Hemolytic Anemias intrinsic defects

hemolytic anemia

increased destruction of RBC

compensated hemolytic process

when bone marrow increases production 6-8x

When destruction exeeds marrows ability to produces RBC, RBC life span is 15-20 days or less, then H-H drops and what develops

hemolytic anemia

extravascular hemolysis

destruction of RBC occurs in the RES

cells removed RES are either

• coated in immunoglobulin or Complement

• abnormal shapes

• inclusions that make them too rigid to go through capilaries

in extravascular hemolysis what chemistry tests change

• increased serum unconjugated bilirubin

• increased urin urobilogen

• increased retic count

• increased polychromasia

Intravascular hemolysis

occurs when rbc are damaged in circulation and destroyed without macrophage involvement

what are the mechanisms of intravascular hemolysis

complement goes through entire sequence mechanical damage from damaged vessels or heart valve

what chemistry changes are seen in intravascular hemolysis

• decreased haptoglobin

• increased plasma Hgb

• increased hemoglobinuria

• May see urine hemosiderin

• increased retic count and polychromasia

When is a corected retic count more accurate

if anemia is present

RPI

takes into account the time needed for retic to mature and be capable of full O2 delivery

What RPI indicates a hemolytic state

>2.5 to 3

what are hereditary RBC defects

• membrane

• Enzymes

• Hemoglobinopathies

• thalassemias

What is an aquired RBC membrane defect

Paroxysmal Nocturnal hemoglobinuria

loss of stability in integral protein (anionen-transport protein, Ankyrin, spectrin) means the RBCs will be

Spherocytes

loss of stability in peripheral proteins (4.1, Actin, spectrin) means the RBC will be

eliptocytes

defects in hereditary spherocytosis include

• decreased spectrin pairs

• decreased integral proteins which anchor the skeleton to the anionexchanger

• defect in the hinge area where spectrin/actin combine

In hereditary spherocytosis what causes the cells to swell up

increased permeability to Na+

With hereditary spherocytosis what causes hemolysis

• cationic pump is run more to try to keep Na+ out

• This uses more ATP

• In the spleen low levels of glucose and ATP cause Na+ to pile up inside

• spleen removes cells

Symptoms of hereditary spherocytosis

• Anemia

• Jaundice

• possible gallstones

• can range from asymptomatic to chronic anemia

CBC:

• WBC and Plts normal

• MCV low end of normal

• MCHC increased >36

• Retic 5-20%

hereditary spherocytosis

Flow cytometry for H. Spheros

• incubate eosin 5’ maleimide wit pts. RBC

• the band 3 portion of the RBC membrane will ind the dye

• look for decreased flourescence

Osmotic fragility uses the concept of

RBC that are sphero will burst closer to the concentration of saline that normal cells

What are some treatments of spherocytosis

• mild cases are left alone

• splenectomy is there is too much hemolysis

  • Removes the site of destruction but not the defect

  • avoid as long as possible

Hereditary elliptocytosis defect involves

• abnormal elasticity of RBC due to spectrin mutations

• cell membrane is leaky to sodium and causes cell to use more ATP than usual

CBC:

• WBC and plts normal

• mild anemis HgB>12

• slight increase in retic <4%

• diff shows more than 90% ovals

• marrow has erythroid hyperplasia

• osmotic fragilityis normal

elliptocytosis

Hereditary pyropoikilocytosis defect

bizzare shapes such as micro sphereocytes and frags form in the blood when exposed to heat

Hereditary stomatocytosis defect

altered cation permeability causes either dehydrated or overhydrated forms

Hereditary Acanthocytosis defect

congential condition that has complete lack of Beta lipoproteins in serum

G6PD deficiency is associated with what populations

mediterranean and black

G6PD can trigger hemolysis episodes when people are exposed to

• oxidative drugs

• newborn stress

• severe infections

• fava beans

What is the mechanism of hemolysis in G6PD def.

• reduced glutathione which is the protection RBCs have against oxidants

• causes globin to get oxidized and globins get denatured

• this creates heinz bodies

G6PD when a hemolytic event occurs does what to the patient

• H-H will fall a little

• few spherocytes or bite cells

• increased plasma hemoglobin

• hemoglobinuria

• decreased haptoglobin and increased bilirubin

what tests diagnose G6PD def.

• quantitative assay for G6PD

• screening test using a hemolysate and a dye

• Flourescent spot test using NADP and NADPH conversion rates

Pyruvate kinase def. most seen in what pop.

N. europeans

PK is used as the last step of what pathway

glycolysis

How do you diagnose PK deficiency

rule everything else out or use fluorescent screening test

What is the mechanism of anemia in PK deficiency

lack of ATP causes issues with ions and water forcing cells to wear out early

Lab data:

• WBC and plt normal

• RBC N/N- no spherocytes

• increased polychromasia

• increased unconjugated bilirubin

• decreased haptoglobin

PK def.

What is the mechanism of paroxysmal nocturnal hemoglobin

missing CD55 ad CD59, makes RBCs more sensitive to complement

causes chronic extravascular hemolysis at night due to respiratory acidosis

What is the screening test for PNH

sucrose lysis test

What is the confirmatory test for PNH

Ham’s acid serum test or just FLOW