Haem IV (Myelodysplastic disorders) Flashcards
Describe what is meant by pancytopaenia
Pancytopaenia refers to a decrease in all peripheral blood cell lines.:
- red blood cells (RBCs)
- white blood cells (WBCs)
- platelets.
What exact values determine that pancytopaenia is present [3]
Haemoglobin:
- < 115 g/L (women), < 130 g/L (men)
Leucocytes:
- < 4.0 x109/L
OR
Neutrophils:
- < 1.5 x 109/L
Platelets:
- < 150 x109/L
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 common characteristic features of pancytopaenia? [3]
Lethargy (anaemia)
Weakness (anaemia)
Pallor
Bruising (low platetlets)
Bleeding
Recurrent infections (leucopaenia)
What examination findings should you look for in a patient with suspected pancytopaenia? [7]
- Lymphadenopathy
- Organomegaly (e.g. splenomegaly, hepatomegaly)
- Scleral findings: pale, jaundiced
- Oral findings: ulcers, thrush (e.g. as immunocompromised)
- Features of cardiac failure (e.g tachypnoea, raised JVP, crackles on auscultation, peripheral oedema): due to symptomatic anaemia
- Skin findings: pale, jaundiced, bruising, petechiae, purpura
- Other: joint pain or swelling, sarcopenia, active bleeding
What peripheral blood film results would indicate pancytopaenia? [6]
Which pathologies would these indicate? [6]
Circulating blasts (i.e. immature white blood cells): suggestive of leukaemia
Abnormal / dysplastic white cells: suggestive of myelodysplastic syndrome
Immature white blood cells: suggestive of myeloproliferative disorder
Hypersegmented neutrophils: suggestive of megaloblastic anaemia (e.g. B12 deficiency)
Schistocytes (fragmented red blood cells): suggestive of peripheral destruction
What follow up testing would you investigate with after a peripheral blood film for suspected pancytopaenia? [4]
- bone marrow aspirate
- biopsy
- flow cytometry
- cytogenetic testing
- molecular studies.
A bone marrow biopsy is particularly important in patients with a suspected primary haematological disorder.
Which further specialist tests would you use to investigate pancytopaenia? [5]
- Autoimmune / vasculitis screen
- Malaria screen
- Viral screen (e.g. HIV, hepatitis B/C)
- Serological tests for infections
- Bone marrow biopsy
- Lymph node biopsy
- CT-PET
Spread beyond LNs
2 or more LN, same side of diaphragm
TLS
Both sides of the diaphragm
EBV
What complications of thrombocytopenia are most concerning? [2]
Intracranial haemorrhage
Gastrointestinal bleeding
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
Which drugs can cause thrombocytopenia? [7]
- Heparin
- Gold
- Alemtuzumab
- Pembrolizumab
- Nivolumab
- Sodium valproate
- Methotrexate
Describe what is meant by the condition Thrombotic Thrombocytopenic Purpura [1]
What results from ^? [3]
Tiny thrombi develop throughout the small vessels, using up platelets. As the problem is in the small vessels, it is described as a microangiopathy. This causes:
- Thrombocytopenia
- Purpura
- Tissue ischaemia and end-organ damage
Get FAT RN:
- Fever
- Anaemia
- Thrombocytopenia
- Renal failure
- Neuro problems
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
Deficiency in the ADAMTS13 protein can be due to? [2]
An inherited genetic mutation (hereditary)
Autoimmune disease, where antibodies are created against the protein (acquired)
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