Haematology Flashcards
Anti-Coagulation: Heparins
What is the mechanism of heparins? What are the differences and indications for unfractionated heparins vs. low molecualr weight heparins?
- Mechanism: glycosaminoglycan extracted from porcine mucosa, causing anticoagulation through binding to anti-thrombin and **potentiating **its activity.
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Heparin: initiates anticoagulation rapidly, but has a short duration. Only used in preference to LMWH when:
- Patients requiring rapid cessation of anticoagulation (e.g. very high bleeding risk)
- Severe renal failure: easier to titrate APTT than relying on anti-Xa levels with LMWH
- **LMWH: **(e.g dalteparin, enoxaparin and tinzeparin) preferred in **prevention **and treatment of VTE, PE, MI etc. due to:
- Lower risk of HIT, no requirement for monitoring at standard prophylactic dose
- Longer duration → OD S/C dosing
- Lower risk of osteoporosis long term
Anticoagulation: Heparins (II)
How are unfractionated and LMW heparins monitored? What are the indications for treatment and prophylaxis? What is the guidance during pregnancy?
- Monitoring: Unfractionated → aPTT, LMWH → anti-factor Xa (aPTT **not **reliable). Monitoring of LMWH only required if high bleeding risk (renal impairment, high or low BMI)
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Treatment:
- DVT and PE: LMWH and warfarin started simultaneously; heparin continued for atleast 5 days, until INR is therapeutic for 2 consecutive days
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Prophylaxis: based upon risk assessment:
- **High risk: **surgical patients for major trauma, #NOF, hip / knee arthroscopy, SCI. 5,000U/day dalteparin to cover surgery
- Pregnancy: heparins do not cross placenta; LMWH preferred due to ↓ osteoporosis and HIT risk. Patients with continued anticoagulation requirements (e.g. prosthetic cardiac valves) are complex; usually heparin used in 1st and 3rd terms, and warfarin in 2nd.
Anticoagulation: Heparins (III)
What are the adverse effects of heparins?
- Haemorrhage: usually treated with withdrawal. If rapid reversal required, protamine sulphate is the specific antidote (but only partially reverses LMWH)
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Heparin-induced thrombocytopenia:
- Immune mediated, developing after 5 - 10 days; may be complicated by thrombosis.
- Measure platelet count just before treatment; signs include ↓50% in platelet count, thrombosis or skin allergy.
- Stop heparin, give alternative anticoagulant (argatroban, danaparoid)
- **Hyperkalaemia **(heparin inhibits aldosterone secretion → increased risk in DM, CKD and acidosis. Monitor [K+] if risk
- Osteoporosis: if prolonged, lower with LMWH
- Alopecia
- Hypersensitivity: urticaria, angiooedema, anaphylaxis
Fondaparinux
What is fondaparinux, what are indications for use?
- Synthetic pentasaccharide, directing antithrombin to selectively inhibit factor Xa. Administered daily without laboratory monitoring.
- 2009 RCT showed equivalence to LMWH in ACS with lower bleeding risk → NICE recommended as antithrombin of choice in ACS
Oral Anticoagulants: Warfarin
What is the mechanism and indication for treatment with warfarin?
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Mechanism:
- Antagonises effects of vitamin K, reducing synthesis of factors II, VII, IX and X. Measured by increased PT / INR
- Required 48 - 72h for activity, and have a paradoxical procoagulant effect initially as they deplete anticoagulant factors more quickly than pro-coagulants; often covered with LMWH.
- Eliminated by hepatic metabolism; multiple interactions
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Indications:
- Treatment of VTE
- Stroke prevention in AF (CHADS2VASC)
- Mechanical heart valves
Warfarin Interactions: Enzyme Inducers
Which drugs are **cytochrome p450 inducers, **thereby decreasing the activity of warfarin?
- Phenytoin
- Carbamazepine
- Barbiturates
- Rifampicin
- Alcohol (chronic use)
- Sulphonylurea / St-John’s wart
Warfarin Interactions: Enzyme Inhibitors
Which drugs inhibit the cytochrome P450 system, and therefore potentiate the action of warfarin
- Omeprazole
- Disulfuram
- Erythromycin
- Valproate
- Isoniazid
- Cimetidine, Ciprofloxacin
- Ethanol (acutely)
- Sulphonamides
Warfarin Reversal
What are the guidelines for reversing warfarin in the setting of major bleeding, non-major bleeding, and raised INR with no bleeding?
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Major Bleeding:
- Stop warfarin
- PCC 30mg / kg,
- Vit K IV 5mg
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Non-Major Bleeding
- If INR > 5, Stop warfarin, give 1-3mg Vit K
- If INR < 5, modify warfarin dose, and consider 1mg Vit K
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No-bleeding, over anti-coagulated
- INR > 12: omit warfarin, 5mg Vit K
- INR 8 - 12: omit warfarin, 2mg Vit K
- INR 5 - 8: omit warfarin, restart at a lower dose when INR < 5
New Oral Anti-Coagulants
What are the NOACs, and what are their mechanisms of action. How do they compare to warfarin?
- Examples:
- Dabigatran: direct thrombin inhibitor
- Rivaroxaban, Apixaban: Factor Xa inhibitors
- Comparison to warfarin:
- Faster onset, shorter half-life
- No requirement for monitoring
- No effective method of reversing haemorrhage
- Require compliance; clot risk if one tablet missed
Anti-Platelets: Aspirin
What are the indications and adverse effects of aspirin?
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Indications:
- Acute treatment of MI and stroke
- Primary prevention: individuals with high vascular risk; 10 year CV risk > 20%, patients over 50 with diabetes
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Adverse Effects:
- Bleeding, particularly GI and intracranial. Dose related.
- Exacerbation of asthma
- Avoid until controlled HTN to ↓ risk of intracranial haemorrhage
Anti-Platelets: Clopidogrel
What is the mechanism, indications and adverse effects of clopidogrel?
- Mechanism: thienopyridine, inhibits platelet aggregation by selectively binding ADP2Y12 receptors (adenylate cyclase coupled)
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Indications:
- Combination with aspirin in short term for ACS and after stent placement.
- 1st Line for ischaemic stroke and TIA
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Adverse effects:
- Bleeding (↑ risk - combined with aspirin)
- Dyspepsia, abdo pain, diarrhoea
- Efficacy may be reduced by clopidogrel (note: think this has been disproven)
Treatment of Anaemia: Iron
For iron (ferrous sulphage, ferrous gluconate) used in treatment of Fe-deficient anaemia, what is the:
- Dose
- Adverse effects
- Duration of Treatment
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Dose:
- Usual elemental Fe-requirement 1-2mg/day; ferrous sulphate 200 provides 65mg - usually given TDS.
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Adverse effects
- GI: nausea, diarrhoea, constipation (very common, cause compliance difficulties)
- Black stool
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Duration:
- Hb increases by ~0.5 - 0.8g/dL/week if cause corrected.
- Treat until Hb normal, then 3 months further to build iron stores
Treatment of Anaemia: Iron (II)
What is the indication for intravenous iron treatment? What are the adverse effects and dose?
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Indication:
- CKD or anaemia of malignancy, use in conjunction with erythropoiesis stimulating agents (ESA). ESAs cause functional iron deficiency (stores adequate, but Fe unavailable to developing RBCs) - only overcome by I.V not P.O iron.
- Poor absorption
- Adverse effects: allergy / anaphylaxis rare. Myalgia reported by some
- Dose: calculate on weight and target Hb. Dose given in oen infusion, or in divided doses over a few weeks
**Anaemia: Vitamin B12 and Folate **
When is B12 given and in what form? What are the indications for folate treatment?
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B12:
- Deficiency (e.g. pernicious anaemia etc). Given prophylactically after gastrectomy / ileal resection
- Given as Hydroxycobalamin: given 3monthly; retained by body well. Initiated with regular I.M injections to replenish depleted stores.
- **Folate: **(deficiency → macrocytic anaemia)
- Pregnancy - increased requirements. Given during pre-conception and 1st trimestered to reduce NTDs.
- Prevention of anaemia in long term methotrexate treatment
- Folinic acid → produced from folate metabolism. Given as folinic acid in resuce therapy for high dose MTX, and patients with ALL.
Vitamin K
What is the mechanism, indication and administration of Vitamin K
- **Mechanism: **fat soluable vitamin, acting as co-factor in the synthesis of factors II, VII, IX and X
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Indication:
- Prevention of haemorrhagic disease of the newborn (phytomenadione)
- Reversal of clotting disorders arising from Vit K deficiency (cirrhosis, warfarin, nutritional deficiency)
- Administration: can be given IV, IM, or orally. Given to reverse coumarins (warfarin). Usually given slowly due to risk of anaphylaxis