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HKMLE HAEMATOLOGY PHARMACOLOGY - ANKI FLASHCARDS
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Generated from: Haematology 💊 Notes
Exam: HKMLE (Papers I, II, III)
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=== SECTION 1: WARFARIN ===

--- Card 1 ---
Q: What is the mechanism of warfarin?
A: Inhibits vitamin K epoxide reductase → blocks activation of clotting factors II, VII, IX, X and anticoagulant proteins C and S.

--- Card 2 ---
Q: What is the mnemonic for warfarin's blocked factors?
A: "WEPT = Warfarin: Extended PT, inhibits 1972" = Factors II, VII, IX, X + Proteins C and S.

--- Card 3 ---
Q: Why does warfarin take 3-5 days to achieve full anticoagulation?
A: Existing circulating clotting factors must be cleared; factor VII (shortest half-life ~6h) disappears first, raising INR early but full anticoagulation takes 3-5 days.
[Trap: common wrong answer is "warfarin works immediately because INR rises" - INR rising ≠ fully anticoagulated, because Protein C/S drop first causing a procoagulant state]

--- Card 4 ---
Q: What is the INR target for AF and DVT/PE?
A: 2.0 - 3.0.

--- Card 5 ---
Q: What is the INR target for mechanical mitral valve?
A: 2.5 - 3.5.
[Trap: common wrong answer is 2.0-3.0 like AF; mechanical mitral valve requires higher anticoagulation than mechanical aortic valve]

--- Card 6 ---
Q: What is the INR target for mechanical aortic valve?
A: 2.0 - 3.0 (some guidelines accept 2.5-3.5).

--- Card 7 ---
Q: What is the INR target for antiphospholipid syndrome?
A: 2.0 - 3.0 (or 3.0-4.0 if recurrent thrombosis).

--- Card 8 ---
Q: HKMLE Pearl: Why must you always bridge warfarin with heparin when starting in acute thrombosis?
A: Warfarin first depletes Protein C and S (short half-lives) before fully anticoagulating → transient procoagulant state → risk of paradoxical thrombosis (e.g. warfarin-induced skin necrosis).

--- Card 9 ---
[c] Warfarin [/c] causes skin necrosis early in therapy because Protein C and S are depleted before full anticoagulation is achieved, especially in protein C deficiency.

--- Card 10 ---
Q: What is warfarin embryopathy and when does it occur?
A: Nasal hypoplasia + stippled epiphyses caused by warfarin exposure during weeks 6-12 of gestation; fetal haemorrhage risk occurs in the third trimester.

--- Card 11 ---
Q: What is the safe anticoagulant in pregnancy?
A: LMWH (e.g. enoxaparin) - does not cross the placenta; warfarin and DOACs are both contraindicated.
[Trap: common wrong answer is "DOACs are safe in pregnancy" - they are teratogenic and cross the placenta]

--- Card 12 ---
Q: What coagulation pathway does INR measure?
A: Extrinsic pathway (factors VII, X, II, V, fibrinogen).

--- Card 13 ---
Q: Name 5 drugs that increase INR (↑ bleeding risk) with warfarin.
A: Amiodarone, fluconazole, metronidazole, ciprofloxacin, clarithromycin (all inhibit CYP2C9 → ↑ warfarin levels).

--- Card 14 ---
Q: What is the mnemonic for warfarin INR-raising drugs?
A: "CAFE MIX" = Clarithromycin/Ciprofloxacin, Amiodarone, Fluconazole, Erythromycin, Metronidazole, Isoniazid, eXcretion inhibitors (statins).

--- Card 15 ---
Q: Name 4 drugs that decrease INR (↓ efficacy) with warfarin.
A: Rifampicin, phenytoin, carbamazepine, St John's Wort (all induce CYP2C9 → ↑ warfarin metabolism).

--- Card 16 ---
Q: What is the mnemonic for warfarin INR-lowering drugs?
A: "PRICARS" = Phenytoin, Rifampicin, Isoniazid (high dose), Carbamazepine, Alcohol (chronic), St John's Wort.

--- Card 17 ---
Q: NSAIDs and warfarin: what is the effect on INR vs bleeding risk?
A: NSAIDs do NOT reliably change INR but significantly increase bleeding risk (GI mucosal damage + platelet inhibition).
[Trap: common wrong answer is "NSAIDs raise INR" - they increase bleeding risk without predictably changing INR]

--- Card 18 ---
Q: HKMLE Pearl: INR 5-8 with no significant bleeding - what do you do?
A: Stop warfarin; give low-dose oral vitamin K 1-2 mg; recheck INR.

--- Card 19 ---
Q: HKMLE Pearl: INR >8 with no/minor bleeding - what do you do?
A: Stop warfarin; give oral vitamin K 5 mg; repeat if INR still high at 24h.

--- Card 20 ---
Q: HKMLE Pearl: Any INR with major bleeding - what is the treatment?
A: Stop warfarin + IV vitamin K 5-10 mg + 4-factor Prothrombin Complex Concentrate (PCC) - preferred over FFP (faster reversal, lower volume).
[Trap: common wrong answer is "give FFP" - 4-factor PCC is now preferred over FFP for urgent warfarin reversal]

--- Card 21 ---
Q: Why is PCC preferred over FFP for urgent warfarin reversal?
A: PCC works faster and requires lower infusion volume than FFP; FFP carries risks of fluid overload and TRALI.

--- Card 22 ---
Q: What factors does 4-factor PCC contain?
A: Factors II, VII, IX, X + Proteins C and S.


=== SECTION 2: HEPARIN (UFH & LMWH) ===

--- Card 23 ---
Q: What is the mechanism of UFH?
A: Binds antithrombin III → inhibits factor IIa (thrombin), Xa, IXa, XIa, XIIa.

--- Card 24 ---
Q: What is the mechanism of LMWH (e.g. enoxaparin)?
A: Binds antithrombin III → preferentially inhibits factor Xa only (smaller chain cannot bridge thrombin to antithrombin).
[Trap: common wrong answer is "LMWH inhibits thrombin like UFH" - LMWH mainly inhibits Xa, not IIa]

--- Card 25 ---
Q: How do you monitor UFH?
A: aPTT (target 1.5 - 2.5x normal).

--- Card 26 ---
Q: How do you monitor LMWH?
A: Usually NOT required; use anti-Xa level if obese, pregnant, or renal impairment.

--- Card 27 ---
Q: Which heparin is safe in pregnancy and why?
A: Both UFH and LMWH do NOT cross the placenta; LMWH is preferred (more predictable, once-daily, less HIT risk).

--- Card 28 ---
Q: Which heparin accumulates in renal failure?
A: LMWH (enoxaparin) - reduce dose or avoid if eGFR <30; UFH is cleared by the reticuloendothelial system (not renally).
[Trap: common wrong answer is "UFH is dangerous in renal failure" - it is actually LMWH that accumulates in renal failure]

--- Card 29 ---
Q: How do you reverse UFH?
A: Protamine sulfate 1 mg per 100 units of heparin (IV slow); risk of hypotension, bradycardia, anaphylaxis (especially fish allergy or prior vasectomy).

--- Card 30 ---
Q: How do you reverse LMWH?
A: Protamine sulfate (only ~60% reversal - partial neutralisation only).

--- Card 31 ---
Q: What is HIT Type I vs HIT Type II?
A: Type I = non-immune, mild platelet drop (>100) within 1-2 days, benign, continue heparin. Type II = immune (IgG vs heparin-PF4 complex), platelets drop >50% from baseline at days 5-10, causes paradoxical THROMBOSIS.

--- Card 32 ---
Q: What is the mnemonic for HIT?
A: "HIT = Heparin Induces Thrombosis (paradoxically) - the 4Ts score" (Thrombocytopenia, Timing, Thrombosis, other causes excluded).

--- Card 33 ---
Q: HKMLE Pearl: HIT causes ___ not just low platelets.
A: HIT causes THROMBOSIS (not just thrombocytopenia) - this is the classic paradox.

--- Card 34 ---
Q: HKMLE Pearl: Management of HIT?
A: Stop ALL heparin (UFH AND LMWH) immediately; start argatroban or fondaparinux; do NOT give platelets; do NOT start warfarin until platelets >150.
[Trap: common wrong answer is "transfuse platelets in HIT" - platelet transfusion is CONTRAINDICATED as it worsens thrombosis]

--- Card 35 ---
Q: Why must warfarin NOT be started in HIT until platelets normalise (>150)?
A: Warfarin depletes Protein C first → hypercoagulable state → risk of venous limb gangrene.

--- Card 36 ---
Q: What is the drug of choice for HIT in a patient with renal failure?
A: Argatroban (direct thrombin inhibitor; hepatic elimination → safe in renal failure).
[Trap: common wrong answer is "fondaparinux in renal failure" - fondaparinux is renally cleared; argatroban is hepatic]

--- Card 37 ---
[c] Argatroban [/c] is preferred over fondaparinux for HIT in renal failure because it undergoes hepatic elimination, not renal clearance.


=== SECTION 3: DIRECT THROMBIN INHIBITORS (DTIs) ===

--- Card 38 ---
Q: What is the mechanism of direct thrombin inhibitors (DTIs)?
A: Directly inhibit thrombin (factor IIa) independently of antithrombin (unlike heparin).

--- Card 39 ---
Q: Name 2 parenteral DTIs and their key uses.
A: Argatroban (HIT, especially in renal failure); Bivalirudin (PCI as heparin alternative).

--- Card 40 ---
Q: Dabigatran is the only oral DTI - what is its reversal agent?
A: Idarucizumab (Praxbind) 5 g IV - monoclonal Ab fragment that binds dabigatran.


=== SECTION 4: DIRECT ORAL ANTICOAGULANTS (DOACs) ===

--- Card 41 ---
Q: What is the mnemonic for DOAC targets?
A: "3 Xas + 1 IIa" = Rivaroxaban, Apixaban, Edoxaban (factor Xa inhibitors) + Dabigatran (factor IIa inhibitor).

--- Card 42 ---
Q: Which DOAC has the lowest bioavailability and why does this matter?
A: Dabigatran (6% bioavailability) - highly P-gp dependent; drug interactions with P-gp inducers/inhibitors significantly affect levels.

--- Card 43 ---
Q: Which DOAC has the highest renal clearance?
A: Dabigatran (~80% renal) - most dangerous in renal failure; avoid if CrCl <30 mL/min.

--- Card 44 ---
Q: Which DOAC is safest in CKD?
A: Apixaban (~27% renal clearance) - least dependent on renal elimination.
[Trap: common wrong answer is "rivaroxaban is safe in CKD" - it has ~33% renal clearance and needs dose reduction in moderate CKD]

--- Card 45 ---
Q: What are the 3 criteria for apixaban dose reduction?
A: 2 of the following 3: age ≥80, weight ≤60 kg, creatinine ≥133 µmol/L.

--- Card 46 ---
Q: DOACs are contraindicated in which 3 clinical situations?
A: Pregnancy (teratogenic), mechanical heart valves (inferior to warfarin - RE-ALIGN trial), triple-positive antiphospholipid syndrome (warfarin preferred).
[Trap: common wrong answer is "DOACs can be used for mechanical heart valves" - the RE-ALIGN trial showed worse outcomes with dabigatran vs warfarin in mechanical valves]

--- Card 47 ---
Q: HKMLE Pearl: Which anticoagulant is used for mechanical heart valves?
A: Warfarin ONLY - DOACs are contraindicated for mechanical heart valves.

--- Card 48 ---
Q: HKMLE Pearl: A patient on rivaroxaban has a major bleed - what do you give?
A: Andexanet alfa (recombinant factor Xa decoy); if unavailable, 4-factor PCC 25-50 units/kg.

--- Card 49 ---
Q: What is the reversal agent for dabigatran?
A: Idarucizumab (Praxbind) 5 g IV.

--- Card 50 ---
Q: What is the reversal agent for Xa inhibitors (rivaroxaban, apixaban, edoxaban)?
A: Andexanet alfa (recombinant Xa decoy that binds Xa inhibitors).

--- Card 51 ---
Q: What is the mnemonic for DOAC reversal?
A: "I-DAR for IIa (dabigatran); AND-exanet for Xa."

--- Card 52 ---
Q: Which class of drugs reduces ALL DOAC efficacy via P-gp/CYP3A4 induction?
A: Rifampicin, phenytoin, carbamazepine, St John's Wort - avoid combination with all DOACs.

--- Card 53 ---
Q: DOACs vs warfarin: what is the key advantage regarding intracranial haemorrhage?
A: DOACs have lower risk of intracranial haemorrhage compared to warfarin.

--- Card 54 ---
Q: Which DOAC has higher GI bleeding risk than warfarin?
A: Dabigatran and rivaroxaban have notably higher GI bleeding rates compared to warfarin.
[Trap: common wrong answer is "all DOACs have lower bleeding risk than warfarin" - only intracranial haemorrhage risk is lower; GI bleeding can be higher]


=== SECTION 5: ANTIPLATELETS ===

--- Card 55 ---
Q: What is the mechanism of aspirin's antiplatelet effect?
A: Irreversibly inhibits COX-1 → ↓ TXA2 synthesis → ↓ platelet aggregation; effect lasts 7-10 days (platelet lifespan).

--- Card 56 ---
Q: Why is aspirin contraindicated in children <12 years?
A: Risk of Reye's syndrome (hepatic encephalopathy).

--- Card 57 ---
Q: What is the mechanism of clopidogrel?
A: Irreversibly blocks P2Y12 ADP receptor on platelets; prodrug requiring CYP2C19 activation.

--- Card 58 ---
Q: HKMLE Pearl: CYP2C19 poor metabolisers on clopidogrel - what happens?
A: Reduced conversion to active drug → reduced antiplatelet efficacy; switch to ticagrelor or prasugrel.

--- Card 59 ---
Q: Which drug interaction reduces clopidogrel efficacy?
A: PPIs (especially omeprazole) compete for CYP2C19 activation → reduce clopidogrel effect.
[Trap: common wrong answer is "all PPIs equally reduce clopidogrel" - rabeprazole/pantoprazole have less interaction than omeprazole]

--- Card 60 ---
Q: What is the mechanism of ticagrelor?
A: Reversibly blocks P2Y12; NOT a prodrug (works directly, no CYP2C19 needed); offset in 3-5 days.

--- Card 61 ---
[c] Ticagrelor [/c] causes dyspnoea because it inhibits adenosine reuptake → ↑ adenosine → vasodilation and dyspnoea; this is NOT bronchospasm.

--- Card 62 ---
Q: HKMLE Pearl: Ticagrelor + dyspnoea - what do you do?
A: Do NOT switch to clopidogrel without good reason; the dyspnoea is adenosine-mediated (not bronchospasm) and usually does not require stopping the drug.
[Trap: common wrong answer is "ticagrelor dyspnoea = bronchospasm = switch drug" - it is adenosine-mediated vasodilation, not bronchospasm]

--- Card 63 ---
Q: HKMLE Pearl: High-dose aspirin + ticagrelor - what happens?
A: High-dose aspirin reduces ticagrelor efficacy (conformational change in COX-1); use low-dose aspirin (75-100 mg) only with ticagrelor.

--- Card 64 ---
Q: What are the contraindications to prasugrel?
A: Prior TIA or stroke (↑ intracranial bleed risk), age >75, weight <60 kg.

--- Card 65 ---
Q: What is the mnemonic for prasugrel contraindication?
A: "Prior TIA/stroke = Prasugrel is PRASUREly dangerous."

--- Card 66 ---
Q: What is DAPT and for how long is it given post-ACS/PCI?
A: Dual antiplatelet therapy = aspirin + P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel); standard duration is 12 months post-ACS/PCI.

--- Card 67 ---
Q: What is the mechanism of dipyridamole?
A: Inhibits phosphodiesterase → ↑ cAMP → ↓ platelet aggregation; also blocks adenosine reuptake (vasodilatory effect).

--- Card 68 ---
Q: HKMLE Pearl: Dipyridamole in cardiac stress testing - what does it do?
A: Acts as an adenosine analogue → dilates coronary arteries → reveals ischaemia (pharmacological stress test - same principle as adenosine stress test).

--- Card 69 ---
Q: What is the mechanism of GPIIb/IIIa inhibitors (tirofiban, eptifibatide)?
A: Block GPIIb/IIIa receptor → prevent fibrinogen binding → inhibit final common pathway of platelet aggregation; IV only, used in high-risk ACS/PCI.

--- Card 70 ---
Q: When do you stop antiplatelets before elective surgery?
A: Clopidogrel/prasugrel: 7-10 days before; ticagrelor: 5 days before; aspirin may be continued for most procedures.


=== SECTION 6: THROMBOLYTICS ===

--- Card 71 ---
Q: What is the mechanism of thrombolytics?
A: Activate plasminogen → plasmin → plasmin cleaves fibrin → dissolves clots.

--- Card 72 ---
Q: What is the mnemonic for thrombolytics?
A: "tPA = turns Plasminogen to Active plasmin → eATs fibrin clots."

--- Card 73 ---
Q: Alteplase (tPA): time window for ischaemic stroke?
A: ≤4.5 hours from symptom onset.

--- Card 74 ---
Q: HKMLE Pearl: Before giving alteplase for ischaemic stroke, what must you do first?
A: CT head to exclude haemorrhagic stroke (haemorrhage is an absolute contraindication).
[Trap: common wrong answer is "give tPA immediately without imaging" - CT head is MANDATORY before thrombolysis]

--- Card 75 ---
Q: HKMLE Pearl: What BP must be achieved before giving stroke thrombolysis?
A: BP must be controlled to <185/110 mmHg before alteplase administration.

--- Card 76 ---
Q: What is the door-to-needle time target for stroke thrombolysis?
A: <60 minutes.

--- Card 77 ---
Q: What is tenecteplase and how does it differ from alteplase?
A: Modified tPA with longer half-life → given as a single IV bolus (more convenient for STEMI); increasingly used for ischaemic stroke.

--- Card 78 ---
Q: What is the problem with streptokinase?
A: Antigenic (bacterial protein) → antibodies form → cannot be reused within 5 years; risk of anaphylaxis; NOT fibrin-selective.
[Trap: common wrong answer is "streptokinase can be repeated" - once antibodies form, reuse within 5 years is ineffective and risks anaphylaxis]

--- Card 79 ---
[c] Streptokinase [/c] can only be used once because it is antigenic (bacterial protein from Streptococcus) → IgG antibodies form → reuse within 5 years is ineffective.

--- Card 80 ---
Q: What is the mnemonic for absolute contraindications to thrombolytics?
A: "BRAIN HURTS" = Bleeding, Recent surgery/trauma, Aortic dissection, Intracranial history, Neurosurgery recent, Haemorrhagic stroke, Uncontrolled BP, Recent head injury, Time window exceeded, Severe bleeding disorder.

--- Card 81 ---
Q: List 4 absolute contraindications to thrombolytics.
A: Prior intracranial haemorrhage; ischaemic stroke within 3 months; suspected aortic dissection; active internal bleeding (not menstruation).

--- Card 82 ---
Q: Name 3 major relative contraindications to thrombolytics.
A: SBP >180 or DBP >110 (uncontrolled); recent major surgery/trauma (2-4 weeks); pregnancy.


=== SECTION 7: ANTIFIBRINOLYTICS - TRANEXAMIC ACID (TXA) ===

--- Card 83 ---
Q: What is the mechanism of tranexamic acid (TXA)?
A: Synthetic lysine analogue → competitively inhibits plasminogen activation (blocks lysine-binding sites on plasminogen/plasmin) → prevents fibrin clot breakdown.

--- Card 84 ---
Q: What is the mnemonic for TXA?
A: "TXA = Tranexamic acid eXActs its effect by Blocking plasmin."

--- Card 85 ---
Q: What is the CRASH-2 trial finding for TXA?
A: TXA given within 3 hours of trauma reduces all-cause mortality (NNT ~67); given after 3 hours = no mortality benefit.

--- Card 86 ---
Q: What is the mnemonic for TXA's time rule?
A: "3 hours or bust" (CRASH-2: must give within 3h of trauma for mortality benefit).

--- Card 87 ---
Q: What is the WOMAN trial finding for TXA?
A: TXA given early in postpartum haemorrhage (PPH) reduces death from bleeding; now WHO-recommended.

--- Card 88 ---
Q: HKMLE Pearl: TXA in PPH - from which trial is the evidence?
A: WOMAN trial (TXA → ↓ death from bleeding in PPH if given early).

--- Card 89 ---
Q: What are the contraindications to TXA?
A: Active thromboembolic disease (DVT/PE/stroke); DIC with consumption; haematuria from upper urinary tract (clots may obstruct ureters).

--- Card 90 ---
[c] Tranexamic acid [/c] is contraindicated in DIC because blocking fibrinolysis worsens consumption and organ failure in DIC.

--- Card 91 ---
Q: Major side effects of TXA?
A: Nausea/vomiting (GI); VTE risk (theoretical); colour vision changes (rare); seizures at high doses.

--- Card 92 ---
Q: What is aminocaproic acid?
A: Similar mechanism to TXA (lysine analogue, antifibrinolytic); used in haemophilia bleeds; less commonly tested than TXA.


=== SECTION 8: HAEMATINICS ===

--- IRON ---

--- Card 93 ---
Q: Which form of oral iron is best absorbed - ferrous or ferric?
A: Ferrous (Fe2+) is better absorbed than ferric (Fe3+); ferrous sulfate is first-line.
[Trap: common wrong answer is "ferric iron is better absorbed" - ferrous (Fe2+) is the form that is absorbed in the duodenum]

--- Card 94 ---
Q: What is the mnemonic for iron absorption?
A: "Vitamin C = ↑ (converts Fe3+ to Fe2+); Tea/antacids = ↓ (chelate iron); Ferrous > Ferric."

--- Card 95 ---
[c] Ferrous sulfate [/c] absorption is increased by Vitamin C because ascorbic acid converts ferric (Fe3+) to ferrous (Fe2+) iron in the gut.

--- Card 96 ---
Q: What reduces oral iron absorption?
A: Antacids, PPIs, tea, coffee, calcium (all chelate iron or raise gastric pH); take iron on an empty stomach.

--- Card 97 ---
Q: How fast should Hb rise with iron supplementation?
A: ~10-20 g/L per 3 weeks; reticulocyte count rises at 1 week (first sign of response).

--- Card 98 ---
Q: When is IV iron indicated over oral iron?
A: Oral failure/intolerance; IBD; CKD on dialysis; severe deficiency in pregnancy; bariatric surgery.

--- Card 99 ---
Q: What is a serious side effect of IV ferric carboxymaltose?
A: Transient hypophosphataemia; anaphylaxis (rare but serious with older formulations).

--- Card 100 ---
Q: What are the contraindications to iron supplementation?
A: Haemochromatosis; haemolytic anaemia (iron is not usually deficient).

--- B12 ---

--- Card 101 ---
Q: What is the mnemonic for B12?
A: "B12 = Big red cells (macrocytic), Bad nerves (subacute combined degeneration), Bypass stomach (intrinsic factor needed)."

--- Card 102 ---
Q: What is pernicious anaemia?
A: Autoimmune destruction of gastric parietal cells → absent intrinsic factor → cannot absorb dietary B12 → macrocytic anaemia + subacute combined degeneration.

--- Card 103 ---
Q: What antibodies are found in pernicious anaemia?
A: Anti-intrinsic factor antibodies (most specific) + anti-parietal cell antibodies.

--- Card 104 ---
Q: What is the treatment for pernicious anaemia?
A: IM hydroxocobalamin 1 mg on alternate days x2 weeks, then every 3 months lifelong.
[Trap: common wrong answer is "oral B12 for pernicious anaemia" - oral B12 requires intrinsic factor for absorption; pernicious anaemia has absent IF → must give IM]

--- Card 105 ---
Q: What neurological syndrome does B12 deficiency cause?
A: Subacute combined degeneration of the spinal cord (posterior columns + lateral corticospinal tracts) → bilateral paraesthesiae, ataxia, spasticity, extensor plantar responses.

--- Card 106 ---
Q: HKMLE Pearl: What is the danger of giving folate alone when B12 deficiency is possible?
A: Folate treats the macrocytic anaemia (blood picture improves) but UNMASKS subacute combined degeneration of the cord → neurological deterioration.
[Trap: this is the classic HKMLE trap - "folate alone for macrocytic anaemia" without ruling out B12 deficiency causes neurological harm]

--- Card 107 ---
Q: What is the mnemonic for B12 vs folate anaemia?
A: "B12 = Bad nerves (subacute combined degeneration); Folate = Fine nerves (no neurological features)."

--- Card 108 ---
Q: What electrolyte disturbance can occur when starting B12 treatment?
A: Hypokalaemia - B12 stimulates RBC production → ↑ K+ uptake into new cells → fall in serum K+.

--- Card 109 ---
Q: Where is B12 absorbed in the gut?
A: Terminal ileum (with intrinsic factor); Crohn's disease or terminal ileal resection → B12 deficiency.

--- FOLATE ---

--- Card 110 ---
Q: What is the mnemonic for folate?
A: "FOLATE = First trimester supplement, Only treats blood (not neuro), Looks same as B12 anaemia, Avoid giving alone if B12 deficiency possible, Treatment oral."

--- Card 111 ---
Q: Standard folate dose for preconception and first trimester?
A: 400 mcg (0.4 mg) daily.

--- Card 112 ---
Q: High-risk folate dose - who gets 5 mg daily?
A: Previous NTD baby, diabetes, antiepileptic use, obesity - all require 5 mg/day starting preconception.

--- Card 113 ---
Q: What dose of folate is given with methotrexate?
A: 5 mg once weekly (to reduce methotrexate toxicity by replenishing folate).

--- Card 114 ---
Q: HKMLE Pearl: Most common cause of folate deficiency in clinical practice?
A: Alcoholism (poor diet + direct effect on folate metabolism).

--- Card 115 ---
Q: What drugs cause folate deficiency?
A: Methotrexate (DHFR inhibitor), trimethoprim, phenytoin.

--- Card 116 ---
Q: How do you differentiate B12 vs folate deficiency macrocytic anaemia?
A: Both cause macrocytosis + hypersegmented neutrophils; B12 deficiency causes neurological features (subacute combined degeneration); folate deficiency does NOT cause neurological symptoms.


=== SECTION 9: HAEMATOPOIETIC GROWTH FACTORS ===

--- EPO / ESAs ---

--- Card 117 ---
Q: What is the mechanism of erythropoietin (EPO)?
A: Recombinant EPO binds EPO receptor on erythroid progenitors in bone marrow → stimulates RBC production.

--- Card 118 ---
Q: What is the mnemonic for EPO?
A: "EPO = Every Patient On dialysis needs this."

--- Card 119 ---
Q: What is the primary indication for EPO/ESAs?
A: Anaemia of chronic kidney disease (CKD); also chemotherapy-induced anaemia, low-risk MDS.

--- Card 120 ---
Q: What is the Hb target when using EPO in CKD?
A: 100-120 g/L; do NOT exceed 130 g/L (↑ cardiovascular events and VTE shown in CHOIR and CREATE trials).
[Trap: common wrong answer is "target normal Hb with EPO in CKD" - targeting normal Hb increases cardiovascular mortality and VTE]

--- Card 121 ---
Q: What is the mnemonic for EPO Hb target?
A: "100-120 g/L, NOT normal" (overcorrection → VTE + CV events).

--- Card 122 ---
Q: Most common side effect of EPO?
A: Hypertension (↑ Hb → ↑ blood viscosity → ↑ BP).

--- Card 123 ---
[c] EPO/ESAs [/c] cause hypertension because rising haemoglobin increases blood viscosity, raising peripheral resistance and blood pressure.

--- Card 124 ---
Q: What is pure red cell aplasia (PRCA) in the context of EPO?
A: Rare but serious: anti-EPO antibodies develop → cross-react with endogenous EPO → sudden worsening anaemia after initial response; stop EPO, consider immunosuppression.

--- Card 125 ---
Q: HKMLE Pearl: Why must iron be checked before starting EPO?
A: Iron deficiency limits ESA response; if iron-deficient, EPO will not work (iron is required for haemoglobin synthesis).

--- G-CSF ---

--- Card 126 ---
Q: What is the mechanism of G-CSF (filgrastim/pegfilgrastim)?
A: Binds G-CSF receptor → stimulates proliferation, differentiation, and survival of neutrophil precursors → ↑ mature neutrophil release from bone marrow.

--- Card 127 ---
Q: What is the mnemonic for G-CSF?
A: "G-CSF = Grows White cells (neutrophils)."

--- Card 128 ---
Q: What are the key indications for G-CSF?
A: Prevention of chemotherapy-induced febrile neutropenia; treatment of neutropenia; stem cell mobilisation before harvest for transplant.

--- Card 129 ---
Q: Most common side effect of G-CSF?
A: Bone pain (due to medullary expansion of bone marrow); treat with paracetamol ± ibuprofen.
[Trap: common wrong answer is "G-CSF commonly causes splenomegaly" - splenomegaly occurs but bone pain is the most common side effect]

--- Card 130 ---
Q: What is the mnemonic for G-CSF's main side effect?
A: "BONE pain" (marrow expansion).

--- Card 131 ---
Q: Rare but serious side effect of G-CSF?
A: Splenic rupture (from splenomegaly due to ↑ splenic workload).

--- TPO Receptor Agonists ---

--- Card 132 ---
Q: What is the mechanism of TPO receptor agonists (romiplostim, eltrombopag)?
A: Bind and activate thrombopoietin receptor (Mpl) → stimulate megakaryocyte proliferation → ↑ platelet production.

--- Card 133 ---
Q: What is romiplostim used for?
A: Immune thrombocytopenia (ITP) - second-line after steroids; SC weekly injection.

--- Card 134 ---
Q: What is eltrombopag used for?
A: ITP, aplastic anaemia (with ciclosporin), thrombocytopenia in HCV/chronic liver disease.

--- Card 135 ---
Q: Side effects of eltrombopag?
A: Hepatotoxicity (monitor LFTs); chelation with polyvalent cations (take without food and away from calcium, iron, antacids); bone marrow reticulin fibrosis with prolonged use.

--- Card 136 ---
Q: Major long-term risk of TPO receptor agonists?
A: Bone marrow reticulin fibrosis (with prolonged use); thrombosis (↑ platelet count → VTE risk).


=== SECTION 10: REVERSAL AGENTS ===

--- Card 137 ---
Q: What is the reversal agent for UFH?
A: Protamine sulfate 1 mg per 100 units UFH (IV slow); risk of hypotension, bradycardia, anaphylaxis.

--- Card 138 ---
Q: Who is at risk of anaphylaxis to protamine sulfate?
A: Fish allergy; prior vasectomy (anti-protamine antibodies may form as protamine is derived from fish sperm).

--- Card 139 ---
Q: What is the reversal for non-urgent warfarin toxicity?
A: Vitamin K (phytomenadione) oral; slow onset 6-12h oral / 1-2h IV; IV administration carries anaphylaxis risk.

--- Card 140 ---
Q: What is the reversal agent for fibrinolytics?
A: No specific antidote; TXA (tranexamic acid) + FFP/cryoprecipitate + supportive care.

--- Card 141 ---
Q: What is the mnemonic for reversal agents?
A: "4Ps + 2Is + 1A" = Protamine (heparin), Phytomenadione/Vitamin K (warfarin), PCC (warfarin/Xa), Platelet transfusion, Idarucizumab (dabigatran), andexanet Alfa (Xa inhibitors), Aminocaproic acid/TXA (fibrinolytics).


=== SECTION 11: HKMLE PEARL CARDS (HIGH-YIELD SCENARIOS) ===

--- Card 142 ---
Q: HKMLE Pearl: A pregnant patient needs anticoagulation - which drug?
A: LMWH (e.g. enoxaparin) throughout pregnancy; warfarin = teratogen (embryopathy weeks 6-12, fetal haemorrhage T3); DOACs = contraindicated (teratogenic + cross placenta).

--- Card 143 ---
Q: HKMLE Pearl: A patient on warfarin needs emergency surgery - what do you give?
A: 4-factor PCC + IV vitamin K 10 mg immediately (fastest warfarin reversal).

--- Card 144 ---
Q: HKMLE Pearl: Dabigatran vs Xa inhibitors - which has the specific antidote?
A: Dabigatran → idarucizumab (specific, approved); Xa inhibitors → andexanet alfa (specific, approved); both now available.

--- Card 145 ---
Q: HKMLE Pearl: A patient develops thrombocytopenia on day 7 of heparin - what is the diagnosis and first step?
A: HIT Type II - stop ALL heparin (UFH and LMWH) immediately; start argatroban or fondaparinux; do NOT give platelets.

--- Card 146 ---
Q: HKMLE Pearl: Patient with macrocytic anaemia and no neurological features - B12 or folate deficiency?
A: Either could be the cause; MUST check B12 and folate levels before treating; do not give folate alone without ruling out B12 deficiency.

--- Card 147 ---
Q: HKMLE Pearl: A patient with prior TIA presents with STEMI - which P2Y12 inhibitor is contraindicated?
A: Prasugrel (contraindicated in prior TIA/stroke due to high intracranial bleed risk); use ticagrelor or clopidogrel.

--- Card 148 ---
Q: HKMLE Pearl: A patient with CrCl 25 mL/min needs a DOAC for AF - which do you choose?
A: Avoid dabigatran (CrCl <30); prefer apixaban (lowest renal clearance ~27%) with dose adjustment if criteria met.

--- Card 149 ---
Q: HKMLE Pearl: Warfarin vs DOAC for AF with antiphospholipid syndrome?
A: Warfarin is preferred for triple-positive APS; DOACs are inferior (higher thrombotic event rates in APS).

--- Card 150 ---
Q: HKMLE Pearl: Patient develops sudden severe anaemia after initially responding to EPO - what do you suspect?
A: Pure red cell aplasia (PRCA) - check anti-EPO antibodies; stop EPO.

--- Card 151 ---
Q: HKMLE Pearl: What must be excluded before giving alteplase for ischaemic stroke?
A: Haemorrhagic stroke (CT head mandatory before thrombolysis); also check BP <185/110.

--- Card 152 ---
Q: HKMLE Pearl: Can streptokinase be given again 2 years after first use?
A: No - antibodies from first dose persist for at least 5 years; reuse within 5 years is ineffective and risks anaphylaxis.

--- Card 153 ---
Q: HKMLE Pearl: TXA for trauma - what is the critical time window?
A: Must be given within 3 hours of injury (CRASH-2 trial); after 3h = no mortality benefit.

--- Card 154 ---
Q: HKMLE Pearl: Patient on heparin post-cardiac surgery develops HIT - what anticoagulant do you use if they also have renal failure?
A: Argatroban (hepatic elimination → safe in renal failure; fondaparinux is renally cleared).

--- Card 155 ---
Q: HKMLE Pearl: High-risk pregnancy (prior NTD) - what is the correct folate dose and timing?
A: 5 mg/day started preconception and continued through first trimester (standard dose = 400 mcg/day for low-risk).

--- Card 156 ---
Q: HKMLE Pearl: Ticagrelor is preferred over clopidogrel for ACS based on which trial?
A: PLATO trial (ticagrelor > clopidogrel for mortality reduction in ACS).

--- Card 157 ---
Q: HKMLE Pearl: Prasugrel is preferred for STEMI post-PCI based on which trial?
A: TRITON trial (prasugrel > clopidogrel in STEMI patients undergoing PCI).

--- Card 158 ---
Q: HKMLE Pearl: INR rises first day after starting warfarin - is the patient anticoagulated?
A: No - early INR rise reflects factor VII depletion only; full anticoagulation requires 3-5 days; Protein C/S also fall early → transient procoagulant state.

--- Card 159 ---
Q: HKMLE Pearl: Patient with APS and recurrent thrombosis on warfarin - what INR target?
A: INR 3.0 - 4.0 (higher target for recurrent thrombosis in APS).


=== SECTION 12: MNEMONIC CARDS ===

--- Card 160 ---
Q: What is the mnemonic for the HKMLE haematology pharmacology master map?
A: "WATCH A GRIP" = Warfarin, Anticoagulants, DOACs, Thrombolytics, Clot stabilisers (TXA), Heparin + DTIs, Antiplatelets, Growth factors, Reversal agents, Iron/B12/Folate, Platelets/coagulation.

--- Card 161 ---
Q: What is the mnemonic for HIT management?
A: "Stop Heparin, Start Argatroban/Fondaparinux, NO platelets, NO warfarin yet."

--- Card 162 ---
Q: What is the mnemonic for BRAIN HURTS (thrombolytic contraindications)?
A: Bleeding, Recent surgery/trauma, Aortic dissection, Intracranial history, Neurosurgery recent, Haemorrhagic stroke, Uncontrolled BP, Recent head injury, Time window exceeded, Severe coagulopathy.

--- Card 163 ---
Q: What is the mnemonic for warfarin-affected factors?
A: "1972" = Factors II (2), VII (7), IX (9), X (10) + Proteins C and S; vitamin K-dependent factors.

--- Card 164 ---
Q: What is the mnemonic for iron absorption?
A: "FERRIC = Ferrous is absorbed, Ferritin stores it, Restores Hb, Iron deficiency = Check cause, Constipation = side effect."


=== SECTION 13: ADDITIONAL HIGH-YIELD TRAP CARDS ===

--- Card 165 ---
Q: HKMLE Pearl: Can DOACs be used for non-valvular AF?
A: Yes - DOACs are first-line for non-valvular AF; warfarin is used for valvular AF (rheumatic mitral stenosis) and mechanical valves.
[Trap: common wrong answer is "DOACs for all AF" - mechanical valves and rheumatic mitral stenosis require warfarin]

--- Card 166 ---
Q: HKMLE Pearl: A patient is on warfarin and prescribed rifampicin for TB - what happens to INR?
A: INR falls (↓ warfarin efficacy) because rifampicin strongly induces CYP2C9 → ↑ warfarin metabolism; warfarin dose must be significantly increased and carefully monitored.

--- Card 167 ---
Q: HKMLE Pearl: A patient on warfarin is given amiodarone - what happens?
A: INR rises (↑ bleeding risk) - amiodarone inhibits CYP2C9 → ↓ warfarin metabolism → warfarin dose must be reduced.

--- Card 168 ---
Q: HKMLE Pearl: How does IV iron differ from oral iron in indications?
A: IV iron (ferric carboxymaltose, iron sucrose) is used when oral iron fails/is intolerated, IBD, CKD on dialysis, severe deficiency in pregnancy, bariatric surgery (poor GI absorption).

--- Card 169 ---
Q: HKMLE Pearl: Why is IM B12 (not oral) used for pernicious anaemia?
A: Pernicious anaemia = absent intrinsic factor → cannot absorb B12 from gut via normal pathway → must bypass GI tract with IM injection (oral cyanocobalamin only for dietary deficiency where IF is present).

--- Card 170 ---
Q: HKMLE Pearl: Warfarin skin necrosis - which patients are most at risk?
A: Patients with underlying Protein C deficiency - warfarin preferentially depletes Protein C first → local thrombosis in skin microvasculature → necrosis.

--- Card 171 ---
Q: HKMLE Pearl: Which P2Y12 inhibitor is NOT a prodrug?
A: Ticagrelor (acts directly; no CYP2C19 needed); clopidogrel and prasugrel are prodrugs requiring CYP2C19 activation.

--- Card 172 ---
Q: HKMLE Pearl: A patient with CKD on EPO is not responding to treatment - what is the most likely cause?
A: Iron deficiency (most common cause of EPO resistance); check ferritin and TSAT; replenish iron before increasing EPO dose.

--- Card 173 ---
Q: HKMLE Pearl: What monitoring parameter is used for UFH vs LMWH?
A: UFH → aPTT (target 1.5-2.5x normal); LMWH → usually no monitoring (anti-Xa level in obese, pregnant, or renal impairment).

--- Card 174 ---
Q: HKMLE Pearl: G-CSF bone pain - how do you manage it?
A: Paracetamol ± ibuprofen; bone pain results from medullary (bone marrow) expansion due to neutrophil proliferation.

--- Card 175 ---
Q: HKMLE Pearl: A patient on eltrombopag has rising liver enzymes - what do you do?
A: Monitor LFTs (hepatotoxicity is a known side effect of eltrombopag); consider dose reduction or stopping if severe.

================================================================
TOTAL: 175 HKMLE HIGH-YIELD ANKI CARDS
Topics covered: Warfarin (22), Heparin/HIT (15), DTIs (3), 
DOACs (14), Antiplatelets (16), Thrombolytics (12), TXA (10), 
Iron/B12/Folate (24), Growth Factors (19), Reversal Agents (5), 
HKMLE Pearls (18), Mnemonics (5), Trap Alerts throughout
================================================================