Pharmacology of blood

Question 1

Acute risks of Red cell transfusion

Answer 1

Allergic/anaphylactic: Acute non-haemolytic transfusion reaction

Allo-immune: haemolytic transfusion reaction, transfusion associated GvHD, acute lung injury, post transfusion purpura.

Transmitted infections

Circulatory overload or iron overload

Question 2

Indications for red cell transfusion

Answer 2

Acute blood loss

Chronic anaemia

Question 3

Parameters used to assess the cause of anaemia

Answer 3

Reticulocyte count

Red cell size

Question 4

Why can reticulocyte count be used to establish causes of anaemia

Answer 4

If there is a high reticulocyte count, this indicates a good BM response to anaemia (hypergenerative). High levels of LDH and low haptoglobin

Seen in haemolysis and acute bleeding. Low count means there is hypogenerative anaemia e.g. iron deficiency. Can indicate problem in bone marrow.

Question 5

Treatment of hyperproliferative anaemia

Answer 5

Caused by haemolysis or acute blood loss.

Corticosteroids
Immunosuppressants: AZT, cyclosporine, rituximab
Folic acid replacement required

Question 6

Causes of anaemia with Low MCV and low Reticulocyte count

Answer 6

Iron deficiency: hypochromic, low ferritin
Anaemia of chronic disease - iron release from stores inhibited
Sideroblastic anaemia
Lead poisoning

Question 7

Treatment of iron deficiency anaemia

Answer 7

Find and treat the cause - GIT, malnutrition, malabsorption

Iron replacement therapy

Question 8

Iron replacement therapy

Answer 8

Ferrous iron salts are given orally e.g. ferrous suphate) taken on an empty stomach for 12 weeks.
Dose should be 100-200mg daily.
Hb should rise by 5g per week. Poor response to treatment means cause is unlikely to be iron deficeiency.

Side effects proportional to dose. Includes: GI irritation, nausea, epigastric pain. Contraindicated in IBD - exacerbates diarrhoea.

Question 9

When is parenteral iron replacement therapy given

Answer 9

When patient is intolerant to oral therapy or there is malabsorption.

Also used for patients with severe renl failure on haemodialysis to obtain a faster Hb.

Question 10

Microscopic appearance of thalassemia

Answer 10

Thalassemia. Low MCV, normal reticulocyte. Normal iron, high ferritin stores

Question 11

Describe anaemia in chronic renal failure

Answer 11

Anaemia of chronic disease arises due to low grade chronic inflammation. This causes macrophages to release IL-6, which stimulates hepcidin release from hepatocytes. Hepcidin reduces iron absorption from the intestine, and reduces release of iron from macrophages, which is required for RBC development.

Diseased kidneys also release less EPO, which is required to stimulate RBC production from the BM.

Question 12

Treatment for anaemia in chronic renal failure

Answer 12

recombinant human EPo is given for symptomatic anemia.

Before treatment iron or folate deficiency is corrected.

Question 13

Causes of anaemia with high MCV and low reticulocyte count

Answer 13

Megaloblastic anaemia - B12 or folate defciency
Primary BM disorders (e.g. leukemias)
Non-megaloblastic: liver disease, drug induced, hypothyroidism

Question 14

Action of B12 in RBC development

Answer 14

Adequate serum levels of B12 are required for the production of tetrahydrofolate - which is necessary for DNA synthesis and RBC producion.

Question 15

Causes of B12 deficiency

Answer 15

Loss of intrinsic factor
Pancreatic insufficiency
Terminal ileum disease
Drugs
Pernicious anaemia
Low dietary intake

Question 16

Drug therapy for immune thrombocytopenia

Answer 16

Corticosteroids
Chronic immunosuppression - AZT, cyclosporine
mAb: rituximab
Splenectomy

Question 17

Anti-thrombotic therapies

Answer 17

Thrombolytic therapy: given within 24hrs of life threatening thrombosis

Antiplatelet therapy: aspirin, used for reduction of CV risk e.g. TIAs

Anticoagulation: low Mw heparins in acute setting for rapid initial anticoagulation in arterial and venous thrombosis. Used in prophylactically in surgery and patients at risk of thrombosis. Warfarin for long term treatment, used in DVTs, PE and AF.

Question 18

Contraindications to use of warfarin

Answer 18

If the patient has: 
Haemorrhagic stroke
Significant bleeding
Hepatic and renal impairment
1st trimester of pregnancy
Do not use 48hrs post partum

Question 19

Action of warfarin

Answer 19

Inhibits vitamin K epoxide reductase in the liver. Vitamin K is a cofactor required to carboxylate (activate) clotting factors.

Mainly affects factor II, VII, IX and X (extrinsic pathway) and anticoagulant protein C and S.

Question 20

Why does warfarin take a few days to have theraputic effect?

Answer 20

Takes 2-4 days because the clotting factors already in the blood need to be metabolised and depleted.

If an immediate effect is required, heparin is given.

May take 2 weeks to stablise INR

Question 21

Why is warfarin contraindicated in pregnancy?

Answer 21

It crosses the placenta.

Question 22

Name 3 drugs which are contraindicated with warfarin use

Answer 22

Cimetidine - H2R antagonist
Erythromycin - macrolide
Tamoxifen - oestrogen receptor antagonist
Acute alcohol intoxication

All increase INR and thus increase the risk of bleeding.

Question 23

Side effects of warfarin

Answer 23

Bleeding
Nausea, vomiting, diarrhoea
Jaundice
Fever
Pancreatitis
Skin necrosis (imbalance between clotting factors and anticlotting factors)

Question 24

How would you reverse the effects of warfarin in a patient?

Answer 24

If INR <8 and no bleeding, stop warfarin
Otherwise stop warfarin and give Vitamin K injuection IV. Will correct INR within 24 hrs.

Prothrombin complex concentrates can be used for rapid administration e.g. severe haemorrhage. Plasma products, and therefore carry risk of transmitted infection. Monitoring needed as high doses can causes thrombosis, PE, and DIC

Question 25

Heparin anticoagulation

Answer 25

Unfractioned heparin: Anti-thrombin. Heterogenous molecules in size and activity. Higher Mw molecules are cleared from the circulation more rapidly. Resticted to hospital. Given IVI.
Risks: Osteoporosis and HITT

Low Mw Heparin: Antifactor Xa. Longer plasma half life and better bioavailability. Administered subcutaneously, no monitoring. Cleared renally. Difficult to reverse.

Question 26

Reversal of heparin

Answer 26

protamine sulphate

Question 27

Adverse effects of Heparin

Answer 27

Haemorrhage, bruising, thrombocytopenia, loss of hair, hypersensitivity.

Risk of osteoporosis, suppression of renal function

Question 28

Heparin induced thrombocytopenia

Answer 28

HIT type 1: presents in the first 2 days. Platelet count normalises with continued heparin. Non-immune disorder due to direct effect of heparin on platelet activation

HIT type 2: occurs 4-10 days. High risk for venous and arterial thromboembolism. Immune mediated. Test for antibodies to heparin-PF4 complex.

Question 29

Causes of thrombocytopenia

Answer 29

Impaired production of platelets: myeloma, leukemia, HIV, Drugs

Excessive destructon/consumption: Immune, AI, Post-transfusion

Squestration: splenomegaly

Question 30

3 safety checks required for red cell transfusions

Answer 30

Centre: donor selection and microbiology

Hospital: ABO and Rh tests, patient Ab screen, Patient-donor cross-match

Bedside: patient checks, peri-transfusion observations