BLOOD PHARMACOLOGY Peer Support 2014

Case 1 Mrs A recently seen one of your colleagues complaining of fatigue. Her blood test results are now back and she has came to your clinic for a follow up appointment. You diagnose her as being anaemic. What are the 3 main classes of anaemia? - Microcytic, Hypochromic - Normocytic, Normochromic - Macrocytic, Normochromic

 Mrs A blood results are as follows: - Hb 9.9 ( g/dL) - MCV 71 (76-96fL) - WCC 7.8 (4-11x10^9/L) - Plts 220 ( x10^9/L) Which class of anaemia is Mrs A suffering from? Microcytic, hypochromic Give 3 causes of this type of anaemia? Iron deficiency Thalasseamias Anaemia of chronic disease Case continued…

2 Causes of Normocytic, Normochromic anaemia? - Acute haemorrhage - Haemolytic anaemia - Bone marrow failure - Pregnancy 2 causes of Macrocytic, Normochromic anaemia? - B12 deficiency - Folate deficiency - Hypothyroidism

 Further blood tests are ordered for Mrs A. She has low ferritin levels, therefore her symptoms are likely due to poor iron intake.  What medication would be suitable for Mrs A to start taking? - Ferrous Sulphate (200mg TDS) Ferrous sulphate is often poorly tolerated by patients. What are possible side effects? - Constipation - Black Stools - GI upset – dyspepsia, nausea

Case 2  Mrs B is an 84 year old gentleman who has been referred to the emergency department as his blood results are abnormal. He takes warfarin for atrial fibrilation.  What blood result is likely to be abnormal? - INR What is INR? - A standardised version of the prothrombin time INR should usually be 1. What is the usual therapeutic range? - 2-3

Case 2 continued… Mr B’s INR is 6. What treatment options do you have? - Conservative: Stop warfarin and wait for his INR to fall before restarting warfarin - Give Vitamin K If Mr B was actively bleeding, what action should be taken? - FFP (Fresh frozen plasma) This will reverse the effect of warfarin immediately

Warfarin – Mechanism of Action  EXTRINSIC Pathway  What enzyme does warfarin inhibit? - Vitamin K Epoxide Reductase (in the liver) – therefore lowering the level of reduced vitamin K. (Vitamin K required as a cofactor for the carboxylation of glutamate residues in some coagulation factors) Which coagulation factors does this have an effect upon? - II, VII, IX and X How long does it usually take for warfarin to have a therapeutic effect? Approx 72 hrs Why is this? - This is how long it takes for the clotting factors already active in the blood to be metabolised and depleted.

Give 3 examples of situations when warfarin must not be given?  Haemmorhagic Stroke  48 hours post partum  During pregnancy  Malignant hypertension Give 2 drugs/substances that may interact with warfarin, causing an INCREASE in INR? - Erythromycin - Acute alcohol intoxication Give 2 that can cause warfarin to have a reduced therapeutic effect? - Barbituates - Phenytoin

Side effects of warfarin, besides bleeding?  Skin Necrosis  Pancreatitis  Alopecia  Hepatitis  Jaundice  NVD Warfarin vs Heparin - PeT PiTT – Try to remember which pathway and the relevant lab tests

Heparin and LMWH  Advantages of LMWH over Heparin? - Longer plasma half life - Better bioavailability - More predictable dose response Give an example of a LMWH drug? - Enoxaparin Mechanism of action of heparin/LMWH? - Bind to and activiate Antithrombin III - Antithrombin III inactivates Thrombin - Factor Xa is also inhibited

If a patients is accidently given a heparin overdose – what can be given to reverse the effect? - Protamine Sulphate – a basic peptide, binds with heparin and prevents its function 2 Side effects of longterm heparin use? - Thrombocytopenia (HIT 2 types) - Alopecia - Osteoperosis