Pharmacology of blood Flashcards
Acute risks of Red cell transfusion
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
Indications for red cell transfusion
Acute blood loss
Chronic anaemia
Parameters used to assess the cause of anaemia
Reticulocyte count
Red cell size
Why can reticulocyte count be used to establish causes of anaemia
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.
Treatment of hyperproliferative anaemia
Caused by haemolysis or acute blood loss.
Corticosteroids
Immunosuppressants: AZT, cyclosporine, rituximab
Folic acid replacement required
Causes of anaemia with Low MCV and low Reticulocyte count
Iron deficiency: hypochromic, low ferritin
Anaemia of chronic disease - iron release from stores inhibited
Sideroblastic anaemia
Lead poisoning
Treatment of iron deficiency anaemia
Find and treat the cause - GIT, malnutrition, malabsorption
Iron replacement therapy
Iron replacement therapy
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.
When is parenteral iron replacement therapy given
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.
Microscopic appearance of thalassemia
Thalassemia. Low MCV, normal reticulocyte. Normal iron, high ferritin stores
Describe anaemia in chronic renal failure
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.
Treatment for anaemia in chronic renal failure
recombinant human EPo is given for symptomatic anemia.
Before treatment iron or folate deficiency is corrected.
Causes of anaemia with high MCV and low reticulocyte count
Megaloblastic anaemia - B12 or folate defciency
Primary BM disorders (e.g. leukemias)
Non-megaloblastic: liver disease, drug induced, hypothyroidism
Action of B12 in RBC development
Adequate serum levels of B12 are required for the production of tetrahydrofolate - which is necessary for DNA synthesis and RBC producion.
Causes of B12 deficiency
Loss of intrinsic factor Pancreatic insufficiency Terminal ileum disease Drugs Pernicious anaemia Low dietary intake
Drug therapy for immune thrombocytopenia
Corticosteroids
Chronic immunosuppression - AZT, cyclosporine
mAb: rituximab
Splenectomy
Anti-thrombotic therapies
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.
Contraindications to use of warfarin
If the patient has: Haemorrhagic stroke Significant bleeding Hepatic and renal impairment 1st trimester of pregnancy Do not use 48hrs post partum
Action of warfarin
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.
Why does warfarin take a few days to have theraputic effect?
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
Why is warfarin contraindicated in pregnancy?
It crosses the placenta.
Name 3 drugs which are contraindicated with warfarin use
Cimetidine - H2R antagonist
Erythromycin - macrolide
Tamoxifen - oestrogen receptor antagonist
Acute alcohol intoxication
All increase INR and thus increase the risk of bleeding.
Side effects of warfarin
Bleeding Nausea, vomiting, diarrhoea Jaundice Fever Pancreatitis Skin necrosis (imbalance between clotting factors and anticlotting factors)
How would you reverse the effects of warfarin in a patient?
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
Heparin anticoagulation
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.
Reversal of heparin
protamine sulphate
Adverse effects of Heparin
Haemorrhage, bruising, thrombocytopenia, loss of hair, hypersensitivity.
Risk of osteoporosis, suppression of renal function
Heparin induced thrombocytopenia
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.
Causes of thrombocytopenia
Impaired production of platelets: myeloma, leukemia, HIV, Drugs
Excessive destructon/consumption: Immune, AI, Post-transfusion
Squestration: splenomegaly
3 safety checks required for red cell transfusions
Centre: donor selection and microbiology
Hospital: ABO and Rh tests, patient Ab screen, Patient-donor cross-match
Bedside: patient checks, peri-transfusion observations
