Week 19 - Polycythemia, Vit B12/Folate deficiency, thalessaemia Flashcards
what is Polycythaemia vera
a raised RBC count, haemoglobin and packed cell volume/haematocrit
what warrants investigation into Polycythaemia
If packed cell volume/haematocrit persistently raised (male >0.52, female >0.48) this warrants investigation
what is the mutation in Polycythaemia and what is the percentage
90% have JAK2 mutation
what is the presentation of Polycythaemia
headaches, dizziness, lethargy, sweating and pruritus
what is there increased risk of in Polycythaemia
thrombosis - especially strokes, and bleeding - hyperviscosity and platelet dysfunction
what may increased cell turnover in Polycythaemia lead to
gout
what are the clinical signs seen in Polycythaemia
plethora,rosacea, palpable splenomegaly
what are the investigations carried out for Polycythaemia
Investigations: elevated WCC, elevated platelets, iron deficiency, EPO estimation normal or low
what is seen in the bone marrow in polycythemia
hypercellularity
what is the management of Polycythaemia Vera
Management: aspirin (75mg/day), venesection (haematocrit to <0.45)
what is given in advanced cases of polycythaemia vera
Advanced disease: hydroxycarbamide to suppress erythropoiesis
what is the median survival in polycythemia vera
Median survival >10 years, 10% transform to myelofibrosis, 5% to AML
polycythaemia vera is the proliferation of what cells
eryhtroid cells
what is found in the blood with polycythemia vera
high haemoglobin
what JAK2 inhibitors are used in treatment
The mutation to remember is JAK2. Treatment might involve JAK2 inhibitors, such as ruxolitinib
what does Myelofibrosis
result from
primary Myelofibrosis, polycythaemia vera or essential thrombocythaemia
what is Myelofibrosis
where the proliferation of a single cell line leads to bone marrow fibrosis, where bone marrow is replaced by scar tissue.
bone marrow is replaced by scar tissue in response to what in Myelofibrosis
in response to cytokines released from the proliferating cells
what is one particular cytokine concerned with Myelofibrosis
fibroblast growth factor
what does fibrosis in Myelofibrosis affect
the production of blood cells and can lead to low haemoglobin (anaemia), low white blood cells (leukopenia) and low platelets (thrombocytopenia)
what happens when the bone marrow is replaced with scar tissue
the production of blood cells haematopoiesis starts to happen in other areas known as extramedullary haemotopoiesis
what does production of blood cells in the liver and spleen cause
hepatomegaly, splenomegaly, and portal hypertension
what happens when extramedullary haematopoeisis happens around the spine
it can cause spinal cord compression
what will a blood film in myelofibrosis show
Teardrop-shaped red blood cells
Anisocytosis (varying sizes of red blood cells)
Blasts (immature red and white cells)
what is the initial presentation of myeloproliferative disorders
initially may be asymptomatic
what are the non specific symptoms that myeloproliferative disorders can present with
Fatigue
Weight loss
Night sweats
Fever
what is the major complication of polycythaemia
gout
what is the most common complication of polycythaemia and thrombocythaemia
Thrombosis is a common complication of polycythaemia and thrombocythaemia, leading to myocardial infarction, stroke or venous thromboembolism (e.g., DVT and PE).
what are the clinical signs of polycythaemia
Ruddy complexion (red face)
Conjunctival plethora (the opposite of conjunctival pallor)
Splenomegaly
Hypertension
what is required to confirm the diagnosis of myelofibrosis
bone marrow biopsy is required to confirm the diagnosis
bone marrow aspiration may be dry with myelofibrosis, as the bone marrow has turned into scar tissue
testing for what genes can help with the diagnosis and management of myelofibrosis
Testing for the JAK2, MPL and CALR genes can help with diagnosis and management.
what is the management of primary myelofibrosis
No active treatment for mild disease with minimal symptoms
Supportive management of complications, such as anaemia, splenomegaly and portal hypertension
Chemotherapy (e.g., hydroxycarbamide) to help control the disease
Targeted therapies, such as JAK2 inhibitors (ruxolitinib)
Allogeneic stem cell transplantation (risky but potentially curative)
what is the management of polycythaemia vera
Venesection to keep the haemoglobin in the normal range
Aspirin to reduce the risk of thrombus formation
Chemotherapy (typically hydroxycarbamide) to help control the disease
what is the management of essential thrombocythaemia
Aspirin to reduce the risk of thrombus formation
Chemotherapy (typically hydroxycarbamide) to help control the disease
Anagrelide is a specialist platelet-lowering agent
what kind of anaemia does vitamin B12 deficiency cause
macrocytic anaemia
what are the key causes of a low B12
Pernicious anaemia
Insufficient dietary B12 (particularly a vegan diet, as
B12 is mostly found in animal products)
Medications that reduce B12 absorption (e.g., proton pump inhibitors and metformin)
what is pernicious anaemia
an autoimmune condition involving antibodies against the parietal cells or intrinsic factor
what is the pathophysiology of pernicious anaemia
the parietal cells of the stomach produce a protein called intrinsic factor
intrinsic factor is essential for the absorption of vitamin B12, in the distal ileum
in pernicious anaemia, autoantibodies target what?
either the partietal cells or intrinsic factor, resulting in a lack of intrinsic factor and a lack of absorption iof btamin B12
what are the neurological symptoms that vitamin B12 deficiency can cause
Peripheral neuropathy, with numbness or paraesthesia (pins and needles)
Loss of vibration sense
Loss of proprioception
Visual changes
Mood and cognitive changes
what are the autoantibodies for pernicious anaemia
Intrinsic factor antibodies (the first-line investigation)
Gastric parietal cell antibodies (less helpful)
what is initially given to patients with B12 deficiency depending on symptoms
Intramuscular hydroxocobalamin
if patient has no neurological symptoms, how long is Intramuscular hydroxocobalamin given for
3 times weekly for two weeks
if the patient has neurological symptoms, how often is Intramuscular hydroxocobalamin given
alternate days until there is no further improvement in symptoms
what does maintenence treatment depend on
the cauase
what is the maintence for penicious anaemia
2-3 monthly injections of Intramuscular hydroxocobalamin for month
what is the maintenance for diet related
Diet-related – oral cyanocobalamin or twice-yearly injections
what is essential to do if there is B12 and folate deficiency together
it is essential to treat the B12 deficiency first before correcting the folate deficinecy.
what happens if you give patients folic acid when they have a B12 deficiency
lead to subacute combined degeneration of the cord, with demyelination in the spinal cord and severe neurological problems.
what is thalassaemia caused by
a genetic defect in the protein chains, that make up haemoglobin
what does normal haemoglobin consist of
two alpha-globin and two beta-globin chains
what do defects in alpha-globin chains lead to
alpha thalassaemia
what do defects in the beta-globin chains lead to
beta thalassaemia
both alpha and beta thalassamia are what?
autosomal recessive
what is the overall effect of thalassaemia
varying degrees of anaemia, depending on the type and mutation
what happens in thalassaemia to the RBCs
they are more fragile and break down easily causing haemolytic anaemia
what does the spleen act as in thalassaemia
the spleen acts as a sieve, filtering the blood and removing older cells. the spleen collects all the destroyed RBCs resulting in splenomegaly
what are the features of thalassaemia
Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
what is used to diagnose globin abnormalities
haemoglobin electrophoresis
why may iron overload occur in thalassaemia
Increased iron absorption in the gastrointestinal tract
Blood transfusions
Iron overload in thalassaemia can cause symptoms and complications of what?
Liver cirrhosis
Hypogonadism
Hypothyroidism
Heart failure
Diabetes
Osteoporosis
what does management of thalassaemia alpha involve
Monitoring
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
what do the gene defects in beta thalassaemia consist of
either abnormal copies that retain some function or deletion genes with no function in the beta-globin.
what are the three types of beta-thalassaemia
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
patients with thalassaemia minor have what?
carriers of abnormally funcitoning beta-globin gene
they have one abnormal and one normal gene
what does thalassaaemia minor cause
mild microcytic anaemia and usually only requires monitoring
what do patients with beta thalassaemia intermedia have
two abnormal copies of the beta-globin gene
what does thalassaemia intermedia cause
more signifianct microcytic anaemia.
patients require monitoring and may need occasional blood transfusions
what is given to prevent iron overload
They may require iron chelation to prevent iron overload.
what are patients with beta thalassaemia major
are homozygous for the deletion genes.
they have no functioning beta globin genes
what are the abnormal features relating to bone changes include
Frontal bossing (prominent forehead)
Enlarged maxilla (prominent cheekbones)
Depressed nasal bridge (flat nose)
Protruding upper teeth
what does management of thalassaemia major involve
regular transfusions, uron chelation and splenectomy
a bone marrow transplant can be curative
