Haemolysis

Question 1

haemolysis

Answer 1

red cell destruction
shortened red cell survival

Question 2

why are red cells susceptible to damage

Answer 2

no nucleus, mitochondria etc

rely on biconcave shape so any problem with shape they are gonna struggle

cant generate new proteins once in circulation

Question 3

compensated haemolysis

Answer 3

increased red cell destruction compensated by increased red cell production

Question 4

haemolytic anaemia

Answer 4

increased rate of rred cell destruction exceeding bone marrow capacity for red cell production

Question 5

consequences of haemolysis

Answer 5

Erythroid hyperplasia

Reticulocytosis

Excess red cell breakdown products eg billirubin

clinical features differ by aetiology and site of red cell breakdown

Question 6

can you directly measure red cell survival

Answer 6

no it relies on detecting the consequences of haemolysis and then investigating the cause

Question 7

bone marrow response to haemolysis

Answer 7

reticulocytosis

erythroid hyperplasia

Question 8

are reticulocytes nucleated cells

Answer 8

no

Question 9

what is erythroid hyperplasia

Answer 9

increase in red cell precursors- erythyroids in bone marrow

Question 10

most commonly used stain for reticulocytes

Answer 10

methylene blue as it stains the residual rna making them appear dark blue granular cells

Question 11

diagnosis of haemolysis criteria

Answer 11

Evidence of increase red cell production
AND
Evidence of increased red cell breakdown products

Question 12

products of red cell destruction

Answer 12

bilirubin

Question 13

what happens if red cell destruction is outside the macrophage

Answer 13

free hb circulates and needs removed

can clog the kidneys and emerge in urine - haemoglobunuria

binds to albumin - methaemalbuminaemia

binds to haptoglobin and removed

Question 14

how do classify where haemolysis is occuring

Answer 14

Pathophysiological approach – by site in the red cell where the problem is occurring

A practical approach by site in the body where the haemolysis is occurring

Extravascular (ie in the macrophage as normal)

Intravascular (ie in the circulation – not normal so generates a short differential list)

Question 15

extravascular red cell destruction

Answer 15

breakdown outside blood vessels particularly in spleen, bone marrow and liver

more common

macrophages eat up aged or damaged cells

Question 16

what does extravascular haemolysis release

Answer 16

protoporphyrin which can then be broken down into bilirubin

normal products but in excess

Question 17

intravascular red cell destruction

Answer 17

red cells destroyed in circulation spilling their contents immediately

not normal

Question 18

reactions occuring in intravascular haemolysis

Answer 18

Haemoglobinaemia (free Hb in circulation)

Methaemalbuminaemia (Hb mopped up by albumin)

Haemoglobinuria: pink urine, turns black on standing

Haemosiderinuria (iron taken up by tubular cells and converted to haemosiderin the cells are later shed into urine)

Question 19

intravascular causes

Answer 19

ABO incompatible blood transfusion

Mechanical RBC trauma (March haemoglobinuria,
DIC, HUS/TTP, valve disease)

G6PD deficiency if severe

Rarer still PNH,PCH, severe malaria, toxins
eg clostridia, some snake venoms

Question 20

extravascular causes

Answer 20

essentially all other causes of haemolysis

Question 21

investigations to confirm haemolytic state

Answer 21

FBC (+ BLOOD FILM) identify causes
Reticulocyte count (raised)
Serum unconjugated bilirubin (raised)
Serum haptoglobins (bind free Hb so will be low as consumed in haemolysis)
Urinary urobilinogen (raised)
Lactate dehydrogenase (raised) – non specific

Question 22

alloimmune haemolysis

Answer 22

make an antibody to someone elses red cells that have been given to you or an antibody is given to you that attacks your cells

Question 23

direct coombs test/ direct antiglobulin test use

Answer 23

lab test used to detect antibodies or complement proteins that are bound to the surface of red blood cells

Question 24

uses of dat

Answer 24

haemolytic anaemia, autoimmune disorders and haemolytic disease of new born

Question 25

igm assoc haemolysis

Answer 25

involved in cold agglutination disease igm antibodies bind to red blood cells at lower temps <30 cause clumping of red blood cells

Question 26

abnormal situations resulting in premature destruction

Answer 26

toxins - chlosridia snake venoms rupture of infected red cells by malaria parasites

Question 27

hereditary spherocytosis

Answer 27

most common cause of hemolytic anaemia caused by mutations in genes that code for proteins involved in the red blood cell membrane These defects lead to the formation of abnormally shaped red blood cells (spherocytes) that are less flexible and more prone to breaking when passing through the spleen. Symptoms include anemia, jaundice, and splenomegaly.

Question 28

what is a spherocyte

Answer 28

abnormally shaped red blood cell that is spherical in shape rather than the typical biconcave disk shape.

Question 29

causes of spherocytes

Answer 29

Hereditary Spherocytosis Warm (IgG) haemolytic anaemia Delayed transfusion reaction Haemolytic disease of the newborn Zieve’s Syndrome Drug induced haemolysis Fresh water drowning (but by a hypotonic effect)

Question 30

g6pd deficiency

Answer 30

geentic disorder affecting red blooc cells leading to haemolysis x linked- male problem usually

Question 31

what does g69pd enzyme play a role in

Answer 31

protecting red blood cells from oxidative stress

Question 32

what is sickle cell disease

Answer 32

abnormal haemoglobin structure caused by a point mutatoin in beta chain result in shortened red cell production

Question 33

warm igg assoc haemolysis

Answer 33

igg antibodies bind to red blood cells at normal body temp leading to their premature destrcution

Question 34

pathophysiology of igg automminune hemolytic anemia

Answer 34

igg autoantibodies coat rbcs recognised by macrpohages in the spleen by fc receptors extravascular hemolysis occurs partially phagocytosed leading to formation of spherocytes