Hematology

where does hematopoiesis occur

in fetus: spleen and liver

after birth: bone marrow

• erythropoiesis specifically in all bones under 5 yrs but in adults only in vertebrae, sternum, ribs and pelvis

Steps of erythropoiesis

• pluripotent stem cell

• proerythroblast (committed stem cell)

• Phase 1: erythroblast

• Phase 2: Normoblast

• Phase 3: reticulocyte

• erythrocyte

phase 1,2,3,= ENR

How is erythropoiesis stimulated

when hypoxemic, kidney release EPO which binds to proerythroblasts in bone marrow to stimulate RBC production

life span of RBC

120 days (4 months)

then removed from circulation by spleen when fragile and old and phagocytes

What causes jaundice

excessive RBC destruction bc heme converts to bilirubin and supposed to be taken to liver by plasma proteins to be excreted via bile

but when excessive, the unconjugated bilirubin accumulates and causes yellow tint

Compostition of blood

55% - Plasma (mostly water, albumin, fibrogen, ions, nutrients, gas)

45% - red blood cells (measured by hematocrite)

buffy white coat (WBC and platelets)

mean corpuscular volume (MCV)

size of RBC

macrocytic = high MCV

microcytic = low MCV

Mean corpuscular hemoglobin concentration (MCHC)

color (from amt of hemoglobin)

hypochromic - low MCV

mean cell hemoglobin

mass of each cell

Anisocytosis

abnormal variation in cell size

(Ani size)

Poikilocytosis

abnormal variation in cell shape

(polka dot shape)

what does “left shift” signify

increased amt of immature WBC “bands” in blood stream = infection

(immature band left)

in blood loss anemia, when is vascular instability reached

when lost 10-15% of total blood volume = circulatory shock

hypovolemic shock

when lost over 40% of blood volume

SS: confused, SOB, diaphoresis, hypotension, tachycardia

(volema was shocked when a 40 y/o sweaty, confused SOB was taking her cartier with no tension)

main concerns of blood loss anemia

hypotension and decreased organ perfusion

Managing acute blood loss anemia

Stop bleeding and replace volume (transfusion)

also iron supplement to help build up iron storage that wsa lost

*takes 6-8 weeks to return to baseline

Hereditary spherocytosis

inherited defect causes loss of lipid bilayer so cell is more spherical rather than biconcave → stuck in spleen and lyse

• splenomegaly

• normocystic, hyperchromic

• spherocytes oon peripheral smear

most sensitive test for hereditary spherocytosis

Osmotic fragility test (OFT)

(spherical people on OF)

how to treat hereditary spherocytosis

blood transfusion, splenectomy

complication of hereditary spherocytosis

aplastic crisis if theres parovirus b19

(spherical skeleton made of a plastic)

patho/etiology of G6PD

caused by drugs (primaquine, sulfonamides, ASA, nitrofurantoin), infection (Hep A/B, typhoid fever, pneumonia), and foods (fava beans, peanuts)

enzyme defect makes RBC vulnerable to oxidative stress (caused by one of the above) and cause episode of hbg denaturing into methemoglobin and creating heinz bodies, bite cells, and bizarre poikilocytes

(G5PD= green at gills (sick); 5fava beans; Primaquine; dapsone)

(stress makes me bite into fava beans with heinz ketchup)

gold standard to diagnose G6PD

Quantitative UV spectrophotometric assay

treating G6PD

1. stop offending agent

2. transfuse as needed

3. folic acid supplement if anemia not severe

triad of symptoms for autoimmune hemolytic anemia

(JAS)

Jaundice, Abrupt and damatic onset, Splenomegaly

Test of choice for autoimmune hemolytic anemia

DAT- direct coombs test

confirms presence of antibodies on RBCs

tx of autoimmune hemolytic anemia

hold transfusions unless life threatening

1st line: prednisone

• can at rituximab w pred

mutation for sickle cell

hemoglobin S: 6th amino acid changes glutamic acid to valine

(VAL kicks GLUTES)

what are the clinical manifestations of sickle trait

asymtomatic

vaso-occlusive crisis

in sickle cell disease pts after physiologic stressor causes acute pain, fever, tachycardia, and anxiety for few hours- 2 weeks

• acute chest syndrome *M/C DEATH

• bone crisis

• renal failure

• retinal vessel occlusion

• splenic injury susceptible to encapsulated bacterial infection

how to confirm sickle cell

hemoglobin electrophoresis

all newborns screened in US

Tx for sickle cell disease

lifelong hydroxyurea - produce more hbF

symptomatic care: IVF, rest, pain med, transfusion, oxygen

definitive cure: bone marrow transplant (only safe in children)

what population is alpha and beta thalassemia common in

alpha - asian

beta - african and meditarranean

describe the mutation of alpha thalassemia

deficiency in synthesizing alpha chain

1 deletetion: silent carrier - asymp

2 deletion: thal minor/trait - mild hemolytic anemia

3 deletion: hemoglobin H disease - moderate chronic hemolytic anemia

4 deletetion: hydrops fetalis - incompatible w life

describe mutation of beta thalassemia

deficient synthesis of beta chain → accumulation of alpha chain which denature → heinz bodies → damage RBC membrane

1 gene mutation: B-thal minor/trait - no hemolysis

2 gene mutation: B-thal major - bone marrow hyperplasia → frontal bossing

treatment of thalassemia

regular blood transfusion, iron chelation therapy (bc iron builds up from sm transfusions),

stem cell transplant *only definitive

complications of thalassemia

iron overload - can cause cardiac, liver, and endocrine disease which is most common cause of morbidity and mortality