Haem III Flashcards
Pancytopaenia may be caused by which three broad mechanisms? [3]
Bone marrow suppression:
- the process of haematopoiesis is reduced preventing blood cell production.
Bone marrow infiltration:
- the bone marrow is infiltrated (e.g. malignant cells, microorganisms) impairing its ability to conduct haematopoiesis.
Blood cell destruction:
- there is an increased turnover of blood cells in the peripheral circulation due to destruction or sequestration in organs (e.g. spleen).
Name causes for the different categories of pancytopaenia:
Haemotological [4]
Metatstatic [3]
Infections [4]
Haemotological:
- Leukaemia
- Lymphoma
- Multiple myeloma
- Myelodysplastic syndromes
Metatstatic:
- Lung cancer
- Breast cancer
- Prostate carcinoma
Infections
- TB
- Fungal
- HiV
- Parvovirus B19
Name causes for the different categories of pancytopaenia:
Nutrional deficiencies [3]
Medications and toxins [4]
Autoimmune disorders [3]
Nutrional deficiencies:
- Vitamin B12
- Folate
- Anorexia nervosa
Medications and toxins:
- Alcohol
- chemotherapy
- azathioprine
- methotrexate,
- carbamazepine
Autoimmune disorders:
- aplastic anaemia
- rheumatoid
- SLE
Name causes for the different categories of pancytopaenia:
Peripheral destruction [1]
Peripheral sequestration [1]
Congenital [2]
Peripheral destruction
- Disseminated intravascular coagulation
Peripheral sequestration
- portal hypertension
Congenital:
- Wiskott Aldrich syndrome,
- Fanconi anemia
What are the top 4 differential diagnosis of abnormal bleeding? [4]
- Thrombocytopenia
- Von Willebrand disease
- Haemophilia A and haemophilia B
- Disseminated intravascular coagulation (usually secondary to sepsis)
Describe what is meant by Immune Thrombocytopenic Purpura [3]
(AKA autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura and primary thrombocytopenic purpura)
- antibodies are created against platelets, leading to their destruction
- antibodies are produced of IgG and target the platelet membrane glycoproteins GPIIb/IIIa
- the bone marrow compensates by making more megakaryocytes
How does ITP typically present? [5]
- petechiae: small red dots on the skin.
- purpura: formed by petechiae joined together, can also occur
- Mild epistaxis is common; can lead to continous epistaxis
- prolonged and heavy menstrual cycles.
- large gastrointestinal bleeds
What are paradoxical thrombotic events in ITP? [1]
patients with ITP may present with strokes and TIA
Desribe the treatment plan for ITP
First line treatment:
- Oral prednisone at 1mg/kg daily with proton pump inhibitors
- Over 2 - 4 weeks and weaned off a few weeks after
AND
- Pooled normal human immunoglobulin (IVIG)
Second line:
- Mycophenolate mofetil- mmunosuppressive agent
AND
- thrombopoietin receptor agonist (e.g romiplostim)
AND
- Rituximab
AND
- Fostamatinib spleen tyrosine kinase (Syk) inhibitor
AND
- Splenectomy
What is meant by Evans syndrome? [1]
Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)
In TTP, thrombi develop due to a problem with a specific protein called [].
Thrombi develop due to a problem with a specific protein called ADAMTS13
In TTP, thrombi develop due to a problem with a specific protein called ADAMTS13. What is the role of this protein? [3]
- Inactivates von Willebrand factor
- Reduces platelet adhesion to vessel walls
- Reduces clot formation
What are the clinical features of TTP? [5]
- Rare, typically adult females
- Fever
- Fluctuating neuro signs (microemboli)
- Microangiopathic haemolytic anaemia
- Thrombocytopenia
- Renal failure
FAT RN
What worsens the TTP? [1]
Abx
What is the basic treatment for TTP? [3]
plasma exchange, steroids, rituximab, Vincristine
Describe the phenomona of Heparin-Induced Thrombocytopenia [2]
Development of antibodies against platelets in response to heparin (usually unfractionated heparin, but it can occur with low-molecular-weight heparin).
Heparin-induced antibodies target a protein on platelets called platelet factor 4 (PF4).
The HIT antibodies activate the clotting system, causing a hypercoagulable state and thrombosis (e.g., deep vein thrombosis)
They also break down platelets and cause thrombocytopenia
How long after adminstering heparin does HIT usually occur? [1]
5-10 days
State the proliferating cell line in each of the following [3]
- Primary myelofibrosis
- Polycythaemia vera
- Essential thrombocythaemia
Primary myelofibrosis:
- Haematopoietic stem cells
Polycythaemia vera:
- Erythroid cells
Essential thrombocythaemia:
- Megakaryocyte
State the blood finding result for each of the following
Primary myelofibrosis [3]
Polycythaemia vera [1]
Essential thrombocythaemia [1]
State the blood finding result for each of the following
Primary myelofibrosis:
- Low haemoglobin
- High or low white cell count
- High or low platelet count
Polycythaemia vera:
- High haemoglobin
Essential thrombocythaemia:
- High platelet count
Describe the pathophysiology of myelofibrosis [4]
cytokines are released from the proliferating cells.: especially: fibroblast growth factor
FIbrosis decreases production of blood cells: ledas to low Hb; leukopaenia and thrombocytopaenia
When the bone marrow is replaced with scar tissue extramedullary haematopoiesis occurs
Production of blood cells in the liver and spleen causes hepatomegaly, splenomegaly, and portal hypertension. When it occurs around the spine, it can cause spinal cord compression.
Describe the initial presentation of myelofibrosis
20% asymptomatic
Hepatosplenomegaly
B symptoms: weight loss, fever and night sweats
Anaemia signs (conjunctival pallor etc)
Thrombembolic events
Portal hypertension (ascites, varices and abdominal pain)
Unexplained bleeding (due to low platelets)
[] is a complication of polycythaemia
Gout is a complication of polycythaemia
What are the symptomatic or palliative treatment options for myelofibrosis? [4]
Ruxolitinib:
- a JAK2 inhibitor
- effective regardless of JAK2 mutation status.
Hydroxyurea / (hydroxycarbamide)
interferon-alpha
It is established that a mutation in [] is present in approximately 95% of patients with polycythaemia vera.
Describe the pathophysiology of PV [2]
established that a mutation in JAK2 is present in approximately 95% of patients with polycythaemia vera
The JAK2 gene encodes for a non-receptor tyrosine kinase involved in signal transduction pathways for various hematopoietic growth factors, including erythropoietin (EPO).
The JAK2 V617F mutation results in constitutive activation of the JAK-STAT signaling pathway, leading to increased proliferation and survival of hematopoietic progenitor cells, independent of EPO stimulation.
In addition to affecting erythropoiesis, the JAK2 V617F mutation also influences the proliferation of other myeloid progenitor cells. Consequently, patients with PV may present with increased white blood cell and platelet counts.
Describe the clinical features of polcythaemia vera
- Ruddy complexion (red face)
- Conjunctival plethora(the opposite of conjunctival pallor)
- Haemorrhage
- Splenomegaly
- Hypertension
- Pruritis after a hot bath
How do you manage PV? [5]
Venesection - first line treatment
- to keep the haemoglobin in the normal range
Aspirin 75mg daily
- to reduce the risk of thrombus formation
Chemotherapy
- (typically hydroxycarbamide: reduces the number of RBC
Phosphorus-32 therapy
5-15% patients go on to develop which two pathologies from PV? [2]
5-15% of patients progress to myelofibrosis
5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)
Which tumours typically cause a rise in EPO? [3]
Renal cell cancer
Wilms’ tumour
Adrenal tumours
Cytoreductive therapy (Hydroxycarbamide / hydroxyurea) is considered in high-risk patients, defined by BSH as? [2]
Age ≥ 65 years and/or
Prior PV-associated arterial or venous thrombosis
Cytoreductive therapy is considered in low risk patients who meet which criteria? [4]
Thrombocytosis (> 1500 × 109/l)
Progressive splenomegaly
Progressive leucocytosis (> 15 × 109/l)
Poor tolerance of venesection
A patient presents with unexplained splenomegaly, leukoerythroblastosis, and peripheral blood cytopenias. Which diagnostic test is most appropriate for confirming the diagnosis of myelofibrosis?
a) Bone marrow biopsy
b) Complete blood count (CBC)
c) Serum erythropoietin levels
d) JAK2 mutation testing
A patient presents with unexplained splenomegaly, leukoerythroblastosis, and peripheral blood cytopenias. Which diagnostic test is most appropriate for confirming the diagnosis of myelofibrosis?
a) Bone marrow biopsy
b) Complete blood count (CBC)
c) Serum erythropoietin levels
d) JAK2 mutation testing
What constitutional symptoms are commonly associated with myelofibrosis?
a) Weight gain and fatigue
b) Night sweats and weight loss
c) Fever and headache
d) Hypertension and bradycardia
What constitutional symptoms are commonly associated with myelofibrosis?
a) Weight gain and fatigue
b) Night sweats and weight loss
c) Fever and headache
d) Hypertension and bradycardia
When should cytoreductive therapy be initiated in myelofibrosis patients, according to NICE guidelines?
a) At the time of diagnosis
b) Only if the patient is symptomatic
c) After confirmation of JAK2 mutation
d) When platelet count exceeds 500 x 10^9/L
When should cytoreductive therapy be initiated in myelofibrosis patients, according to NICE guidelines?
a) At the time of diagnosis
b) Only if the patient is symptomatic
c) After confirmation of JAK2 mutation
d) When platelet count exceeds 500 x 10^9/L
What is the recommended first-line therapy for myelofibrosis with intermediate-2 or high-risk disease, according to NICE guidelines?
a) Hydroxyurea
b) Ruxolitinib
c) Interferon-alpha
d) Allogeneic stem cell transplant
What is the recommended first-line therapy for myelofibrosis with intermediate-2 or high-risk disease, according to NICE guidelines?
a) Hydroxyurea
b) Ruxolitinib
c) Interferon-alpha
d) Allogeneic stem cell transplant
For a patient with significant splenomegaly causing discomfort and early satiety, what is the first-line approach recommended by NICE?
a) Splenectomy
b) Radiation therapy
c) Ruxolitinib
d) Supportive care only
For a patient with significant splenomegaly causing discomfort and early satiety, what is the first-line approach recommended by NICE?
a) Splenectomy
b) Radiation therapy
c) Ruxolitinib
d) Supportive care only
Which complication should be actively monitored in myelofibrosis patients receiving long-term hydroxyurea therapy?
a) Thrombocytosis
b) Pulmonary hypertension
c) Gastrointestinal bleeding
d) Secondary malignancies
Which complication should be actively monitored in myelofibrosis patients receiving long-term hydroxyurea therapy?
a) Thrombocytosis
b) Pulmonary hypertension
c) Gastrointestinal bleeding
d) Secondary malignancies
Hydroxyurea
