0-Finals Haem

Question 1

When would you see these common blood film findings?

Anisocytosis (variation in RBC size)

Target cells

Heinz bodies (individual blobs seen in the rbcs)

Howell Jolly bodies (dna blobs seen in rbc)

Reticulocytes (immature rbcs that are larger than standard rbcs)

Schistocytes (fragments of rbcs)

Sideroblasts (immature rbcs with iron blobs in them)

Smudge cells (ruptured wbcs)

Spherocytes

Answer 1

Anisocytosis = myelodysplastic syndrome

Target cells = iron def, post splenectomy

Heinz bodies = G6PD and alpha-thalassaemia

Howell Jolly Bodies = post splenectomy or severe anaemia where rbcs are being regenerated v quickly

Reticulocytes = rapid turnover of cells like haemolytic anaemia (when bone marrow is actively replacing lost cells)

Schistocytes = (indicate physical trauma to rbcs eg due to networks of clots in blood vessels) Haemolytic uraemic syndrome, DIC, TTP, metalic heart valves, haemolytic anaemia

Sideroblasts = myelodysplastic syndrome

Smudge cells = chronic Lymphocytic Leukaemia

Spherocytes = autoimmune haemolytic anaemia, hereditary spherocytosis

Question 2

What are some causes of microcytic anaemia?

Answer 2

T = thalassaemia

A = anaemia of chronic disease (different to iron def as there is high/normal ferritin)

I = iron deficiency anaemia

L = lead poisoning

S = sideroblastic anaemia

Question 3

What are some causes of normocytic anaemia?

Answer 3

2Hs and 3As

H = haemolytic anaemia

H = hypothyroidism

A = aplastic anaemia

A = anaemia of chronic disease

A = acute blood loss

Question 4

What are some causes of macrocytic anaemia?

Answer 4

Either megaloblastic or normoblastic.

Megaloblastic = impaired DNA synthesis. Ie B12 deficiency, Folate deficiency.

Normoblastic = alcohol, reticulocytosis, hypothyroidism, liver disease, drugs like azathioprine

Question 5

What are some signs of anaemia?

(also specific signs of specific anaemias)

Answer 5

• General = pale skin, conjunctival pallor, tachycardia, raised resp rate
• Iron def = pica, hair loss, koilonychia (spoon nails), angular chelitis, brittle hair and nails
• atrophic glossitis is also a sign of iron def
• Jaundice in haemolytic anaemia
• Bone deformities in thalassaemias
• oedema, htn, excoriations = CKD

Question 6

How is iron absorbed?

Answer 6

• absorbed in the duodenum and jejunum
  
  • therefore conditions like coeliac or crohns interfere with iron absorption
• acid from the stomach converts it from ferric (fe3+) to soluble ferrous (fe2+) form
  
  • therefore meds like PPIs can interfere with iron absorption

Question 7

What are some common causes for iron def?

Answer 7

• blood loss
  
  • think menstruation in women (esp menorrhagia)
  • in non menstruating women/men, think GI bleed. Rule out cancer
  • differentials = oesophagitis, gastritis, IBD
• Dietary insufficiency common in kids
• Poor iron absorption
• Increased dietary requirements eg in pregnancy

Question 8

What tests would you do for iron deficiency?

Answer 8

• Understand that Iron travels around the blood as ferric (fe3+) ions bound to transferrin protein.
• Total Iron Binding Capacity is the space on transferrin for iron to bind.
  
  • TIBC is easier to measure than transferrin.
  • TIBC and transferrin both increase in iron deficiency and decrease in iron overload.
• Transferrins saturation is the proportion of transferrin molecules that are bound to iron.
  
  • usually around 30% in adults
  • Less iron in the body means the body transferrin will be less saturated
  • Obviously saturation temporarily goes up after an iron rich meal, so most accurate test is on fasting sample
• Ferritin is the form if iron that is stored in cells.
  
  • Therefore low ferritin usually means iron deficiency.
  • However ferritin is also released from cells during inflammation, so can be abnormally high in inflammation eg infection or cancer.
  • Therefore a man with cancer that has a normal ferritin, could still have iron def anaemia.
• Serum iron varies throughout the day (higher in the mroning and after iron rich meals) therefore it is not so useful

False high values giving the impression of iron overload

= suplementation with iron or acute liver damage (lots of iron stored in the liver)

Question 9

How would you manage iron deficiency?

Answer 9

• treat underlying cause
• blood transfusion
  
  • good for anaemia, but does not correct underlying iron def
• iron infusion eg. cosmofer
  
  • avoid during sepsis as iron “feeds” bacteria
• Oral iron eg ferrous sulphate (se constipation and black stools)
  
  • unsuitable where malabsorption is the cause

Question 10

How does pernicious anaemia (ie B12 deficiency anaemia) happen?

Answer 10

Either just a dietary lack of B12 or

Pernicious anaemia...

• Parietal cells in the stomach produce intrinsic factor
• Intrinsic factor helps absorb vitamin B12 in the Ileum
• Pernicious anaemia = an autoimmune condition where there are antibodies against the parietal cells or intrinsic factor
  
  • This obviously interferes with B12 absorption

Question 11

How would you manage pernicious anaemia?

Answer 11

• 1st line = Test for intrinsic factor antibody
  
  • Gastric Parietal Cell antibody less useful
• oral replacements like Cyanocobalamin can treat dietary deficiency
• In pernicious anaemia this is inadequate so give 1mg IM Hydroxycobalamin 3x weekly for 2 weeks
• In folate deficiency, treat B12 def first!!!
  
  • treating b12 deficiency with folic acid can lead to subacute combined degeneration of the cord

Question 12

What are haemolytic anaemias?

What are some inherited and acquired

Answer 12

Where there is destruction of RBCs (haemolysis) leading to anaemia.

Inherited Haemolytic Anaemias

• hereditary spherocytosis
• hereditary elliptocytosis
• thalassaemia
• sickle cell anaemia
• G6PD def

Acquired Haemolytic Anaemias

• autoimmune haemolytic anaemia
• alloimmune haemolytic anaemia (trasnfusion reactions and haemolytic disease of the newborn)
• Paroxysmal nocturnal haemoglobinuria
• Microangiopathic haemolytic anaemia
• Prosthetic valve related haemolysis

Question 13

How would hereditary spherocytosis present?

Management and presentation is typically the same for hereditary elliptocytosis***

Answer 13

• autosomal dominant, common in northern europe
• causes sphere shaped RBCs that easily break when passing through the spleen
• Presents with jaundice, gallstones, splenomegaly
  
  • also aplastic crisis with Parvovirus

Management

• do blood film = spherocytes
• Mean Corpuscular Haemoglobin Conc and Reticulocytes are raised
• Manage with folate supplementation and Splenectomy.
• Do a cholecystectomy with gallstones

Question 14

How does G6PD deficiency present?

Answer 14

• X linked recessive, a defect in enzyme G6PD
• triggered by infections, fava beans, medications (antimalarials like primaquine, ciprofloxacin, sulfonylureas, sulfasalazine, etc)
  
  • results in haemolytic crises
• Will present with jaundice, gallstones, anaemia, splenomegaly, Heinz bodies on blood film
• Do G6PD enzyme assay

Question 15

What are the two types of autoimmune haemolytic anaemias?

Answer 15

AIHA overall is when antibodies are created against the patients RBCs resulting in haemolysis.

Warm type AIHA is more common…

• Haemolysis occurs at normal or above normal temp
• typically idiopathic

Cold type AIHA

• also called cold agglutinin disease
• at low temperatures like below10C the antibodies attach themselves to RBCs and cause them to clump = agglutination
• the immune system is activated by these clumps and destroys them in the spleen.
• Cold type AIHA is typically secondary to lymphoma, leukaemia, SLE, or infections (EBV, CMV, HIV, mycoplasma)

Question 16

How would you manage autoimmune haemolytic anaemias?

Answer 16

• Blood transfusions
• Prednisolone
• Rituximab
• Splenectomy

Question 17

What is thalassaemia?

Answer 17

Understand that normal Haemoglobin is 2 alpha and 2 beta globin chains.

Thalassaemia is a genetic defect in the protein chains in Hb.

Defects in the alpha-globin chains = alpha thalassaemia

Defects in the beta-globin chains = beta thalassaemia

These conditions are autosomal recessive.

The defective RBCs are fragile and constantly get destroyed and collected in the spleen = splenomegaly.

The bone marrow expands to produce extra RBCs to make up for this chronic anaemia = susceptibilty to fractures, features like pronounced forehead and malar eminences

Question 18

How would you manage alpha thalassaemia?

Answer 18

• this is due to defects on the genes coding for alpha-globin chains = chromosone 16

Management

• monitor fbc
• monitor for complications like iron overload (monitor ferritin)
  
  • manage with limiting transfusions and doing iron chelation
• blood transfusions
• splenectomy
• bone marrow transplant can be curative

Question 19

How would you manage beta thalassaemia?

Answer 19

• Chromosome 11 defects
• the mutations can cause abnormal copies of the genes or deletion genes

Thalassaemia minor = pts are carriers of one abnormal beta globin gene and one normal gene

• mild microcytic anaemia
• no need treatment, just monitor

Thalassaemia intermedia = 2 abnormal genes, or 1 abnormal and 1 deletion

• significant microcytic anaemia
• needs monitoring and occasional blood transfusions
• potentially iron chelation to prevent iron overload if they have more transfusions

Thalassaemia major = homozygous for deletion genes

• severe microcytic anaemia
• failure to thrive in early childhood
• splenomegaly
• bone deformities
• You need regular transfusions and iron chelation
• Also splenectomy
• Bone marrow transplant can be curative
  *

Question 20

How does sickle cell anaemia happen?

Answer 20

• Foetal haemoglobin (HbF) is usually replaced by Haemoglobin A (HbA) at around 6 weeks old.
• Patients with sickle cell have Haemoglobin S (HbS) instead, resulting in the sickle shape.
• They are autosomal recessive and are due to an abnormal beta globin gene on chromosome 11
  
  • one copy of the gene = sickle cell trait
  • two abnormal copies = sickle cell disease

*** sickle cell trait reduces malaria severity so there is a selective advantage of having sickle cell gene in areas of malaria

Question 21

When would you test for sickle cell?

Answer 21

Newborn screening heel prick test at 5 days old

Question 22

What are some complications of sickle cell?

Answer 22

• anaemia
• increased infection risk
• stroke
• avascular necrosis in joints like the hip
• pulmonary hypertension
• priapism
• CKD
• sickle cell crises
• acute chest syndrome

Question 23

How would you manage sickle cell? generally

Answer 23

• avoid dehydration and other crises triggers
• ensure vaccines are up to date
• antibiotic prophylaxis eg. pencillin V (phenoxymethylpenicillin)
• Hydroxycarbamide to stimulate production of HbF (protects against crises and ACS)
• Blood transfusions for anaemia
• Bone marrow transplant = curative

Question 24

What are some sickle cell crises?

Answer 24

Vaso-occlusive Crisis

• sickle shaped RBCs clogging capillaries = distal ischaemia
• associated with dehydration and haematocrit
• present with pain, pyrexia, trigger symptoms eg dehydration symptoms
• Can cause priapism in men = aspirate!!!

Splenic sequestration crisis

• RBCs block blood flow in the spleen = acutely enlarged painful spleen
• pooling of blood in the spleen = severe anaemia and circulatory collapse (hypovolaemic shock)
• Give blood transfusions and fluid resus!!!
• Splenectomy in recurrent cases! obvi give prophylactic antibiotics etc as per post splenectomy

Aplastic crisis

• Parvovirus B infection can result in a temporary loss of new blood cell production
• Manage with blood transfusions. typically spontaneously resolves within a week

Question 25

What is acute chest syndrome?

Answer 25

Diagnosis requires

• fever/resp symptoms
• With new infiltrates on a CXR

Manage

• antibiotics or antivirals
• blood transfusions
• incentive spirometry
• artificial ventilation eg NIV

Question 26

What are myeloproliferative disorders?

Ie. primary myelofibrosis, Polycythaemia vera, Essential Thrombocythaemia

Answer 26

Uncontrolled proliferation of a single type of stem cell! They are considered a kind of bone marrow cancer.

They have the potential to turn into AML.

Associated with JAK2, MPL, CALR

Primary myelofibrosis = proliferation of haematopoietic stem cells

Polycythaemia vera = proliferation of erythroid cells

Essential thrombocythaemia = proliferation of megakaryocyte cell line

Question 27

What is myelofibrosis?

Answer 27

• This is when proliferation of a cell line leads to fibrosis of bone marrow, so it is replaced by scar tissue.
• This is because prolferating cells release cytokines (like fibroblast growth factor) that trigger this fibrosis
• This fibrosis can cause anaemia
• Haematopoiesis also gets moved to the liver and spleen (extramedullary haematopoiesis) due to the bone marrow being replaced by scar tissue
• this causes hepatomegaly and splenomegaly
• this can result in portal hypertension
• Can also cause spinal cord compression if it occurs near the spine
  *

Question 28

What are 3 key signs of polycythaemia vera?

Answer 28

• Conjunctival plethora (excessive redness)
• Ruddy complexion
• Splenomegaly

Question 29

What are the key investigations for myeloproliferative disorders?

Answer 29

• FBC
  
  • Polycythaemia = raised hb
  • Primary Thrombocythaemia = raised platelets
  • Myelofibrosis = anaemia, leukocytosis/leukopenia, Thrombocytosis/thrombocotypenia
    
    • These findings depend on if it is primary myelofibrosis or secondary to PV, PT.
• Blood film
  
  • Myelofibrosis = teardrop RBCs, Poikilocytosis (varying shaped RBCs), and Blasts (immature RBC and WBC)
• Bone marrow biopsy
  
  • bone marrow aspiration typically dry due to scar tissue
• Test for JAK2, MPL, CALR

Question 30

How would you manage Primary Myelofibrosis?

Answer 30

• allogenic stem cell transplant
• chemotherapy
• supportive and monitoring

Question 31

How would you manage Polycythaemia vera?

Answer 31

• venesection 1st line
• Aspirin to prevent blood clots
• Chemotherapy

Question 32

How would you manage essential thrombocythaemia?

Answer 32

• aspirin to reduce thrombus formation
• Chemotherapy

Question 33

What is myelodysplastic syndrome?

Answer 33

• caused by myeloid bone marrow cells not maturing properly
• this results in unhealthy blood cells being produced
• It therefore presents with low levels of the blood components that originate from the myeloid cell line
  
  • anaemia (fatigue, pallor, SOB)
  • neutropenia (severe/frequent infections)
  • thrombocytopaenia (purpura, bleeding)
• Can transform into AML

Management

• bone marrow aspiration and biopsy gold standard
• blasts on blood film
• Manage with supportive treatment like blood transfusions if severely anaemic
• Stem cell transplantation
• Chemotherapy
  *

Question 34

What are some causes of Thrombocytopaenia?

Answer 34

Problems with production

• sepsis
• b12 or folic acid deficiency
• liver failure resulting in reduced thrombopoietin production
• leukaemia
• myelodysplastic syndrome

Problems with destruction

• meds like sodium valproate, methotrexate, isotretinoin, antihistamines, PPIs
• alcohol
• ITP
• TTP
• Heparin induced thrombocytopaenia
• HUS

Question 35

What are some key differentials for abnormal or prolonged bleeding?

Answer 35

• von willebrand disease
• thrombocytopaenia
• haemophilia A
• haemophilia B
• Disseminated Intravascular Coagulation (typically secondary to sepsis)

Question 36

What is ITP?

Answer 36

Immune Thrombocytopenic Purpura

• antibodies are created against platelets causing their destruction

Management

• prednisolone
• IV immunoglobulins
• Rituximab
• Splenectomy
• monitor platelets and educate patients to seek help if persistent headaches or melaena
• monitor BP and suppress menstrual periods

Question 37

What is TTP?

Answer 37

Thrombotic Thrombocytopenic Purpura

• Microangiopathy where tiny clots develop in small vessels of the body, using up platelets
• this causes thrombocytopaenia, bleeding under the skin, etc.
• The blood clots develop due to ADAMTS13 deficiency (either genetic or autoimmune)
  
  • this protein typically inactivates von willebrand factor and reduces platelet adhesion to vessel walls and clot formation
  • A shortage in this protein results in von willebrand factor overactivity and loads of clots forming
  • The clots also result in rbc damage when they flow past them = haemolytic anaemia

Management

• haematology referral
• plasma exchange
• steroids
• rituximab

Question 38

What is Von Willebrand disease?

Answer 38

• Most common inherited casue of abnormal bleeding!
• most causes are autosomal dominant
• typically absence or malfunctioning of a glycoprotein called von willebrand factor
• type 1-3, 3 is most severe

Presentation

• bleeding gums with brushing
• nose bleeds
• menorrhagia
• heavy bleeding during surgery
• Fhx of von willebrand or heavy bleeding

Management

• Desmopressin to stimulate VWF release
• VWF infusions
• factor VIII often infused along with plasma derived VWF
• menorrhagia = Tranexamic acid/ mefanemic acid/ norethisterone/ COCP/ Mirena . Hysterectomy last resort

Question 39

What is haemophilia?

Answer 39

• Haemophilia A and B are severe X linked recessive bleeding disorders
  
  • therefore almost exclusively male as men only need one abnormal X, while women have 2 Xs and are only a carrier with one copy
• Haemophilia A = factor VIII deficiency
• Haemophilia B = factor IX deficiency

Presentation

• spontaneous haemorrhage eg gums, GI, haematuria, retroperitonea, etc.
• neonates = intracranial haemorrhage, haematomas, cord bleeding
• severe = haemoarthrosis and spontaneous muscle bleeding

Question 40

How would you manage haemophilia?

Answer 40

• replace factor VIII or factor VIX with IV infusions
  
  • either prophylactically or in response to bleeding
  • however you can form antibodies against the clotting factor and this treatment can become useless
• Acute episodes or bleeding or prevention of excessive bleeding in surgery
  
  • infusions of factor VIII or IX
  • desmopressin to stimulate VWF
  • antifibrinolytics like tranexamic acid