Tutorial

Tutorial

باطنية
د. خالد نافع

عدد الاوراق (4)

30-4-2013

Erythropoesis-Brief Hematology Review

Bone marrow
Pluripotent stem cells
Chemical regulation
Cytokines
Erythroid specific growth factor
Erythropoietin (EPO)
Life span
Reticulocyte- 4 days
RBC –120 days


RBC-The important players
Hemoglobin
reversibly binds and transports 02 from lungs to tissues
4 globin chains & iron

RBC-The important players (2)

Iron
key element in the production of hemoglobin
absorption is poor
Transferrin
iron transporter
Ferritin
iron binder, measure of iron stores, *also acute phase reactant*

Definitions

Anemia-values of hemoglobin, hematocrit or RBC counts which are more than 2 standard deviations below the mean
HGB<13.5 g/dL (men) <12 (women)
HCT<41% (men) <36 (women)

CASE

ML is a 64-year old male who has not had any primary care for several years. When he tried to give blood last week, he was told that he was anemic. He presents for evaluation.
What would you do??


Evaluation of the Patient
HISTORY
Is the patient bleeding?
Actively? In past?
Is there evidence for increased RBC destruction?
Is the bone marrow suppressed?
Is the patient nutritionally deficient? Pica?
PMH including medication review, toxin exposure

Evaluation of the Patient (2)

REVIW OF SYMPTOMS
Decreased oxygen delivery to tissues
Exertional dyspnea
Dyspnea at rest
Fatigue
Signs and symptoms of hyperdynamic state
Bounding pulses
Palpitations
Life threatening: heart failure, angina, myocardial infarction
Hypovolemia
Fatiguablitiy, postural dizziness, lethargy, hypotension, shock and death


Evaluation of the Patient (3)
PHYSICAL EXAM
Stable or Unstable?
-ABCs
-Vitals
Pallor
Jaundice
-hemolysis
Lymphadenopathy
Hepatosplenomegally
Bony Pain
Petechiae
Rectal-? Occult blood

Laboratory Evaluation

Initial Testing
CBC w/ differential (includes RBC indices)
Reticulocyte count
Peripheral blood smear

Laboratory Evaluation (2)

Bleeding
Serial HCT or HGB
Iron Deficiency
Iron Studies
Hemolysis
Serum LDH, indirect bilirubin, haptoglobin, coombs, coagulation studies
Bone Marrow Examination
Others-directed by clinical indication
hemoglobin electrophoresis
B12/folate levels


Differential Diagnosis
Classification by Pathophysiology
Blood Loss
Decreased Production
Increased Destruction
Classification by Morphology
Normocytic
Microcytic
Macrocytic

Blood Loss

Acute
Traumatic
Variety of sources
Melena, hematemesis,
Chronic
Occult bleeding
Colonic polyp/carcinonma

Decreased Production

Infectious
Neoplastic
Endocrine
Nutritional Deficiency
Anemia of Chronic Disease
Decreased ProductionINFECTIOUS


Bacterial
Tuberculosis

Viral

HIV
Parvovirus

Decreased ProductionNEOPLASTIC

Leukemia
Lymphoma/Myeloma
Myeloproliferative Syndromes
Myelodysplasia

Decreased ProductionENDOCRINE

Thyroid Dysfunction
Hypothyroidism
Erythropoietin Deficiency
Renal Failure

Decreased ProductionNUTRITIONAL DEFICIENCY

Iron
B12
Folate


Macrocytic Anemia
MCV > 100
Megaloblastic:Abnormalities in nucleic acid metabolism
B12, Folate
Non-megaloblastic:Abnormal RBC maturation
Myelodysplasia
liver dz, hypothryroidism, chemotherapy/drugs

Microcytic Anemia

MCV <80
Reduced iron availability
Reduced heme synthesis
Reduced globin production

Microcytic AnemiaREDUCED IRON AVAILABILTY

Iron Deficiency
Deficient Diet/Absorption
Increased Requirements
Blood Loss
Iron Sequestration
Anemia of Chronic Disease
Low serum iron, low TIBC, normal serum ferritin
MANY!!
Chronic infection, inflammation, cancer, liver disease


Microcytic AnemiaREDUCED HEME SYNTHESIS
Lead poisoning
Acquired or congenital sideroblastic anemia
Characteristic smear finding: Basophylic stippling

Microcytic AnemiaREDUCED GLOBIN PRODUCTION

Thalassemias
Smear Characteristics
Hypochromia
Microcytosis
Target Cells
Tear Drops

Lab tests of iron deficiency of increased severity



Differential Diagnosis-Revisited

Classification by Pathophysiology
Blood Loss
Decreased Production
Increased Destruction


INCREASED DESTRUCTION
Immune Mediated
Non-immune Mediated

Increased DestructionIMMUNE MEDIATED

Cold Agglutinin
Paroxysmal nocturnal hemoglobinuria
Post mycoplasmal hemolytic anemia
Warm Agglutinin
Drug induced
Autoimmune hemolytic anemia
Transfusion reaction

Increased DestructionNON-IMMUNE MEDIATED

Extra-corpuscular
Macro-circulatory
Hypersplenism
Extracorporeal circulation
Micro-circulatory
DIC
TTP
HUS
Intra-corpuscular
RBC Wall (membrane or enzyme defects)
Heme or globin abnormalities (HbS, C)


Back to M.L.-You appropriately decide to obtain more history!
HPI: Ive been a little more tired than usual, but Ive been busy at work. Im getting close to retirement. Nothing else is unusual. I avoid doctors if I can
PMH: Inguinal hernia repair 20 yrs ago
FH: F & MGF-heart attack(age 80), brother-alcoholism
SH: Married x44yr, smokes 1ppd, a couple beers/night
MEDS: daily multivitamin
ALLERGIES: none
ROS:+fatigue, +urine seems a little darker lately

More on M.L.

P.E. findings
HR 98 Resp 20 BP 112/70
Gen: NAD, appears younger than stated age
HEENT: skin and conjunctiva slightly pale
NECK: no adenopathy or thyromegally
Chest:
CV: no murmur
ABD: no HSM, soft, normoactive bowel sounds
GU: normal male
Rectal: no masses, prostate smooth/not enlarged, guaiac negative stool


M.L.s Initial Labs
Only a CBC w/ diff was obtained:
WBC: 8.2, HCT 32.2, MCV 79, Platelets 221, differential - normal

Initial Thoughts?

Blood loss?
Age places him at risk for colon CA
Decreased Production?
Alcohol use, Iron deficiency
Increased Destruction?
Darker urine lately
Further Work-up
questions
Peripheral Blood Smear
Reticulocyte count
Iron Studies
Ferritin
TIBC
% Saturation
Urinalysis
colonoscopy referral


More Results
screen reveals no positive responses
Smear reveals microcytic, hypochromic RBCs
Retic count is interpreted as low
Urinalysis negative for hemoglobin

Iron Studies

Ferritin: 10
TIBC: 350
% Sat: 15

Whats next?

Rule out Sources of Bleeding
Counseling regarding colon CA and referral for colonoscopy
Consider oral iron therapy
Dietary counseling (iron sources, limiting etoh, etc)
Encourage follow-up for health care maintenance
Vaccinations (Tetnus/pneumovax)
Other cancer screening
Cholesterol Screen


Diagnosis
Colonoscopy revealed small suspicious lesion in sigmoid colon, pathology revealing adenocarcinoma. Excised surgically,
Routine labs, one year later, reveal an HCT of 40%. He feels better than ever!









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