Haematology Flashcards
What hormone stimulates the bone marrow to produce erythrocytes?
erythropoietin
What is the difference between adult and foetal haemoglobin?
Adult haemoglobin= 2a, 2b chains
Foetal haemoglobin = 2a, 2y chains
What is lymphoproliferative disease?
Neoplastic, clonal proliferation of lymphoid cells.
“a cancer of white blood cells “
typically affects lymph nodes
can be extranodal - bone marrow/liver/spleen/anywhere
What is a paraprotein?
Non-functional immunoglobulin produced by plasma cells in multiple myeloma.
What is myeloma?
A cancer of differentiated B-lymphocytes (plasma cells) in the bone marrow.
What is multiple myeloma?
A cancer of the plasma cells affecting multiple areas of the body
What are the features of multiple myeloma?
Calcium excess
Renal failure
Anaemia
Bone lytic lesions
Bleeding
Infection
What are the risk factors for multiple myeloma?
- Monoclonal gammopathy of undetermined significance (MGUS = plasma cells develop unusually in bone marrow)
- Family history of MM
- Radiation exposure
What is the pathophysiology of multiple myeloma?
- increase in bone resorption
- decrease in bone formation
- uncoupling of resorption and formation leading to rapid bone loss
What are the different types of multiple myeloma?
- monoclonal gammopathy of undetermined significance (MGUS)
- smouldering myeloma
- symptomatic myeloma
What is MGUS?
Monoclonal gammopathy of undetermined significance = excess of a single antibody or antibody components without other features of myeloma or cancer. May progress to myeloma.
What is smouldering myeloma?
Progression of MGUS with higher levels of antibody/antibody components. Premalignant and high risk of developing into myeloma.
What are the risk factors for myeloma?
Family history of myeloma
Radiation exposure
Older age
Male
Black african ethnicity
obesity
What are the key presentations of MM?
Old - 70+
C - hyperCalcaemia (increased bone resorption) -> bones, stones, abdo moans, and psychological groans
R - Renal failure (hypercalcaemia -> calcium oxalate renal stones), creatinine>173mmol/L
A - Anaemia (BM failure)
B - Bone lesions (BM failure = painful, new onset back pain in the elderly)
What are the investigations for MM?
FBC + blood film -> normocytic normochromic + increased ESR, Rouleaux formation (aggregation of RBCs together, abnormal)
GS: bone marrow biopsy >/=10% plasma cells
Urine dipstick indicating Bence Jones proteins (light chains)
What is the treatment for MM?
*Only treat symptomatic MM
- bisphosphonates (alendronate, clodronate, zoledronic acid or pamidronate)
- chemotherapy (bortezomid, thalidomide, dexamethasone)
- dialysis
- consider BM stem cell transplant
What is sickle cell anaemia?
An autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in production of sickle cell haemoglobin (HbS).
What is the pathophysiology of sickle cell anaemia?
On the 6th codon of B-globin glutamic->valine causing irreversible RBC sickling.
Sickled RBCs are more fragile and have a decreased SA so are less efficient and die quicker with increased risk of sequestration.
What are the symptoms of SCA?
general anaemia + jaundice
+ complications:
- acute sickle crisis = vessel occluded, extremely painful and medical emergency (can be in pulmonary vessel = acute chest crisis –> resp. distress)
- splenic sequestration - can cause autosplenectomy (basically non-functional spleen)
- osteomyelitis (caused by salmonella)
What are the investigations for SCA?
- Newborns are screened in heel prick test
- FBC + blood film = normocytic normochromic w/ increased reticulocytes, sickled RBCs+ Howell Joly bodies (nuclear remnants found in the RBCs of patients with reduced or absent splenic function)
- Hb electrophoresis
What is the management of SCA?
prevent complications whenever possible (stay warm + hydrated, vaccinations, monitoring, regular blood transfusion, hydroxycarbamide - ↑HbF
- only curative therapy = bone marrow transplant (signifciant risks)
- iron chelation (treats iron overload)
Acute attacks: IV fluid + analgesia + O2
What is splenic sequestration in SCA?
Occurs when blood cells get stuck in the spleen and block the passage of platelets out of the spleen. This can result in 90% of circulating platelets becoming sequestered in the spleen and is a medical emergency.
What is thalassaemia?
Overarching term for several conditions which result in lack of haemoglobin production.
What is alpha thalassaemia?
Abnormality of a-globin gene
- less common than b thalassaemia
- 4 genes on chromosome 16
- deletions, associated with HbH (abnormal isoform where b-chain tetramers form)
What is beta thalassaemia?
Abnormality of b-globin gene
- 2 genes on chromosome 11
- mutations, normal Hb isoforms
- just deletion of b-chains
What are the clinical classifications of beta thalassaemia?
- thalassaemia major - transfusion dependent
- thalassaemia intermedia - less severe and can survive without regular blood transfusions
- thalassaemia carrier - asymptomatic
What are the risk factors for thalassaemia?
- FH
- More common in people of African, Mediterranean and Southeast Asian descent
What are the key clinical manifestations of b-thalassaemia?
variable depending on number of mutations:
- general anaemia
- chipmunk facies (enlarged forehead and cheekbones)
- hepatosplenmegaly
- failure to thrive
What are the investigations for thalassaemia?
FBC, peripheral smear, reticulocyte test
genetic testing to confirm diagnosis
XR skull, long bones, abdo US
What is the treatment for thalassaemia?
Bone marrow stem cell transplant only curative option
Regular blood transfusions needed for survival (complications: iron overload, iron chelation)
What is Hodgkin’s lymphoma?
Cancer of the lymph nodes where white blood cells grow out of control, causing swollen lymph nodes and growths throughout the body.
What are the types of Hodgkin’s lymphoma?
- Nodular sclerosis HL
- Mixed cellularity HL
- Lymphocyte-depleted HL
- Lymphocyte-rich HL
What are the risk factors for HL?
- History of Epstein-barr virus infection (aka glandular fever)
- FH of hodgkin’s lymphoma
- Young adults from higher socio-economic class
- HLA types
- More commonly diagnosed in older people and teenagers
- HIV infection
What are the key presentations of Hodgkin’s lymphoma?
B symptoms (=fever, night sweats, unintentional weight loss)
Painless rubbery lymphadenopathy (painful after drinking alcohol)
What are the investigations for HL?
- Lymph node biopsy (Reed Sternberg +ve = large abnormal lymphocytes)
- CT/MRI chest, abdo, pelvis for staging
What is the treatment for HL?
ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine)
Radiotherapy
What are the 4 stages in Ann Arbour lymphoma staging?
1 - Single lymph node
2 - 2 ≤ lymph nodes on same side of diaphragm
3 - Lymph nodes on both sides of diaphragm
4 - Extra-nodal organ spread
What is the distinguishing factor between Hodgkin’s and Non-Hodgkin’s lymphoma?
The presence of Reed-Sternberg cells in Hodgkin’s lymphoma
What is Non-Hodgkin’s lymphoma?
A group of lymphomas e.g. Burkitt Lymphoma (associated with EBV, malaria and HIV), MALT lymphoma (Mucosa-associated lymphoid tissue, associated with H.pylori infection), Diffuse large B cell lymphoma (65+, rapid-growing)
What are the risk factors for NHL?
HIV
EBV
H.pylori
Hepatitis B or C
Exposure to pesticides
Family History
What is the management for NHL?
watchful waiting
chemotherapy (R-CHOP)
radiotherapy
monoclonal antibodies
stem cell transplant
What is R-CHOP chemotherapy?
An immunochemotherapy regimen consisting of Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Vincristine (Oncovin) and Prednisone used to treat both indolent and aggressive forms of non-Hodgkin lymphoma.
What is indolent lymphoma?
Form of NHL which is slow growing and only presents with symptoms at an advanced stage.
What is ABVD chemotherapy?
ABVD is the name of a chemotherapy combination that includes doxorubicin, bleomycin, vinblastine and dacarbazine. It is a treatment for Hodgkin lymphoma
What is leukaemia?
cancer of a particular line of the stem cells in the bone marrow resulting in unregulated production of certain types of blood cells.
What are the 4 main types of leukaemia?
Acute myeloid leukaemia
Chronic myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic lymphocytic leukaemia
What are the progressive ages of leukaemias?
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
What is acute myeloid leukaemia?
A heterogeneous clonal malignancy characterised by immature myeloid cell proliferation and bone marrow failure.
What are the risk factor for AML?
- Myelodysplastic Syndromes
- Most patients with chronic myeloid leukaemia eventually develop a blast phase indistinguishable from AML
- Radiation
- Some congenital disorders (Down’s, Bloom’s syndrome, congenital neutropenia)
What are the key presentations of AML?
- Anaemia (SOB, light-headedness, fatigue, worsening angina)
- Neutropenia (frequent infections)
- bleeding
- splenomegaly
- bone pain
What are the investigations for AML?
FBC + blood film (key feature Auer rods in abnormal leukocytes)
Bone marrow aspirate
Trephine biopsy
CXR
What are some differential diagnoses for AML?
- B12/folate or mixed haematinic deficiency
- Infection (e.g. retroviral disease, herpesvirus)
- Medications
- Autoimmune
- Liver disease (e.g. cirrhosis)
What are the 2 phases of chemotherapy treatment for AML?
induction: cytarabine, daunorubicin and gemtuzumab ozogamin
post-remission consolidation: chemotherapy with stem cell replacement therapy
What is chronic myeloid leukaemia?
A malignant clonal disorder of the haematopoietic stem cell resulting in marked myeloid hyperplasia of the bone marrow.
What is the cause of CML?
Caused by characteristic cytogenetic change which is the translocation of genes between chromosome 9 and 22 called the Philadelphia chromosome (t(9:22))
This causes dysregulation of haematopoiesis arises due to a BCR-ABL fusion gene that causes tyrosine kinase to be irreversibly switched on resulting in an abnormal expansion of myeloid cells in the bone marrow and peripheral blood.
What are the 3 phases of CML?
Chronic phase = often asymptomatic and is often diagnosed incidentally with a raised white cell count.
Accelerated Phase = occurs where the abnormal blast cells take up 10-20% of the cells in the bone marrow and blood. Patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
Blast phase = even higher proportion of blast cells in the blood (>30%) causing severe symptoms and pancytopenia, is often fatal.
What are the key presentations of CML?
Splenomegaly
SOB on exertion
Epistaxis due to thrombocytopenia or abnormal platelet function
Arthralgia
Sternal tenderness
What are the investigations for CML?
FBC (pancytopenia but granulocytosis)
BM Biopsy (increased granulocytes)
Genetic testing (philadelphia chromosome)
What is the management for CML?
Chemotherapy + Imantinib (Tyrosine kinase inhibitor)
Consider allopurinol (lowers uric acid levels)
What is ALL?
Malignant change of one of the lymphocyte precursor cells - causes acute proliferation of a single type of lymphocyte (usually B lymphocytes) which leads to replacement of other cell types being created in the bone marrow ⇒ pancytopenia.