Haem Revision Notes

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Haematology Notes
Neutrophilia
Primary
Neoplasia e.g. CML
Eosinophilia
Neoplasia e.g. HL, T-cell
NHL
Monocytosis
Neoplasia e.g. CML
Basophilia
Lymphocytosis
Neoplasia e.g. CML
Neoplasia e.g. CML/
lymphoma
Coagulation Cascade
Secondary
Infection - Bacterial infection
Inflammation - autoimmune
Infection - Parasitic infection
Inflammation - allergic disease
Infection - usually chronic (e.g.
TB, CMV)
Infection - pox virus
Infection - EBV, CMV
Others
Steroids
DKA
Idiopathic
hyperoesinophilic
syndrome
Haemostasis
 Vasoconstriction
 Formation of loose platelet plug (primary)
 Stabilisation (secondary)
 Fibrinolysis
Key Diagnosic Tests
Common Pathway
Intrinsic Pathway
Extrinsic Pathway
Factors
X, V, platelets, prothrombin/thrombin,
fibrinogen/fibrin,
VIII, IX, XI, XII
TF, VII
Investigations
PT
APTT
PT
Haemorrhagic Disorders
Site of bleeding
Petechiae
Ecchymoses
Hemarthrosis/muscle
Bleeding after surgery
Platelet problem
Skin, mucous
membranes
Yes
Small, superficial
No
Immediate
Platelet Disorders
 Normal count: 150-400
 < 50 - petechiae, ecchymoses
 < 20 - mucocutaneous bleeds (GI bleeding, haematuria)
Coagulation problem
Soft tissues, joints,
muscles
No
Large, deep
Yes
Delayed (days)
Clotting Disorders
Disease
Haemophilia A (VIII
deficiency)
Haemophilia B (IX
deficiency)
vWD
Inheritance
X-linked
Recessive
X-linked
Type 1 - AD +
partial deficiency
Type 2 - AD + loss
of multimers
altered quality
Type 3 - AR +
complete
deficiency
Liver disease
Vitamin K deficiency
DIC
Presentation
< 1%: haemarthroses + deep muscle
haematoma
1-5%: severe bleeding after injury
> 5%: mild bleeding after injury. Late
dx
Same features as haemophilia A
↓Platelet adhesion
↓Stabilising factor for VIII:C
Presents as a platelet problem
Investigations
Tx: Factor concentrate,
Desmopressin (mild
disease)
Desmopressin
ineffective
Bleeding time prolonged
PT & APTT – normal
Tx: Desmopressin, VIII +
vWF concentrates
Malnutrition, drugs or
Malabsorption causes ↓ Vit K, ↓
factor production + functional
abnormalities
↓ II, VII, IX and X
Sepsis, Malignancy, Severe liver
disease, Haemolytic transfusion
reactions, Obstetric causes and
Trauma causes Widespread
intravascular coagulation
(Consumption
of platelets + Consumption of
clotting factors and fibrin
generation), Secondary fibrinolysis
Leads to bleeding and clotting
↑ PT + APTT
Prolonged PT and APTT
Prolonged TT
↑FDPs/D-dimer
Thrombocytopenia
Tx: Support + treat
underling cause
Thrombotic Disorders
Virchow’s Triad
 Hypercoagulability
 Stasis
 Vessel wall
Inherited
Thrombophilia
Factor V Leiden
Prothrombin G20210A
Protein C deficiency
Protein S deficiency
Anti-thrombin deficiency
Features
Normal pro-coagulant, abnormal anti-coagulation
Elevated prothrombin
Autosomal dominant – early thrombosis (<40y)
Tx – protein C/protein S concentrate
Inherited (AD) or acquired (nephrotic syndrome)
Inherited present early
Acquired
Thrombophilia
Immobility/stasis
Surgical (tissue trauma -- pro-coagulant)
Malignancy (? pro-coagulant molecule)
Anti-phospholipid syndrome
Hyper-oestrogen state
Anti-coagulant therapy
Heparin
 Immediate effect
 Potentiates anti-thrombin III
 2 types:
o Unfractionated heparin
o LMWH (1 daily s.c.)
 Aim for APPT 1.5-2.5
Features
Hospital in-patients, elderly with loss of mobility
Orthopaedics and gynaecology
Young women with: Recurrent DVT, miscarriages
and stroke
Pregnancy/COCP/HRT
Increased coagulation factors and reduced anticoagulation factors
Warfarin
 Long term therapy
 Vitamin K antagonist
 Initial procoagulant effect
 Monitored with PT/INR
Anaemia
 Hb < reference range for age, sex and gender of an individual.
o Men < 13.5 g/dl
o Women < 11.5 g/dl
 Reduced red cell count (RCC)
 Reduced packed cell volume (PCV)
Classical Signs
 Conjunctival pallor
 Koilonychia
 Glossitis
 Angular stomatitis


Post-cricoid webs (Plummer-Vinson
Syndrome)
High-flow murmur
May be classified according to:
 Size
o Microcytic (IDA, thalassaemia)
o Normocytic (Acute blood loss, chronic disease, leukoerythroblastic)
o Macrocytic (Vitamin B12 deficiency, folate deficiency, alcoholism, hypothyroidism, liver
disease)

Pathophysiology
o Reduced production (Haematinic deficiency, bone marrow infiltration, chronic disease)
o Reduced life-Span (Haemolysis)
o Pooling (Splenomegaly)
Reduced Production
Pathology
↓Fe
Causes
Reduced intake
Malabsorption
Blood loss
↑Demand
↓Vit B12
↓ intake
Impaired absorption
Pernicious Anaemia (AI, ↓IF)
↓Folate
↓ intake
Malabsorption
↑Demand
Drugs (methotexate, ETOH, anticonvulsants)
Destruction/competition with
normal bone marrow
Can be cellular or hypocellular
Bone Marrow Infiltration
Myelodysplasia
Anaeamia of Chronic Disease
Mild malignancy of early myeloid
progenitor cells
Elderly
Chronic infection
Chronic inflammation
Malignancy
Neoplasia
Increased Destruction
 Extravascular
o Common
o Occurs in spleen (macrophages)
Clinical Features
 Variable
 No anaemia
 Chronic haemolytic anaemia
 Folate deficiency
Key haematological features
 Raised unconjugated bilirubin
 ↓ haptoglobin
 ↓ LDH
Features
↓ MCV, ↓ ferritin, ↑ TIBC
Hypochromia, poikilocytosis,
anisocytosis
Tx: Ferrous Sulphate, Paraenteral
Fe
Macrocytosis (megaloblast)
Hypersegmented neutrophils
Thrombocyopaenia
Peripheral neuropathy
Tx: Hydroxycobalamin
↓ RBC folate
Tx: Folate
Cellular
Myeloproliferation, myelofibrosis,
malignant spread
Hypocellular
Idiopathic (50%), Cytotoxic drugs
+ radiation, Infections, Immune
Reduction in cell line function
BM: increased cellularity +
abnormal myeloid precursors
↓Hb, ↔/↓MCV, ↔/↑Ferritin
Tx: Erythropoietin

Intravascular
o Rare
o Occurs in blood



Acute episodes
Crises
Aplastic anaemia


↑ urinary urobilinogen
Reticulocytes
Inherited:
Spherocytosis
Inheritance
AD
Features
Variable
Elliptocytosis
AD
Mild Course
G6PD
X-linked
Enzyme needed to produce NADPH
Used with glutathione to protect from
oxidative damage
Sickle cell
Thalassaemia
Point Mutation
(β globin chain)
α - Gene
deletions
β- Point
mutations
Very common
Africa/Americans/Mediterraneans
Chronic haemolytic anaemia
Acute haemolytic episodes
- Drugs
- Fava beans
- Infection
Shortened red cell survival
• Chronic haemolysis
• Splenomegaly
• Gallstones
• Folate defiency
• Vulnerable to aplastic anaemia
Vaso-occlusive disease
• Impaired passage of cells in
microcirculation
• Obstruction of small vessel +
infarction
• Consequences
• Crises
• Organ dysfunction
β:
Major - homozygous (Cooley’s
anaemia), present in first year, require
blood transfusion
Minor/Intermedia – heterozygous,
asymptomatic, mild haemolytic picture
α:
Severity deficiency
4 - incompatible with life (hydrops
fetalis)
3 - moderate anaemia + splenomegaly
1or2 - asymptomatic with mild anaemia
Haematological Malignancies
Leukaemia: malignant cells in peripheral blood/bone marrow
Lymphoma: solid tumour (malignant cells in lymph nodes)
Myeloma: malignant cells in bone marrow and production of paraprotein
Diagnostic tests
DAT neg, osmotic fragility
Tx: Splenectomy + folate
Blood film
Tx: Nil
Heinz Bodies
Bite Cells
DAT test – Negative
Beutler Fluorescent Spot
test
Dx: Hb electrophoresis +
sick solubility tests
Tx: Acute sickle crisis
prevention, Vaccination,
penicillin prophylaxis + folic
acid, hydroxycarbamide
Leukaemias
Subtypes
ALL
B cell
T cell
Burkitt’s leukaemia
AML
M0-M7/WHO
classification
CLL
B cell (95%)
T cell (5%)
Features
Children
De novo
Presentation: Bone marrow failure,
Lymphadenopathy, hepatosplenomegaly,
Testicular infiltration
Adults
De novo or secondary
Presentation: Bone marrow failure,
Bleeding tendency, GUM/Skin/CNS
infiltration
Elderly
Indolent course with good prognosis
Usually presents on FBC
Myeloproliferative Disorders
Disease
Polycythaemia rubra vera
Cell line
RBCs
Essential thrombocythaemia
Platelets
Chronic myeloid leukaemia
Granulocytes
Myelofibrosis
Megakaryocyte
proliferation
Investigations
Full blood count: Anaemia,
thrombocytopenia +
leucopenia, Leucocytosis
Blood film: Blasts
Bone marrow biopsy:
Hypercellular with blasts
Immunophenotyping: B cell
vs. T cell
Cytogenetics: Prognosis
Auer Rods
FBC: ↑lymphocytes
Film: smear cells
Marrow: lymphocytic
infiltration
Features
Elderly
Non-specific - Tiredness, depression, vertigo, visual
disturbance, Hypertension, angina, intermittent
claudication
Specific – Erythomyalgia, Gout + peptic ulceration,
Plethoric
Ix:↑ Hb & PCV, Erythroid hyperplasia
Tx: (keep PCV < 0.45), Venesection, Hydroxyurea +/radioactive 32P
Benign natural history
Features: Thrombosis (increased number), Bleeding
(reduced quality)
Ix: Platelets > 1000 + hypercellular marrow
Tx - hydroxyurea
40 -60y
Slowly progressive course
Non-specific presentation (Generally unwell with
splenomegaly+ hepatomegaly)
Ix: ↑WBC, Blood film: Granulocytes, Philadelphia
chromosome
Tx: Imatinib, stem cell transplant
Megakaryocyte proliferation leading to Fibrosis +
Ineffective Erythropoiesis
Features: BM failure + splenomegaly
BM very helpful:
• Dry tap
• Fibrotic trephine biopsy
• Lack of Philadelphia chromosome
Myelodysplastic Syndromes
Disease
Lymphoma
Features
Hodgkin’s - Reed-Sternberg Cells
Non-Hodgkin’s – B-cell or T-cell/NK
cell
Non-specific - Fatigue, loss of
appetite, Lymphadenopathy
Specific - Fever/night sweats,
Itching, ETOH-induced pain,
Splenomegaly
Multiple Myeloma
Bone resorption
• Vertebral collapse
• Spinal cord compression
• Hypercalcaemia + associations
Paraprotein
• Infections
• Pneumonia + pyelonephritis
• Hyperviscosity
• Visual loss
• Renal failure
Monoclonal Gammopathy of
Undetermined Significance
Investigations
FBC: nil specific
BM: Normal
Hodgkin
Radiotherapy + chemotherapy
Non-Hodgkin
Watch and wait (follicular)
Radiotherapy
Chemotherapy (e.g. CHOP)
Monoclonal antibodies (rituximab)
Stem cell transplants
FBC: BM infiltration, ↑calcium
BM: abnormal plasma cell
infiltration
Serum/urine electrophoresis
Tx: Treat complications, Suppress
the disease
< 65 – chemo then stem cell
transplant
> 65 - chemo roglobulin
Often occurs in elderly
Paraprotein present but no other
symptoms/signs or laboratory
findings to suggest myeloma
Natural history is not well defined
Porphyria
 Group of disorders caused by deficiencies in haem synthesis enzymes
 The major problem is the build up of toxic haem precursors
Type
Neurovisceral
Cutaneous
Severity
Severe
Mild
Features
Psychosis, seizures ,abdominal pain, polyneuropathy
Photo-sensitive vesicular rash
Acute Intermittent Porphyria
 Archetypal neurovisceral porhyria
 Autosomal dominant inheritance
 Precipitated by stress
 Port urine
 Tx - analgesia and carbohydrates
Transfusion Complications
Type
Febrile non-haemolytic reaction
M.O.A - white cell antibodies vs.
donor blood
Bacterial infection
Transfusion related acute lung
injury (rare)
M.O.A. - HLA Ab in donor vs. HLA
antigen on patient WBC
Post-transfusion purpura
M.O.A - Patient ab. vs. donor
platelet antigen
Delayed haemolytic transfusion
reaction
M.O.A. - Red cell ab. not detected
Iron overload
Viral Infections
Graft vs. host disease (rare)
M.O.A - lymphocytes from donor
vs. receipient
Features
Fever only
No features of haemolysis
Treatment
Slow down the transfusion
Sudden onset fever
Very unwell
Sudden onset SOB & hypoxia
No features of haemolysis/other
anaphylactic features
Stop transfusion
Broad spectrum antibiotics
Stop blood
Ventilate
~ 1 week after transfusion
Brusing as platelets very low
IVIG
Delayed
Features of haemolysis
(may cause renal failure)
Transfusions for many years
Damage to heart, liver and
gonads
Many possible
Hepatitis e.g. C/B, HIV, CMV,
HTLV
Must be already
immunosuppressed
Skin rashes, organ failure, marrow
failure
Treat renal failure
Repeat CXM
Avoid transfusion, Chelating
agent e.g. desferioxamine
Screen blood
Treat infection
Irradiate blood
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