Pathology - RBC

Question 0

Macrocytic anaemias suggest?

Answer 0

Abnormalities in bone marrow erythropoid precursor maturation.

Question 1

Microcystic, hypochromic anaemias suggest?

Answer 1

Disorders with Hb synthesis (most often iron deficiency).

Question 2

Release of new RBC in acute blood loss occurs when?

This is heralded by what?

Heralding cells peak when?

Answer 2

Day 5.

Release of new RBCs is heralded by increased numbers of reticulocytes, peaking at 10-15% at day 7.

Question 3

Patients with IV haemolysis have what in their blood?

Compared with EV haemolysis

Answer 3

In addition to anaemia, reduced haptoglobin, and jaundice:

they have haemoglobinaemia, haemoglobinuria, haemosiderinuria, methalbuminaemia.

They do not have splenomegaly as haemolysis is not occurring there!

Question 4

What is renal haemosiderosis?

Answer 4

An accumulation of iron released from haemoglobin (from free haemoglobin and free methaemoglogin) present due to IV haemolysis.

Question 5

What is G6PD deficiency?

Answer 5

G6PD is an enzyme which reduces NADP to NADPH. In turn NADPH reduces RBC glutathione.

If deficient, oxidative stress causes denaturation and Heinz bodies build up causing haemolysis and increased splenic destruction.

Question 6

G6PD is X-linked. Which two variants lead to clinically significant haemolysis?

Answer 6

G6PD- and Mediterranean G6PD, the latter is worse.

Question 7

What is sickle cell disease?

Answer 7

Sickle cell disease is an autosomal recessive haemoglobinopathy resulting from substitution of valine for glutamic acid at the 6th position of the beta globin chain. This leads to mutant HbS replacing normal B-globin.

Question 8

Why is sickle cell disease not manifest in newborns?

Answer 8

HbF interferes with HbS (sickle) so that infants do not manifest until ~6 months when their HbF levels are closer to adults’.

Question 9

Occlusion by sickle cells is a function of?

Answer 9

Percentage of sickle cells AND increased expression of adhesion molecules.

Also, free Hb released by ruptured RBCs bonds NO causing local vasospasm.

Question 10

Effects of Sickle cells on the spleen?

Answer 10

Children get splenomegaly from trapping sickle cells.

Adults get autosplenectomy from repeated episodes of vaso-occlusion.

Question 11

What is the mainstay of Sickle cell treatment?

Answer 11

Hydroxyurea increases HbF levels and reduces the WBC population which reduces inflammation.

Question 12

What are the thalassemia syndromes?

Answer 12

Inheritable disorders of mutations that reduce alpha or beta globin chain synthesis.

Common in the med, Africa, and SEA.

Question 13

Where are the thalassemia genes?

Answer 13

Beta chains are coded by a single gene on chromosome 11.

Alpha chains are coded by two closely linked genes in chromosome 16.

Question 14

What is the Direct Coombs Test?

Answer 14

A test to detect antibodies on RBCs:

A direct Coombs involves mixing the patient’s RBCs with plasma known to contain antibodies against human Ig or complement. Agglutination means the test is positive.

Question 15

What is the Indirect Coombs Test?

Answer 15

A test to detect antibodies on RBCs:

An indirect Coombs involves assessing a patient’s serum for its ability to agglutinate when mixed with test RBCs containing specific surface antigens.

Question 16

What is the most common immunohaemolytic anaemia?

Answer 16

Warm body type where IgG anti-RBC coats the RBCs causing opsonisation.

Cold-agglutinin type is caused by IgM antibodies that agglutinate at low temperatures.

Question 17

Schistocytes are a feature of?

Answer 17

Traumatic haemolytic anaemia.

Caused by increased shear force or valves.

Question 18

Describe normal B12 metabolism:

Answer 18

B12 is bound to salivary R-binders

R-B12 complexes are digested in Duodenum by pancreatic proteases, released B12 is bound to IF.

IF-B12 binds to IF receptors in DI.

Absorbed B12 complexes with transcobalamin and is transported to tissues.

Question 19

Which antibodies are present in pernicious anaemia?

Answer 19

Type 1 (present in 75% of pts) block B12 binding to IF

Type 2 block IF or IF-B12 binding to the ileal receptor

Type 3 antibodies (present in 85-90% of pts) are directed against PP proteins affecting acid secretion.

Question 20

What distinguishes folate from B12 deficiency?

Answer 20

Lack of neurological symptoms and gastric atrophy.

Question 21

What is the role of Hepcidin?

Answer 21

Hepcidin is a hepatic peptide that blocks duodenal iron transepithelial transport by inducing degradation of ferroportin.

Question 22

Why does chronic disease cause anaemia?

Answer 22

Chronic inflammation increases circulating IL-6 which increases Hepcidin production.

Question 23

Which virus is associated with RBC precursor destruction?

Answer 23

B19 parvovirus.

Question 24

What are the effects of Chronic ITP in aPTT, INR, and bleeding time?

Answer 24

Normal INR and aPTT.

Bleeding time is increased.

Question 25

What is HIT?

Answer 25

Heparin Induced Thrombocytopaenia.

Type 1 - occurs immediately after Heparin is given, due to clumping of platelets. Not that bad.

Type 2 - occurs after 5-14 days due to anti-platelet:heparin antibodies. Can be limb and life threatening. Requires anticoagulant therapy.

Question 26

HUS is associated with which pathogen?

Answer 26

Vero-toxin producing E. coli.

Question 27

How does Aspirin affect platelets?

Answer 27

Aspirin irreversibly inhibits COX and can suppress the synthesis of TXA2 which is necessary for platelet aggregation.

Question 28

What is von Willebrand factor?

Answer 28

vWF is a molecule which mediates stele adhesion to endothelium by bridging platelet glycoprotein Ib-IX and collagen. It also stabilises circulating factor VIII such that reduction in vWF lead to reductions in factor VIII

Question 29

What is von Willebrand disease?

Answer 29

A common heritable bleeding disorder. Various types of which type 3 is the most clinically significant.

Treated with desmopressin or infusions with missing factor.

Question 30

What is Haemophilia A?

What is Haemophilia B?

Answer 30

The most common hereditary (XLR) disease associated with life threatening bleeding. Reduced amount of activity of factor VIII. Severe disease occurs when levels are 2-5% of normal.

Haemophilia B or Christmas disease is an X-linked recessive disease caused by factor IX deficiency.

Question 31

What are the 2 most common causes of DIC?

Answer 31

Obstetric complications ~50%

Carcinomatosis ~33%

Sepsis and trauma are responsible for the rest.

Question 32

Cells likely to be seen in peripheral blood of a patient with extensive myelofibrosis includes?

Answer 32

Normoblasts, myelocytes, and myeloblasts.

NOt megaloblasts, which are reflective of B12 deficiency.

Question 33

Which drugs induce haemolysis in patients with G6PD?

Answer 33

Antimalarials (primaquine, chloroquine)
Sulfonamides
Nitrofurantoins
Aspirin
Probenacid

Question 34

How does Desmopressin increase platelet function?

Answer 34

Desmopressin exerts a strong Haemostatic effect by increasing expression of vWF from endothelium.

Question 35

The indication “par excellence” for splenectomy is?

Answer 35

Hereditary spherocytosis.

Question 36

What is Hereditary Spherocytosis?

Answer 36

A haemolytic anaemia caused by cytoskeletal or membrane protein defects that render RBCs spheroidal and less deformable, and thus vulnerable to splenic sequestration. It is autosomal dominant in 75%