaly.
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Case (Cont’)
Physical Exam (cont’): EXT: chronic venous insufficiency changes. DERM: no rashes. PSYCH: appropriate. NEURO:
distal reflexes decreased. distal sensation decreased. able to ambulate. normal speech pattern.
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Case (Cont’)
LAB:
G: 20%, M: 15%, L: 65%MCV: 108, RDW: 13
Ferritin: < 10 (39-150) B12: > 700 pg/mL MMA: not elevated Folic acid: normal LDH: 210 (60-200) Liver and Renal: normal
PBS: Severe leukopenia Few (< 1 per HPF/avg)
hypersegmented neutrophils No blasts Macrocytic RBC without
fragmentation
Bone Marrow: Hypercellular: 70% Trilineage dysplasia Ringed sideroblasts < 5% blasts
Cytogenetics: normal
5.61000 65000
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Case Overview
Bariatric surgeryHematologic abnormalities
Pancytopenia
Neurological deficits
Constitutional symptoms
Sore throatDOE/Fatigue
43 y/o man
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Obesity and Bariatric Surgery
According to 2000 US Census: 63 million adult Americans with obesity, BMI ≥ 30, and 10.5 million with morbid obesity, BMI ≥ 40.
Annual obesity-related medical expenditures were substantial.
The rise in the prevalence of obesity is associated with increases in the prevalence of obesity comorbidities.
The loss of life expectancy due to obesity is profound. In 1991, NIH established bariatric surgery guidelines:
BMI ≥ 40 or ≥ 35 in the presence of significant comorbidities.
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Gastrointestinal Tract
B12, ZincCopper, Phosphorus
Vitamins
CalciumIron, Phosphorus, zinc
Copper, Vitamins
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Bariatric surgery techniques
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The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects.
Age 37-60, BMI > 34 for male, BMI > 38 for female.
Conventional treatment: 2037 Bariatric surgery: 2010 Average follow-up: 10.9 years Surgical group had a hazard
ratio of 0.76 compared to control group ( 95% confidence interval, 0.59 – 0.99, P = 0.04)
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University of Oklahoma Health Science Center. Neurology 2002;59:1953-1456
136 articles and 22094 patients.JAMA, October 13, 2004 - Vol 292.Results:
Resolution of DM: 76.8 % Resolution of HTN: 61.7 % Improvement of lipid: 83 % Resolution of OSA: 85.7 %
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Neurologic Complication of Bariatric Surgery
Encephalopathy Behavior abnormalities Cranial nerve palsies Ataxia Seizure Myelopathy Plexopathy Mononeuropathy Myopathy Myotonia Peripheral neuropathy
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Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN.
Neurology 2004; 63:1462-1470. Retrospective review study, 1985 - 2001. Open Cholecystectomy: 300; BS: 435.
BS: 16 % Peripheral Neuropathy: P < 0.001
Open Chol: 3 %
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Neuropathic characteristics of PN after BS
Sensory-predominant PNInsidious onsetChronic course
Distal LE/UE
MononeuropathyCarpal Tunnel Syndrome
Radiculoplexus neuropathyLumbosacral
Cervical
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Risk factors for PN after BS: A greater absolute weight loss A faster rate of weight loss A lower postsurgery BMI Lower serum albumin Lower transferrin concentrations Prolonged postsurgery GI symptoms Less MVI and Ca supplement Not attending nutritional clinics
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Symmetric Polyneuropathies
Inflammatory/Immune-Mediated Neuropathies Guillain-Barre syndrome Chronic inflammatory
demyelinating polyradiculoneuropathy
Vasculitic neuropathy Sarcoid neuropathy Neuropathies associated with
connective tissue disease
Toxic Neuropathies Drugs, metals, alcohol
Neuropathies Associated with Cancer Remote effects of cancer Direct tumor infiltration
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Symmetric Polyneuropathies
Inherited Neuropathies Hereditary motor sensory
neuropathies Giant axonal neuropathy Porphyric neuropathies Lysosomal enzyme deficiency
(Fabry disease) Lipoprotein disorders
Neuropathies Associated with Infection HIV Leprosy Lyme disease
Neuropathies Associated with Organ System Failure Kidney, lung, liver Critical illness polyneuropathy Organ transplantation
Diabetic Polyneuropathy
Vitamin Deficiencies Cobalamin (B12) Vitamin E Thiamine (B1) Pyridoxine (B6)
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Neurologic Manifestations of Cobalamin (B12) Deficiency
Distal paresthesiasUnsteady gaitDeficit in vibratory sensation and
proprioceptionDiffuse hyperreflexiaLoss of reflex at ankleNeurobehavioral changes: apathy,
irritability, memory loss.
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Neurologic Manifestations of Vitamin E Deficiency
Progressive gait ataxia Night blindness Loss of vibratory sensation and proprioception Absent reflexes Ptosis/Ophthalmoplegia Dysarthric speech Intention tremor
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Neurologic Manifestations of Thiamine (B1) Deficiency
Fatigue/IrritabilityDistal paresthesias affecting feet with
burning painDistal sensory lossHyporeflexiaWernicke-Korsakoff syndrome: mental
confusion, ataxia, ophthalmoplegiaCerebellar degeneration
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Neurologic Manifestations of Pyridoxine (B6) Deficiency
Paresthesias in distal limbs Gait instability Distal areflexia with normal muscle strength Lhermitte sign (Barber Chair Phenomenon) EMG:
Absent or reduced sensory nerve potentials Normal motor nerve conduction
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Gastrointestinal Tract
B12, ZincCopper, Phosphorus
Vitamins
CalciumIron, Phosphorus, zinc
Copper, Vitamins
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Department of Neurology and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Neurology 2004;63:33-39 Chart review of 13
patients with known copper deficiency and neurologic deficits.
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University of Oklahoma Health Science Center. Neurology 2002;59:1953-1456
45 y/o woman Persistent LE paresthesias
and difficulty ambulating PE: Marked pallor and
palpable spleen
Neuro: Hyperactive reflexes Markedly decreased vibratory
sense LE Extremely ataxic gait Cognition normal
BM: Hypercellular Ringed sideroblasts
45 y/o man 4-month hands and feet
paresthesias Progressive weakness,
exertional dyspnea, difficulty ambulating
PE: Marked pallor and mild hepatosplenomegaly
Neuro: Slow and clumsy toe tapping Decreased vibratory sensation
and proprioception Marked truncal ataxia Brisk reflexes
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Copper Deficiency Causes Demyelination
O2
O2
H2O2
Superoxide Dismutase
2 Atoms of Copper
↑Oxidadive damages
DNAProteinsLipids
Demyelination
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Macrocytic Anemia
Drugs Alcoholism Reticulocytosis Liver disease Hypothyroidism Vitamin B12
deficiency
Folate deficiency Multiple myeloma Aplastic anemia Acute leukemia Myelodysplastic
syndrome
Chemotherapeutic agents DiureticsCyclophosphamide TriamtereneHydroxyurea Anticonvulsant
agentsMethotrexate PhenytoinAzathioprine PrimidoneMercaptopurine Valproic acid5-Fluoracil Anti-inflammatory
Antiretroviral SulfasalazineZidovudine Stavudine
HypoglycemiaMetformin
AntimicrobialsPyrimethamineSulfamethoxazoleTrimethoprimValacyclovir
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Myelodysplastic Syndrome
MDS comprises a heterogeneous group of malignant stem cell disorders characterized by dysplastic and ineffective blood cell production.
These disorders may occur de novo or arise years after exposure to potentially mutagenic therapy.
The precise incidence of de novo MDS is not known.
MDS manifests as symptomatic anemia (60-80%), neutropenia (50-60%), and thrombocytopenia (40-60%).
Clinical presentations: Incidental findings on routine laboratory studies. Fatigue, malaise, and a general sense of tiredness. Petechiae, ecchymoses, nose and gum bleeding. Fever or shock.
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Myelodysplastic Syndrome
Physical Exam: Pale, petechiae, purpura Hepatomegaly, splenomegaly, LN Tachycardia, fever
PBS: Macrocytic with oval-shaped RBC Basophilic stippling, Howell-Jolly bodies Neutropenia Thrombocytopenia
Bone Marrow: Hypercellularity with trilineage dysplastic changes Ringed sideroblasts
Cytogenetics: Normal, 5q-, 7q-, 20q-, trisomy 8+
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FAB Criteria for MDS Subgroups
Type BM blasts (%)
Peripheral blood
blasts (%)
Auer rods
Monocytes > 1000/ul
Ringed sideroblasts
> 15% of nucleated erythroid cells
RA (21%) <5 ≤1 No No No
RARS (17%) <5 ≤1 No No Yes
RAEB (37%) 5-20 <5 No No ±
CMML (13%) ≤ 20 <5 No Yes ±
RAEB-T (12%)
(AML)
21-30 or ≥5 ± ± ±
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Myelodysplastic Syndrome
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Myelodysplastic Syndrome
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Myelodysplastic Syndrome
Treatment: Supportive care:
Transfusion as needed Iron chelation
Low-intensity therapy: Anemia: EPO ± G-CSF (ringed sideroblast and serum Epo levels < 500
mU/mL) Neutropenia: G-CSF or GM-CSF Thrompocytopenia: IL-11, thrombopoietin, danazol 5-azacytidine Immunosuppressive therapy: ATG and cyclosporine Anti-TNF, anti-angiogenesis agents
High-intensity therapy: Chemotherapy Hemopoietic stem cell transplantation (HSCT)
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Copper Deficiency
Copper Deficiency
Central/peripheralneuropathy
AnemiaLeukopenia
MDS?
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Baylor College of Medicine, Houston, Tx; and the Department of Pathology, University of Alabama at Birmingham.
Blood, 15 August 2002. Vol 22, number 4: 1493-1495.
44 y/o woman with h/o gastric resection with Billroth II for peptic ulcer who presents with macrocytic anemia and leukopenia.
WBC: 1.5 with 19% neutrophils, hemoglobin 6.4 g/dl, MCV: 102, platelet count: 192.
B12, folate, and ferritin were elevated. PBS: macrocytic, oval shaped RBC Bone marrow: dyserythropoiesis, dysmyelopoiesis, ringed
sideroblasts, and prominent hemosiderin in plasma cell. Cytogenetic studies were normal.
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She was diagnosed with MDS, FAB subtype refractory anemia with ringed sideroblasts (RARS).
Treated with G-CSF and EPO.Referred for BM transplantation.Treated with 6 weeks of IV copper
chloride. Normalized hematologic abnormalities and
bone marrow aspiration.
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Department of Neurology, University of Michigan, MI. Arch Neurol 2003: 60;1303-1306.
46 y/o male c/o: CP/SOB Progressive numbness and weakness of both LE Poor balance
Neurologic Exam: Intact cranial nerves Normal mentation Brisk DTR’s in LE’s Bilateral plantar flexor response Markedly reduced vibratory sensation and propioception Wide based gait
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Lab: Hemoglobin: 7.9 g/dL Copper: < 10 ug/dL (80 – 120 ug/dL) Zinc: 184 ug/dL (80 – 120 ug/dL) 24-hour urine copper: 0.04 mg/d ( 0.03 – 0.05 mg/d) 24-hour urine zinc: 5.01 mg/d ( 0.24 – 0.4 mg/d)
Treatment: Started copper supplement 2 mg/d
Normalize hematologic abnormalities Worsening neurologic deficits
Increased to 8 mg/d Improving neurologic deficits
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Hyperzincemia Induces Copper Deficiency
↑ Zinc
↑ Metallothionein
Metallothionein competes Copper receptors in GI
↓ GI Copper Absorption
Copper Deficiency
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Iron Metabolism Depends on Copper
Ferrous IronFe++
ApotransferrinApo Tf
Ferric IronFe+++ Transferrin
Ceruloplasmin
Copper (6 atoms)
Abnormal iron metabolism
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82 of 3-5 day-old pigs: Control with no iron Control with PO iron Control with IM iron Exp with PO iron Exp with IM iron
Study over 14 weeks
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Conclusion
Copper deficiency
Peripheral polyneuropathyMyelodysplastic syndrome
RARS
Neutropenia
Neutropenic fever
Macrocytic anemia
Fatigue, DOE
Thrombocytopenia
Abnormal iron metabolism
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Lab/Study
Dr. Hurley:
Dr. Starr:
Copper and Ceruloplasmin LevelComplete iron panelDr. Clark:
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References
Xylina T. Gregg, Vishnu Reddy, and Josef T. Prchal. Copper deficiency masquerading as myelodysplastic syndrome. Blood 2002; 100: 1493-1495.
P. Thaisetthawatkul, M.L. Collazo-Clavell, M.G. Sarr, J.E. Norell, and P.J.B. Dyck. A controlled study of peripheral neuropathy after bariatric surgery. Neurology 2004; 63: 1462-1470.
Katalin Juhasz-Pocsine, Stacy A. Rudnicki, Robert L. Archer, Sami I. Harik. Neurlogic complications of gastric bypass surgery for morbid obesity. Neurology 2007:68:1843-1850.
Jerry R. Mendell, John T. Kissel, David R. Cornblath. Diagnosis and Management of Peripheral Nerve Disorders. Oxford University Press, Inc. New York, NY, 2001.
Henry Buchwald, Yoav Avidor, Eugene Braunwald, Michael K. Jensen, Walter Pories, Kyle Fahrbach, Karen Schoelles. Bariatric Surgery. JAMA 2004;292:1724-1728.
Neeraj Kumar, John B. Gross, and Eric Ahlskog. Copper deficiency myelopathy porduces a clinical picture like subacute combined degeneration. Neurology 2004;63:33-39.
P Peter L. Greenberg, Neal S. Young, and Norbert Gattermann. Myelodysplastic Syndromes. Hematology 2002; 136-161.
G. Richard Lee, Sergio Nacht, John N. Lukens, and G. E. Cartwright. Iron Metabolism in Copper-Deficient Swine. The Journal of Clinical Investigation 1968; 47:2058-2069.
Florence Aslinia, Joseph J. Mazza, Steven H. Yale. Megaloblastic Anemia and Other Causes of Macrocytosis. Clinical Medicine & Research 2006;4: 236-241.
Edward H. Livingston. Complications of Bariatric Surgery. Surgical clinics of North America 2005;85:853-868. C.I. Prodan, N.R. Holland, P.J. Wisdom, S.A. Burstein, S.S. Bottomley. CNS Demyelination Associated with
copper Deficiency and Hyperzincemia. Neurology 2002;59:1453-1456. Neeraj Kumar, John B. Gross, J. Eric Ahlskog. Myelopathy due to Copper Deficiency. Neurology 2003;61: 273-
274. Peter Hedera, John K. Fink, Paula L. Bockenstedt, George J. Brewer. Myelopolyneuropathy and Pancytopenia
due to copper Deficiency and High Zinc Levels of Unknown Origin. Arch Neurol 2003;60:1303-1306.
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Trivia
Jon Brower Minnoch (USA, 1941-1983).
Weights 1397 lbs (635 kg).
Heaviest person.
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Trivia
Manuel Uribe from Monterrey, Mexico.
40 years old and weights 1225 lbs.
In March 2006, underwent most extreme BS in Italy.
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