Theme 7: Haematology Flashcards
Which physiological developmental process gives rise to the cellular components of blood?
Haemopoiesis
Which type of cell replication increases the stem cell pool, generating no differentiated progeny?
Symmetrical self-renewal
Stem cell divides forming 2 daughter stem cells
With reference to haemopoietic stem cells, what is asymmetric self-renewal?
Division maintains the stem cell pool (no increase, no decrease). This is achieved by forming one stem cell and one differentiated cell.
With reference to haemopoietic stem cells, what is lack of self-renewal?
Can mean 2 things:
- maintain the stem cell pool, no division takes place
- deplete the stem cell pool, each division generates 2 differentiated daughter cells
Which haemopoietic stem cell lineage produces erythrocytes?
Myeloid
Which haemopoietic stem cell lineage produces platelets?
Myeloid
Which haemopoietic stem cell lineage produces B-lymphocytes?
Lymphoid
Which haemopoietic stem cell lineage produces basophils?
Myeloid
Which haemopoietic stem cell lineage produces T-lymphocytes?
Lymphoid
Haemopoiesis starts at day 27 in the __1__ region, expands rapidly at day 35 and disappears at day __2__.
1) aorta gonad mesonephros (AGM)
2) 40
The disappearance of the aorta gonad mesonephros region at day 40 coincides with what event?
Migration of the haemopoietic stem cells into the foetal liver, which becomes the new site of haemopoiesis
Reduced erythrocyte count is called what?
Anaemia
What term describes a state of raised RBC count?
Polycythaemia
What term describes a state where the % of RBC in the blood is raised because the volume of plasma is reduced?
Relative polycythaemia
The RBC count isn’t raised, but as the plasma volume has dropped it appears to be high in comparison with the plasma
What is the most common white cell in adults?
Neutrophils
Which of the following facts about neutrophils is incorrect?
a) They are phagocytic
b) They live for only a few hours in the blood
c) Malignant conditions (such as myelodysplasia) can increase the number of lobes on the nucleus
d) Numbers are usually raised in response to a bacterial infection
c) Malignant conditions (such as myelodysplasia) can increase the number of lobes on the nucleus
Neutrophil have multi-lobed nuclei. The number of lobes can be:
- reduced in malignant conditions (e.g. myelodysplasia); or,
- increased (hypersegmented neutrophils) in anaemia, B12 deficiency, folate deficiency.
What term means:
Raised number of neutrophils
Neutrophilia
Causes include bacterial infection and inflammation
What term means:
Decreased number of neutrophils
Neutropenia
Causes include drug side effects
Which WBCs are granulocytes?
Neutrophils, eosinophils, basophils
Which granulocyte has a bi-lobed nucleus?
Eosinophil
What effect might a parasitic infection have on numbers of eosinophils?
Cause eosinophilia (increased number)
Which granulocyte has a dark cytoplasm with lots of granules?
Basophils
What effect can chronic myeloid leukaemia have on numbers of basophils?
CML can cause basophilia: increased numbers
Raised basophil count is diagnostic of CML. This is because it is the only condition that causes basophilia. It also increases the numbers of the other myeloid lineage, but other things can also cause that.
What is the difference between a monocyte and a macrophage?
They are the same cells, but monocytes are in circulation and become known as macrophages or histiocytes when they enter the tissues.
What are Kupffer cells?
Macrophages in the liver
What are Langerhans cells?
Macrophages in the skin
What effect might TB have on numbers of monocytes?
Monocytosis: increased numbers of monocytes
Which WBCs are phagocytic & antigen-presenting cells?
Monocytes
Which of the following is likely to lead to lymphopenia?
a) Glandular fever
b) Bone marrow transplant
c) Chronic lymphocytic leukaemia
d) Pertussis
b) Bone marrow transplant
It can take years for lymphocyte numbers to normalise following a bone marrow transplant as they generate quite slowly.
The other conditions would all lead to lymphocytosis.
Which type of lymphocyte(s) form part of the innate immune system?
Natural killers (NK)
These lymphocytes identify self and non-self; launching an attack on non-self.
Which lymphocytes include multiple subtypes, such as CD4 and CD8?
T-lymphocytes
Are T-lymphocytes part of the innate immune system or the adaptive immune system?
Adaptive
Are B-lymphocytes part of the innate immune system or the adaptive immune system?
Adaptive
Platelets are derived from __?__ in the bone marrow
Megakaryocytes
Fragments of these large cells break off and enter circulation as platelets.
What results are included with a FBC?
- Haemoglobin concentration
- Red cell parameters: mean cell volume (MCV) and mean cell Hb (MCH)
- WCC
- Platelet count
What three things are assayed as part of the coagulation screen?
Prothrombin time
Thrombin time
Activated partial thromboplastin time
Which test involves hollow-needle biopsy from the posterior iliac crest of the pelvis under local anaesthetic?
Bone marrow aspirate and trephine
Liquid marrow is aspirated and then a core is removed using a trephine (a cylindrical hole saw used in surgery to remove a circle of tissue or bone)
What term is used to describe the proportion of abnormal results correctly classified by a test?
Sensitivity
Sensitivity (also called the true positive [sick] rate) measures the proportion of actual positives that are correctly identified as such (e.g., the percentage of sick people who are correctly identified as having the condition)
What is meant by specificity of a test?
Specificity (also called the true negative rate) measures the proportion of actual negatives that are correctly identified as such (e.g., the percentage of healthy people who are correctly identified as not having the condition)
Which type of anaemia is associated with a low MCV and low MCH?
Microcytic hypochromic anaemia
The RBCs will appear small and pale.
Low MCV = small size
Low MCH = low Hb level = pale
Examples: iron deficiency, thalassaemia, anaemia of chronic disease, lead poisoning, sideroblastic anaemia
Which type of anaemia is associated with a normal MCV and normal MCH?
Normocytic normochromic anaemia
RBCs appear normal, but their numbers are depleted.
Examples: Haemolytic anaemia, anaemia of chronic disease, acute haemorrhage, renal disease, mixed deficiencies, bone marrow failure (inc. chemo, malignancy)
Which type of anaemia is associated with a high MCV?
Macrocytic
Two types: megaloblastic and non-megaloblastic
- Megaloblastic: B12/folate deficiency
- Non-megaloblastic: alcohol abuse, liver disease, myelodysplasia, aplastic anaemia
What is the number one cause of macrocytic anaemia?
Alcohol abuse
What is the characteristic appearance of erythrocytes in iron-deficiency anaemia?
Small and pale (low MCV, low MCH)
Varying shape and size: pencil cells - long and thin
Which type of anaemia results in hypersegmented neutrophils and oval macrocytes?
B12 deficiency
At what temperature are RBCs stored?
4 degrees C
At what temperature are platelets stored?
22 degrees C (room temp)
At what temperature is FFP stored?
-30 degrees C
How are platelets collected?
Two ways:
1) Pooled platelets: 1 unit of platelets is removed from a unit of whole blood. 4-6 of these units are pooled together from different donors into a single pack
2) Apheresis platelets: Donor’s blood passes through apheresis machine which removes the platelets and returns all other blood products to the donor. This method takes a full pack of platelets from a single donor (equivalent to 4-6 units of pooled platelets)
What is the adult therapeutic dose for platelets?
4-6 units from random donors (pooled platelets) or a single donation from apheresis
A single dose of platelets would be expected to increase patient’s count by how much?
20-60x10^9 per L
Which product contains all clotting factors at physiological levels?
Fresh frozen plasma (FFP)
Which product contains high concentration of vitamin K-dependent factors?
Prothrombin complex concentrate (factor IX complex)
Contains high concentrations of factors II, VII, IX, and X
What is cryoprecipitate?
Blood product extracted from FFP during the freezing process.
Contains fibrinogen, vWF, factor VIII, and factor XIII
Which of the following is most appropriate for a patient deficient in factor IX?
a) FFP
b) Whole blood
c) Cryoprecipitate
d) Prothrombin complex concentrate
d) Prothrombin complex concentrate
They don’t need FFP or whole blood as they only have a single deficiency. Cryoprecipitate contains fibrinogen, vWF, factor VIII, and factor XIII - therefore would not improve factor IX. PCC contains factors II, VII, IX, and X.
Why should FFP only be thawed immediately before use?
6 hours after thawing, levels of the labile factors (V and VIII) begin to diminish.
What term is being described:
The Hb concentration at or below which RBCs are usually ordered for transfusion of asymptomatic patients with anaemia.
Transfusion threshold
True or false: RBC transfusion is a suitable option for treatment of chronic anaemia caused by iron or vitamin deficiency.
False.
Red cell transfusion should be avoided in patients with chronic anaemia due to Fe or vitamin deficiency, unless it is so severe there is an imminent risk of death
Why might you transfuse platelets?
Treatment of bleeding due to severe thrombocytopenia or platelet dysfunction
Prevention of bleeding in patients with severe thrombocytopenia or platelet dysfunction
According to NICE guidelines, what are the target values when transfusing patients in the following groups:
a) Haemorrhaging patient
b) Anaemia with severe symptoms
c) Acute anaemia with mild symptoms
d) Chronic anaemia
a) Haemorrhaging patient:
Maintain normovolaemia, transfuse based on Hb
b) Anaemia with severe symptoms:
Until symptoms resolve (but not >100g/L)
c) Acute anaemia with mild symptoms:
<70g/L if no CV disease
< 80g/L if CV disease
d) Chronic anaemia:
Individualised plan, commonly 80-100g/L
What alternatives can be considered instead of RBC transfusion?
Correction of treatable causes of anaemia:
- Fe deficiency
- B12/folate deficiency
- EPO treatment for renal disease
Correction of coagulopathy:
- Discontinue anti-platelets
- Administer anti-fibrinolytics
Which of the following is an appropriate situation for transfusion of FFP?
a) treat single factor deficiency
b) correct abnormal clotting prior to invasive procedure
c) reverse warfarin
d) correct abnormal clotting in patients that are not bleeding
b) correct abnormal clotting prior to invasive procedure
Which of the following product requires ABO testing of patient’s blood:
a) Albumin
b) Cryoprecipitate
c) Clotting factors
d) Prothrombin complex concentrate
b) Cryoprecipitate
Requires ABO testing:
- RBC
- Platelets
- FFP
- Cryoprecipitate
No need to ABO test:
- Prothrombin complex concentrate
- Clotting factors
- Albumin
What treatment is used to replace clotting factors in patients with multiple factor deficiencies (acquired coagulopathies), i.e. liver disease, disseminated intravascular coagulation etc
FFP transfusion
What are the acute transfusion reactions?
Immunological:
- Acute haemolytic transfusion reaction due to incompatibility
- Allergic/anaphylactic reaction
- Transfusion-related acute lung injury (TRALI)
Non-immunological:
- Bacterial contamination
- Transfusion-associated circulatory overload (TACO)
- Febrile non-haemolytic transfusion reaction (FNHTR)
Which transfusion product contains fibrinogen, vW, factor VIII and factor XIII?
Cryoprecipitate
What are the most common reactions following a transfusion?
Febrile (FNHTR)
- 10-30% after platelets
- 1-2% after RBC
Anaphylaxis (0.5-1%)
According to NICE guidelines, what are the target values when transfusing patients in the following groups:
a) Haemorrhaging patient
b) Anaemia with severe symptoms
c) Acute anaemia with mild symptoms
d) Chronic anaemia
a) Haemorrhaging patient:
Maintain normovolaemia, transfuse based on Hb
b) Anaemia with severe symptoms:
Until symptoms resolve (but not >100g/L)
c) Acute anaemia with mild symptoms:
<70g/L if no CV disease
< 80g/L if CV disease
d) Chronic anaemia:
Individualised plan, commonly 80-100g/L
What alternatives can be considered instead of RBC transfusion?
Correction of treatable causes of anaemia:
- Fe deficiency
- B12/folate deficiency
- EPO treatment for renal disease
Correction of coagulopathy:
- Discontinue anti-platelets
- Administer anti-fibrinolytics
Which test involves mixing patient’s plasma with aliquots of donor red cells to see if agglutination or haemolysis occurs?
Crossmatching
Which of the following product requires ABO testing of patient’s blood:
a) Albumin
b) Cryoprecipitate
c) Clotting factors
d) Prothrombin complex concentrate
b) Cryoprecipitate
Requires ABO testing:
- RBC
- Platelets
- FFP
- Cryoprecipitate
No need to ABO test:
- Prothrombin complex concentrate
- Clotting factors
- Albumin
Which of the following treatments require crossmatching:
a) Red blood cell transfusion only
b) RBC and FFP
c) RBC, FFP and cryoprecipitate
d) RCP, FFP, cryoprecipitate and platelets
a) Red blood cell transfusion only
If the question asked which required a group and save or ABO testing, the answer would be d.
What are the delayed transfusion reactions?
Immunological:
- Graft vs Host disease (GvHD)
- Post-transfusion purpura
- Immunomodulation
- Immunosuppression
Non-immunological:
- Transfusion transmitted infection (TTI)
- Haemochromatosis
What are the most common reactions following a transfusion?
Febrile (FNHTR)
- 10-30% after platelets
- 1-2% after RBC
Anaphylaxis (0.5-1%)
Primary myelofibrosis is frequently associated with which genetic change?
JAK2 mutation
The JAK2 gene is mutated in approximately half of cases of myelofibrosis. It is also mutated in 55% of cases of essential thrombocythaemia and almost all cases of polycythaemia vera.
A 49-year-old woman is admitted to hospital with severe anaemia. The haemoglobin concentration is 43 g/l, white cell count 28 × 10^9/l, platelet count 220 × 10^9/l.
92% of the white cells are mature looking lymphocytes and some smear cells are noted. Further examination of the blood film showed polychromasia and spherocytes. The bilirubin is elevated at 67 μmol/l (normal 3‒17). The patient is known to have chronic lymphocytic leukaemia.
The most likely cause of the anaemia is?
Autoimmune haemolytic anaemia
About 10% of patients with chronic lymphocytic leukaemia (CLL) develop autoimmune haemolytic anaemia. The diagnosis could be confirmed by finding a positive Coombs’ test.
Bone marrow failure can cause anaemia in patients with CLL but you would also expect thrombocytopenia and there would not be polychromasia (implying a reticulocytosis). Infection with parvovirus causes red cell aplasia in some susceptible patients. In such patients, you would not find polychromasia. The reticulocyte count would be very low.
There is no evidence of iron deficiency and in bleeding you would not expect to find spherocytes in the blood film.
A 60-year-old woman presents with severe anaemia and jaundice. She is thought to have an autoimmune haemolytic anaemia.
To support this diagnosis, what are the the most likely abnormalities on the blood film?
Polychromasia, spherocytes and nucleated red cells
The blood film of someone with an autoimmune haemolytic anaemia typically shows polychromasia, spherocytes and, if severe, nucleated red blood cells. A direct antiglobulin test (DAT or Coombs’ test) would be positive in most patients. The red cells may be macrocytic but this would not be the most likely blood film comment. Patients with myelofibrosis or metastatic malignancy involving the marrow often have polychromasia, tear drop red cells and leuco-erythroblastic changes.
A patient who has had a splenectomy for trauma requires vaccination against which diseases?
Haemophilus influenzae type b, Meningococcus, Pneumococcus
The patient is at increased risk of malaria but vaccination is not the solution. The patient is at increased risk of Haemophilus influenzae type b, pneumococcus and meningococcus and available vaccinations should be given. The patient is not at increased risk of hepatitis B.
A 58-year-old woman with severe rheumatoid arthritis is feeling increasingly tired. She has been taking non-steroidal anti-inflammatory drugs (NSAID) and recently started a tumour-necrosis factor (TNF) inhibitor.
Her haemoglobin concentration is 90 g/l, mean red cell volume 76 fl (normal range 77 – 98) and mean cell haemoglobin 26.5 pg (normal range 28 – 32). Her ferritin is 155 μg/l and her estimated glomerular filtration rate is >60 ml/min.
The most likely cause of her anaemia is?
Anaemia of chronic disease
If a patient has both iron deficiency anaemia and the anaemia of chronic disease the ferritin is usually low in the normal range. The value in this patient suggests that this is anaemia of chronic disease without iron deficiency. The anaemia of chronic disease is most commonly normochromic, normocytic but when severe is hypochromic microcytic.
__?__ is a neoplastic disorder of lymphoid tissue usually associated with t(14;18)
Follicular lymphoma
Widespread activation of the clotting cascade resulting in the formation of clots throughout the small blood vessels?
Disseminated intravascular coagulation
A genetic blood disorder resulting in a rigid abnormally shaped red blood cell
Sickle cell anaemia
Which organ is essential to the maintenance of normal levels of coagulation factors?
Liver
Chromosomal abnormality seen in CML
Philadelphia Chromosome t(9;22)
Clopidogrel is an __1__ agent that inhibits __2__.
1) anti-platelet
2) P2Y12
What is the most common heritable bleeding disorder?
von Willebrand disease
The brand name of the small molecule specifically designed to block the active site in the Bcr-Abl tyrosine kinase
Gleevec
The process of mixing a patient’s plasma with aliquots of donor red cells to see if a reaction occurs
Crossmatching
Increase in the number of red blood cells
Polycythaemia
Neoplasm where the proliferation of abnormal haematopoietic stem cells leads to scarring of the marrow
Myelofibrosis
Type of lymphoma characterised by the presence of Reed-Sternberg cells
Hodgkin Lymphoma
Possible severe complication of intensive chemotherapy in acute leukaemia
Neutropenic sepsis
Type of anaemia associated with atrophic gastritis
Pernicious
Tyrosine kinase inhibitor that is effective in CML
Imatinib
Malignant clonal proliferation of plasma cells
Myeloma
What is a common cause of subacute combined degeneration of the cord?
B12 deficiency
Type of anaemia commonly resulting in a microcytic hypochromic picture
Iron deficiency anaemia
A type of anaemia associated with folic acid deficiency
Megaloblastic
An X-linked recessive disorder resulting in factor VIII deficiency
Haemophilia
