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HKMLE HAEMATOLOGY PHARMACOLOGY - ANKI FLASHCARD DECK
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Format key: Type 1 = Basic Q&A | Type 2 = Cloze | Type 3 = Mnemonic | Type 4 = HKMLE Pearl
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SECTION 1: WARFARIN (VITAMIN K ANTAGONIST)
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--- Type 3 ---
Q: What is the mnemonic for warfarin's factor targets?
A: "WEPT" = Warfarin: Extended PT, inhibits 1972 (factors II, VII, IX, X + Proteins C and S)

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

--- Type 1 ---
Q: Why does warfarin require 3-5 days to reach full anticoagulant effect?
A: It must wait for existing clotting factors to be depleted; factor VII has the shortest half-life (6h) so INR rises first but full anticoagulation takes 3-5 days.
[Trap: common wrong answer is "warfarin acts immediately like heparin" because the INR rises early — but early INR rise reflects factor VII depletion only, not full anticoagulation]

--- Type 1 ---
Q: What is the monitoring parameter for warfarin?
A: INR (international normalised ratio).

--- Type 1 ---
Q: What is the target INR for AF and DVT/PE?
A: 2.0-3.0.

--- Type 1 ---
Q: What is the target INR for a mechanical mitral valve?
A: 2.5-3.5.
[Trap: common wrong answer is 2.0-3.0 (same as AF) — mechanical mitral valves are higher risk than aortic valves and require higher INR target]

--- Type 1 ---
Q: What is the target INR for a mechanical aortic valve?
A: 2.0-3.0 (some guidelines accept 2.5-3.5).

--- Type 1 ---
Q: What is the target INR for recurrent PE or antiphospholipid syndrome?
A: 2.5-3.5.

--- Type 1 ---
Q: What is warfarin's most dangerous major side effect?
A: Intracranial haemorrhage (and GI bleeding — most common bleeding site).

--- Type 1 ---
Q: What causes warfarin-induced skin necrosis?
A: Warfarin preferentially depletes short-lived Protein C/S before full anticoagulation → transient procoagulant state → microvascular thrombosis → skin necrosis; especially in protein C deficiency.
[Trap: common wrong answer is "direct skin toxicity" — it is actually a thrombotic complication from early Protein C/S depletion]

--- Type 4 ---
Q: HKMLE Pearl: A patient starts warfarin for DVT. On day 2 her INR is 3.2. Is she fully anticoagulated?
A: No — early INR rise reflects factor VII depletion only; full anticoagulation requires depletion of all clotting factors (3-5 days); always bridge with heparin/LMWH.

--- Type 2 ---
[c] Warfarin [/c] is Category X in pregnancy because it causes warfarin embryopathy (nasal hypoplasia, stippled epiphyses) in weeks 6-12 and fetal haemorrhage in T3.

--- Type 1 ---
Q: What are the absolute contraindications to warfarin?
A: Pregnancy (all trimesters), active bleeding, recent intracranial surgery or haemorrhage.

--- Type 1 ---
Q: What enzyme mediates most warfarin drug interactions?
A: CYP2C9.

--- Type 3 ---
Q: What is the mnemonic for drugs that INCREASE warfarin INR?
A: "CAFE MIX" = Clarithromycin/ciprofloxacin, Amiodarone, Fluconazole, Erythromycin, Metronidazole, Isoniazid, eXcretion inhibitors (statins)

--- Type 3 ---
Q: What is the mnemonic for drugs that DECREASE warfarin INR?
A: "PRICARS" = Phenytoin, Rifampicin, Isoniazid (high dose), Carbamazepine, Alcohol (chronic), Rifampicin, St John's Wort

--- Type 1 ---
Q: Does amiodarone increase or decrease warfarin INR?
A: Increases INR (inhibits CYP2C9 → reduced warfarin metabolism → higher warfarin levels → ↑ bleeding risk).

--- Type 1 ---
Q: Does rifampicin increase or decrease warfarin INR?
A: Decreases INR (induces CYP2C9 → increased warfarin metabolism → reduced efficacy).

--- Type 1 ---
Q: Do NSAIDs change the INR on warfarin?
A: Variable/no direct change to INR, but NSAIDs increase bleeding risk via GI mucosal damage and platelet inhibition.

--- Type 1 ---
Q: INR is 5-8 with no significant bleeding — what is the management?
A: Stop warfarin and give low-dose oral vitamin K 1-2mg.

--- Type 1 ---
Q: INR >8 with no or minor bleeding — what is the management?
A: Stop warfarin and give oral vitamin K 5mg (repeat at 24h if INR still high).

--- Type 1 ---
Q: Any INR with major bleeding — what is the management?
A: Stop warfarin + IV vitamin K 5-10mg + 4-factor PCC (preferred over FFP — faster, lower volume).
[Trap: common wrong answer is FFP alone — PCC is preferred because it acts faster and requires less volume]

--- Type 1 ---
Q: Life-threatening intracranial bleed on warfarin — immediate management?
A: PCC + IV vitamin K 10mg immediately.

--- Type 4 ---
Q: HKMLE Pearl: Why must warfarin always be started with heparin when treating acute thrombosis?
A: Warfarin first depletes Protein C/S (short half-lives) → transient procoagulant state → risk of worsening thrombosis if not covered by heparin.

--- Type 1 ---
Q: What does INR specifically measure?
A: The extrinsic coagulation pathway — factors VII, X, II, V, and fibrinogen.


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SECTION 2: HEPARIN (UFH AND LMWH)
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--- Type 3 ---
Q: What is the mnemonic for heparin?
A: "HEPARIN" = Helps Every Patient And Requires INR-free monitoring (except UFH)

--- Type 1 ---
Q: What is UFH's mechanism of action?
A: Binds antithrombin III → inhibits factor IIa (thrombin) and Xa (and IXa, XIa, XIIa).

--- Type 1 ---
Q: What is LMWH's mechanism of action and how does it differ from UFH?
A: Binds antithrombin III → preferentially inhibits factor Xa only (smaller chain cannot bridge thrombin to antithrombin).

--- Type 1 ---
Q: How is UFH monitored?
A: aPTT (target 1.5-2.5x normal).

--- Type 1 ---
Q: How is LMWH monitored?
A: Usually NOT required; anti-Xa level used if obese, pregnant, or renal impairment.

--- Type 1 ---
Q: What is the half-life of IV UFH?
A: ~1.5 hours.

--- Type 1 ---
Q: What reverses UFH?
A: Protamine sulfate (fully neutralises UFH).

--- Type 1 ---
Q: What reverses LMWH?
A: Protamine sulfate (only ~60% reversal — partial).
[Trap: common wrong answer is "protamine fully reverses LMWH like UFH" — it only partially reverses LMWH (~60%)]

--- Type 1 ---
Q: Is LMWH safe in pregnancy?
A: Yes — does not cross placenta; more predictable than UFH; preferred in pregnancy.

--- Type 1 ---
Q: Why must LMWH be dose-reduced or avoided in severe renal failure?
A: LMWH accumulates in renal failure (renal clearance) → avoid if eGFR <30.
[Trap: common wrong answer is "UFH also needs dose reduction in renal failure" — UFH is metabolised by the reticuloendothelial system, not the kidneys, so renal failure does not affect UFH accumulation]

--- Type 1 ---
Q: Which has higher HIT risk — UFH or LMWH?
A: UFH (5-10%), though LMWH can still cause HIT.

--- Type 1 ---
Q: When is UFH preferred over LMWH?
A: ICU, unstable patients, perioperative settings where rapid reversal is needed.

--- Type 3 ---
Q: What is the mnemonic for HIT?
A: "HIT" = Heparin Induces Thrombosis (paradoxically) — use the 4Ts score

--- Type 1 ---
Q: What is HIT Type I?
A: Non-immune; mild platelet drop (>100) within 1-2 days; benign; continue heparin.

--- Type 1 ---
Q: What is HIT Type II?
A: Immune; IgG antibodies against heparin-PF4 complex → platelet activation → paradoxical thrombosis; platelet count drops >50% from baseline at days 5-10.

--- Type 1 ---
Q: What are the 4Ts in the 4Ts score for HIT?
A: Thrombocytopenia (severity), Timing (days 5-10), Thrombosis, other causes of Thrombocytopenia excluded.

--- Type 1 ---
Q: What test confirms HIT Type II?
A: Anti-PF4/heparin ELISA or serotonin release assay.

--- Type 1 ---
Q: What is the management of HIT Type II?
A: Stop ALL heparin (UFH AND LMWH); start alternative anticoagulant (argatroban or fondaparinux); do NOT give platelets; do NOT start warfarin until platelets >150.

--- Type 4 ---
Q: HKMLE Pearl: A patient on heparin develops a falling platelet count and a new DVT on day 7. What is the diagnosis and immediate action?
A: HIT Type II — stop ALL heparin immediately and start argatroban or fondaparinux; do NOT give platelet transfusion.

--- Type 4 ---
Q: HKMLE Pearl: Why are platelet transfusions contraindicated in HIT?
A: HIT causes thrombosis (not just bleeding) — transfusing platelets worsens platelet activation and thrombus formation.

--- Type 4 ---
Q: HKMLE Pearl: Why should warfarin not be started in HIT until platelets >150?
A: Warfarin depletes Protein C → thrombotic state → risk of venous limb gangrene while platelets are still low.

--- Type 2 ---
[c] Fondaparinux [/c] is used in HIT because it inhibits only factor Xa with no cross-reactivity with PF4 antibodies.


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SECTION 3: DIRECT THROMBIN INHIBITORS (DTIs)
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--- Type 1 ---
Q: What is the mechanism of direct thrombin inhibitors (DTIs)?
A: Directly inhibit thrombin (factor IIa) → block fibrin formation and thrombin-mediated platelet activation; act independently of antithrombin (unlike heparin).

--- Type 1 ---
Q: What is argatroban's key feature that makes it useful in HIT with renal failure?
A: Hepatic elimination — safe to use when renal failure is present (unlike most other anticoagulants).

--- Type 4 ---
Q: HKMLE Pearl: Which anticoagulant is the drug of choice for HIT in renal failure?
A: Argatroban (hepatic elimination — safe in renal failure).

--- Type 1 ---
Q: What is bivalirudin used for?
A: PCI (percutaneous coronary intervention) as an alternative to heparin; short-acting; renally eliminated.

--- Type 1 ---
Q: Is there a reversal agent for argatroban?
A: No specific antidote — stop the infusion (short half-life ~50 min).


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SECTION 4: DIRECT ORAL ANTICOAGULANTS (DOACs)
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--- Type 3 ---
Q: What is the mnemonic for DOAC targets?
A: "3 Xas + 1 IIa" = Rivaroxaban, Apixaban, Edoxaban (factor Xa inhibitors) + Dabigatran (factor IIa inhibitor)

--- Type 1 ---
Q: Which DOAC is the only oral direct thrombin inhibitor?
A: Dabigatran (factor IIa inhibitor).
[Trap: common wrong answer is rivaroxaban or apixaban — these are factor Xa inhibitors, NOT thrombin inhibitors]

--- Type 1 ---
Q: Name the three factor Xa inhibitor DOACs.
A: Rivaroxaban, Apixaban, Edoxaban.

--- Type 1 ---
Q: What is dabigatran's bioavailability?
A: Only 6% (very low — this is why it is dosed twice daily and why excess is dangerous).

--- Type 1 ---
Q: What is dabigatran's renal clearance and why does it matter?
A: 80% renally cleared — avoid if CrCl <30 mL/min (accumulates → bleeding risk).

--- Type 1 ---
Q: Which DOAC is safest in CKD and why?
A: Apixaban — least renally cleared (~27%); dose reduce only if 2 of: age ≥80, weight ≤60kg, creatinine ≥133 µmol/L.
[Trap: common wrong answer is "all DOACs are equally safe in CKD" — dabigatran is most dangerous in CKD due to 80% renal clearance]

--- Type 1 ---
Q: What drug interactions reduce efficacy of ALL DOACs?
A: P-gp inducers/CYP3A4 inducers: rifampicin, St John's Wort, carbamazepine, phenytoin.

--- Type 1 ---
Q: What are the key indications for DOACs?
A: Non-valvular AF (stroke prevention), DVT/PE treatment and prevention, post-surgical VTE prophylaxis.

--- Type 1 ---
Q: What are the major side effects of DOACs?
A: Bleeding (GI bleeding particularly high with dabigatran and rivaroxaban vs warfarin).

--- Type 1 ---
Q: Name three absolute contraindications to DOACs.
A: Pregnancy (teratogenic), mechanical heart valves (DOACs inferior — RE-ALIGN trial), severe renal impairment (especially dabigatran).
[Trap: common wrong answer is "DOACs can be used in mechanical heart valves because they are 'newer'" — the RE-ALIGN trial showed DOACs are INFERIOR to warfarin for mechanical valves]

--- Type 4 ---
Q: HKMLE Pearl: Can a DOAC be used in triple-positive antiphospholipid syndrome?
A: No — warfarin is preferred; DOACs are inferior in APS (especially triple-positive).

--- Type 3 ---
Q: What is the mnemonic for DOAC reversal?
A: "I-DAR for IIa (dabigatran), AND-exanet for Xa"

--- Type 1 ---
Q: What is the reversal agent for dabigatran?
A: Idarucizumab (Praxbind) 5g IV — monoclonal Ab Fab fragment; reverses dabigatran within minutes.

--- Type 1 ---
Q: What is the reversal agent for rivaroxaban and apixaban?
A: Andexanet alfa (recombinant factor Xa decoy); alternative = 4F-PCC 25-50 units/kg if unavailable.

--- Type 4 ---
Q: HKMLE Pearl: A patient on rivaroxaban has a major haemorrhage. Idarucizumab is available. Should you use it?
A: No — idarucizumab reverses dabigatran only; use andexanet alfa (or 4F-PCC) for rivaroxaban.
[Trap: common wrong answer is using idarucizumab for all DOACs — idarucizumab is SPECIFIC to dabigatran only]

--- Type 1 ---
Q: What monitoring is used for DOACs?
A: Not routinely needed; anti-Xa assay (for Xa inhibitors) or modified thrombin time (for dabigatran) if needed.

--- Type 1 ---
Q: What are the advantages of DOACs over warfarin?
A: No routine monitoring, fewer drug interactions, predictable dosing, faster onset/offset, lower risk of intracranial haemorrhage.

--- Type 1 ---
Q: Apixaban dose reduction criteria — name the rule?
A: Dose reduce if 2 of 3: age ≥80, weight ≤60kg, creatinine ≥133 µmol/L.

--- Type 1 ---
Q: If a patient took rivaroxaban within 2 hours and has a non-major bleed, what is the first step?
A: Activated charcoal (especially if within 2 hours of ingestion, particularly useful for dabigatran).


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SECTION 5: ANTIPLATELETS
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--- Type 1 ---
Q: What is aspirin's mechanism of antiplatelet action?
A: Irreversibly inhibits COX-1 → ↓ TXA2 → ↓ platelet aggregation; effect lasts 7-10 days (platelet lifespan).

--- Type 1 ---
Q: What dose of aspirin is used for antiplatelet therapy?
A: Low dose 75-150mg daily.

--- Type 1 ---
Q: Why should aspirin never be given to children under 12?
A: Risk of Reye's syndrome.

--- Type 1 ---
Q: What is clopidogrel's mechanism?
A: Irreversibly blocks P2Y12 ADP receptor on platelets; prodrug requiring CYP2C19 activation.

--- Type 1 ---
Q: What affects clopidogrel efficacy?
A: CYP2C19 poor metabolisers = reduced efficacy; PPIs reduce efficacy via CYP2C19 competition.

--- Type 1 ---
Q: What is ticagrelor's mechanism and how does it differ from clopidogrel?
A: Reversibly blocks P2Y12 — NOT a prodrug (no CYP2C19 activation needed); more potent than clopidogrel.

--- Type 1 ---
Q: What is ticagrelor's most notable side effect?
A: Dyspnoea (adenosine-mediated — NOT bronchospasm; do not automatically switch to clopidogrel).
[Trap: common wrong answer is "ticagrelor dyspnoea = bronchospasm → stop drug" — it is adenosine-mediated, not true bronchospasm; do not switch without reason]

--- Type 4 ---
Q: HKMLE Pearl: Ticagrelor is used with aspirin post-ACS. What dose of aspirin should be used?
A: Low dose only — high-dose aspirin reduces ticagrelor efficacy.

--- Type 1 ---
Q: What is prasugrel's mechanism and when is it preferred?
A: Irreversibly blocks P2Y12; prodrug (more efficient activation than clopidogrel); preferred in STEMI post-PCI (TRITON trial).

--- Type 1 ---
Q: What are prasugrel's contraindications?
A: Prior stroke/TIA (↑ intracranial bleed), age >75, weight <60kg.
[Trap: common wrong answer is "prasugrel can be used post-TIA because it is more potent" — it is CONTRAINDICATED in prior stroke/TIA due to high intracranial bleed risk]

--- Type 3 ---
Q: What is the mnemonic for prasugrel contraindication?
A: "Prior TIA/stroke = Prasugrel is PRASUREly dangerous"

--- Type 1 ---
Q: What is dipyridamole's mechanism?
A: Inhibits phosphodiesterase → ↑ cAMP → ↓ platelet aggregation; also blocks adenosine reuptake (vasodilatory).

--- Type 1 ---
Q: What is dipyridamole used for clinically?
A: Secondary stroke prevention (combined with aspirin = Aggrenox); cardiac pharmacological stress testing (adenosine analogue effect — dilates coronary arteries).

--- Type 1 ---
Q: What is DAPT?
A: Dual antiplatelet therapy = aspirin + P2Y12 inhibitor (e.g. clopidogrel or ticagrelor); standard post-ACS/PCI for 12 months.

--- Type 1 ---
Q: How long before elective surgery should clopidogrel/prasugrel be stopped?
A: 7-10 days before surgery (platelet lifespan).

--- Type 1 ---
Q: What is the mechanism of GPIIb/IIIa inhibitors (tirofiban, eptifibatide)?
A: Block GPIIb/IIIa receptor — the final common platelet aggregation pathway; IV only; used in high-risk ACS/PCI.


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SECTION 6: THROMBOLYTICS (FIBRINOLYTICS)
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--- Type 3 ---
Q: What is the mnemonic for thrombolytics' mechanism?
A: "tPA = turns Plasminogen to Active plasmin → eATs fibrin clots"

--- Type 1 ---
Q: What is the mechanism of all thrombolytics?
A: Activate plasminogen → plasmin → plasmin cleaves fibrin → dissolves clots.

--- Type 1 ---
Q: What is alteplase (tPA)?
A: Recombinant tissue plasminogen activator; fibrin-selective; gold standard for ischaemic stroke (≤4.5h), massive PE, and STEMI if PCI unavailable; short t½ (5 min).

--- Type 1 ---
Q: What is the time window for alteplase in ischaemic stroke?
A: Within 4.5 hours of symptom onset.

--- Type 4 ---
Q: HKMLE Pearl: Before giving alteplase for stroke, what must be excluded and how?
A: Haemorrhagic stroke must be excluded with CT head first (never give thrombolysis without CT).
[Trap: common wrong answer is "give alteplase first, CT later if bleeding" — CT head is MANDATORY before thrombolysis]

--- Type 4 ---
Q: HKMLE Pearl: What BP must be achieved before giving thrombolysis for ischaemic stroke?
A: <185/110 mmHg — BP must be controlled before alteplase.

--- Type 1 ---
Q: What is tenecteplase (TNK-tPA)?
A: Modified tPA; longer t½ → single IV bolus (more convenient for STEMI); increasingly used for ischaemic stroke.

--- Type 1 ---
Q: What makes streptokinase unique among thrombolytics?
A: Bacterial protein (Streptococcus) → antigenic → can only be used ONCE (antibodies formed → reuse within 5 years ineffective); NOT fibrin-selective; cheapest.
[Trap: common wrong answer is "streptokinase can be repeated if needed" — repeat use within 5 years is ineffective due to antibody formation]

--- Type 1 ---
Q: What is the time window for thrombolytics in STEMI when PCI is unavailable?
A: ≤12 hours from onset (ideally <6h); use tenecteplase or streptokinase.

--- Type 3 ---
Q: What is the mnemonic for absolute contraindications to thrombolytics?
A: "BRAIN HURTS" = Bleeding (active), Recent surgery/trauma, Aortic dissection, Intracranial history (haemorrhage), Neurosurgery (recent), Haemorrhagic stroke, Uncontrolled BP, Recent head injury, Time window exceeded, Severe bleeding disorder

--- Type 1 ---
Q: Name 4 absolute contraindications to thrombolytics.
A: Any prior intracranial haemorrhage; ischaemic stroke within 3 months; suspected aortic dissection; active internal bleeding.

--- Type 1 ---
Q: Name 4 major relative contraindications to thrombolytics.
A: SBP >180 or DBP >110 mmHg; recent major surgery/trauma (2-4 weeks); active peptic ulcer/GI bleed; pregnancy.


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SECTION 7: ANTIFIBRINOLYTICS (TXA)
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--- Type 3 ---
Q: What is the mnemonic for tranexamic acid?
A: "TXA = Tranexamic acid eXActs its effect by Blocking plasmin"

--- Type 1 ---
Q: What is tranexamic acid's (TXA) mechanism?
A: Synthetic lysine analogue → competitively inhibits plasminogen activation (blocks lysine-binding sites) → prevents fibrin clot breakdown → preserves haemostasis.

--- Type 1 ---
Q: What are TXA's key indications?
A: Trauma haemorrhage (CRASH-2), postpartum haemorrhage (WOMAN trial), heavy menstrual bleeding, elective surgery (↓ transfusion), hereditary angioedema prophylaxis.

--- Type 4 ---
Q: HKMLE Pearl: What does the CRASH-2 trial show about TXA in trauma?
A: TXA given within 3 hours of injury reduces all-cause mortality; given after 3 hours — no mortality benefit.
[Trap: common wrong answer is "TXA works up to 6 hours in trauma like stroke thrombolysis" — the CRASH-2 benefit is strictly within 3 hours]

--- Type 3 ---
Q: What is the mnemonic for TXA timing in trauma?
A: "3 hours or bust" (CRASH-2: must give within 3h of trauma)

--- Type 4 ---
Q: HKMLE Pearl: What does the WOMAN trial show about TXA?
A: TXA reduces death from bleeding in postpartum haemorrhage when given early; now WHO recommended.

--- Type 1 ---
Q: What are TXA's contraindications?
A: Active thromboembolic disease (DVT, PE, stroke); DIC with consumption (worsens DIC); haematuria from upper urinary tract (clots in ureter).

--- Type 1 ---
Q: What are TXA's major side effects?
A: Nausea/vomiting; VTE risk; colour vision changes (rare); seizures at high doses.

--- Type 1 ---
Q: Is TXA an anticoagulant reversal agent?
A: No — it prevents fibrin breakdown but does not reverse anticoagulants or replace blood products.

--- Type 2 ---
[c] Aminocaproic acid [/c] has the same mechanism as TXA and is used in haemophilia bleeds; less commonly tested in HKMLE.


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SECTION 8: HAEMATINICS
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--- 8a: IRON ---

--- Type 3 ---
Q: What is the mnemonic for iron therapy?
A: "FERRIC" = Ferrous is absorbed, Ferritin stores it, Restores Hb, Iron deficiency = Check cause, Constipation = side effect

--- Type 1 ---
Q: Why is ferrous (Fe²⁺) preferred over ferric (Fe³⁺) for oral iron?
A: Fe²⁺ is better absorbed from the gut than Fe³⁺; ferrous sulfate is the first-line oral preparation.

--- Type 1 ---
Q: What enhances oral iron absorption?
A: Vitamin C (ascorbic acid) — converts Fe³⁺ → Fe²⁺ and reduces it for absorption; take on an empty stomach.

--- Type 1 ---
Q: What reduces oral iron absorption?
A: Antacids, PPIs, tea, coffee, calcium chelate iron — take iron away from these.

--- Type 1 ---
Q: What is the earliest sign of response to iron therapy?
A: Reticulocyte count rises at ~1 week (reticulocyte crisis); Hb rises by ~10-20g/L per 3 weeks.

--- Type 1 ---
Q: What is the most common side effect of oral iron?
A: Constipation (also nausea, epigastric pain, dark stools).

--- Type 4 ---
Q: HKMLE Pearl: A patient on ferrous sulfate reports black stools. Is this a cause for alarm?
A: No — dark stools are a harmless side effect of oral iron; warn the patient.

--- Type 1 ---
Q: When is IV iron indicated?
A: Oral failure/intolerance, IBD, CKD on dialysis, severe deficiency in pregnancy, bariatric surgery.

--- Type 1 ---
Q: What is a serious side effect of IV ferric carboxymaltose?
A: Transient hypophosphataemia; anaphylaxis (rare but serious with older formulations); infusion reactions.

--- Type 1 ---
Q: What are the contraindications to iron supplementation?
A: Haemochromatosis, haemolytic anaemia (iron usually not deficient).

--- 8b: VITAMIN B12 ---

--- Type 3 ---
Q: What is the mnemonic for B12 deficiency?
A: "B12 = Big red cells (macrocytic), Bad nerves (subacute combined degeneration), Bypass stomach (intrinsic factor needed)"

--- Type 1 ---
Q: What is B12's mechanism in haematopoiesis?
A: Cofactor for DNA synthesis (methylcobalamin → methionine synthesis); cofactor for myelin formation (adenosylcobalamin → succinyl-CoA → Krebs cycle).

--- Type 1 ---
Q: What causes pernicious anaemia?
A: Autoimmune destruction of gastric parietal cells → absent intrinsic factor → inability to absorb dietary B12.

--- Type 1 ---
Q: What antibody is most specific for pernicious anaemia?
A: Anti-intrinsic factor antibodies (most specific); anti-parietal cell antibodies (more sensitive but less specific).

--- Type 1 ---
Q: What is the formulation and route for pernicious anaemia?
A: IM hydroxocobalamin 1mg alternate days for 2 weeks, then every 3 months lifelong.
[Trap: common wrong answer is "oral B12 is fine for pernicious anaemia" — pernicious anaemia means NO intrinsic factor → oral B12 cannot be absorbed → must give IM]

--- Type 1 ---
Q: What are the neurological features of B12 deficiency?
A: Subacute combined degeneration of spinal cord (posterior columns + lateral corticospinal tracts): bilateral paraesthesiae, ataxia, spasticity, extensor plantar responses.

--- Type 1 ---
Q: Name other clinical features of B12 deficiency.
A: Macrocytic anaemia, hypersegmented neutrophils, glossitis ("beefy red tongue"), megaloblastic changes.

--- Type 1 ---
Q: What sites are involved in B12 absorption?
A: Stomach (intrinsic factor from parietal cells) + terminal ileum (site of B12 absorption — affected in Crohn's, resection).

--- Type 4 ---
Q: HKMLE Pearl: A patient with macrocytic anaemia is given folic acid alone. What is the danger?
A: Folic acid treats the blood picture but UNMASKS subacute combined degeneration of the spinal cord if B12 deficiency is the underlying cause — neurological deterioration can occur.
[Trap: this is a classic HKMLE trap — never give folic acid alone without checking B12 level first]

--- Type 1 ---
Q: What is a side effect when starting B12 treatment?
A: Hypokalaemia — B12 stimulates RBC production → ↑ K⁺ uptake into new cells.

--- 8c: FOLATE ---

--- Type 3 ---
Q: What is the mnemonic for folate?
A: "FOLATE" = First trimester supplement, Only treats blood (not neuro), Looks same as B12 anaemia, Avoid in B12 deficiency alone, Treatment oral

--- Type 1 ---
Q: What is folate's mechanism?
A: Required for one-carbon transfer reactions → DNA synthesis; converted to THF → needed for purine/pyrimidine synthesis.

--- Type 1 ---
Q: What is the standard preconception/T1 folate dose?
A: 400 mcg (0.4mg) daily.

--- Type 1 ---
Q: What is the high-risk preconception folate dose and what qualifies as high-risk?
A: 5mg daily; high-risk = previous NTD, diabetes, antiepileptics, obesity.

--- Type 1 ---
Q: What is the folate dose for methotrexate co-prescription?
A: 5mg once weekly (not daily — given to reduce MTX side effects).

--- Type 1 ---
Q: What is the most common cause of folate deficiency in clinical practice?
A: Alcoholism (also poor diet, pregnancy, malabsorption, methotrexate).

--- Type 1 ---
Q: How do you differentiate B12 from folate deficiency anaemia?
A: Both cause macrocytic anaemia — differentiate with B12/folate blood levels + neurological features (B12 deficiency has neuro symptoms; folate deficiency does NOT cause subacute combined degeneration).

--- Type 1 ---
Q: What drugs cause folate deficiency?
A: Methotrexate (DHFR inhibition), trimethoprim, phenytoin.


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

--- 9a: EPO/ESAs ---

--- Type 3 ---
Q: What is the mnemonic for EPO?
A: "EPO = Every Patient On dialysis needs this"

--- Type 1 ---
Q: What is EPO's mechanism?
A: Recombinant human erythropoietin → binds EPO receptor on erythroid progenitors in bone marrow → stimulates RBC production.

--- Type 1 ---
Q: What are the key indications for ESAs?
A: Anaemia of CKD (primary use), chemotherapy-induced anaemia, myelodysplastic syndrome (low-risk), autologous blood donation pre-surgery.

--- Type 1 ---
Q: What is the target Hb when treating anaemia of CKD with EPO?
A: 100-120 g/L — do NOT exceed 130 g/L (↑ CV events — CHOIR and CREATE trials).
[Trap: common wrong answer is "target normal Hb (>130)" — overcorrection increases VTE and cardiovascular mortality]

--- Type 1 ---
Q: What must be checked and corrected before starting EPO?
A: Iron stores (ferritin and TSAT) — iron deficiency prevents ESA response.

--- Type 1 ---
Q: What is the most common side effect of EPO?
A: Hypertension (↑ Hb → ↑ blood viscosity → ↑ BP).

--- Type 1 ---
Q: What is pure red cell aplasia (PRCA) in the context of EPO?
A: Rare: anti-EPO antibodies develop → sudden worsening anaemia after initial response; stop EPO and start immunosuppression.

--- Type 1 ---
Q: What are the contraindications to EPO?
A: Uncontrolled hypertension, active malignancy (some tumours express EPO receptors), adequate Hb already.

--- 9b: G-CSF ---

--- Type 3 ---
Q: What is the mnemonic for G-CSF?
A: "G-CSF = Grows White cells (neutrophils)"

--- Type 1 ---
Q: What is G-CSF's mechanism?
A: Binds G-CSF receptor → stimulates proliferation, differentiation, and survival of neutrophil precursors → ↑ mature neutrophil release from bone marrow.

--- Type 1 ---
Q: What are the key indications for G-CSF (filgrastim/pegfilgrastim)?
A: Chemotherapy-induced febrile neutropaenia prevention; treatment of neutropaenia (post-chemo, congenital, drug-induced); stem cell mobilisation before harvesting for transplant.

--- Type 1 ---
Q: What is the most common side effect of G-CSF?
A: Bone pain (medullary expansion — treat with paracetamol ± ibuprofen).
[Trap: common wrong answer is "G-CSF causes bleeding" — the most common side effect is bone pain from marrow expansion, NOT haematological]

--- Type 1 ---
Q: What are other side effects of G-CSF?
A: Splenomegaly (rare: splenic rupture), elevated LDH/uric acid, leukocytosis (if overdosed).

--- 9c: TPO RECEPTOR AGONISTS ---

--- Type 1 ---
Q: What is the mechanism of TPO receptor agonists?
A: Bind and activate thrombopoietin receptor (Mpl) → stimulate megakaryocyte proliferation → ↑ platelet production.

--- Type 1 ---
Q: What is romiplostim used for?
A: Immune thrombocytopaenia (ITP) — second-line after steroids; SC weekly.

--- Type 1 ---
Q: What is eltrombopag used for?
A: ITP, aplastic anaemia (with ciclosporin), thrombocytopaenia in HCV/CLD; oral.

--- Type 1 ---
Q: What are the major side effects of TPO receptor agonists?
A: Bone marrow reticulin fibrosis (prolonged use), thrombosis (↑ platelet count → VTE risk), headache.

--- Type 1 ---
Q: How should eltrombopag be taken?
A: Without food and away from polyvalent cations (chelation reduces absorption); monitor LFTs (hepatotoxicity risk).


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SECTION 10: REVERSAL AGENTS
================================================================

--- Type 3 ---
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/TXA (fibrinolytics)

--- Type 1 ---
Q: What reverses UFH?
A: Protamine sulfate 1mg per 100 units heparin (IV slow).

--- Type 1 ---
Q: What are the risks of protamine sulfate administration?
A: Hypotension, bradycardia, anaphylaxis (especially in fish allergy or prior vasectomy).

--- Type 1 ---
Q: What reverses warfarin non-urgently?
A: Vitamin K (phytomenadione) oral or IV; slow onset (6-12h oral, 1-2h IV); IV form has anaphylaxis risk.

--- Type 1 ---
Q: What reverses warfarin urgently in major bleeding?
A: 4-factor PCC (Beriplex) + IV vitamin K — faster and lower volume than FFP; contains factors II, VII, IX, X + Proteins C and S.

--- Type 1 ---
Q: What reverses dabigatran major bleeding?
A: Idarucizumab (Praxbind) 5g IV — reverses within minutes; no anticoagulant effect itself.

--- Type 1 ---
Q: What reverses rivaroxaban/apixaban/edoxaban major bleeding?
A: Andexanet alfa (recombinant Xa decoy); alternative = 4F-PCC 25-50 units/kg if unavailable.

--- Type 1 ---
Q: What reverses fibrinolytics (e.g. alteplase overdose)?
A: No specific antidote — TXA + FFP/cryoprecipitate + supportive care (antifibrinolytic approach).

--- Type 4 ---
Q: HKMLE Pearl: Which is preferred for urgent warfarin reversal — PCC or FFP?
A: PCC — faster onset, lower infusion volume, more predictable factor delivery; FFP is second choice.


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SECTION 11: PREGNANCY & ANTICOAGULATION
================================================================

--- Type 1 ---
Q: Which anticoagulant is safe in ALL trimesters of pregnancy?
A: LMWH (e.g. enoxaparin) — does not cross the placenta.

--- Type 1 ---
Q: Why is warfarin contraindicated in pregnancy?
A: Teratogen — warfarin embryopathy (nasal hypoplasia, stippled epiphyses) weeks 6-12; fetal haemorrhage risk in T3; Category X.

--- Type 1 ---
Q: Why are DOACs contraindicated in pregnancy?
A: Teratogenic and cross the placenta.

--- Type 4 ---
Q: HKMLE Pearl: A pregnant woman with a DVT needs anticoagulation. What is the only safe option?
A: LMWH throughout pregnancy — neither warfarin nor DOACs are safe; DOACs are teratogenic.

--- Type 1 ---
Q: What folate dose is given preconceptionally in a high-risk pregnancy (e.g. epileptic on phenytoin)?
A: 5mg daily preconception and throughout T1.


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SECTION 12: INTEGRATION / CLINICAL SCENARIO PEARLS
================================================================

--- Type 4 ---
Q: HKMLE Pearl: A patient is on mechanical mitral valve replacement. Which anticoagulant should be used?
A: Warfarin (target INR 2.5-3.5) — DOACs are contraindicated for mechanical heart valves (RE-ALIGN trial).

--- Type 4 ---
Q: HKMLE Pearl: A patient on warfarin for AF is started on amiodarone. What happens to the INR?
A: INR increases — amiodarone inhibits CYP2C9 → reduced warfarin metabolism → higher warfarin levels → increase bleeding risk; reduce warfarin dose.

--- Type 4 ---
Q: HKMLE Pearl: A patient starting warfarin for a DVT develops leg pain and skin necrosis on day 3. What happened?
A: Warfarin-induced skin necrosis — early Protein C/S depletion before full anticoagulation; confirms the need to always bridge with heparin when starting warfarin.

--- Type 4 ---
Q: HKMLE Pearl: How does aPTT monitoring differ from anti-Xa for LMWH?
A: LMWH is typically NOT monitored by aPTT (aPTT monitors UFH); anti-Xa level is used for LMWH in special situations (obesity, pregnancy, renal impairment).

--- Type 4 ---
Q: HKMLE Pearl: A patient with IDA is found to have a normal Hb after 3 weeks on oral iron. When should treatment stop?
A: Continue iron for 3 months after Hb normalises to replenish iron stores (ferritin); stopping too early risks recurrence.

--- Type 4 ---
Q: HKMLE Pearl: Which haematinic supplement should ALL pregnant women take from preconception?
A: Folic acid (400mcg standard; 5mg high-risk) — prevents neural tube defects.

--- Type 4 ---
Q: HKMLE Pearl: A CKD patient on EPO develops sudden severe anaemia after initial improvement. What is the diagnosis?
A: Pure red cell aplasia (PRCA) — anti-EPO antibodies; stop EPO immediately and consider immunosuppression.

--- Type 4 ---
Q: HKMLE Pearl: A patient on G-CSF complains of severe bone pain. What is the cause and treatment?
A: Medullary bone expansion from neutrophil proliferation — treat with paracetamol ± ibuprofen.

--- Type 1 ---
Q: What is the perioperative management of clopidogrel before elective surgery?
A: Stop 7-10 days before surgery; aspirin may be continued for most procedures.

--- Type 4 ---
Q: HKMLE Pearl: A patient with ITP fails steroids. What second-line options are available?
A: TPO receptor agonists (romiplostim SC or eltrombopag oral); splenectomy; rituximab.


================================================================
QUICK REFERENCE MNEMONICS SUMMARY (TYPE 3 CARDS)
================================================================

--- Type 3 ---
Q: What is the master mnemonic for haematology pharmacology topics?
A: "WATCH A GRIP" = Warfarin, Anticoagulants, DOACs (Xa + IIa), Thrombolytics (tPA), Clot stabilisers (TXA), Heparin + DTIs, Antiplatelets, Growth factors, Reversal agents, Iron/B12/Folate, Platelets/fibrin

--- Type 3 ---
Q: What is the mnemonic for warfarin factors inhibited?
A: "1972" = factors 1 (fibrinogen), 9, 7, 2 + Proteins C and S (factors II, VII, IX, X)

--- Type 3 ---
Q: What is the mnemonic for HIT management?
A: "Stop Heparin, Start Argatroban/Fondaparinux, NO platelets, NO warfarin yet"

--- Type 3 ---
Q: What is the mnemonic for iron absorption?
A: "Vitamin C = ↑ absorption; Tea/antacids = ↓ absorption; Ferrous > Ferric (better absorbed)"

--- Type 3 ---
Q: What is the mnemonic for B12 vs folate anaemia?
A: "B12 = Bad nerves (subacute combined degeneration); Folate = Fine nerves (no neuro)"

--- Type 3 ---
Q: What is the EPO target mnemonic in CKD?
A: "100-120 g/L, NOT normal" (overcorrection → VTE + CV events)

--- Type 3 ---
Q: What is the G-CSF side effect mnemonic?
A: "BONE pain" (bone marrow expansion from neutrophil proliferation)

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END OF DECK — TOTAL: ~130 FLASHCARDS
COVERS: Warfarin, Heparin/LMWH, HIT, DTIs, DOACs, Antiplatelets, Thrombolytics, TXA, Iron, B12, Folate, EPO, G-CSF, TPO agonists, Reversal Agents, Pregnancy Anticoagulation
================================================================