HAEMATOLOGY Flashcards
(327 cards)
1
Q
ANAEMIA
what is it?
A
low concentration of haemoglobin in the blood
2
Q
ANAEMIA
what are the different categories of causes of anaemia?
A
- microcytic (low MCV)
- normocytic (normal MCV)
- macrocytic (high MCV)
3
Q
ANAEMIA
what are the causes of microcytic anaemia?
A
TAILS
- Thalassaemia
- Anaemia of chronic disease (often CKD)
- Iron deficiency anaemia
- Sideroblastic anaemia
(also lead poisoning)
4
Q
ANAEMIA
what are the causes of normocytic anaemia?
A
3As and 2Hs
- Acute blood loss
- Anaemia of chronic disease
- Aplastic anaemia
- Haemolytic anaemia
- Hypothyroidism
5
Q
ANAEMIA
what are the different types of causes of macrocytic anaemia?
A
- megaloblastic (impaired DNA synthesis, preventing cells from dividing normally)
- normoblastic
6
Q
ANAEMIA
what are the causes of megaloblastic macrocytic anaemia?
A
- B12 deficiency
- folate deficiency
7
Q
ANAEMIA
what are the causes of normoblastic macrocytic anaemia?
A
- alcohol
- reticulocytosis (haemolytic anaemia or blood loss)
- hypothyroidism
- liver disease
- drugs (e.g. azathioprine)
8
Q
ANAEMIA
what are the generic clinical features?
A
SYMPTOMS
- tiredness
- SOB
- headaches
- dizziness
- palpitations
- worsening other conditions such as angina, HF or peripheral arterial disease
SIGNS
- pale skin
- conjunctival pallor
- tachycardia
- raised respiratory rate
9
Q
IRON DEFICIENCY ANAEMIA
what is the pathophysiology?
A
lack of iron leads to a deficiency in haemoglobin so smaller (microcytic) blood cells are produced
10
Q
IRON DEFICIENCY ANAEMIA
what is the epidemiology?
A
- most common cause of anaemia globally
- most commonly affects children, women of reproductive age + elderly
11
Q
IRON DEFICIENCY ANAEMIA
what are the causes?
A
DECREASED INTAKE
- low dietary iron (vegetarian/vegan diet, prematurity, poverty)
- malabsorption (coeliac, IBD, h.pylori, gastric surgery)
INCREASED IRON REQUIREMENT
- pregnancy
- breastfeeding
- growing children
INCREASED IRON LOSS
- blood loss (menorrhagia, malignancy, peptic ulcers, schistosomiasis, hookworm)
12
Q
IRON DEFICIENCY ANAEMIA
what are the clinical features?
A
SYMPTOMS
- fatigue
- dizziness/syncope
- poor concentration
- SOB
- chest pain
SIGNS
- pallor (skin + subconjunctival)
- koilonychia
- atrophic glossitis
- angular cheilitis
- aphthous ulcers
- restless leg syndrome
- PICA
13
Q
IRON DEFICIENCY ANAEMIA
what are the investigations?
A
BLOOD TESTS
- FBC (low Hb, low haematocrit, low MCV)
- iron studies (low iron, low ferritin, high transferrin, high TIBC)
- blood film (microcytic + hypochromic RBCs)
To consider
- TTG (if suspecting coeliac)
- OGD/colonoscopy (to investigate IBD and malignancy, should be considered in men and >60 where there is no obvious cause of iron deficiency anaemia)
14
Q
IRON DEFICIENCY ANAEMIA
what would iron studies show?
A
- low iron
- low ferritin
- high transferrin
15
Q
IRON DEFICIENCY ANAEMIA
what is the management?
A
1st line
- treat underlying cause
- oral iron (ferrous sulphate)
- IV iron (for severe anaemia or for IBD/HF)
2nd line
- packed red cell (PRC) transfusion (only if Hb <70, haemodynamically unstable or symptomatic)
16
Q
IRON DEFICIENCY ANAEMIA
what is a common side effect of oral iron?
A
black stools
17
Q
B12 DEFICIENCY
how is vitamin B12 absorbed?
A
- binds to intrinsic factor in the terminal ileum (intrinsic factor is produced by parietal cells of stomach)
18
Q
B12 DEFICIENCY
where is intrinsic factor produced?
A
parietal cells of the stomach
19
Q
B12 DEFICIENCY
what is the pathophysiology?
A
- lack of B12 impairs DNA synthesis
- this results in large, nucleated cells (megaloblasts)
- megaloblasts undergo apoptosis, leading to anaemia
- causes demyelination which leads to peripheral neuropathy + subacute combined degeneration of the spinal cord (SCDC)
20
Q
B12 DEFICIENCY
what are the causes?
A
- autoimmune = pernicious anaemia (anti-parietal cell antibodies damage parietal cells + stop intrinsic factor)
- malabsorption = coeliac disease, crohns disease, terminal ileum resection
- malnutrition = lack of meat, poultry, milk + eggs
- medications = PPIs, colchicine, metformin
21
Q
B12 DEFICIENCY
where is vitamin B12 stored?
A
in the liver
22
Q
B12 DEFICIENCY
which medications can cause B12 deficiency anaemia?
A
- PPIs
- colchicine
- metformin
23
Q
B12 DEFICIENCY
what are the clinical features that are unique to B12 deficiency anaemia?
A
SUBACUTE COMBINED DEGENERATION OF THE SPINAL CORD
- dorsal columns = sensory, vibration + proprioception loss
- lateral corticospinal tracts = UMN signs e.g. spastic paraparesis, brisk knee jerk + upgoing plantar
- spinocerebellar tract = ataxia
PERIPHERAL NEUROPATHY
- absent ankle jerk reflex
OPTIC NEUROPATHY
COGNITIVE IMPAIRMENT
24
Q
B12 DEFICIENCY
what are the investigations?
A
BLOODS
- FBC = macrocytic anaemia
- blood film = megaloblasts + hypersegmented neutrophils
- vitamin B12 + folate levels
To consider
- anti-parietal cell antibodies (raised in pernicious anaemia)
- intrinsic factor antibodies (raised in pernicious anaemia)
- LFTs + TFTs (to look for other causes of macrocytosis)
25
B12 DEFICIENCY
what is the management?
- dietary advice (eggs, meat, dairy, salmon)
- hydroxocobalamin IM
if not dietary related (e.g. pernicious anaemia) = IM hydroxocobalamin given every 2-3 months
if dietary related = cyanocobalamin 50-150 micrograms daily or twice-yearly hydroxocobalamin injection
following treatment initiation, do FBC 7-10 days after to see Hb rise
26
B12 DEFICIENCY
what are the complications?
NEUROLOGICAL
- subacute combined degeneration of the spinal cord
- peripheral neuropathy
- optic neuropathy
- neuropsychiatry (dementia)
HAEM
- macrocytic anaemia
- pancytopaenia
FOETAL
- neural tube defects (spina bifida)
27
FOLATE DEFICIENCY
what food is folate (folic acid) found in?
leafy green vegetables
legumes
fruits
28
FOLATE DEFICIENCY
where is folic acid absorbed?
in the jejunem
29
FOLATE DEFICIENCY
what are the causes?
MALNUTRITION (most common)
- lack of leafy green veg, legumes + fruits
ALCOHOL (most common)
MEDICATION
- methotrexate
- trimethoprim
- 5-fluorouracil
- anticonvulsants e.g. phenytoin
MALABSORPTION
- coeliac disease
- crohn's disease
- small bowel resection (particularly jejunem)
PREGNANCY
- increased demand for folate
- can lead to neural tube defects
30
FOLATE DEFICIENCY
which medications can cause folate deficiency?
- alcohol
- methotrexate
- trimethoprim
- 5-fluorouracil
- anticonvulsants e.g. phenytoin
31
FOLATE DEFICIENCY
what is the pathophysiology?
- folate deficiency results in impaired DNA synthesis
- results in large, nucleated cells (megaloblasts)
- megaloblasts undergo apoptosis resulting in anaemia
folate deficiency alone does not cause any neurological symptoms
32
FOLATE DEFICIENCY
what are the clinical features?
generic anaemia features
- lethargy
- pallor
- glossitis
- angular stomatitis
no neurological symptoms with folate deficiency alone
33
FOLATE DEFICIENCY
what are the investigations?
same as B12 deficiency
BLOODS
- FBC = macrocytic anaemia
- blood film = megaloblasts + hypersegmented neutrophils
- vitamin B12 + folate levels
34
FOLATE DEFICIENCY
what is the management?
DIETARY ADVICE
- asparagus, broccoli, brown rice, brussels sprouts, chickpeas + peas
FOLIC ACID
- 5mg daily for 4 months
- 400mcg daily for 12 weeks pregnancy (5mg if risk factors)
if patient has B12 + folate deficiency, treat B12 deficiency first to avoid neurological features
35
FOLATE DEFICIENCY
what are the complications?
HAEM
- macrocytic anaemia
- pancytopaenia
FOETAL
- neural tube defects (spina bifida, anencephaly, encephalocele)
36
HYPOSPLENISM
what are the functions of the spleen?
- activation of lymphocytes
- removal of damaged/effete RBCs from circulation
- sequestration of platelets for release during times of stress
- site of haematopoiesis in utero
37
HYPOSPLENISM
what is the pathophysiology?
reduced/absent splenic activity which leads to increased susceptibility to infections + haematological abnormalities
38
HYPOSPLENISM
what are types of causes?
- anatomical = loss or absence of splenic tissue
- functional hyposplenism = anatomically normal spleen does not function correctly
39
HYPOSPLENISM
what are the causes of anatomical hyposplenism?
- post-splenectomy
- auto-splenectomy (atrophy of spleen, seen in sickle cell disease)
- congenital asplenia
40
HYPOSPLENISM
what are the causes of functional hyposplenism?
- coeliac disease
- IBD
- haematological malignancies (leukaemias, lymphomas, myeloproliferative disorders)
- alcoholic liver disease (due to portal hypertension)
- chronic graft-vs-host disease (secondary to bone marrow transplant)
41
HYPOSPLENISM
what are the clinical features?
Does not cause any distinct signs/symptoms
Increased risk of infection
- N.Meningitidis
- H.Influenzae
- S.Pneumoniae
increased risk of severe falciparum malaria
increased risk of thrombotic events
42
HYPOSPLENISM
what are the investigations?
BLOODS
- FBC = thrombocytosis
- peripheral blood smear = Howell-Jolly bodies
- CT/MRI abdomen = atrophic/absent spleen
To consider
- pitted red cell count (PRC)
43
HYPOSPLENISM
what is the management?
IMMUNISATION
- vaccination to n.meningitidis, h.influenzae + s.pneumoniae
- annual flu vaccine
PROPHYLACTIC ANTIBIOTICS
- oral penicillins/macrolides if at high risk of pneumococcal infections
PATIENT EDUCATION
- comply with prophylactic measures
- wear medical bracelet
- avoid travel to malaria-endemic regions
- seek prompt medical attention if they develop signs/symptoms of infection
44
ALL
what is acute lymphoblastic leukaemia (ALL)?
Uncontrolled proliferation of immature lymphoblast cells (lymphoid progenitor cells)
affects lymphoid progenitor cells and lymphoblasts
45
ALL
what is the epidemiology?
- most common childhood malignancy
- 75% of cases occur <6yrs old
- bimodal distribution (1st peak = 4-5yrs, 2nd peak = >50)
- white males most commonly affected
46
ALL
what are the risk factors?
- previous chemotherapy
- radiation exposure
- down syndrome (20 x increased risk)
- benzene exposure (painters, petroleum, rubber manufacturers)
- family history
47
ALL
which cell lineage is most commonly affected?
B-cell = 75%
T-cell = 25%
48
ALL
what are the clinical features?
SYMPTOMS
- fatigue
- loss of appetite
- easy bruising, prolonged bleeding + mucosal bleeding (due to thrombocytopaenia)
- bone pain (due to bone marrow infiltration)
- weight loss
- recurrent infections (due to neutropaenia)
- fever
SIGNS
- lymphadenopathy
- hepatosplenomegaly
- pallor
- flow murmur (due to anaemia)
- parotid infiltration
- testicular swelling
- CNS involvement (meningism + CN palsies)
49
ALL
what are the investigations?
BLOODS
- FBC = lymphocytosis, thrombocytopaenia + normocytic anaemia with low reticulocyte count
- blood film = lymphoblasts
- bone marrow aspiration + trephine biopsy = >20% lymphoblasts (is diagnostic)
- immunophenotype = CD10 indicates B-cell ALL
- cytogenic + molecular studies
To consider
- lumbar puncture
- CXR (to identify mediastinal mass
50
ALL
what is the management?
- corticosteroids + chemotherapy
- intrathecal therapy for CNS infiltration
- often have maintenance therapy for 2 years
2nd line
- bone marrow transplant
51
ALL
what are the complications?
- myelosuppression + neutropaenic sepsis
- extramedullary involvement (CNS, testicular + renal involvement)
- infertility
52
AML
what is it?
Neoplastic proliferation of blast cells (immature blood cells)
affects myeloid progenitor cells and myeloblasts
53
AML
what is the epidemiology?
- most common acute leukaemia in adults
- uncommon <45yrs old
- is a rare malignancy
54
AML
what are the risk factors?
- increasing age
- myelodysplastic syndromes
- myeloproliferative neoplasms
- previous chemotherapy or radiation exposure
- benzene (painters, petroleum + rubber manufacturers)
55
AML
what are the clinical features?
SYMPTOMS
- fatigue
- loss of appetite (anorexia)
- bruising + mucosal bleeding
- weight loss
- fever
- recurrent infections
SIGNS
- pallor
- lymphadenopathy
- hepatosplenomegaly
56
AML
what are the investigations?
BLOODS
- FBC = leukocytosis, thrombocytopaenia + anaemia
- blood film = myeloblasts with AUER RODS
- clotting screen = DIC
- bone marrow aspirate + biopsy = >20% myeloblasts (diagnostic)
- cytogenic + molecular studies
57
AML
what is the management?
- chemotherapy
- corticosteroids
2nd line = stem cell transplant
58
AML
what are the complications?
- myelosuppression + neutropaenic sepsis
- DIC
- extramedullary involvement (rare)
59
CLL
what is it?
Chronic lymphocytic leukaemia is where there is slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes
60
CLL
what is the epidemiology?
- most common adult leukaemia
- usually affects >60yrs old
- twice as common in men
61
CLL
what are the clinical features?
often asymptomatic
SYMPTOMS
- fatigue
- easy bruising + prolonged bleeding
- loss of appetite
- weight loss
- fever
- recurrent infection
SIGNS
- lymphadenopathy
- hepatosplenomegaly
- signs of anaemia
It can cause warm autoimmune haemolytic anaemia
62
CLL
what are the investigations?
BLOODS
- FBC = lymphocytosis (thrombocytopaenia + anaemia may be present)
- blood film = increased number of mature lymphocytes + SMUDGE CELLS
- immunoglobulins = hypogammaglobinaemia
To consider
- bone marrow biopsy
- lymph node biopsy
- Coombs test
63
CLL
what is the management?
EARLY DISEASE
- monitoring via blood every 3-12 months
ACTIVE +/- ADVANCED DISEASE
- chemotherapy
- allogenic stem cell transplant
64
CLL
what are the complications?
- hypogammaglobinaemia
- warm autoimmune haemolytic anaemia
- Richter transformation (into non-hodgkins lymphoma)
65
CML
what is it?
Uncontrolled clonal proliferation of myeloid cells (basophils, eosinophils and neutrophils)
66
CML
what is the epidemiology?
- generally considered a disease of the elderly
- peak diagnosis is 65-74yrs
- more common in males
67
CML
which chromosome is present in 95% of patients with CML?
Philadelphia chromosome
forms a fusion gene BCR/ABL on chromosome 22 – has tyrosine kinase activity – simulate cell division
68
CML
why does the philadelphia chromosome cause CML?
Froms fusion gene BCR/ABL on chromosome 22 --> tyrosine kinase activity --> stimulates cell division
69
CML
what are the different phases?
CHRONIC PHASE
- lasts many years + may be asymptomatic
- may have non-specific symptoms e.g. fever, weight loss + splenomegaly
ACCELERATED PHASE
- further progression of disease
- may develop anaemia, thrombocytopaenia + immunodeficiency
BLAST CRISIS
- terminal phase
- blast cells make up >20% of blood
- has severe symptoms + pancytopaenia
70
CML
what are the clinical features?
SYMPTOMS
- fatigue
- weight loss, fever + night sweats
- SOB
- easy bruising + bleeding
- bone pain
- recurrent infections
SIGNS
- splenomegaly
- abdominal tenderness
- signs of anaemia
- pyrexia
71
CML
what are the investigations?
BLOODS
- FBC = leukocytosis, granulocytosis + anaemia (thrombocytosis seen in 30% of patients)
- blood film = increase is all stages of maturing granulocytes
- bone marrow biopsy = myeloblast infiltration
- cytogenic + molecular studies = PHILADELPHIA CHROMOSOME
72
CML
what is the management?
- tyrosine kinase inhibitor (imatinib)
- chemotherapy
- stem cell transplant if above fails
73
CML
what are the complications?
- myelosuppression + neutropaenic crisis
- predisposition to infection
- blast crisis
74
TUMOUR LYSIS SYNDROME
what is it?
results from chemicals released when cells are destroyed by chemotherapy.
Results in:
- high uric acid
- high K+
- high phosphate
- low calcium
75
TUMOUR LYSIS SYNDROME
how can it be prevented?
- good hydration + urine output
- allopurinol to suppress uric acid levels
76
LYMPHOMA
what is it?
cancer affecting lymphocytes inside the lymphatic system
cancerous cells proliferate inside the lymph nodes causing the lymph nodes to become abnormally large
77
LYMPHOMA
what are the different types?
- Hodgkin's lymphoma (specific disease)
- Non-Hodgkin's lymphoma (which includes all other types)
78
HODGKIN'S LYMPHOMA
what is it?
lymphoma with the presence of Reed-Sternberg cells
79
HODGKINS LYMPHOMA
what is the epidemiology?
- has bimodal distribution (1st peak = 20-25yrs, 2nd peak = 80yrs)
80
HODGKINS LYMPHOMA
what are the risk factors?
- EBV infection
- HIV
- autoimmune conditions (rheumatoid arthritis + sarcoidosis)
- family history
81
HODGKINS LYMPHOMA
what are the clinical features?
often presents with painless lymphadenopathy
SYMPTOMS
- B symptoms (fever, weight loss + night sweats)
- Pel-Ebstein fever (intermittent fever every few weeks)
- pruritus
- dyspnoea
SIGNS
- lymphadenopathy (painless, hard, rubbery, fixed, contiguous spread)
- splenomegaly (rare)
82
HODGKINS LYMPHOMA
what are the investigations?
FBC - leukocytosis
LDH - often elevated
lymph node USS
lymph node biopsy - REED-STERNBERG CELLS (Owl's eye nuclei)
staging imaging - CXR, CT neck, chest + abdomen + PET
immunophenotyping - reed-sternberg is CD15+CD30 positive
83
HODGKINS LYMPHOMA
how is it staged?
ANN ARBOR STAGING
1 = single lymph node region
2 = 2 or more lymph node regions on same side of diaphragm
3 = lymph node involvement on both sides of diaphragm
4 = involvement of one or more extralymphatic organs
84
HODGKINS LYMPHOMA
what is the management?
- chemotherapy (ABVD)
- radiotherapy
- rituximab
85
NON-HODGKINS LYMPHOMA
what is it?
lymphoma without the presence of Reed-Sternberg cells
86
NON-HODGKINS LYMPHOMA
what are the different types?
there are many different types
- diffuse B-cell lymphoma
- Burkitt lymphoma (associated with EBV)
- MALT lymphoma (usually around stomach)
87
NON-HODGKINS LYMPHOMA
what are the risk factors?
- HIV
- EBV
- h-pylori infection (associated with MALT lymphoma)
- Hep B + hep C infection
- exposure to pesticides
- exposure to trichloroethylene
- family history
88
NON-HODGKINS LYMPHOMA
what are the clinical features?
SYMPTOMS
- B symptoms (fever, weight loss + night sweats)
SIGNS
- lymphadenopathy (painless, hard, rubbery, fixed, non-contiguous spread)
- splenomegaly
- extranodal disease (bone marrow, thyroid, salivary gland, GI tract + CNS)
89
NON-HODGKINS LYMPHOMA
how is it staged?
Lugano classification
1 = confined to 1 node or group of nodes
2 = in more than one group of nodes on same side of diaphragm
3 = affects lymph nodes on both sides of diaphragm
4 = widespread involvement, including non-lymphatic organs such as the liver or lungs
90
NON-HODGKINS LYMPHOMA
what are the investigations?
FBC - leukocytosis
LDH + uric acid - often raised
lymph node USS
lymph node biopsy
bone marrow biopsy
to consider
- staging imaging
- genetic testing
- immunophenotype
91
NON-HODGKINS LYMPHOMA
what is the management?
depends on type + stage
may involve:
- watchful waiting
- chemotherapy (R-CHOP)
- monoclonal antibodies (rituximab)
- radiotherapy
- stem cell transplant
92
DIC
what is disseminated intravascular coagulation (DIC)?
A complex systemic disorder characrerised by simultaneous activation of coagulation + fibrinolysis
93
DIC
what is the pathophysiology?
It is typically a secondary complication of underlying conditions that trigger widespread inflammation + endothelial damage
simultaneous activation of coagulation + fibrinolysis
leads to microvascular thrombosis + subsequent consumption of clotting factors + platelets
this may result in bleeding, organ dysfunction + death
94
DIC
which organs are typically affected?
kidneys
liver
lungs
brain
95
DIC
which conditions are associated with DIC?
- sepsis (most common)
- malignancy
- trauma
- obstetric complications (placental abruption, amniotic fluid embolism, HELLP, retained stillbirth + acute fatty liver of pregnancy)
- acute haemolytic transfusion reactions
- organ transplant rejection
- severe organ dysfunction (acute liver failure, severe acute pancreatitis)
96
DIC
what are the clinical features?
SYMPTOMS
- bleeding from wounds
- haematuria or haematochezia
- epistaxis or gingival bleeding
- dyspnoea
- chest pain
SIGNS
- petechiae or ecchymoses
- prolonged bleeding
- altered mental state
- focal neurological deficits (if cerebral involvement)
97
DIC
what are the investigations?
FBC - thrombocytopaenia, anaemia + leukocytosis
Clotting studies - prolonged PT + APTT
Fibrinogen levels - decreased
D-dimer - raised
Blood cultures - identify cause
98
DIC
what is the management?
1st line
- treat underlying cause
- blood product transfusion (packed RBCs, FFP or platelets depending on blood results)
- anticoagulants = low dose heparin in severe disease
2nd line
- recombinant activated protein C (rhAPC)
99
DIC
what are the complications?
- intracranial bleeding
- life-threatening haemorrhage
- multi-organ failure (renal failure, hepatic failure, ARDS)
- gangrene or digital loss
100
HAEMOPHILIA
how is it inherited?
X-linked recessive - therefore primarily affects males
Haemophilia A = factor VIII deficiency
Haemophilia B = factor IX deficiency
101
HAEMOPHILIA
how can females be affected?
would require an affected father + a mother who is a carrier or affected
102
HAEMOPHILIA
what is the pathophysiology?
deficiency of factor VIII or IX (essential parts of intrinsic pathway of coagulation)
delayed clot formation due to reduced thrombin generation
leads to excessive bleeding
103
HAEMOPHILIA
what are the risk factors?
family history
male sex
104
HAEMOPHILIA
what are the clinical features?
SYMPTOMS
- spontaneous bleeding (into joint + muscles)
- excessive bleeding (with limited trauma, post dental surgery)
- easy bruising
- fatigue
SIGNS
- hemarthrosis (in knees, elbows and ankles)
- prolonged bleeding following heel-prick test in neonates
- cutaneous purpura
105
HAEMOPHILIA
what are the investigations?
- aPTT - prolonged
- plasma factor VIII and IX levels - decreased or absent
- mixing study
- FBC - to rule out thrombocytopaenia
- plasma von willebrand factor
LFTs - to exclude liver disease
106
HAEMOPHILIA
what is the management?
MILD-MODERATE
- education
- avoidance of high risk activity
- joint strengthening exercises
SEVERE
- as above
- prophylactic clotting factors (IV replacement)
107
HAEMOPHILIA
what is the management of an acute haemorrhage?
- ABCDE assessment
- urgent haematology input
- urgent clotting factor administration
- antifibrinolytic agents (tranexamic acid)
- desmopressin (in haemophilia A)
108
HAEMOPHILIA
what are the complications?
- joint or muscular damage
- compartment syndrome
- life-threatening haemorrhage
- inhibitory antibodies to factor VIII or IX
- blood borne infection (from blood products)
109
MULTIPLE MYELOMA
what is it?
myeloma = type of cancer affecting plasma cells (B lymphocytes that produce antibodies)
multiple myeloma = myeloma that affects multiple bone marrow areas in the body
110
MULTIPLE MYELOMA
why does it cause hypercalcaemia?
- caused by neoplastic cells releaseing cytokines
- this causes activation of osteoclasts via RANK receptor
- this leads to bone resorption, resulting in bone pain + lytic lesions on x-ray
111
MULTIPLE MYELOMA
how does it cause renal insufficiency?
- deposition of light chains (Bence Jones proteins) in the kidney tubules
- this disrupts kidney function
- calcium deposition in the kidney also causes renal failure
112
MULTIPLE MYELOMA
how does it cause anaemia?
- bone marrow infiltration by plasma cells results in reduced haematopoiesis
- this leads to anaemia, thrombocytopaenia + leukopaenia
113
MULTIPLE MYELOMA
what are the risk factors?
- older age (65-69)
- male
- black ethnic origin
- family history
- obesity
- radiation exposure
114
MULTIPLE MYELOMA
what are the clinical features?
CRAB
- hypercalcaemia
- renal failure
- anaemia
- bone lesions
SYMPTOMS
- hypercalcaemia (bones, stones, abdo groans, psychiatric moans)
- fatigue
- bleeding + bruising
- recurrent infections
SIGNS (due to amyloidosis)
- macroglossia
- carpal tunnel syndrome (Tinel's + Phalens test positive)
- peripheral neuropathy
115
MULTIPLE MYELOMA
what are the main clinical signs?
old CRAB
- old = >75
- hypercalcaemia
- renal failure
- anaemia
- bone lesions
116
MULTIPLE MYELOMA
what are the investigations?
- urine electrophoresis = BENCE-JONES PROTEIN
- serum electrophoresis = monoclonal paraprotein band
- bone marrow aspirate + biopsy (required for diagnosis)
- FBC + blood film = anaemia, Rouleux formation (aggregation of RBCs)
- U&Es (renal failure)
- bone profile = hypercalcaemia + raised ALP
- imaging = MRI (1st line) or CT (2nd line)
- x-ray
117
MULTIPLE MYELOMA
what would you expect to see on the x-ray?
- lytic 'punched-out' lesions (pepper pot (raindrop) skull + vertebral collapse)
- abnormal fractures
- osteoporosis
118
MULTIPLE MYELOMA
what is the diagnostic criteria?
One or more biomarkers:
- bone marrow plasma cells >60%
- >1 focal lesion on MRI
- involved : uninvolved serum free light chain ratio >100
or evidence of end-organ damage (CRAB)
- hypercalcaemia
- renal insufficiency
- anaemia
- bone lesions
119
MULTIPLE MYELOMA
what is the management?
disease is incurable + has relapsing and remitting course
- chemotherapy
- stem cell transplant
- bisphosphonates
- radiotherapy
- orthopaedic surgery to stabilise bones
120
MULTIPLE MYELOMA
what are the complications?
- recurrent infections
- myelosuppression + neutropaenic sepsis
- pancytopaenia
- AL amyloidosis
- pathological fracture
- hyperviscosity syndrome
- chronic pain
- fatigue
121
PANCYTOPENIA
what is it?
a reduction in RBCs, WBCs and platelets
122
PANCYTOPENIA
what are the causes?
REDUCED PRODUCTION IN BONE MARROW
- vitamin B12, folate or iron deficiencies
- aplastic anaemia
- myelodysplastic syndromes
- haematological malignancies
- bone marrow infiltration by metastatic cancer
- viral infections (HIV, parvovirus B19, CMV + EBV)
INCREASED DESTRUCTION
- splenic sequestration (TB, cirrhosis + malaria)
- autoimmune conditions (SLE, rheumatoid arthritis)
123
PANCYTOPENIA
what is the epidemiology?
- bimodal distribution (1st peak in children, 2nd peak in 4th decade)
- more common in men
124
PANCYTOPENIA
what are the risk factors?
- co-morbid autoimmune diseases
- recent viral infections (HIV, EBV, CMV)
- malabsorption syndromes
- history of cancer
- family history of aplastic anaemia
125
PANCYTOPENIA
what are the clinical features?
SYMPTOMS
- fatigue
- recurrent infections
- epistaxis
- B symptoms (weight loss, fever, night sweats if malignancy)
SIGNS
- pallor
- petechiae
- splenomegaly
126
PANCYTOPENIA
what are the investigations?
FBC - decreased RBC, WBC + platelets
peripheral blood smear
viral serology
autoimmune screen
serum B12 + folate
to consider
- genetic studies
- bone marrow biopsy
127
PANCYTOPENIA
what is the management?
- replacement therapy (blood/platelet transfusion, iron, B12 or folate supplementation
- stop any offending agents
- stem cell transplantation
128
PANCYTOPENIA
what are the complications?
- infection risk
- severe fatigue, cardiac overload or syncope
- bleeding risk
129
APLASTIC ANAEMIA
what is it?
bone marrow hypocellularity secondary to primary haematopoietic failure
type of pancytopaenia
130
APLASTIC ANAEMIA
what are the different causes?
- fanconi anaemia
- radiation
- carbimazole
- carbamazepine
- chloramphenicol
- chemotherapy
- benzene
131
FANCONI ANAEMIA
what is the inheritance pattern?
can be autosomal dominant or recessive
132
FANCONI ANAEMIA
what are the features?
- pancytopaenia in first decade of life
- organ hypoplasia
- bone defects (e.g. absent thumbs)
133
POLYCYTHAEMIA
what is it?
a myeloproliferative disorder characterised by neoplasia of mature myeloid cells
134
POLYCYTHAEMIA
what gene mutation is seen?
JAK2 gene
135
POLYCYTHAEMIA
what are the risk factors?
- age >40
- family history
- budd-chiari syndrome
136
POLYCYTHAEMIA
what are the clinical features?
SYMPTOMS
- headache
- pruritus
- erythromelalgia
- facial flushing
SIGNS
- splenomegaly
- palmar erythema
- plethoric complexion
- HTN
137
POLYCYTHAEMIA
what are the investigations?
- FBC = raised Hb + haematocrit
- U&Es + LFTs
- ABG (pO2 normal in primary but low in secondary)
- ferritin
- erythropoietin = (primary = low, secondary = raised)
- JAK2 mutation
138
POLYCYTHAEMIA
what is the management?
1st line = venesection (maintain haematocrit below 0.45)
hydroxyurea (in high risk patients)
aspirin 75mg
manage modifable CVD risk factors (diabetes, HTN, smoking, hyperlipidaemia)
139
POLYCYTHAEMIA
what are the complications?
- thrombosis
- haemorrhage
- leukaemia
- treatment-induced leukaemia
- myelofibrosis
140
ITP
what is immune thrombocytopenic purpura (ITP)?
autoimmune disorder where platelets are destroyed by antibodies, leading to low platelet counts and increased risk of bleeding.
141
ITP
what is the criteria?
- isolated thrombocytopenia
- purpuric rash
- normal haemoglobin + white cell count
142
ITP
what is the difference in disease course for children and adults?
CHILDREN
- triggered by recent viral infection
- follows an acute course
- typically resolves within 6 months
ADULTS
- chronic
143
ITP
what are the causes?
PRIMARY ITP - no underlying clear cause
SECONDARY ITP
- SLE
- CLL
- drugs (penicillin, heparin, quinine)
- viruses (HIV, hep C, varicella zoster, CMV)
- pregnancy
144
ITP
what are the risk factors?
- female
- increasing age
- co-morbid autoimmune diseases
145
ITP
what are the clinical features?
SYMPTOMS
- bruising
- epistaxis
- menorrhagia
SIGNS
- petechiae (<4mm bleed into skin)
- purpura (4-10mm bleed into skin)
- ecchymosis (>10mm bleed into skin)
- mucosal bleeding
cutaneous bleeding is more common on lower limbs
146
ITP
what are the investigations?
considered a diagnosis of exclusion
- FBC = low platelet count, screen for underlying blood cancers
- peripheral blood smear = assess platelet size
to consider
- bone marrow aspiration
- blood-borne virus serology (hep C + HIV)
147
ITP
what is the management?
NO SIGNIFICANT BLEEDING/MILD THROMBOCYTOPAENIA
- observation
- corticosteroids (PREDNISOLONE)
- +/- IVIG
SIGNIFICANT BLEEDING
- corticosteroids
- IVIG
- platelet transfusion
SECOND LINE
- splenectomy (if refractory case)
- immunosuppression (rituximab) if not responded to corticosteroids
148
TTP
what is thrombotic thrombocytopaenic purpura (TTP)?
a clinical syndrome characterised by the presence of:
- thrombocytopaenic purpura (low platelets with haemorrhagic rash)
- microangiopathic haemolytic anaemia
149
TTP
what are the causes?
- congenital deficiency
- autoimmune attack of ADAMTS13 protease
150
TTP
what is the pathophysiology?
- lack of ADAMTS13 protease causes platelet aggregation + activation of clotting
- leads to microthrombi in small vessels, platelet consumption + haemolytic anaemia
151
TTP
what are the risk factors?
- female
- obesity
- ethnicity (afro-caribbean)
- autoimmune diseases
- pregnancy
- HIV
- pancreatitis
- medications (quinine, clopidogrel)
152
TTP
what is the classic pentad of features?
- thrombocytopaenic purpura
- microangiopathic haemolytic anaemia
- neurological dysfunction
- renal dysfunction
- fever
153
TTP
what are the clinical features?
SYMPTOMS
- confusion
- seizures
- headache
- bleeding (menorrhagia, epistaxis, prolonged bleeding, severe internal bleeding)
- chest pain (myocardial ischaemia)
- abdominal pain (mesenteric ischaemia)
SIGNS
- coma
- fever
- jaundice
- puerperal rash
154
TTP
what are the investigations?
- FBC - confirm thrombocytopenia + anaemia
- U&Es - raised creatinine
- LDH - raised in haemolysis
- haptoglobin
- blood film - schistocytes (fragmented red blood cells)
- ADAMTS13 activity
155
TTP
what is the management?
1st LINE
- plasma exchange (replenish ADAMTS13)
- corticosteroids (PREDNISOLONE)
- caplacizumab
2nd LINE
- rituximab
156
TTP
what are the complications?
- renal failure
- neurological damage
- death (if untreated)
157
HIT
what is heparin-induced thrombocytopenia?
involves the development of antibodies against platelets in response to heparin (usually unfractionated)
158
HIT
what is the pathophysiology?
- heparin-induced antibodies target a protein on platelets called platelet factor 4 (PF4)
- this activates the clotting system, causing a hypercoagulable state + thrombosis
- they also break down platelets + cause thrombocytopenia
159
HIT
when does it tend to present?
5-10 days after starting treatment with heparin
160
HIT
what is the clinical presentation?
- pain, swelling, redness or tenderness in arm/leg
- sudden sharp chest pain
- HTN
- feeling dizzy, faint or lightheaded
- tachycardia
- coughing/wheeze
- SOB
- excessive sweating
161
HIT
what are the investigations?
- HIT antibodies (PF4 antibodies)
- platelet levels
- FBC
162
HIT
what is the scoring system for working out the likelihood of having HIT?
4Ts test
- Thrombocytopenia (how low is platelet count?)
- Timing of reaction to heparin
- Thrombosis (signs of clot?)
- other causes of thrombocytopenia
163
HIT
what is the management?
- stop heparin
- use alternative anticoagulant (e.g. fonaparinux or argatroban)
164
THALASSAEMIA
what is it?
condition caused by a genetic defect in protein chains that make up haemoglobin
defects in alpha-globin chains = alpha thalassaemia
defects in beta-globin chains = beta-thalassaemia
165
THALASSAEMIA
what is the inheritance pattern?
autosomal recessive
166
THALASSAEMIA
what are the different types?
defects in alpha-globin chains = alpha thalassaemia
defects in beta-globin chains = beta-thalassaemia
167
THALASSAEMIA
what is the cause of alpha-thalassaemia?
gene mutation on chromosome 16
168
THALASSAEMIA
what is the cause of beta thalassaemia?
gene mutation on chromosome 11
169
THALASSAEMIA
what are the different types of alpha-thalassaemia?
- silent carrier = 1 gene deletion, no symptoms
- alpha thalassaemia trait = 2 gene deletions, mildly anaemic
- HbH = 3 gene deletions, unable to form alpha chains, causes moderate-severe disease
- Hb Barts (alpha thalassaemia major) = 4 gene deletions, die in utero
170
THALASSAEMIA
what are the different types of beta thalassaemia?
- beta thalassaemia trait (thalassaemia minor) = 1 normal + 1 abnormal gene, mild microcytic anaemia
- beta thalassaemia intermedia = 2 defective genes OR 1 defective + 1 deletion gene, microcytic anaemia
- beta thalassaemia major = homozygous for deletion, no functioning beta-globin, severe anaemia, failure to thrive
171
THALASSAEMIA
what are the clinical features of beta-thalassaemia major?
- anaemic symptoms (fatigue, weakness, SOB, palpitations)
- failure to thrive
- hepatosplenomegaly
- neonatal jaundice
- frontal bossing (prominent forehead)
- enlarged maxilla (prominent cheekbones)
- depressed nasal ridge (flat nose)
- protruding upper teeth
172
THALASSAEMIA
what are the investigations?
- FBC = microcytic anaemia with reticulocytosis
- blood film = microcytic, hypochromic erythrocytes, target cells + Howell-Jolly bodies
- Hb electrophoresis (diagnostic)
to consider
- skull x-ray = hair-on-end appearance in beta thalassaemia intermedia + major
173
THALASSAEMIA
what is the management?
ALPHA + BETA THALASSAEMIA TRAIT
- usually does not require treatment
HbH + BETA THALASSAEMIA MAJOR
- regular blood transfusions (when Hb <70 or symptomatic)
- iron chelation (DESFERRIOXAMINE)
- folate supplementation
- splenectomy
- stem cell transplantation (only curative option, recommended in severe disease)
174
THALASSAEMIA
what are the complications?
- heart failure
- hypersplenism
- aplastic crisis
- iron overload
- gallstones
175
SICKLE CELL DISEASE
what is it?
genetic condition that causes sickling of RBCs, making cells more fragile + easily destroyed
this leads to haemolytic anaemia
176
SICKLE CELL DISEASE
what is the pathophysiology?
people with sickle cell disease have abnormal variant called haemoglobin S (HbS)
It is an autosomal recessive mutation of beta haemoglobin chains, results in glutamic acid (hydrophilic) substituted for valine (hydrophobic).
1 gene mutation = sickle cell trait
2 genes mutated = sickle cell disease
177
SICKLE CELL DISEASE
what is the inheritance pattern?
autosomal recessive
178
SICKLE CELL DISEASE
what are the risk factors?
- african - highest prevalence in sub-saharan africa
- family history
- triggers of sickling (dehydration, acidosis, infection, hypoxia)
179
SICKLE CELL DISEASE
what is the effect of sickle cell disease on malaria?
sickle cell trait is protective against malaria
180
SICKLE CELL DISEASE
how is sickle cell disease screened for?
newborn blood spot test (Guthrie test)
pregnant women at high risk of being carriers are offered testing
181
SICKLE CELL DISEASE
what are the investigations?
- newborn screening (Guthrie heel prick)
- FBC = normocytic anaemia with reticulocytosis
- blood film = sickled RBCs, target cells, Howell Jolly bodies
- Hb electrophoresis + solubility (diagnostic)
182
SICKLE CELL DISEASE
what is the general long term management?
- Pain management - regularly prescribe medication for chronic pain
- hydroxycarbamide
- lifelong phenoxymethylpenicillin (if hyposplenic)
- regular vaccinations
- blood transfusion
- folic acid supplementation
183
SICKLE CELL DISEASE
what are the complications?
- vaso-oclusive crisis
- splenic sequestration crisis
- aplastic crisis
- acute chest syndrome
184
SICKLE CELL DISEASE
what is a vaso-occlusive crisis?
painful vaso-occlusive episodes when RBCs sickle in various organs
RBCs clog capillaries causing distal ischaemia
185
SICKLE CELL DISEASE
what are the clinical features of a vaso-occlusive crisis?
Presents with pain + swelling in hands or feet but can affect chest, back or other areas.
It can be associated with fever.
BONE
- dactylitis
- avascular necrosis
- osteomyelitis
LUNGS
- acute chest syndrome (dyspnoea, chest pain, hypoxia, pulmonary infiltrates on CXR)
SPLEEN
- along with sequestration, can cause autosplenectomy
CNS
- stroke
GENITALIA
- priapism (very common)
186
SICKLE CELL DISEASE
what is a splenic sequestration crisis?
RBCs block blood flow within the spleen
It causes an acutely enlarged + painful spleen
It can lead to severe anaemia + hypovolaemic shock
187
SICKLE CELL DISEASE
what is the presentation of a splenic sequestration crisis?
- abdominal pain (caused by splenomegaly)
- hypovolaemic shock
188
SICKLE CELL DISEASE
what is the management of a splenic sequestration crisis?
SUPPORTIVE
- blood transfusions
- fluid resuscitation
- splenectomy in recurrent cases
189
SICKLE CELL DISEASE
what is an aplastic crisis?
it is the temporary absence of the creation of new red blood cells
usually triggered by parvovirus B19
leads to significant anaemia (aplastic anaemia)
190
SICKLE CELL DISEASE
what usually triggers an aplastic crisis?
infection with parvovirus B19
191
SICKLE CELL DISEASE
what is the management of an aplastic crisis?
supportive
blood transfusions if necessary
usually resolves spontaneously within a week
192
SICKLE CELL DISEASE
what is acute chest syndrome?
occurs when vessels supplying the lungs become blocked
it is a medical emergency with high mortality
193
SICKLE CELL DISEASE
what are the clinical features of acute chest syndrome?
fever
SOB
chest pain
cough
hypoxia
CXR shows pulmonary infiltrates
194
SICKLE CELL DISEASE
what is the management of acute chest syndrome?
- analgesia
- good hydration (IV fluids may be required)
- antibiotics/antivirals
- blood transfusions for anaemia
- incentive spirometry
- respiratory support
195
MYELOPROLIFERATIVE DISORDERS
what are they?
uncontrolled proliferation of a single type of stem cell
they are considered a form of cancer in the bone marrow, although they tend to develop and progress slowly.
they have the potential to progress into ALL
196
MYELOPROLIFERATIVE DISORDERS
what are the different types?
- primary myelofibrosis
- polycythaemia vera
- essential thrombocythaemia
197
MYELOPROLIFERATIVE DISORDERS
what can they result in?
transformation into ALL
198
MYELOFIBROSIS
what is it?
a type of myeloproliferative disorder
a clonal haematopoietic stem cell disorder
is characterised by:
- bone marrow fibrosis
- extramedullary haematopoiesis
- splenomegaly (often)
199
MYELOFIBROSIS
what are the characteristics?
- bone marrow fibrosis
- extramedullary haematopoiesis
- splenomegaly (often
200
MYELOFIBROSIS
what are the risk factors?
- age >60
- JAK2 mutation
- polycythaemia vera
- essential thrombocythaemia
201
MYELOFIBROSIS
what are the clinical features?
SYMPTOMS
- fatigue
- weight loss
- night sweats
SIGNS
- anaemia
- massive splenomegaly
- hepatomegaly
202
MYELOFIBROSIS
what are the investigations?
- FBC = low Hb, low WCC
- peripheral blood smear = teardrop poikilocytes + aniosocytosis (differing cell sizes)
- bone marrow biopsy = increased fibrosis (collagen deposition) + abnormal cell lines, dry tap
To consider
- urate + LDH
- molecular testing (JAK2)
203
MYELOFIBROSIS
what is the management?
supportive care
- blood transfusions (for anaemia)
- erythropoiesis stimulating agents
Ruxolitinib (JAK2 inhibitor)
Chemotherapy (hydroxycarbamide)
allogenic stem cell transplant
204
MYELOFIBROSIS
what are the complications?
progressive bone marrow failure
thrombosis + DIC
haemorrhage
transformation to leukaemia
205
ESSENTIAL THROMBOCYTHAEMIA
which cell line is affected?
megakaryocyte - high platelet count
206
ESSENTIAL THROMBOCYTHAEMIA
what is the management?
- aspirin
- chemotherapy (hydroxycarbamide)
- anagrelide
207
ESSENTIAL THROMBOCYTHAEMIA
what is the difference between essential thrombocythaemia + thrombocytosis?
thrombocythaemia - high platelet count that isn't related to another condition
thrombocytosis = high platelet count because of another condition
208
ESSENTIAL THROMBOCYTHAEMIA
what are the clinical features?
- signs + symptoms of blood clots
209
HAEMOLYTIC ANAEMIA
what is haemolytic anaemia?
- premature breakdown of RBCs before normal lifespan
210
HAEMOLYTIC ANAEMIA
Describe the pathophysiology of haemolytic anaemia
RBC destroyed before 120 day lifespan --> compensatory reticulocytes from BM --> RBC destruction
211
HAEMOLYTIC ANAEMIA
what are the different types of haemolytic anaemia?
- inherited
- acquired
212
HAEMOLYTIC ANAEMIA
what are the inherited causes of haemolytic anaemia?
- hereditary spherocytosis
- hereditary elliptocytosis
- thalassaemia
- sickle cell anaemia
- G6PD deficiency
213
HAEMOLYTIC ANAEMIA
what are the acquired causes of haemolytic anaemia
autoimmune haemolytic anaemia
alloimmune haemolytic anaemia (transfusion reactions + haemolytic disease of the newborn)
paroxysmal nocturnal haemoglobinuria
microangiopathic haemolytic anaemia
prosthetic valve related haemolysis
214
HAEMOLYTIC ANAEMIA
what are the clinical features of haemolytic anaemia?
1. Anaemia (pallor)
2. Jaundice
3. Splenomegaly
215
HAEMOLYTIC ANAEMIA
What is the management for haemolytic anaemia
Treat according to the cause
Dietary = folate and iron supplementation
AI cause = immunosuppression
Surgical = splenectomy
216
HAEMOCHROMATOSIS
what is it?
autosomal recessive genetic condition resulting in iron overload
there is excessive total body iron + deposition of iron in tissues (it is an iron storage disorder)
217
HAEMOCHROMATOSIS
what is the inheritance pattern?
autosomal recessive
gene located on chromosome 6 - C282Y mutations
218
HAEMOCHROMATOSIS
what is the pathophysiology?
autosomal recessive condition
C282Y mutation on chromosome 6
this results in unregulated absorption of iron from the gut, resulting in iron overload
most commonly affects the liver, pancreas and heart
219
HAEMOCHROMATOSIS
which organs does it most commonly affect?
- liver
- pancreas
- heart
220
HAEMOCHROMATOSIS
what is the epidemiology?
- most common in Northern Europeans
221
HAEMOCHROMATOSIS
what are the risk factors?
middle age (40-50yrs)
male gender
family history
history of chronic transfusion (only relevant in acquired haemochromatosis)
222
HAEMOCHROMATOSIS
what are the clinical features?
SYMPTOMS
- early symptoms = lethargy, arthralgia (hands) + erectile dysfunction
- loss of libido (hypogonadism due to cirrhosis + pituitary dysfunction)
- polyuria + dysuria (T2DM)
SIGNS
- skin hyperpigmentation (bronze skin)
- arthritic joints
- testicular atrophy
- features of chronic liver disease (hepatomegaly)
- features of heart failure (peripheral oedema)
223
HAEMOCHROMATOSIS
what are the investigations?
PRIMARY CARE
- serum ferritin
- fasting serum transferrin saturation (TS)
SECONDARY CARE
1st line
- serum transferrin saturation = elevated
- serum ferritin = elevated
- LFTs = deranged due to liver deposition
- HbA1c = elevated due to damage to pancreatic beta cells
- initial screening (requires FBC, transferrin, serum ferritin + serum iron)
genetic testing
- C282Y + H63D mutations
liver biopsy
- show iron accumulation using Prussian blue (Perls) staining
ECG
Joint x-rays = show chondrocalcinosis
224
HAEMOCHROMATOSIS
what is the management?
LIFESTYLE
- avoid alcohol
- low iron diet
PHLEBOTOMY/VENESECTION
- remove small amount of blood, initially weekly
IRON CHELATION
- desferrioxamine
FAMILY SCREENING
225
HAEMOCHROMATOSIS
what are the complications?
LIVER
- cirrhosis
- HCC
ENDOCRINE
- T2DM
- hypogonadism
CARDIAC
- dilated cardiomyopathy
- congestive heart failure
MSK
- pseudogout
- osteoporosis
DERMATOLOGICAL
- skin hyperpigmentation
226
BLOOD TRANSFUSION REACTIONS
what are the different types of reactions?
- immunological (acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis)
- transfusion-related acute lung injury (TRALI)
- transfusion-associated circulatory overload (TACO)
- other (hyperkalaemia, iron overload, clotting)
227
BLOOD TRANSFUSION REACTIONS
what is acute haemolytic transfusion reaction?
reaction that results from mismatch of ABO blood group
result of RBC destruction by IgM
Symptoms begin minutes after transfusion has started
228
BLOOD TRANSFUSION REACTIONS
what is the mechanism of action for acute haemolytic transfusion reactions?
ABO incompatibility
RBC destruction by IgM antibodies
229
BLOOD TRANSFUSION REACTIONS
when do symptoms appear for acute haemolytic transfusion reaction?
within minutes
230
BLOOD TRANSFUSION REACTIONS
what are the clinical features for acute haemolytic transfusion reaction?
symptoms appear within minutes of transfusion starting
- fever
- abdominal pain
- chest pain
- agitation
- hypotension
231
BLOOD TRANSFUSION REACTIONS
what is the management for acute haemolytic transfusion reaction?
- immediate transfusion termination
- send blood for direct Coombs test, repeat typing + cross match
- fluid resuscitation with IV saline
232
BLOOD TRANSFUSION REACTIONS
what are the complications for acute haemolytic transfusion reaction?
- DIC
- renal failure
233
BLOOD TRANSFUSION REACTIONS
what is a non-haemolytic febrile reaction?
thought to be caused by antibodies reacting with WBC fragments in blood product and cytokines from leaked blood cells during storage
caused by WBC HLA antibodies
often result of sensitisation by previous pregnancies or transfusions
234
BLOOD TRANSFUSION REACTIONS
what is the mechanism of action for non-haemolytic febrile reactions?
due to white blood cell HLA antibodies
235
BLOOD TRANSFUSION REACTIONS
how does non-haemolytic febrile reaction present?
fever
chills
236
BLOOD TRANSFUSION REACTIONS
what is the management for non-haemolytic febrile reactions?
- slow or stop transfusion
- paracetamol
- monitor
237
BLOOD TRANSFUSION REACTIONS
what are the features of a mild allergic reaction?
- pruritus
- urticaria
238
BLOOD TRANSFUSION REACTIONS
what is the mechanism of action for mild allergic reaction?
thought to be caused by foreign plasma proteins
239
BLOOD TRANSFUSION REACTIONS
what is the management for a minor allergic reaction?
- temporarily stop transfusion
- antihistamine (cetirizine)
- once symptoms resolve, transfusion may be continued with no need for further work up
240
BLOOD TRANSFUSION REACTIONS
what are the features of anaphylaxis?
- hypotension
- dyspnoea
- wheezing
- angioedema
241
BLOOD TRANSFUSION REACTIONS
what can cause anaphylaxis?
patients with IgA deficiency who have anti-IgA antibodies
242
BLOOD TRANSFUSION REACTIONS
what is the management for anaphylaxis?
- stop transfusion
- IM adrenaline
- antihistamine
- corticosteroids
- bronchodilators
243
BLOOD TRANSFUSION REACTIONS
what is transfusion-related acute lung injury (TRALI)?
characterised by development of hypoxaemia/ acute respiratory distress syndrome (ARDS) within 6 hours of transfusion
244
BLOOD TRANSFUSION REACTIONS
what are the clinical features for transfusion-related acute lung injury (TRALI)?
- hypoxia
- fever
- hypotension
- pulmonary infiltrates on CXR
245
BLOOD TRANSFUSION REACTIONS
what is the mechanism of action for transfusion-related acute lung injury (TRALI)?
non-cardiogenic pulmonary oedema
thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
246
BLOOD TRANSFUSION REACTIONS
what is the management for transfusion-related acute lung injury (TRALI)?
- stop transfusion
- supportive care
- oxygen
247
BLOOD TRANSFUSION REACTIONS
what is transfusion-associated circulatory overload (TACO)?
fluid overload resulting in pulmonary oedema
248
BLOOD TRANSFUSION REACTIONS
what is the mechanism of action for transfusion associated circulatory overload (TACO)?
- excessive rate of transfusion
- pre-existing HF
249
BLOOD TRANSFUSION REACTIONS
what are the clinical features of transfusion-associated circulatory overload (TACO)?
- pulmonary oedema
- hypertension
250
BLOOD TRANSFUSION REACTIONS
what is the management for transfusion associated circulatory overload (TACO)?
- slow or stop transfusion
- consider loop diuretic (furosemide)
- consider oxygen
251
BLOOD TRANSFUSION REACTIONS
which pathogens are at risk of being transmitted in RBCs?
- HIV
- HBV
- HCV
bacteria are rarer in RBCs, usually coming from skin flora during collection
252
BLOOD TRANSFUSION REACTIONS
which pathogens are at risk of being transmitted in platelets?
staph epidermidis
b.cereus
this is because platelets are stored at room temperature, which increases the risk of bacterial proliferation
253
BLOOD TRANSFUSION REACTIONS
which prions are at risk of being transmitted in blood transfusions?
CJD
254
BLOOD TRANSFUSION REACTIONS
what steps are in place to reduce spread of CJD through blood transfusions?
- removal of WBCs from blood donations
- recipients of blood components are excluded from donating blood
255
SPHEROCYTOSIS
what is it?
inherited haemolytic anaemia
autosomal dominant
256
SPHEROCYTOSIS
what is the inheritance pattern?
autosomal dominant
can be autosomal recessive (rarer)
257
SPHEROCYTOSIS
what is the pathophysiology?
- defect in RBC membrane proteins
- RBCs appear spherical
- there is accelerated degradation of RBCs in spleen, resulting in normocytic anaemia
- splenomegaly occurs as spleen has to work harder
- haemolysis increases bilirubin, which increases risk for gallstones + cholecystitis
258
SPHEROCYTOSIS
what are the clinical features?
SYMPTOMS
- fatigue
- dizziness
- palpitations
- RUQ pain (gallstones)
- neonatal jaundice
- failure to thrive
SIGNS
- splenomegaly
- signs of anaemia (conjunctival pallor)
- jaundice
- tachycardia
- flow murmur
259
SPHEROCYTOSIS
what are the investigations?
- FBC = normocytic anaemia + raised MCHC
- blood film = spherocytosis
- Coomb's test = negative
to consider
- EMA binding test
- cryohaemolysis
- gel electrophoresis
- osmotic fragility test
260
SPHEROCYTOSIS
what is the management?
- phototherapy or exchange transfusion
- blood transfusion
- folic acid
- splenectomy (must be >6yrs old)
261
SPHEROCYTOSIS
what are the complications?
- gallstones
- aplastic crisis
- bone marrow expansion
- post-splenectomy sepsis
262
FEBRILE NEUTROPENIA
What is the definition of febrile neutropenia?
neutrophil count <0.5 x109 with either temp >38.0 or other signs + symptoms of sepsis
263
FEBRILE NEUTRPENIA
Give 4 risk factors for febrile neutropenia
1. If the patient had chemotherapy <6 weeks ago
2. Any patient who has had a stem cell transplant <1 year ago
3. Any haematological condition causing neutropenia
4. Bone marrow infiltration
5. those on methotrexate, carbimazole and clozapine
264
FEBRILE NEUTRPENIA
what conditions create a high risk for febrile neutropenia?
- AML
- ALL
- relapsed AML or ALL
- stage 4 neuroblastoma
- B-cell non-hodgkins lymphoma
- Burkitts lymphoma
- osteosarcoma
- ewing sarcoma
265
FEBRILE NEUTROPENIA
what are the most common causes?
- staph. epidermidis
most commonly occurs 7-14 days after chemotherapy
266
FEBRILE NEUTRPENIA
what is given as prophylaxis?
fluoroquinolone - if they are suspected to be likely to have neutrophil count <0.5 x 109
267
FEBRILE NEUTRPENIA
what is the management?
- do not wait for WBC
- empirical antibiotics (piperacillin with tazobactam (tazocin))
- if central line access, add vancomycin
- if still febrile after 48hrs change antibiotic to menopenem +/- vancomycin
- if not responding after 4-6 days investigate for fungal infection
268
FEBRILE NEUTRPENIA
what are the clinical features?
symptoms of sepsis
- tachycardia
- tachypnoea
- hypotension
- increased CRT
- mottled/ashen skin
- cyanosis
269
FEBRILE NEUTRPENIA
what are the investigations?
- blood gas (including glucose + lactate)
- blood culture
- FBC
- CRP (for inflammation)
- U&Es
- LFTs
- clotting screen
- urine analysis, MS + C
270
ANTICOAGULANTS
what are the different types?
- warfarin
- DOACs
- low molecular weight heparin (LMWH)
- unfractionated heparin
271
DOACs
what are the indications?
- prevention of stroke in non-valvular AF (with other risk factors e.g. prior stroke, HTN, DM, HF, >75)
- prevention of VTE following hip/knee surgery
- treatment of DVT and PE
272
DOACs
what is the mechanism of action?
Rivaroxaban, apixaban and edoxaban= direct factor Xa inhibitor
Dabigatran = direct thrombin inhibitor
273
DOACs
how are they excreted?
Rivaroxaban = majority liver
Apixaban = majority faecal
Edoxaban = majority faecal
Dabigatran = majority renal
274
DOACs
how can they be reversed?
Rivaroxaban + apixaban = andexanet alpha
Dabigatran = idarucizumab
Edoxaban = no reversal agent
275
LMWH
what is the mechanism of action?
activates antithrombin III
forms a complex that inhibits factor Xa
276
LMWH
how can it be reversed?
- protamine sulfate
277
UNFRACTIONATED HEPARIN
what is the mechanism of action?
- activates antithrombin III
- forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
278
UNFRACTIONATED HEPARIN
what are the side effects?
- bleeding
- heparin induced thrombocytopenia
- osteoporosis
279
UNFRACTIONATED HEPARIN
how is it monitored?
APTT (activated partial thromboplastin time)
280
UNFRACTIONATED HEPARIN
how is it reversed?
protamine sulfate
281
WARFARIN
what is the mechanism of action?
vitamin K antagonist
reduces hepatic synthesis of factors II, VII, IX and X
282
WARFARIN
what are the indications?
- mechanical valves
- 2nd line after DOACs
283
WARFARIN
what is the target INR?
venous thromboembolism = 2.5
AF = 2.5
284
WARFARIN
how is it monitored?
using international normalised ratio (INR)
285
WARFARIN
what general things can interact with warfarin?
- liver disease
- antiepileptics (phenytoin, carbamazepine)
- rifampicin
- st Johns wort
- chronic alcohol intake
- smoking
- cranberry juice
- NSAIDs
- antibiotics (ciprofloxacin, clarithromycin, erythromycin)
- isoniazid
- amiodarone
- allopurinol
- SSRIs (fluoxetine, sertraline)
- sodium valproate
286
WARFARIN
what are the side effects?
- haemorrhage
- teratogenic (can be used in breastfeeding)
- skin necrosis
- purple toes
287
WARFARIN
how would you manage INR > 8?
MAJOR BLEED OR REQUIRE SURGERY
- stop warfarin
- give IV vitamin K
- give dried prothrombin complex concentrate (PCC) or Fresh frozen plasma (FFP) if PCC is unavailable
MINOR BLEED
- stop warfarin
- IV vitamin K
- repeat vitamin K dose after 24hrs if INR still too high
- restart warfarin when INR<5
NO BLEED
- stop warfarin
- oral vitamin K
- repeat vitamin K dose after 24hrs if INR still too high
- restart warfarin when INR <5
288
WARFARIN
how would you manage INR 5-8?
MINOR BLEED
- stop warfarin
- give IV vitamin K
- restart warfarin when INR<5
NO BLEED
- withhold 1-2 doses of warfarin
- reduce subsequent maintenance dose
289
ANTIPLATELETS
what are the different types?
aspirin
adenosine diphosphate (ADP) receptor inhibitors = clopidogrel
290
ANTIPLATELETS
what is the 1st and 2nd line antiplatelet for ACS?
1st line
- aspirin (lifelong) + ticagrelor (12 months)
2nd line
- clopidogrel (lifelong)
291
ANTIPLATELETS
what is the 1st and 2nd line antiplatelet for PCI?
1st line
- aspirin (lifelong) + prasugrel /ticagrelor (12 months)
2nd line
- clopidogrel (lifelong)
292
ANTIPLATELETS
what is the 1st and 2nd line antiplatelet for TIA?
1st line
- clopidogrel (lifelong)
2nd line
- Aspirin (lifelong) + dipyridamole (lifelong)
293
ANTIPLATELETS
what is the 1st and 2nd line antiplatelet for ischaemic stroke?
1st line
- clopidogrel
2nd line
- aspirin (lifelong) + dipyridamole (lifelong)
294
ANTIPLATELETS
what is the 1st and 2nd line antiplatelet for peripheral arterial disease?
1st line
- clopidogrel (lifelong)
2nd line
- aspirin (lifelong)
295
ADP RECEPTOR INHIBITORS
give some examples?
- clopidogrel
- prasugrel
- ticagrelor
- ticlopidine
296
ADP RECEPTOR INHIBITORS
what is the mechanism of action?
- inhibit binding of ADP to P2Y12 receptor (antagonist)
- this blocks platelet activation and aggregation
297
ADP RECEPTOR INHIBITORS
what are the interactions?
clopidogrel interacts with PPIs
298
ASPIRIN
what is the mechanism of action?
- blocks cyclo-oxygenase 1 and 2
- this prevents thromboxane A2 formation
- this reduces the platelets ability to aggregate
299
ASPIRIN
what does it interact with?
- warfarin
- steroids
- oral hypoglycaemics
300
ASPIRIN
why should it not be used in children under 16?
due to the risk of Reye's disease
exception is in Kawasakis disease when benefits outweigh risks
301
MALARIA
what spreads the disease?
anopheles mosquito bite
302
MALARIA
what are the different species of malaria?
- Plasmodium falciparum (most common + most severe)
- Plasmodium vivax
- Plasmodium ovale
- Plasmodium malariae
- Plasmodium knowlesi
303
MALARIA
what is the life cycle of malaria?
- spread by female anopheles mosquito
- mosquito sucks up infected blood
- parasites reproduce in mosquito's gut + produces thousands of sporozoites
- when mosquito bites someone the sporozoites are injected
- sporozoites travel to the liver + mature into merozoites
- merozoites enter the blood + infect RBCs
- merozoites reproduce in RBCs + cause RBCs to rupture (causing haemolytic anaemia)
304
MALARIA
what are the risk factors?
- travel to endemic area
- absent chemoprophylaxis
- absent use of mosquito net
- pregnancy
- extremes of age
- immunocompromise
305
MALARIA
what is the epidemiology?
90% of cases occur in africa
most are caused by p.falciparum
306
MALARIA
what are the clinical features?
SYMPTOMS
- cyclical fever
- headache
- weakness
- myalgia
- arthralgia
- anorexia
- diarrhoea
- abdominal pain
- nausea and vomiting
SIGNS
- hepatosplenomegaly
- jaundice
- pallor
307
MALARIA
what are the clinical features of severe disease?
- GCS<11
- oliguria
- acidosis
- hypoglycaemia
- respiratory distress
- hypotension
- seizures
- spontaneous bleeding (DIC)
- parasitaemia >10%
308
MALARIA
what are the investigations?
- thick and thin blood films
- rapid diagnostic test (RDT)
- FBC = anaemia
- clotting screen = PT may be prolonged
- U&Es = AKI from dehydration + hypotension
- LFTs = unconjugated hyperbilirubinaemia + deranged ALT/AST
- blood glucose = hypoglycaemia
- urinalysis
- ABG = metabolic acidosis (in severe disease)
to consider
- PCR for malaria
- CXR
- HIV test
- CT head
309
MALARIA
what is the management?
UNCOMPLICATED FALCIPARUM
- oral chloroquine/hydroxychloroquine (if chloroquine sensitive)
- oral artemether/lumefantrine (if chloroquine resistant)
SEVERE FALCIPARUM
- 1st line = IV artesunate
- 2nd line = IV artemether
- supportive care (IV fluids, airway protection, control of seizures, blood products)
NON-FALCIPARUM
- 1st line = oral chloroquine or hydroxychloroquine
- oral primaquine if p.vivax or p.ovale
310
MALARIA
what are the complications?
- AKI
- hypoglycaemia
- metabolic acidosis
- severe anaemia
- DIC
- sepsis
- blackwater fever
- ARDS
- cerebral malaria
311
MALARIA
how can infection be prevented?
- avoid outdoor activity after sunset
- insect repellents
- wear long sleeved clothing + trousers
- insecticide-treated bedding nets
- anti-malarial chemoprophylaxis
312
MALARIA
what medications can be used to prevent malaria infection?
- chloroquine (weekly tablet, start 1 week before + finish 4 weeks post-travel)
- atorvaquone (unsuitable for pregnancy)
- doxycycline (unsuitable in pregnancy)
- mefloquine (contraindicated in epilepsy)
313
ENTERIC FEVER
what is it?
refers to typhoid and paratyphoid infections
314
TYPHOID
what causes typhoid?
salmonella typhi
315
TYPHOID
how is it spread?
through faecal oral transmission
316
TYPHOID
what are the risk factors?
- poor sanitation
- poor hygiene
- travelling to developing regions
317
TYPHOID
what are the clinical features?
SYMPTOMS
- high fever
- weakness and myalgia
- bradycardia
- abdominal pain
- constipation
- headaches
- vomiting
- skin rash with rose-coloured spots (common in exams)
- confusion
318
TYPHOID
what is the onset of symptoms following exposure?
symptoms generally appear 6-30 days after exposure
it's typically a gradual onset
319
TYPHOID
what are the investigations?
- blood culture
- stool culutre
- bone marrow aspirate culture (gold standard)
- ECG (esp if bradycardic)
- bloods (FBC, U&Es, CRP, ABG/VBG, LFTs, group and save, cross match, clotting)
- imaging
320
TYPHOID
what is the management?
- antibiotics (azithromycin or ceftriaxone)
- infection control measures
321
TYPHOID
what are the complications?
- osteomyelitis (esp in sickle cell anaemia)
- GI bleeding/perforation
- rarely, meningitis
322
DENGUE
what is it?
a viral infection that can progress to viral haemorrhagic fever
323
DENGUE
what is the cause of dengue fever?
dengue virus (RNA virus)
transmitted by Aedes aegypti mosquito
324
DENGUE
what is the incubation period?
7 days
325
DENGUE
what are the clinical features?
- fever
- headache (often retro-orbital)
- myalgia, bone pain and arthralgia (break bone fever)
- facial flushing
- maculopapular rash
SIGNS
- haemorrhagic manifestations (positive tourniquet test, petechiae, purpura/ecchymosis, epistaxis)
- warning signs (abdominal pain, hepatomegaly, persistent vomiting, ascites, pleural effusion)
326
DENGUE
what are the investigations?
FBC, U&Es, LFTs
- leukopaenia
- thrombocytopaenia
- raised aminotransferases
DIAGNOSTIC TESTS
- serology
- nucleic acid amplification tests for RNA
- NS1 antigen test
327
DENGUE
what is the management?
- entirely symptomatic e.g. fluid resuscitation, blood transfusion etc
