HEMOLYSIS Flashcards
What component of hemolysis is responsible for the manifestation of jaundice ?
- Bilirubin release from the red cells
Define hemolysis.
- premature red cell destruction
avg lifespan is 120 days
WHy are red cells susceptible to damage?
- biconcave shape to transit —-so ANY CHANGE in shape of the red cell is bad
- limited metabolic reserve (no mitochondria; relies completely on GLUCOSE )
- can’t generate new proteins ! Since leaving the bm)
Define compensated hemolysis.
- incr. red cell destrcution compensated by INCR. red cell prodn (with incr. erythropoitin prodn)
- —Hb is MAINTAINED
What occurs in hemolytic anemia that becomes in a decompensated state?
- red cell destruct. EXCEEDING THE bone marrow CAPACITY to compensate for loss
- –Hb FALLS
Consequences of hemolysis.
- erthryoid hyperplasia
- excess red cell destrc. products (BILIRUBIN)
What is the issue with diagnosing hemolytic anaemia?
- rely on DETECTING the CONSEQUENCES of hemolysis and investigating the cause
How does the Bone marrow respond to hemolysis?
- reticulocytosis
- erythroid hyperplasia
Are reticulocytes nucleated cells?
Are they diagnostic of Hemolysis?
NO
- –appear bluer d.t ribosomal RNA
- —appear BIGGER than red cells
NO; just means the BONE marrow is able to RESPOND to the anemia
How does the blood film of a hemolytic pt look like?
POLYCHROMASIA (RIBOSOMAL rna)
How does automated reticulocyte counting occur ?
- RIBOSOMAL RNA is labelled with flurochrome
- cells are COUNTED
How does the bone marrow appear under the miscroscope in erythroid hyperplasia? -
Large no.s of erythroblasts
What is meant by intra-vascular hemolysis? -
break down of the red cells IN THE blood vessels
Where does extravascular hemolysis occur?
- at the reticuloendothelial sys. (LIVER AND SPLEEN)
- commoner
- HYPERPLASIA at site of the destruct.
- release of PROTOPORPHYRIN
What is seen with release of protoporphyin?
- unconjugated bilirubinemia
- JAUNDICE
- GALL stones
- urobilinogenuria
What is seen in lab findings with intravascular hemolysis?
- Hemoglobinemia
- Methaemalbmuninaemia
- hemoglobinuria (PINK urine; BLACK ON STANDING )
- hemosiderinuria (IRON in the urine)
What are the causes of Intravascular hemolysis?
- ABO incompatible blood transfusion
- G6PD deficiency
- Severe falciparum malaria (Blackwater Fever)
- Rarer still PNH,PCH
What is G6PD?
red cell enzyme
What causes extravascular anemia?
- all other causes of hemolysis
- less life threatening !
How to confirm hemolytic state?
What are Haptoglobins responsible for?
- FBC (+ BLOOD FILM)
- Reticulocyte count
- Serum unconjugated bilirubin
- Serum haptoglobins (REDUCES; binds to free Hb)
- Urinary urobilinogen
What may the blood film help in identifying?
Membrane damage (SPHEROCYTES) Mechanical damage (red cell fragm.) Oxidative damage (Heinz bodies) others (HbS)
WHat do red cell fragments indicate?
vascular hemolysis
What are special ivx for AUTOIMMUNE hemolysis?
- DIRECT COOMBS’ TEST and others
How can hemolysis be classified by?
- the SITE of red cell defect .
What are the diff. sites of red cell defects?
- abnormal cell membrane
- abnormal red cell metabolism
- abnormal Hb
- premature destrc. of NORMAL red cells (autoimmune
What Abs do autoimmune hemolysis include?
WARM (IgG)
Cold (IgM)
When may warm Abs be produced?
- idiopathic (commonest)
- AUTOIMMUNE d.o (SLE)
- Drugs (penicillins at v.high doses IM- not seen )
- Infections
- CLL (lymphoproliferative d.o)
When are COLD Abs produced?
- infections (EBV/ mycoplasma)
idiopathic
lymphoproliferative d.o
How is direct coomb’s test performed
identifies Abs BOUND to OWN red cell
- patients own RBCs are mixed with a mouse Anti-human IgG—PRESENCE OF THE
What is an ALLOIMMUNE hemolysis?
-“allo”= other
—-immune response to Non-self Ag from members of the SAME species
Abs produced as an IMMUNE RESPONSE!
(iMMEDIATE IgM release intravscularly)
(delayed IgG EXTRAVASCULARLY)
When may alloimmune hemolysis occur?
HEMOLYTIC TRANSFUSION RXN
HEMOLYTIC DISEASE OF NEW BORN (Rh D/ ABO compatibility/ anti-Kell)
How may MECHANICAL red cell destruct. occur?
- DIC
- Hemolytic uremic syndrome (E.coli)
- TTP
- LEaking Heart Valve
- malarial infections
What is seen the blood film on slide 36?
- microspherocytes
(seen with BURNS) —-RED CELLS ARE SHEARED through DAMAGED capillaries
When may red cell membrane defects occur?
VERY RARE conditions:
Liver Disease (Zieve’s Syndrome)
Vitamin E deficiency
Paroxysmal Nocturnal Haemoglobinuria
What is seen in Zieve’s Syndrome?
Anaemia
Polychromatic macrocytes – reticulocytes
Irregularly contracted cells
WHat are the clinical findings of Zieve’s Syndrome?
- hemolysis
- alcoholic liver disease
- hyperlipidemia
Name some example of red cell membrane abnormalities .
Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen causes extravascular red cell destruction
Hereditary Spherocytosis
What is an example of abnormal red cell metabolism?
- failure to COPE with OXIDANT stress
- failure to gen. ATP
What is seen with G6PD def. in the blood film?
- BITE CELLS
- contracted cells
What are ex. of abnormal Hb cause of hemolytic anaemia?
- sickle cell disease—shortens red cell survival !
- –point mutation in BETA-GLOBIN chain
- –assymptomatic if a trait
What occurs in hereditary spherocytosis, for it to cause anaemia?
- d.t inherited defects in red cell membrane skeleton—-loss of typical biconcave shape.
- instead form non-deformable red cells, vulnerable to sequestration and destruction by the spleen
Explain the pathophysiology of G6PD .
- G6PD is required in the rate-limiting step of the hexose monophosphate shunt,in which is CONVERTS NADP to NADPH
- NAPH is needed to generate glutathione from Oxidative glutathione! —-so low amounts of glutathione is produced
Why is glutathione important?
- important for the protecting the red cell from reactive oxygen species.
Why does splenomegaly occur in hereditary spherocytosis?
- site of spherocyte sequestration and destruction
- —d.t congestion of splenic cords (and incr. no. tissue marcophages)
What may exacerbate hereditary spherocytosis? Why?
APLASTIC CRISIS!
- Parvovirus B19 - infects and destroys erythroblasts in the bone marrow
- spherocytes already have a SHORTENED life span—-incr. destruction
- so even a few days of decr. prodn of red cells d.t Parvovirus b19—> rapid progression of ANAEMIA within days !