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🩸 Hematology Exam Notes - From Robbins Pathology

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1. ANEMIA

Definition

Classification by Cause

Classification by RBC Size

• Microcytic (low MCV): Iron deficiency, thalassemia
• Macrocytic (high MCV): Folate or B12 deficiency; also elevated reticulocyte count
• Normocytic: Hereditary spherocytosis, sickle cell disease (shape changes visible on smear)

Clinical Features

• Acute anemia: Shortness of breath, organ failure, shock
• Chronic anemia: Insidious pallor, fatigue, lassitude
• Extravascular hemolysis: Jaundice + gallstones
• Ineffective erythropoiesis: Iron overload → heart and endocrine failure
• Severe congenital anemia: Growth retardation + bone deformities from marrow hyperplasia

Key Hemolytic Anemias Summary

Source: Robbins & Kumar Basic Pathology, block4 ~p.433

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2. SICKLE CELL ANEMIA

Genetics

• Autosomal recessive - mutation in β-globin gene
• Substitution: Valine replaces glutamic acid at position 6 of β-globin
• Result: HbS instead of HbA; on deoxygenation → HbS polymerizes

Epidemiology

• Most common familial hemolytic anemia
• Prevalent in equatorial Africa, India, Southern Europe, Middle East - areas where falciparum malaria is endemic
• Protective against falciparum malaria (hence high allele frequency)
• US: ~8% of African-descent individuals are HbS carriers; ~1 in 600 have sickle cell anemia

Pathogenesis

1. Deoxygenation → HbS polymers form via intermolecular contacts at abnormal valine residue
2. Polymers distort RBC → elongated crescentic (sickle) shape
3. Initially reversible on reoxygenation, but repeated sickling → calcium influx → loss of K+ and water → membrane damage → irreversibly sickled cells

Three Factors Determining Severity

1. Level of other hemoglobins: HbF and HbA inhibit HbS polymerization (heterozygotes rarely sickle; newborns protected until HbF falls ~5-6 months)
2. MCHC (mean corpuscular Hb concentration): Higher concentration = more polymerization
3. Transit time through microcirculation: Longer transit → more sickling

Peripheral Blood Smear

Complications

• Vaso-occlusive crises: Pain crises, tissue infarction, stroke, acute chest syndrome
• Hemolytic anemia with jaundice, pigment gallstones
• Bacterial infections: Functional asplenia (autoinfarction of spleen) → susceptible to encapsulated organisms (Streptococcus pneumoniae, H. influenzae)
• Aplastic crisis: Parvovirus B19 infection
• Splenic sequestration crisis: Acute pooling of blood in spleen

Heterozygotes (Sickle Cell Trait)

• ~40% HbS, 60% HbA - very little in vivo sickling
• Generally asymptomatic but can manifest under extreme hypoxia

Source: Robbins & Kumar Basic Pathology, block4 lines 1695-1764

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3. THALASSEMIA

Definition

1. Hemoglobin deficiency
2. Intracellular precipitates from excess unpaired normal globin chains → RBC damage + hemolysis

Genetics

• Endemic in Mediterranean, Africa, Asia (malaria belt - similar protective mechanism as HbS)
• β-globin: Single gene on chromosome 11 (point mutations)
• α-globin: Two genes in tandem on chromosome 16 (gene deletions)

β-Thalassemia Classification

α-Thalassemia Classification

Molecular Mutations

• β-thalassemia: Mainly point mutations affecting transcription, splicing, or translation of β-globin mRNA
• α-thalassemia: Mainly gene deletions

Pathophysiology of β-Thal Major

1. Deficient β-chain synthesis → excess α chains precipitate in RBC precursors → ineffective erythropoiesis in marrow
2. Those cells that leave marrow are destroyed in spleen → hemolysis
3. Erythroid marrow hyperplasia → "crew-cut" skull X-ray, "chipmunk facies," bone thinning
4. Chronic hemolysis → hepatosplenomegaly (extramedullary hematopoiesis)
5. Repeated transfusions → iron overload → hemosiderosis affecting heart, liver, endocrine organs

Source: Robbins & Kumar Basic Pathology, block4 lines 1765-1850

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4. LEUKAEMIA

Overview

Acute Lymphoblastic Leukemia/Lymphoma (ALL)

• Neoplasms of immature B or T cells (lymphoblasts)
• 85% are B-ALL (childhood acute leukemia)
• T-ALL: Adolescent males, often as thymic mass
• Most common cancer in children (~2500 new cases/year US, peak age ~3 years for B-ALL)

• Chromosomal aberrations in ~90%: most common is hyperploidy (>50 chromosomes)
• Key mutations: NOTCH1 (T-ALL), PAX5, TCF3, ETV6, RUNX1, BCR::ABL1 (B-ALL)
• Philadelphia chromosome [t(9;22)] → BCR::ABL1 fusion → most important adverse prognostic factor
• Mutations disturb "master" regulatory transcription factors → maturation arrest + self-renewal

• Fatigue, fever, bleeding (marrow failure → anemia, thrombocytopenia, neutropenia)
• Bone pain (marrow expansion)
• Lymphadenopathy, hepatosplenomegaly
• CNS involvement (headache, nerve palsies)

Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL)

• Most common leukemia of adults in Western world
• CLL = >5000 lymphocytes/µL in blood; SLL = predominantly lymph node involvement (4% of NHLs)
• Indolent - increased tumor cell survival (not proliferation) is key

• High levels of BCL2 (anti-apoptotic) - loss of chromosome 13q miRNA regulation
• BTK (Bruton tyrosine kinase) signaling via B-cell receptor is critical
• Immune dysregulation: Hypogammaglobulinemia; paradoxically 15% develop warm autoantibodies

• Small, resting lymphocytes with dark round nuclei, scant cytoplasm
• Proliferation centers = foci of larger dividing cells → pathognomonic for CLL/SLL
• Immunophenotype: CD5+ B cell (key - co-expression of CD5 and CD23 is characteristic)

Acute Myeloid Leukemia (AML)

• Tumor of hematopoietic progenitors with mutations that impede differentiation → immature myeloid blasts accumulate
• Incidence rises with age, peaks after 60 years
• Results in marrow failure → anemia, thrombocytopenia, neutropenia

Source: Robbins, Cotran & Kumar PBD, block6 lines 3028-3100 and block7 lines 266-292

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5. HODGKIN LYMPHOMA

What Sets HL Apart from NHL

1. Distinctive neoplastic Reed-Sternberg (RS) giant cells
2. Robust but ineffective host immune response - tumor cells are only a small fraction of the mass
3. Arises in a single node or chain and spreads in stepwise contiguous fashion
4. Cell of origin: Germinal center B cells (proven by immunoglobulin gene rearrangement studies)

Reed-Sternberg Cell - The Hallmark

• Very large cell: 15-45 µm in diameter
• Enormous multilobate nucleus
• Exceptionally prominent "owl-eye" nucleoli (large acidophilic nucleoli surrounded by clear halo in mirror-image lobes)
• Immunophenotype: CD15⁺, CD30⁺, CD45⁻, B/T-cell marker negative

Five Subtypes

Pathogenesis Highlights

• EBV found in RS cells in ~70% of mixed-cellularity subtype
• RS cells secrete IL-5 (attracts eosinophils), TGF-β (fibrosis), IL-13 (autocrine RS growth)
• Immune escape: RS cells lose MHC class I (loss of β2-microglobulin); express PD-L1 and PD-L2 (checkpoint inhibition) → anti-PD-1 antibodies are highly effective even in refractory disease

Staging (Ann Arbor)

• Stage I: Single node region
• Stage II: Two or more node regions, same side of diaphragm
• Stage III: Both sides of diaphragm
• Stage IV: Disseminated (liver, bone marrow, lung)
• "B" symptoms: Fever, night sweats, weight loss >10% → worse prognosis

Source: Robbins & Kumar Basic Pathology, block4 lines 2728-2850

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6. PURPURA

Definition

• Petechiae: Pinpoint (<3mm)
• Purpura: 3mm-1cm
• Ecchymoses: >1cm (bruises)

Immune Thrombocytopenic Purpura (ITP)

1. Chronic ITP - most common; women 20-40 years
2. Acute ITP - mostly children after viral infection; self-limited

• Antibodies (IgG) against platelet membrane glycoproteins IIb/IIIa or Ib/IX complexes in ~80% of cases
• Spleen = major site of antiplatelet antibody production + site of IgG-coated platelet destruction
• Bone marrow shows increased megakaryocytes (reactive increase)

• Insidious onset
• Petechiae, easy bruising, epistaxis, gum bleeding
• Serious intracranial hemorrhage is uncommon

• Immunosuppressive agents
• Splenectomy normalizes platelet count and induces complete remission in >2/3 patients

Thrombotic Thrombocytopenic Purpura (TTP)

• Pentad: Fever + thrombocytopenia + microangiopathic hemolytic anemia + transient neurologic deficits + renal failure
• Widespread platelet-rich thrombi in microcirculation
• Due to deficiency of ADAMTS13 (metalloprotease that cleaves large vWF multimers)
• Very large vWF multimers → platelet aggregation

Heparin-Induced Thrombocytopenia (HIT)

• Develops in 3-5% of patients after 1-2 weeks of unfractionated heparin
• IgG antibodies bind platelet factor 4 in a heparin-dependent manner
• Platelet activation → thrombosis (paradox - both thrombocytopenia AND thrombosis)
• Treatment: Stop heparin; switch to direct thrombin inhibitors

Source: Robbins & Kumar Basic Pathology, block4 lines 3089-3115

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7. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

Definition

1. Microthrombi → tissue hypoxia, microinfarcts
2. Bleeding → consumptive coagulopathy (factors and platelets depleted)

DIC Pathophysiology Diagram

Triggers (Two Main Mechanisms)

1. Release of tissue factor/procoagulants into circulation:
   • Obstetric complications (placental release)
   • Tumors (especially acute promyelocytic leukemia (APL) and adenocarcinoma)
   • Bacterial sepsis: endotoxins stimulate tissue factor expression on monocytes + cytokines (IL-1, TNF) stimulate tissue factor on endothelial cells + decrease thrombomodulin (→ less protein C activation)
2. Widespread endothelial cell injury:
   • Antigen-antibody complexes (SLE)
   • Temperature extremes (heat stroke, burns)
   • Infections (meningococci, rickettsiae)
   • Systemic inflammatory response syndrome (SIRS)

Common Clinical Causes

Lab Findings in DIC

Clinical Presentation

• Bleeding from multiple sites (venipuncture sites, skin, mucous membranes, GI, urinary)
• Thrombotic manifestations: renal failure, stroke, adrenal infarction
• Both simultaneously in many patients

Source: Robbins & Kumar Basic Pathology, block4 lines 3023-3088

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8. BLOOD GROUPING (ABO and Rh System)

ABO Blood Group System

Key Principles

• ABO antibodies (anti-A, anti-B) are naturally occurring IgM antibodies - no prior sensitization needed
• Formed early in life against environmental antigens that cross-react with A/B antigens
• IgM antibodies fix complement → acute intravascular hemolytic transfusion reaction if mismatched
• ABO system is the most important blood group in transfusion medicine

Rh Blood Group System

• Based on the RhD antigen (most immunogenic)
• Rh positive (Rh⁺): RhD antigen present on RBC surface
• Rh negative (Rh⁻): RhD antigen absent
• ~85% of population is Rh positive

• NOT naturally occurring - require prior sensitization (transfusion or pregnancy)
• IgG antibodies (unlike ABO's IgM) → can cross the placenta

Hemolytic Disease of the Newborn (HDN / Erythroblastosis Fetalis)

• Rh⁻ mother × Rh⁺ father → Rh⁺ baby
• First pregnancy: exposure of Rh⁻ mother to fetal Rh⁺ RBCs at delivery → she forms anti-RhD IgG (sensitization)
• Second Rh⁺ pregnancy: Anti-RhD IgG crosses placenta → destroys fetal RBCs → hemolytic anemia, hydrops fetalis, kernicterus (bilirubin deposition in brain)
• Prevention: Administer Rh immune globulin (RhoGAM) to Rh⁻ mother at 28 weeks and within 72 hours of delivery → passively neutralizes fetal RBCs before maternal sensitization

ABO HDN

• Can occur in first pregnancy (naturally occurring IgG anti-A or anti-B in group O mothers)
• Usually milder than Rh HDN

Blood Type Compatibility in Transfusion

• Always test ABO + Rh before transfusion
• Cross-match: Mix patient serum + donor RBCs to detect unexpected antibodies
• Type and Screen: ABO/Rh typing + antibody screen for less urgent situations

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QUICK COMPARISON TABLE - Leukemia Types

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KEY HIGH-YIELD MNEMONICS

• Hodgkin: RS cells, CD15⁺/CD30⁺, contiguous spread, better prognosis
• NHL: No RS cells, non-contiguous spread, diverse group

• Sickle cell: Structural defect (wrong protein)
• Thalassemia: Quantitative defect (less protein)

• ITP: Immune destruction, splenomegaly absent, treat with steroids/splenectomy
• TTP: Microangiopathic, neurological symptoms, ADAMTS13 deficiency, treat with plasma exchange

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ROBBINS MUST-KNOW MORPHOLOGY IMAGES

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All content sourced directly from:

• Robbins & Kumar Basic Pathology (ISBN 9780323790185)
• Robbins, Cotran & Kumar Pathologic Basis of Disease (ISBN 9780443264528)All 8 topics are covered above. Here is a summary of what was taught and what to focus on tonight before your exam:

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Your Exam Prep Summary - All 8 Topics from Robbins

What to focus on (high-yield for each topic):

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🩸 HEMATOLOGY EXAM MASTER NOTES

Sourced directly from Robbins & Kumar Basic Pathology + Robbins, Cotran & Kumar Pathologic Basis of Disease

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1. ANEMIA

Definition & Classification

1. Blood loss (hemorrhage - acute or chronic)
2. Increased destruction (hemolysis - intravascular or extravascular)
3. Decreased production (marrow failure - aplastic, megaloblastic, iron deficiency)

Classification by RBC Size (MCV)

Clinical Features

Hemolysis - Key Distinction

• Hyperbilirubinemia and jaundice
• Splenomegaly
• Pigment gallstones (if chronic)
• Iron is recycled - NO iron deficiency

• Hemoglobinemia, hemoglobinuria, hemosiderinuria
• Iron loss → can cause iron deficiency
• Both types: ↓ serum haptoglobin (binds free Hb, then removed)

Summary of Key Hemolytic Anemias (Robbins)

Robbins & Kumar Basic Pathology, p. 384-385

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2. SICKLE CELL ANEMIA

The Basics

• Most common familial hemolytic anemia
• Autosomal recessive (AR)
• Gene: β-globin mutation on chromosome 11
• Mutation: Valine substitutes for Glutamic acid at position 6 of β-globin
• Result: HbS (sickle hemoglobin) instead of HbA

Why It's Prevalent (Epidemiology)

• Protective against Plasmodium falciparum malaria - hence high frequency in:
  • Equatorial Africa, India, Southern Europe, Middle East
• USA: ~8% of African-Americans are HbS carriers; ~1 in 600 have sickle cell disease

Pathogenesis - Step by Step

1. Deoxygenation → HbS molecules undergo conformational change
2. HbS polymerizes via intermolecular contacts at the abnormal valine residue
3. Polymers distort RBC into elongated crescentic (sickle) shape
4. Initially reversible on reoxygenation
5. With repeated sickling: Ca²⁺ influx → K⁺ and water loss → membrane damage → irreversibly sickled cells → prone to hemolysis

Peripheral Blood Smear (Robbins Fig. 10.3)

Three Factors Determining Sickling Severity

Clinical Manifestations

Sickle Cell Trait vs. Sickle Cell Disease

• Trait (HbAS): ~40% HbS, ~60% HbA → very little in vivo sickling → asymptomatic (protective against malaria)
• Disease (HbSS): 100% HbS → symptomatic

Robbins & Kumar Basic Pathology, p. 384-392

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3. THALASSEMIA

Definition

Key Points

• Common in Mediterranean, Africa, Asia (malaria endemic regions - same protective logic as HbS)
• β-globin: Single gene on chromosome 11 → mainly point mutations (splicing, transcription, translation defects)
• α-globin: Two genes in tandem on chromosome 16 → mainly gene deletions

β-Thalassemia Classification (Robbins Table 10.3)

β⁰ = no β-globin produced; β⁺ = reduced β-globin produced

α-Thalassemia Classification

Pathophysiology of β-Thalassemia Major

Deficient β-chains
        ↓
Excess α-chains precipitate in RBC precursors
        ↓
Ineffective erythropoiesis (marrow destroys its own cells)
        ↓
Severe anemia → EPO ↑↑ → Erythroid marrow hyperplasia
        ↓
Skeletal changes: "crew-cut" skull X-ray, chipmunk facies, bone thinning
Extramedullary hematopoiesis → hepatosplenomegaly
        ↓
Repeated transfusions → Iron overload (hemosiderosis)
        ↓
Heart failure, liver cirrhosis, endocrine failure (diabetes, hypogonadism)

Robbins & Kumar Basic Pathology, p. 392-400

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4. LEUKAEMIA

Overview

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A. Acute Lymphoblastic Leukemia / Lymphoma (ALL)

Key Facts

• Neoplasm of immature B or T cells (lymphoblasts)
• 85% are B-ALL (childhood leukemia)
• T-ALL: Adolescent males, thymic mass
• Most common cancer of children; peak B-ALL at age ~3 years

Pathogenesis

• 90% have chromosomal changes; most common = hyperploidy (>50 chromosomes)
• Key mutations:
  • T-ALL: NOTCH1 mutations
  • B-ALL: PAX5, TCF3, ETV6, RUNX1, BCR::ABL1, KMT2A, PBX1
• Philadelphia chromosome [t(9;22)] → BCR::ABL1 = most important adverse prognostic factor in ALL

Immunophenotype

Clinical Features

• Bone pain, fatigue, fever, bleeding
• Lymphadenopathy, hepatosplenomegaly
• CNS involvement (headache, cranial nerve palsies)

Prognosis

• Children: 85% cure rate with chemotherapy
• Adults/Philadelphia chromosome positive: poor without targeted therapy

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B. Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL)

Key Facts

• Most common leukemia of adults in the Western world
• CLL = peripheral blood lymphocytes >5000/µL; SLL = mostly lymph node involvement
• Less common in Asia
• Indolent - survival measured in years

Pathogenesis

• Increased tumor cell survival (not proliferation) is key
• High BCL2 levels (anti-apoptotic) - from loss of chr 13q miRNAs that suppress BCL2
• BTK (Bruton tyrosine kinase) signaling via B-cell receptor promotes survival
• Immune dysregulation: Hypogammaglobulinemia; paradoxically 15% develop warm autoantibodies

Morphology

• Sheets of small, resting lymphocytes, dark round nuclei, scanty cytoplasm
• Proliferation centers (foci of larger dividing cells) = pathognomonic for CLL/SLL
• Peripheral blood: smudge cells (fragile lymphocytes crushed during smear preparation)
• Immunophenotype: CD5⁺ CD23⁺ B cell (co-expression of CD5 is the key)

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C. Acute Myeloid Leukemia (AML)

Key Facts

• Tumor of hematopoietic progenitors; differentiation is blocked → immature myeloid blasts accumulate
• Incidence rises with age, peaks after age 60
• Diagnosis: ≥20% blasts in bone marrow

Key Genetic Subtypes (WHO Classification - Robbins Table 13.10)

Robbins, Cotran & Kumar PBD, p. 553-570

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5. HODGKIN LYMPHOMA

What Makes HL Unique (Robbins)

1. Distinctive neoplastic Reed-Sternberg (RS) cells
2. RS cells make up only a small fraction of tumor mass; the rest is reactive inflammatory cells
3. Arises in single lymph node/chain → spreads in stepwise contiguous fashion
4. Cell of origin: Germinal center B cells (proven by identical Ig gene rearrangements in all RS cells)

The Reed-Sternberg Cell (Robbins Fig. 10.23)

RS Cell Features (MEMORIZE)

• Size: 15-45 µm (giant)
• Nucleus: Binucleate or bilobed (mirror-image)
• Nucleoli: Large, inclusion-like, acidophilic = "owl-eye" appearance
• Immunophenotype: CD15⁺ CD30⁺ CD45⁻ (negative for B and T cell markers in classic HL)

Five Subtypes of HL

Pathogenesis Highlights

• EBV in RS cells in 70% of mixed cellularity subtype (identical integration site in all RS cells)
• RS cells secrete: IL-5 (attracts eosinophils), TGF-β (causes fibrosis), IL-13 (autocrine growth)
• Immune evasion: Loss of MHC class I (β₂-microglobulin loss); overexpression of PD-L1/PD-L2 on chromosome 9 → Anti-PD-1 antibodies are highly effective even in refractory disease

Staging - Ann Arbor

• Stage I: Single node region
• Stage II: Two+ regions, same side of diaphragm
• Stage III: Both sides of diaphragm
• Stage IV: Disseminated (liver, bone marrow, lungs)
• "B" symptoms (fever, night sweats, weight loss >10%) = worse prognosis

Robbins & Kumar Basic Pathology, p. 415-420

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6. PURPURA

Definition

• Petechiae: <3 mm (pinpoint)
• Purpura: 3-10 mm
• Ecchymoses: >1 cm (bruises)

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A. Immune Thrombocytopenic Purpura (ITP)

Two Forms

Pathogenesis (Chronic ITP)

• IgG autoantibodies against platelet membrane glycoproteins IIb/IIIa or Ib/IX in ~80% cases
• Spleen = major site of antiplatelet Ab production AND destruction of IgG-coated platelets
• Bone marrow: Increased megakaryocytes (compensatory; reactive to accelerated platelet destruction)

Clinical Features

• Petechiae, easy bruising, epistaxis, gum bleeding
• Serious intracranial hemorrhage = uncommon
• Splenomegaly is absent in uncomplicated chronic ITP

Treatment

• Immunosuppressive agents (steroids first-line)
• Splenectomy → complete remission in >2/3 patients
• IVIG, thrombopoietin receptor agonists

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B. Heparin-Induced Thrombocytopenia (HIT)

• Occurs in 3-5% of patients on unfractionated heparin after 1-2 weeks
• IgG antibodies bind platelet factor 4 (PF4) in a heparin-dependent way
• Immune complexes bind platelet Fc receptors → platelet activation → THROMBOSIS (paradox!)
• Both venous and arterial thrombosis → can cause limb loss, death
• Treatment: Stop heparin immediately; use direct thrombin inhibitors

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C. Thrombotic Thrombocytopenic Purpura (TTP)

Classic Pentad (FATMR)

1. Fever
2. Thrombocytopenia
3. Microangiopathic hemolytic anemia (schistocytes on smear)
4. Renal failure
5. Transient neurologic deficits

Pathogenesis

• ADAMTS13 deficiency (metalloprotease that cleaves large von Willebrand factor multimers)
• Uncleaved ultra-large vWF multimers → platelet aggregation → platelet-rich thrombi in microcirculation
• Treatment: Plasma exchange (replaces ADAMTS13, removes antibodies)

TTP vs HUS

Robbins & Kumar Basic Pathology, p. 429-432

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7. DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

Definition

1. Microthrombosis → ischemia, microinfarcts, microangiopathic hemolytic anemia
2. Bleeding → consumptive coagulopathy (factors + platelets used up) + fibrin degradation products inhibit remaining coagulation

Pathophysiology Diagram (Robbins Fig. 10.30)

Two Triggering Mechanisms

1. Release of Tissue Factor / Procoagulants

• Obstetric complications: Placenta releases thromboplastin (abruptio placentae, amniotic fluid embolism, retained dead fetus, eclampsia)
• Cancer cells: Especially Acute Promyelocytic Leukemia (APL/M3) and adenocarcinoma
• Sepsis: Endotoxins → tissue factor expression on monocytes; IL-1 + TNF from monocytes → tissue factor on endothelial cells + ↓ thrombomodulin (→ less protein C activation)

2. Widespread Endothelial Cell Injury

• Antigen-antibody complexes (SLE)
• Temperature extremes (heat stroke, burns)
• Infections (meningococci, rickettsiae)
• SIRS/sepsis

Major Disorders Causing DIC (Robbins Table 10.10)

DIC Lab Findings

Organs Affected by Microthrombi

• Kidneys (most common): Glomerular fibrin thrombi → bilateral renal cortical necrosis
• Adrenal glands (Waterhouse-Friderichsen syndrome in meningococcemia)
• Brain, heart

Robbins & Kumar Basic Pathology, p. 427-429

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8. BLOOD GROUPING

ABO Blood Group System

Key Principles of ABO System

• ABO antibodies are naturally occurring IgM - formed early in life against environmental antigens cross-reacting with A/B antigens (no prior transfusion needed)
• IgM antibodies fix complement → acute intravascular hemolytic transfusion reaction if mismatched
• ABO system is the most important in transfusion medicine
• Incompatible ABO transfusion = life-threatening emergency (fever, chills, back pain, hemoglobinuria, renal failure, shock)

Rh Blood Group System

Why Rh Matters: Hemolytic Disease of the Newborn (HDN / Erythroblastosis Fetalis)

Rh⁻ mother × Rh⁺ father
         ↓
First Rh⁺ pregnancy: Fetal RBCs enter maternal circulation at delivery
         ↓
Mother forms anti-RhD IgG (sensitization - usually occurs at delivery)
         ↓
SECOND Rh⁺ pregnancy: Anti-RhD IgG crosses placenta
         ↓
Destroys fetal RBCs → hemolytic anemia → hydrops fetalis
         ↓
↑ Bilirubin → Kernicterus (bilirubin in brain = brain damage)

• Administered to Rh⁻ mother at 28 weeks gestation and within 72 hours of delivery
• Passively neutralizes fetal Rh⁺ RBCs before maternal sensitization occurs

ABO HDN (Robbins note)

• Can occur in first pregnancy (naturally occurring IgG anti-A/anti-B in group O mothers)
• Usually milder than Rh HDN

Cross-Match Before Transfusion

1. ABO and Rh typing of both donor and recipient
2. Antibody screen - detect unexpected antibodies
3. Crossmatch - mix patient serum + donor RBCs → look for agglutination/hemolysis

Robbins & Kumar Basic Pathology

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EXAM HIGH-YIELD COMPARISON TABLES

Leukemia Quick Reference

Hodgkin vs. Non-Hodgkin Lymphoma

ITP vs TTP vs HIT

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QUICK MNEMONICS FOR EXAM DAY

• S - Sepsis, Snake bite
• T - Trauma, Transfusion reactions
• O - Obstetric (amniotic fluid, abruptio, eclampsia)
• P - Promyelocytic leukemia (APL/M3)
• M - Malignancy (pancreas, lung, prostate)
• N - Necrosis (burns, surgery)
• T - Temperature extremes

• F - Fever
• A - (micro)Angiopathic hemolytic anemia
• T - Thrombocytopenia
• R - Renal failure
• N - Neurological symptoms

• 1 gene = Silent
• 2 genes = Trait (mild)
• 3 genes = HbH disease (moderate)
• 4 genes = Hydrops fetalis (Fatal)

• Val→Glu = sickle cell anemia

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All notes sourced directly from:

• Robbins & Kumar Basic Pathology (ISBN 9780323790185)
• Robbins, Cotran & Kumar Pathologic Basis of Disease (ISBN 9780443264528)

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Tonight's Study Priority Order

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🩸 SHORT NOTES - HEMATOLOGY

(From Robbins Pathology)

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1. ANEMIA

• Blood loss (hemorrhage)
• ↑ Destruction (hemolysis)
• ↓ Production (marrow failure)

• Microcytic → Iron deficiency / Thalassemia
• Macrocytic → B12 / Folate deficiency
• Normocytic → Spherocytosis / Sickle cell

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2. SICKLE CELL ANEMIA

• Deoxygenation → HbS polymerizes → sickle shape
• Reversible initially → repeated sickling → Ca²⁺ influx → irreversible sickled cells → hemolysis

1. Other Hb levels (HbF/HbA inhibit polymerization)
2. MCHC (↑ = worse)
3. Transit time through microcirculation

• Vaso-occlusion → pain crises, stroke, acute chest
• Hemolytic anemia + jaundice
• Functional asplenia → susceptible to S. pneumoniae, H. influenzae
• Aplastic crisis → Parvovirus B19

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3. THALASSEMIA

• Major (homozygous) → Severe anemia; transfusion-dependent
• Intermedia → Moderate; transfusions not required
• Minor (heterozygous) → Asymptomatic / mild

• 1 gene → Silent carrier
• 2 genes → Thal trait (mild)
• 3 genes → HbH disease (moderate; β₄ tetramers)
• 4 genes → Hydrops fetalis (lethal in utero; HbBart = γ₄)

• Erythroid hyperplasia → "Crew-cut" skull X-ray, chipmunk facies
• Extramedullary hematopoiesis → hepatosplenomegaly
• Transfusion iron overload → heart/liver/endocrine failure

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4. LEUKAEMIA

ALL (Acute Lymphoblastic Leukemia)

• Most common childhood cancer; B-ALL peak age 3 years
• 85% B-ALL; T-ALL = adolescent males (thymic mass)
• TdT⁺ (key marker)
• B-ALL: CD10⁺ CD19⁺ | T-ALL: CD3⁺
• Philadelphia chromosome t(9;22) → BCR::ABL1 = worst prognosis
• 90% have chromosomal changes; most common = hyperploidy (>50 chr)

CLL/SLL (Chronic Lymphocytic Leukemia)

• Most common adult leukemia (Western world)
• CLL = blood lymphocytes >5000/µL
• Indolent; BCL2 overexpression (chr 13q deletion)
• CD5⁺ CD23⁺ B cell (key immunophenotype)
• Morphology: Smudge cells + proliferation centers (pathognomonic)
• Hypogammaglobulinemia; BTK signaling important

AML (Acute Myeloid Leukemia)

• ≥20% blasts in marrow; peaks >60 yrs
• Auer rods = pathognomonic (crystallized granules)

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5. HODGKIN LYMPHOMA

Reed-Sternberg Cell (MUST KNOW)

• Size: 15-45 µm
• "Owl-eye" nucleoli (large acidophilic, mirror-image lobes)
• CD15⁺ CD30⁺ CD45⁻

5 Subtypes

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6. PURPURA

ITP (Immune Thrombocytopenic Purpura)

• Chronic ITP: Women 20-40 yrs; autoimmune
• Acute ITP: Children after viral infection; self-limited
• IgG against platelet glycoproteins IIb/IIIa or Ib/IX
• Spleen = Ab production site + platelet destruction site
• Marrow: ↑ megakaryocytes
• Symptoms: petechiae, epistaxis, gum bleed, easy bruising
• Splenectomy → complete remission in >2/3 patients
• NO splenomegaly in uncomplicated ITP

HIT (Heparin-Induced Thrombocytopenia)

• 3-5% on unfractionated heparin after 1-2 weeks
• IgG against platelet factor 4 (PF4) + heparin complex
• Paradox: thrombocytopenia + THROMBOSIS
• Treatment: Stop heparin → switch to direct thrombin inhibitors

TTP (Thrombotic Thrombocytopenic Purpura)

• FAT RN pentad: Fever, microAngiopathic hemolytic anemia, Thrombocytopenia, Renal failure, Neurological symptoms
• ADAMTS13 deficiency → ultra-large vWF multimers → platelet thrombi
• Treatment: Plasma exchange

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7. DIC (Disseminated Intravascular Coagulation)

• Thrombosis → ischemia/infarcts/microangiopathic hemolytic anemia
• Bleeding → consumptive coagulopathy (factors + platelets used up)

1. Tissue factor release - obstetric (placenta), APL, cancer, sepsis (endotoxin → monocytes → IL-1/TNF)
2. Endothelial injury - SLE, heat/burns, meningococci, rickettsiae

Sepsis | Trauma | Obstetric | Promyelocytic leukemia (APL) | Malignancy | Necrosis | Temperature extremes

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8. BLOOD GROUPING

ABO System

• ABO antibodies = naturally occurring IgM
• Mismatch → acute intravascular hemolysis (life-threatening)

Rh System

• RhD antigen: 85% Rh⁺, 15% Rh⁻
• Rh antibodies = IgG (NOT naturally occurring; requires sensitization)
• IgG = crosses placenta → HDN

HDN (Hemolytic Disease of Newborn)

Rh⁻ mother + Rh⁺ fetus
→ 1st pregnancy: sensitization (anti-RhD IgG forms at delivery)
→ 2nd Rh⁺ pregnancy: IgG crosses placenta → fetal RBC destruction
→ Hydrops fetalis / Kernicterus

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ONE-PAGE QUICK SUMMARY

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