Chapter_06.

indd 94

94 Haematology Map 6.1 Anaemia

What is anaemia?
MAP 6.1 Anaemia Anaemia occurs when the haemoglobin (Hb) concentration is low.
This condition may be classified as microcytic, macrocytic or normocytic.

TABLE 6.1 Anaemia

Type of
anaemia Causes Symptoms Signs Investigations Treatment Complications

Microcytic Iron deficiency of Fatigue Pallor FBC Treat cause Fatigue

varying cause, e.g. Palpitations Nail changes, • Microcytic, hypochromic Ferrous sulphate Increased risk
• Menorrhagia Headache e.g. koilonychia anaemia of infection
• Pregnancy Dyspnoea Angular cheilitis • ¯ MCV (<80 fL) Heart failure
• Gastrointestinal tract Atrophic glossitis • ¯ MCH
malignancy • ¯ Ferritin
• Oesophagitis • ¯ Iron
• Gastro-oesophageal • - Total iron binding
reflux disease capacity (TIBC)
• Coeliac disease Blood film: anisocytosis and
• Hookworm poikilocytosis
• Schistosomiasis Investigate causes, e.g.
• Diet low in iron endoscopy, stool
Thalassaemia: see page 96 microscopy, barium enema

Macrocytic Remember these as Fatigue Pallor FBC Treat cause Fatigue

FAT RBC: Palpitations Glossitis • ¯ Hb If pernicious Heart failure
Folate deficiency Headache Angular cheilitis • - MCV (>96 fL) anaemia then Splenomegaly
Alcohol Dyspnoea Paraesthesiae • ¯ Vitamin B12 treat with Neuropsychiatric
Thyroid (hypothyroidism) Irritability Subacute • ¯ Folate hydroxocobalamin and neurological
09/12/14 3:52 PM

Depression degeneration of the • ¯ Reticulocytes injections complications

p
spinal cord • ¯ Platelets ((if severe))
Chapter_06.indd 95

Reticulocytosis • ¯ WCC (if severe)

B12 (vitamin B12 Blood film: hypersegmented
deficiency)/ polymorphs (folate and
pernicious anaemia vitamin B12 deficiency);
Cytotoxic drugs target cells observed in
liver disease
Normocytic Haemolytic anaemia of Fatigue Pallor FBC Treat cause Fatigue
varying cause, e.g. Palpitations Signs of underlying • ¯ Hb Heart failure
• Glucose-6-phosphate Headache disease • Normal MCV
dehydrogenase Dyspnoea • Normal or - ferritin
deficiency Symptoms
• Hereditary of underlying
spherocytosis disease
• Erythroblastosis fetalis
• Sickle cell disease
• Warm antibody
autoimmune
haemolytic
anaemia and
cold agglutinin
disease
• Anaemia of chronic
disease, e.g. rheumatoid
arthritis Aplastic
anaemia
08/12/14 6:16 PM

95 Haematology Table 6.1 Anaemia

Chapter_06.indd 96

96 Haematology Map 6.2 Thalassaemia

What is thalassaemia?
Thalassaemias are genetic conditions, inherited in an autosomal recessive pattern,
MAP 6.2 Thalassaemia that produce a picture of microcytic anaemia due to a problem in globin
chain production. This subsequently alters haemoglobin (Hb) synthesis.
Thalassaemia may be classified into a-thalassaemia and b-thalassaemia.

TABLE 6.2 Thalassaemia

Types of Populations
thalassaemia affected Causes Investigations Treatment Complications
a-thalassaemia More prominent in ¯ a-globin synthesis due to Blood films: in a-thalassaemia Conservative: patient Iron overload
African and Asian a-globin gene mutation on target cells (or Mexican hat education, genetic Splenomegaly
populations chromosome 16; this cells) may be seen counselling Increased risk of
subsequently results in excess FBC: infection
b-globin production • Microcytic, hypochromic Medical: Heart failure
anaemia • Management of Arrhythmias
In a-thalassaemia any number • ¯ MCV a-thalassaemia Bone abnormalities,
between 1 and 4 genes may • ¯ MCH and b-thalassaemia e.g. cranial bossing
be deleted: • Ferritin normal is based on patient Gallstones
• 1 gene deleted = no • Iron normal symptoms and
significant anaemia Hb electrophoresis: - HbA2 overall state of
• 2 genes deleted = trait and - HbF health
disease High performance • Transfusions are
• 3 genes deleted = HbH liquid chromatography usually required
disease Radiology: X-ray for when Hb <7 g/dL or
08/12/14 6:16 PM

bone abnormalities, when the patient is

e.g.
g frontal bossingg g y symptomatic
highly y p
Chapter_06.indd 97

• 4 genes deleted = death – • Patients who have

Bart’s hydrops fetalis repeated blood
b-thalassaemia More prominent Point mutatioin in b-globin transfusions are at
in European chain on chromosome 11; risk of haemochro-
populations this subsequently results in matosis and,
excess a-globin production therefore, require
iron chelation
b-thalassaemia may be therapy, e.g.
subdivided into 3 different desferroxamine.
traits:
1 Minor: usually asymptomatic; Surgical:
carrier state; mild anaemia • Splenectomy
2 Intermediate: • Stem cell
moderate anaemia; no blood transplant
transfusions required
3 Major: aka Cooley’s
anaemia; abnormalities in all
b-globin chains results in
severe anaemia;
characteristic cranial bossing
seen due to extramedullary
haematopoiesis
08/12/14 6:16 PM

97 Haematology Table 6.2 Thalassaemia

Chapter_06.indd 98

98 Haematology Map 6.3 Bleeding Disorders

BERNARD–SOULIER SYNDROME CLOT FORMATION HAEMOPHILIA

What is Bernard–Soulier syndrome?
This is an autosomal recessive bleeding disorder.
Causes
This is a hereditary condition that leads to
deficiency of glycoprotein (Gp) Ib.
Investigations
• - Bleeding time, normal or ¯ platelet count.
Treatment
• Conservative: patient education.
• Medical:
○ Desmopressin may decrease bleeding time.
○ Recombinant activated factor VII.
This consists of 4 steps. Defects
in steps 2–4 may lead to a bleeding
disorder.
1 Vessel constriction.
2 Platelet adhesion and aggregation:
Glanzmann’s thrombasthenia, von
Willebrand disease, Bernard–Soulier
syndrome.
3 Blood coagulation: haemophilia.
4 Fibrinolysis: antiplasmin deficiency.
What is haemophilia?
This is an inherited condition that impairs the
body’s ability to coagulate the blood.
Causes
This is a hereditary condition. There are two
forms of haemophilia:
• Type A: lack of factor VIII.
• Type B: lack of factor IX.
Investigations
• Normal prothrombin time, - partial
thromboplastin time.
Treatment
• Conservative: patient education. Avoid aspirin,
NSAIDs, heparin and warfarin.
• Medical: replace deficient clotting factor with
regular infusions.

MAP 6.3 Bleeding Disorders

08/12/14 6:16 PM
Chapter_06.indd 99

VITAMIN K INSUFFICIENCY GLANZMANN’S THROMBASTHENIA VON WILLEBRAND DISEASE

What is vitamin K insuffiency? What is Glanzmann’s thrombasthenia? What is von Willebrand disease?
This avitaminosis occurs when there is decreased This is a rare autosomal recessive or acquired This is the most common hereditary coagulation
vitamin K1 or vitamin K2 or both. This results in: autoimmune condition in which platelets are disorder, which involves a defect in von
• ¯ Synthesis of factors II, VII, IX and X. deficient of GpIIb/IIIa. GpIIb/IIIa binds fibrinogen. Willebrand factor (VWF). The function of von
• ¯ Synthesis of proteins C and S. Willebrand factor is to bind GpIb receptor on
Causes platelets to subendothelial collagen.
Causes Disease of hereditary or acquired
• Drugs, e.g. warfarin. autoimmune cause. Causes
• Malnutrition. Hereditary condition. There are many different
• Malabsorption. Investigations types of von Willebrand disease, but the most
• Alcoholism. • - Bleeding time. common are type 1, type 2, type 3 and type
• Cystic fibrosis. Normandy.
• Chronic kidney injury. Treatment
• Cholestatic disease. • Conservative: patient education. Avoid Investigations
aspirin and nonsteroidal anti-inflammatory • - Activated partial thromboplastin time,
Investigations drugs (NSAIDs). - Bleeding time, normal prothrombin time,
• - Prothrombin time, normal or - partial • Medical: ¯ VWF antigen, ¯ factor VIIIc.
thromboplastin time. ○ Desmopressin.
○ Recombinant activated factor VII. Treatment
Treatment • Conservative: patient education. Avoid aspirin
• Conservative – patient education. Dietary and NSAIDs.
advice about food rich in vitamin K • Medical: desmopressin may be useful, but is
• Medical – treat cause. Vitamin K supplements. not helpful in type 3 von Willebrand disease.
08/12/14 6:16 PM

99 Haematology Map 6.3 Bleeding Disorders

Chapter_06.indd 100

100 Haematology Map 6.4 Leukaemia

What is leukaemia? Causes

This is a rare neoplasm of the blood or bone marrow. Neoplasm Cause Comment
It is classified into lymphoid and myeloid neoplasms
that may present chronically or acutely. These 4 ALL Possibly a genetic susceptibility Commonest cancer in children
classifications are: coupled with an environmental Often spreads to central nervous system
1 Acute lymphoblastic leukaemia (ALL). trigger Associations – DIP:
2 Chronic lymphocytic leukaemia (CLL). • Down’s syndrome
3 Acute myeloid leukaemia (AML). • Ionising radiation
4 Chronic myeloid leukaemia (CML). • Pregnancy
Signs and symptoms CLL Exact cause unknown Usually affects adults over 60 years old
Neoplasm Clinical features Affects B lymphocytes
Positive ZAP-70 marker is associated with
ALL Bone marrow failure a worse prognosis
Bruising
Shortness of breath AML Exact cause unknown Commonest leukaemia in adults
Purpura Risk factors include: Rapidly progressing
Malaise • Myeloproliferative disease Auer rods on microscopy are
Weight loss • Alkylating agents diagnostic
Night sweats • Ionising radiation exposure
• Down’s syndrome
CLL Asymptomatic
Bone marrow failure CML Exact cause unknown Usually affects males 40–60 years old
Nontender lymphadenopathy Risk factor: ionising radiation 80% associated with the Philadelphia
Hepatosplenomegaly exposure chromosome t[9;22], forming
Malaise bcr-abl fusion gene
Weight loss
Night sweats
08/12/14 6:16 PM
Chapter_06.indd 101

AML Bone marrow failure MAP 6.4 Leukaemia Complications

Malaise • Death.
Weight loss • Increased risk
Night sweats of infection.
Investigations
• Haemorrhage:
CML Bone marrow failure pulmonary,
• Bloods: FBC, WCC, platelets, U&Es, LFTs, ESR, CRP. intracranial.
Hepatosplenomegaly • Bone marrow biopsy, lymph node biopsy.
Malaise • Depression.
• Radiology: X-ray, ultrasound scan, CT scan, MRI.
• Complication of
Weight loss • AML and ALL are classified using the
Night sweats chemotherapy.
French–American–British (FAB) classification.

Treatment
Treatment ALL CLL AML CML
Conservative Patient education; refer to Macmillan nurses
Medical Induce remission and maintenance Chlorambucil Patients <60 years: Imatinib
To induce remission: Fludarabine chemotherapy with an anthracycline and Patients <60 years may be
• Dexamethasone Rituximab cytarabine or methotrexate considered for allogeneic stem
• Vincristine Prednisolone cell transplantation
• Anthracycline antibiotics Cyclophosphamide Patients >60 years: Other treatments
• Cyclophosphamide palliative anthracycline, cytarabine or include alpha-interferon,
Maintenance: mitoxantrone vincristine, prednisolone,
• Methotrexate cytarabine and
• Mercaptopurine If M3 type AML, i.e. acute promyelocytic daunorubicin
• Cytarabine leukaemia (APML), then add all-trans
• Hydrocortisone retinoic acid to the therapeutic regime
08/12/14 6:16 PM

101 Haematology Map 6.4 Leukaemia

Chapter_06.indd 102

102 Haematology Map 6.5 Hodgkin’s vs. Non-Hodgkin’s Lymphoma

MAP 6.5
Hodgkin’s vs. Non-Hodgkin’s lymphoma

HODGKIN’S LYMPHOMA NON-HODGKIN’S LYMPHOMA

What is hodgkin’s lymphoma? What is non-Hodgkin’s lymphoma?
This is a group of uncommon malignancies; the 4 most common histological This is a group of malignancies that are either B cell or T cell in origin.
subtypes are:
1 Lymphocyte-predominant. B cell neoplasms T cell neoplasms
2 Nodular sclerosing. Burkitt’s lymphoma: Adult T cell lymphoma; caused by human
3 Mixed cellularity. • Associated with EBV T-lymphotrophic virus-1 (HTLV-1)
4 Lymphocyte-depleted. • t[8;14] Sézary syndrome
Diffuse large B cell lymphoma
Cause Mantle cell lymphoma: t[11;14]
Exact cause is unknown. Follicular lymphoma:
Risk factors include: • t[14;18]
• Male sex. • bcl-2 expression
• Infection with Epstein–Barr virus (EBV).
• Immunosuppression, e.g. HIV patients. Cause
• Exotoxin exposure. Exact cause is unknown.
Risk factors include:
Signs and symptoms • Male sex.
• Painless lymphadenopathy. • Infection, e.g. EBV, Helicobacter pylori, human herpes virus (HHV)-8,
• Unintentional weight loss. hepatitis C.
08/12/14 6:16 PM

• Fever (constitutional ‘B signs’: fever >38˚C, night sweats, weight loss). • Immunosuppression, e.g. HIV patients.
Chapter_06.indd 103

• Dyspnoea. Signs and symptoms

• Splenomegaly. • Painless lymphadenopathy.
• Hepatomegaly. • Unintentional weight loss.
• Fever.
Investigations • Dyspnoea.
• Bloods: FBC, WCC, U&Es, CRP, ESR, lactate dehydrogenase, creatinine, • Splenomegaly.
alkaline phosphatase, serum cytokine levels. • Hepatomegaly.
• Histology: Reed–Sternberg cells are seen.
• Radiology: X-ray, CT scan, PET scan. Investigations
• Other: lymph node biopsy (Ann Arbor classification). • Bloods: FBC, WCC, U&Es, CRP, ESR, lactate dehydrogenase, creatinine,
alkaline phosphatase, serum cytokine levels, soluble CD25 level.
Treatment • Radiology: X-ray, CT scan, PET scan.
• Conservative: patient education and referral to Macmillan nurses. • Other: lymph node biopsy (Ann Arbor classification).
• Medical: depends on Ann Arbor classification; AVBD regimen:
doxorubicin, vinblastine, bleomycin, dacarbazine; BEACOPP regimen: Treatment
bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, • Conservative: patient education and referral to Macmillan nurses.
procarbazine, prednisolone. • Medical: depends on causes and severity (Ann Arbor classification);
R-CHOP regimen: rituximab, cyclophosphamide, hydroxydaunomycin,
Complications vincristine, prednisolone; other agents used are cisplatin, etoposide and
• Increased risk of infection. methotrexate.
• Recurrence and metastasis.
• Increased risk of cardiovascular disease. Complications
• Complications of chemotherapy. • Increased risk of infection.
• Neurological complications. • Recurrence and metastasis.
• Increased risk of cardiovascular disease.
• Complications of chemotherapy.
• Neurological complications.
08/12/14 6:16 PM

103 Haematology Map 6.5 Hodgkin’s vs. Non-Hodgkin’s Lymphoma

Chapter_06.indd 104

104 Haematology Map 6.6 Myeloma

What is myeloma? Signs and symptoms Investigations

This is a malignant neoplasm
of the plasma cells.
Causes
Exact cause is unknown.
Risk factors include:
• Monoclonal gammopathy
of unknown significance.
• Pernicious anaemia.
• History of thyroid cancer.
• Exposure to certain exotoxins,
e.g. benzene, Agent Orange.
• Past history of radiation exposure.
• Fatigue. • Bloods: FBC (normocytic, normochromic anaemia),
• Unintentional weight loss. U&Es, creatinine, LFTs, ESR, CRP, calcium levels,
• Pathological fractures. alkaline phosphatase, beta-2 microglobulin.
• Vertebral collapse (may lead to spinal cord compression). • Blood film: rouleaux formation.
• Hypercalcaemia. • Serum and urine electrophoresis: paraprotein
• Anaemia. (M protein), Bence Jones proteinuria.
• Infection. • Bone marrow biopsy.
• Renal impairment. • Radiology:
• Bruising. ○ X-ray for bone deformities, e.g. pepper pot
skull and generalised skeletal osteopaenia.
○ MRI scan may be useful.
MAP 6.6 Myeloma

Treatment
• Conservative: patient education. Refer to Macmillan nurses.
• Medical: medical therapy in multiple myeloma depends on the age of the patient and their state of health. If they are <70 years Complications
and without significant co-morbidities then they are eligible for autologous bone marrow transplant, which is the most effective • Spinal cord
treatment. This involves an induction phase using the VAD regimen: vincristine, adriamycin, dexamethasone. After transplant the compression.
patient receives long-term therapy with melphalan. • Pathological fracture.
○ Patients who are ineligible for autologous bone marrow transplant receive long-term treatment with melphalan and • Hypercalcaemia.
prednisolone. • Acute kidney injury.
○ Other medical therapy is targeted to treating symptoms: analgesia, bisphosphonates, prednisolone, blood transfusion. • Increased risk of
08/12/14 6:16 PM

○ Radiotherapy may be required to treat bone pain and spinal cord compression. infection.
• Surgical: kyphoplasty may be required. • Anaemia.
Chapter_07.indd 105

Chapter Seven Infectious Disease

MAP 7.1 Malaria 106

FIGURE 7.1 Malaria Lifecycle 107

MAP 7.2 Tuberculosis (TB) 108

FIGURE 7.2 Mode of Infection of Pulmonary TB 109

MAP 7.3 Human Herpes Virus (HHV) 110

MAP 7.4 Human Immunodeficiency Virus (HIV) 112

MAP 7.5 Sexually Transmitted Infections (STIs) 114

MAP 7.6 Bacterial Infections 116

MAP 7.7 Viral Infections 118

MAP 7.8 Vaccines 120

06/12/14 3:35 AM

105 Infectious Disease