Flashcards in Haematology (Laz's) Deck (301)
Name three genes that are associated with myeloproliferative disorders
Outline the treatment options for essential thrombocythaemia.
Anagrelide (specifically inhibits platelet function but rarely used because of side-effects)
NOTE: hydroxycarbamide is an antimetabolite that suppresses cell turnover)
What might you expect to see in the blood film of a patient with primary myelofibrosis?
Tear drop poikilocytes (dacrocytes)
NOTE: can cause Budd-Chiari syndrome
What might you see on histological analysis of a trephine biopsy in primary myelofibrosis?
Increased reticulin and collagen fibrosis
Prominent megakaryocyte hyperplasia and clustering
New bone formation
Outline the treatment options for primary myelofibrosis.
Supportive – RBC and platelet transfusions (usually ineffective because of splenomegaly)
Hydroxycarbamide (may worsen anaemia)
Ruxolitinib – JAK2 inhibitor
Allogeneic stem cell transplantation
Splenectomy – dangerous operation but may provide symptomatic relief
List some diagnostic techniques used to identify the disease (CML) and monitor response to treatment.
FBC and leucocyte count
Cytogenetics and detection of Philadelphia chromosome (FISH)
RT-PCR to detect and quantify the number of copies of Bcr-Abl1 fusion transcript
NOTE: RT-PCR transcript % is the most sensitive
Bcr = breakpoint cluster region; Abl = ableson tyrosine kinase
What are the next steps in treatment if the first-line treatment of CML fails?
1st line fails (no complete cytogenetic response at 1 year or initial response is followed by resistance) switch to 2nd or 3rd generation
2nd line fails (inadequate response or disease progresses to accelerated or blast phase) allogeneic stem cell transplantation
How much more folate is needed in pregnancy than when non-pregnant?
200 µg/day more
What proportion of pre-eclampsia patients will develop thrombocytopaenia?
50% - probably due to increased activation and consumption
NOTE: also associated with coagulation activation
How is ITP in pregnancy treated?
Anti-D (if RhD-negative)
List the main changes in coagulation factors that occurs in pregnancy.
Factor 8 and vWF – increase 3-5 fold
Fibrinogen – increase 2 fold
Factor 7 – increase 0.5 fold
Protein S – falls by 0.5
PAI-1 – increase 5 fold
PAI-2 – produced by the placenta
NOTE: all of these changes lead to a procoagulant state
List some other conditions in pregnancy that can increase the risk of thromboembolic disease.
Age (> 35 years)
Ovarian hyperstimulation (IVF)
In women receiving anticoagulant therapy because of high VTE risk, when should it be stopped?
When labour begins or at the time of a planned delivery
Which type of haemoglobin variant cannot be identified using HPLC?
What are the possible complications that a mother with sickle cell disease may encounter during pregnancy?
More frequent vaso-occlusive crises
Foetal growth restriction
Which antigens do myeloma cells test positive for on immunohistochemistry?
Monotypic cytoplasmic immunoglobulin
Light chain restriction
NOTE: CD38, CD138 and cytoplasmic Ig are present on normal plasma cells
Which antigens do myeloma cells test negative for on immunohistochemistry?
CD20 (unlike B cell lymphomas and CLL)
Describe how the antibody screen of a patient’s plasma works.
Conducted using the indirect antiglobulin test (IAT)
2 or 3 reagent red blood cells are used which contain all the important red cell antigens
The patient’s serum is incubated with these screening cells
Anti-human immunoglobulin is added to the solution which allows bridging of red cells that are coated with IgG
This results in the formation of a visible clump
This is a group and screen
What is a full crossmatch?
Uses indirect antiglobulin test
Patients plasma is incubated with DONOR red cells at 37 degrees for 30-40 mins
Anti-human immunoglobulin is added to allow cross-linking of antibodies
Formation of a clump would suggest that antibodies against donor red cell antigens are present in the patient’s plasma
What is the adult dose of FFP?
List some causes of delayed transfusion reactions.
Delayed haemolytic transfusion reaction
Infection (viral, malaria, vCJD)
Outline the mechanism of TRALI.
Anti-WBC antibodies in donor blood interact with WBC in the patient
Aggregates of WBCs get stuck to pulmonary capillaries resulting in the release of neutrophil proteolytic enzymes and toxic oxygen metabolites
This leads to lung damage
Which patient group tends to be affected by post-transfusion purpura?
HPA-1a negative patients who have previously been immunised by pregnancy or transfusion
How is post-transfusion purpura treated?
If anti-D antibodies are detected in a pregnant women, what further steps should be taken?
Check if the father has the antigen
Monitor the level of antibody
Monitor foetus for signs of anaemia (MCA Doppler ultrasound)
Deliver the baby early because it gets a lot worse around term
What factor (related to stem cell harvesting) does the success of a bone marrow transplant depend on?
Number of CD34 cells per kg of weight of the recipient
List some clinical features of poorly controlled beta thalassemia major.
Anaemia heart failure, growth retardation
Erythropoietic drive bone expansion, hepatomegaly, splenomegaly
Iron overload heart failure, gonadal failure
How is a diagnosis of acute promyelocytic leukaemia confirmed?
Cytogenetic/FISH/molecular genetic analysis
15;17 translocation forming the PML: RARA fusion gene
How is acute promyelocytic leukaemia treated?
All-trans-retinoic acid (ATRA)
NOTE: 90% 5-year survival