Hemolytic anaemia with emphasis on lab diagnosis Flashcards
What is hamolysis
premature destruction of RBCs
How do hemolytic anemias arise
When the RBCs are being destroyed at a faster rate than the body can compensate for
What is a hemolytic disorder
A condition that leads to the reduction in mean lifespan of RBCs
Haemolytic anemia is silent until
Mean lifespan of RBC is about 30 days
What is erythroid hyperplasia
increased activity of the bone marrow in order to compensate for increase in destruction of RBCs
Breakdown of haemoglobin
haemoglobin
- haem group—-> Iron and protoporphyrin ring
- globin group—–> Amino acids
Iron in haem group function
Iron is ferried to erythroblasts via transferrin and used in the formation of red blood cells. It is reused
Protoporphyrin ring is made up of
bilirubin and Co2
CO2 leave the body via expiration
Bilirubin is conjugated by the liver and expelled as stercobilin through feces and urobilinogen in urine
Why do RBCs rely on glycolysis for energy
Because they lack mitochondria they rely on glycolysis for materials required to prevent oxidative damage. Limitations in glycolysis however make them more susceptible to oxidative damage
Classification of hemolytic anemias
Site of hemolysis
site of defect
inherited or acquired
What are the types of hemolysis that occur at a site
intravascular hemolysis
extravascular hemolysis
combination of both intra and extravascular hemolysi
What is intravascular hemolysis
Release of broken down RBC into vascular space or blood stream. This causes the release of free Hb into the system,which on its own is toxic to the body
How does free Hb cause toxicity in the body
Free Hb binds to haptogloblin
Haptoglobin binding prevents the binding of heam and albumin from happening
, If this doesnt happen, Free Hb oxidizes and releases heam group which binds to albumin or hemopexin
this causes increased methemalbumin and oxidative stress
What is extravascular hemolysis
This is when macrophages of reticular endothelial system destroy RBCs
Lab signs of extravascular hemolysis
erythroid hyperplasia
hemosiderosis ( collection of iron deposits on tissues)
hyperbilirubinemia
increased excretion of bilirubin
Clinical states that present with extravascular hemolysis
Autoimmune hemolysis Hereditary spherocytosis haemoglobinopathies i.e SSD, thalassemia Delayed hemolytic transfusion reactions Hypersplenism
Clinical states associated with intravascular hemolysis
Sepsis severe burns paroxysmal nocturnal hemoglobinuria acute hemolytic transfusion reactions severe microangiopathic reactions physical trauma
Site of defect types
- defect found in red cell- intrinsic defect.
i. e in sickle cell disease there is a problem wrong with Hb - defect found in RBC environment, nothing fundamentally wrong with RBC- extravascular defect
i. e antibodies cause destruction of RBCs
inherited hemolytic anemia are usually
intrinsic in nature
Acquired hemolytic anemias
are usually extrinsic in nature
This acquired hemolytic anemia is intrinsic in nature
Paroxysmal nocturnal hemoglobinuria
Conditions that cause inherited hemolytic anemia
- Membrane defects
i. e hereditary spherocytosis - Metabolic defects
i. e G6PD deficiency - Hb defects
i. e Sickle cell anemia
Conditions that cause acquired hemolytic anemia
Paroxysmal nocturnal hemoglobinuria Chemical and physical agents infections march hemoglobinuria red cell fragmentation syndromes Immune conditions i.e autoimmune hemolytic anemia
How to diagnose hemolytic anemia
- family history
- history of infections,behaviours
- Ethnic origin i.e G6PD deficiency very common in chinese
- Past history i.e neonatal jaundice
Clinical features of hemolytic anemia
pallor of mucus membrane jaundice splenomegaly dark urine due to hb in urine pigment gall stones ulcers around ankle; due to hb mopping up vasodilator NO--> vasoconstriction--> decreased blood and nutrient supply--> tissue necrosis hypertrophic skeletal changes i.e bone marrow overworks and enlarges growth retardation aplastic changes
Lab features of increased red blood cell breakdown
increased urine urobilinogen increased fecal stercobilinogen raised serum bilirubin reduced serum hemopexin increased free haptoglobin, because haptoglobins are produced in excess to bind free Hb which is toxic in its free form increased lactate dehydrogenase
Peripheral blood film features of hemolytic anemia
- normocytic/macrocytic cells
- polychromasia–bluish young RBC mixed with pinkish older RBC. Staining done with Leishman stain
- Nucleated RBCs– young RBCs are nucleated before losing it as they grow. Due to increased production of young RBC into blood stream, cells are seen as nucleated
- Schistocytes-red cell fragments
- Micro spherocytes - spherical instead if biconcave hence will lose area of central pallor
- Elliptocytes
- Helment cells i.e. in G6PD deficiency
- Reticulocytes -young RBCs. Staining done with supravital stains
- Howell Jolly bodies
Heinz bodies in G6PD deficiencies
are bitten off to look like helments
Tests for hemolytic anemia
coombs test
osmotic fragility test
Stain for reticulocytes
cresyl blue
methylene blue
Dark urine is a feature of
intravascular hemolysis
blood rich in free Hb is filtered by kidney–>Hb present in urine
Lab features of intravascular hemolysis
hemoglobinuria
hemoglobinemia- increased Hb in plasma
hemosiderinuria - iron deposits in urine
methemoglobin - Hb plus albumin complex. Detected by schumms test
Autoagglutiation
A form of autoimmune hemolytic anemia, where red cells stick together
