Path - Haematology Flashcards
Infection with which virus is associated specifically with adult T-cell leukaemia/lymphoma?
A. HPV B. HIV C. Epstein-Barr virus D. HTLV1 E. Human herpes virus 8
D. HTLV1
Particularly prevalent in the Caribbean and Japan
Hyper-lobated nuclei may be seen - flower cells
A 45 year-old male presents to his GP with a 3 week history of sore throat. He has recently had an episode of shingles. His EBV IgG serology is positive, and an FBC shows a lymphocytosis. The blood film shows normal mature lymphocytes. Flow cytometry is carried out and reveals 82% of the proliferated lymphocytes express kappa chains, and 0% express lambda chains.
What is the most likely diagnosis?
A. Viral pharyngitis B. Acute lymphoblastic lymphoma C. B-cell lymphoma D. Adult T-cell leukaemia/lymphoma E. Infectious mononucleosis
C. B-cell lymphoma
Though parts of this case sound as though they describe a normal response to infection, the flow cytometry shows light chain restriction - an indicator of monoclonal B-cell proliferation. This excludes infectious causes, as well as T-cell malignancy. The blood film features only mature cells, which excludes a lymphoblastic leukaemia.
The positive IgG result is significant because it implies past infection with Epstein-Barr virus, which increases the risk of many haematological malignancies, including B-cell lymphomas.
A 29 year-old woman presents with fatigue, weight loss, fever, and night sweats of one month duration. Lymphoma is diagnosed, and PET scanning reveals involvement of cervical, axillary and mesenteric lymph nodes, and of the spleen.
What would the staging of this cancer be?
A. Stage 2b B. Stage 3a C. Stage 3b D. Stage 4a E. Stage 4b
C. Stage 3b
Stage 1 - one group of lymph nodes affected
Stage 2 - >one group of lymph nodes affected, but above the diaphragm
Stage 3 - spread below the diaphragm
Stage 4 - spread outside the lymph nodes/ spleen
Either ‘a’ or ‘b’ is then added as a suffix: if there are one or more constitutional symptoms present (fever, weight loss, night sweats) then a ‘b’ is added, if not an ‘a’ is used
NB: for purposes of staging, the spleen is counted as a lymph node
A patient presents with epigastric pain which is particularly pronounced at mealtimes, as well as dark, offensive-smelling stools. An ODG reveals a peptic ulcer, and a stool antigen test reveals the presence of H. pylori.
Which cancer is this man at increased risk of due to chronic infection with H. pylori?
A. Enteropathy-associated T-cell Non-Hodgkin lymphoma
B. Marginal zone lyphoma of the parotid gland
C. Gastric MALT lymphoma
D. Gastric carcinoma
E. Adult T-cell leukaemia/lyphoma
C. Gastric MALT lymphoma
H. pylori is not only strongly associated with gastric ulcers, chronic infection can cause gastric MALT lymphoma. However this is a low grade lymphoma, and treatment usually centres on eradicating the H. pylori infection, as the lymphoma will often resolve once that stimulus is removed.
Which of the following stains would be useful in detecting hepatic siderosis?
A. Ziehl-Neelson B. Prussian blue C. Sudan black D. Congo red E. Rhodamine
B. Prussian blue
Also known as Perl’s stain, Prussian blue is commonly used to detect iron, e.g. in hepatic siderosis (iron accumulation in the liver).
Which of the following is the most aggressive form of lymphoma?
A. Diffuse large B-cell lymphoma B. Follicular lymphoma C. Marginal zone lymphoma D. Burkitt's lymphoma E. Mantle cell lymphoma
D. Burkitt’s lymphoma
Burkitt’s lymphoma is the most aggressive of the lymphomas here. Burkitt’s lymphoma may produce a mass in the abdomen or jaw and is associated with younger patients. A ‘starry sky’ appearance on histopathology is pathognomic of Burkitt’s lymphoma.
Mantle-cell lymphomas and diffuse large B-cell lymphoma are also aggressive, Mantle-cell lymphoma typically over expresses cyclin D1. It presents in older patients, and is often widespread at the time of presentation, hence prognosis is poor.
Marginal zone lyphomas and follicular lymphomas are low-grade
Marginal zone lymphomas often arise at extra-nodal sites and are associated with specific diseases: gastric MALT lymphoma - H. pylori infection, thyroid marginal zone lymphoma - Hashimoto’s disease, parotid marginal zone lymphoma - Sjogren’s disease.
A blood film shows scattered tingible-body macrophages (macrophages filled with apoptotic remains) on a background of lymphoblasts.
What is the most likely cause of this histological appearance?
A. Acute lymphoblastic leukaemia B. Chronic lymphocytic leukaemia C. Sarcoidosis D. Burkitt's lymphoma E. Hodgkin's lymphoma
D. Burkitt’s lymphoma
This is a description of the classic ‘starry sky’ appearance of Burkitt’s lymphoma - a highly aggressive yet often very treatable cancer associated with Epstein-Barr virus infection which is more common in the developing world.
Burkitt’s lymphoma is an acute B-cell lymphoblastic lymphoma, and the lymphoblasts are tightly grouped together. These are stained blue which creates the appearance of the ‘sky’, whilst the presence of macrophages filled with debris from apoptosed tumour cells (tingible-body macrophages) creates the appearance of the ‘stars’, as upon fixation of the sample the cytoplasm of macrophages is lost leaving white gaps.
A patient presents with lympahdenopathy, fever, and fatigue. They have a previous history of EBV infection.
What would suggest a diagnosis of non-Hodgkin lymphoma rather than Hodgkin lymphoma?
A. Lymph nodes in both the groin and anterior cervical chain affected
B. Bence-Jones proteins in the urine
C. Lymph nodes in both the anterior cervical and sub-mandibular chains affected
D. Reed-Sternberg cells seen on histopathology
E. Previous history of infectious mononucleosis
A. Lymph nodes in both the groin and anterior cervical chain affected
Non-Hodgkin lymphoma more frequently features involvement of multiple groups of lymph nodes, and they are more likely to be in discontiguous groups.
Age is often a useful clue in differentiating between the two diseases, as Hodgkin’s lymphoma has a bimodal peak affecting both young and old patients, wheres Non-Hodgkin lymphoma favours older patients only.
What is the mechanism driving proliferation in CML?
A. Loss of chromosomes (hypodiploidy)
B. Inappropriate activation of retinoic acid receptors
C. Transcription factor mutation
D. Inappropriate activity of tyrosine kinase
E. Addition of chromosomes (hyperdiploidy)
D. Inappropriate activity of tyrosine kinase
CML is caused by a 9, 22 translocation leading to formation of the Philadelphia chromosome. The Abl gene encodes a tyrosine kinase protein. When the 9-22 translocation occurs, the BCR-Abl fusion gene produces a constitutively active tyrosine kinase. The presence of the Philadelphia chromosome is 100% sensitive for CML but not totally specific as it may also be found in ALL.
Which of the following options accurately describes polycythaemia vera?
A. A malignant proliferation of RBCs driven by mutation of a kinase bound to the EPO receptor
B. Hyper-production of RBCs driven by an EPO-secreting tumour (e.g. renal cell carcinoma, uterine myoma)
C. A deceptive increase in haematocrit and haemoglobin due to loss of plasma volume rather than abnormal RBC production
D. A block in differentiation of lymphocytes which, in combination with increased proliferation, leads to large numbers of ineffective blasts in the peripheral blood which also crowd out the bone marrow
E. A physiological response to chronic hypoxia (e.g. cyanotic heart disease, living at high altitude, high affinity haemoglobin disorders)
A. A malignant proliferation of RBCs driven by mutation of a kinase bound to the EPO receptor
The kinase mentioned is JAK2, which is bound to the erythropoietin (EPO) receptor and is phosphorylated upon activation of the receptor. Polycythaemia is considered a myeloproliferative Philadelphia (Ph) negative neoplasm. The other myeloproliferative Ph negative neoplasms are essential thrombocytopenia and primary myelofibrosis, which are also associated with JAK2 mutations.
‘B’ describes inappropriate true secondary polycythaemia, and ‘E’ describes appropriate true secondary polycythaemia. In both cases the bone marrow is functioning normally, but is stimulated to produce more RBCs either as part of an appropriate physiological response to hypoxia, or in response to ectopic EPO production.
‘C’ describes a relative or pseudo polycythaemia: the actual red cell mass is unchanged, but loss of plasma volume concentrates red cells to give that impression.
‘D’ describes the pathology of ALL.
Which of the following options describes the aetiology of febrile non-haemolytic transfusion reaction?
A. IgG antibodies react against Rhesus D antigen
B. Endotoxin contamination causing systemic reaction
C. IgM antibodies react against A or B antigens
D. Cytokines in donor plasma cause an inflammatory reaction
E. Mast cell degranulation as IgE are crosslinked by an antigen in the donor plasma
D. Cytokines in donor plasma cause an inflammatory reaction
These reactions are generally mild and can be treated using paracetamol before restarting transfusion. They are rarer since the advent of leucodepeletion of blood.
During routine obs, a patient on the wards is noted to have a BP of 100/60, resp rate of 29, and an HR of 110. They are also noted to be febrile. Their notes reveal they received a blood transfusion 1 hour beforehand.
What is the most likely diagnosis?
A. ABO incompatibility
B. IgG haemolytic reaction
C. Febrile non-heamolytic transfusion reaction
D. Transfusion-associated circulatory overload
E. Anaphylaxis
A. ABO incompatibility
In the rare event that an error leads to blood being given to someone with an incompatible ABO status, a severe haemolytic reaction will ensue very quickly. This is mediated by IgM (in contrast to the IgG-mediated reaction against D antigens which is also a delayed haemolytic reaction) and causes circulatory shock (low BP, high HR) and fever along with chest/ loin pain, vomiting, collapse, flushing, and haemoglobinuria (later).
As it sounds, this is a medical emergency and it is the reason you should always LABEL AT THE BEDSIDE.
Bacterial contamination presents essentially identically, and so should be a differential in this patient.
This patient would need blood samples taking for FBC, coagulation, X-match, and direct anti-globulin test. You would then need to urgently consult a haematologist.
During routine obs, a patient on the ward is noted to have an increased resp rate, decreased O2 saturations, increased blood pressure, and dyspnoea. They received a transfusion 13 hours prior, and their past medical history includes diabetes and hypertension. A CXR shows increased opacity in a bilateral ‘bat-wing’ shape.
What is the most likely diagnosis?
A. Febrile non-haemolytic transfusion reaction
B. Transfusion-associated circulatory overload
C. Nephrotic syndrome
D. Allergic reaction
E. Delayed haemolytic transfusion reaciton
B. Transfusion-associated circulatory overload
This patient has renal impairment as a result of their diabetes and/or hypertension which has resulted in fluid overload from the transfusion (the ‘bat-wing’ appearance on CXR indicates pulmonary oedema). To avoid this, furosemide can be prescribed along with transfused blood. This is comfortably the most common cause of transfusion complications
During routine obs, a patient on the post-natal ward is noted to have an increased resp rate, fever, decreased O2 saturations, increased blood pressure, and dyspnoea. They received a blood transfusion 4 hours prior after major post-partum haemorrhage, though there were no risk factors for this and they have no significant PMHx. A CXR shows bilateral infiltrates, and also indicates pulmonary oedema.
What is the most likely diagnosis?
A. Transfusion-related acute lung injury
B. ABO incompatibility
C. Anaphylaxis
D. Febrile non-haemolytic transfusion reaction
E. Transfusion-associated circulatory overload
A. Transfusion-related acute lung injury
TRALI is caused by aggregation of host WBCs by donor antibodies. The aggregated WBCs become stuck in pulmonary capillaries and release proteolytic enzymes and toxic O2 metabolites which damages the lung parenchyma. TRALI presents very acutely (usually within 4 hours) which helps to differentiate it from other transfusion reactions.
TRALI will cause an ARDS-type clinical picture and can be difficult to differentiate from TACO. The key here is that there are no pre-existing conditions that would predispose this otherwise healthy woman to develop circulatory overload. Furthermore the fever is suggestive of TRALI.
Which of the following features of a blood film would most suggest AML?
A. Myeloblasts with azurophillic crystal formations
B. Absence of granules within the neutrophil
C. Ringed sideroblasts
D. Dyserythropoiesis
E. Pelger-Huet anomaly
A. Myeloblasts with azurophillic crystal formations
The azurophillic crystal formations described here are Auer rods, which are particularly associated with acute myeloid leukaemia. All the other features are more commonly seen in myelodysplasia:
Neutrophils may show reduced granulation
Ringed sideroblasts are an abnormal type of red cell produced when the body has enough iron available, but the bone marrow is not functioning well enough to incorporate it into haemoglobin. These cells can be identified with a Perl stain.
Dyserythropoiesis refers to generic production of dysmorphic RBCs
A Pelger-Huet anomaly is a bi-lobed neutrophil. This can be seen as a result of an autosomal dominant genetic disorder, or may be the result of myelodysplasia
Which of the following is not a component of the IPSS-R criteria for assessing prognosis of myelodysplasia?
A. Platelet count B. Blast percentage in peripheral blood C. Neutrophil morphology D. Karyotype E. Haemoglobin
C. Neutrophil morphology
The Revised International Prognosis Scoring System (IPSS-R) for myelodysplasia prognosis consists of five variables: peripheral blood blast percentage, karyotype, neutrophil count, platelet count, and haemoglobin. Although changes in neutrophil morphology are associated with myelodysplasia, that does not affect the scoring of this prognostic system.
Which of the following is true of myelodysplasia?
A. Myelodysplasia has a bimodal age distribution
B. The primary modality of treatment of myelodysplasia is intensive chemotherapy
C. One third of myelodysplasia patients who die can be expected to die from leukaemic transformation
D. There is no good correlation between the severity of cytopenias and overall life expectancy
E. White cell function is frequently well preserved in myelodysplasia
C. One third of myelodysplasia patients who die can be expected to die from leukaemic transformation
Myelodysplasia generally affects only the elderly (60+). Whilst intensive chemotherapy is one of only two options for curing myelodysplasia (the other being stem cell transplant), patients are typically too elderly and not fit enough to tolerate these treatments. Accordingly, primary treatment is more often supportive (antibiotics, blood products, growth factors like EPO, low-dose chemo, immunomodulation).
There is correlation between severity of cytopenias and survival, which is why each cytopenia is factored into the R-IPSS. White cell function is frequently decreased in myelodysplasia, because it causes qualitative as well as quantitative deficiency.
Which option is true regarding aplastic anaemia?
A. Immunosuppressive treatment is used only for a minority of patients
B. If treated with immunosuppression, relapse occurs in <15% of cases
C. The cure rate using sibling-donated stem cell transplants is >70%
D. Severe aplastic anaemia is differentiated from non-severe using cytogenetic abnormalities of the bone marrow
E. Leucodepletion of blood products is only done in exceptional circumstances for these patients
C. The cure rate using sibling-donated stem cell transplants is >70%
Immunosuppressive therapy is used as the primary treatment where bone marrow transplant is unsuitable (i.e. elderly patients). Immunosuppression is used because there is a theorised autoimmune component to idiopathic aplastic anaemia, and immunosuppression has been shown to work. However there is a ~35% chance of relapse and a ~20% chance of haematological malignancy following treatment with immunosuppression.
Sibling-donated stem cell transplant is ideal as cure rates range as high as 80%, but the procedure has a high mortality rate especially in older patients.
Severe aplastic anaemia is defined by cytopenia below a certain threshold of two of platelets, neutrophils, or RBCs along with a hypocellular bone marrow. This is the Camitta criteria.
Leucodepletion is standard practice for blood products to prevent febrile transfusion reactions.
Which statement regarding Fanconi’s anaemia is false?
A. Aplastic anaemia occurs in 90% of affected individuals
B. It may be inherited in either an autosomal recessive or an x-linked fashion
C. It may be associated with abnormal growth of the thumbs
D. 60% of individuals have no associated malformations
E. It is the most common form of inherited aplastic anaemia
D. 60% of individuals have no associated malformations
Only 30% of patients have no associated malformations. Conditions associated with Fanconi anaemia may include microcephaly, hydrocephalus, abnormalities of the thumb, hypopigmented spots, cafe au lait macules, short stature, developmental delay, and hypogonadism
Which of the following statements is true?
A. Telomere function is unrelated to the pathophysiology of dyskeratosis congenita
B. Development of malignancy is an uncommon complication of Fanconi anaemia
C. Fanconi anaemia is a single gene defect
D. Fanconi anaemia is usually inherited in an autosomal dominant fashion
E. Telomeric shortening may be a feature of both dyskeratosis congenita and idiopathic aplastic anaemia
E. Telomeric shortening may be a feature of both dyskeratosis congenita and idiopathic aplastic anaemia
Telomeres protect chromosomes from degradation, and allow them to continue replicating. Shortening of the telomeres reduces the number of times a cell may divide before it reaches its limit (Hayflick limit). Although shortened telomeres may be present in both dyskeratosis congenita and idiopathic aplastic anaemia, it is more classically associated with DC.
Which of the following is least likely to occur as a side-effect of treatment with ABVD chemotherapy?
A. Pulmonary fibrosis B. Infertility C. Hair loss D. Cardiomyopathy E. Nausea
B. Infertility
The major advantage of the ABVD regime over its predecessor (MOPP) is that it tends to preserve fertility, which is particularly important in women as fertility preservation techniques for women have a lower success rate than freezing perm does for men. ABVD is used to treat classical Hodgkin lymphoma.
Fertility preservation is particularly useful for patients with nodular sclerosing subtype of classical Hodgkin lymphoma as it most commonly affects young women, in whom fertility preservation is often a priority. The other sub-types are mixed cellularity, lymphocyte rich, and lymphocyte depleted. These sub-types are more common in the second age peak of Hodgkin lymphoma and have a good prognosis apart from the lymphocyte depleted type.
R-CHOP is the most common regimen used to treat non-Hodgkin lymphoma.
Which of the following lymphomas is considered incurable?
A. Burkitt's lymphoma B. Follicular lymphoma C. Mantle cell lymphoma D. Diffuse B-cell lymphoma E. Gastric MALT lymphoma
B. Follicular lymphoma
It is a strange paradox that the indolent lymphomas are incurable, whereas the aggressive diseases (e.g. Burkitt’s) are considered very curable, though lethal if treatment is not given.
The median survival time for follicular lymphoma is 12-15 years, so it often warrants a ‘watch and wait’ policy until there are complications (e.g. swollen lymph node compressing vena cava, trachea, gut, or ureter, or recurrent infections, or pain). Follicular lymphoma is often associated with a mutation causing over expression of the anti-apoptosis protein bcl2.
Which of the following is associated with coeliac disease?
A. Gastric MALT lymphoma B. Marginal zone lymphoma of the parotid C. Enteropathy-associated T-cell lymphoma D. Diffuse B-cell lymphoma E. Adult T-cell leukaemia/lymphoma
C. Enteropathy-associated T-cell lymphoma
EATL occurs more often in coeliac patients, particularly if their disease is poorly managed. It is an aggressive lymphoma that respond poorly to chemotherapy.
Which of the following is a normal immunophenotype of a mature peripheral B-cell?
A. CD3+, CD5+, CD19- B. CD3+, CD5+, CD19+ C. CD3-, CD5-, CD19+ D. CD3-, CD5+, CD19- E. CD3-, CD5-, CD19-
C. CD3-, CD5-, CD19+
CD3 is present on all T-cells, and CD19 is present on B-cells from an early stage of maturation. CD5 is only briefly present on immature B-cells at a specific stage of their maturation, and so should not be present on mature cells. CD5 presence may indicate a range of diseases, including CLL, but is normal on mature T-cells.
In which four ways does blood stasis promote coagulation?
- Activated factors can accumulate
- Platelets can more easily adhere to the vessel wall and each other
- Leukocytes can more easily adhere to vessel wall and cross it
- Local hypoxia develops which causes inflammation of the vessel wall, which is pro-thrombotic
How does protamine sulphate reverse the effects of heparin?
Protamine is alkaline in solution, and reacts with the acidic heparin to form a stable salt, which is then excreted.
Which of the following increases the risk of thrombosis?
A. Reduced prothrombin B. Thrombocytopenia C. Reduced protein C D. Elevated antithrombin E. Increased fibrinolysis
C. Reduced protein C
Protein C is a protease which lyses peptide bonds in Va and VIIIa, thereby reducing thrombin production.
Why is warfarin initially pro-coagulant?
Warfarin inhibits vitamin k epoxide reductase which recycles vitamin K for use in making clotting factors 2, 7, 9, and 10. It takes some time for the factors already made and in the bloodstream to degrade, and so warfarin is not immediately an anti-coagulant. However warfarin does immediately inhibit Protein C and Protein S (co-factor to Protein C), which has a pro-thrombotic effect. Accordingly, warfarin should be accompanied by LMWH initially.
Which factor confers the highest risk of thrombosis?
A. Factor V Leiden B. Antithrombin deficiency C. Family history of thrombosis D. Reduced factor VIII level E. 3 hour plane flight
B. Antithrombin deficiency
It is important to remember that two predisposing factors may combine to have an effect greater than the sum of their parts. E.g. patients with Factor V Leiden who are taking the COCP have a drastically increased risk of thromboembolism compared to the individual risks of each factor alone.
A 66 year-old man presents to their GP with fatigue and breathlessness. Further questioning reveals the patient has lost 6kg over the last month or so and has been having night sweats. Their medical records show they were seen two weeks ago for a very painful and inflamed 1st MTP joint in their big toe. Abdominal examination reveals massive splenomegaly.
A panel of blood tests shows a pancytopenia. The blood film shows dacrocytes, leucoblasts, erythroblasts, and circulating megakaryocytes. An attempted bone marrow tap fails to produce a sample, but a trephine bone marrow biopsy reveals significant collagen deposition.
Which of the following would support the most likely diagnosis in this case?
A. A promising prognosis B. Susceptibility to Imatinib C. Development of clotting derangement D. JAK2 and CALR mutations E. The presence of smudge cells in a blood film
D. JAK2 and CALR mutations
Primary myelofibrosis is a rare (~1 in 100,000) Philadelphia negative myeloproliferative neoplasm. In primary myelofibrosis clonal proliferation leads to a reactive bone marrow fibrosis; this fibrosis is hinted at in the question by mention of collagen deposition.
Presentation of myelofibrosis does little to distinguish it from other haematological malignancies, as it presents with B symptoms, consequences of pancytopenia, and consequences of gout, all of which are non-specific. The degree of hepatosplenomegaly is a potentially useful differentiator in narrowing down options form a surgical sieve, as only a few things can cause massive splenomegaly (chronic malaria, leishmaniasis, Gaucher disease, certain myeloproliferative diseases). This is a result of extra-medullary haematopoiesis taking up the slack from the impaired bone marrow, and from infiltration by abnormal cells.
The ‘dry tap’ is an important clue - a result of the fibrosed bone marrow.
CALR and JAK2 mutations can both be associated with primary myelofibrosis, and high uric acid levels may be found in any condition featuring high cell turnover. A poor response to treatment and a poor prognosis are unfortunately likely.
A 50 year-old man presents with an episode of transient blindness in his left eye, which he describes as “like a curtain coming down over my vision”. A cranial nerve exam is normal, but an abdominal exam reveals massive splenomegaly. Routine blood tests are also performed and show the following:
Haemoglobin: 13g/dL
WBC: 184x10^9/L
Platelets: 500x10^9/L
The blood film shows a mature myelocytosis with neutrophilia, eosinophilia, and basophilia. The patient is diagnosed with chronic myeloid leukaemia, and started on imatinib. Their response to treatment is assessed 12 months later.
Which option would meet the minimum standard for a major/ complete response?
A. <0.1% bcr-abl transcripts detected on PCR
B. A WCC of 11x10^9 or less
C. 20% metaphasic cells sampled Ph negative
D. 10% metaphasic cells sampled Ph negative
E. 5% metaphasic cells sampled Ph negative
A. <0.1% bcr-abl transcripts detected on PCR
Generally, response to treatment is based on molecular assessment: the percentage reduction in transcripts of the bcr-abl fusion gene expressed by CML cells. A major molecular response requires there to be <0.1% bcr-abl transcripts on PCR.
Response may also be assessed on either cytogenetic or haematological response. Complete cytogenetic response requires 0% Philadelphia positive cells to be seen in a metaphase culture. Complete haematological response requires a WCC <10x19^9
How does imatinib inhibit the Bcr-Abl fusion protein?
It is a competitive inhibitor of ATP; it bins to the ATP-binding pocket to prevent activation of the fusion protein.
Which of the following options is not a factor in the pathophysiology of anaemia of chronic disease?
A. Up-regulation of an iron transporter leading to increased uptake of iron by macrophages
B. Suppression of ferritin expression leading to a reflex decrease in transferrin levels
C. IL-6 release stimulates hepcidin production in the liver
D. Suppression of erythropoiesis by the action of inflammatory cytokines on the MAPK and JAK/STAT pathways
E. Decreased ferroportin expression, reducing iron uptake from the gut and release from macrophages
B. Suppression of ferritin expression leading to a reflex decrease in transferrin levels, reducing iron transport from the gut
