Haematology Study Index and Classifications

Written by Betra Youhanna, a medical student and not a doctor — check every detail against your own teaching.

Deck-derived, exam-triage reference. 44 disease entities · 29 criteria & scores.

C/P

Inves

Mng

Special — pathognomonic

Thrombophilia — Acquired

3 entries

Antiphospholipid Syndrome (APS)

C/P

Recurrent venous/arterial thrombosis (any tissue or organ)
Recurrent spontaneous pregnancy loss (≥3 consecutive abortions <10wk; fetal death ≥10wk; premature birth ≤34wk from eclampsia / severe pre-eclampsia / placental insufficiency)
Primary (idiopathic) or secondary (SLE most common)

Inves

Sapporo criteria — ≥1 clinical + ≥1 lab criterion required
Lab triad: Lupus anticoagulant; Anti-cardiolipin IgG/IgM (≥40 GPL/MPL or ≥99th percentile); Anti-β2 glycoprotein I IgG/IgM (≥99th percentile)
Antibodies must be persistently positive on ≥2 occasions ≥12 weeks apart
Prolonged APTT not corrected by normal plasma
Thrombosis confirmed by imaging or histopathology

Mng

Anticoagulation (long-term)
DOACs contraindicated in high-risk (triple-positive) APLS — use warfarin

Special

Paradox: in vivo thrombosis + in vitro APTT prolongation (antibodies bind reagent phospholipid)
Target = anionic phospholipid–protein complex (β2-GPI / prothrombin), not phospholipid directly
Placental annexin shield disruption → pregnancy loss

Heparin-Induced Thrombocytopenia & Thrombosis (HITT)

C/P

Platelet drop within 4–10 days of heparin exposure
New or extending thrombosis despite low platelets (paradoxical)
Associated with unfractionated and high-molecular-weight heparin (rare with LMWH)

Inves

Baseline CBC + APTT before starting heparin
Daily CBC monitoring on heparin
IgG against PF4-heparin complex

Mng

Stop heparin immediately
Switch to non-heparin anticoagulant
HIT history = absolute contraindication to all heparin

Special

Mechanism: IgG anti-(PF4–heparin) → binds Fc-γ-RIIa on platelets → platelet activation + consumption + thrombosis
Thrombocytopenia is consumptive (cells trapped in clots), not marrow suppression

Drug-Induced Warm AIHA

C/P

Haemolytic anaemia in patient on offending drug
IgG-coated RBCs, spherocytes on film, extravascular haemolysis

Inves

Direct Coombs (DAT) positive
Drug history is diagnostic

Mng

Stop offending drug
Supportive transfusion if severe

Special

Three mechanisms by drug:
- True AIHA — Methyldopa (breaks self-tolerance)
- Drug-dependent (hapten) — Penicillin binds covalently to RBC → IgG against drug
- Complement deposition (immune complex) — Rifampicin

Thrombophilia — Inherited

10 entries

Antithrombin Deficiency

C/P

Autosomal dominant; recurrent venous thrombosis in young (<40)
Pregnancy-related VTE
Arterial thrombi occasionally
Higher thrombosis risk than Protein C/S deficiency

Inves

Normal range 0.8–1.2 IU/mL; <0.7 IU/mL = inherited deficiency
Heparin resistance (excess heparin without APTT prolongation) — qualitative mutation at heparin-binding site / reactive site / both
NEVER measure AT levels while on heparin (consumed)

Mng

Long-term anticoagulation

Special

AT inhibits Factors XIIa, XIa, IXa, Xa, IIa (thrombin); heparin accelerates this
Acquired deficiency: nephrotic syndrome (loss); DIC (consumption); severe liver disease (synthesis)

Heparin Cofactor II Deficiency

C/P

Congenital autosomal dominant; thrombotic tendency

Inves

Functional assay

Mng

Anticoagulation as for other thrombophilias

Special

Acquired causes: liver disease; DIC

Protein C Deficiency (Heterozygous adult)

C/P

Venous thromboembolism in adults (heterozygous)
PT and aPTT normal
Warfarin-induced skin necrosis on initiation

Inves

Normal level 65–135 IU/dl
Autosomal dominant, variable penetrance
Vitamin K-dependent

Mng

Anticoagulation
When starting warfarin, bridge with heparin (avoid skin necrosis from transient Protein C drop)

Special

Protein C = serine protease activated by thrombin-thrombomodulin complex → cleaves Factor Va & VIIIa at Arg 306, 506, 679 (Factor V Leiden mutates Arg 506)
Inhibits PAI-3 → ↑ fibrinolysis
Acquired causes: liver disease; vitamin K deficiency; warfarin

Homozygous Protein C Deficiency (Purpura Fulminans)

C/P

Severe DIC or purpura fulminans in infancy
Purplish-black, oval, tender lesions with erythematous rim
Gangrenous fingers; bilateral soles + left hip distribution

Inves

Abnormal basic coagulation consistent with DIC
Severely reduced Protein C activity

Mng

Protein C concentrate
FFP
Anticoagulation

Special

Widespread dermal microvascular thrombosis with haemorrhagic skin necrosis in neonates

Warfarin-Induced Skin Necrosis

C/P

Skin necrosis appearing days after warfarin initiation
Large necrotic plaques

Inves

History of recent warfarin start; pre-existing heterozygous Protein C (or S) deficiency

Mng

Stop warfarin
Heparin bridging
Protein C concentrate / FFP

Special

Mechanism: Protein C has short t½ (6h) — falls faster than Factors II, IX, X when warfarin started (because warfarin blocks vitamin K reductase) → transient hypercoagulable window → dermal microthrombi
Prevented by always bridging warfarin with heparin

Protein S Deficiency

C/P

8% of thrombosis cases in patients <45 years
Venous thromboembolism

Inves

Free PS (40%, active) reduced
Total PS may be normal in acute phase (C4b-binding protein traps PS as inactive bound form)
Modern assays measure free, antigenic PS

Mng

Anticoagulation

Special

Cofactor for activated Protein C — anchors APC to phospholipid surface
Two forms: C4b-bound PS (60%, inactive); Free PS (40%, active)
Acute-phase ↑ C4b-binding protein → falsely low free PS

Factor V Leiden / Activated Protein C Resistance (APCR)

C/P

Most common inherited thrombophilia
Mainly venous thrombosis
Often triggered by "second hit" (long flight, pregnancy, OCP)

Inves

92% of APCR = Factor V Leiden (G1691A → Arg506Gln)
8% other mutations (Arg306 → Thr/Gly)
PCR screening for mutation (simple, widely performed)

Mng

Anticoagulation if symptomatic
Avoid OCP / HRT
Pregnancy prophylaxis if prior VTE

Special

Mutated FVa lacks primary Arg506 cleavage site for APC → partial resistance (slower cleavage at Arg306/Arg679) → enhanced thrombin generation
Acquired APCR causes: pregnancy; oral contraceptive pills; cancer
Combined heterozygous Factor V Leiden + MTHFR can present as superior mesenteric vein thrombosis in young patient post-anticoagulation

Prothrombin G20210A Mutation

C/P

Increased risk of venous thrombosis
Often unprovoked or second-hit

Inves

Single point mutation in 3' untranslated region: G→A at nucleotide 20210
PCR diagnosis
Elevated prothrombin level and activity

Mng

Anticoagulation per VTE protocols

Special

Mutation in 3'UT increases mRNA stability → higher prothrombin levels (no protein structure change)
C20209T = a separate prothrombin mutation (NOT Factor V Leiden)

Hyperhomocysteinaemia

C/P

Premature arterial thrombosis > venous (e.g., MI in young patient)
Young female with proximal LAD occlusion, family history of early death

Inves

Plasma homocysteine (raised, e.g., 31.47 µmol/L)
Vitamin B12 + folate levels (often low)
MTHFR mutation testing
Methionine → Homocysteine → Cysteine (CBS + B6) OR recycled to Methionine (MTHFR + THF + B12 + folate)

Mng

Replace B12, folate, B6
Smoking cessation
Statin / aspirin per cardiovascular risk

Special

Direct endothelial dysfunction
Acquired risk factors: B12/folate deficiency; drugs; renal damage; smoking; male sex; post-menopausal / age
Favours arterial > venous occlusion (unique among thrombophilias)

Defect in Fibrinolytic System

C/P

Variable thrombotic tendency

Inves

Specific plasminogen, tPA, PAI assays
Lp(a) level

Mng

Anticoagulation per event

Special

Causes:
- Dysfibrinogenaemia — rarely thrombosis; commonly bleeding (defective fibrin); thrombosis if clottable by thrombin but not degraded by plasmin
- Plasminogen abnormality — qualitative or quantitative
- ↓ tPA + ↑ PAI — endothelium produces both; PAI-II ↑ in pregnancy
- Lipoprotein (a) — structurally similar to plasminogen → competes for binding to fibrin & endothelium → inhibits fibrinolysis; correlates with LDL; associated with atherosclerosis

Venous Thromboembolism

6 entries

Deep Venous Thrombosis (DVT) — Lower Limb

C/P

Unilateral leg swelling and erythema (clinically unreliable)
Pain, warmth, calf tenderness and induration
Lower limb = far commonest site; proximal DVT source of >90% acute PE
Distal (calf) DVT less likely to embolise but can propagate → monitor

Inves

Wells Score stratifies pre-test probability
D-dimer if "DVT Unlikely" (high NPV; raised in pregnancy, malignancy, post-op, soft-tissue injury)
Duplex ultrasound = investigation of choice (highly sensitive for proximal, less so for calf)
CT venography for IVC / iliac
MR venography (contrast-enhanced) — time/cost limited
Contrast venography = historical gold standard, superseded
DDx: cellulitis (erysipelas — demarcated); ruptured Baker's cyst (popliteal fossa, OA/RA); calf haematoma (bruising); compartment syndrome; muscle tear; lymphoedema / lymphangitis

Mng

Immediate LMWH; warfarin started simultaneously
Overlap LMWH ≥5 days AND until INR 2.0–3.0 for 2 consecutive days
Cancer-provoked: LMWH for 6 months (more effective than warfarin)
Provoked (surgery/transient): warfarin 3 months (6 in practice)
Unprovoked: warfarin ≥6 months; consider lifelong
Recurrent unprovoked: lifelong
Graduated compression stockings + early mobilisation (reduces post-thrombotic syndrome); contraindicated in PVD
Outpatient unless: HIT/heparin allergy; severe comorbidities; PCD; CrCl <30; poor adherence/communication; bleeding risk; poor social/mobility

Special

IVC filter if: anticoagulation absolutely contraindicated; recurrent VTE despite adequate anticoagulation; serious anticoagulant complications; free-floating iliofemoral/caval thrombus; extremely limited pulmonary reserve

Upper Limb DVT (Paget-Schroetter / Thoracic Outlet)

C/P

Swelling, pain or discolouration of upper limb
Collateral veins on upper arm, neck, chest wall

Inves

Ultrasound imaging (investigation of choice)

Mng

Anticoagulation as for lower limb DVT

Special

Defined: thrombosis of subclavian, axillary, or brachial vein
Primary syndromes: thoracic outlet syndrome (idiopathic compression); Paget-Schroetter (strenuous arm/shoulder use)
Secondary: central venous catheters; malignancy (mainly via catheters)
Complications: acute PE; post-thrombotic syndrome

Pulmonary Embolism (PE)

C/P

Three presentation patterns:
- Pulmonary infarction syndrome (60%) — pleuritic chest pain, dyspnoea, haemoptysis (may have normal SpO2 and normal ECG)
- Isolated breathlessness (25%)
- Sudden circulatory collapse + acute right heart failure (15%)
97% have ≥1 of: breathlessness, tachypnoea, pleuritic pain
Symptoms: fainting, fever, cough ± haemoptysis, rapid breathing, SOB, sharp stabbing chest pain worse on inspiration, low BP (<90/60), tachycardia, prior DVT symptoms

Inves

Wells Score (two-level) stratifies → "Likely" (>4) vs "Unlikely" (≤4)
Geneva Score alternative
D-dimer only if Wells ≤4 (PE Unlikely); reliably excludes PE
D-dimer false positives: severe infection, trauma, inflammation, DIC, sickle crisis, vasculitis, superficial phlebitis, cancer
CTPA = first-choice investigation; useful in cardiorespiratory disease and can confirm alternative diagnosis
V/Q scan good alternative; normal scan virtually excludes; unreliable if abnormal CXR or COPD
Pregnancy test mandatory in women of child-bearing age before V/Q
Ultrasound (DVT) if Wells >4 or +ve D-dimer but negative CTPA
Echo diagnoses massive PE — acute RV strain/failure
Pulmonary angiography most accurate but invasive
ABG: O2 sats may be normal in young; check if <94%
Troponin T elevated → risk stratification (RV injury)
ECG: most commonly sinus tachycardia; RV strain signs = RBBB, S1Q3T3, P-pulmonale, antero-septal T-wave inversion, ST depression (only with larger emboli)
CXR often normal

Mng

Low risk — treat as DVT (LMWH + warfarin); outpatient possible
Intermediate risk (submassive) — IV UFH bolus 5000–10000 U (80 U/kg) → daily s/c LMWH → warfarin; cardiac-monitored bed; thrombolyse if haemodynamic decompensation
High risk (massive) — thrombolysis first line; may thrombolyse on clinical grounds if cardiac arrest imminent; UFH infusion → warfarin post-thrombolysis; less complete dissolution than coronary thrombosis; bleeding risk
Duration: provoked 3 months (6 in practice); cancer LMWH ×6 months; first unprovoked ≥6 months ± lifelong; recurrent unprovoked lifelong

Special

Saddle embolus = massive embolus occluding pulmonary arteries (fatal PE pathology)
Severity defined by haemodynamic stability and RV strain, NOT clot size
High risk = SBP <90 OR BP drop ≥40 mmHg for >15 min (not from arrhythmia/hypovolaemia/sepsis)

Phlegmasia Cerulea Dolens (PCD)

C/P

Medical emergency
Sudden, painful, massive purplish swelling of entire limb
Neurological deficits (numbness, weakness)
Can progress to venous gangrene

Inves

Duplex ultrasound — ilio-femoro-popliteal DVT

Mng

IV heparin immediately
Catheter-directed thrombolysis (treatment of choice in endovascular era) OR emergent venous thrombectomy
6 months anticoagulation post-event
Goal: restore venous outflow

Special

Pathophys: extensive venous obstruction → ↑↑ interstitial tissue pressure → arrest of capillary flow → tissue ischaemia → gangrene
Massive venous block overcomes arterial perfusion pressure
One of only 2 indications for thrombolysis in VTE (other = massive PE)

Post-Thrombotic Syndrome

C/P

Chronic complication of DVT
Leg swelling, pain, occasional venous ulceration
Visible: venous ectasia, hyperpigmentation, skin induration, venous ulcer

Inves

Clinical diagnosis

Mng

Graduated compression stockings (prevention)
Wound care for ulcers

Special

Mechanism: venous valvular incompetence (valve damage) AND/OR persistent venous outflow obstruction (incomplete recanalisation)

Paradoxical Embolism

C/P

Systemic circulation infarction as a consequence of PE

Inves

Echocardiography (look for atrial septal defect / PFO)

Mng

Anticoagulation; consider closure

Special

Requires atrial septal defect (or PFO) — clot crosses from venous to systemic circulation

Myeloproliferative

2 entries

Polycythaemia

C/P

Acquired thrombophilia (hyperviscosity)

Inves

Peripheral blood film: crowded RBCs with lack of normal spacing (increased red cell mass)

Mng

Per myeloproliferative protocol (not detailed in deck)

Special

Increases blood viscosity → contributes to Virchow's triad (stasis)

Essential Thrombocythaemia

C/P

Acquired thrombophilia

Inves

Peripheral blood film: very high platelet counts >1000 × 10⁹/L

Mng

Per myeloproliferative protocol (not detailed in deck)

Special

Marked thrombocytosis directly promotes hypercoagulable state

Anaemia — General

3 entries

Anaemia (Definition & Compensation)

C/P

Fatigue, headaches, concentration/memory problems, loss of appetite, dizziness/vertigo, reduced energy, reduced libido, disrupted sleep
General signs: pallor (mucous membranes / lower-eyelid conjunctiva — skin unreliable); hyperdynamic circulation (rapid bounding pulse, flow murmurs); heart failure (severe cases, elderly, CV disease)
Mouth: glossitis, angular stomatitis, ulcers, telangiectasia
Compensation: ↑ cardiac output; redistribution to brain/myocardium; ↑ 2,3-DPG (rightward shift)

Inves

FBC (indices first: micro/normo/macro), blood film, reticulocyte count (0.5–2.5%; absolute 25–125 × 10⁹/L)
Haematinics: B12, folate, iron studies
Biochemistry: U&Es, LFTs, inflammatory markers
Haemolysis screen (retics + DAT) if indicated
Bone marrow examination (aspirate + trephine ± Prussian blue) — not always indicated; reserved when blood workup fails
Imaging: x-ray for myeloma; CT for lymphoma
Endoscopy/colonoscopy especially in old age

Mng

Treat underlying cause (raises Hb)
Treat the patient not the haemoglobin
Mild anaemia usually needs no correction
Tolerant anaemias (sickle cell, MDS) need treatment only if Hb falls significantly below baseline
Transfusion only if Hb very low, symptomatic, or acute blood loss (guided by symptoms + CV state, not Hb alone)

Special

Acute blood loss: Hb may be near normal initially; doesn't reflect true loss
Classification: by cause; morphology (micro/normo/macro/hypochromic/megaloblastic/leucoerythroblastic); pathophysiology (haemolytic/aplastic)

Aplastic Anaemia

C/P

Pancytopenia symptoms
Cause of normocytic-normochromic OR non-megaloblastic macrocytic anaemia

Inves

Bone marrow trephine biopsy: fatty spaces replacing cells

Mng

Treat underlying cause; transfusion support (deck does not detail further)

Special

Pathophysiological classification of anaemia alongside haemolytic anaemia

Leucoerythroblastic Reaction

C/P

Sign of severe marrow stress

Inves

Stained blood film shows both myeloid precursor (myelocyte) AND erythroid precursor (normoblast)

Mng

Investigate and treat underlying cause

Special

Causes:
- Infiltration / replacement of bone marrow cells
- Severe bleeding (increased cell production)
- Acute haemolysis (increased cell production)

Microcytic Anaemia

5 entries

Iron Deficiency Anaemia

C/P

General: tiredness, exertional dyspnoea
Tissue features: angular stomatitis; koilonychia (spoon-shaped nails); painful glossitis; atrophic glossitis (smooth red tongue); dysphagia (rare pharyngeal web); irritability; cognitive impairment in children
Functional: abnormal mental/motor development in infancy; impaired work capacity; premature delivery; ↑ maternal/infant mortality

Inves

FBC: low MCV (microcytosis); low MCH/MCHC (hypochromia); thrombocytosis common; anaemia is last feature to develop
Blood film: microcytic hypochromic with ↑ central pallor; pencil cells; target cells
Iron studies: LOW serum iron; ↑ TIBC; LOW ferritin; ↑ soluble transferrin receptor; transferrin saturation <15% diagnostic
Reference ranges: ferritin 15–300 µg/L (men), 15–200 µg/L (women); serum iron 10–30 µmol/L; TIBC 47–70 µmol/L; transferrin sat 16–50%; sTfR 2.8–8.5 mg/L
Lab stages: ferritin drops first → transferrin sat + erythrocyte ZPP + sTfR → finally Hb + MCV + %Hypo + CHr
Bone marrow Prussian blue (Perl's) very reliable but invasive
Coeliac screen: anti-tissue glutaminase + duodenal biopsy
Gastroscopy/colonoscopy: GI symptoms or unexplained weight loss (rule out colorectal cancer)
Capsule endoscopy for inaccessible small bowel
Faecal occult blood test

Mng

Oral ferrous sulphate 200 mg TDS × 4–6 months (most cost-effective)
Continue until tissue stores replete (Hb normalises first)
Causes of poor response: poor compliance (most common); malabsorption; wrong diagnosis (thalassaemia trait misdiagnosed); uncontrolled bleeding
Parenteral iron (IV) only when: oral intolerance; ineffective; malabsorption (Crohn's, coeliac, IBD proximal small bowel, post-gastrectomy, small bowel resection); CKD on HD + EPO; demand exceeds oral capacity
Parenteral formulations: iron dextran (IV or deep IM); sodium ferric gluconate (IV); iron sucrose (IV)
High-MW iron dextran → highest anaphylaxis risk → test dose first
IV iron raises Hb at same rate as oral; only stores fill faster

Special

Stages: depletion of stores → morphological abnormalities → anaemia
Body iron: ~75% in erythron (Hb); transferrin pool small (3–5 mg) but most active
Iron absorption: duodenum; Fe2+ (ferrous) form needed; gastric acid keeps iron reduced
Iron absorption efficiency: Heme > Fe2+ > Fe3+
Causes: limited supply (single-food infant diet, fasting, coeliac, gastrectomy); increased demand (pregnancy, prematurity, adolescent growth spurt, EPO therapy); blood loss (menorrhagia, GI — peptic ulcer, gastric cancer, colon cancer; hookworm worldwide commonest; haemosiderinuria from intravascular haemolysis; exercise; blood donation)
Older patient + unexplained iron deficiency = exclude malignancy

Anaemia of Chronic Disease

C/P

2nd most common anaemia worldwide
Symptoms of chronic inflammatory disorder / infection / autoimmune disease (especially RA)
Initially normocytic; with time becomes microcytic

Inves

LOW serum iron + LOW TIBC + NORMAL/RAISED ferritin (key contrast with iron deficiency)

Mng

Treat the underlying inflammatory / infectious / autoimmune disease

Special

Pathophys: chronic inflammation → acute phase response → ↑ hepcidin → sequesters iron in macrophages → marrow erythroid precursors deprived → defective Hb synthesis → microcytic anaemia
Evolutionary defence to starve bacteria of iron
Iron supplementation may worsen TB, HIV, malaria

Thalassaemia Syndromes

C/P

Inherited haemoglobin disorder (alpha and beta thalassaemia)
Three grades: trait; intermediate; transfusion-dependent

Inves

Beta trait: Hb usually >9 g/dL; HbA2 elevated in majority
Persisting microcytosis and hypochromia despite normal iron studies → suggestive of thalassaemia
Differential for microcytic hypochromic anaemia

Mng

Not detailed in this deck

Special

Thalassaemia patients can co-develop iron deficiency — confirm iron studies normal before attributing microcytosis to thalassaemia alone

Sideroblastic Anaemia

C/P

Anaemia symptoms; MCV may be low, normal, or high

Inves

Bone marrow: ring sideroblasts = marrow red cell precursors with a ring of iron granules (mitochondria) surrounding the nucleus (Prussian blue)

Mng

Treat underlying cause; remove offending drug/alcohol

Special

Defect in incorporation of iron into haemoglobin → iron accumulates in mitochondria
Primary type = one of the myelodysplastic syndromes
Secondary causes: malignancy; alcohol; drugs; heavy metal poisoning; collagen diseases

Acute Iron Toxicity

C/P

Young children who accidentally ingest iron tablets
As few as 10 tablets can be lethal
Initial (necrotizing gastroenteritis): vomiting, abdominal pain, bloody diarrhoea
Subsequent: shock, lethargy, dyspnoea
Late (after transient improvement): severe metabolic acidosis, coma, death

Inves

Clinical + ingestion history; serum iron level

Mng

Whole bowel irrigation (flushes unabsorbed pills)
IV deferoxamine (chelates absorbed iron → urinary/faecal excretion)
Supportive: GI bleeding; metabolic acidosis; shock
Activated charcoal ineffective — does not adsorb iron

Special

Iron is directly corrosive to GI mucosa AND mitochondrial toxin systemically

Macrocytic / Megaloblastic Anaemia

4 entries

Megaloblastic Anaemia — Vitamin B12 Deficiency / Pernicious Anaemia

C/P

Megaloblastic anaemia (may be absent in early disease)
Cytopenias: neutropenia, thrombocytopenia
Oral: atrophic glossitis, angular stomatitis
Sterility
Neurological (may occur even without anaemia): peripheral neuropathy; myelopathy (subacute combined degeneration); optic atrophy; neuropsychiatric/cognitive problems (dementia)

Inves

FBC: anaemia (may be absent); MCV >100 fl; ± neutropenia/thrombocytopenia; pancytopenia in severe
Blood film: oval macrocytes (earliest); neutrophil hypersegmentation (>5% of neutrophils with >5 lobes — "shift to right"); reticulocytopenia
LFTs: ↑ unconjugated bilirubin; ↑ LDH (ineffective erythropoiesis)
Intrinsic factor antibodies (specific for pernicious anaemia)
Gastric parietal cell antibodies (non-specific)
Coeliac screen if suspected
Schilling Test (B12 absorption — availability reduced due to radioactive material rules)
Bone marrow (not usually required): megaloblastic change; hypercellular; late erythroblast with fine open chromatin (megaloblast)

Mng

Hydroxocobalamin 1 mg IM ×3/week × 2 weeks (initial)
Then 1 mg IM 3-monthly for life if B12 malabsorption (pernicious anaemia, terminal ileal disease)
Cyanocobalamin orally if NO malabsorption (dietary only)
Neurological involvement: injections 1–2 weekly × 6 months before monthly
Bariatric patients: large oral doses OR sublingual OR parenteral monthly (cyanocobalamin)
Co-supplement folate + iron in severe anaemia (high cell turnover depletes stores)
Folic acid must NEVER be given before B12 — corrects anaemia but allows neurological deterioration

Special

Megaloblastic morphology = nuclear-cytoplasmic dyssynchrony (nuclear lag from impaired DNA synthesis)
B12 absorption pathway: stomach (proteolytic release → bind IF from parietal cells) → terminal ileum (IF-B12 receptor) → portal circulation (Transcobalamin II carrier, β-globulin, liver-synthesized) → bone marrow
B12 functions: methionine synthesis (methylcobalamin; activates folate for DNA synthesis); methylmalonyl-CoA → succinyl-CoA
B12 stores: 3–4 mg in liver; last ~3 years; deficiency develops slowly
Causes:
- Dietary — vegans, vegetarians (B12 only in animal foods)
- Impaired absorption — pernicious anaemia (anti-IF / anti-parietal cell); terminal ileal disease/resection (Crohn's); gastrectomy; bacterial overgrowth; alcoholism; tropical sprue; fish tapeworm (Diphyllobothrium latum)
- Metabolic inhibition — nitrous oxide (Entonox) on prolonged use (safe for labour)
- Inherited — Transcobalamin II deficiency

Megaloblastic Anaemia — Folate Deficiency

C/P

Similar to B12 deficiency presentation
Less neurological involvement than B12
Neural tube defects in foetus (e.g., spina bifida) — high incidence

Inves

Serum folate + red cell folate (red cell folate = better tissue store indicator)
Same megaloblastic FBC + film findings as B12

Mng

Folic acid 5 mg orally daily × 3–4 months (acute)
Dietetic advice if dietary deficiency
Indefinite if malabsorption / dietary inadequacy
Prophylaxis: 400 µg daily pre-conceptually to prevent fetal NTDs
Other prophylaxis: pregnant women; premature infants; severe chronic haemolytic anaemia (haemoglobinopathies e.g. sickle cell)
Methotrexate toxicity treatment/prevention

Special

Folate stores ~10 mg; last ~4 months only — deficiency develops rapidly
Folate sources: green vegetables, liver, dried beans, fortified cereals, yeast
Heat-labile; destroyed by cooking at high temp in large water volume
Absorption: polyglutamates → monoglutamates (brush border) → duodenum/jejunum as N-5-methyl-THF (inactive) → activated by MTHFR to THF (requires B12 as methylcobalamin during homocysteine→methionine reaction)
Functions: one-carbon transfer; DNA synthesis; homocysteine → methionine; SAM formation
Causes: dietary (old age, alcoholism, poverty); malabsorption (coeliac, tropical sprue); excessive demands (pregnancy, prematurity, chronic haemolysis, myelofibrosis, malignancy, exfoliative dermatitis, Crohn's, severe psoriasis); drugs (anticonvulsants, sulphasalazine, methotrexate, pyrimethamine, trimethoprim); liver disease; dialysis

Subacute Combined Degeneration of the Spinal Cord

C/P

Classic myelopathy of severe B12 deficiency
May occur even with normal blood counts

Inves

Vitamin B12 (low)
MRI spinal cord

Mng

Hydroxocobalamin IM (frequent dosing 1–2 weekly × 6 months before monthly)
NEVER give folate before B12 (precipitates/aggravates neurological complications)

Special

Treat as soon as possible after diagnosis — neurological damage can be irreversible

Non-megaloblastic Macrocytic Anaemia

C/P

Macrocytic anaemia without megaloblastic marrow findings

Inves

MCV >100 fl
Normal B12 and folate
Investigate underlying cause (LFTs, TFTs, alcohol history)

Mng

Treat underlying cause

Special

Causes: alcoholism; liver disease; hypothyroidism; aplastic anaemia; reticulocytosis (reticulocytes are larger than mature RBCs); myelodysplasia

Anaemia — Other

1 entry

Anaemia of Chronic Kidney Disease

C/P

Anaemia in patient with renal failure
EPO levels typically low

Inves

Low EPO (kidneys cannot produce)

Mng

Erythropoiesis-Stimulating Agents (ESAs) — most likely to respond
- Epoetin alfa (IV in HD, SC otherwise; 3× weekly; t½ 4–13h IV; not cleared by dialysis)
- Darbepoetin alfa (heavily glycosylated; 2–3× longer t½; weekly)
- Methoxy polyethylene glycol-epoetin beta (pegylated; 2-weekly or monthly)
- Target Hb up to 10–12 g/dL; never rise >1 g/dL per 2 weeks; reduce/stop if Hb >10 g/dL
- Onset: reticulocytes ↑ ~10 days; HCT/Hb ↑ ~2–6 weeks (no use in acute anaemia)
- Co-supplement iron (nearly all CKD patients) + folate
Daprodustat (oral HIF-PH inhibitor; first oral treatment for CKD anaemia; requires ≥4 months prior dialysis)
- Stabilises HIF-1α → ↑ EPO + ↓ hepcidin
- Starting dose: Hb <9 → 4 mg; Hb 9–10 → 2 mg; Hb >10 → 1 mg; switching from ESA 4–12 mg

Special

ESAs may also be used for: AIDS anaemia (zidovudine); myelosuppressive chemo; non-cardiac/non-vascular elective surgery; autologous blood donation prep; premature infants (unpreserved formulation only — benzyl alcohol = fatal toxic syndrome); chronic inflammatory conditions (RA, investigational)
ESA / Daprodustat severe risks if Hb >11–12 g/dL or rises too fast: thrombosis; severe hypertension; MI; stroke; ↑ death; shortened time to tumor progression
Other ESA effects: arthralgia; rare allergic reaction (long-term SC)
HIF pathway: normal O2 → HIF-PH degrades HIF-1α; hypoxia/Daprodustat → HIF-1α stable → dimerises with HIF-β → binds Hypoxia Response Elements (HREs) on DNA → induces EPO gene

Haemolytic Anaemia

10 entries

Warm AIHA

C/P

Idiopathic OR secondary (autoimmune — SLE, RA; lymphoproliferative — lymphoma, CLL; infection — HIV)
Mostly extravascular haemolysis (splenic clearance) → jaundice, spherocytes

Inves

Direct Coombs (DAT) positive (IgG ± complement)
Spherocytes on blood film

Mng

Treat underlying cause
Folic acid 5 mg daily (high cell turnover)
Transfusion if severe/life-threatening
Specific treatment per cause

Special

Autoantibody most active at 37°C
Red cells become spherical → destroyed
Drug-induced mechanisms (see Disease 3): methyldopa (true AIHA); penicillin (drug-dependent); rifampicin (complement deposition)

Cold AIHA

C/P

Acute febrile illness presentation
Red cell agglutination in cooler extremities
Idiopathic OR secondary (infection — Mycoplasma, EBV; lymphoproliferative)
Mostly intravascular haemolysis (complement-mediated lysis)

Inves

DAT positive for complement
Red cell agglutination on blood film
Positive Mycoplasma IgM if Mycoplasma-related

Mng

Treat underlying cause
Avoid cold exposure
Supportive

Special

Mediated by IgM (stronger than IgG for complement activation)
Cells return to warm core where MAC completes lysis intravascularly

Alloimmune Haemolytic Anaemia (Transfusion Reaction + HDN)

C/P

ABO incompatible transfusion — acute presentation: severe back pain, dark red urine, acute anaemia
Delayed transfusion reaction — haemolysis a few days after transfusion
Haemolytic disease of the newborn — affects 2nd baby; intrauterine death

Inves

Delayed: positive DAT + demonstration of new red cell alloantibody
ABO incompatibility: clinical + haemoglobinuria

Mng

Stop transfusion; supportive
Rh prophylaxis in HDN (not detailed in deck)

Special

ABO incompatibility = intravascular haemolysis
Delayed reaction = mainly extravascular

Microangiopathic Haemolytic Anaemia (MAHA)

C/P

Schistocytes (fragmented RBCs) on blood film

Inves

Fragmented RBCs / schistocytes on blood film
Underlying disease workup

Mng

Treat underlying syndrome

Special

Definition: lysis of red cells in small blood vessels by fibrin mesh (acts like cheese wire)
Fibrin mesh causes: inappropriate activation of coagulation; vascular endothelial abnormalities; trauma
Causes: HUS; TTP; DIC; pre-eclampsia/HELLP; vasculitides; AV malformations

Thrombotic Thrombocytopenic Purpura (TTP)

C/P

Classic pentad — F.A.T. R.N.
- Fever
- Neurological problems
- Renal impairment
- Thrombocytopenia
- Red cell fragmentation (MAHA — schistocytes)

Inves

Reduced ADAMTS 13 activity is diagnostic
Blood film: schistocytes
Low platelets

Mng

Urgent plasma exchange (replaces missing ADAMTS13)

Special

ADAMTS 13 normally cleaves von Willebrand Factor multimers into normal size
Missing ADAMTS 13 → uncleaved giant vWF multimers trap platelets → platelet-vWF microthrombi occlude flow + shear passing RBCs

Haemolytic Uraemic Syndrome (HUS)

C/P

Example of microangiopathic haemolytic anaemia (MAHA)

Inves

Schistocytes; renal impairment

Mng

Supportive (deck does not detail further)

Special

MAHA pathway: fibrin mesh in small vessels

Disseminated Intravascular Coagulation (DIC)

C/P

Listed as MAHA cause; consumptive coagulopathy

Inves

Coagulopathy + thrombocytopenia + schistocytes
Can cause acquired antithrombin deficiency (consumption)
Can cause acquired heparin cofactor II deficiency
Can cause acquired Protein C deficiency

Mng

Treat underlying trigger (deck does not detail)

Special

Homozygous Protein C deficiency presents as severe DIC / purpura fulminans in infancy

Paroxysmal Nocturnal Haemoglobinuria (PNH)

C/P

Anaemia
Abdominal pain
Thrombosis (severe hypercoagulable state)
Intermittent haemoglobinuria (classically at night/morning)

Inves

Flow cytometry for CD55/CD59 (deck describes mechanism, not test detail)

Mng

Per specialist protocol (deck does not detail)

Special

Acquired clonal stem cell disorder
Normal RBCs protected from complement by CD55 (decay-accelerating factor) and CD59 (MAC-inhibitory protein), anchored by GPI
PNH RBCs are CD55⁻ CD59⁻ → unprotected → lysed by complement (MAC = membrane attack complex)
Causes intravascular haemolysis + thrombosis

Mechanical Haemolysis (Cardiac Valves / Arterial Grafts)

C/P

Haemolysis in patient with prosthetic cardiac valve or arterial graft

Inves

Schistocytes on film; intravascular haemolysis markers

Mng

Per cardiology / surgical assessment

Special

RBCs physically fragmented as they hit cardiac valves
Listed under "Other fragmentation syndromes" alongside burns; infections (malaria, clostridial); PNH; march haemoglobinuria; liver disease; renal disease

March Haemoglobinuria

C/P

Haemoglobinuria after sustained physical exertion (e.g., long march)

Inves

Intravascular haemolysis markers

Mng

Reduce mechanical trauma

Special

Listed as miscellaneous cause of non-immune haemolytic anaemia

Diagnostic Criteria

1 entry

Sapporo Criteria for APS

At least one clinical + one laboratory criterion is mandatory.

Clinical Criteria

Domain	Criterion
Thrombosis	Arterial, venous, or small vessel thrombosis in any tissue/organ, confirmed by imaging or histopathology
Pregnancy — fetal death	≥1 morphologically normal fetal death ≥10th gestational week
Pregnancy — premature birth	≥1 morphologically normal neonate, premature birth ≤34th week from eclampsia, severe pre-eclampsia, or placental insufficiency
Pregnancy — abortions	≥3 unexplained consecutive spontaneous abortions ≤9th week (maternal anatomic/hormonal and chromosomal abnormalities excluded)

Laboratory Criteria

Any 1 of 3; confirmed on ≥2 occasions ≥12 weeks apart.

Antibody	Cutoff	Method
Lupus anticoagulant	Per ISTH guidelines	—
Anti-cardiolipin IgG/IgM	Medium/high titer (≥40 GPL or MPL or ≥99th percentile)	Standard ELISA (serum/plasma)
Anti-β2 glycoprotein I IgG/IgM	≥99th percentile	Standard ELISA (serum/plasma)

Testing Guidelines

ISTH (SSC) 2009
BCSH 2012
CLSI 2014

Risk / Probability Scores

5 entries

Wells Score — DVT

Clinical Features

Feature	Score
Active cancer (treatment within previous 6 months or palliative)	+1
Recent cast immobilisation of lower extremities	+1
Bedridden ≥3 days, or major surgery within previous 12 weeks (GA/regional)	+1
Localised tenderness along distribution of deep venous system	+1
Entire leg swelling	+1
Calf swelling ≥3 cm larger than asymptomatic side (measured 10 cm below tibial tuberosity)	+1
Pitting oedema confined to symptomatic leg	+1
Non-varicose collateral superficial veins	+1
Previously documented DVT	+1
Alternative diagnosis at least as likely as DVT	-2

Probability

Low: -2 to 0
Moderate: 1 to 2
High: 3 to 8

Wells Score — PE (Two-Level)

Clinical Features

Feature	Score
Clinical signs/symptoms of DVT (minimum leg swelling + pain with palpation)	+3
Alternative diagnosis less likely than PE	+3
Heart rate >100 bpm	+1.5
Immobilisation >3 days OR surgery in previous 4 weeks	+1.5
Previous DVT/PE	+1.5
Haemoptysis	+1
Malignancy (on treatment, treated last 6 months, or palliative)	+1

Simplified Interpretation

PE Likely: >4
PE Unlikely: ≤4

Geneva Score — PE

Scoring

Variable	Score	Simplified
Age >65 years	1	1
Active malignancy (cure <1 year)	2	1
Surgery or lower limb fracture within 1 month	2	1
Previous PE or DVT	3	1
Haemoptysis	2	1
Unilateral lower limb pain	3	1
Lower limb deep venous palpation tenderness + unilateral oedema	4	1
Heart rate 75–94 bpm	3	1
Heart rate ≥95 bpm	5	2

PE Severity Classification

Risk Groups

Risk Group	Haemodynamics	RV Strain	Treatment Niche
High (Massive)	SBP <90 mmHg OR BP drop ≥40 mmHg for >15 min (not from arrhythmia/hypovolaemia/sepsis)	—	Thrombolysis first line
Intermediate (Submassive)	Stable (SBP >90)	Present (elevated troponin T; RV strain on CTPA/echo)	LMWH + cardiac monitor; thrombolyse if decompensates
Low	Stable	Absent	Treat as DVT; outpatient possible

Majority of patients fall into low-risk category.

PE Clinical Presentation Patterns

Patterns

Pattern	Proportion	Features
Pulmonary infarction syndrome	60%	Pleuritic chest pain + dyspnoea + haemoptysis (may have normal SpO2 and ECG)
Isolated breathlessness	25%	—
Sudden circulatory collapse + acute right heart failure	15%	Previously well OR poor cardiorespiratory reserve

97% have ≥1 of: breathlessness, tachypnoea, pleuritic pain.

Anatomical / Classification

15 entries

Virchow's Triad

Components

Endothelial injury (vessel wall) — less important in venous; important in sepsis + indwelling catheter
Abnormal blood flow (stasis) — cardiac failure, stroke, prolonged immobility
Hypercoagulability (blood composition) — congenital/acquired thrombophilia

Provoked vs Unprovoked VTE

Comparison

	Provoked	Unprovoked
Risk factor	Transient	None identified, OR persistent + irremovable
Recurrence risk	↓ when risk factor removed	High
Duration	3 (–6) months	≥6 months; consider lifelong

WHO Hb Diagnostic Cutoffs

By Age & Sex

Group	Hb cutoff
At birth	<14 g/dL
3–6 months	<11 g/dL
2–6 years	<11 g/dL
6–12 years	<11.5 g/dL
Adult male	<13 g/dL
Adult female	<12 g/dL
Pregnant	<11 g/dL

Anaemia Classification by Indices

By MCV / MCH

Class	MCV	MCH	Causes
Microcytic hypochromic	<80 fl	<27 pg	Iron deficiency; thalassaemia; anaemia of chronic disease (some); lead poisoning / sideroblastic (some)
Normocytic normochromic	80–100 fl	27–32 pg	Many haemolytic anaemias; anaemia of chronic disease (some); after blood loss; renal disease / mixed deficiencies / bone marrow failure
Macrocytic megaloblastic	>100 fl	—	Vitamin B12 deficiency; folate deficiency
Macrocytic non-megaloblastic	>100 fl	—	Alcohol; liver disease; myelodysplasia; aplastic anaemia

Anaemia Classification Approaches

Three Approaches

By cause — iron deficiency; folate deficiency; B12 deficiency; blood loss
By morphology — normocytic; microcytic; macrocytic; hypochromic; megaloblastic; leucoerythroblastic
By pathophysiology — haemolytic anaemia; aplastic anaemia

Macrocytic Anaemia Classification

Subtypes

Subtype	Pancytopenia	Causes
Megaloblastic	Yes (associated)	Vitamin B12 deficiency; folic acid deficiency; congenital dyserythropoietic anaemia
Non-megaloblastic (normoblastic)	No	Alcoholism; liver disease; hypothyroidism; aplastic anaemia; reticulocytosis

Inherited Haemolytic Anaemia Classification

Category	Example
Membrane disorders	Hereditary spherocytosis
Enzyme disorders	G6PD deficiency
Haemoglobin disorders	Sickle cell disease; thalassaemia

Coombs Tests — Direct (DAT) vs Indirect (IAT)

Comparison

Test	Detects	Mechanism	Indication
Direct (DAT / DCT)	Antibodies already bound to patient's RBCs in vivo	Patient's washed RBCs + antihuman antibodies (Coombs reagent) → agglutination if antibodies present	Immune-mediated haemolysis (autoimmune)
Indirect (IAT)	Free-flowing antibodies in patient's serum	Patient serum + test RBCs + antihuman antibodies	Transfusion reaction risk assessment

Interpretation

Positive DAT → immune haemolysis
Negative DAT → non-immune (very few exceptions)

Extravascular vs Intravascular Haemolysis

Contrast Table

Feature	Extravascular	Intravascular
Destruction cell	Reticuloendothelial macrophages	Lysed directly in circulation
Sites	Spleen (predominant), liver, bone marrow	Blood vessels
Trigger	IgG-coated / irregular RBC → phagocytosis	Shear stress; toxins; complement
Products	Bilirubin (predominantly unconjugated) → biliary clearance	Free haemoglobin → haptoglobin → renal tubular excretion if capacity exceeded
Clinical	Jaundice (visible if bilirubin >6 mg/dL); spherocytes; splenomegaly; pigment gallstones in chronic	Haemoglobinaemia; haemoglobinuria (red urine, acute); ↓↓ haptoglobin; ↑↑ LDH; haemosiderinuria (later); methaemalbuminaemia (positive Schumm's test)

Biochemical Markers of Haemolysis

↑ Bilirubin (unconjugated)
↑ LDH
↓ Serum haptoglobins
↑ Urinary urobilinogen

Investigation Algorithm — 4 Questions

Is there evidence of haemolysis?
Is it immune or non-immune?
Is haemolysis extravascular or intravascular?
What is the specific cause?

Hemostatic Balance — Procoagulant vs Anticoagulant

Components

Procoagulant	Anticoagulant
PAI-1	Protein S
Antiplasmin	Protein C
Tissue factor	TFPI
Clotting factors	Fibrinolytic system
—	Antithrombin III (ATIII)

Coagulation Screening Tests — Interpretation

Bleeding Time (primary haemostasis)

PFA-100 = modern modified version
Prolonged by: thrombocytopenia, platelet dysfunction (aspirin), von Willebrand disease, vascular defect (Ehlers-Danlos), low haematocrit in CRF

PT — Extrinsic + Common Pathway

Measures VII, X, V, II (prothrombin), I (fibrinogen); normal 11–16 s
Monitors warfarin → reported as INR = (PT_patient / mean-normal PT)^ISI
Prolonged by: factor VII/X/V/II/I deficiency, liver disease, vitamin K deficiency (II, VII, IX, X), obstructive jaundice, haemorrhagic disease of newborn, DIC, massive transfusion, warfarin

APTT — Intrinsic + Common Pathway

Measures VIII, IX, XI, XII (+ X, V, II, I); normal 26–40 s
Monitors unfractionated heparin
Prolonged by: factor XII/XI/IX/VIII (+ X/V/II/I) deficiency, liver disease, vitamin K deficiency, DIC, massive transfusion, warfarin, heparin

Thrombin Time (TT)

Reflects fibrinogen level + inhibitors
Prolonged by: dys-/hypofibrinogenaemia, liver disease, DIC, raised FDPs / D-dimer, heparin

Iron Absorption Modifying Factors

Category	Factors
Form (efficiency)	Heme > Fe²⁺ (ferrous) > Fe³⁺ (ferric)
High gastric pH (↓ absorption)	Hemigastrectomy; vagotomy; pernicious anaemia; H2 blockers + calcium-based antacids
Intestinal disruption	Crohn's disease; coeliac disease; ↑ hepcidin; absent DMT-1
Dietary inhibitors	Phytates; tannins; soil clay; laundry starch; iron overload
Metal competitors	Cobalt; lead; strontium
Dietary facilitators	Ascorbate; citrate; amino acids

Iron Studies Reference Ranges

Reference Ranges

Parameter	Reference range
Ferritin (men)	15–300 µg/L
Ferritin (women)	15–200 µg/L
Serum iron	10–30 µmol/L
TIBC	47–70 µmol/L
Transferrin saturation	16–50%
Soluble transferrin receptor (sTfR)	2.8–8.5 mg/L

Key Patterns

Diagnostic threshold for iron deficiency: transferrin saturation <15%
TIBC = UIBC + Serum Iron
Iron-deficiency pattern: ↓ serum iron + ↑ TIBC + ↓ ferritin (+ ↑ sTfR)
ACD pattern: ↓ serum iron + ↓ TIBC + normal/↑ ferritin

Iron Deficiency Laboratory Stages

Sequential Lab Changes

Stage	Abnormal Parameters
Store depletion	Serum ferritin (drops first)
Iron-deficient erythropoiesis (normal Hb)	+ Transferrin saturation; erythrocyte ZPP; serum TfR
Anaemia	+ Haemoglobin; MCV; % hypochromic; CHr

Differential Diagnosis — Occult GI Blood Loss

GI — Common

Source	Frequency
Aspirin/NSAID use	10–15%
Colonic carcinoma	5–10%
Gastric carcinoma	5%
Benign gastric ulceration	5%
Angiodysplasia	5%

GI — Uncommon

Source	Frequency
Oesophagitis	2–4%
Oesophageal carcinoma	1–2%
Gastric antral vascular ectasia	1–2%
Small bowel tumours	1–2%
Ampullary carcinoma	<1%
Ancylomasta duodenale	<1%

Malabsorption

Source	Frequency
Coeliac disease (common)	4–6%
Gastrectomy (common)	<5%
H. pylori colonisation (common)	<5%
Gut resection (uncommon)	<1%
Bacterial overgrowth (uncommon)	<1%

Non-GI

Source	Frequency
Menstruation (common)	20–30%
Blood donation (common)	5%
Haematuria (uncommon)	1%
Epistaxis (uncommon)	<1%

Treatment / Monitoring

8 entries

INR Targets — Warfarin

By Indication

Indication	Target	Range
First DVT or PE	2.5	2.0–3.0
Recurrent VTE while therapeutically anticoagulated	3.5	3.0–4.0

Warfarin Overdose Algorithm

By Scenario

Scenario	Action
INR 6–8 (no/minor bleeding)	Stop warfarin 24–48h → recheck INR → re-introduce at lower dose, retest in 2–7 days
INR >8 (no/minor bleeding)	Stop warfarin 48h → retest day 3 before restarting at lower dose. Oral Vitamin K 2.5 mg (Menadiol) OR IV Vitamin K 1–2 mg slow injection (Phytomenadione — faster onset, ≥6h to therapeutic effect)
Life/limb-threatening bleeding	Stop warfarin. Prothrombin Complex Concentrate (Beriplex — contains Factors II, VII, IX, X + Protein C/S; prothrombotic risk). IV Vitamin K 2–5 mg

Key Notes

Risk threshold: INR >5.0 = significantly increased bleeding risk
Common bleed sites: GI tract; intracranial cavity
Commonest cause of overdose: alcohol + drug interactions
FFP not recommended — does not completely reverse warfarin at recommended doses; ≥30 min to thaw + large volume needed compared to Beriplex
Large Vitamin K doses can interfere with subsequent control for several weeks (12–24h for full effect)

Anticoagulant Contraindications

Comparison

Absolute	Relative
Haemorrhagic diathesis	Uraemia
Severe hypertension	Liver disease
Previous cerebral haemorrhage	Chronic alcoholism
CNS trauma	Subacute bacterial endocarditis
GI bleeding	—
Heparin hypersensitivity or HIT history	—

Breastfeeding NOT a contraindication (provided baby has received Vitamin K).

DOACs — 2025 Dosing Table

By Indication

Indication	Apixaban	Rivaroxaban	Dabigatran
VTE prevention (post hip/knee)	2.5 mg BD	10 mg OD	110 mg 1–4h post-surgery → 220 mg OD
VTE treatment — initiation	10 mg BD × 7 days	15 mg BD × 21 days	—
VTE treatment — maintenance	5 mg BD (consider 2.5 mg BD beyond 6m)	20 mg OD (consider 10 mg OD beyond 6m)	150 mg BD or 110 mg BD
Atrial fibrillation	5 mg BD (or 2.5 mg BD)	20 mg OD (or 15 mg OD)	150 mg BD (or 110 mg BD)
Stable atherosclerotic vascular disease	—	2.5 mg BD + aspirin	—

DOACs — Scenarios Where Not Advised

Contraindications

Category	Detail
Mechanical prosthetic heart valves	Use warfarin
Moderate–severe mitral stenosis (including rheumatic)	Use warfarin
Pregnancy and breastfeeding	—
Severe kidney disease	Apixaban <25 mL/min; Dabigatran <30 mL/min; Rivaroxaban <15 mL/min
Severe liver disease	Apixaban contraindicated in Child-Pugh C; Rivaroxaban in Child-Pugh B and C; Dabigatran if liver enzymes >2× ULN
High-risk APLS	Triple-positive (lupus anticoagulant + anticardiolipin + anti-β2 glycoprotein) AND/OR history of arterial thrombosis

Measure DOAC-Specific Effect When

Major bleeding
Urgent surgery
New/deteriorating renal impairment
Weight >120 kg
Recurrence/extension of thromboembolism
Concomitant CYP inducers/inhibitors
Before thrombolysis

Antiplatelets — Therapy Choice Table

By Diagnosis

Diagnosis	1st line	2nd line
Acute coronary syndrome (medically treated)	Aspirin (lifelong) + Ticagrelor (12 months)	Clopidogrel (lifelong) if aspirin contraindicated
Percutaneous coronary intervention	Aspirin (lifelong) + Prasugrel OR Ticagrelor (12 months)	Clopidogrel (lifelong) if aspirin contraindicated
TIA	Clopidogrel (lifelong)	Aspirin (lifelong) + Dipyridamole (lifelong)
Ischaemic stroke	Clopidogrel (lifelong)	Aspirin (lifelong) + Dipyridamole (lifelong)
Peripheral arterial disease	Clopidogrel (lifelong)	Aspirin (lifelong)

Classes of Antiplatelets

Aspirin — non-selective irreversible COX 1,2 inhibitor; 75–81 mg low dose; GI bleeding
ADP receptor inhibitors — clopidogrel, prasugrel, ticagrelor (reversible), ticlopidine — block P2Y12, prevent GP IIb/IIIa expression
GP IIb/IIIa inhibitors
PDE inhibitors — dipyridamole, cilostazol — ↑ cAMP → antiplatelet + vasodilator; preferred in peripheral arterial disease

ESA Dosing & Hb Targets

Parameters

Parameter	Recommendation
Route — renal dialysis	IV
Route — other indications	SC
Maximum target Hb	Up to (not exceeding) 10–12 g/dL
Maximum allowed rise	Not >1 g/dL per 2 weeks
Action if Hb >10 g/dL	Reduce dose or discontinue
Onset — reticulocytes	~10 days
Onset — HCT/Hb	~2–6 weeks
Acute anaemia	No use (delayed onset)
Co-supplements	Iron (nearly all CKD); folate (some)

Daprodustat Dosing Tiers

By Baseline Hb (ESA-naïve)

Baseline Hb	Starting dose
<9 g/dL	4 mg daily
9–10 g/dL	2 mg daily
>10 g/dL	1 mg daily
Switching from ESA	4–12 mg daily (based on ESA regimen)

Primary goal: lowest dose sufficient to reduce RBC transfusion need; do not target Hb >11 g/dL.

Anticoagulant Drugs — Mechanism, Monitoring & Reversal

Drug	Mechanism	Monitoring	Reversal & notes
Unfractionated heparin (UFH)	Accelerates antithrombin inhibition of factor Xa + IIa (thrombin)	APTT	Protamine sulphate (t½ ~1h → often just stop infusion). Preferred if high bleeding risk (renal impairment), rapid reversal needed, massive PE post-thrombolysis, or LMWH failing in proximal DVT. SE: bleeding, HIT (rare), osteoporosis (long-term)
LMWH	Low-MW fractions of UFH; mainly anti-Xa	Anti-Xa assay (not usually needed)	Longer t½ → once-daily s.c.; simple weight-based dosing; outpatient DVT; HIT very rare; less reversible by protamine than UFH
Warfarin	Vitamin K antagonist (↓ factors II, VII, IX, X)	PT / INR	Oral, long t½; max effect only after 3–5 days (overlap heparin until then); teratogenic (crosses placenta); many interactions (antibiotics, fluconazole, aspirin). Reverse: vitamin K / PCC (Beriplex)
DOAC — direct thrombin inhibitor	Dabigatran — blocks fibrin-bound + circulating thrombin	None routine	Antidote: idarucizumab
DOAC — factor Xa inhibitors	Rivaroxaban, Apixaban (direct, oral)	None routine	Antidote: andexanet alfa
Fondaparinux	Synthetic pentasaccharide — binds antithrombin → accelerates Xa inhibition (does NOT inhibit thrombin); parenteral s.c.	—	Indirect Xa inhibitor; option in HIT

DOACs/NOACs vs Warfarin

Advantages: wider therapeutic index, faster onset, predictable PK/PD → no routine monitoring, fewer drug interactions
Disadvantages: GI bleeding risk; lecture noted "no specific antidote" (now: idarucizumab / andexanet alfa available)

Anticoagulant Therapy — Categories & Adjuncts

Thrombolysis — indications

Massive PE
Phlegmasia cerulea dolens (PCD) — massive DVT → cold, painful, cyanotic limb; medical emergency (venous gangrene / limb loss); catheter-directed thrombolysis is treatment of choice

IVC filter — indications

Anticoagulation absolutely contraindicated
Recurrent VTE despite adequate anticoagulation
Serious complications of anticoagulant therapy
Free-floating iliofemoral or caval thrombus
Extremely limited pulmonary reserve (may not survive another PE)

Drugs for Anaemia — Haematinic Agents

Iron — Oral

Dose: ~200 mg elemental iron/day in 2–3 divided doses (some extended-release once daily); treat 4–6 months. ~25% of a ferrous salt is absorbed; 50–100 mg incorporated into Hb daily
Kept in reduced ferrous form by gastric acid → absorbed in duodenum
AEs (dose-related, GI): flatulence, abdominal pain, nausea/vomiting, constipation/diarrhoea, metallic taste, tooth staining, dark stools

Oral formulation	Elemental Fe	Note
Ferrous sulphate	20%	Most common; low cost, good tolerability
Ferrous gluconate / fumarate	30%	Higher cost than sulphate
Ferric ammonium citrate	12%	Less elemental Fe, similar tolerability
Carbonyl iron (ER)	100%	Purified microparticles; less toxic (slow release)
Polysaccharide-iron complex (ER)	100%	Tasteless; must be reduced to ferrous in gut

Iron — Parenteral (iron dextran IV/deep IM, ferric gluconate IV, iron sucrose IV)

Give when: cannot tolerate oral iron; advanced CKD on haemodialysis + EPO; post-gastrectomy; small-bowel resection; IBD (proximal small bowel); malabsorption; extensive chronic anaemia not maintained on oral
AE: fatal hypersensitivity/anaphylactoid reactions (esp high-MW iron dextran) → give a test dose first; monitor for iron overload (chelate with deferoxamine)

Folic acid

Dose: 1–5 mg PO daily until cause corrected. Pregnancy prophylaxis 400 mcg/day to prevent fetal neural-tube defects. Also for methotrexate toxicity, chronic haemolysis

Vitamin B12

Hydroxocobalamin preferred (over cyanocobalamin — longer plasma levels). Usually parenteral (most deficiency is malabsorption): IM/deep SC — loading 100–1000 mcg every 1–2 wk, then maintenance 100–1000 mcg IM every 2–3 months for life; if neurological signs → 1–2-weekly × 6 months first

Key rule

Determine the cause of megaloblastic anaemia — do NOT treat with folate alone. Folate alone corrects the anaemia but masks B12 deficiency, which can progress to severe/irreversible neurological dysfunction. Treat with folate + B12

ESAs and Daprodustat (HIF-PH inhibitor) — see their own dosing cards.