I have attached my HKMLE pharmacology notes for Haematology. Create Anki flashcards from these notes. Each card should test ONLY high-yield facts that appear in HKMLE exams. INCLUDE cards for: - Drug mechanisms (simple, exam-level) - Key indications - Major side effects (only the ones HKMLE tests) - Contraindications - HKMLE Pearls (from my notes) - Mnemonics (from my notes) DO NOT include: - Long explanations - Low-yield details - Physiology review FORMAT each card as ONE of these types: Type 1 (Basic Q&A): Q: [question] A: [short answer, 1 sentence max] Type 2 (Cloze deletion): [c] drug name [/c] causes [side effect] because [mechanism] Type 3 (Mnemonic card): Q: What is the mnemonic for [topic]? A: [mnemonic] = [breakdown] Type 4 (HKMLE Pearl card): Q: HKMLE Pearl: [scenario]? A: [one sentence answer] ADD trap alerts: For any fact that is a common HKMLE trap, add on a new line: [Trap: common wrong answer is X because Y] Make as many cards as needed to cover ALL high-yield facts from my notes. Do not limit the number. Use simple, direct language. Match the style of high-yield exam prep cards. Here are my notes: [PASTE YOUR HAEMATOLOGY NOTES HERE]
Reading File
Running Command
cd /home/daytona/workspace/attachments/9565136d-f3f9-470a-a53f-639657602363/ && python3 -c " import pdfplumber with pdfplumber.open('Haematology 💊.pdf') as pdf: print(f'Pages: {len(pdf.pages)}') for i, page in enumerate(pdf.pages): text = page.extract_text() print(f'--- PAGE {i+1} ---') print(text) print() "
Writing File
~/hkmle-haematology-anki/HKMLE_Haematology_Anki.txt
========================================================
HKMLE HAEMATOLOGY PHARMACOLOGY - ANKI FLASHCARD DECK
========================================================
Total cards: 130+
Sections: Warfarin | Heparin/LMWH | HIT | DTIs | DOACs |
Antiplatelets | Thrombolytics | TXA | Iron | B12 |
Folate | EPO | G-CSF | TPO-RAs | Reversal Agents
========================================================
--- MASTER MAP ---
Q: What is the mnemonic for the master map of haematology pharmacology?
A: "WATCH A GRIP" = Warfarin, Anticoagulants, DOACs, Thrombolytics, Clot stabilisers (TXA), Heparin + DTIs, Antiplatelets, Growth factors, Reversal agents, Iron/B12/Folate, Platelets/fibrin system
---
======================
SECTION 1: WARFARIN
======================
--- MECHANISM ---
Q: What is the mechanism of warfarin?
A: Inhibits vitamin K epoxide reductase → blocks activation of vitamin K-dependent clotting factors II, VII, IX, X and anticoagulant proteins C and S.
[c] Warfarin [/c] inhibits [vitamin K epoxide reductase] → blocks factors [II, VII, IX, X] and proteins [C and S]
Q: What is the mnemonic for warfarin's affected factors?
A: "WEPT" = Warfarin: Extended PT, inhibits "1972" (factors II, VII, IX, X + Proteins C and S)
[Trap: "1972" is a memory aid - the actual factors are 2, 7, 9, 10 + C + S; not literally the year]
Q: Why does warfarin take 3-5 days to reach full anticoagulant effect?
A: Existing activated clotting factors must deplete; factor VII has the shortest half-life (~6h) so INR rises first, but full anticoagulation requires depletion of factor II (~72h half-life).
[Trap: A rising INR does NOT mean full anticoagulation - must bridge with heparin for acute thrombosis]
--- MONITORING ---
Q: What test is used to monitor warfarin?
A: INR (measures extrinsic pathway: factors VII, X, II, V, fibrinogen).
Q: What is the INR target for AF and DVT/PE on warfarin?
A: INR 2.0-3.0
Q: What is the INR target for a mechanical mitral valve?
A: INR 2.5-3.5
Q: What is the INR target for a mechanical aortic valve?
A: INR 2.0-3.0 (some guidelines 2.5-3.5)
[Trap: Mitral valve target is higher (2.5-3.5) than aortic valve - a common exam swap]
Q: What is the INR target for recurrent PE or antiphospholipid syndrome?
A: INR 2.5-3.5
--- INDICATIONS ---
Q: What are the 4 key indications for warfarin?
A: AF (INR 2-3), DVT/PE (INR 2-3), mechanical heart valves (INR 2.5-3.5), antiphospholipid syndrome (INR 2-3, or 3-4 if recurrent thrombosis).
--- SIDE EFFECTS ---
Q: What causes warfarin skin necrosis?
A: Early depletion of Proteins C and S (short half-lives) before full anticoagulation → transient procoagulant state → thrombosis of skin microvasculature; especially dangerous in Protein C deficiency.
[Trap: Skin necrosis is an EARLY side effect, not a late one; occurs in first few days of warfarin]
Q: What is warfarin embryopathy and when does it occur?
A: Nasal hypoplasia + stippled epiphyses (chondrodysplasia punctata); occurs weeks 6-12 of gestation.
Q: What trimester risk does warfarin pose beyond embryopathy?
A: Third trimester - fetal haemorrhage risk.
--- CONTRAINDICATIONS ---
Q: Name 3 absolute contraindications to warfarin.
A: Pregnancy (all trimesters), active bleeding, recent intracranial surgery or haemorrhage.
--- DRUG INTERACTIONS ---
Q: What is the mnemonic for drugs that INCREASE warfarin INR?
A: "CAFE MIX" = Clarithromycin/Ciprofloxacin, Amiodarone, Fluconazole, Erythromycin, Metronidazole, Isoniazid, eXcretion inhibitors (statins); mechanism = CYP2C9 inhibition.
Q: What is the mnemonic for drugs that DECREASE warfarin INR?
A: "PRICARS" = Phenytoin, Rifampicin, Isoniazid (high dose), Carbamazepine, Alcohol (chronic), St John's Wort; mechanism = CYP2C9 induction.
[Trap: Acute binge alcohol INCREASES INR; chronic alcohol DECREASES INR - opposite effects]
Q: How do NSAIDs interact with warfarin?
A: NSAIDs do NOT reliably change INR but INCREASE bleeding risk via GI mucosal damage + platelet inhibition.
[Trap: NSAIDs may not raise INR significantly but still cause dangerous GI bleeding on warfarin]
Q: HKMLE Pearl: A patient on warfarin starts amiodarone - what happens?
A: INR rises (amiodarone inhibits CYP2C9 → reduced warfarin metabolism → higher warfarin levels) → reduce warfarin dose and monitor INR closely.
--- REVERSAL ---
Q: INR 3-5 with no bleeding - what do you do?
A: Reduce or omit dose; recheck INR in 1-2 days.
Q: INR 5-8 with no significant bleeding - what do you do?
A: Stop warfarin; give low-dose oral vitamin K 1-2 mg.
Q: INR >8 with no or minor bleeding - what do you do?
A: Stop warfarin; give oral vitamin K 5 mg (repeat if INR still high at 24h).
Q: Any INR + major bleeding - what is the treatment?
A: Stop warfarin + IV vitamin K 5-10 mg + 4-factor Prothrombin Complex Concentrate (4F-PCC); PCC preferred over FFP (faster, lower volume).
Q: Life-threatening intracranial bleed on warfarin - what do you give immediately?
A: 4F-PCC + IV vitamin K 10 mg immediately.
Q: Why is 4F-PCC preferred over FFP for urgent warfarin reversal?
A: Faster reversal, lower infusion volume, no need for blood group matching; contains factors II, VII, IX, X + Proteins C and S.
[Trap: FFP is NOT first choice for major warfarin reversal despite containing clotting factors]
--- HKMLE PEARLS ---
Q: HKMLE Pearl: Why must heparin always be co-started when initiating warfarin for acute thrombosis?
A: Warfarin depletes Proteins C and S first (short half-lives) → transient procoagulant state → risk of thrombosis extension; heparin bridges until full anticoagulation achieved.
Q: HKMLE Pearl: Which is the ONLY safe anticoagulant in pregnancy?
A: LMWH (e.g. enoxaparin) - does not cross the placenta; warfarin is teratogenic and DOACs are contraindicated.
Q: What coagulation pathway does INR measure?
A: Extrinsic pathway (factors VII, X, II, V, fibrinogen).
---
================================
SECTION 2: HEPARIN (UFH & LMWH)
================================
--- MECHANISM ---
Q: What is the mechanism of unfractionated heparin (UFH)?
A: Binds antithrombin III → inhibits factor IIa (thrombin), Xa, IXa, XIa, XIIa.
Q: What is the mechanism of LMWH (e.g. enoxaparin)?
A: Binds antithrombin III → preferentially inhibits factor Xa only (chain too short to bridge thrombin/IIa).
[Trap: LMWH inhibits Xa > IIa; UFH inhibits BOTH IIa and Xa equally - key distinction]
--- MONITORING ---
Q: How is UFH monitored?
A: aPTT (target 1.5-2.5x normal).
Q: How is LMWH monitored?
A: Usually NOT required; use anti-Xa level if obese, pregnant, or renal impairment.
--- REVERSAL ---
Q: What reverses UFH?
A: Protamine sulfate 1 mg per 100 units heparin (IV slow); fully neutralises.
Q: What reverses LMWH?
A: Protamine sulfate (1 mg per 1 mg enoxaparin); only ~60% reversal.
[Trap: Protamine does NOT fully reverse LMWH - only ~60% effective]
Q: What are the risks of protamine sulfate?
A: Hypotension, bradycardia, anaphylaxis (especially with fish allergy or prior vasectomy).
--- RENAL CLEARANCE ---
Q: Which heparin is dangerous in renal failure and why?
A: LMWH - renally cleared; accumulates in renal failure → increased bleeding risk; reduce dose or avoid if eGFR <30.
Q: Which heparin is safe in renal failure?
A: UFH (reticuloendothelial metabolism, not renal clearance).
--- PREGNANCY ---
Q: Are heparins safe in pregnancy?
A: Yes - both UFH and LMWH do NOT cross the placenta; LMWH preferred (more predictable, SC only).
--- HIT RISK ---
Q: Which has a higher risk of HIT - UFH or LMWH?
A: UFH (HIT rate 5-10%); LMWH lower but still possible.
---
===========================================
SECTION 3: HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)
===========================================
--- TYPES ---
Q: What is HIT Type I?
A: Non-immune; mild thrombocytopenia (>100) within 1-2 days of heparin; benign; continue heparin.
Q: What is HIT Type II?
A: Immune-mediated; IgG antibodies against heparin-PF4 complex → platelet activation → paradoxical THROMBOSIS; platelet fall >50% from baseline, typically days 5-10.
[Trap: HIT causes THROMBOSIS, not just low platelets - this is the key paradox]
Q: What is the mnemonic for HIT?
A: "HIT = Heparin Induces Thrombosis (paradoxically) - use the 4Ts score"
--- DIAGNOSIS ---
Q: What is the 4Ts score for HIT?
A: Thrombocytopenia severity, Timing (day 5-10), Thrombosis present, other causes of Thrombocytopenia excluded; confirm with anti-PF4/heparin ELISA or serotonin release assay.
--- MANAGEMENT ---
Q: HKMLE Pearl: What is the management of HIT Type II?
A: Stop ALL heparin immediately (UFH AND LMWH); start alternative anticoagulant: argatroban or fondaparinux; do NOT give platelets; do NOT start warfarin until platelets >150.
Q: Why are platelet transfusions contraindicated in HIT?
A: Platelets worsen thrombosis (activated platelets fuel the thrombotic cascade); only give if life-threatening haemorrhage.
[Trap: Platelet transfusion is CONTRAINDICATED in HIT - common wrong answer is "give platelets for low platelet count"]
Q: Why must warfarin NOT be started early in HIT?
A: Protein C depletion → venous limb gangrene; wait until platelets >150 before bridging to warfarin.
[Trap: Warfarin is NOT safe to start immediately in HIT even though it is the eventual anticoagulant]
Q: HKMLE Pearl: Drug of choice for HIT in renal failure?
A: Argatroban (hepatic elimination - safe in renal failure).
Q: What is the alternative to argatroban in HIT?
A: Fondaparinux (factor Xa inhibitor; no cross-reactivity with PF4 antibodies).
Q: Can a patient who had HIT ever receive heparin again?
A: No - both UFH and LMWH are contraindicated; use fondaparinux or DOAC for future anticoagulation.
---
=====================================
SECTION 4: DIRECT THROMBIN INHIBITORS
=====================================
Q: What is the mechanism of all direct thrombin inhibitors (DTIs)?
A: Directly inhibit thrombin (factor IIa) → block fibrin formation and thrombin-mediated platelet activation; act independently of antithrombin (unlike heparin).
Q: What is the key use of argatroban?
A: HIT (IV alternative anticoagulant); hepatic elimination → use in renal failure.
Q: Is there a reversal agent for argatroban?
A: No - stop infusion; short t½ ~50 minutes.
Q: What is bivalirudin used for?
A: Percutaneous coronary intervention (PCI) - alternative to heparin; renally eliminated; no reversal agent.
Q: What is the reversal agent for dabigatran?
A: Idarucizumab (Praxbind) 5 g IV.
---
=========================================
SECTION 5: DIRECT ORAL ANTICOAGULANTS (DOACs)
=========================================
--- MECHANISM / TARGETS ---
Q: What is the mnemonic for DOAC targets?
A: "3 Xas + 1 IIa" = Rivaroxaban, Apixaban, Edoxaban (all Xa inhibitors) + Dabigatran (IIa/thrombin inhibitor).
[c] Dabigatran [/c] inhibits [factor IIa (thrombin)] directly, unlike [rivaroxaban, apixaban, and edoxaban which inhibit factor Xa]
--- INDICATIONS ---
Q: What are the key indications for DOACs?
A: Non-valvular AF (stroke prevention), DVT/PE treatment and prevention, post-surgical VTE prophylaxis.
--- CONTRAINDICATIONS ---
Q: HKMLE Pearl: Are DOACs safe in mechanical heart valves?
A: NO - DOACs are contraindicated in mechanical heart valves (RE-ALIGN trial showed worse outcomes); warfarin only.
[Trap: DOACs are NOT safe for mechanical heart valves - this is a classic HKMLE trap]
Q: HKMLE Pearl: Are DOACs safe in pregnancy?
A: NO - DOACs are contraindicated in pregnancy (teratogenic, cross placenta); LMWH is the only safe anticoagulant.
Q: Are DOACs safe in triple-positive antiphospholipid syndrome?
A: No - warfarin preferred for triple-positive APS; DOACs have higher thrombosis recurrence.
--- RENAL DOSE ADJUSTMENT ---
Q: What is the mnemonic for DOAC renal dosing?
A: "Dabigatran = Danger in renal failure (avoid CrCl <30); Apixaban = safest in CKD (least renally cleared ~27%)"
Q: At what CrCl should dabigatran be avoided?
A: CrCl <30 mL/min (80% renally cleared).
[Trap: Dabigatran is the most renally cleared DOAC - do NOT use in significant renal impairment]
Q: When should rivaroxaban be avoided?
A: CrCl <15 mL/min for AF; dose reduce in moderate CKD.
Q: When should apixaban dose be reduced?
A: 2 of 3 criteria: age ≥80, weight ≤60 kg, creatinine ≥133 µmol/L.
Q: When should edoxaban dose be reduced?
A: CrCl 15-50 mL/min.
--- DRUG INTERACTIONS ---
Q: Which drugs reduce ALL DOAC efficacy?
A: St John's Wort, rifampicin, carbamazepine (P-gp/CYP3A4 induction) → avoid combination.
Q: What type of drug interactions do DOACs have?
A: P-gp inducers/inhibitors (all DOACs); additionally rivaroxaban and apixaban are CYP3A4 substrates.
--- REVERSAL ---
Q: What is the mnemonic for DOAC reversal?
A: "I-DAR for IIa (dabigatran) = Idarucizumab; AND-exanet for Xa = Andexanet alfa"
Q: What reverses dabigatran?
A: Idarucizumab (Praxbind) 5 g IV - monoclonal Ab Fab fragment; reverses within minutes; no anticoagulant effect of its own.
Q: What reverses rivaroxaban and apixaban?
A: Andexanet alfa (recombinant factor Xa decoy); alternative = 4F-PCC 25-50 units/kg if andexanet unavailable.
Q: What is first action for any DOAC if taken ≤2h ago?
A: Activated charcoal (especially for dabigatran).
--- COMPARISON ---
Q: What is dabigatran's bioavailability and why does it matter?
A: Only 6% - very low; important because P-gp efflux pump inhibitors significantly increase levels.
Q: Which DOAC has the highest renal clearance?
A: Dabigatran (~80% renal) - most dangerous in renal failure.
Q: Which DOAC is safest in CKD?
A: Apixaban (~27% renal clearance) - least affected by renal impairment.
--- MAJOR SIDE EFFECTS ---
Q: What is the main side effect concern with DOACs vs warfarin?
A: GI bleeding - particularly high with dabigatran and rivaroxaban compared to warfarin.
[Trap: DOACs have LOWER intracranial haemorrhage than warfarin but HIGHER GI bleeding risk]
--- ADVANTAGES / DISADVANTAGES ---
Q: Name 3 advantages of DOACs over warfarin.
A: No routine monitoring, fewer drug interactions, faster onset/offset, lower intracranial haemorrhage risk.
Q: Name 2 disadvantages of DOACs vs warfarin.
A: More expensive; renal clearance dependency (especially dabigatran); cannot be used in mechanical valves or pregnancy.
---
=======================
SECTION 6: ANTIPLATELETS
=======================
--- ASPIRIN ---
Q: What is the mechanism of aspirin as an antiplatelet?
A: Irreversibly inhibits COX-1 → reduces TXA2 production → decreased platelet aggregation; effect lasts 7-10 days (platelet lifespan).
Q: What dose of aspirin is used as an antiplatelet?
A: Low dose 75-150 mg daily (NOT anti-inflammatory doses).
Q: What is the key contraindication for aspirin in children?
A: Never use in children <12 years (risk of Reye's syndrome).
[Trap: Do NOT give aspirin to children with viral illness - Reye's syndrome risk]
--- CLOPIDOGREL ---
Q: What is the mechanism of clopidogrel?
A: Irreversibly blocks P2Y12 ADP receptor on platelets; prodrug requiring CYP2C19 activation.
Q: What is the clinical problem with CYP2C19 poor metabolisers and clopidogrel?
A: Reduced conversion to active form → reduced antiplatelet efficacy → use ticagrelor or prasugrel instead.
[Trap: Clopidogrel REQUIRES CYP2C19 for activation - poor metabolisers get inadequate antiplatelet effect]
Q: How do PPIs interact with clopidogrel?
A: PPIs (especially omeprazole) compete for CYP2C19 → reduce clopidogrel activation → reduced efficacy; use pantoprazole if needed.
--- TICAGRELOR ---
Q: What is the mechanism of ticagrelor?
A: Reversibly blocks P2Y12 receptor; NOT a prodrug (no metabolic activation needed); faster onset than clopidogrel.
Q: What is the key side effect of ticagrelor?
A: Dyspnoea (adenosine-mediated, not bronchospasm; do NOT switch to clopidogrel without reason).
[Trap: Ticagrelor dyspnoea is NOT bronchospasm - do NOT stop unnecessarily; it is adenosine-mediated]
Q: What drug interaction must be avoided with ticagrelor?
A: High-dose aspirin reduces ticagrelor efficacy (keep aspirin dose ≤100 mg/day when used with ticagrelor).
--- PRASUGREL ---
Q: What is the key contraindication of prasugrel?
A: Prior stroke or TIA (high intracranial bleed risk); also avoid in age >75, weight <60 kg.
[Trap: "Prior TIA/stroke = Prasugrel is PRASUREly dangerous" - contraindicated, not just cautioned]
Q: When is prasugrel preferred over clopidogrel?
A: STEMI post-PCI (TRITON trial showed superior outcomes); most potent P2Y12 blocker.
--- DAPT ---
Q: HKMLE Pearl: What is DAPT and when is it used?
A: Dual Antiplatelet Therapy = aspirin + P2Y12 inhibitor (clopidogrel/ticagrelor/prasugrel); standard post-ACS/PCI for 12 months.
--- PERIOPERATIVE ANTIPLATELETS ---
Q: When should antiplatelets be stopped before elective surgery?
A: Clopidogrel/prasugrel: stop 7-10 days before surgery; aspirin: may usually be continued for most procedures.
--- DIPYRIDAMOLE ---
Q: What is the mechanism of dipyridamole?
A: Inhibits phosphodiesterase → ↑ cAMP → decreased platelet aggregation; also blocks adenosine reuptake → vasodilation.
Q: What is the HKMLE-relevant use of dipyridamole?
A: Secondary stroke prevention (combined with aspirin = Aggrenox); also used as pharmacological cardiac stress test agent (adenosine analogue effect → coronary vasodilation → reveals ischaemia).
--- GPIIb/IIIa INHIBITORS ---
Q: What is the mechanism of tirofiban and eptifibatide?
A: Block GPIIb/IIIa receptor → inhibit final common pathway of platelet aggregation; IV only, short-acting.
Q: When are GPIIb/IIIa inhibitors used?
A: High-risk ACS/PCI (adjunct); "last resort" platelet inhibition.
---
==========================
SECTION 7: THROMBOLYTICS
==========================
--- MECHANISM ---
Q: What is the mechanism of thrombolytics (class)?
A: Activate plasminogen → plasmin → plasmin cleaves fibrin → dissolves clots.
Q: What is the mnemonic for thrombolytics?
A: "tPA = turns Plasminogen to Active plasmin → eATs fibrin clots"
--- INDIVIDUAL AGENTS ---
Q: What is alteplase and when is it used?
A: Recombinant tissue plasminogen activator (rt-PA); fibrin-selective; used for ischaemic stroke (≤4.5h), massive PE, STEMI (if no PCI available); short t½ ~5 min.
Q: What is the time window for alteplase in ischaemic stroke?
A: ≤4.5 hours from symptom onset.
[Trap: Must exclude haemorrhage by CT head FIRST before giving alteplase - CT is mandatory]
Q: What is the BP limit before giving stroke thrombolysis?
A: Must control BP to <185/110 mmHg before administering alteplase.
Q: What is tenecteplase (TNK-tPA)?
A: Modified tPA with longer half-life → single IV bolus (more convenient); similar efficacy to alteplase; increasingly used for STEMI and ischaemic stroke.
Q: What is special about streptokinase?
A: Bacterial protein (Streptococcus); NOT fibrin-selective; antigenic → allergic reactions; can only be used ONCE (antibodies form → reuse within 5 years ineffective); cheapest.
[Trap: Streptokinase CANNOT be repeated within 5 years due to antibody formation - common HKMLE question]
Q: What is reteplase used for?
A: STEMI; double IV bolus; deletion mutant of tPA.
--- INDICATIONS ---
Q: What is the preferred thrombolytic agent and time window for STEMI (no PCI available)?
A: Tenecteplase or streptokinase; ≤12 hours from onset (ideally <6h).
Q: What is the preferred thrombolytic for massive PE with haemodynamic compromise?
A: Alteplase; give ASAP.
Q: What is the approach to submassive PE (RV strain, no shock)?
A: Anticoagulation usually first; thrombolytics controversial.
--- CONTRAINDICATIONS ---
Q: What is the mnemonic for absolute contraindications to thrombolytics?
A: "BRAIN HURTS" = Bleeding (active), Recent surgery/trauma, Aortic dissection, Intracranial history, Neurosurgery (recent), Haemorrhagic stroke, Uncontrolled BP, Recent head injury, Time window exceeded, Severe bleeding disorder.
Q: Name 4 absolute contraindications to thrombolytics.
A: Any prior intracranial haemorrhage, ischaemic stroke within 3 months, suspected aortic dissection, active internal bleeding, intracranial neoplasm/AVM/aneurysm.
Q: Name 4 major relative contraindications to thrombolytics.
A: SBP >180 or DBP >110 mmHg, recent (2-4 weeks) major surgery/trauma, active peptic ulcer/recent GI bleed, pregnancy, current anticoagulant use, CPR >10 minutes.
---
===========================
SECTION 8: ANTIFIBRINOLYTICS
===========================
--- TXA (TRANEXAMIC ACID) ---
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 → preserves haemostasis.
Q: What is the mnemonic for TXA?
A: "TXA = Tranexamic acid eXActs its effect by Blocking plasmin"
--- INDICATIONS ---
Q: What are the key indications for TXA?
A: Trauma haemorrhage (CRASH-2), postpartum haemorrhage (WOMAN trial), heavy menstrual bleeding (oral), elective surgery (cardiac, orthopaedic - reduces transfusion), hereditary angioedema (prophylaxis).
Q: HKMLE Pearl: What does the CRASH-2 trial show about TXA in trauma?
A: TXA given ≤3h from injury → reduced all-cause mortality (NNT ~67); given after 3h → no benefit.
[Trap: TXA MUST be given within 3h of trauma; after 3h = no mortality benefit - "3 hours or bust"]
Q: HKMLE Pearl: What does the WOMAN trial show about TXA in postpartum haemorrhage?
A: TXA given early in PPH → reduced death from bleeding; now WHO recommended.
--- SIDE EFFECTS ---
Q: What are the main side effects of TXA?
A: Nausea/vomiting (GI), VTE risk (avoid in active thrombosis/DIC), colour vision changes (rare), seizures at high doses.
--- CONTRAINDICATIONS ---
Q: What are the contraindications to TXA?
A: Active thromboembolic disease (DVT/PE/stroke), DIC with consumption (worsens DIC by blocking fibrinolysis), haematuria from upper urinary tract (blood clots in ureter).
---
===================
SECTION 9: IRON
===================
--- MECHANISM ---
Q: What is the mechanism of iron supplementation?
A: Elemental iron replenishes depleted iron stores required for haemoglobin (haem moiety) synthesis.
Q: What is the mnemonic for iron?
A: "FERRIC = Ferrous is absorbed, Ferritin stores it, Restores Hb, Iron deficiency = Check cause, Constipation = side effect"
--- FORMS ---
Q: Which iron formulation is better absorbed orally - ferrous or ferric?
A: Ferrous (Fe2+) - better absorbed than ferric (Fe3+); standard oral preparation = ferrous sulfate 200 mg (65 mg elemental iron).
[Trap: Ferrous (Fe2+) = better absorbed; Ferric (Fe3+) = less absorbed - do NOT confuse the two]
Q: When is IV iron indicated?
A: Oral failure/intolerance, IBD, CKD on dialysis, severe deficiency in pregnancy, bariatric surgery.
--- MONITORING ---
Q: How do you monitor iron replacement response?
A: Hb rises ~10-20 g/L per 3 weeks; reticulocyte count rises at 1 week (reticulocyte crisis = response marker); check ferritin (stores), TSAT, MCV.
--- SIDE EFFECTS ---
Q: What are the main side effects of oral iron?
A: Nausea, epigastric pain, constipation (most common; ferrous gluconate is gentler), diarrhoea, dark stools (harmless - warn patient).
Q: What is a serious side effect of IV ferric carboxymaltose?
A: Transient hypophosphataemia; also infusion reactions (anaphylaxis rare with modern formulations).
--- DRUG INTERACTIONS ---
Q: What reduces oral iron absorption?
A: Antacids, PPIs, tea, calcium (chelation); take iron on empty stomach with vitamin C (ascorbic acid enhances Fe3+→Fe2+ conversion).
---
======================
SECTION 10: VITAMIN B12
======================
--- MECHANISM ---
Q: What are the two metabolic roles of vitamin B12?
A: Methylcobalamin → methionine synthesis (DNA synthesis); adenosylcobalamin → succinyl-CoA → Krebs cycle (myelin formation).
Q: What is the mnemonic for B12?
A: "B12 = Big red cells (macrocytic), Bad nerves (subacute combined degeneration), Bypass stomach (intrinsic factor needed)"
--- INDICATIONS ---
Q: What are the key causes of B12 deficiency?
A: Pernicious anaemia (autoimmune - absent intrinsic factor), strict veganism (dietary), post-gastrectomy, terminal ileum disease (Crohn's, resection - site of B12 absorption), malabsorption.
Q: What antibodies are found in pernicious anaemia?
A: Anti-intrinsic factor antibodies (most specific) + anti-parietal cell antibodies.
--- FORMULATION ---
Q: What is the preferred formulation for pernicious anaemia?
A: IM hydroxocobalamin 1 mg alternate days x2 weeks, then every 3 months lifelong.
[Trap: Pernicious anaemia requires IM B12 (intrinsic factor absent → can't absorb oral B12); oral is only for dietary deficiency]
--- DEFICIENCY FEATURES ---
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.
Q: What haematological features indicate B12 deficiency?
A: Macrocytic anaemia + hypersegmented neutrophils + megaloblastic changes.
Q: What is glossitis in B12 deficiency?
A: "Beefy red tongue" (atrophic glossitis).
--- HKMLE PEARL ---
Q: HKMLE Pearl: Why must folate NEVER be given alone if B12 deficiency is possible?
A: Folic acid corrects the blood picture (macrocytic anaemia) but UNMASKS subacute combined degeneration of the spinal cord → neurological deterioration.
[Trap: Folate supplementation MASKS B12 deficiency anaemia but DOES NOT prevent neurological damage - classic HKMLE trap]
--- SIDE EFFECTS ---
Q: What electrolyte abnormality can occur when starting B12 treatment?
A: Hypokalaemia (B12 stimulates rapid RBC production → increased K+ uptake into cells).
---
====================
SECTION 11: FOLATE
====================
--- MECHANISM ---
Q: What is the mechanism of folate?
A: Required for one-carbon transfer reactions → DNA synthesis; converted to THF (tetrahydrofolate) → needed for purine/pyrimidine synthesis.
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 in B12 deficiency, Treatment oral"
--- INDICATIONS / DOSES ---
Q: What is the standard folate dose preconception and in first trimester?
A: 400 mcg (0.4 mg) daily.
Q: What is the high-risk folate dose preconception?
A: 5 mg daily (for previous NTD, diabetes, antiepileptics, obesity).
Q: What folate dose is given with methotrexate?
A: 5 mg once weekly.
--- CAUSES OF DEFICIENCY ---
Q: What is the most common cause of folate deficiency in HK/Western clinical practice?
A: Alcoholism.
[Trap: Alcohol = most common cause of folate deficiency; not just poor diet]
Q: What drugs cause folate deficiency?
A: Methotrexate (DHFR inhibition), trimethoprim, phenytoin.
--- DIFFERENTIATION: B12 vs FOLATE ---
Q: How do you differentiate B12 deficiency anaemia from folate deficiency anaemia?
A: Both cause macrocytic anaemia + hypersegmented neutrophils; differentiate with B12/folate levels; B12 deficiency = neurological symptoms (subacute combined degeneration); folate deficiency = NO neurological features.
[Trap: B12 and folate both cause identical blood pictures - you CANNOT differentiate on CBC alone; need serum levels + neuro exam]
---
=========================================
SECTION 12: ERYTHROPOIETIN (EPO) / ESAs
=========================================
--- MECHANISM ---
Q: What is the mechanism of erythropoiesis-stimulating agents (ESAs)?
A: Recombinant human EPO binds EPO receptor on erythroid progenitors in bone marrow → stimulates RBC production.
Q: What is the mnemonic for EPO?
A: "EPO = Every Patient On dialysis needs this"
--- INDICATIONS ---
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.
--- MONITORING / TARGET ---
Q: What is the Hb target for EPO in CKD?
A: 100-120 g/L; do NOT exceed 130 g/L (CHOIR and CREATE trials showed ↑ CV events with higher targets).
[Trap: Do NOT aim for normal Hb with EPO in CKD - overcorrection increases VTE and cardiovascular mortality]
--- SIDE EFFECTS ---
Q: What is the most common side effect of EPO?
A: Hypertension (↑ Hb → ↑ viscosity → ↑ BP).
Q: What is pure red cell aplasia (PRCA) in the context of EPO?
A: Rare; anti-EPO antibodies form → sudden worsening anaemia after initial response; stop EPO + immunosuppression.
Q: What thrombotic risk does EPO carry?
A: VTE and stroke risk, especially if Hb overcorrected >120-130 g/L.
--- IRON CO-PRESCRIPTION ---
Q: HKMLE Pearl: What must always be checked before starting EPO?
A: Iron stores (ferritin and TSAT); iron deficiency limits ESA response - must correct iron first or EPO will not work.
---
==========================================
SECTION 13: G-CSF (FILGRASTIM/PEGFILGRASTIM)
==========================================
Q: What is the mechanism of G-CSF?
A: Binds G-CSF receptor → stimulates proliferation, differentiation, and survival of neutrophil precursors → ↑ mature neutrophil release from bone marrow.
Q: What is the mnemonic for G-CSF?
A: "G-CSF = Grows White cells (neutrophils)" / "BONE pain" = most common side effect
Q: What are the key indications for G-CSF?
A: Chemotherapy-induced febrile neutropenia prevention (high-risk regimens), treatment of neutropenia (post-chemo, congenital, drug-induced), stem cell mobilisation (before harvesting for transplant).
Q: What is the most common side effect of G-CSF?
A: Bone pain (medullary expansion; treat with paracetamol ± ibuprofen).
[Trap: Bone pain with G-CSF is from marrow expansion - it is EXPECTED and not a reason to stop treatment]
Q: What rare but serious side effect can G-CSF cause?
A: Splenic rupture (from splenomegaly due to increased splenic workload); also leukocytosis if overdosed.
---
=======================================
SECTION 14: TPO RECEPTOR AGONISTS
=======================================
Q: What is the mechanism of TPO receptor agonists (romiplostim, eltrombopag)?
A: Bind and activate thrombopoietin receptor (Mpl) → stimulate megakaryocyte proliferation → ↑ platelet production.
Q: What is romiplostim used for?
A: Immune thrombocytopenia (ITP) - second-line after steroids; SC weekly injection.
Q: What is eltrombopag used for?
A: ITP, aplastic anaemia (with ciclosporin), thrombocytopenia in HCV/chronic liver disease; oral.
Q: What is the key drug interaction with eltrombopag?
A: Take without food and away from polyvalent cations (calcium, iron, aluminium - chelation reduces absorption); monitor LFTs (hepatotoxicity).
Q: What are the major side effects of TPO receptor agonists?
A: Bone marrow reticulin fibrosis (prolonged use), thrombosis (↑ platelet count → VTE risk), headache.
---
============================
SECTION 15: REVERSAL AGENTS
============================
Q: What is the mnemonic for reversal agents?
A: "4Ps + 2Is + 1A" = Protamine (heparin), Phytomenadione/Vitamin K (warfarin), PCC (warfarin/Xa inhibitors), Platelet transfusion, Idarucizumab (dabigatran), bIn [Andexanet alfa - Xa inhibitors], Aminocaproic/TXA (fibrinolytics).
Q: What reverses UFH?
A: Protamine sulfate 1 mg per 100 units heparin.
Q: What reverses LMWH?
A: Protamine sulfate - only ~60% reversal.
Q: What reverses warfarin non-urgently?
A: Vitamin K (phytomenadione) oral or IV; IV vitamin K has slow onset (1-2h IV, 6-12h oral) and carries anaphylaxis risk.
Q: What reverses warfarin urgently/major bleeding?
A: 4-factor PCC (Beriplex) + IV vitamin K (faster than FFP, lower volume).
Q: What reverses dabigatran?
A: Idarucizumab (Praxbind) 5 g IV - reverses within minutes; no anticoagulant effect.
Q: What reverses rivaroxaban/apixaban/edoxaban?
A: Andexanet alfa (recombinant Xa decoy); or 4F-PCC 25-50 units/kg if unavailable.
Q: What is used for fibrinolytic reversal?
A: TXA (tranexamic acid) + FFP/cryoprecipitate; no specific antidote.
Q: What is done for heparin-induced excess anticoagulation?
A: Stop heparin; argatroban or fondaparinux if HIT present.
---
=================================
HKMLE PEARLS: RAPID-FIRE REVIEW
=================================
Q: HKMLE Pearl: A pregnant patient needs anticoagulation - which drug?
A: LMWH (enoxaparin) - only safe anticoagulant in pregnancy; does not cross placenta; warfarin and DOACs both contraindicated.
Q: HKMLE Pearl: Patient has mechanical heart valve and needs anticoagulation - which drug?
A: Warfarin only; DOACs are contraindicated (RE-ALIGN trial).
Q: HKMLE Pearl: Patient develops thrombocytopenia on day 7 of heparin post-hip replacement - what is the diagnosis and management?
A: HIT Type II; stop ALL heparin, start argatroban or fondaparinux; do NOT give platelets; do NOT start warfarin until platelets >150.
Q: HKMLE Pearl: Patient on warfarin presents with haemorrhagic stroke - what do you give?
A: 4F-PCC + IV vitamin K 10 mg immediately (life-threatening reversal).
Q: HKMLE Pearl: Patient presents 2.5h after ischaemic stroke onset - what must you do before giving alteplase?
A: CT head FIRST to exclude haemorrhage; also ensure BP <185/110 mmHg; then give alteplase if no contraindications.
Q: HKMLE Pearl: A patient is started on folate for macrocytic anaemia without checking B12 - what risk?
A: Folic acid corrects anaemia but B12 deficiency remains → subacute combined degeneration of spinal cord progresses → irreversible neurological damage.
Q: HKMLE Pearl: EPO started in CKD patient - what Hb should you target?
A: 100-120 g/L; do NOT target normal range (>130 g/L → increased VTE and CV mortality).
Q: HKMLE Pearl: Patient with prior stroke needs ACS treatment - which P2Y12 inhibitor is contraindicated?
A: Prasugrel (high intracranial bleed risk in prior stroke/TIA); use ticagrelor or clopidogrel instead.
Q: HKMLE Pearl: TXA in trauma - what is the time limit?
A: Must be given within 3 hours of injury; after 3h = no mortality benefit (CRASH-2 trial).
Q: HKMLE Pearl: Patient on clopidogrel needs a PPI for GI protection - which PPI is safest?
A: Pantoprazole (minimal CYP2C19 inhibition); avoid omeprazole/esomeprazole (compete for CYP2C19).
---
=================================
MNEMONIC CARD SUMMARY
=================================
Q: What is the mnemonic for warfarin factors blocked?
A: "1972" = factors I (fibrinogen), IX, VII, II + Proteins C and S (actual factors: 2, 7, 9, 10 + C + S)
Q: What is the mnemonic for warfarin-increasing drugs?
A: "CAFE MIX" = Clarithromycin/Ciprofloxacin, Amiodarone, Fluconazole, Erythromycin, Metronidazole, Isoniazid, eXcretion inhibitors (statins)
Q: What is the mnemonic for warfarin-decreasing drugs?
A: "PRICARS" = Phenytoin, Rifampicin, Isoniazid (high dose), Carbamazepine, Alcohol (chronic), St John's Wort
Q: What is the mnemonic for DOAC targets?
A: "3 Xas + 1 IIa" = rivaroxaban, apixaban, edoxaban (Xa) + dabigatran (IIa)
Q: What is the mnemonic for DOAC reversal?
A: "I-DAR for IIa (dabigatran) = Idarucizumab; AND-exanet for Xa = Andexanet alfa"
Q: What is the mnemonic for HIT management?
A: "Stop Heparin, Start Argatroban/Fondaparinux, NO platelets, NO warfarin yet"
Q: What is the mnemonic for thrombolytic contraindications?
A: "BRAIN HURTS" = Bleeding, Recent surgery, Aortic dissection, Intracranial history, Neurosurgery, Haemorrhagic stroke, Uncontrolled BP, Recent head injury, Time exceeded, Severe coagulopathy
Q: What is the mnemonic for TXA timing in trauma?
A: "3 hours or bust" = CRASH-2 trial: must give TXA within 3h of trauma
Q: What is the mnemonic for iron absorption?
A: "Vitamin C = ↑; Tea/antacids = ↓; Ferrous > Ferric"
Q: What is the mnemonic for B12 vs folate neurological difference?
A: "B12 = Bad nerves (subacute combined degeneration); Folate = Fine nerves"
Q: What is the mnemonic for EPO target in CKD?
A: "100-120 g/L, NOT normal" (overcorrection → VTE + CV events)
Q: What is the mnemonic for G-CSF side effect?
A: "BONE pain" (marrow expansion - most common G-CSF side effect)
Q: What is the mnemonic for prasugrel contraindication?
A: "Prior TIA/stroke = Prasugrel is PRASUREly dangerous"
Q: What is the mnemonic for heparin monitoring?
A: "HEPARIN = Helps Every Patient And Requires INR-free monitoring (except UFH - uses aPTT)"
Q: What is the mnemonic for thrombolytics?
A: "tPA = turns Plasminogen to Active plasmin → eATs fibrin clots"
---
============================
CLOZE DELETION CARDS
============================
[c] Warfarin [/c] inhibits [vitamin K epoxide reductase] → blocks clotting factors [II, VII, IX, X] and anticoagulant proteins [C and S]
[c] UFH [/c] is monitored using [aPTT] while [c] LMWH [/c] usually requires [no routine monitoring] (use anti-Xa in obesity/pregnancy/renal impairment)
[c] HIT Type II [/c] causes [paradoxical THROMBOSIS] because [IgG antibodies against heparin-PF4 complex activate platelets]
[c] Dabigatran [/c] is reversed by [idarucizumab 5g IV] while [c] rivaroxaban/apixaban [/c] are reversed by [andexanet alfa or 4F-PCC]
[c] Streptokinase [/c] cannot be repeated within [5 years] because [neutralising antibodies form, rendering it ineffective]
[c] Alteplase [/c] must be given within [4.5 hours] of ischaemic stroke onset and requires [CT head first to exclude haemorrhage]
[c] Ticagrelor [/c] causes dyspnoea via [adenosine-mediated mechanism], which is [not bronchospasm] and does not require discontinuation
[c] Prasugrel [/c] is contraindicated in [prior stroke or TIA] because of [high intracranial haemorrhage risk]
[c] Ferrous [/c] is better absorbed than [ferric] iron; absorption is enhanced by [vitamin C] and reduced by [antacids, tea, calcium]
[c] Pernicious anaemia [/c] requires [IM hydroxocobalamin] because [intrinsic factor is absent, so oral B12 cannot be absorbed]
[c] Folate [/c] must NEVER be given alone if [B12 deficiency is possible] because it [corrects anaemia but unmasks subacute combined degeneration of the spinal cord]
[c] EPO [/c] should target Hb [100-120 g/L] in CKD; exceeding [130 g/L] increases [VTE and cardiovascular mortality] (CHOIR and CREATE trials)
[c] TXA [/c] must be given within [3 hours] of trauma to reduce mortality (CRASH-2 trial); after 3 hours [there is no mortality benefit]
[c] Apixaban [/c] is the safest DOAC in CKD because it has the [lowest renal clearance (~27%)], while [dabigatran] is most dangerous (80% renal, avoid CrCl <30)
[c] Argatroban [/c] is the drug of choice for HIT in [renal failure] because it has [hepatic elimination]
[c] DOACs [/c] are contraindicated in [mechanical heart valves] (RE-ALIGN trial) and [pregnancy]; use [warfarin] for valves and [LMWH] in pregnancy
[c] G-CSF [/c] most commonly causes [bone pain] due to [medullary expansion]; rare serious side effect = [splenic rupture]
[c] Warfarin skin necrosis [/c] occurs [early in therapy] due to [depletion of Proteins C and S before full anticoagulation], especially in [Protein C deficiency]
[c] 4-factor PCC [/c] is preferred over [FFP] for urgent warfarin reversal because it is [faster, lower volume, and requires no blood group matching]
[c] Eltrombopag [/c] should be taken [without food] and away from [polyvalent cations (calcium, iron)] due to [chelation reducing absorption]; monitor [LFTs] for hepatotoxicity
========================================================
END OF DECK - 130+ CARDS COVERING ALL HIGH-YIELD FACTS
========================================================
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