Haematology - Other Flashcards
What is the cause of myeloma?
Genetic changes (c14 translocation, hyperdiploidy) that occur during the terminal differentiation of B lymphocytes into plasma cells.
What is a paraprotein?
A monoclonal antibody found in blood as a result of cancer
What are the paraproteins found in the serum in myeloma?
IgG most commonly
Then IgA
What is found in the urine in myeloma and how?
Bence-Jones protein (light chains)
Urine electrophoresis
What are the patient demographics of myeloma patients?
Median age 70y
Commoner in males and Black Africans
What are the main symptoms of myeloma?
C - hypercalcaemia
R - renal failure
A - anaemia
B - bone lesions
What are the symptoms of hypercalcaemia?
Polyuria and polydipsia
Constipation and nausea
Renal stones
Confusion
How does bone marrow failure result from myeloma?
Plasma cells infiltrate the bone marrow, leading to anaemia, neutropenia, and thrombocytopenia.
How does renal failure occur in myeloma?
Deposition of light chains in renal tubules
What causes the lytic lesions of myeloma?
Dysregulation of bone remodelling; unopposed osteolysis from increased osteoclast activity due to increased production of RANK ligand –> hypercalcaemia
Myeloma cells produce DKK1 which inhibit osteoblast activity
Where are lytic lesions commonly found in myeloma?
Vertebrae - back pain
Skull - pepperpot
Long bones and ribs
The paraprotein in myeloma can cause hyperviscosity; what are the symptoms?
Blurred vision
Dizziness
Epistaxis
Confusion
How is myeloma diagnosed, other than urine electrophoresis?
FBC for BM failure ESR high High Ca2+ Rouleaux on blood film Serum protein electrophoresis and immunofixation BM aspirate Skeletal survey - MRI
What are rouleaux?
4 red blood cells in a row from paraprotein
What is seen on radiological investigation in myeloma?
Lytic lesions
Plasmacytomas
What are the differentials for presence of monoclonal proteins in the blood?
MGUS Light chain amyloidosis Plasmacytoma CLL B-cell lymphoma
What does MGUS stand for and what is it?
What percentage of patients progress to myeloma?
Monoclonal gammopathy of unknown significance. An isolated finding of paraprotein in the serum. 20% Progresses to multiple myeloma in 25 years (Rate = 1% per year)
Define smouldering/indolent myeloma and what is the rate of progression?
Asymptomatic myeloma: significant paraproteinaemia but no end organ damage.
Rate of progression is 10%/year
What protease inhibitor medication is used to induce remission in myeloma, as well as stem cell transplant if possible?
Bortezumib (protease inhibitor)/Thalidomide
+
Alkylating agent +/- dexamethasone
What are some alternative medications used for relapse of myeloma?
2nd stem cell transplant
Daratumumab
Ixazomib
Name three supportive treatments of multiple myeloma.
Bone pain - radiotherapy and bisphosphonates
Infection - flu vac
Anaemia - transfusion + EPO
Vertebral fractures - kyphoplasty
What is the main side effect of bortezomib?
Peripheral neuropathy
What is lymphoma?
A group of lymphoproliferative malignancies (neoplastic transformation of B or T cells)
What are Reed-Sternberg cells and in what condition are they found?
Neoplastic B cells with mirror image nuclei
Hodgkins’ lymphoma
What are the main presentations of lymphomas?
Painless cervical/mediastinal lymphadenopathy
B symptoms - weight loss, night sweats, fatigue, anorexia, fever
Hepatosplenomegaly
What are the main diagnostic techniques in lymphoma?
Lymph node ultrasound and fine needle aspiration/biopsy Bone marrow biopsy FBC and blood films U&Es, LFTs, LDH, uric acid CT scan
What is the chemotherapy regimen used in Hodgkin’s lymphoma?
ABVD 2-8 cycles depending on stage
Doxorubicin, bleomycin, vinblastine, dacarbazine
What is the chemotherapy regimen used for B-cell lymphomas?
R-CHOP
Rituximab (not T cell), cyclophosphamide, doxorubicin, vincristine, prednisolone
What are two risk factors for Burkitt’s lymphoma and what is the main symptom?
EBV and AIDS
Jaw tumour
What staging system is used for lymphoma?
Ann Arbor
Give three risk factors for general lymphoma.
Smoking
EBV
HIV
What factors suggest a poor prognosis in lymphoma?
Increasing age Constitutional symptoms Anaemia/leucopenia/leucocytosis Increased ESR or low albumin Male gender Lymphocyte-depleted subtype
How is neutropenia managed in lymphoma patients?
Antibiotic prophylaxis
rhG-CSF
What is the general treatment of lymphoma?
High dose chemotherapy and autologous stem cell transplant
What are the risks of high dose chemotherapy?
Squamous cell carcinomas and other cancers
Immunesuppression and neutropenic sepsis
What are three risk factors for ALL?
Genetics - Philadelphia chromosome
Trisomy 21
High dose radiation
What are the main symptoms of leukaemia?
Anaemia Frequent infection Bruising and petechiae Lymphadenopathy Hepatosplenomegaly Orchidomegaly Bone pain
How is ALL diagnosed?
BM biopsy
FBC shows BM suppression but this is a late feature
Blood film - blast cells
Increased LDH and uric acid
What percentage of serum/BM blasts are required for diagnosis of ALL?
> 20%
Which type of leukaemia has Auer rods on blood film?
AML
What is the treatment of ALL?
Stem cell transplant
Chemotherapy
Allopurinol
What is the purpose of allopurinol in treatment of leukaemia?
Prevents tumour lysis syndrome
What is Kymriah?
New ALL CAR-T cell therapy
What is the management of ALL with CNS involvement?
CNS irradiation
Intrathecal methorexate
How does CLL present?
Often asymptomatic; insidious onset.
How is CLL diagnosed?
Lymphocytosis
BM infiltration with lymphocytes
Blood film - smudge cells (small lymphocytes w/o blasts)
What are the three phases of CML?
Chronic phase
Accelerated phase
Blast phase
What is CLL?
Uncontrolled proliferation of one or more cell lines: erythroid, platelet, or myeloid
What is the extra treatment of CML?
Imatinib - tyrosine kinase inhibitor
What is immune thrombocytopenic purpura?
Autoimmune destruction of platelets in response to an unknown stimulus
How is lymphoma classified?
High grade and low grade
Define the thrombocytopenia in ITP?
Platelets <100x10^9
What investigations should be done in suspected ITP?
FBC and blood film BM exam if uncertain Any investigation for secondary ITP Screen for HIV and Hep C Test Ig levels if over 60
What triggers ITP in young children?
Viral infection or immunization
What are the symptoms of ITP?
Asymptomatic Petechiae/bruising Nosebleeds Menorrhagia/GI bleed Cranial bleed
How is ITP managed?
Majority - monitoring only
Prednisolone/IVIG
Platelet transfusion if emergency
When is splenectomy indicated in ITP?
Life threatening bleeding
Severe unremitting ITP
How does ITP present in adults, compared to children?
No trigger
Less insidious onset
What medication can be tried in unremitting ITP in adults?
Romiplostin - thrombopoietin receptor agonists
Increase platelet production
What are the differentials for ITP?
DIC Leukaemia Fanconi anaemia von Willebrand disease TTP Aplastic anaemia
What is Thrombotic Thrombocytopenic Purpura?
A rare thrombotic microangiopathy consisting of:
- microangiopathic haemolysis
- thrombocytopenia
- fever
- neurological abnormalities
- renal dysfunction
What is the main risk factor for TTP?
Pregnancy and postpartum
What is the cause of TTP?
Deficiency of von Willebrand factor cleaving protein: ADAMTS13
What is seen on examination in TTP?
Jaundice Splenomegaly Fever Hypertension Petechiae/purpura Signs of anaemia
How is TTP diagnosed?
Massively increased LDH
Reticulocytes
Schistocytes
ADAMTS13 levels and anti-ADAMTS13 antibodies
What is the main treatment of TTP?
Plasmaphresis
Define DIC.
A syndrome characterized by the systemic activation of blood coagulation, which generates intravascular fibrin, leading to thrombosis of small and medium sized vessels, and eventually organ dysfunction.
What is the main pathophysiology of DIC?
Initial thrombosis
Followed by a bleeding tendency
What are the risk factors for DIC?
Obstetric emergencies
Septicaemia
Malignant disease
Trauma
How does DIC present/?
Shock
Bleeding from >3 sites including venepuncture sites
Widespread ecchymoses
Fever and confusion
How is DIC diagnosis?
PT, APTT, TT very prolonged Decreased fibrinogen Increase FDPs including D-dimer Thrombocytopenia Fragmented RBC on film
What is myelodysplasia?
A form of bone marrow failure where a line of myeloid blasts are produced rapidly, do not mature, and usually die, causing a deficiency in that line of cells.
What can myelodysplasia progress to?
Acute myeloid leukaemia
What is the prevention and treatment of tumour lysis syndrome?
Prevention - allopurinol
Treatment - rasburicase
Apart from the electrolyte abnormalities, what is required to diagnose tumour lysis syndrome?
Increased serum creatinine, a cardiac arrhythmia, or a seizure
What are the symptoms of von Willebrand’s disease?
Epistaxis and menorrhagia
Behaves like a platelet disorder
How is von Willebrand disease diagnosed?
Prolonged bleeding time
Prolonged APTT
Diseases causing secondary haemostasis, such as Haemophilia, have symptoms such as…
Intramuscular and intra-articular bleeds
Which conditions are associated with thymomas?
Myasthenia gravis
Red cell aplasia
Dermatomyositis
SLE
Define end organ damage in myeloma.
Calcium normal
Hb normal
Creatinine normal
No bone lesions
What is the diagnostic criteria for MGUS?
Presence of monoclonal antibody in serum and:
- No end organ damage
- Plasma cells less than 10% in BM
- Serum paraprotein <30g/L
What is the diagnostic criteria for smouldering myeloma?
Presence of monoclonal antibody in serum/urine and:
- No end organ damage
- Plasma cells >10% in BM
- Serum paraprotein <30g/L
What is the treatment of a patient with major bleeding who is taking warfarin?
Stop warfarin
Vitamin K
Prothrombin complex concentrates (FFP less effective)
What is the treatment of polycythaemia?
Venesection aiming for haematocrit <45%
Low dose aspirin
Hydroxyurea
What are the causes of polycythaemia?
Relative reduction in plasma volume (idiopathic)
Increase in circulating EPO
What is the prognosis of polycythaemia?
Survival of 10 years or more
May transform to acute leukaemia or myelofibrosis
