Dr. Sachin Verma MD, FICM, FCCS, ICFC

Fellowship in Intensive Care Medicine

Infection Control Fellows Course

Consultant Internal Medicine and Critical Care

Web:- http://www.medicinedoctorinchandigarh.com

Mob:- +91-7508677495

• Bone marrow– Pluripotent stem cells– Chemical regulation

• Cytokines• Erythroid specific growth factor• Erythropoietin (EPO)

– Life span• Reticulocyte- 4 days• RBC –120 days

Anemia-values of hemoglobin, hematocrit or RBC counts which are below the values expected for age and sex matched normal subjects.

HGB<13 g/dL (men) <12 (women)HCT<41% (men) <36 (women)

HISTORY - family history - ethnicity geographical distribution

-Is the patient bleeding?Actively? In past?

-Is there evidence for increased RBC destruction?-jaundice, gall stone etc-Is the bone marrow suppressed?-Is the patient nutritionally deficient? Pica?-medication review, toxin exposure-history of chronic diseases,fever ,weight loss etc.

REVIW OF SYMPTOMSDecreased oxygen delivery to tissues

-Exertional dyspnea-Dyspnea at rest-FatigueSigns and symptoms of hyperdynamic state

-Bounding pulses-Palpitations

Life threatening: heart failure, angina, myocardial infarction

Hypovolemia-Fatiguablitiy, postural dizziness, lethargy,hypotension, shock and death

PHYSICAL EXAM•Stable or Unstable?

-ABCs-Vitals

•Pallor•Jaundice

-hemolysis•Lymphadenopathy•Hepatosplenomegally•Bony Pain•Petechiae•Rectal-? Occult blood

Functional Classification :HypoproliferativeIneffective erythropoesisIncreased Destruction/hemolytic or blood loss

Classification by Morphology:NormocyticMicrocyticMacrocytic

I.Complete blood count (CBC)     A. Red blood cell count   1. Hemoglobin 2. Hematocrit 3. Reticulocyte count     B. Red blood cell indices 1. Mean cell volume (MCV) 2. Mean cell hemoglobin (MCH) 3. Mean cell hemoglobin concentration (MCHC) 4. Red cell distribution width (RDW)     C. White blood cell count 1. Cell differential 2. Nuclear segmentation of neutrophils     D. Platelet count E. Cell morphology   1. Cell size 2. Hemoglobin content 3. Anisocytosis 4. Poikilocytosis 5. Polychromasia

    II. Iron supply studies     A. Serum iron B. Total iron-binding capacity C. Serum ferritin     III. Marrow examination     A. Aspirate     1. M/E ratioa

2. Cell morphology 3. Iron stain     B. Biopsy     1. Cellularity 2. Morphology

An accurate reticulocyte count is key to the initial classification of anemia. Normally, reticulocytes are red cells that have been recently released from the bone marrow. They are identified by staining with a supravital dye that precipitates the ribosomal RNA (Fig. 58-12). These precipitates appear as blue or black punctate spots. This residual RNA is metabolized over the first 24–36 h of the reticulocyte's lifespan in circulation. Normally, the reticulocyte count ranges from 1–2% and reflects the daily replacement of 0.8–1.0% of the circulating red cell population. A reticulocyte count provides a reliable measure of red cell production.In order to use the reticulocyte count to estimate marrow response, two corrections are necessary

The first correction adjusts the reticulocyte count based on the reduced number of circulating red cells. With anemia, the percentage of reticulocytes may be increased while the absolute number is unchanged.For this second correction, the peripheral blood smear is examined to see if there are polychromatophilic macrocytes present. These cells, representing prematurely released reticulocytes, are referred to as "shift" cells. The correction is necessary because these prematurely released cells survive as reticulocytes in circulation for >1 day, thereby providing a falsely high estimate of daily red cell production. If polychromasia is increased, the reticulocyte count, already corrected for anemia, should be divided again by a factor of 2 to account for the prolonged reticulocyte maturation time

Correction #1 for anemia:

  This correction produces the corrected reticulocyte count

  In a person whose reticulocyte count is 9%, hemoglobin 7.5 g/dL, hematocrit 23%, the absolute reticulocyte count = 9 x (7.5/15) [or x (23/45)]= 4.5%

Correction #2 for longer life of prematurely released reticulocytes in the blood:

  This correction produces the reticulocyte production index will

  In a person whose reticulocyte count is 9%, hemoglobin 7.5 gm/dL, hematocrit 23%, the reticulocyte production index will be 4.5/2(maturation time correction)     

MCV

Microcytic(MCV<80)

Normocytic(80<MCV<100)

Macrocytic(MCV>100)

-The presence of anemia with an inappropriately low reticulocyte production index, macro- or microcytosis on smear, and abnormal red cell

-divided into two categories: nuclear maturation defects, associated with macrocytosis and abnormal marrow development, and cytoplasmic maturation defects, associated with microcytosis and hypochromia usually from defects in hemoglobin synthesis.

-The inappropriately low reticulocyte production index is a reflection of the ineffective erythropoiesis that results from the destruction within the marrow of developing erythroblasts.

-Bone marrow examination shows erythroid hyperplasiaoglobin synthesis

Anemia of Chronic Disease

Iron Deficiency

Lead PoisoningThalassemia

Sideroblastic

Gold Standard?Bone marrow aspirate

Lab studies?FerretinSerum ironTotal Iron Binding CapacityFe Saturation

FerritiFerritinn

Serum Serum FeFe

TIBCTIBC RDWRDW

Fe deficFe defic decreadecreass

decreadecreass

increasincreasee

(>15)(>15)

AOCDAOCD N/N/increincre

decreadecreass

decreasdecreas NN

SideroblastSideroblasticic

N/N/increincre

N/increN/incre NN NN

ThalassemiThalassemiaa

N/N/increincre

N/increN/incre NN N/N/

Normal serum iron:50-150ug/dl Normal serum ferritin:100ug/L (male)and 30ug/L (female)

Normal TIBC :300-360ug/dl Normal percentage saturation(serum

iron/TIBCx100):25-50% MCV(hamatocritx10)/ (red cell

countx10 ):82-98 MCH(hemoglobinx10/(red cell

countx10 ):27-33 MCHC (MCH/MCV) :31-34

General examination : Jaundice, pallor Other physical findings : Spleen may be

enlarged; bossing of skull in severe congenital cases

Hemoglobin  :From normal to severely reduced MCV, MCH : Usually increased

Reticulocytes : Increased Bilirubin : Increased (mostly unconjugated) LDH : Increased (up to 10X normal with

intravascular hemolysis)  Haptoglobin : Reduced to absent

Intracorpuscular DefectsHereditary: Hemoglobinopathies   Enzymopathies     Membrane-cytoskeletal defects   Acquired :Paroxysmal nocturnal hemoglobinuria (PNH)

Extracorpuscular Factors Familial hemolytic uremic syndrome

(HUS)   Mechanical destruction

(microangiopathic)     Toxic agents   Drugs     Infectious     Autoimmune

Mismatched blood transfusion PNH Septicemia Microangiopathic March hemoglobinuria In all these cases hemoglobinuria is the

unique feature

-comprises 75% of all anemias -reflects absolute or relative marrow failure in

which the erythroid marrow has not proliferated appropriately for the degree of anemia.

-can result from marrow damage, iron deficiency, or inadequate EPO stimulation.

-loewEPO production may reflect impaired renal function, suppression of EPO production by inflammatory cytokines such as interleukin 1, or reduced tissue needs for O2 from metabolic disease such as hypothyroidism

Pancytopenia with Hypocellular Bone Marrow 

Acquired aplastic anemia Constitutional aplastic anemia (Fanconi's

anemia, dyskeratosis congenita) Some myelodysplasia Rare aleukemic leukemia (AML) Some acute lymphoid leukemia Some lymphomas of bone marrow

Pancytopenia with Cellular Bone Marrow  Primary bone marrow diseases   Myelodysplasia   Paroxysmal nocturnal hemoglobinuria   Myelofibrosis   Some aleukemic leukemia   Myelophthisis   Bone marrow lymphoma   Hairy cell leukemia Secondary to systemic diseases   Systemic lupus erythematosus   Hypersplenism   B12, folate deficiency   Overwhelming infection   Alcohol   Brucellosis   Sarcoidosis   Tuberculosis   Leishmaniasis