Pernicious Anaemia and Haemolytic anaemia

Question 1

B12 deficiency

Answer 1

can be caused by insufficient dietary intake or pernicious anaemia / coeliac / malabsorption / bacterial overgrowth of bowel

COCP and pregnancy and metformin lower your b12 levels

Question 2

what is the pathophysiology of pernicious anaemia

Answer 2

parietal cells of the stomach produce intrinsic factor which is needed for the absorption of vitamin b12 and iluem.

perinicious anaemia is an autoimmune condtioin where antibodies are created against the parietal cells or intrinsic factor thus preventing the absorption of vitamin b12

Question 3

symptoms of b12 deficiency

Answer 3

(neurological)
Peripheral neuropathy with numbness or paraesthesia (pins and needles)
Loss of vibration sense or proprioception
Visual changes
Mood or cognitive changes

Question 4

investigation for pernicious anaemia

Answer 4

auto antibodies

1. intrinsic factor
2. gastric parietal cell antibody (less helpful)

Question 5

management of pernicious anaemia

Answer 5

if due to a dietary deficiency then oral replacement of vitamin b12 with cyanocobalamin

if due to pernicious anaemia than usually oral intake would be inadequate as the problem is due to absorption.

1mg of IM hydroxocobalamin 3 times weekly for 2 weeks then every 3 months apart.

more intense regimes- 1mg every other day until symptoms improve.

if folate deficiency then treat b12 first because treating folic acid when they have a b12 deficiency can lead to subacute combined degeneration of the cord?

Question 6

What is haemolytic anaemia?

Answer 6

Destruction of RBC (haemolysis) leading to anaemia

lots of inherited conditions that can cause RBC to be more fragile and vulnerable to breaking down

lots of acquired condition that cause the increased break down of RBC

Question 7

inherited haemolytic anaemia

Answer 7

Hereditary Spherocytosis
Hereditary Elliptocytosis
Thalassaemia
Sickle Cell Anaemia
G6PD Deficiency

Question 8

acquired haemolytic anaemia

Answer 8

Autoimmune haemolytic anaemia
Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn)
Paroxysmal nocturnal haemoglobinuria
Microangiopathic haemolytic anaemia
Prosthetic valve related haemolysis

Question 9

clinical features of haemolytic anaemia

Answer 9

anaemia (reduced RBC circulating)
splenomegaly (spleen is filled with destroyed RBC)
jaundice (bilirubin is released during the destruction of RBC)

Question 10

investigations of haemolytic anaemia

Answer 10

Full blood count shows a normocytic anaemia
Blood film shows schistocytes (fragments of red blood cells)
Direct Coombs test is positive in autoimmune haemolytic anaemia

Question 11

inherited haemolytic anaemia: hereditary spherocytosis

Answer 11

most common in northern europeans
autosomal dominant

RBC are fragile so easily break down when passing through the spleen

clinical features:
jaundice
gall stones
splenomegaly
aplastic crissi in the presence of parvovirus
FHx

investigations
spherocytes on blood film
MCHC raised
reticulocytes

tx: folate and splenectomy
cholecystectomy of gallstones

Question 12

inherited haemolytic anaemia: hereditary elliptocytosis

Answer 12

similar to hereditary spherocytosis
RBC are ellipse shaped
autosomal dominant

same presentation and mx as hereditary spherocytosis.

Question 13

inherited haemolytic anaemia: G6PD deficiency

Answer 13

defect in the RBC enzyme G6PD

more common in Mediterranean and African patients
X linked recessive
‘Crisis’ are triggered by infections, medications (e.g antimalarial primaquine, Ciprofloxacin, sulfonylureas, sulfasalazine, fava beans (broad beans)

clinical features:
jaundice (neonatal period)
gall stones
anaemia
splenomegaly

investigate:
Heinz bodies on blood film
G6PD enzyme assay

Question 14

autoimmune haemolytic anaemia

Answer 14

antibodies are created against the patient’s RBC
two types based on the temperature the antibodies function at.

1. warm type: common. haemolysis occurs at normal or above temperatures. idiopathic
2. cold type / cold agglutinin disease. at temp lower than 10’C the antibodies against RBC agglutinate and destroy. usually secondary to other conditions- lymphoma, leukaemia, SLE, myocplasma, EBV, CMV, HIV.

Question 15

management of autoimmune haemolytic anaemia

Answer 15

Blood transfusions
Prednisolone (steroids)
Rituximab (a monoclonal antibody against B cells)
Splenectomy

Question 16

alloimmune haemolytic anaemia

Answer 16

occurs when there are foreign RBC circulating in bloodstream (which patients immune system destroys) OR foreign ANTIBODY circulating which attacks the patients RBC

• transfusion reaction
• haemolytic disease of the newborn

Question 17

haemolytic disease of the newborn

Answer 17

antibodies cross the placenta from the mother to fetus

maternal antibodies target the antigen on the RBC of the fetus

Question 18

haemolytic transfusion reaction

Answer 18

RBC is transfused into the patient. the immune system produces antibodies against antigens on the foreign RBC. creates an immune response which leads to the destruction of the RBC

Question 19

paroxysmal nocturnal haemoglobinuria

Answer 19

rare condition
specific genetic mutation in haematopoetic stem cells in the bone marrow occurs.

this leads to a loss of proteins on RBC which usually inhibits the complement cascade so now there is activation of he complement cascade- destruction of RBC

red urine- HB and haemosiderin
anaemia
predisposed to thrombosis
smooth muslce dystonia

tx:
ecluzimab
bone marrow transplantation

Question 20

microangiopathic haemolytic anaemia (MAHA)

Answer 20

small blood vessels have structural abnormalities which cause haemolysis of the red blood cells as they pass through.

mesh inside the small blood vessels shredding the RBC. usually secondary to:
Haemolytic Uraemic Syndrome (HUS)
Disseminated Intravascular Coagulation (DIC)
Thrombotic Thrombocytopenia Purpura (TTP)
Systemic Lupus Erythematosus (SLE)
Cancer

Question 21

prosthetic valve haemolysis

Answer 21

a complication of a prosthetic heart valve
bioprosthetic and metallic

the turbulence around the valve causes a collision of RBC = break down

mx:
Monitoring
Oral iron
Blood transfusion if severe
Revision surgery may be required in severe cases

Question 22

risk of giving hb when really needed it b12

Answer 22

bone marow is full of cells when there is b12 deficiency. when you correct it and give b12, all the cells which could not make start releasing loads of hb they start maturing

EPO was still being produced

pancytopenia is typical in severe b12. b12 deficiency affects RBC then platelets then WBC.

remove lots of blood

Question 23

jaundice in b12

Answer 23

lots of rbc but cannot mature because of b12 so they break down into bilirubin = yellowing. unconjugated bilirubin.