Blood Flashcards
What is the definition of anaemia
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
What is haemoglobin
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
How is anaemia diagnosed
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)
How is anaemia categorised
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
What are the causes of microcytic anaemia
TAILS
T- Thalassaemia A- Anaemia of chronic disease I- Iron deficiency anaemia L- Lead poisoning S- Sideroblastic anaemia
What are the causes of normocytic anaemia
3As and 2Hs
Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism
What are the causes of macrocytic anaemia
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
What are the symptoms of anaemia
Tiredness SOB Headaches Dizziness Palpitations Worsening of other conditions such as angina, heart failure or peripheral vascular disease
What are the signs of anaemia
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
How is anaemia investigated
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
What is the clinical relevance of iron absorption
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.
What are the causes of iron deficiency anaemia
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.
How does iron travel in the body
Travels as ferric ions (Fe3+) bound to a carrier protein called transferrin.
What is TIBC
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.
How is iron deficiency testing understood
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
What are the normal ranges in iron deficiency anaemia
Serum ferritin 41-400ug/L
Serum iron 12-30umol/L
TIBC 45-80umol/L
Transferrin saturation 15-50%
How is iron deficiency managed
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
What is an acute transfusion reaction
Acute reactions occur within 24 hours of transfusion and include:
- Acute haemolytic,
- Febrile non-haemolytic
- Allergic
- Transfusion related acute lung injury (TRALI)
What is a delayed transfusion reaction
Delayed reactions occurdays to weeks after the transfusion and include:
- Delayed haemolytic transfusion reactions
- Transfusion associated graft versus host disease
- Post transfusion purpura
What is the aetiology of the 4 types of acute transfusion reactions
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
What is the aetiology of the 3 types of delayed transfusion reactions
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
What is the pathophysiology of acute haemolytic type transfusion reaction
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
What is the pathophysiology of allergic type transfusion reaction
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
What is the pathophysiology of febrile non-haemolytic type transfusion reaction
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
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
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
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.
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.
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)
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
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
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
What are the differentials in suspected transfusion reactions
Transfusion-associated sepsis
Non-immune mediated haemolysis
Transfusion-associated circulatory overload
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.
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.
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
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)
What is haemolytic anaemia
It encompasses a number of conditions that result in the premature destruction of RBCs.
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
