ICC-2 Haematology — Disease Index

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

Exam-triage finals revision · 21 disease entries · 18 criteria/scores · derived from TheStudyFix Year 3 ICC-2 Haematology deck (7 lectures)

C/P

Inves

Mng

Special — pathognomonic

A. Approach

1 entries

Haemostasis & bleeding — approach

C/P

Platelet/vessel (primary) defect → SUPERFICIAL/mucocutaneous bleeding: petechiae (<2 mm, non-blanching, not palpable), purpura (2–10 mm), ecchymoses (>10 mm), epistaxis, gum bleeding, menorrhagia, immediate post-cut bleeding
Coagulation-factor (secondary) defect → DEEP bleeding: haemarthrosis, muscle/soft-tissue haematomas, large deep ecchymoses, delayed post-surgical bleeding
"Wet purpura" (oral cavity) = severe thrombocytopenia

Inves

First line: FBC + blood film (platelet count/morphology), PT, APTT, TT ± fibrinogen
Bleeding time — platelet-plug function only (no coag factors); unreliable, rarely done
PFA-100 — platelet function + VWF; not sensitive to vascular collagen disorder
Mixing study (50:50) — corrects → factor deficiency; fails to correct → inhibitor (antibody)
Factor assays when screen/mixing shows a coagulation defect; then VWF studies, aggregometry, flow cytometry

Mng

Directed at the specific disorder (see entries)

Special

PT = extrinsic (VII) + common; APTT = intrinsic (XII, XI, IX, VIII) + common; TT = fibrinogen→fibrin; INR = standardised PT for warfarin
Vitamin K-dependent factors: II, VII, IX, X + protein C + protein S
Cell-based model: initiation (TF+VIIa) → amplification (thrombin activates platelets, V, VIII, XI) → propagation (tenase VIIIa/IXa + prothrombinase Va/Xa → thrombin burst) → termination (XIIIa cross-links fibrin)

B. Platelet & Thrombotic disorders

5 entries

Immune Thrombocytopenia (ITP)

C/P

Isolated thrombocytopenia: petechiae/purpura, mucocutaneous bleeding
NO organomegaly or lymphadenopathy (distinguishes from CLD/malignancy)
Children 5/100,000; adults F>M; Middle East — younger, more female-predominant

Inves

CBC (isolated low platelets) + peripheral smear NORMAL (excludes fragmentation/blasts/hypersegmentation)
Diagnosis of exclusion; TPO paradoxically low
Screen secondary causes: HIV/HBV/HCV, SLE, antiphospholipid, drugs

Mng

Treat if platelets <30×10⁹/L or bleeding; observe if >30 and stable; life-threatening if <10
1st line: corticosteroids (~15 days then taper; max 6 weeks)
IVIG — fast but transient (~4 days), bridging; reduces antibody-mediated splenic destruction
2nd line: TPO-receptor agonists (↑ production), immunosuppressants, splenectomy
Platelet transfusion nearly useless (autoantibody destroys them, lasts 4–6 h) — only for active bleeding/surgery/life-threatening
Refractory = platelets <20×10⁹/L &/or bleeding despite splenectomy

Special

Antiplatelet antibodies → splenic destruction; TPO low despite low platelets

Disseminated Intravascular Coagulation (DIC)

C/P

Simultaneous bleeding + thrombosis; petechiae, purpura, line/venepuncture oozing; microthrombi → ischaemia/organ failure/shock
Triggers: sepsis, obstetric (amniotic fluid embolism, abruption), trauma (head injury, fat embolism), toxins (snake venom), malignancy, transplant rejection

Inves

↑D-dimer, ↓fibrinogen, ↓platelets, ↑PT/APTT/TT; film: schistocytes
Early/hypercoagulable phase may show near-normal counts before consumptive phase

Mng

Treat the underlying cause (critical first step)
Late/bleeding phase: FFP + cryoprecipitate + platelets; do NOT give packed RBCs (dilutes clotting factors)
Early/thrombotic phase: anticoagulation (e.g. COVID)
Coagulation-inhibitor concentrate (antithrombin) in specific settings

Special

Consumption of platelets + factors drives bleeding; fibrinolysis generates FDPs (inhibit fibrin monomers) + D-dimer

Thrombotic Thrombocytopenic Purpura (TTP)

C/P

Microangiopathic haemolytic anaemia + thrombocytopenia; microvascular thrombi

Inves

ADAMTS13 activity <10% = TTP (>10% → other diagnosis); anti-ADAMTS13 IgG positive → autoimmune; gene analysis → inherited (USS)
Film: schistocytes + thrombocytopenia; COOMBS NEGATIVE (differentiates from autoimmune haemolytic anaemia)

Mng

Acquired: daily therapeutic plasma exchange (plasmapheresis) ± steroids until remission; add rituximab if unresponsive/exacerbation
Congenital: plasma transfusion (FFP)
If labs unavailable but Coombs negative + picture fits → treat as TTP

Special

ADAMTS13 deficiency (mutation or autoantibody) → uncleaved ultra-large VWF multimers → unregulated platelet aggregation

Bernard-Soulier Syndrome

C/P

Inherited platelet ADHESION defect → mucocutaneous bleeding

Inves

Blood film: GIANT platelets

Mng

Supportive / platelet transfusion for bleeding

Special

GpIb receptor deficiency (VWF cannot anchor platelet to subendothelium)

Glanzmann Thrombasthenia

C/P

Inherited platelet AGGREGATION defect → mucocutaneous bleeding

Inves

Aggregometry: absent aggregation to most agonists

Mng

Supportive / platelet transfusion for bleeding

Special

GpIIb-IIIa complex deficiency (fibrinogen bridge cannot form between platelets)

C. Coagulation Factor disorders

5 entries

von Willebrand Disease (VWD)

C/P

Most common inherited bleeding disorder; commonest bleeding disorder in women (10% of heavy menstrual bleeders)
Mucocutaneous: bruising, epistaxis, gum bleeding, menorrhagia, post-extraction bleeding; worsen with age

Inves

VWF:Ag (quantity), VWF:RCo / ristocetin cofactor (function), FVIII; APTT prolonged only if FVIII <30 IU/dL
Multimer analysis for subtyping; platelet count normal EXCEPT type 2B (thrombocytopenia)
Ristocetin induces VWF-mediated platelet agglutination (artificial shear-stress mimic)

Mng

Desmopressin (DDAVP) — releases VWF + FVIII from endothelium; SC/IV/intranasal; for most patients + mild haemophilia A (SE: flushing, headache, water retention, hyponatraemia)
VWF/FVIII concentrates (major bleeding/surgery, or DDAVP-unresponsive incl. type 3)
Adjuncts: tranexamic acid (antifibrinolytic), OCP (hormonal); FFP/cryoprecipitate also contain VWF

Special

VWF mediates platelet adhesion via GPIb + carries/stabilises FVIII
Acquired vWS: shearing (aortic stenosis = Heyde syndrome), tumour adsorption (Waldenström), autoimmune inhibitor
Type 2N mimics haemophilia A (↓FVIII binding); type 2B → thrombocytopenia

Haemophilia A

C/P

Deep bleeding: haemarthrosis (70–80% of bleeds → synovitis → haemophilic arthropathy), muscle haematomas, prolonged post-surgical/dental bleeding
Presents: bleeding after circumcision, marked bruising, spontaneous joint bleeds when walking begins
Intracranial haemorrhage — most serious; markedly more frequent; often spontaneous; commonest in neonatal period

Inves

Platelets + PT normal; APTT prolonged; 1:1 mixing corrects (factor deficiency); FVIII activity ≤40%
Anti-FVIII antibodies negative at diagnosis; genetics (F8 inversion in severe cases)

Mng

FVIII concentrate replacement; desmopressin for MILD only; adjuncts: antifibrinolytics, platelets; cure: liver transplant, gene therapy
Prophylaxis (keep FVIII >1 IU/dL, IV 2–3×/week): primary (before age 3 / after first joint bleed) vs secondary
Emicizumab — bispecific antibody bridging FIXa + FX (mimics FVIIIa; works despite inhibitors)
Inhibitors: low-titre (<5 BU) → higher-dose FVIII; high-titre (≥5 BU) → bypassing agent (rFVIIa) or immune tolerance induction (~70% success)

Special

X-linked recessive; F8 gene, Xq28; >99% male; affected father → all daughters obligate carriers
FVIII carried/stabilised by VWF — always order VWF in FVIII deficiency

Haemophilia B

C/P

Clinically identical deep-bleeding phenotype to haemophilia A (joint/muscle bleeds)

Inves

APTT prolonged, corrects on mixing; FIX activity decreased (assay confirms)

Mng

FIX concentrate replacement; prophylaxis as for A

Special

Factor IX deficiency; X-linked recessive; rarer (1 in 30,000 males vs 1 in 5,000 for A)

Liver Disease Coagulopathy

C/P

Bleeding from varices (portal HTN), peptic ulcer, gastritis + generalised coagulopathy

Inves

Prolonged PT + APTT; mild thrombocytopenia (hypersplenism); fibrinogen initially normal (or dysfibrinogenaemia); ↓ vitamin K stores
PT/INR are POOR indicators of liver function/bleeding risk (anticoagulant factors also low)

Mng

Vitamin K 10 mg (often ineffective — synthesis is the problem)
FFP 12–15 mL/kg or prothrombin complex concentrate (immediate, temporary)
Low fibrinogen → cryoprecipitate / fibrinogen concentrate

Special

Liver makes both procoagulant factors AND anticoagulants (antithrombin III, protein C/S) + clears activated factors → can be hypercoagulable, predisposes to DIC
Mechanisms: ↓ factor synthesis, dysfibrinogenaemia, ↑ fibrinolysis, DIC, hypersplenic thrombocytopenia

Vitamin K Deficiency

C/P

Bleeding tendency; haemorrhagic disease of the newborn (low stores at birth, sterile gut)

Inves

Prolonged PT (more prominent) ± APTT

Mng

Vitamin K replacement (FFP/PCC if acute bleeding)

Special

Cofactor for II, VII, IX, X + protein C + protein S
Causes: obstructive jaundice (no bile salts → no fat-soluble vitamin absorption), chronic diarrhoea, liver disease, newborns

D. Transfusion Medicine

10 entries

Acute Haemolytic Transfusion Reaction (AHTR)

C/P

Onset during / immediately after transfusion
Chills + fever; hypotension + tachycardia
Heat / pain in the vein at the infusion site; constricting chest pain; loin (lumbar) back pain
Uncontrolled bleeding (DIC); haemoglobinuria; hyperbilirubinaemia

Inves

Intravascular haemolysis: haemoglobinaemia / haemoglobinuria, ↓ haptoglobin
"Ghost cells" (empty RBC membranes) on film; DAT positive; recheck component vs patient ID

Mng

STOP transfusion immediately → acute-reaction protocol (keep line open with saline)
ABO incompatibility may require haemofiltration

Special

Cause = ABO incompatibility → intravascular haemolysis (usually IgM/complement)
Underlying cause almost always clerical / misidentification error (wrong blood in tube ≈1:2,000–4,000) — the commonest cause of a fatal acute haemolytic reaction
Most dangerous acute reaction

Delayed Haemolytic Transfusion Reaction (DHTR)

C/P

Days–weeks after transfusion: falling Hb, jaundice, low-grade fever

Special

Anamnestic response — alloantibody to a minor RBC antigen (e.g. Kidd, Rh) that was below detection at crossmatch
Extravascular haemolysis; DAT becomes positive (delayed immune reaction)

TRALI (Transfusion-Related Acute Lung Injury)

C/P

Acute hypoxia + bilateral pulmonary infiltrates within 4 h of a component
NO evidence of heart failure; not easily distinguished from ARDS

Mng

Supportive / ITU, high-flow O₂; life-threatening (death 30–50%)

Special

Antibodies (often anti-HLA) in the transfused product vs recipient WBC (50–70%) → pulmonary capillary leak
Implicated donors: parous women

Anaphylactic Transfusion Reaction

C/P

Rare but life-threatening; more risk with plasma-containing components

Mng

Stop; adrenaline, steroids, bronchodilators, high-flow O₂

Special

IgA-deficient patient with anti-IgA antibodies (classic); IgE (occasionally IgG) to a specific allergen
Anaphylactoid (milder) — e.g. donor ate something the recipient is allergic to

Post-Transfusion Purpura (PTP)

C/P

Usually female patients; 5–12 days after transfusion
Severe thrombocytopenia + bleeding

Special

Platelet-specific alloantibodies → immune-mediated thrombocytopenia (delayed immune reaction)

TA-GvHD

C/P

Onset 4 days – 6 weeks post-transfusion
Fever, skin rash, pancytopenia, liver failure, renal failure

Mng

Usually fatal (mortality 75–90%); no effective treatment → prevention with irradiated blood

Special

Donor T-cells attack the recipient (recipient often immunodeficient)

Bacterial Contamination / Infective Shock

C/P

Rigors, fever, shock — usually during transfusion of the first 100 ml; high mortality

Mng

Stop; blood cultures; broad-spectrum antibiotics; resuscitate (acute-reaction protocol)

Special

Platelets >> RBC > FFP (platelets stored at room temp)
Precautions: check for tears/pinholes, correct storage temp, use within 6 h of leaving fridge, don't pre-warm, inspect for haemolysis

Transfusion-Associated Iron Overload

C/P

Chronically transfused (transfusion-dependent) patients — e.g. thalassaemia

Special

200 mg Fe per unit of packed RBC (non-immune reaction)
Major cause of morbidity & mortality in transfusion-dependent disease

Haemolytic Disease of the Newborn (HDN)

C/P

Neonatal alloimmune disorder (Rh disease of the newborn): fetal/neonatal haemolytic anaemia, jaundice

Special

Maternal alloantibody (classically anti-D) crosses the placenta → fetal RBC haemolysis
Classified with the delayed immune transfusion reactions; prevented by anti-D prophylaxis

Acquired Haemolytic Anaemia (overview)

C/P

Features of haemolysis: anaemia, reticulocytosis (polychromasia), macrocytosis, unconjugated hyperbilirubinaemia, morphological change (spherocytes / fragments)

Inves

Intravascular: haemoglobinaemia / haemoglobinuria, ↓ haptoglobin (sensitive), methaemalbumin (Schumm's test +), urinary haemosiderin
Extravascular: RES uptake of damaged RBC; marrow hypertrophy/hyperplasia

Special

Immune (autoimmune, alloimmune, hyperhaemolysis) vs non-immune (hypersplenism, PNH, renal/liver disease, chemicals/toxins/infections)
Intravascular usually IgM or complement (cf PNH, ABO-incompatible transfusion)

Bleeding Patterns & Tests

3 entries

Platelet/VWF vs Coagulation-factor bleeding

Platelet / VWF disorder

Site: skin, mucous membranes, epistaxis, GI/GU
Petechiae YES; small superficial ecchymoses
Haemarthrosis rare; bleeds after cuts
Post-op usually mild + immediate

Coagulation factor (haemophilia)

Site: deep soft tissue, joints, muscles
Petechiae NO; large deep ecchymoses
Haemarthrosis common; no bleeding after minor cuts
Post-op often severe + delayed

Clotting-time interpretation

PT prolonged only → Factor VII
APTT prolonged only → Factor VIII, IX, or XI (or XII/contact — clinically insignificant, no bleeding)
Both PT + APTT → common pathway (II, V, X) or fibrinogen
TT prolonged → fibrinogen (low/abnormal) or heparin

Platelet count thresholds

<10×10⁹/L — spontaneous bleeding risk
>30 + stable — observe
>80 — bleeding or pre-op; >100 — bleeding into eye or brain
Transfusion targets: >10 (prophylaxis/chemo); >80 (pre-op/bleeding); >100 (eye or brain)

Severity & Classification

3 entries

Haemophilia severity (by factor level)

Severe <1 IU/dL (<1%) — spontaneous joint/muscle bleeds
Moderate 1–<5 IU/dL — bleeding with mild injury
Mild 5–40 IU/dL — bleeding with surgery/trauma
Normal factor range 50–150 IU/dL

VWD classification

Type 1 — mild quantitative (AD, incomplete penetrance); ↓VWF:Ag, Ag=Ac; DDAVP + tranexamic acid
Type 2 — qualitative (AD/AR); Ag>Ac, abnormal multimers; DDAVP + tranexamic acid + concentrate
Type 3 — severe quantitative (AR); near-absent VWF; concentrate

Type 2 subtypes

2A — loss of high-molecular-weight multimers
2B — ↑GPIb binding → thrombocytopenia
2M — preserved multimers
2N — ↓FVIII binding (mimics haemophilia A)

ITP phases

Newly diagnosed <3 months
Persistent 3–12 months
Chronic >1 year
Refractory = <20×10⁹/L &/or bleeding despite splenectomy

Reference

3 entries

Coagulation complexes

Extrinsic tenase: VIIa + TF + PL + Ca → Xa
Intrinsic tenase: IXa + VIIIa + PL + Ca → Xa
Prothrombinase: Xa + Va + PL + Ca → thrombin (IIa)

Blood products & transfusion

Products (from whole blood)

Packed RBCs · FFP (frozen plasma) · cryoprecipitate (fibrinogen, VWF, FVIII, XIII) · PCC (prothrombin complex concentrate) · single-factor concentrates

Transfusion basics

ABO: iso-agglutinins (anti-A/anti-B); Bombay (hh) phenotype; Rh D typing
Pre-transfusion = grouping + antibody screen + crossmatch (indirect antiglobulin test)

Vitamin K-dependent factors

Factors II, VII, IX, X + protein C + protein S
Deficiency prolongs PT (more prominent) ± APTT

Transfusion Medicine

9 entries

ABO / RhD Compatibility — Red Cells & Plasma

Red cells (give antigen the patient lacks-safe)

Patient	Can receive RBC from
A	A, O
B	B, O
O	O only
AB	AB, A, B, O (universal recipient)
RhD +	RhD + or −
RhD −	RhD − only

Plasma (FFP / cryo — OPPOSITE to red cells)

Patient	Can receive plasma from
A	A, AB
B	B, AB
O	O, A, B, AB (universal recipient for plasma)
AB	AB only (universal plasma donor)

O negative = universal RBC donor · AB = universal plasma donor · RhD irrelevant for plasma

Blood Components — Specs & Indications

Component	Storage / shelf-life	Dose	Indications
Red cells	4°C / 35 days (~280 ml/unit)	3 ml/kg ↑ Hb by 1 g/dL	Active bleeding; marrow failure; suppress/exchange abnormal cells (thalassaemia, sickle); rarely haematinic deficiency. Hb triggers: <70 g/L strong indication · 70–100 grey zone (transfuse if symptomatic / poor cardiopulmonary reserve) · >100 not indicated · critical care 70 (90 if cardiac)
Platelets	22°C agitated / 7 days (bacterial risk)	10 ml/kg or 1 pool; know group, no crossmatch	Thresholds: bleeding/pre-op >80, eye/brain >100, marrow failure >10, neonates >30; platelet dysfunction (e.g. bypass)
FFP	−30°C / 1 year; thaw & give within 1 h	12–15 ml/kg (≈2–3 units); same group, no x-match	Bleeding + abnormal PT/APTT; warfarin reversal for urgent surgery. NOT for volume
Cryoprecipitate	−30°C / 1 year	From 10 donors	Massive bleeding + very low fibrinogen (contains fibrinogen + factor VIII)

Special Blood Requirements

Irradiated → prevents TA-GvHD (inactivates donor T-lymphocytes): BMT, Hodgkin, DiGeorge, fludarabine
CMV-negative → prevents CMV transmission: pregnancy, intrauterine transfusion, neonates
Washed / plasma-depleted → removes plasma proteins: IgA deficiency, severe allergic history
Phenotype-matched → prevents alloimmunisation in chronic transfusion (sickle, thalassaemia) — match Rh + Kell
Young blood → less K⁺ leak, longer viability

Major Haemorrhage — Definitions

Any one of:

Entire blood volume replaced in 24 h
>8–10 units packed RBC in 24 h
>50% of blood volume lost in 3 h
Blood loss ≥150 ml/min
≥4 units RBC in 1 h + ongoing bleeding
Anticipated ≥8 units in 2 h

Deaths from major haemorrhage are often preventable.

Transfusion Reaction Classification

Immune — acute

Acute haemolytic (AHTR) · TA-GvHD · anaphylactic

Immune — delayed

Delayed haemolytic (DHTR) · post-transfusion purpura · HDN (Rh disease of newborn)

Non-immune

Infective (bacterial / viral / prion) · iron overload · (TRALI — antibody-mediated lung injury)

Acute Transfusion Reaction — Management

STOP transfusion, keep IV line open with saline
Urgent medical review ± ITU; tell blood bank + haematology transfusion registrar
Check component vs patient ID; take blood cultures; send component to lab
Monitor temp, pulse, BP, RR, O₂ sats (± blood gases), urine output
ABO incompatibility → may need haemofiltration
Steroids, adrenaline ± inotropes, bronchodilators, high-flow O₂, antibiotics as indicated

Pretransfusion Testing

Forward group: patient RBC + anti-A / anti-B (antigen typing)
Reverse group: patient serum + known A / B cells (confirms the naturally-occurring antibodies)
Antibody screen (IAT): patient serum vs panel cells — detect atypical RBC antibodies
Crossmatch: immediate-spin (ABO check) or full IAT crossmatch; electronic crossmatch if antibody screen negative
DAT = antibody already bound to patient RBC in vivo; IAT = antibody free in serum

Blood Provision by Urgency

Urgency	Product
Extreme emergency	O-negative emergency stock ("flying squad") — instant, no testing
Urgent	Group-specific — ABO/Rh matched, no full crossmatch (minutes)
Standard	Fully crossmatched — full compatibility testing (longest, safest)

Decide with the on-call haematologist + blood bank

Thrombocytopenia — Causes by Mechanism

↓ Production: bone-marrow failure / suppression (→ often pancytopenia)
↑ Destruction: immune (ITP) or non-immune (DIC, TTP/HUS)
Sequestration: splenomegaly / hypersplenism (+ pancytopenia)
Dilution: massive transfusion
Gestational: physiological, usually third trimester