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📚 Haematology Study Guide - Important Topics

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1. LEUKAEMIA

Classification:

Key Clinical Features:

• Symptoms: Fatigue, pallor, fever, bleeding, recurrent infections, bone pain
• Signs: Lymphadenopathy, splenomegaly, hepatomegaly
• Diagnosis: Blood film + bone marrow examination

Pulmonary Involvement (Leukaemia):

• Leukaemic infiltration found at autopsy in ~2/3 of patients
• Usually asymptomatic - rarely visible on CXR
• Leukostasis (in AML): WBC >100,000-300,000 cells/mm³ - leukaemic cells obliterate small pulmonary vessels causing dyspnoea
• T-cell leukaemias: massive mediastinal adenopathy that responds rapidly to chemo/radiotherapy
• Granulocytic sarcoma (chloroma): pleural mass of myeloid leukaemia cells - named for its green appearance

Robbins & Kumar Basic Pathology; Grainger & Allison's Diagnostic Radiology

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2. ANAEMIA

Classification by Mechanism:

Classification by MCV:

• Microcytic (MCV <80 fL): Iron deficiency, thalassaemia, chronic disease
• Normocytic (MCV 80-100 fL): Acute blood loss, haemolysis, chronic disease
• Macrocytic (MCV >100 fL): B12/folate deficiency, liver disease, hypothyroidism

Clinical Features:

• Pallor, fatigue, exertional dyspnoea, palpitations, tachycardia
• Severe: angina, heart failure

Pye's Surgical Handicraft; Bailey and Love's Short Practice of Surgery

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3. PURPURA

Classification:

• Trauma, solar/senile purpura, steroid purpura, stasis purpura
• Systemic causes: Thrombocytopenia (ITP), abnormal platelet function, clotting factor defects

• Leukocytoclastic vasculitis, HSP (Henoch-Schonlein Purpura)

Important Systemic Causes:

ITP (Immune Thrombocytopenic Purpura):

• Antiplatelet IgG autoantibodies against platelet membrane glycoproteins
• Acute (children): follows viral infection, self-resolving
• Chronic (adults): persists >6 months; mainly females aged 15-50 years; associated with SLE
• Treatment: corticosteroids, IVIG, splenectomy

Harrison's Principles of Internal Medicine 22E; Andrews' Diseases of the Skin; Bailey and Love

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4. HODGKIN LYMPHOMA (HL)

Reed-Sternberg Cells:

• Large cells with abundant cytoplasm and multiple or bilobed nuclei ("owl-eye" appearance)
• Classic HL: CD15+ and CD30+ (B and T cell antigens usually negative)
• Lymphocyte-predominant HL (LPHL): CD20+, CD45+, CD15-

Clinical Features:

• Bimodal age distribution: 15-40 years (young adults) and >55 years
• Presents with painless peripheral adenopathy - most commonly cervical and supraclavicular
• B symptoms (in ~25% of patients):
  • Fever >38°C (persistent)
  • Drenching night sweats
  • Unexplained weight loss >10% body weight in 6 months
• Severe generalised pruritus - more common in HL than NHL, often precedes diagnosis by months
• B symptoms + pruritus are due to cytokine production by R-S cells

Ann Arbor Staging (Cotswolds Modification):

• "B" suffix: B symptoms present
• "E" suffix: contiguous extranodal involvement
• "X": bulky disease (>1/3 mediastinal widening or >10 cm nodal mass)

Treatment:

• ABVD chemotherapy (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) ± radiotherapy
• Excellent prognosis - one of the most curable malignancies

Cummings Otolaryngology Head & Neck Surgery

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5. THALASSAEMIA

Types:

Pathophysiology:

• Reduced chain synthesis → intracellular precipitates called Heinz bodies → premature RBC destruction
• Severity: Heterozygous = thalassaemia minor (mild/carrier); Homozygous = thalassaemia major (severe)

Thalassaemia Major (Cooley's Anaemia / Mediterranean Anaemia):

• Chronic anaemia, jaundice, splenomegaly
• Retarded growth
• Enlarged head with slanting eyes and depressed nose (due to extramedullary haematopoiesis)
• Leg ulcers, abdominal distension

• Microcytic, hypochromic red cells
• Small, thin, misshapen RBCs with resistance to osmotic lysis
• Nucleated RBCs + other immature blood cells in severe forms

• Blood transfusions (may become transfusion-dependent)
• Splenectomy: for hypersplenism requiring frequent transfusions or when haemolytic antibodies develop
• Iron chelation (desferrioxamine) to prevent transfusion iron overload
• Bone marrow transplant (curative)

Bailey and Love's Short Practice of Surgery; Grainger & Allison's Diagnostic Radiology

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6. SICKLE CELL ANAEMIA

Pathophysiology:

• Point mutation: Glutamic acid → Valine at position 6 of the beta-globin chain
• Under low oxygen tension: HbS crystallises → distorts and elongates the RBC into a sickle shape
• Consequences: increased blood viscosity → microvascular occlusion → ischaemia and infarction

Epidemiology:

• Mainly those of African origin
• Sickle cell trait (HbAS carrier): 9% of Africans - usually asymptomatic
• Sickle cell disease (HbSS): ~1% of Africans

Clinical Features (Vaso-occlusive Crises):

Diagnosis:

• Blood film: sickle-shaped cells
• Haemoglobin electrophoresis (gold standard - has largely replaced blood film)

Treatment:

• Hydroxyurea (increases HbF production)
• Prophylactic penicillin + vaccinations (due to functional asplenia)
• Analgesia for crises; IV fluids, O₂
• Blood transfusion for severe crises
• Bone marrow transplant (curative)

Bailey and Love's Short Practice of Surgery

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7. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

Paradox of DIC:

• Excessive clotting AND bleeding coexist in the same patient
• More commonly causes bleeding than all congenital coagulation disorders combined

Pathogenesis (2 main triggers):

1. Release of tissue factor / procoagulants into circulation:
   • Obstetric complications (amniotic fluid embolism, abruptio placentae)
   • Cancer cells (especially acute promyelocytic leukaemia, adenocarcinoma)
   • Bacterial sepsis (endotoxins stimulate tissue factor on monocytes → IL-1 + TNF → tissue factor on endothelium + downregulation of thrombomodulin)
2. Widespread endothelial injury:
   • Antigen-antibody complexes (SLE)
   • Temperature extremes (heat stroke, burns)
   • Infections (meningococci, rickettsiae)

Result:

• Microvascular thrombi → ischaemic tissue damage
• Consumption of platelets + clotting factors → bleeding
• Secondary fibrinolysis → fibrin split products → inhibit thrombin, platelet aggregation, fibrin polymerization → further bleeding
• Microangiopathic haemolytic anaemia (RBCs sheared by fibrin strands)

Labs:

Causes (mnemonic - STOP Making New Thrombi):

• Sepsis (most common)
• Trauma / massive tissue injury
• Obstetric emergencies (abruption, eclampsia, amniotic fluid embolism)
• Promyelocytic leukaemia (M3 AML)
• Malignancy
• Necrotising pancreatitis
• Transfusion reactions

Robbins & Kumar Basic Pathology, p.427

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8. BLOOD GROUPING (ABO System)

Molecular Basis:

• All individuals produce a common core glycan
• H antigen: core glycan + fucose (added by fucosyltransferase) - the precursor
• A allele: adds terminal N-acetylgalactosamine to H antigen → A antigen
• B allele: adds terminal galactose to H antigen → B antigen
• O allele: no enzymatic activity → only H antigen expressed

Blood Group Summary:

Why Do We Have Natural Antibodies?

• Anti-A and Anti-B antibodies form against glycolipids of intestinal bacteria that cross-react with ABO antigens
• Individuals are tolerant to their own antigens - they only make antibodies against the antigens they lack

Special Note - Bombay Blood Group (hh):

• Rare mutation in fucosyltransferase gene → cannot produce H antigen
• Result: cannot produce H, A, or B antigens
• Makes antibodies against H, A, and B - incompatible with all standard blood groups

Rh System:

• D antigen is the most clinically significant
• Rh+ = D antigen present; Rh- = absent
• Anti-D antibodies are immune (not naturally occurring) - form after exposure to Rh+ blood
• Critical in: haemolytic disease of the newborn (HDN/erythroblastosis fetalis)

Cellular and Molecular Immunology; Histology: A Text and Atlas; Emery's Elements of Medical Genetics and Genomics

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Quick Comparison Table

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🩸 Blood Disorders - Simply Explained

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1. 🔴 ANAEMIA - "Not Enough Good Blood"

Why does it happen?

• Not making enough RBCs - lack of iron, B12, folate, or bone marrow problems
• Destroying RBCs too fast - sickle cell, thalassaemia, immune attack
• Losing blood - bleeding from ulcer, heavy periods, injury

Symptoms (all make sense when you understand "less oxygen delivery"):

• Tired all the time 😴
• Pale skin, pale inner eyelids
• Breathless on exertion
• Fast heartbeat
• Headache, dizziness

Quick Test:

• Check Haemoglobin (Hb) - low = anaemia
• Check MCV (size of RBCs):
  • Small RBCs = iron deficiency or thalassaemia
  • Normal RBCs = bleeding or chronic disease
  • Big RBCs = B12/folate deficiency

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2. ⚪ LEUKAEMIA - "Blood Cancer"

Types - easy way to remember:

• Acute = immature cells (blasts) - more dangerous, needs urgent treatment
• Chronic = more mature cells - slower progression

Why do patients get sick?

• ❌ Not enough RBCs → anaemia (tired, pale)
• ❌ Not enough platelets → bleeding, bruising
• ❌ Not enough normal WBCs → recurrent infections
• ✅ Too many useless white cells → swollen lymph nodes, enlarged liver/spleen

Diagnosis: Blood film + Bone marrow biopsy

Treatment: Chemotherapy (targeted therapy for CML - Imatinib/Gleevec)

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3. 🟣 PURPURA - "Blood Spots Under the Skin"

Two main types:

• Small spots = petechiae
• Larger patches = ecchymosis (bruise)
• Cause: too few platelets (thrombocytopenia) or clotting problem

• You can feel them
• Cause: vasculitis (inflamed blood vessels)

Most Important Cause - ITP (Immune Thrombocytopenic Purpura):

• Your immune system makes antibodies that attack your OWN platelets
• Kids: after a viral infection → usually gets better on its own
• Adults (usually young women): becomes chronic (>6 months)
• Platelets are low, but PT and aPTT are normal (clotting factors are fine)
• Treatment: Steroids first → IVIG → Splenectomy (spleen is where platelets are being destroyed)

Rule to remember:

Purpura = bleeding into skin = does NOT blanch on pressure ✅ Red rash from inflammation = DOES blanch on pressure ❌

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4. 🎗️ HODGKIN LYMPHOMA - "Cancer of Lymph Nodes with an Owl-Eye Cell"

The STAR of this disease - Reed-Sternberg Cell:

• Huge cell with two big nuclei that look like owl eyes 🦉
• This is the diagnostic cell - if you see it in a biopsy, it's Hodgkin
• It releases cytokines that cause most of the symptoms

Who gets it?

• Young adults (15-40 years) - or elderly (>55)
• Starts in the neck/supraclavicular lymph nodes

Classic Symptoms:

• Painless swollen lymph nodes (usually neck)
• B symptoms:
  • Fever >38°C
  • Drenching night sweats
  • Weight loss >10% in 6 months
• Itch (pruritus) - often the first clue, months before diagnosis
• Pain in lymph nodes after drinking alcohol (unique to Hodgkin!)

Staging - Ann Arbor System:

• Stage I = one area
• Stage II = two areas, same side of diaphragm
• Stage III = both sides of diaphragm
• Stage IV = organs involved (liver, bone marrow, lungs)
• Add "B" if B symptoms present

Treatment: ABVD chemotherapy ± radiotherapy

Prognosis: EXCELLENT - one of the most curable cancers 🎉

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5. 🧬 THALASSAEMIA - "Broken Haemoglobin Factory"

The chains of Haemoglobin:

• Normal adult Hb (HbA) = 2 alpha chains + 2 beta chains
• Beta-thalassaemia = can't make enough beta chains (most common)
• Alpha-thalassaemia = can't make enough alpha chains

Severity:

Thalassaemia Major - what happens:

• Severe anaemia from first year of life
• The bone marrow works overtime trying to make RBCs → bones expand → characteristic facial features:
  • Large head
  • Prominent cheekbones
  • Slanting eyes, depressed nose bridge
  • "Chipmunk facies"
• Jaundice (from RBC destruction)
• Massive splenomegaly (spleen trying to clear broken RBCs)
• Growth retardation
• Leg ulcers

The broken RBCs:

• Unmatched chains form Heinz bodies (clumps inside RBC) → premature destruction
• RBCs are small, thin, misshapen
• Resistant to osmotic lysis (important lab finding)

Diagnosis: Haemoglobin electrophoresis (shows HbF↑, HbA2↑, HbA↓)

Treatment:

• Regular blood transfusions (but patient can become dependent)
• Iron chelation (desferrioxamine) - transfusions load the body with iron
• Splenectomy if hypersplenism or haemolytic antibodies develop
• Bone marrow transplant = only cure

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6. 🌙 SICKLE CELL ANAEMIA - "Blood Cells That Turn Into Sickles"

The Mutation (dead simple):

• One letter change in DNA
• Glutamic acid → Valine at position 6 of beta-globin chain
• This makes HbS instead of HbA
• Under low O₂: HbS crystallises → RBC becomes a sickle

Who gets it?

• Mainly people of African origin
• Trait (HbAS): one copy - usually no symptoms, slight protection against malaria
• Disease (HbSS): two copies - full disease

What goes wrong (Vaso-occlusive Crisis):

Key Complication: Autosplenectomy

• Repeated splenic infarcts destroy the spleen
• Patient becomes functionally asplenic → vulnerable to encapsulated bacteria (Pneumococcus, Meningococcus, Haemophilus)
• These patients MUST be on prophylactic penicillin + vaccines

Diagnosis: Sickle cells on blood film → confirmed by haemoglobin electrophoresis

Treatment:

• Hydroxyurea - increases HbF (fetal haemoglobin) which doesn't sickle - best medical treatment
• Analgesia + IV fluids + O₂ for crises
• Prophylactic penicillin + vaccinations
• BMT = only cure

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7. ⚡ DIC - "The Body That's Trying to Clot AND Bleed at the Same Time"

What is it?

• Normally, clotting is a local, controlled process
• In DIC, something triggers whole-body clotting activation at once
• All the clotting factors and platelets get used up
• Then when you actually need to clot, you CAN'T → you BLEED

The Paradox:

Clotting + Bleeding happening at the SAME time in the same patient

What triggers it?

• Sepsis (most common - bacteria release endotoxins)
• Obstetric emergencies (amniotic fluid embolism, placental abruption, eclampsia)
• Trauma / burns (tissue factor release)
• Acute Promyelocytic Leukaemia (M3-AML - cancer cells release procoagulants)
• Cancer (mucin-secreting adenocarcinomas)
• Transfusion reactions

What happens step by step:

1. Trigger activates tissue factor everywhere
2. Widespread microvascular clots form → organs get ischaemic damage
3. Clotting factors + platelets all get consumed
4. Fibrinolysis (clot-busting) gets activated → fibrin split products form
5. These split products inhibit further clotting → massive BLEEDING
6. RBCs get chopped up passing through fibrin strands → microangiopathic haemolytic anaemia (schistocytes on blood film)

Lab Findings (everything is deranged):

Treatment:

• Treat the underlying cause (most important!)
• FFP (fresh frozen plasma) - replaces clotting factors
• Platelet transfusion
• Cryoprecipitate (for fibrinogen)
• Heparin in some cases (controversial)

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8. 🅰️🅱️ BLOOD GROUPING - "Your Blood's ID Card"

ABO System - The 4 Flags:

How the flags are made (simple chemistry):

• Everyone starts with a base "H antigen"
• Gene A adds a sugar → makes A antigen
• Gene B adds a different sugar → makes B antigen
• Gene O does nothing → only H antigen remains

Why do you have antibodies against flags you've never been transfused with?

• Because gut bacteria have similar sugars on their surface
• Your immune system accidentally makes antibodies against the ABO antigens it doesn't have (via cross-reaction with bacteria)
• So Anti-A and Anti-B are naturally occurring - you have them from birth

Bombay Blood Group (hh) - Super Rare:

• Can't even make the H antigen (the base)
• So can't make A, B, or O antigens
• Makes anti-H, anti-A, and anti-B antibodies
• Incompatible with ALL normal blood groups
• Must receive blood from other Bombay donors only

Rh System:

• D antigen = most important after ABO
• Rh+ (most people) = have D antigen
• Rh- = no D antigen
• Danger: Rh- mother carrying Rh+ baby
  • During delivery, baby's blood enters mother's circulation
  • Mother makes Anti-D antibodies
  • In next pregnancy, Anti-D crosses placenta → attacks baby's RBCs → Haemolytic Disease of the Newborn (HDN)
  • Prevented by giving Anti-D immunoglobulin to Rh- mothers

Before Transfusion - 3 Steps:

1. ABO + Rh typing (which group is the patient?)
2. Antibody screen (does patient have unexpected antibodies?)
3. Cross-match (mix donor RBCs with patient serum - no reaction = safe to transfuse)

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🧠 The Big Picture - How They All Connect

BLOOD DISORDERS

├── Too FEW RBCs → ANAEMIA
│     ├── Production problem → Iron deficiency, B12, thalassaemia
│     ├── Destruction → Sickle cell, thalassaemia, DIC
│     └── Blood loss → Haemorrhage
│
├── WRONG RBCs → SICKLE CELL & THALASSAEMIA
│     ├── Wrong shape (sickle) → blocks vessels → pain crises
│     └── Wrong chains (thalassaemia) → fragile cells → haemolysis
│
├── White cell CANCER → LEUKAEMIA
│     └── Crowds out good cells → anaemia + bleeding + infections
│
├── Lymph node CANCER → HODGKIN LYMPHOMA
│     └── Reed-Sternberg cells, B symptoms, owl-eye nuclei
│
├── BLEEDING into skin → PURPURA
│     └── Low platelets (ITP) or vasculitis
│
└── System-wide CLOTTING CHAOS → DIC
      └── Triggered by sepsis/trauma/cancer
          └── Clot everywhere + bleed everywhere

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🔑 The 10 Most Exam-Important Facts

1. Anaemia - MCV tells you the cause (small=iron/thal, big=B12/folate)
2. Leukaemia - blasts on bone marrow; acute=more aggressive
3. Purpura = does NOT blanch on pressure
4. ITP - low platelets only; PT/aPTT normal; treat with steroids first
5. Hodgkin Lymphoma - Reed-Sternberg cells (CD15+, CD30+); B symptoms; excellent prognosis
6. Thalassaemia major - chipmunk facies + splenomegaly + Heinz bodies; diagnosed by Hb electrophoresis
7. Sickle cell - HbS crystallises under low O₂; autosplenectomy → needs penicillin prophylaxis; hydroxyurea is treatment
8. DIC - consumptive coagulopathy; ↑PT, ↑aPTT, ↓platelets, ↓fibrinogen, ↑D-dimers, schistocytes
9. Blood group O = universal donor; AB = universal recipient
10. Bombay group = can't make H antigen; incompatible with all normal blood

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