Haematology Flashcards
(240 cards)
1
Q
What is anaemia?
A
Decrease of haemoglobin in blood below reference level for age and sex of an individual
Can be due to low red cell mass or increased plasma volume
Due to reduced production of RBCs from bone marrow or increased loss or RBCs ie by spleen, liver, bone marrow and blood loss
2
Q
How are the different types of anaemia classified?
A
Mean corpuscular volume (MCV) which is average volume of RBCs or size
3
Q
What are the different types of anaemia?
A
Hypochromic (pale) microcytic - low MCV
Normochromic normocytic - normal MCV
Macrocytic - high MCV
4
Q
What occurs to the body in anaemia?
A
Reduced O2 transport
Tissue hypoxia
Compensatory changes - increased tissue perfusion, increased O2 transfer to tissues, increased RBC production
Pathological consequences - myocardial fatty changes, fatty change in lever, aggravates angina and claudication, skin and nail atrophic changes, CNS cell death (cortex and basal ganglia)
5
Q
What are the symptoms of anaemia?
A
Fatigue, headaches, faintness Dyspnoea Angina Anorexia Intermittent claudication Palpitations
6
Q
What are the signs of anaemia?
A
May be absent even in severe anaemia Pallor Pale mucous membranes Tachycardia Systolic flow murmur Cardiac failure
7
Q
How is anaemia diagnosed?
A
Test to determine whether bone marrow production issue - look at reticulocyte count (reticulocyte count low if is)
If removal then reticulocyte count will be high
Reduction in plasma volume will lead to falsely high haemoglobin seen in dehydration
8
Q
What type of anaemia is anaemia of chronic disease?
A
Normocytic
But can be microcytic especially in rheumatoid arthritis and Crohn’s disease
9
Q
What is anaemia of chronic disease?
A
Anaemia secondary to chronic disease, bone marrow also affected by chronic disease therefore anaemic
Second most common anaemia
Commonest anaemia in hospital patients
Occurs in individuals with - TB, Crohn’s disease, rheumatoid arthritis, SLE, malignant disease, CKD
These conditions can cause either a shortening of RBC cell life or reducing RBC production
10
Q
Why does chronic disease cause anaemia?
A
Decreased release of iron from bone marrow to developing erythroblasts
Inadequate erythropoietin response to anaemia (cytokine which increases RBC production)
Decreased RBC survival
11
Q
How does anaemia of chronic disease present?
A
Fatigue, headache, faintness Dyspnoea Angina is pre-existing coronary disease Anorexia Intermittent claudication Palpitations
12
Q
How is anaemia of chronic disease diagnosed?
A
Serum iron and total iron-binding capacity low
Serum ferritin normal or raised due to inflammatory process
Serum soluble transferrin receptor level normal
Blood count and film - RBCs normal or microcytic and hypochromic as in RA and Crohn’s
13
Q
How is anaemia of chronic disease treated?
A
Treat underlying chronic cause
Erythropoitein effective in raising haemoglobin level - used in anaemia of renal disease and inflammatory disease
Side effects - flu-like symptoms, hypertension, mild risk in platelet count and thromboembolism
14
Q
What type of anaemia is folate deficiency anaemia?
A
Megaloblastic anaemia - inhibition of DNA synthesis, RBCs cannot progress onto mitosis causing continuing growth without division
15
Q
What is folate deficiency anaemia?
A
Impairment of DNA synthesis resulting in delayed nuclear maturation resulting in large RBCs and decreased RBC production in bone marrow due to lack of green vegetables in diet
16
Q
What can cause folate deficiency anaemia?
A
Poor intake - poverty, alcoholics, elderly
Increased demand - pregnancy, increased cell turnover (haemolysis, malignancy, inflammatory disease, renal dialysis)
Malabsorption - coeliac/Crohn’s disease
Antifolate drugs - methotrexate, trimethoprim
17
Q
Name 5 risk factors for developing folate deficiency anaemia
A
Elderly Poverty Alcoholic Pregnant Crohn's or coeliac disease
18
Q
How might folate deficiency anaemia present?
A
Asymptomatic
Symptoms of anaemia
Glossitis
No neuropathy
19
Q
How is folate deficiency anaemia diagnosed?
A
Blood count and film - megaloblastic anaemia, RBCs macrocytic, peripheral film shows oval macrocytes with hypersegmented neutrophil polymorphs with 6/more lobes in nucleus
Serum and RBC folate low
GI investigation - small bowel biopsy to exclude GI disease
Serum bilirubin raised due to ineffective erythropoiesis - increased RBC breakdown
Erythrocyte folate level - indicated reduced body stores
20
Q
How is folate deficiency anaemia treated?
A
Treat underlying cause
Folic acid tablets daily for 4 months - never without B12 as well as low B12 may precipitate or worsen subacute combined degeneration of spinal cord
21
Q
What type of anaemia is haemolytic anaemia?
A
Normocytic or macrocytic
22
Q
What is haemolytic anaemia?
A
Premature breakdown of RBCs before normal lifespan of 120 days
Macrocytic if many young RBCs (larger) due to excessive destruction of old RBCs
23
Q
What can cause haemolytic anaemia?
A
Inherited - membranopathies, enzymopathies, haemoglobinopathies
Acquired - autoimmune, infections, secondary to systemic disease
24
Q
What happens in haemolytic anaemia?
A
RBCs rapidly destroyed in circulation - haemoglobin released
Initially bound to haptoglobin but soon becomes saturated
Excess free plasma haemoglobin filtered by renal glomerulus and enters urine, small amounts reabsorbed by renal tubules
Haemoglobin broken down in renal tubular cells and deposited in cells as haemosiderin
Reticuloendothelial system also broken down
Shortened survival of RBCs - compensation of increase in RBC production in bone marrow - compensated haemolytic diseases
Bone marrow can increase output by 6-8 times by increasing proportion of cells committed to erythropoiesis and by expanding volume of active marrow
Larger than mature cells, macrocytic, stain with light blue tinge on peripheral blood film
25
How is haemolytic anaemia diagnosed?
```
High serum unconjugated bilirubin
High urinary urobilinogen
High faecal stercobilinogen
Splenomegaly
Bone marrow expansion
Reticulocytosis - increased reticulocytes
FBC - reduced Hb
Blood film - schistocytes
```
26
What are the two different types of marcocytic anaemia?
Megaloblastic - presence of erythroblasts with delayed nuclear maturation because of delayed DNA synthesis - megaloblasts, large, no nuclei
Non-megaloblastic - erythroblasts normal
27
What can cause megaloblastic anaemia?
Vitamin B12 deficiency
| Folate deficiency
28
What can cause non-megaloblastic anaemia?
```
Alcohol
Liver disease
Hypothyroidism
Bone marrow failure
Bone marrow infiltration
Antimetabolite therapy
Myeloma
```
29
What in microcytic anaemia?
Low MCV
Not enough iron, therefore not enough haemoglobin
Most common cause of anaemia
14% menstruating women
Develops when inadequate iron for haemoglobin synthesis
30
What can cause microcytic anaemia?
Blood loss - menorrhagia, GI bleed, hookworm
Poor diet - poverty
increased demand - growth, pregnancy
Malabsorption - poor intake, coeliac disease
31
Name 4 risk factors for developing microcytic anaemia
Undeveloped countries
High vegetable diet
Premature infants
Introduction of mixed feeding delayed - since breast milk contains low iron
32
How does less iron lead to microcytic anaemia?
Less iron for haem synthesis - decrease in haemoglobin so smaller RBCs leading to microcytic anaemia
33
How does microcytic anaemia present?
General anaemic symptoms
Brittle nails and hair
Spoon-shaped nails - koilonychia
Atrophy of papillae of tongue - atrophic glossitis
Angular stomatitis/cheilosis - ulceration of corners of mouth
34
What could be a differential diagnosis for microcytic anaemia?
Thalassaemia
Sideroblastic anaemia
Anaemia of chronic disease
35
How is microcytic anaemia diagnosed?
Blood count and film - microcytic and hypochromic (pale), poikilocytosis (variation in RBC shape) and anisocytosis
Serum ferritin - low, low amount of stored iron, could be normal in malignancy/infection
Serum iron - low, total iron binding capacity raised
Serum soluble transferrin receptors - number increases
Reticulocyte count low
Further investigations into cause
36
How is microcytic anaemia treated?
Treat cause
Oral iron - side effects nausea, abdominal discomfort, diarrhoea/constipation, black stools
Ferrous gluconate
Parenteral iron - IV or IM in extreme cases
37
What can cause normocytic anaemia?
```
Acute blood loss
Anaemia of chronic disease
Endocrine disorders such as hypopituitarism, hypothyroidism, hypoadrenalsim
Renal failure
Pregnancy
```
38
How does normocytic anaemia present?
```
Fatigue, headaches, faintness
Dyspnoea
Angina if pre-existing coronary disease
Anorexia
Palpitations
Intermittent claudication
```
39
How is normocytic anaemia diagnosed?
Normal B12 and folate
Raised reticulocytes
Hb down
Blood film and count - RBCs normocytic
40
How is normocytic anaemia treated?
Treat underlying cause
Improve diet with plenty of vitamins
Erythropoietin injections
41
What type of anaemia is B12 deficiency anaemia?
Megaloblastic anaemia
42
What is B12 deficiency anaemia?
Pernicious anaemia is a type - caused by autoimmune destruction of parietal cells/intrinsic factor
Impairment of DNA synthesis resulting in delayed nuclear maturation resulting in large RBCs as well as decreased RBC production in bone marrow
Bone marrow most affected - most active in terms of division
43
Who is more at risk of pernicious anaemia?
Common in elderly over 60
More common in fair-haired, blue-eyed individuals
More common in those with blood group A
More common in women
Associated with other autoimmune diseases such as thyroid disease and Addison's disease
44
What can cause B12 deficiency anaemia?
```
Diet - vegans
Malabsorption - lack of intrinsic factor or terminal ileum removed
Pernicious anaemia
Atrophic gastritis
Gastrectomy
Crohn's
Coeliac
(Affect intrinsic factor production by parietal cells in stomach or affect absorption in ileum
```
45
Why does pernicious anaemia cause B12 deficiency?
Parietal cell antibodies present in serum
Intrinsic factor antibodies present in less patients but specific for diagnosis
Autoimmune gastritis affecting fundus with plasma cell and lymphoid infiltration
Parietal and chief cells replaced by mucin secreting cells
Achlorhydia (reduced HCl production) and absent secretion of intrinsic factor
46
How does B12 deficiency anaemia present?
Anaemia - insidious onset, progressively increasing symptoms
Lemon yellow skin - combination of pallor and mild jaundice by excess haemoglobin breakdown
Red sore tongue
Angular stomatitis/cheilosis
Neurological - symmetrical paraesthesia in fingers and toes, early loss of vibration sense and proprioception, progressive weakness and ataxia, paraplegia, dementia, psychiatric problems, hallucinations, delusions, optic atrophy, specific to pernicious anaemia
47
What could be a differential diagnosis for pernicious anaemia?
Folate deficiency
Need to differentiate from other causes of B12 deficiency anaemia
Any disease in terminal ileum/bacterial overgrowth in small bowel
Gastrectomy
48
How is pernicious anaemia diagnosed?
Blood count and film - macrocytic, oval macrocytes with hypersegmented neutrophil polymorphs with 6/more lobes in nuclei
Serum bilirubin raised - ineffective erythropoiesis resulting in increased RBC breakdown
Serum B12 low
Hb low
Reticulocyte low
Intrinsic antibodies - diagnostic but lower sensitivity
49
How is B12 deficiency anaemia treated?
If not pernicious - treat cause
If due to malabsorption - injections required of vitamin B12
Dietary - oral B12
Replenish B12 stores giving IM hydroxocobalamin
NOT FOLIC ACID
50
What is pernicious anaemia?
Autoimmune condition resulting in B12 deficiency and anaemia
51
What is sickle cell disease?
Disorder of quality
Abnormal molecule or variant haemoglobin
Autosomal recessive disorder causing production of abnormal beta-globin chains
Normocytic anaemia
52
Where is sickle cell disease most common?
Commonest in Africans but also in India, Middle East and Southern Europe
53
What are the risk factors of developing sickle cell disease?
African
| Family history
54
How does one get sickle cell anaemia?
Sickle cell haemoglobin single based mutation of adenine to thymine producing a substitution of valine for glutamic acid at 6th codon of beta-haemoglobin chain
HbF normal so disease not present until HbF decreases to adult levels at about 6 months
Insoluble and polymerises when deoxygenated
Flexibility of cell decreased and become rigid and take up sickled appearance
Initially reversible but with repeated sickling, cells lose membrane flexibility and become irreversibly sickled
Dehydrated and dense and won't return to normal when oxygenated
Shortened RBC survival resulting in haemolysis
Impaired passage of cells through microcirculation leading to obstruction of small vessels and tissue infarction and thus intense pain
Will feel well despite being anaemic as HbS releases O2 more readily to tissue than normal
55
How does sickle cell disease present?
Vaso-occlusive crisis - acute pain in hands and feet due to vaso-occlusion of small vessels and avascular necrosis of bone marrow in children, pain in long bones due to avascular necrosis of bone marrow in adults, CNS infarction in children leading to stroke, seizures, cognitive defects, attacks vary in frequency
Acute chest syndrome - vaso-occlusive crisis of pulmonary vasculature, pulmonary hypertension and chronic lung disease, infection, fat embolism from necrotic bone marrow/pulmonary infarction, SOB, chest pain, hypoxia
Pulmonary hypertension - greater than 25mmHg, damage from repeated crises and repeated thromboembolism and intravascular haemolysis, increases risk of hypoxaemia and worsening sickle cell crisis
Anaemia - splenic sequestration (acute painful enlargement of spleen and acute fall in Hb, fibrotic, non-functioning spleen), bone marrow aplasia
Long term problems with growth and development (low weight, short, delayed sexual maturation), bones (chronic infarcts from vaso-occlusive crises, avascular necrosis of hips, shoulders, compression of vertebrae and shortening of bones in hands and feet
Osteomyelitis
Infections
Cardiomegaly, arrhythmias, iron overload cardiomyopathy, MI
TIA, fits, cerebral infarction, coma
Chronic hepatomegaly, liver dysfunction due to trapped sickle cells
Chronic tublointersitial nephritis
Retinopathy, vitreous haemorrhage, retinal detachments
56
What problems can sickle cell disease cause in pregnancy?
Impaired placental blood flow resulting in spontaneous abortion
57
How is sickle cell disease diagnosed?
Blood count - Hb 60-80g/L, raised reticulocyte count
Sickled erythrocytes on blood film
Sickle solubility test positive
Hb electrophoresis - confirms diagnosis, shows 80-95% HbS, absent HbA, aim for diagnosis at birth to prompt pneumococcal prophylaxis
58
How is sickle cell disease treated?
Precipitating factors eg infection, cold, dehydration avoided or treated quickly
Folic acid to all haemolysis patients
Acute painful attacks - IV fluids, analgesia (morphine, codeine, paracetamol, NSAIDs), O2 and antiboitics
Anaemia - blood transfusion for acute chest syndrome, acute anaemia due to acute splenic sequestration, aplastic crisis, stroke, HF
Oral hydroxycarbamide - increases HbF concentration
Stem cell transplant
59
What are the 3 main causes of microcytic anaemia?
Iron deficiency
Chronic illness
Thalassaemia
60
What are the 3 main causes of normocytic anaemia?
Combined
Acute blood loss
Chronic disease
61
What are the 3 main causes of macrocytic anaemia?
Vitamin B12 deficiency (pernicious anaemia)/folate deficiency
Hypothyroidism
Liver disease
62
What is a DVT?
Formation of one or two blood clots in one of the bodies larger veins - tends to be in lower limbs
Inappropriate coagulation
Fibrin rich clot - requires anticoagulants
63
How common are DVTs?
25,000 people die of DVT and PE per year in UK
50% preventable, premature mortality
More than RTA, AIDS, and breast cancer combined
64
What are the main risk factors for DVT and PE?
Surgery, immobility and leg fracture - on thromboprophylaxis
OC pill, HRT, pregnancy
Long haul flights/travel
Inherited thrombophilia - genetic predisposition
65
What are the circumstantial causes of DVT?
```
Surgery
Immobilisation
Oestrogens
Malignancy
Long haul flights
Pregnancy
```
66
What are the genetic causes of DVT?
```
Higher risk in Caucasian population
Factor V Leiden
PT20120A
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Plasminogen deficiency
Thrombophilia
```
67
What are the acquired causes of DVT?
Anti-phospholipid syndrome
Lupus anticoagulant
Hyperhomocysteinaemia
Varicose veins
68
What are the main symptoms of a DVT?
Pain particularly when walking
Swelling in ankles
Unilateral
Redness
69
What are the main signs of DVT?
Tenderness
Swelling
Warmth
Discolouration
70
How are DVTs diagnosed?
Clinical not sufficient
D-dimer - normal excludes it, positive doesn't confirm diagnosis, blood test, also raised in infection, pregnancy ect, used to determine who to give ultrasound to
Ultrasound compression test - identify vein, push with ultrasound probe and squashes = empty, if not = full, likely to be with clot
Coagulation screen
FBC - including platelets
Wells score
71
How do you treat a DVT?
Low molecular weight heparin s/c od for min 5 days, weight adjusted dose
Oral wafarin INR 2-3 for 3 months
Direct oral anticoagulatns for 3 months
Compression stockings - prevents swelling and symptomatic relief
Treat underlying cause - malignancy, thrombophilia
Spontaneous DVT more likely to recur than provoked
NOACS
72
How do you prevent a DVT?
Mechanical - hydration, early mobilisation, compression stockings, foot pumps, leg elevation
Chemical - LMW heparin once daily injections, small dose so will not cause bleeding during surgery
Thromboprophylaxis
73
What is a pulmonary embolism?
Blockage of an artery in lungs by a substance that has moved elsewhere
Often a piece of/a thrombus
74
What are the signs of a pulmonary embolism?
Hypotension, cyanosis, severe dyspnoea, right heart strain/failure
75
What are the symptoms of a PE?
```
Sudden, sharp, pleuritic chest pain
Dyspnoea - sudden
Signs/symptoms of DVT
Risk factors
No other diagnosis more likely
Coughing up blood
Fainting
```
76
What are the signs of a PE?
```
Tachycardia
Tachypnoea
Pleural rub
Anxiety
Cor pulmonae (RHF)
Cyanosis
Raised JVP
Pleural effusion
Hypoxic
```
77
How do you diagnose a PE?
Chest x-ray usually normal - no signs of pneumonia
ECG - sinus tachycardic
Blood gases - T1 respiratory failure, decreased O2 and CO2
D-dimer
Ventilation/perfusion scan
CTPA spiral CT with contrast
78
What could be a differential diagnosis for a PE?
Chest infection
79
How do you treat a PE?
```
Same as DVT
Ensure normal Hb, platelets, renal function and baseline clotting
LMW heparin s/c od weight adjusted
DOAC
Oral warfarin 6 months
Treat cause
IVC filter
Admit to ITU
```
80
How is PE prevented?
Same as DVT
81
What is the main complication of a PE?
Sudden death
82
What are the main differences in the signs and symptoms of arterial and venous thrombosis?
Venous - warm limb, pulse, pain, redness, cramps, tenderness
| Arterial - cold, decreased/no pulse, pain in affected area due to hypoxia, pallor, paraesthesia, claudication
83
What are the 6 main signs of acute limb ischaemia?
```
6Ps
Perishingly cold
Paraesthesia
Pallor
Pain
Pulselessness
Paralysis
```
84
What is Virchow's triad?
Triad of three things that can cause blood clotting
Stasis - lack of movement
Hypercoagulability
Vessel wall injury
85
What is the difference in the treatment of arterial and venous thrombosis?
Arterial thrombosis - treatment with drugs that target platelets
Venous thrombosis - treatment with drugs that target fibrin
86
What is leukaemia?
Rapidly proliferating immature blast blood cells in bone marrow that are non-functional
Neoplasm within bone marrow
Generally unwell - systemic B symptoms
Generalised cytopenia - infection bleeding - progenitors can't mature, too many blasts
87
What are the 4 different types of leukaemia?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
88
What is ALL?
Most common between 2-4 years
Malignancy of immature lymphoid cells
Affects B/T lymphocytes, arrests maturation and promotes uncontrolled proliferation of immature blast cells/lymphoid cells
Majority B cell precursors
Increased proliferation of immature lymphoblast cells in bone marrow - if all B cells children, if all T cells adults
Commonest cancer in childhood
Combination of genetic susceptibility and environmental trigger
Ionising radiation during pregnancy and Down's syndrome associated
CNS involvement common
89
What is AML?
Neoplastic proliferation of blast cells derived from marrow myeloid elements
Progresses rapidly with death in 2 months if untreated
Commonest acute leukaemia of adults
Associated with radiation and Down's syndrome
90
What is CML?
Uncontrolled clonal proliferation of myeloid cells
Disease of adults
40-60 most common age
Slight male predominance
More than 80% have Phiadelphia chromosome which forms a fusion gene - stimulates cell division
91
What is CLL?
Commonest leukaemia
Occurs later in life
Accumulation of mature B cells that have escaped programmed cell death and undergone cell-cycle arrest
Mutations, trisomies and deletions influence risk
Pneumonia triggering event sometimes
92
What is the pathophysiology of leukaemia?
Divide rapidly but serve no function so wasting energy making useless cells and so less energy available to make functional cells
Due to rapid replication cells take up a lot of space in bone marrow meaning little space and less food for other cells to grow
Bone marrow makes fewer functioning cells and so fewer functioning cells in blood giving symptoms of leukaemia
No longer space in bone marrow, leukaemia cells present into blood too
Can occur at any age but type depends on age
93
What is the pathophysiology of CLL?
Many stable for years and may regress
Death often due to complication of infection
May transform into aggressive lymphoma - Richter's syndrome
94
How does ALL present?
Marrow failure
- Anaemia low Hb, SOB, fatigue, angina, claudication, pallor, cardiac flow murmur
- Infection low WCC
- Bleeding low platelets
- Bone marrow infiltration = bone pain
- Liver/spleen infilatration = hepatosplenomeglay
- Node infiltration = lymphadenopathy
- CNS infiltration = headache, cranial nerve palsies
- Mediastinum infiltration resulting in mediastinal masses with SVC obstruction
95
How does AML present?
Marrow failure
- Anaemia
- Infection
- Bleeding
- Hepatomegaly and splenomegaly due to infiltration
Gum hypertrophy
DIC occurs in subtype of AML where release of thromboplastin
96
How does CML present?
```
Symptomatic anaemia
Abdominal discomfort - splenomegaly
Weight loss
Tiredness
Pallor
Fever and sweats in absence of infection
Features of gout due to purine breakdown
Bleeding due to platelets dysfunction
```
97
How does CLL present?
```
Often no symptoms - diagnosed on routine FBC
Anaemia/infection prone
Severe - weight loss, sweats, anorexia
Hepatosplenomegaly
Enlarged, rubbery, non-tender nodes
```
98
How is ALL diagnosed?
FBC and blood film - WCC high, blast cells on film and in bone marrow
CXR and CT scan for mediastinal and abdominal lymphadenopathy
Lumbar puncture for CNS involvement
99
How is AML diagnosed?
WCC raised, can be normal/low
Few blast cells in peripheral blood
Bone marrow biopsy
Differentiation from ALL based on microscopy, immunophenotyping and molecular methods
100
How is CML diagnosed?
Blood count - high WCC, low Hb (normochromic, normocytic), platelets low, normal or raised
Bone marrow aspirate - hypercellular
101
How is CLL diagnosed?
Normal/low Hb, raised WCC with v high lymphocytes
| Blood film - smudge cells seen in vitro
102
How is ALL treated?
Blood and platelet transfusions
Neutropenia may lead to deadly infections - prophylactic antivirals, antibacterial and antifungals
Allopurinol - prevents tumour lysis syndrome
IV fluids - insert Hickman line so can easily take blood for testing and administer drugs and fluids
Chemotherapy
Marrow transplant
103
How is AML treated?
Blood and platelet transfusion
Neutropenia - prophylactic antivirals, antibacterial and antifungals
Allopurinal to prevent tumour lysis syndrome
IV fluids - Hickman line
Chemo
Marrow transplant
104
How is CML treated?
Oral imatinib - specific BCR/AB, tyrosine kinase inhibitor
| Stem cell transplant
105
How is CLL treated?
```
Blood transfusions
Human IV immunoglobulins
Chemo/radiotherapy
Stem cell transplant
Prognosis - rule of 3
- 1/3 will never progress
- 1/3 will progress slowly
- 1/3 will progress actively
```
106
What are the complications of CLL?
Autoimmune haemolysis
Increased infection risk due to hypogammaglobinaemia, bacterial and viral especially herpes zoster
Marrow failure
107
What is the MCV of microcytic anaemia?
MCV < 80
108
What is the MCV of normocytic anaemia?
MCV 80-100
109
What is the MCV of macrocytic anaemia?
MCV > 100
110
How does iron deficiency cause anaemia?
Iron absorbed in duodenum
Iron necessary for formation of haem
Low iron = lack of effective red blood cells = anaemia
111
What can cause iron deficiency?
```
Low iron diet
Blood loss
Breast feeding
Hookworm
Malabsorption
Pregnancy
```
112
What are the signs of iron deficiency anaemia?
Brittle hair and nails
Atrophic glossitis (tongue inflammation with depapillation)
Kolionychia (spoon shaped nails)
Angular stomatitis (inflammation of corners of mouth)
113
How do you investigate iron deficiency anaemia?
FBC - hypochromic microcytic anaemia
Serum ferritin - low
Reticulocyte count - low
Endoscopy - possible G bleed related cause
114
What are the possible side effects of iron deficiency anaemia treatment?
```
Black stools
Constipation
Diarrhoea
Nausea
GI upset
Epigastric abdominal pain
```
115
What are the complications of pernicious anaemia?
HF
Angina
Neuropathy
116
What are the signs and symptoms of haemolytic anaemia?
Gallstones (excess bilirubin)
| Signs - jaundice (excess bilirubin), leg ulcers, splenomegaly, signs of underlying disease (SLE)
117
How is haemolytic anaemia treated?
Folate and iron supplements
Immunosuppressives
Splenectomy
118
What is bone marrow failure and how does it cause anaemia?
Reduction in number of pluripotent stem cells causes lack of haemopoiesis (production of blood cells and platelets)
Reduced number of new RBCs produced to replace the old ones causes anaemia
119
What are the causes of bone marrow failure?
Congenital
Acquired (aplastic anaemia)
Cytotoxic drugs/radiation
Infections
120
What are the specific signs/symptoms of bone marrow failure?
Increased susceptibility to infection
Increased bruising
Increased bleeding (especially from nose and gums)
121
How do you diagnose aplastic anaemia?
FBC - pancytopenia
Reticulocyte count - low
Bone marrow biopsy - hepatocellular marrow with increased fat spaces
122
How do you treat aplastic anaemia?
Removal of causative agent
Blood/platelet transfusion
Bone marrow transplant
Immunosuppressive therapy
123
What could be a differential diagnosis of DVT?
Cellulitis
124
What is lymphoma?
Disorders caused by a malignant proliferation of lymphocytes
Accumulate in lymph nodes causing lymphadenopathy, may also be found in peripheral blood or infiltrate organs (bone marrow, liver, spleen)
125
What are the two different types of lymphoma?
Hodgkin's lymphoma
| Non-Hodgkin's lymphoma
126
How common is Hodgkin's lymphoma?
```
Male predominance
Majority cases 13-19 and elderly (two peaks of incidence)
EBV suggested role in pathogenesis
Rare-ish
Staged with Ann Arbor system
```
127
What is Non-Hodgkin's lymphoma?
All lymphomas w/o Reed-sternberg cells
80% B cell origin, diffuse large B cell lymphoma commonest
20% T cell origin
Generally more varied in presentation, sub-types, treatments and outcomes
Not all centre on nodes
Strong link to EBV and Burkitt's lymphoma
Median survival 20 yrs
Can be low grade, high grade (diffuse large B cell lymphoma)/very high grade (Burkitt's lymphoma)
128
What are the two types of Hodgkin's lymphoma?
Classical Hodgkin's lymphoma - Reed-Sternberg cells with mirror image nuclei 90-95% cases
Nodular lymphocyte predominant Hodgkin's lymphoma (Reed-Sternberg variant)
129
What can cause lymphoma?
```
Primary immunodeficiency
Secondary immunodeficiency - HIV/AIDS, transplant recipients
Infection - EBV
Autoimmune disorders (RA, SLE, Sjorgrens)
```
130
What is the difference between Non-Hodgkin's lymphoma and Hodgkin's lymphoma?
Reed-Sternberg cells in Hodgkin's lymphoma
Bone marrow infiltration earlier in NHL
Many more different types in NHL
Found in elderly NHL
131
How does EBV lead to an increased risk of lymphoma?
Impaired immunosurveillance of EBV infected cells
| Infected B cells escape regulation and proliferate autonomously
132
What can increase your risk of getting Hodgkin's lymphoma?
```
Affected sibling
EBV
SLE
Obesity
Post-transplantation
```
133
What can increase your risk of getting Non-Hodgkin's lymphoma?
FHx - minor increased risk
AIDS
Autoimmune conditons
134
How does lymphoma present?
```
Enlarged lymph glands
Constitutional B symptoms:
- Loss of appetite
- Loss of weight
- Night sweats
- Fever
Hepatosplenomegaly
```
135
How does Hodgkin's lymphoma present?
Painless cervical lymphadenopathy
Localised to mediastinum with cough (mediastinal lymphadenopathy)
Emergency presentation:
- Infection, SVC obstruction with increased JVP, sensation of fullness in head, dyspnoea, blackouts, facial oedema
136
How does non-Hodgkin's lymphoma present?
Nodal disease - superficial lymphadenopathy
Extra-nodal disease - skin (espcially T cell lymphomas), oropharynx, gut, small bowel, bone, CNS, lungs
Pancocytopenia - anaemia, infection, bleeding (due to reduced platelets), due to marrow involvement
137
How is non-Hodgkin's lymphoma classified?
Low/indolent
- Follicular lymphoma, slow growing, usually advanced at presentation, incurable, median survival 9-11 yrs
High grade
- Diffuse large B cell lymphoma, nodal presentation, 1/3 have extra-nodal involvement
138
How is lymphoma diagnosed?
```
Blood film and bone marrow biopsy
Lymph node biopsy
Immunophenotyping - CD20, also gives treatment indication
Cytogenetics - karotyping, FISH
PCR
```
139
How is Hodgkin's lymphoma diagnosed?
CT/MRI chest, pelvis, abdomen for staging
Lymph node excision/bone marrow biopsy
Bloods - high ESR/low Hb, high serum lactate dehydrogenase
PET scan
140
What is the Ann Arbor classification?
For Hodgkin's lymphoma
I - confined to single lymph node region
II - involvement of 2 or more nodal areas on same side of diaphragm
III - involvement of nodes on both sides of diaphragm
IV - spread beyond lymph nodes eg liver/bone marrow
A or B - A no systemic symptoms other than pruritus, B presence of B symptoms
141
How is Non-Hodgkin's lymphoma diagnosed?
Raised lactose dehydrogenase reflects worse prognosis as sign of increased cell turnover and thus cell proliferation
Lymph node excision/bone marrow biopsy for classification
CT/MRI of chest, abdo, pelvis
142
What could be a differential diagnosis for lymphoma?
LN lump
Reactive LN - infective (bacterial, viral, TB), inflammatory
Malignant - lymphoma, metastatic, primary head and neck
Arising from neck structures behind - thyroid
Embryonic remnant
143
How is Hodgkin's lymphoma treated?
Combination therapy - ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)
Stage I-A to II-A with less than 3 areas involved = short course ABVD w/radiotherapy
Stage II-A to IV-B with more than 3 areas involved = long course ABVD
Relapses - autologous bone marrow transplant
V treatable so good long term survival - want to minimise long term effects of treatment
144
How is non-Hodgkins lymphoma treated?
R-CHOP
- Rituximab (targets CD20), cyclophosphamide, hydroxy-daunorubicin, vincristine, prednisolone
Low grade - no Tx may be required, watch and wait, radiotherapy in localised disease
High grade
- Early 3m R-CHOP w/radiotherapy
- Late 6m R-CHOP w/radiotherapy
145
What is Burkitt's lymphoma?
V high grade non-Hodgkin's lymphoma
| Usually B cell with jaw lymphadenopathy in children
146
What are the complications of lymphoma treatment?
```
Infertility
Anthracyclines - cardiomyopathy
Bleomycin - lung damage
Vinca alkaloids - peripheral neuropathy
Second cancer
Psychological issues
```
147
What is myeloma?
Neoplastic proliferation of bone marrow plasma cells
Cancer of differentiated B lymphocytes (plasma cells)
Accumulation of malignant plasma cell in bone marrow leads to progressive bone marrow failure
148
When is myeloma more common?
```
Peak age 70
More common in Afro-Caribbean's than Caucasians
40 cases per million
Prevalence 180-270 cases
100,000 per population
More common in men
```
149
What is the pathophysiology of myeloma?
Normal plasma cell produce a wide range of immunoglobulins but in myeloma malignant plasma cells produce an excess of one type of immunoglobulin - monoclonal paraprotein (mostly IgG 55% and IgA 20%)
Often other Ig levels low resulting in immunoparesis meaning increased susceptibility to infections (infection main cause of death in myeloma patients)
Malignant plasma cells release factors that result in activation of osteoclasts = increasing bone turnover and resulting in bone breakdown and lytic lesions (RANK ligand and IL-3 result in osteoclast activation, inhibition of osteoblasts thus decreasing new bone formation
150
How does myeloma present?
OLD CRAB
Old age
Calcium elevated - confudion
Renal failure - nephrotic syndrome due to raised immunoglobulins that precipitate and deposit in organs, especially in kidneys
Anaemia - neutropenia/thrombocytopenia resulting in infection, bleeding, fatigue and pallor
Bone lytic lesions - back pain
Recurrent bacterial infections due to neutropenia
151
How is myeloma diagnosed?
Blood - normocytic normochromic anaemia, raised ESR, Rouleaux formation on blood film (stacks/aggregations of erythrocytes)
U&Es - high Ca, high alkaline phosphatase
Bence-Jones protein in urine
X-ray (skull, chest, pelvis) - lytic punched out lesions pepper-pot skull, vertebral collapse, fractures, osteoporosis
Serum and urine electrophoresis - B2-microglobulin present and prognostic
Monoclonal protein band in serum or urine, increase plasma cells on bone marrow biopsy
MRI - spinal cord compression?
Bone marrow aspiration - showing excess plasma cells
152
How is myeloma treated?
Bone pain - analgesia but avoid NSAIDs due to risk of renal impairment
Bisphosphonate - reduce fractures, and bone pain
Anaemia - transfusion of RBCs and erythropoietin
Rehydrate and ensure adequate fluid intake of 3L per day to prevent further renal damage
Renal dialysis to treat acute renal failure
Treat infections with broad spectrum antibiotics quickly
Chemo - CTD (cyclophosphamide, thalidomide, dexamethasone max 8 cycles for less fit people) or VAD (vincristine, adriamycin, dexamethasone in fitter people max 6 cycles)
Stem cell transplant
High infection precautions
153
What is disseminated intravascular coagulation?
Systemic activation of coagulation either by release of procoagulant material such as tissue factor or via cytokine pathways as part of inflammatory response
Generation of fibrin within blood vessels and consumption of platelets and coagulation factors causing secondary activation of fibrinolyisis
Initial thrombosis followed by bleeding tendency
Never occurs in isolation
Rare but life threatening
154
What can cause DIC?
```
Massive activation of coagulation cascade
Initiating factors - extensive damage to vascular endothelium thereby exposing tissue factor, enhance expression of tissue factor by monocytes in response to cytokines
Sepsis
Major trauma and tissue destruciton
Advanced cancer
Obstetric complications
Infections
Haemolytic transfusion reactions
Liver disease
```
155
What is the pathophysiology of DIC?
Activation of coagulation leads to widespread generation of fibrin and depositing in blood vessels leading to thrombosis and multi-organ failure
Consumption of platelets and clotting factors with increased risk of bleeding
Cytokine release in response to SIRS usually caused by sepsis, trauma, pancreatitis, obstetric emergency or malignancy
Widespread systemic generation of fibrin within blood vessels caused by initiation of coagulation pathway
Microvascular thrombosis and thus organ failure or consumption of platelets and coagulation factors leading to bleeding by inhibiting fibrin polymerisation
156
How does DIC present?
Patient often acutely ill and shocked
Bleeding from mouth, nose, venepuncture sites
Widespread ecchymoses
Confusion
Bruising
Thrombotic events occur as a result of vessel occlusion by fibrin and platelets - any organ may be involved but skin, brain and kidneys most affected
157
How is DIC diagnosed?
Severe thrombocytopenia
Suggested from history
Elevated FDPs - D-dimer due to intense fibrinolytic activity that is stimulated by presence of fibrin in circulation
Blood film shows fragmented RBCs
Prolonged prothrombin time, activated partial thromboplastin time, thrombin time
158
How is DIC treated?
Treat underlying condition - maintain blood volume and tissue perfusion
Replace platelets if very low via transfusion
Fresh frozen plasma to replace coagulation factors
Cryoprecipitate to replace fibrinogen and some coagulation factors
Red cell transfusion
Activated protein C
159
What kind of patients might be over coagulated?
Vit K antagonists - warfarin
| NOACS - apixiban
160
Why might patients be over coagulated?
Bad patient compliance
Artificial valves
New/interacting drugs
161
What are the symptoms of over anti-coagulation?
```
Bruising
Bleeding
Melena (black, tarry stools)
Epistaxis (nose bleed)
Haematemesis (vomiting blood)
Haemoptysis (coughing blood)
```
162
How do you assess bleeding?
APTT (activated partial thromboplastin time) - intrinsic pathway
PTT (prothrombin time) - extrinsic pathway
163
What is heparin induced thrombocytopenia?
Development of IgG antibody against complex formed between platelets and heparin
IgG binds to complex forming IgG/PF4/heparin which in turn binds to and activates platelets
Results in platelet consumption and thus thrombocytopenia
Also leads to thrombosis and skin necrosis
164
What are the risk factors for developing heparin induced thrombocytopenia?
Recent cardiac bypass surgery (lots of heparin used)
| Those on unfractionated heparin treatment
165
How does heparin induced thrombocytopenia present?
Sharp fall in platelets 5-10 days after starting heparin treatment
166
How is heparin induced thrombocytopenia treated?
Life threatening - stop heparin immediately and try alternative anticoagulation even if platelets low
Never re-expose patient to heparin
167
What can cause thrombocytopenia?
Reduced platelet production in bone marrow
Excessive peripheral destruction of platelets
Problems of an enlarged spleen
168
What is immune thrombocytopenia purpura?
Thrombocytopenia due to immune destruction of platelets
Antibody coated platelets removed following binding to Fc receptors on macrophages
IgG antibodies form to platelets and megakaryocytes
Often triggered by viral infection or malignancy
169
What are the different types of immune thrombocytopenia purpura?
Primary - ITP in children, acute, 2-6 years, acute onset with muco-cutaneous bleeding, history or recent viral infection including varicella zoster/measles
May also follow immunisation, life threatening haemorrhage rare, sudden self-limiting purpura (skin haemorrhages)
Secondary - adults, chronic, seen in women, associated with other autoimmune disorders such as SLE, thyroid disease, autoimmune haemolytic anaemia
Seen in patients with CLL, solid tumours, after infections with viruses like HIV, Hep C, platelets autoantibodies
170
How does ITP present?
```
Easy bruising
Epistaxis
Menorrhagia
Purpura (red/purple spots on skin caused by bleeding underneath skin)
Gum bleeding
Major haemorrhage rare
Splenomegaly rare
```
171
How is ITP diagnosed?
Bone marrow examination - increased/normal megakaryocytes in marrow, thrombocytopenia
Platelets autoantibodies
172
How is ITP treated?
First line - corticosteroids (prednisolone), IV immunoglobulin (IV IgG raises platelet count more rapidly that steroids), anti-D
Second line - splenectomy, if splenectomy fails then immunosuppression
173
What is thrombocytopenia?
Deficiency of platelets in blood
| Can be due to either decreased production or increased destruction
174
What conditions might cause decreased production of platelets?
Congenital thrombocytopenia - absent/reduced/malfunctioning megakaryocytes in bone marrow
Infiltration of bone marrow
Reduced platelets production by bone marrow - low B12/folate, reduced thrombopoietin, medications (methotrexate), toxins, infections, aplastic anaemia
Dysfunctional production of platelets in bone marrow
175
What conditions may cause increased deconstruction of platelets?
Autoimmune - ITP
Hypersplenism
Drug related immune destruction - heparin induced thrombocytopenia
Consumption of platelets - DIC, TTP
176
What is thrombotic thrombocytopenia purpura?
Widespread adhesion and aggregation of platelets leading to microvascular thrombosis in small vessels and thus consumption of platelets - results in low platelet count and organ damage
Reduction in ADAMTS-13 - protease responsible for degradation of vWF
Large multimers of vWF form resulting in platelet aggregation and fibrin deposition in small vessels leading to microthrombi
Less common than ITP
177
What may cause TTP?
```
Idiopathic
Autoimmune eg SLE
Cancer
Pregnancy
Drug associated eg quinine
```
178
How does TTP present?
```
Florid purpura
Fever
Fluctuating cerebral dysfunction
Haemolytic anaemia with red cell fragmentation
Easy bruising
Epistaxis/menorrhagia
AKI
```
179
How is TTP diagnosed?
Coagulation screen normal
Lactate dehydrogenase raised due to haemolysis
Normal/increased megakaryocytes
180
How is TTP treated?
Plasma exchange to remove antibody to ADAMTS-13 and provide a source of ADAMTS-13
IV methylprednisolone
IV rituximab
181
What are the two types of haemophilia?
Haemophilia A - factor 8 deficiency - treat with IV factor 8
| Haemophilia B - factor 9 deficiency
182
What is haemophilia?
X-linked recessive disorders, females are rarely severely affected
Haemophilia A more common
Symptoms anything associated with excess bleeding
Normal PTT
but prolongued
APTT
183
What is good about sickle cell gene?
Carriers are protected from falciparum malaria
184
What are the symptoms of sickle cell disease?
Chronic haemolysis produces stable Hb level
Often don't have anaemia symptoms
If Hb falls suddenly get symptoms
Possible causes of symptoms
- Splenic sequestration/infarction
- Bone marrow aplasia, destroyed erythrocyte precursors
- Further haemolysis drugs/acute infection
- Gallstones, leg ulcers, AVN of femoral head
185
What are the potential consequences of sickle cell disease?
Acute - painful crisis, sickle cell chest crisis, haemolytic, mesenteric ischaemia
Chronic - renal impairment, pulmonary hypertension, joint damage
186
How do you test for sickle cell disease?
Screen neonates - blood/heel prick test
FBC - Hb, reticulocyte count
Hb electropharesis for dx - HbSS present and absent HbA
187
How do you treat sickle cell disease?
Supportive - aggressive analgesia ie opiates, treat underlying cause eg antibiotics, fluids, folic acid, transfuse with falling Hb
Disease modifying treatment - hydroxycarbamide, transfusion, stem cell transplant
If hyposplenic - prophylactic Abx, pneumococcal and meningococcal vaccines
188
What is polycythaemia?
Increase in red blood cell mass (erythrocytosis)
| Increase in haemoglobin, packed cell volume, haematocrit and red cell count
189
What happens in polycythaemia rubra vera?
Vast majority of cases point mutation that causes substitution of phenylalanine for valine at position 617
Commoner over 60
JAK2 cytoplasmic tyrosine kinase that transduces signals especially those triggered by haemopoietic growth factors such as erythropoietin
190
What are the primary causes of polycythaemia?
Increases sensitivity of bone marrow cells to EPO - increased RBC production
Polycythaemia rubra vera - genetic mutation in JAK2 gene
Primary familial and congenital polycythaemia - mutation in EPOR gene
191
What are the secondary causes of polycythaemia?
More RBCs due to more circulating EPO
Chronic hypoxia
Poor O2 delivery - high altitude
Abnormal RBC structure and tumours that release high levels of EPO (renal carcinoma, hepatocellular carcinoma)
192
What are the relative causes of polycythaemia?
Decreased plasma volume and normal RBC mass
Apparent polycythaemia - chronic form associated with obesity, hypertension, high alcohol and tobacco intake
Dehydration - acute
193
What occurs during polycythaemia rubra vera?
Clonal stem cell disorder resulting in malignant proliferation of a clone derived from one pluripotent marrow stem cell
Erythroid progenitor offspring are unusual in not feeding erythropoietin and avoid apoptosis
Excess proliferation of RBCs, WBCs and platelets which causes a raised haematocrit (packed cell volume) resulting in hyperviscosity and thrombosis
Major complications of thrombosis and haemorrhage
194
How does polycythaemia present?
```
Asymptomatic and only detected on FBC
Over 60
Vague symptoms due to hyperviscosity - headaches, itching, tiredness, dizziness, tinnitus, visual disturbance
Severe itching after hot bath/when patient war,
Erythromelagia - burning sensation in fingers and toes
Gout due to increased turnover
Hypertension
Angina
Intermittent claudication
Plethoric complexion
Hepatosplenomegaly
Risk of thrombosis and haemorrhage
Easy bleeding/bruising
```
195
How is polycythaemia diagnosed?
Blood count - raised WCC and platelets
Raised Hb
Presence of JAK2 mutation on genetic screen
Bone marrow biopsy showing prominent erythroid, granulocytic and megakaryocytic proliferation
Serum EPO low
196
How is polycythaemia treated?
No cure - just aim to maintain normal blood count
Venesection - lower PCV and platelet count, removal of 400-500ml blood weekly
Chemotherapy - hydroxycarbamide and low dose bulsulfan
Low dose aspirin
Radioactive phosphorua but only those over 70 due to increased risk of acute leukaemia
Allopurinol to block uric acid production and reduce gout
Secondary - treat cause
197
What is thalassaemia?
Genetic disease of unbalanced Hb synthesis, under production or no production of one Hb chain
Precipitation of globin chains in RBC precursors and causes ineffective erythropoiesis (reduced production)
Precipitation of globin chains in mature red cells causes haemolysis (premature rupture/destruction of RBCs)
198
Where is thalassaemia most common?
Common in Mediterranean and Far East
| Autosomal recessive
199
What are the two types of thalassaemia?
Beta - reduced B chain synthesis
| Alpha - reduced A chain synthesis
200
What is the pathophysiology of beta-thalassaemia?
Excess alpha chains and little/no production of beta chains
Excess alpha combine which whatever delta/gamma chains produced
Increased HbA2 (Hb delta) and HbF resulting in ineffective erythropoiesis and haemolysis
Point mutations
Defects in transcription, RNA splicing and modification, translation via frame shifts and nonsense codons producing highly unstable beta globin which cannot be used
Heterozygous usually asymptomatic microcytosis with/without mild anaemia
201
What is the pathophysiology of alpha thalassaemia?
Gene deletions
Alpha-globin chain duplicated on both chromosomes 16, deletions of one or both
4 genes control alpha globin chain production
Presentation varies from mild anaemia to severe condition incompatible with life
202
How do the different numbers of deletions present in alpha thalassaemia?
4 deletions = no a-chain synthesis, only Hb Barts which cannot carry O2, incompatible with life, stillborns
3 deletions - common in parts of Asia, low levels of HbA and Hb Barts, severe haemolytic anaemia and splenomegaly, sometimes transfusion dependent
2 deletions - asymptomatic with possible mild anaemia
1 deletion - blood picture normal
Carriers protected from falciparum malaria
203
How does minor beta-thalassaemia present?
Common carrier state
Heterozygous
Asymptomatic
Anaemia mild/absent
RBCs hypochromic and microcytic with low MCV
Can be confused with iron deficiency but can be distinguished since serum ferritin and iron stores normal
204
How does intermediate beta-thalassaemia present?
```
Symptomatic with moderate anaemia
Don't require regular transfusions
Splenomegaly
Bone deformities
Recurrent leg ulcers
Gallstones
Infections
```
205
How does major beta-thalassaemia present?
In children with homozygous in 1st yr of life
Failure to thrive with recurrent bacterial infections
Severe anaemia from 3-6 months
Extramedullary haematopoiesis resulting in hepatosplenomegaly and bone expansion
Hypertrophy of ineffective bone marrow leads to bone abnormalities - skull bossing and thalassaemic facies
Skull x-ray shows hair on end sign due to increased marrow activity
MCV v low
Blood film - large and small irregular hypochromic RBCs
Serum ferritin normal
206
How is beta-thalassaemia diagnosed?
FBC and film - Hyperchronic microcytic anaemia
Raised reticulocyte count
Nucleated RBCs in peripheral circulation
Hb electrophoresis - Increased HbF and absent/less HbA
207
How is beta-thalassaemia treated?
Regular life-long transfusions to keep Hb above 90g/L and to suppress ineffective extramedullary haematopoiesis and to allow normal growth
Iron chelating agents to prevent iron overload - oral deferiprone and SC desderrioxamine
Large doses of ascorbic acid to increased urinary excretion of iron
Spenomegaly if hypersplensim persists with increasing transfusion requirements - after childhood to reduce infection risks
Bone marrow transplant
Long term folic acid
Promote fitness and healthy diet
208
What is membranopathy?
Autosomal dominant condition
Deficiency in protein used to make red cell membrane resulting in deformed cells that get trapped in spleen (extravascular haemolysis)
Spherocytosis (vertical deformity) and eliptocytosis (horizontal deformity)
209
How does membranopathy present?
```
Neonatal jaundice and haemolytic anaemia exacerbated during infection (splenomegaly)
Excess bilirubin (gallstones)
```
210
How do you diagnosed membranopathy?
FBC and reticulocyte count
| Blood film - omotic fragility tests (RBCs show fragility in hypotonic solutions_
211
How do you treat membranopathy?
Folic acid and splenectomy
212
What is glucose-6-phosphate deficiency?
X-linked disorder but can affect women
Mainly affects men in Mediterranean, Africa and Middle/Far East
Rarely symptomatic
213
What crisis can you get with glucose-6-phosphate deficiency?
Oxidative crisis
Precipitated by drugs or illness
In attacks - rapid haemolysis, jaundice, anaemia
214
How doe you diagnosed glucose-6-phosphate deficiency?
Film - bite and blister cells
| Enzyme assay
215
How do you treat glucose-6-phosphate deficiency?
Avoid precipitants like henna
| Transfusion if severe
216
What is tumour lysis syndrome?
Condition where a large number of cancer cells die within short period of time
Chemo given -> cancer cell broken down -> release contents (hyperkalaemia, nuclei acid) -> produce crystals and get deposited in kidneys -> damage/loss of function
217
How do you prevent tumour lysis syndrome?
Allopruinol (xantine oxidase inhibitor)
218
How do you treat tumour lysis syndrome?
IV fluids and correct electrolytes
219
What is malaria?
Protozoan infection caused by plasmodia spp
| Transmitted by bite of female anopheles' mosquito bit indoors at night
220
What are the 4 most important species of plasmodia?
P falciparum
P ovale
P vivax
P malariae
221
How common is malaria?
```
300-500 million cases per year
700,000 - 2.7 million deaths per year
50% fever in African children under 5
50% worlds population at risk
Increasing incidence
```
222
Why is there an increasing incidence of malaria?
Increasing resistance to anti-malarial drugs
Increased resistance of mosquito to insecticides
Ecological and climate changes so mosquitoes found in more countries
Increased travel to endemic areas
223
When may you be immune to malaria?
Genetic - sickle cell carriers, glucose-6-phosphate dehydrogenase deficiency, thalassaemias
Acquired - recurrent infection gives semi-immunity but lost if not re-infected after a couple of years, maternal transmission of antibodies across placenta but diminishes over time
224
What is the pathophysiology of a malaria infection?
Vector - female anopheles mosquito, mainly bites at night and indoors
Mosquito infected for life (3-4 weeks), lifecycle depends on water
Anaemia - haemolysis of infected RBCs, haemolysis of non-infected RBCs (Black water fever), splenomegaly, folate depletion
Cytokine release
Widespread organ damage - if P falciparum, RBCs containing schizonts adhere to lining of capillaries in brain, kidneys, gut, liver and other organs
Causes microcirculation obstruction (tissue hypoxia - cerebral malaria, ARDS, hypoglycaemia, renal failure, shock) and schizonts rupture releasing toxins stimulating further cytokine release
Parasite matures in RBC, knobs on RBC surface, infected cells bind to each other and receptors on endothelial cell walls
Sequestration in small vessels becoming trapped
225
How does malaria present?
```
Fever
Exotic travel
Chills, sweats
Jaundice
Anaemia
Hepatosplenomegaly
Fatigue
Black urine (black water fever)
Headache
Myalgia
Nausea and vomiting
Diarrhoea
```
226
How does P vivax/ovale present?
Relatively mild
Anaemia develops slowly and tender hepatosplenomegaly
Generally spontaneous recovery after 2-6 wks but hypnozoites in liver cna cause relapses after yrs
227
How does P malariae present?
Relatively mild illness, runs more chronic course
| Parasitaemia may persist for years with/without symptoms
228
How does P falciparum present?
Self-limiting illness
Serious complications, causes vast majority of deaths
High parasitaemia indicator of severe disease
Cerebral malaria - diminished consciousness, confusion, convulsions progressing to coma and death
Reduced brain perfusion caused by schizonts adhering to endothelial cells of capillaries - hypoxia to brain
Blackwater fever - widespread intravascular haemolysis, affecting both parasitized and unparasitized red cells diving rise to dark urine
229
How does malaria present in adults?
Coma, ARDS, anaemia, jaundice, hepatosplenomegaly, hypoglycaemia (parasites use glucose), blackwater fever, renal failure due to hypovolaemia, microvascular blockade due to schizonts, shock secondary to bacterial sepsis
230
How does malaria present in children?
Non-specific stop, crying, playing and eating, tachypnoea, anaemia, hypoglycaemia, cerebral malaria, raised intracranial pressure, convulsions, rule out meningitis
231
How is malaria diagnosed?
Thick and thin blood films - thick (sensitive but low resolution, tells you if malaria present), thin (can identify morphological features and quantification of parasitaemia, tells you type and parasite count, identification of species on thin film
RDT - rapid diagnostic test - detected plasmodium antigens in blood
Rule out meningitis
Pregnancy test
232
How is malaria treated?
Quinine and doxycycline
233
What is the lifecycle of the plasmodia spp?
Becomes infected after taking blood meal containing gametocytes
Developmental cycle in mosquito takes 7-10 days culminating in migration of infective sporozoites into insects salivary glands
Sporozoites inoculated into new human host and those not destroyed by immune system rapidly taken up by liver
Multiply inside hepatocytes as merozoities
Infected hepatocytes rupture releasing merozoites into blood, where rapidly taken up by erythrocytes
P vivax and P ovale - few parasites remain dormant in liver as hyponozoites where can reactivate at any time causing relapse infection (important for 2 yr travel history)
Inside RBCs, parasites multiply changing from merozoites to trophozoites to schizonts and appearing as 8-24 new merozoites
Erythrocytes rupture, releasing merozoites to further infect cells
Each cycle takes up to 48 hrs
P vivax and ovale mainly attack reticulocytes and young erythrocytes
P malaria - attacks older cells P falciparum - attacks any stage
A few merozoites with not develop into trophozoites but into gametocytes - not released from RBCs but taken up by mosquito blood meal to complete lifecycle
234
Name 4 haematological emergencies
Neutropenic sepsis temp > 38 and absolute neutropil count > 1x10^9 - antibiotics immediately
Acute sickle cell crisis - pain relief and IV fluid
Chest crisis - IV fluid, Abx, closely monitor
Spinal cord compression - steroid and MRI
235
Name an anti-emetic drug
Ondansetron
| 5HT3 antagonist
236
How does heparin work?
Often used in bypass surgery IV
Glycoaminoglycan
Binds to antithrombin 3 and increases its activityAT3 inactivated thrombin, factor Xa and other proteases involved in clotting cascade preventing clotting
Indirect thrombin inhibitor
Monitor with activated parital thromboplastin time (APTT)
Given by contunuous IV infusions
Easily reversed by proteamine
237
When is low molecular weight heparin used?
```
Smaller molecule
Less variation in does
Renally excreted
Given OD, weight-adjusted does give s/c
Used for treatment and prophylaxis
```
238
How does aspirin work?
Inhibits COX enzyme irreversibly
Acts for lifetime of platelets which is around 7-10 days
Inhibits thromboxane formation and hence platelet aggregation
Used in arterial thrombosis - given orally once daily
Clopidogrel similar but inhibits ADP induced platelet aggregation
Need to stop aspirin 5 days before surgery so platelets can recover
239
How does warfarin work?
Orally active
Prevents synthesis of active factors II, VII, IX, X (1972)
Antagonist/blocker of vitamin K (which is required for 1972 synthesis) as makes post-translation changes on them to make them active
Long half life (36 hrs)
Prolongs prothrombin time
Can reverse with vit K but takes time to produce new factors
Difficult to use - due to presence of vit K in diet so if vit K increases then warfarin requirement will also need to increase
Need to monitor used INR
Usual range 2-3
Higher range 3-4.5
240
How does NOACs work?
Orally active
Direct action on facto II or X
No blood tests or monitoring required
Shorter half-life so given twice/once daily
Used to extend thromboprophylaxis and treatment of AF and DVT and PE
Effect equivalent to INR 2-3, not higher, thus cannot be used with heart valves
Not used in pregnancy
