Conditions - Cardio&Haem Flashcards
(135 cards)
1
Q
STEMI Definition
A
Clinical event characterised by transmural myocardial ischaemia resulting in myocardial injury or necrosis.
The mismatch between myocardial oxygen demand and delivery is almost always caused by total occlusion of a coronary artery from atherosclerotic plaque rupture and subsequent thrombus formation. The severity is dependent on the size, location, and duration of the occlusion.
2
Q
STEMI Signs and symptoms
A
Chest pain
Low-grade fever
Pale, cool and/or clammy skin
Signs of acute heart failure
Systolic murmur due to acute mitral regurgitation or ventricular septal rupture and/or pericardial rub
Chest pain described as:
Central or left-sided chest pain
Usually lasting > 15 minutes “Crescendo pain” with increasing severity over several minutes
Described as substernal pressure
Varying severity
Radiating to left arm, shoulders, neck, or jaw
3
Q
STEMI investigations
A
12-lead ECG → ST segment elevation
4
Q
STEMI ECG
A
Left anterior descending (LAD) occlusion produces ST elevation in the precordial leads (V1-3)
Right coronary artery (RCA) occlusions produce ST changes in the inferior leads (II-III-AVF)
Left circumflex artery (LCA) occlusions produce ST elevation in the lateral leads (I, AVL and V5-6)
5
Q
STEMI Management
A
Morphine
Oxygen (saturations under 94%)
Nitrates
Aspirin (300mg loading dose)
Perfusion therapy (primary percutaneous coronary intervention if available <120 minutes of presentation or thrombolysis if PCI is not possible within 120 minutes)
6
Q
NSTEMI About
A
There are more varied causes of mismatch including partial coronary artery obstruction from a ruptured plaque (most common), partial occlusion from a stable plaque, coronary artery vasospasm (Prinzmetal’s angina) or coronary arteritis.
Can lead to necrosis
7
Q
NSTEMI Signs and symptoms
A
Sudden onset central crushing chest pain radiating to the left arm and/or jaw lasting longer than 20 minutes
Diaphoresis
Nausea
Shortness of breath
Signs of respiratory distress, pallor, diaphoresis, or fluid overload
Tachycardia
High or low blood pressure
S4 heart sound: due to reduced ATP production impairing left ventricular relaxation
Signs of papillary muscle dysfunction (e.g. mitral regurgitation)
Pulmonary oedema, due to acute left-sided heart failure
8
Q
NSTEMI Investigations
A
12-lead ECG → ST segment depression
High sensitivity troponin → elevated
9
Q
NSTEMI ECG
A
Regional ST-segment depression
T wave inversion or flattening
Any dynamic or new Q or T wave changes
10
Q
NSTEMI Management
A
Antiplatelet therapy: aspirin 300mg
Analgesia: either GTN or intravenous opioids
Initial antithrombin therapy: fondaparinux if low bleeding risk and the patient is not undergoing immediate angiography. Unfractionated heparin can be used for patients with renal impairment.
Supplemental oxygen should be offered only to patients with SpO2 of less than 94%.
Coronary angiogram
11
Q
Unstable Angina About
A
Defined by the absence of biochemical evidence of myocardial damage.
It is characterised by specific clinical findings of:
- prolonged (>20 minutes) angina at rest
- new onset of severe angina
- angina that is increasing in frequency, longer in duration, or lower in threshold
- angina that occurs after a recent episode of myocardial infarction
12
Q
Unstable Angina Signs and symptoms
A
Chest pain
13
Q
Unstable Angina Investigations
A
Diagnosis is based on clinical assessment
14
Q
Unstable Angina ECG
A
May be normal
15
Q
Unstable Angina management
A
Antiplatelet therapy: aspirin 300mg
Analgesia: either GTN or intravenous opioids
Initial antithrombin therapy: fondaparinux if low bleeding risk and the patient is not undergoing immediate angiography. Unfractionated heparin can be used for patients with renal impairment.
Supplemental oxygen should be offered only to patients with SpO2 of less than 94%.
Coronary angiogram
16
Q
Systolic HF definition
A
Inability of the heart to contract efficiently to eject adequate volumes of blood to meet the body metabolic demand [most common].
17
Q
Diastolic HF definition
A
Reduction in the heart compliance resulting in compromised ventricular filling and therefore ejection [pericardial disease, restrictive cardiomyopathy, tamponade]. Increasingly recognised as an important cause of heart failure – it is often present in elderly patients with a normal CXR and otherwise unexplained shortness of breath on exertion.
18
Q
Left HF
A
Inability of the left ventricle to pump adequate amounts of blood, leading to pulmonary circulation congestions and pulmonary edema. Usually results in RHF due to pulmonary hypertension. Defined as an ejection fraction of <40%.
19
Q
Right HF definition
A
Inability of the right ventricle to pump adequate amounts of blood, leading to systemic venous congestion, therefore peripheral edema and hepatic congestion and tenderness. Most commonly the result of respiratory disease – especially COPD. The presence of raised JVP and peripheral oedema are suggestive of right HF in particular.
20
Q
Congestive HF definition
A
Failure of both right and left ventricles, which is common.
21
Q
Low-output HF definition
A
Heart failure resulting from reduced cardiac output [most common type] – also referred to as HFrEF (Heart Failure reduced Ejection Fractions).’Pump dysfunction’. Systolic heart failure. Causes decreased contractability (e.g. MI, myocarditis), decreased blood supply to the heart, increased afterload (e.g. hypertension) and impaired mechanical function (e.g. valve disease).
22
Q
High-output HF definition
A
Heart failure that occurs in normal or high cardiac output due to metabolic demand and supply mismatch, either due to reduced blood oxygen carrying capacity [anaemia] or increase body metabolic demand [thyrotoxicosis] – also referred to as HFpEF (Heart Failure preserved Ejection Fraction). ‘Filling dysfunction’. Diastolic heart failure. Causes restrictive cardiomyopathy (‘stiff heart’ (amyloid, sarcoid), valve disease, hypertension)
23
Q
Acute HF definition
A
Acute onset of symptom presentation often, but not always due to an acute event [MI, persistent arrhythmia, mechanical event (ruptured valve, ventricular aneurysm)]. Often an acute presentation to hospital. May be the first presentation, or may be “acute-on-chronic”.
24
Q
Chronic HF definition
A
Slow symptoms presentation usually due to slow progressive underlying disease [CAD, HTN].
25
Acute-on-chronic HF definition
Acute deterioration of a chronic condition, usually following an acute event [anaemia, infections, arrhythmias, MI].
26
Right Bundle Branch Block Pathophysiology
The sino-atrial node acts as the initial pacemaker
Depolarisation reaches the atrioventricular node
Depolarisation through the bundle of His occurs only via the left bundle branch. The left branch still depolarises the septum as normal.
The left ventricular wall depolarises as normal.
The right ventricular walls are eventually depolarised by the left bundle branch, this occurs by a slower, less efficient pathway.
27
Right Bundle Branch Block Diagnostic Criteria
Broad QRS complex: >120 ms (3 small squares)
RSR’ pattern in V1-V3: an initial small upward deflection (R wave), a larger downward deflection (S wave), then another large upward deflection (a second R wave, which is indicated as R’)
Wide, slurred S wave in lateral leads: I, aVL, V5-V6
28
Right Bundle Branch Block Clinical Relevance
RBBB can be either physiological or the result of damage to the right bundle branch. Causes of damage include underlying lung pathology (COPD, pulmonary emboli, cor pulmonale), primary heart muscle disease (ARVC), congenital heart disease (e.g. ASD), ischaemic heart disease and primary degeneration of the right bundle.
29
Left Bundle Branch Block Pathophysiology
The sino-atrial node acts as the initial pacemaker
Depolarisation reaches the atrioventricular node
Depolarisation down the bundle of His occurs only via the right bundle branch. The septum is abnormally depolarised from right to left.
The right ventricular wall is depolarised as normal.
The left ventricular walls are eventually depolarised by the right bundle branch, this occurs by a slower, less efficient pathway.
30
Left Bundle Branch Block Diagnostic criteria
Broad QRS complex: >120 ms (3 small squares)
Dominant S wave in V1
Broad, monophasic R wave in lateral leads: I, aVL, V5-V6
Absence of Q waves in lateral leads
Prolonged R wave >60ms in leads V5-V6
31
Left Bundle Branch Block Clinical relevance
LBBB is always pathological. Left bundle branch block may be due to conduction system degeneration or myocardial pathologies such as ischaemic heart disease, cardiomyopathy and valvular heart disease.
LBBB may also occur after cardiac procedures, which damage the left bundle branch or His bundle. A STEMI presenting as chest pain with LBBB is exceedingly rare.
Due to the relatively greater mass of the left ventricle, disruptions in the depolarisation of the left ventricular muscle can cause cardiac axis changes. The left bundle branch splits into anterior and posterior fascicles. Each branch of the left bundle branch may be damaged in isolation. Anterior fascicle block, which is much more common, causes left axis deviation. Posterior fascicle block may cause right axis deviation. However, the posterior fascicle does much less work than the anterior fascicle, so it can be blocked without any obvious ECG changes.
32
1st Degree Heart Block About
First-degree AV block involves the consistent prolongation of the PR interval (defined as >0.20 seconds) due to delayed conduction via the atrioventricular node.
Every P wave is followed by a QRS complex (i.e. there are no dropped QRS complexes, unlike some other forms of AV block discussed later).
First-degree AV block is common and can often be an incidental finding.
33
First Degree Heart Block Causes
Enhanced vagal tone (often seen in athletes)
Post myocardial infarction
Lyme disease
Systemic lupus erythematosus
Congenital
Myocarditis
Electrolyte derangements
Drugs, particularly AV blocking drugs
Thyroid dysfunction
34
First Degree Heart Block Signs and symptoms
Usually asymptomatic
35
First Degree Heart Block Investigations
12-lead ECG
36
First Degree Heart Block ECG
Rhythm: regular
P wave: every P wave is present and followed by a QRS complex
PR interval: prolonged >0.2 seconds (5 small squares)
QRS complex: normal morphology and duration (<0.12 seconds)
37
First Degree Heart Block Management
If symptomatic, pacemaker may be considered
38
2nd Degree Heart Block Mobitz I About
Also known as the Wenckebach phenomenon.
Typical ECG findings in Mobitz type 1 AV block include progressive prolongation of the PR interval until eventually the atrial impulse is not conducted and the QRS complex is dropped.
AV nodal conduction resumes with the next beat and the sequence of progressive PR interval prolongation and the eventual dropping of a QRS complex repeats itself.
39
2nd Degree Heart Block Mobitz I Causes
Increased vagal tone (often seen in athletes)
Drugs, particularly AV blocking drugs
infarction
Myocarditis
Cardiac surgery
40
2nd Degree Heart Block Mobitz I Signs and Symptoms
Usually asymptomatic
Some can develop symptomatic bradycardia and present with symptoms such as pre-syncope and syncope
Irregular pulse
41
2nd Degree Heart Block Mobitz I Investigations
12-lead ECG
42
2nd Degree Heart Block Mobitz I ECG
Rhythm: irregular
P wave: every P wave is present, but not all are followed by a QRS complex
PR interval: progressively lengthens before a QRS complex is dropped
QRS complex: normal morphology and duration (<0.12 seconds), but are occasionally dropped
43
2nd Degree Heart Block Mobitz I Management
AV blocking drugs should be stopped.
Usually, no intervention is required if the patient is asymptomatic.
If the patient is symptomatic a pacemaker may be considered.
44
2nd Degree Heart Block Mobitz II About
Typical ECG findings in Mobitz type 2 AV block include a consistent PR interval duration with intermittently dropped QRS complexes due to a failure of conduction.
The intermittent dropping of the QRS complexes typically follows a repeating cycle of every 3rd (3:1 block) or 4th (4:1 block) P wave.
Mobitz type 2 AV block is always pathological, with the block typically occurring at either the bundle of His (20%) or the bundle branches (80%).
45
2nd Degree Heart Block Mobitz II Causes
Myocardial infarction
Idiopathic fibrosis
Cardiac surgery
Inflammatory conditions
Autoimmune
Infiltrative myocardial disease
Hyperkalaemia
Drugs, particularly AV blocking drugs
Thyroid dysfunction
46
2nd Degree Heart Block Mobitz II Signs and symptoms
Palpitations
Pre-syncope/Syncope
Regular irregular pulse
47
2nd Degree Heart Block Mobitz II Investigations
12-lead ECG
48
2nd Degree Heart Block Mobitz II ECG
Rhythm: irregular (may be regularly irregular in 3:1 or 4:1 block)
P wave: present but there are more P waves than QRS complexes
PR interval: consistent normal PR interval duration with intermittently dropped QRS complexes
QRS complex: normal (<0.12 seconds) or broad (>0.12 seconds)
The QRS complex will be broad if the conduction failure is located distal to the bundle of His
49
2nd Degree Heart Block Mobitz II Management
Patients should be placed on a cardiac monitor as soon as possible.
Treatment of underlying cause
Temporary pacing or isoprenaline may be required if the patient is haemodynamically compromised due to bradycardia.
A permanent pacemaker is usually inserted if there are no reversible causes identified.
50
3rd Degree Heart Block About
Third-degree (complete) AV block occurs when there is no electrical communication between the atria and ventricles due to a complete failure of conduction. Cardiac function is maintained by a junctional or ventricular pacemaker.
Typical ECG findings include the presence of P waves and QRS complexes that have no association with each other, due to the atria and ventricles functioning independently.
51
3rd Degree Heart Block Causes
Congenital structural heart disease
Idiopathic fibrosis
Ischaemic heart disease
Non-ischaemic heart disease
Iatrogenic, e.g. post-ablative therapies and pacemaker implantation, post-cardiac surgery
Drugs, particularly AV blocking drugs
Infections
Autoimmune conditions
52
3rd Degree Heart Block Signs and symptoms
Palpitations
Pre-syncope/syncope
Confusion
Shortness of breath
Chest pain
Sudden cardiac death
Irregular pulse
Profound bradycardia
Haemodynamic compromise (e.g. prolonged capillary refill time and hypotension)
53
3rd Degree Heart Block Investigations
12-lead ECG
54
3rd Degree Heart Block ECG
Rhythm: variable
P wave: present but not associated with QRS complexes
PR interval: absent (as there is atrioventricular dissociation)
QRS complex: narrow (<0.12 seconds) or broad (>0.12 seconds) depending on the site of the escape rhythm
Narrow-complex escape rhythms (QRS complexes of <0.12 seconds duration) originate above the bifurcation of the bundle of His. A typical heart rate would be >40bpm.
Broad-complex escape rhythms (QRS complexes >0.12 seconds duration) originate from below the bifurcation of the bundle of His. These escape rhythms produce slower, less reliable heart rates and more significant clinical features (e.g. heart failure, syncope).
55
3rd Degree Heart Block Management
Patients should be placed on a cardiac monitor.
Transcutaneous pacing/temporary pacing wire or isoprenaline infusion may be required. Some rhythms (particularly narrow-complex escape rhythms) may respond to atropine.
A permanent pacemaker is usually required.
56
Acute Myeloid Leukaemia About
Malignant proliferation of myeloblasts.
Mainly seen in adults.
Associated with Down’s syndrome.
5-year survival rate: 15%
57
Acute Myeloid Leukaemia Signs and Symptoms
Anaemia (low Hb) → fatigue, etc.
Infection (low WCC) → mouth ulcers, etc.
Bleeding (low plt) → bruising.
Gum hypertrophy
Hepatosplenomegaly.
58
Acute Myeloid Leukaemia Investigations
1st Line: Clinical diagnosis + blood film (shows auer rods).
Gold Standard: Bone marrow biopsy.
59
Acute Myeloid Leukaemia Treatment
Chemotherapy
Allopurinol (prevent tumour lysis syndrome).
60
Chronic Myeloid Leukaemia About
Malignant proliferation of myeloid stem cells.
Mainly seen in adults 40-60 years.
Males > females.
61
Chronic Myeloid Leukaemia Signs and symptoms
Anaemia
Gout
Swollen lymph nodes
62
Chronic Myeloid Leukaemia Investigations
1st Line: Clinical diagnosis + FBC (raised WBC, low Hb).
Gold Standard: Bone marrow biopsy, genetic testing
(philadelphia chromosome).
63
Chronic Myeloid Leukaemia Treatment
Oral Imatinib (BCR/ABL tyrosine kinase inhibitor)
64
Acute Lymphoid Leukaemia About
Malignant proliferation of lymphoblasts.
Mainly seen in children <6 years.
Associated with Down’s syndrome.
65
Acute Lymphoid Leukaemia Signs and symptoms
Anaemia (low Hb) → fatigue, etc.
Infection (low WCC) → mouth ulcers, etc.
Bleeding (low plt) → bruising.
Hepatosplenomegaly.
66
Acute Lymphoid Leukaemia Investigations
1st Line: Clinical diagnosis + blood film (shows blast cells).
Gold Standard: Bone marrow biopsy.
67
Acute Lymphoid Leukaemia Treatment
Chemotherapy
Allopurinol (prevent tumour lysis syndrome).
68
Chronic Lymphoid Leukaemia About
Failure of apoptosis, resulting in accumulation of mature B cells.
Mainly seen in elderly.
Risk factors include mutations, trisomies, deletions, pneumonia.
Complications include Richter’s syndrome (an aggressive lymphoma).
69
Chronic Lymphoid Leukaemia Signs and symptoms
Often asymptomatic
Anaemia
Hepatosplenomegaly
70
Chronic Lymphoid Leukaemia Investigations
1st Line: Clinical diagnosis + blood film (shows smudge cells).
- Gold Standard: Peripheral flow cytometry.
71
Chronic Lymphoid Leukaemia Treatment
Chemotherapy
IVIg
72
Multiple myeloma About
Cancer of plasma cells, which cause bone marrow failure.
Myeloma cells produce an excess of one type of Ig (“monoclonal
paraprotein”), usually IgG (55%) or IgA (20%).
Immunoparesis occurs (= suppression of uninvolved Ig) so patients are
susceptible to infection.
Occurs in >70 yrs.
Predominance in those who are Afro-Caribbean.
73
Multiple myeloma Signs and symptoms
Recurrent bacterial infections.
“Spikey Old CRAB”
Spikey → “spike” on electrophoresis.
Old age.
Calcium raised.
Renal failure.
Anaemia.
Bone lytic lesions / Back pain.
74
Multiple myeloma Investigations
1st line:
X-ray (shows osteolytic bone lesions, e.g. “pepper-pot skull”).
Blood film (shows Rouleaux formation).
Gold Standard:
Serum/urine electrophoresis → paraprotein IgG spike.
Serum free light chain assay → Bence Jones proteins.
Bone marrow biopsy → >10% plasma cells.
75
Multiple myeloma Treatment
1st line: VAD (Vincristine, Adriamycin, Dexamethasone).
Symptomatic: Bisphosphonates.
76
Non-Hodgkin’s lymphoma About
All lymphomas WITHOUT reed-sternberg
cells (diverse group).
Most derived from B cell lines.
Diffuse large B cell lymphoma (DLBCL) is most
common.
7th most commonly diagnosed cancer.
Uncommon before the age of 50 and incidence
increases with age.
77
Non-Hodgkin’s lymphoma Signs and symptoms
Nodal disease (75%) = superficial lymphadenopathy.
Extranodal disease (25%) = skin, gut, CNS and lungs (more
common than in Hodgkin’s).
78
Non-Hodgkin’s lymphoma Investigations
Lymph node excision or bone marrow biopsy - NO reed-sternberg cells.
CT/MRI/PET of chest, abdomen and pelvis.
Lactose dehydrogenase (if raised then worse prognosis).
79
Non-Hodgkin’s lymphoma Treatment
Low grade → no treatment needed, watch and wait/active surveillance.
High grade → chemotherapy R-CHOP regimen + radiotherapy.
Burkitt’s lymphoma → cyclical chemotherapy.
80
Hodgkin’s lymphoma About
Uncommon haematological malignancy arising from mature B cells.
-Characteristic cells with MIRROR-IMAGE NUCLEI called REED-STERNBERG CELLS.
Male predominance.
2 peaks of incidence → teenagers and elderly.
Risk factors include Epstein-Barr virus (glandular fever).
81
Hodgkin’s lymphoma Signs and symptoms
Painless cervical lymphadenopathy.
Swollen lymph nodes in armpit/groin
Weight loss
Fever and night sweats
82
Hodgkin’s lymphoma Investigations
CT/MRI/PET scan of chest, abdomen
and pelvis → helps staging.
Lymph node excision/bone marrow
biopsy → will see reed-sternberg cells.
83
Hodgkin’s lymphoma Treatment
Combination chemotherapy.
Stages I-A to II-A (<3 areas involved) =
short course of chemotherapy followed
by radiotherapy.
Stages II-A to IV-B (>3 areas involved) =
longer course of chemotherapy.
84
Myelodysplasia About
Heterogenous group of clonal stem cell disorders.
Bone marrow cells fail to make adequate numbers of healthy blood cells.
Both quantity and quality of the cells can be affected.
Mean diagnostic age of 76 years.
85
Myelodysplasia Signs and Symptoms
Anaemia
Neutropenia
Thrombocytopenia
86
Myelodysplasia Investigations
FBC → low blood counts
Blood film → demonstrates dysplastic features
Bone marrow aspirate and trephine biopsy
87
Myelodysplasia Treatment
Dependent upon:
How good / intermediate / poor risk is the disease
Other health problems and comorbidities
Patient performance
Fitness
Blast %
88
Iron deficiency anaemia About
Microcytic anaemia
Haemoglobin <130g/L in men aged >15 and <120g/L in non-pregnant women >15.
Most common cause of anaemia worldwide.
More common in young children and in premenopausal women.
Less iron is available for haemoglobin synthesis (crucial for haemoglobin production) →
Reduction in iron = reduction iron haemoglobin → Leads to smaller red blood cells resulting in microcytic anaemia
Absorbed in duodenum and upper jejunum. Approx. 1mg/day absorbed and 15mg/day in a normal diet.
Body stores 4g.
Causes:
Blood loss.
Increased demands (growth and pregnancy).
Poor diet or malabsorption
Unknown cause.
89
Iron deficiency anaemia Signs and symptoms
Fatigue
Headaches
Faintness
Dyspnoea + breathlessness.
Intermittent claudication.
Palpitations.
Brittle nails and hair.
Spoon-shaped nails (koilonychia).
Atrophy of papillae of tongue (atrophic glossitis).
Angular stomatitis/cheilosis.
90
Iron deficiency anaemia Investigations
Blood count and film → microcytic and hypochromic.
Serum ferritin → low.
Reticulocyte count → low.
Total iron binding capacity → high.
91
Iron deficiency anaemia Management
Find and treat cause
Oral iron replacement → ferrous sulphate.
Parenteral iron → IV iron or deep intramuscular iron.
92
Folate deficiency anaemia About
Megaloblastic macrocytic anaemia
The body produces abnormally large red blood cells that cannot function properly.
Folate is essential for DNA synthesis. In folate deficiency there is an impairment in DNA synthesis, resulting in delayed nuclear maturation → larger
red blood cells → decreased red blood cell production in bone marrow.
Condition commonly occurs in countries without folic acid fortification.
Absorbed in proximal jejunum.
0.1-0.2mg/day required.
Minimal body stores → last 3-4 months.
Causes:
Poor intake.
Increased demand.
Malabsorption (coeliac disease,
Crohn’s disease).
Antifolate drugs (methotrexate,
trimethoprim).
93
Folate deficiency anaemia Signs and Symptoms
Patients may be asymptomatic.
May present with symptoms of anaemia → pallor, fatigue, dyspnoea, anorexia, headache.
NO neuropathy (unlike B12 deficiency).
94
Folate deficiency anaemia Investigations
Blood count and film → red blood cells are macrocytic, hypersegmented neutrophils.
Serum folate → low.
95
Folate deficiency anaemia Management
Treat the underlying cause.
Give folic acid tablets daily for 4 months.
Never give folic acid without B12 as well. This is because in low B12 states, it may precipitate/worsen
subacute combined degeneration of spinal cord.
96
B12 deficiency anaemia About
Megaloblastic macrocytic anaemia
Decrease in red blood cells that occurs when the intestines cannot
properly absorb vitamin B12.
Common in fair-headed, blue-eyed individuals.
More common in females than males.
Association with other autoimmune diseases such as thyroid disease.
B12 is essential for thymidine and thus DNA synthesis. Deficiency results in delayed nuclear maturation and so large red blood cells result as well as decreased RBC production.
Absorbed in terminal ileum → must bind to intrinsic factor, produced by gastric parietal cells.
Exclusively found in animal-derived products → meat, fish, eggs, dairy.
Body stores last 3 years.
Causes:
Gastrectomy/ileal resection
Vegan diet
Bacterial overgrowth
Oral contraceptives
Hypochloridia
Nitric oxide
97
B12 deficiency anaemia Signs and symptoms
Onset is insidious with progressively increasing symptoms of anaemia (e.g., fatigue, headache, pallor, palpitations).
May have lemon-yellow skin colour due to the combination of pallor and mild jaundice.
Neurological symptoms only occur with very low levels of B12 and include symmetrical paraesthesia (burning or prickling pain) in fingers and toes
98
B12 deficiency anaemia Investigations
Blood count and film → red blood cells are macrocytic, hypersegmented neutrophils.
Serum vitamin B12 → low.
99
B12 deficiency anaemia Management
Treat cause
100
Pernicious anaemia About
Megaloblastic macrocytic anaemia
B12 deficiency due to autoimmune disorder of the parietal cells of the stomach.
Anti-parietal cell antibodies:
Causes autoimmune atrophy.
Inflammatory infiltrates in gastric mucosa causes loss of intrinsic factor production.
Anti-intrinsic factor antibodies:
Blocks binding of B12 to intrinsic factor.
Blocks binding of intrinsic factor to receptors in ileum.
101
Pernicious anaemia Signs and symptoms
Onset is insidious with progressively increasing symptoms of anaemia (e.g., fatigue, headache, pallor, palpitations).
May have lemon-yellow skin colour due to the combination of pallor and mild jaundice.
Neurological symptoms only occur with very low levels of B12 and include symmetrical paraesthesia (burning or prickling pain) in fingers and toes.
102
Pernicious anaemia Investigations
Blood count and film → red blood cells are macrocytic, hypersegmented neutrophils.
Serum vitamin B12 → low.
103
Pernicious anaemia Management
Injections of B12 (IM hydroxocobalamin)
104
Aplastic anaemia About
Defined by pancytopenia with hypocellular marrow and no abnormal cells.
Most often an idiopathic disorder but can also result from certain drug exposure.
In most cases the pathogenesis is thought to be a CD4 T cell-mediated autoimmune attack directed against the haematopoietic system.
105
Aplastic anaemia Signs and symptoms
Additional paroxysmal nocturnal haemoglobinuria (PNH)
Recent hepatitis
History of recurrent infections
Fatigue
Pallor
History of bleeding or easy bruising
Tachycardia
Dyspnoea
Persistent warts
106
Aplastic anaemia Investigations
FBC with differential → haemoglobin <100 g/L (<10 g/dL), platelets <50 × 10⁹/L, absolute neutrophil count <1.5 × 10⁹/L
Reticulocyte count → corrected reticulocyte percentage <1%
Bone marrow biopsy and cytogenetic analyses → hypocellular marrow with no abnormal cells
107
Aplastic anaemia Management
Immunosuppressive therapy
Blood transfusion
Stem cell transplant
108
Autoimmune haemolytic anaemia About
Normocytic anaemia
Immune mediated destruction of red cells, causing anaemia.
Antibodies and/or complements bind to the surface of red cells causing increased destruction of IgG coated red cells by macrophages in the spleen, increased destruction of complement coated red cells by macrophages in the liver and complement mediated intravascular haemolysis. Partial phagocytosis of red cells results in removal of only a proportion of the membrane. Remaining circulating cells become spherocytic.
109
Autoimmune haemolytic anaemia Signs and symptoms
Pallor
Jaundice
Fatigue
Shortness of breath
Dizziness
Splenomegaly
Active infections
Episodic dark urine (haemoglobinuria)
Triggered by exposure to cold
110
Autoimmune haemolytic anaemia Investigations
Blood film → spherocytes, polychromasia, red cell fragments
Reticulocyte count → increased
Bilirubin, including unconjugated bilirubin → elevated
Lactate dehydrogenase → high
Haptoglobin → low
Direct antiglobulin test → positive
111
Autoimmune haemolytic anaemia Management
Blood transfusion
Corticosteroids
Blood and bone marrow stem cell transplants
112
Anaemia of chronic disease About
Due to an inflammation-mediated reduction in RBC production and sometimes in RBC survival.
Commonly found in acute and chronic infections; autoimmune disorders; chronic diseases; malignancy; after major trauma, surgery, or critical illness; and among older adults.
113
Anaemia of chronic disease Signs and Symptoms
Those of underlying disorder
Absent history of bleeding
Physical finding suggesting infection
Physical finding suggesting neoplasm
Physical finding suggesting autoimmune disorder
Shortness of breath
Fatigue
Pallor
114
Anaemia of chronic disease Investigations
FBC
Serum ferritin → increased
Serum iron → decreased
Transferrin saturation → reduced
Blood smear → RBCs can be microcytic, hypochromic; WBCs and platelets are generally normal in appearance
115
Anaemia of chronic disease Management
Treatment of underlying condition
Blood transfusion
116
Disseminated Intravascular Coagulation (DIC) About
Widespread generation of fibrin within blood vessels.
Acquired syndrome characterised by activation of coagulation pathways.
Results in formation of intravascular thrombi and depletion of platelets and coagulation factors, leading to bleeding by inhibiting fibrin polymerization. Thrombi might lead to vascular obstruction/ischaemic and multi-organ failure.
Results from massive activation of the clotting cascade. Cytokine release in response to systemic inflammatory caused by sepsis, trauma, pancreatitis, malignancy.
117
Disseminated Intravascular Coagulation (DIC) Signs and Symptoms
Acutely ill and shocked.
Bleeding from mouth, nose and venipuncture sites.
Widespread discolouration of skin due to bleeding.
Confusion.
Bruising.
Thrombotic events.
118
Disseminated Intravascular Coagulation (DIC) Investigations
Platelet count → decreased
Prothrombin time → prolonged
APTT → prolonged
Fibrinogen → decreased
D-Dimer → increased
*Diagnosis can be suggested from history → severe sepsis, trauma or malignancy + clinical presentation + thrombocytopenia.
119
Disseminated Intravascular Coagulation (DIC)
Treat underlying condition.
Replace platelets if very low via transfusion.
Fresh Frozen Plasma to replace coagulation factors.
Cryoprecipitate to replace fibrinogen.
Red cell transfusion in bleeding patients.
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Haemophilia A About
Factor VIII deficiency.
X-linked recessive inheritance.
Caused by a mutation in the gene coding for factor VIII situated near the tip of the long arm of the X chromosome Xq2.6.
Incidence of 30-100 per million.
Only affects males as it is X-linked.
Categorised according to the percentage factor VIII activity as:
<1%: Severe (frequent spontaneous bleeds, joint deformity)
1-5%: Moderate (occasional spontaneous bleeds, post traumatic bleeding)
5 – 20%: Mild (post traumatic bleeding)
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Haemophilia A Signs and Symptoms
Early in life, or after surgery/trauma.
Bleeds into joints.
Nosebleeds (take time to stop).
Bleeding gums.
Bleeding from wounds for a long time.
Easily bruised skin.
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Haemophilia A Investigations
aPTT → prolonged
Plasma factor VIII and IX → decreased or absent factor VIII or IX levels
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Haemophilia A Management
Avoid NSAIDs and IM injections.
IV infusion of recombinant factor VIII
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Haemophilia B About
Factor IX deficiency.
Also called Christmas Disease
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Haemophilia B Signs and symptoms
Early in life, or after surgery/trauma.
Bleeds into joints.
Nosebleeds (take time to stop).
Bleeding gums.
Bleeding from wounds for a long time.
Easily bruised skin.
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Haemophilia B Investigations
aPTT → prolonged
Plasma factor VIII and IX → decreased or absent factor VIII or IX levels
127
Haemophilia B Management
Treat with factor IX concentrates.
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Von Willebrand’s Disease About
Von Willebrand factor deficiency
Von Willebrand Factor has 3 roles in clotting:
1. To bring platelets into contact with exposed
sub-endothelium.
2. To make platelets bind to each other.
3. To bind factor VIII, protecting it from
destruction in circulation.
Deficiency in vWF = defective platelet function + factor VIII deficiency.
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Von Willebrand’s Disease Signs and Symptoms
Bruising.
Epistaxis.
Menorrhagia.
Increased bleeding post tooth extraction.
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Von Willebrand’s Disease Investigations
APTT and bleeding time → raised.
Factor VIII clotting activity → decreased
vWF → decreased
INR and platelets → normal
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Von Willebrand’s Disease Management
Desmopressin used in mild bleeding.
vWF containing factor VIII concentrate used
for surgery and major bleeds.
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Acquired Haemophilia About
The body produces antibodies (known as inhibitors) that attack clotting factors, most often factor VIII. Affected individuals develop complications associated with abnormal, uncontrolled bleeding into the muscles, skin and soft tissue that can occur spontaneously, during surgery or following trauma.
Much rarer than congenital haemophilia.
Commonly in the elderly, those with viral, autoimmune, malignant and LPD disorders and in the pregnant.
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Acquired Haemophilia Signs and Symptoms
Looks like vWD
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Acquired Haemophilia Investigations
aPTT → prolonged
Plasma factor VIII and IX → decreased or absent factor VIII or IX levels
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Acquired Haemophilia Management
Priority is to stop the bleeding (FEIBA or VIIa)
immunosuppression (steroids +/- cyclophosphamide (if renal function and Hb allow) +/- rituximab)
VIII inhibitors may be time dependant
Consider plasma exchange in reference cases
Mild cases – W&W can spontaneously remit
