Blood Flashcards
(98 cards)
1
Q
What is the definition of anaemia
A
A low level of haemoglobin in the blood
This is the result of an underlying disease and is not the disease itself
The prefix an- means without
The suffix -aemia refers to blood
2
Q
What is haemoglobin
A
A protein found in red blood cells.
It picks up oxygen in the lungs and transports this to the cells of the rest of the body
3
Q
How is anaemia diagnosed
A
Low haemoglobin on blood test (normal: F 120-165, M 130-180)
Then look at mean cell volume (MCV) to determine the size of the red blood cells (normal: F 80-100, M 80-100)
4
Q
How is anaemia categorised
A
Based on the size of the red blood cell (MCV)
Microcytic: low MCV so small RBCs
Normocytic: normal MCV so normal sized RBCs
Macrocytic: large MCV so large RBCs
5
Q
What are the causes of microcytic anaemia
A
TAILS
T- Thalassaemia A- Anaemia of chronic disease I- Iron deficiency anaemia L- Lead poisoning S- Sideroblastic anaemia
6
Q
What are the causes of normocytic anaemia
A
3As and 2Hs
Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism
7
Q
What are the causes of macrocytic anaemia
A
Macrocytic anaemia can be megaloblastic or normoblastic
Megaloblastic anaemia is the result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps browning into a larger abnormal cell. This is caused by a vitamin deficiency
Megaloblastic:
- B12 deficiency
- Folate deficiency
Normoblastic:
- Alcohol
- Reticulocytosis (usually from haemolytic anaemia or blood loss)
- Hypothyroidism
- Liver disease
- Drugs such as azathioprine
8
Q
What are the symptoms of anaemia
A
Tiredness SOB Headaches Dizziness Palpitations Worsening of other conditions such as angina, heart failure or peripheral vascular disease
9
Q
What are the signs of anaemia
A
Generic:
- pale skin
- conjunctival pallor
- tachycardia
- raised respiratory rate
Signs of specific causes of anaemia:
- Koilonychia: spoon shaped nails, can indicate iron deficiency
- Angular chelitis: can indicate iron deficiency
- Atrophic glossitis: a smooth tongue due to atrophy of the papillae and can indicate iron deficiency
- Brittle hair and nails: can indicate iron deficiency
- Jaundice occurs in haemolytic anaemia
- Bone deformities occur in thalassaemia
- Oedema, hypertension and excoriations on the skin can indicate chronic kidney disease
10
Q
How is anaemia investigated
A
Bloods:
- Haemoglobin
- MCV
- B12
- Folate
- Ferritin
- Blood film
Further investigations:
- Oesophago-gastroduodenoscopy (OGD) and colonoscopy to investigate for a GI cause of unexplained iron deficiency anaemia. (On urgent cancer referral for suspected GI cancer)
- Bone marrow biopsy may be required if the cause is unclear
11
Q
What is the clinical relevance of iron absorption
A
Iron is mainly absorbed in the duodenum and jejunum. It requires the stomach acid to keep the iron in the soluble ferrous (fe2+) form. When the acid drops it changes to the insoluble ferric (fe3+) form. Therefore, medications that reduce stomach acid such as PPI can interfere with iron absorption. Conditions that result in inflammation of the duodenum or jejunum such as coeliac disease or Crohn’s disease can also cause inadequate iron absorption.
12
Q
What are the causes of iron deficiency anaemia
A
Blood loss (most common cause in adults)
Dietary insufficiency (most common cause in growing children)
Poor iron absorption
Increased requirements during pregnancy
Be suspicious of a GI tract cancer, oesophagitis and gastritis are the most common causes of GI tract bleeding. Inflammatory bowel disease (Crohn’s and Ulcerative colitis) should also be considered.
13
Q
How does iron travel in the body
A
Travels as ferric ions (Fe3+) bound to a carrier protein called transferrin.
14
Q
What is TIBC
A
Total iron binding capacity basically means the total space on the transferrin molecules for the iron to bind. Therefore, total iron binding capacity is directly related to the amount of transferrin in he blood.
15
Q
How is iron deficiency testing understood
A
If measure the iron in the blood, and then the total iron binding capacity (TIBC) of the blood, can calculate the proportion of the transferrin molecules that are bound to iron. This is called the transferrin saturation and is expressed as a percentage.
The formula is:
Transferrin saturation = serum iron/ total iron binding capacity
Ferritin is the form iron takes when it is deposited and stored in cells. Extra ferritin is released from cells in inflammation, such as with infection or cancer. If ferritin in the blood is low it is highly suggestive of iron deficiency. If ferritin is high then this is difficult to interpret and is likely to be related to inflammation rather than iron overload. A patient with normal ferritin can still have iron deficiency anaemia, particularly if hey have reasons to have high ferritin such as infection.
Serum iron varies significantly throughout the day with higher levels in the morning and after eating iron containing meals. On its own it is not a useful measure.
TIBC can be used as a marker for how much transferrin is in the blood. It is an easier test to perform than measuring transferrin. Both TIBC and transferrin levels increase in iron deficiency and decrease in iron overload.
Transferrin saturation gives a good indication of the total iron in the body. In normal adults it is ~30%, however if there is less iron in the body transferrin will be less saturated and is iron levels of up transferrin will be more saturated. It can temporarily increase after eating a meal rich in iron or taking iron supplements so a fasting sample gives the most accurate results.
Acute liver damage can increase serum ferritin, serum iron, transferrin saturation and can decrease TIBC, due to the liver being a large store of iron
16
Q
What are the normal ranges in iron deficiency anaemia
A
Serum ferritin 41-400ug/L
Serum iron 12-30umol/L
TIBC 45-80umol/L
Transferrin saturation 15-50%
17
Q
How is iron deficiency managed
A
New iron deficiency without a clear cause should be investigated with suspicion. This involves doing an OGD and a colonoscopy to look for cancer of the GI tract.
Management involves treating the underlying cause and correcting the anaemia. The anaemia can be treated in three ways depending on severity.
- Blood transfusion: this will immediately correct eh anaemia but not the underlying iron deficiency and also carries risks
- Iron infusion eg cosmofer: there is a very small risk of anaphylaxis but it quickly corrects the iron deficiency. Should be avoided in sepsis s iron “feeds” the bacteria
- Oral iron eg ferrous sulfate 200mg TDS: Slowly corrects the iron deficiency. Can cause constipation and black stools. It is unsuitable when malabsorption is the cause of the anaemia.
When correcting iron deficiency anaemia with iron you can expect the haemoglobin to rise by ~10g/L per week
18
Q
What is an acute transfusion reaction
A
Acute reactions occur within 24 hours of transfusion and include:
- Acute haemolytic,
- Febrile non-haemolytic
- Allergic
- Transfusion related acute lung injury (TRALI)
19
Q
What is a delayed transfusion reaction
A
Delayed reactions occurdays to weeks after the transfusion and include:
- Delayed haemolytic transfusion reactions
- Transfusion associated graft versus host disease
- Post transfusion purpura
20
Q
What is the aetiology of the 4 types of acute transfusion reactions
A
Acute haemolytic:
- Usually the result of ABO red-cell incompatibility
- Caused by clerical error resulting in mistransfusion
Allergic:
-Hypersensitivity reactions to allergens in the transfused component
Febrile non-haemolytic transfusion:
-Considered to be immune-mediated, although the mechanism appears to be multifactorial
Transfusion related acute lung injury (TRALI):
-Occurs as a result of granulocyte activation in the pulmonary vasculature, resulting in increased vascular permeability
21
Q
What is the aetiology of the 3 types of delayed transfusion reactions
A
Delayed haemolytic transfusion reactions:
-Generally non-preventable, and the result of an anamnestic antibody response to non-ABO red cell antigens
Transfusion-associated graft-versus-host disease:
-Primarily observed in immunodeficient patients in which transfused white cells react with recipient antigens
Post transfusion purpura:
-Occurs as a result of prior sensitisation to foreign platelet antigen, usually during pregnancy
22
Q
What is the pathophysiology of acute haemolytic type transfusion reaction
A
Typically result from ABO incompatibility.
The presence of preformed recipient antibodies to donor antigens results in complement activation, leading to intravascular haemolysis and its associated severe acute inflammatory cascade, which may ultimately progress to disseminated intravascular coagulation, shock and/or acute renal failure
23
Q
What is the pathophysiology of allergic type transfusion reaction
A
Typically manifests as urticaria caused by a hypersensitivity reaction to allergen proteins in donor plasma.
In the most severe form, anaphylaxis (IgE mediated) may occur.
In IgA deficient patients, an anaphylacticoid (since non-IgE mediated) can occur as a result of anti-IgA antibodies in the recipient interacting with donor IgA
24
Q
What is the pathophysiology of febrile non-haemolytic type transfusion reaction
A
May result in part from interaction between recipient antibodies directed against leukocytes present in the red-cell or plately unit transfused.
The formation of antigen-antibody complexes may result in complement binding and release of endogenous pyrogens.
May also result from the transfusion of proinflammatory substances inclusing cytokines, complement fragments and lipid compounds that are contained in the transfused unit’s plasma supernatant
25
What is the pathophysiology of transfusion related acute lung injury
Occurs secondary to priming of granulocytes in the pulmonary vasculature. This phenomenon may be the result of antigranulocyte antibodies contained in donor plasma, priming by bioreactive substances such as lipids present in the transfused component, or a combination of the two mechanisms
26
What is the pathophysiology of delayed haemolytic type transfusion reaction
Result from non-ABO antigen-antibody incompatibilities.
Typically, the recipient has had prior exposure to a foreign red cell antigen following pregnancy, previous transfusion, or transplantation.
Exposure to the same antigen results in an anamnestic antibody response, leading to haemolysis, which is typically extravascular (in the reticuloendothelial system) and relatively benign
27
What is the pathophysiology of transfusion associated graft versus host disease type transfusion reaction
Occurs because viable transfused passenger lymphocytes in donor components mount an immunological attack against the recipient, who is almost always immunocompromised (by leukaemia, lymphoma, or congenital immunodeficiency)
It may also occur in immunocompetent patients who are heterozygous for an HLA haplotype for which the donor is homozygous.
28
What is the pathophysiology of post-transfusion purpura type transfusion reaction
An immune thrombocytopenia that occurs after transfusion of a platelet-containing component (platelets, red cells, granulocytes)
The recipient has been sensitised to a foreign platelt antigen (usually human platelet antigen 1a), most often during pregnancy or alternatively from a past transfusion.
Both the antigen positive donor platelets and antigen negative recipient platelets are destroyed, resulting in thrombocytopenia.
29
What are the risk factors for transfusion reaction
ABO incompatibility (unusual and typically results from clerical error)
Prior pregnancy (delayed haemolytic transfusion reactions, and post-transfusion purpura)
Previous transfusion (delayed haemolytic transfusion reactions)
History of transplantation (Delayed haemolytic transfusion reactions, and transfusion associated graft versus host disease
IgA deficiency (anaphylactoid)
Immunocompromise (transfusion associated graft versus host disease)
History of transfusion reaction (all)
30
What are the signs and symptoms of transfusion reaction
Common:
- Presence of risk factors
- Chills
- Flushing
- Dyspnoea
- Fever
- Headache
- Nausea and vomiting
- Anxiety
- Pain along the infused extremity
- Pruritus
- Urticaria
- Angio-oedema
- Jaundice
- Rales
Uncommon:
- Chest, abdominal, flank, and back pain
- Hypotension
- Bleeding from mucous membranes, GI tract or urinary tract
- Red urine
- Stridor or bronchospasm
- Pallor
- Maculopapular rash
- Diarrhoea
- Disseminated purpura
- Exfoliative dermatitis with mucocutaneous involvement
31
How is a potential transfusion reaction investigated
1st line:
- Direct antiglobulin test
- Visual inspection of post-transfusion blood sample
- Repeat ABO testing on post-transfusion blood sample
- Post transfusion urinalysis
Other investigations to consider:
- Serum IgA levels
- Anti-IgA antibody testing
- Serum alloantibody screen
- Serum LDH
- Serum bilirubin
- Gram stain and culture of component and post-transfusion recipient samples
- Skin biopsy
- HLA typing
- Platelet antibody screen
- Serum haptoglobin
- Serum potassium
- Serum bicarbonate
- Serum calcium
- Serum creatinine
- FBC
- D-dimer
- PT and PTT
- Chest X-ray
- ABG
32
What is a direct antiglobulin test
Performed to identify whether antibodies or complement are bound to the donor cells
Recipient's post transfusion red cells are washed and incubated with antihuman globulin (Coombs reagent)
Observation of agglutination is considered a positive test
33
What are the differentials in suspected transfusion reactions
Transfusion-associated sepsis
Non-immune mediated haemolysis
Transfusion-associated circulatory overload
34
How are the types of transfusion reactions managed:
- Acute haemolytic transfusion reaction
- Anaphylactic reaction or severe allergic reaction
- Urticarial reaction without anaphylaxis
- Febrile non-haemolytic transfusion reaction
- Transfusion-related acute lung injury (TRALI)
- Delayed haemolytic transfusion reaction
- Transfusion-associated graft versus host disease
- Post-transfusion purpura
Prompt recognition of onset
Immediate cessation of transfusion
Specific treatment of the various immune-mediated reactions
Acute haemolytic transfusion reaction:
- Crystalloid resuscitation
- Urine output goal of >100ml/hr
- Consider forced diuresis if not meeting urine goal
- Mannitol is the diuretic of choice as it acts as a free radical scavenger, so mitigating renal cellular injury
- Prior to diuresis, intravascular volume depletion to be excluded by evidence of central venous pressure or pulmonary artery catheter monitoring
- Organ supportive treatment (Eg intubation, vasopressor and dialysis)
Anaphylactic:
- Immediate administration of IM adrenalin (repeat every 5 mins as needed to alleviate stridor and improve blood pressure)
- IV adrenaline infusion may be given in cardiac arrest or profound hypotension refractory to IM adrenaline
- Secure the airway with intubation and initiation of mechanical ventilation
- Crystalloid administration to support circulation
- IV glucagon if taking beta blockers
- Bronchospasm may benefit from adjunctive salbutamol
- Adjunct antihistamines
- Corticosteroid administration in those in severe or prolonged attack
Urticarial reaction without anaphylaxis:
- Temporarily discontinue transfusion
- Administer antihistamine
- Once symptoms resolve, can restart transfusion unless severe
- Severe reactions may require corticosteroids
- Monitor for onset of anaphylaxis
Febrile:
- Antipyretic (eg paracetamol), for patient comfort
- Avoid aspirin in thrombocytopenia
- Discontinue transfusion until haemolytic reaction has been ruled out
- Once symptoms resolve, continue to transfuse with new component
- Do not transfuse remainder of implicated component
TRALI:
- Supportive management (eg O2 from mask to ventilation, depending on severity)
- Resolution of the syndrome generally occurs rapidly, typically within <7 daysafter transfusion
Delayed:
-No specific treatment is required
Transfusion-associated graft-versus-host disease:
- It tends to lead to marrrow aplasia, with rapid progress towards death
- Treament immunosuppressive regimens have been tried but are not useful
- Treatment is supportive
Post-transfusion purpura:
-High dose IV immune globin (immunoglobulin) is the therapy of choice and should correct the associated thrombocytopenia in a matter of days.
35
How are transfusion reactions prevented
Primary:
-Adherence to existing safety protocols and checklists
Secondary:
- Prophylactic paracetamol oftengiven but little evidence to support this
- Pre-storage leukoreduction
- Premedication with antihistamine (little evidence)
- Plasma transfusion for patients with known IgA deficiency should come from IgA deficient donors. Red cells and platelts should undergo pre transfusion washing, which effectively removes the plasma proteins
- Patients with a history of post-transfusion purpura should recieve future components from antigen matched donors (consult with blood bank)
- Irradiation to eliminate the lymphocytes responsible for the cell-mediated immune response that causes graft-versus-host disease
- Warm blood components to avoid hypothermia risk
- As WBC antibodies are more prevalents in female than in male donors, a strategy to prevent TRALI is to exclude females from the plasma donor pool.
36
What is the prognosis for each type of transfusion reactions
Acute haemolytic transfusion reaction:
- Severity varies greatly, and is related to the volume of incompatieble blood transfused
- ~5% of episodes progress to death
Febrile non-haemolytic:
-Benign and self-limited, resolving shortly after discontinuation of transfusion
Allergic:
- Usually mild urticaria
- Anaphylaxis may resilt in severe morbidity (eg anoxic brain injury) or mortality if hypoxia is profound and/or prolonged
Delayed:
-Usually benign and self-limited or subclinical
Transfusion-associated graft-versus-host disease:
-Almost always fatal
Post-transfusion purpura:
-Spontaneous recovery, usually within a few weeks
37
What are the potential complications of transfusion reactions
Acute renal failure (short-term, low likelihood)
Acute respiratory failure (short-term, low likelihood)
Hypothermia (short-term, low likelihood)
Thrombocytopenia (long-term, low likelihood)
Iron overload (long-term, low likelihood)
Anoxic brain injury (variable, low likelihood)
Disseminated intravascular coagulation (DIC) (variable, low likelihood)
Death (low likelihood)
38
What is haemolytic anaemia
It encompasses a number of conditions that result in the premature destruction of RBCs.
39
What are the causes of haemolysis
Hereditary:
- Inherited RBC defects (membrane defects) - hereditary spherocytosis, elliptocytosis, pyropoikilocytosis
- Enzyme deficiencies - G6PD deficiency, pyruvate kinase deficiency
- Abnormal Hb production - sickle cell anaemia, thalassaemia
Acquired:
- Immune and non-immune aetiologies
- Autoantibodies cause immune-mediated haemolytic anaemias, most often as part of other autoimmune conditions (eg SLE, rheumatoid arthritis, scleroderma) or related to a lymphoproliferative disorder (non-hodgkin's lymphoma, chronic lymphocytic leukaemia)
- Immune haemolytic anaemias can be warm or cold depending on the temperature at which the antibody binds most avidly to RBCs
- Alloimmune haemolytic anaemias include haemolytic disease of the newborn or transfusion reaction
- Drug associated
- Non-immune mediated causes:
- - Infection
- - Trauma
- - DIC
- - Thrombotic thrombocytopenic purpura
- - Haemolytic uraemic syndrome
- - Malignant hypertension
- - Eclampsia
- - HELLP syndrome
- - Hypersplenism
- - Liver disease
- Paroxysmal nocturnal haemoglobinuria is a rare disorder resulting in an acquired RBC membrane defect and subsequent haemolysis
40
What is the pathophysiology of haemolytic anaemia
Results from either intravascular or extravascular RBC destruction.
Extravascular haemolysis results from accelerated red cell destruction by cells of the reticuloendothelial system, due to immune targeting by antibodies, as occurs in warm haemolytic anaemia.
Intravascular haemolysis results from red cell destruction within the vasculature, due to complement mediated lysis or direct red cell trauma from a prosthetic heart valve or microangiopathic process
Autoimmune haemolysis is most often due to extravascular destruction of red cells coated with an autoantibody (Coombs' positive).
41
What are the signs and symptoms of haemolytic anaemia
Common:
- Presence of risk factors
- Pallor
- Jaundice
- Fatigue
- SOB
- Dizziness
- Splenomegaly
Uncommon:
- Active infections
- Episodic dark urine (haemoglobinuria)
- Triggered by exposure to cold
42
What are the risk factors for haemolytic anaemia
Strong:
- Autoimmune disorders
- Lymphoproliferative disorders
- Prosthetic heart valve
- Family origin in Mediterranean, Middle East, Africa, or Southeast Asia
- Family hisotry of haemoglobinopathy or RBC membrane defects
- Paroxysmal nocturnal haemoglobinuria
- Recent exposure to cephalosporins, penicillins, quinine derivatives or NSAIDs
- recent exposure to naphthalene or fava beans
- thermal injury
Weak:
- Exceptional exertion
- Recent exposure to nitrites, dapsone, ribavirin, or phenazopyridine
- Recent paraquat ingestion
- Malaria
- Babesiosis
- Bartonellosis
- Ieishmaniasis
- Clostridium perfringens infection
- Haemophilus influenza type B infection
- Liver disease
43
How is haemolytic anaemia
1st investigations:
- FBC
- MCHC
- Reticulocyte count
- Peripheral smear
- Unconjugated (indirect) bilirubin
- LDH
- Haptoglobin
- Urinalysis
Investigations to consider:
- Direct antiglobulin test (DAT or Coombs')
- Creatinine, urea
- LFTs
- Donath-Landsteiner antibody
- Hb electrophoresis
- Flow cytometry for CD55/CD59
- G6DP fluorescent spot test and spectrophotometry
- ANA (SLE screen)
44
How is haemolytic anaemia
Supportive care indicated in all aetiologies of haemolytic anaemia - this includes transfusions and folate supplementation
Acquired (Coombs' positive):
- Immune mediated disease process
- Supportive care plus removal of insult (infection drug etc) if present.
- Corticosteroids to decrease antibody production
- Splenectiomy to remove site of antibody production as it is the predominant site of RBC destruction (if patients do not respond to corticosteroids)
- Third line: ritumixmab, IV immunoglobulin, cytotoxic agents
Acquired (Coombs' negative):
- Non-immune disease mechanism
- No corticosteroids
- Supportive care along with removal of an offending agent if present
- March haemolysis resolves when exceptional physical exertion stops
- Prosthetic valve haemolysis needs urgent cardiology evaluation as suggests valve dysfunction
- Thrombotic thrombocytopenic purpura treated with plasma exchange with the intent of stoppin gthe causative process
- Paroxysmal noctonrla haemoglobinuria can be started with corticosteroids and if unresponsive then can start eculizumab (noval monoclonal antibody)
Inherited disorders:
- Red cell membrane disorders - splenectomy will often result in significant decrease in haemolysis
- Red cell enzyme defects - avoid drugs which are contraindicated in G6DP deficiency and; supportive therapy or splenectomy in pyruvate kinase deficiency
- Haemoglobinopathies - supportive care, adjunctive therapies in sickle cell crisis can include O2, pain control, aggressive hydration, and treatment of concurrent stressors (eg infection)
45
What are the differentials in suspects haemolytic anaemia
Anaemia due to blood loss
Underproduction anaemia
Transfusion reaction
46
How is haemolytic anaemia prevented
Secondary prevention:
-Patients with G6PD deficiency should avoid trigger substances such as naphthalene, fava beans, sulphonamides, nitrofurantoin, salicylates, nitrates, dapsone, ribavirin, phenazopyridine, or paraquat
Vaccination against encapsulated organisms sich as Haemophilus influenzae and streptococcus pneumonia should be perfomed as early as possible in cases that may be treated with splenectomy.
47
What are potenital complications of haemolytic anaemia
Complications of multiple transfusions
Cholelithiasis
Iron overload from chronic transfusions
Thromboembolism
48
What is the prognosis for those with haemolytic anaemia
Autoimmune:
-Can be transient in children but often recurrent in adults
If related to lymphoproliferative disorder, may parallel the course of underlying disease
Infection or toxin related will usually resolve with treatment or removal of underlying cause
Congenital disorders:
- RBC membrane defects will often improve with splenectomy
- Enzyme defects will persis and require long term avoidance of precipitating drugs
- Haemoglobinopathies will persist and require supportive care in repeated exacerbations.
49
What is Hodgkin's lymphoma
AKA Hodgkin's disease
An uncommon haematological malignancy arising from mature B cells
It is characterised by the presence of Hodgkin's cells and Reed-Sternberg cells
50
What are the signs and symptoms of Hodgkin's lymphoma
Common:
- Presence of risk factors
- Lymphadenopathy (painless and most commonly involving the cervical and/or supraclavicular nodal chain) (most common symptom)
Uncommon:
- Unexplained fevers
- Night sweats
- Weight loss
- Dyspnoea
- Cough
- Chest pain
- SVC syndrome
- Abdo pain
- Generalised pruritus
- Alcohol induced pain at involved sites
- Hepatomegaly and/or splenomegaly
- Tonsillar enlargement
51
What are the risk factors for Hodgkin's lymphoma
Strong:
- Hx EBV infection
- FHx of Hodgkin's lymphoma
- Young adults from higher socio-economic class
- Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
- HIV
Weak:
- HLA types
- Jewish ancestry
52
What are the investigations for Hodgkin's lymphoma
1st line:
FBC
LDH (lactate dehydrogenase) - raised in Hodgkin's but not specific and canc be raised in other cancerous and non-cancerous diseases
Metabolic panel
ESR
Chest X-ray
PET-CT scan
Gallium scan
Contrast CT neck, chest and abdomone/pelvis
Excisional lymph node biopsy (key diagnostic test
Immunohistochemical studies
```
Additional:
Bone marrow biopsy
Thyroid function tests
Echocardiogram or multi-gated acquisition (MUGA) scan
Pulmonary function tests
```
53
What are lymphomas
A group of cancers that affect the lymphocytes inside the lymphatic system
The cancerous cells proliferate within the lymph nodes and cause the lymph nodes to become abnormally large (lymphadenopathy)
54
How common is Hodgkin's lymphoma
1 in 5 lymphomas are Hodgkin's lymphoma
There is a bimodal age distribution with peaks around aged 20 and 75 years.
55
What are B symptoms
The symstemic symptoms of lymphoma
Fever
Weightless
Night sweats
56
What are Reed-sternberg cells
The key finding from lymph node biopsy in patients with Hodgkin's lymphoma
Abnormally large B cells that have multiple nuclei that have nucleoli inside of them.
This gives the cells the appearance of the face of an owl with large eyes
57
What is Ann Arbor staging
Used in both Hodgkins and non-Hodgkins lymphoma
Puts importance on whether the affected nodes are above or below the diaphragm.
Stage 1: Confined to one region of lymphnodes
Stage 2: In more thanone region but on the same side of the diaphragm (either above or below)
Stage 3: Affects lymph nodes both above and below the diaphragm
Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver
58
How is Hodgkin's lymphoma managed
Early-stage (1 and 2):
-Combined modality therapy consisting of combination chemotherapy (typically ABVD) followed by involved-field radiotherapy
Advanced stage (3 and 4):
- Combination chemotherapy (eg ABVD or escalated BEACOPP)
- Interim PET scan response can inform decisions re esclation or de-escalation of chemotherapy
- Controversial use of consolidation radiotherapy in advanced HL but is recommended in bulky disease (>5cm) or for those recieving stanford V chemotherapy.
- Consolidation radiotherpay can be avoided in patients with negative end of treatment PET scans
For patients who fail initial treatments, high dose chemotherapy with radiotherapy (if eligible), followed by autologous stem cell transplantation is preferred.
Immunotherapeutic agents are available for patients with relapsed or refractory classical HL
59
What are potential complications of Hodgkin's lymphoma
Radiotherapy-related thyroid abnormalities
Chemotherapy and radiotherapy related secondary malignancy
Chemotherapy and radiotherapy related cardiac disease
Chemotherapy and radiotherapy related pulmonary toxicity
Chemotherapy and radiotherapy related ovarian dysfunction
Chemotherapy and radiotherapy related testicular dysfunction
Impaired immunity
60
What is the prognosis following hodgkin's lymphoma
Early favourable HL:
- Long term disease control of 85%-90% after brief chemo followed by low dose involved field radiotherapy
- Recurrent HL is the leading cause of death in first 15 years after treatment
- Continued follow-up patients more likely to die from secondary malignancies or cardiac disease
Early unfavourable HL:
-Long term disease control of 80-90% post combined modality therapy
Advanced HL:
-After treatment, long term disease control ~60-80%
61
What are non-hodgkins lymphomas
Heterogenous group of malignancies of the lymphoif system
Notable ones are:
- Burkitt lymphoma - associated with EBV, malaria and HIV
- MALT lymphoma - affects the mucosa-associated lymphoid tissue, usually around the stomach, and is associated with H.pylori infection
- Diffuse large B cell lymphoma - often presents as a rapidly growing painless mass in over 65y/os
62
What are the risk factors for Non-hodgkin's lymphoma
```
Age >50 y/o
Male
HTLV-1
Coeliac disease
Sjogren syndrome
HIV
EBV
H.pylori (MALT lymphoma)
Hep B or C
Exposure to pesticide and the chemical trichlorethylane (used in several industrial processes)
Family history
```
63
How does Non-hodgkin's lymphoma present
Often similarly to Hodgkin's lymphoma and only then differentiated by biopsy
```
Lymphadenopathy
Splenomegaly
Night sweats
Weight loss
Fatigue
Fever
Hepatomegaly
SOB
Cough
Abdominal discomfort
Headache
Change in mental status
Dizziness and ataxia
Chest pain
Bone pain
Back pain
Jaundice
Pallor
Purpura
Skin lesions
Neurological abnormalities on examination
```
64
How is non-hodgkin's lymphoma managed
Combination of treatments depending on the type and staging:
- Watchful waiting
- Chemotherapy
- Monoclonal antibodies such as rituximab
- Radiotherapy
- Stem cell transplant
65
How is suspected non-hodgkin's lymphoma investigated
```
FBC (thrombocytopenia, pancytopenia, lymphocytosis)
Blood smear
Lymph node biopsy
Skin biopsy
Bone marrow biopsy
Basic metabolic panel
LFTs
Lactate dehydrogenase (LDH)
```
66
What are the differentials in suspected Non-hodgkin's lymphoma
```
Hodgkin's lymphoma
Acute lymphocytic leukaemia
Infectious mononucleosis
Hepatitis C
Cytomegalovirus infection
Tuberculosis
HIV
Syphilis
Sarcoidosis
Rheumatoid arthritis
System lupus erythematosus
```
67
What is myeloma
A cancer of the plasma cells
These are a type of B lymphocytes that produce antibodies
Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced
68
How common is myeloma
Accounts for ~1% of all cancers
69
What is multiple myeloma
Where the myeloma affects multiple areas of the body
70
What is MGUS
Monoclonal gammopathy of undetermined significance
Where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer.
Often an incidental finding in an otherwise healthy person and with unclear significance.
It may progress to myeloma and so patients are often routinely followed up to monitor for progression
71
What is smouldreing myeloma
Where there is progression of MGUS with higher levels of antibodies or antibody components.
It is premalignant and more likely to progress to myeloma than MGUS
72
What is Waldenstrom's macroglobulinemia
A type of smouldering myeloma where there is excessive IgM specifically
73
What is apparent in measured immunoglobulins with myeloma patients
One of the 5 main types of immunoglobulin (A, G, M, D and E) will be significantly abundant.
More than 50% of the time this is IgG
74
How do myeloma patients have anaemia
The cancerous plasma cells invade the bone marrow.
This is described as bone marrow infiltration.
This causes suppression of the development of other blood lines leading to anaemia, neutropenia and thrombocytopenia.
75
What is myeloma bone disease
A result of increased osteoclast activity and suppressed osteoblast activity. This results in the metabolism of bone becoming imbalanced as more is reabsorbed than constructed. This is caused by cytokines released from the plasma cells and the stromal cells when they are in contact with the plasma cells.
76
What are the roles of osetoclasts and osteoblasts
Osteoclasts absorb bone
Osteoblasts deposit bone
77
Where are the common sites of myeloma bone disease and how does this disperse
Skull
Spine
Long bones
Ribs
The abnormal bone metabolism is patchy menaing that in some areas the bone becomes very thin whereas other areas remain normal.
78
What is an osteolytic lesion
The patches of thin bone in myeloma bone disease
The weak points in bone lead to pathological fractures
79
How does hypercalcaemia result in myeloma bone disease
All the osteoclast activity causes a lot of calcium to be reabsorbed from the bone into the blood, resulting in high blood calcium (hypercalcaemia)
80
What are plasmacytomas
Can develop in myeloma
Individual tumours made up of the cancerous plasma cells
They can occur in the bones, replacing normal bone tissue, or can occur outside the bones in the soft tissue of the body
81
How does myeloma renal disease occur
Often myeloma patients develop renal impairment due to a number of factors:
- High levels of immunoglobulins can block the flow through the tubules
- Hypercalcaemia impairs renal function
- Dehydration
- Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys
82
What is the relevance of hyperviscocity in myeloma
Plasma viscocity increases when there are more proteins (eg. immunoglobulins and fibrinogen) in the blood
Therefore the large amounts of immunoglobulins in myeloma causes increased plasma viscosity
Raised plasma viscosity can cause many issues:
- Easy bruising
- Easy bleeding
- Reduced or loss of sight due to vascular disease in the eye
- Purple discolouration to the extremities (purplish palmar erythema)
- Heart failure
83
What are the key four features of myeloma
CRAB
C- Calcium
R- Renal failure
A- Anaemia (normocytic, normochromic), from replacement of bone marrow
B- Bone lesions/pain
84
What are the risk factors for myeloma
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Older age
Male
Black african ethnicity
Family history
Obesity
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85
When should myeloma be suspected
In anyone over 60 y/0 with persisten bone pain, particularly back pain, or an unexplained fracture
86
What are the inital investigations to be performed in suspected myeloma
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FBC (Low white blood cell count)
Calcium (raised
ESR (raised)
Plasma viscosity (raised)
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If any are positive or if still suspective of myeloma, do an urgen serum protein electrophoresis and a urine Bence-Jones protein test
Follow BLIP
B- Bence-Jones protein (request urine electrophoresis)
L- serum free Light chain assay
I- serum Immunoglobulins
P- serum Protein electrophoresis
Bone biopsy to confirm diagnosis and to get more information on the disease
Imaging to assess for bone lesions. Order of preference:
- Whole body MRI
- Whole body CT
- Skeletal survey
Patients only require one investigation but may not tolerate or be suitable for MRI or CT
87
What is a skeletal survey
Xray images of the full skeleton
88
How will myeloma present on Xray
Punched out lesions (Lytic lesions)
"Raindrop skull" caused by many punched out (lytic) lesions throughout the skills that give the appearance of raindrops splashing on the surface
89
How is myeloma managed
The aim of treatment is to control disease. It usually takes a relapsing-remitting course and treatment aims to improve quality and quantity of life. Managed under haematology and oncology mdt.
First line:
-Combination chemo with bortezomid, thalidomidem and dexamethasone
Stem cell transplant in clinical trial
Reguire VTE prophylaxis with aspirin or low molecular weight heparin whilst on certain chemotherapy as incresaed risk of developing a thrombus
90
How is myeloma bone disease managed
Bisphosphonates to suppress osteoclast activity
Radiotherapy to bone lesions can improve bone pain
Orthopaedic surgery can stabilise bones (eg by inserting a prophylactic intramedullary rod) or treat fractures
Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain.
91
What are potential complications of myeloma
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Infection
Pain
Renal failure
Anaemia
Hypercalcaemia
Peripheral neuropathy
Spinal cord compression
Hyperviscocity
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92
What is folate deficiency
Megaloblastic macrocytic anaemia without neuropathy.
Folate (AKA vit B9) is present in green veg, legumes and some fruits.
Deficiency arises due to malabsorption, drugs and toxins, increased demand or dietary deficiency.
93
How does folate deficiency present
```
Common:
Prolonged diarrhoea
Loss of appetite and weight loss
Fatigue
SOB
Dizziness
Pallor
Headache
Tachycardia
Heart murmur
Signs of heart failure
Signs of chronic alcohol misuse
Signs of haemolytic anaemia
Signs of exfoliative dermatitis
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Uncommon:
Painful swallowing
Petechiae
Glossitis
Angular stomatitis
Neurological deficits in children
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94
What are the risk factors for follate deficiency
Strong:
- Low dietary folate intake
- Age >65y/o
- Alcohol use disorder
- Pregnant or lactating
- Prematurity
- Intestinal malabsorption disorders
- Use of trimethoprim, methotrexate, sulfasalazine, pyrumethamine or anticonvulsants (eg phenytoin, phenobarbital)
- Infantile intake of goats' milk
- Congential defects in folate absorption and metabolism
Weak:
- States of increased cell turnover
- Intake of special diet
- Chronic dialysis
95
How is suspected folate deficiency investigated
1st line:
Peripheral blood smear
FBC
Reticulocyte count
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Investigations to consider:
Serum folate
Red blood cell folate
Serum vitamin B12
Serum LDH
Serum unconjugated bilirubin
Serum iron panel
Plasma or serum methylmalonic acid
Plasma homocysteine
Bone marrow aspirate/biopsy
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96
What are the differentials in suspected folate deficiency
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VitB12 deficiency
Thiamine responsive megaloblastic anaemia
Hereditarty orotic aciduria
Alcoholic liver disease
Hypothyroidism
Myelodysplastic syndrome
Aplastic anaemia
Pure red blood cell aplasia
Drug-induced macrocytosis
Diphyllobothriasis
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97
How is folate deficiency managed
Oral folic acid replacement
Must rule out VitB12 deficiency before starting folic acid as this can then be masked
Consider concomitant dolic acid and VitB12 therapy
If severe anaemia, consider packed RBC slow transfusion
98
What is the prognosis of folate deficiency anaemia
In aquired folate-deficient megaloblastic anaemia, daily folic acid supplementation brings about haematological remission and replenishes body stores within ~4 months
Some patients will require ongoing folate supplementation and in such cases it is important to monitor periodically the folate and vitB12
