Haematology Flashcards
Plasma cell dyscrasias (disorders)
MGUS - Monoclonal gammopathy of undetermined significance Myeloma Solitary plasmacytoma Multiple solitary plasmacytoma Extramedullary plasmacytoma Waldenstrom's macroglobulinemia
Multiple myeloma
Bone marrow cancer
Neoplastic proliferation of bone marrow plasma cells
Characterised by - a monoclonal protein in serum or urine, lytic bone lesions (tend to be in skull, spine, pelvis), CRAB (elevated Ca, Renal failure, Anaemia, Bone lesions)
Multiple myeloma - Presentation
Tiredness, malaise
Bone/back pain (sometimes with fractures)
Infections
Purpura
Proteinuria
Raynaud’s
Lab - anaemia/abnormal FBC, renal failure, hypercalcaemia, raised globulins, raised ESR, serum/urine paraprotein
Blood film - Rouleaux
Peripheral blood smear
The commonest type of myeloma
IgG
Myeloma - Chromosomal abnormalities
t (11;14) - most common
13q - associated with treatment resistance
Myeloma - Investigations
CT/MRI/PET
Rouleaux blood film
Bone marrow aspiration/biopsy
Cause of death in myeloma
Infection
Amyloidosis
Proteinuria
Lower limb swelling
Amyloidosis
When an abnormal protein called amyloid builds up in your tissues and organs.
When it does, it affects their shape and how they work.
Myeloma - Treatment (CTD)
Supportive - Antibiotics
Radiotherapy - spot welding
Chemo (CTD) - Cyclophosphamide, Thalidomide, Dexamethasone
Myeloma vs lymphoma
Myeloma - plasma cells
Lymphoma - lymphocytes
Lymphoma - Common features
Enlarged lymph gland
Loss of appetite/weight loss
Night sweats
Lymphoma - Signs
Lymph gland enlargement
Lymphoma - Investigations
Biopsy bone marrow
Bloods - Hb, WBC, Platelets
Lump in the neck - Differential diagnosis
Infective lymph node (bacterial/viral) - TB (tender)
Tumour (solid)
Lymphoma - Treatment
Chemo - R-CHOP (Non-Hodgkin’s - specific)
Rituximab (Monoclonal Ab treatment)
Chlorambucil
Radiotherapy (local)
Immune thrombocytopenic purpura (ITP)
Bleeding disorder in which the immune system destroys platelets
Too few platelets in the blood
Lymphoma
Malignant growth of WBCs - lymphocytes
Commonly in lymph nodes
Also in blood, bone marrow, liver, spleen
Lymphoma vs leukaemia
Lymph glands - Lymphoma
Bloods - Leukaemia
Both involve lymphocytes
Lymphoma - Causes
Immunodeficiency - HIV
Infection - EBV, H-pylori
Autoimmune
Lymphoma - Investigations
Blood film Bone marrow aspirate Lymph node biopsy Immunophenotyping (CD20 expressed by B lymphocytes) - Rituximab (MAb) targets CD20 Cytogenetics - FISH PCR
Lymphoma - Staging
Blood tests - FBCs, LFTs Viral serology CT - chest, abdo CXR PET Bone marrow biopsy
Lymphoma - subtypes
Hodgkin
Non-hodkin
Lymphoma - Hodgkin’s
Histological feature - Reed-Sternberg cells
Painless
Hodgkin’s - Staging
Stage 1-4
Hodgkin’s - Treatment
Radio
Chemo - ABVD (Anthracyclines and bleomycin are examples of one of these)
Bone marrow transplant
Non-Hodgkin’s - Grades
Low grade (Follicular) - slow-growing, incurable
Treatment of low-grade - MAb
High grade (diffuse large B cell lymphoma) - Nodal presentation, curable
Treatment of high grade - MAb
MAb
Rituximab
Targeted treatment
Anti CD-20
Targets CD20 expressed on cell surface of B-cells
Chimeric protein (mix of mouse/human proteins)
Minimal SEs (as opposed to chemo)
Acute leukaemia - Investigation
FBC - Hb, Plts, WBCs
Blood film
U&Es - B12, folate, iron levels
LFTs
Bone marrow aspirate and biopsy - identify blasts (large cells with very little cytoplasm
Immunophenotyping (confirms cells type - myeloid or lymphoid)
Acute leukaemia - Symptoms
Symptomatic anaemia - Tiredness, fatigue, lightheadedness, palpitations, SOB (on exertion)
Symptomatic thrombocytopenia - Bruising/bleeding
Symptomatic low WBC - Infections
Symptomatic high WBC - Due to leukostasis or tumour lysis
Extramedullary disease - disease infiltration in skin, gums (hypertrophied)
Coagulopathy - DIC due to sepsis
Acute leukaemia - Differential diagnosis
CML
AML
Severe sepsis
Cytopenias (Differentials for eachother)
B12/Folate/iron deficiencies DIC Infections - HIV (viral), TB (bacterial) Lymphoma Leukemia Myeloma
Bone marrow biopsy and aspirates
Identify blasts - large cells with very little cytoplasm
Leukaemia - Types
AML ALL CML CMML CLL
AML - Blast
Myeloblast
ALL - Blast
Lymphoblast
CML - Blast
Phils
CMML - Blast
Monocytes
CLL - Blast
B lymphocyte
Blast maturity and leukaemia prognosis
Immature - Acute
Mature - Chronic
AML - Treatment
Chemo - Anthracycline
Supportive
Hickman line aids delivery of medication and taking of bloods
Allogeneic stem cell transplant
Chemo - SEs
Loss of appetite Allergy Fatigue Cytopenias Hair loss
Anaemia
Reduced red cell mass (reduced Hb conc)
Hb is THE identifiable component
3rd trimester of pregnancy
Increased RCM
Reduced Hb
Anaemia - Consequences
Reduced oxygen transport
Tissue hypoxia
Physiological compensatory changes - increase tissue perfusion (tachycardia), increase oxygen transfer to tissues, increase RBC production
Anaemia - Pathological consequences
Myocardial fatty change Aggravate angina/claudication Fatty change in liver Skin and nail atrophic changes CNS cell death (cortex and basal ganglia)
RBC balance
Production - bone marrow
Removal - Spleen, liver, bone marrow, blood loss
Test - reticulocytes level
Anaemia - Types
Microcytic - small - iron deficiency, thalassaemia (Hb inherited condition)
Normocytic - normal - acute blood loss
Macrocytic - large - B12/folate deficiency, alcohol/liver
MCV
Mean cell volume (size)
Iron deficiency anaemia
Test - Ferritin (storage marker for iron)
Tends to be caused by cancer
B12 deficiency - Investigation
Intrinsic factor Ab
Schilling test
Coeliac Ab
Combined haematinic deficiency
Malabsorption
Anaemia - Tests
FBC Blood film Reticulocyte count U/Es LFTs TSH B12 Folate Ferritin
Iron deficiency
Microcytic hyperchromic anaemia
B12 deficiency
Macrocytic anaemia with polysegmented neutrophils
Hemoglobinopathies
Disorders of quality - Sickle cell disease (abnormal molecule/variant Hb)
Disorders of quantity - Thalassaemia (reduced prod)
Hemoglobin S
Variant due to point mutation
Sickle cell disease
Carriers of HbS are symptom free
Carriage offers protection against facliparum malaria
Multi-system disorder
Excruciating bone pain
Strokes tend to occur in children
Blockage of small vessels is root of problem
Sickle cell disease - Presentation
Acute - painful crisis, sickle chest syndrome, stroke
Chronic - Renal impairment, pulmonary hptn, joint damage
Sickle cell disease - Treatment
Transfusion
Hydroxycarbamide
Stem cell transplant
Thalassaemia
Globin chain disorders, diminished synthesis of one or more globin chains, reduction in Hb as a result Genetic lesions (deletions and mutations) - Alpha and beta thal
Beta thalassemia major
Infants
Symptoms - Pale
Treatment - Transfusion, iron chelation
Monitoring - Ferritin, DEXA scan (bone health)
Membranopathies
Deficiency of red cell membrane proteins caused by a variety of genetic lesions
Elliptocytosis (horizontal), spherocytosis (vertical)
Children
Jaundice
Gall stones
Treatment - folic acid, splenectomy
Parvovirus
Decreased RBC prod
Poor prognosis in sickle cell disease
Lead to haemolytic anaemia
Enzymopathies
G6PD deficiency
Pyruvate kinase deficiency
Lead to haemolytic anaemia
Platelet abnormalities
Number
Function
Platelet physiology
Produced in bone marrow
Megakaryocyte fragments (anuclear)
Regulated by thrombopoietin (produced in liver) - stimulates prod
Adhesion and aggregation to form platelet plug
Removed by spleen
Platelets - Surface proteins
ABO
HPA
Glycoprotein 1a
Platelets activated by adhesion to VWF via GP1b and collagen via GP1a
Platelet activation leads to release of alpha granules containing fibrinogen
Platelet - Mechanism of function
Adhesion
Release
Aggregation
Procoagulant healing
Platelets - Tests
FBC - Levels
Blood film - Appearance
PFA (Platelet function analysis)
Bleeding - Causes
Injury Vascular disorders Low platelets Abnormal platelet function Defective coagulation
Platelet dysfunction - Clinical features
Mucosal bleeding
Easy bruising
Haematomas
Purpura
Low platelets - Causes
Prod failure - Marrow failure/suppression, drugs
Increased removal - Splenomegaly
Impaired platelet function - Causes
Glanzmann disorder - Deficiency of GP1a/b
VW disease
Thrombocytopenia
Decreased prod by bone marrow
Low B12/folate
Reduce TPO due to liver disease
Infection
Increased destruction (ITP-Immune thrombocytopenia)
Consumption of platelets (DIC - Disseminated intravascular coag, TTP - Thrombotic thrombocytopenic purpura)
Medications which affect platelet function - Clopidogrel, Aspirin
Immune thrombocytopenia
IgG Ab bind to platelets
Treatment - Steroids (immunosuppression), IV Ig, platelets
TTP
Spontaneous platelet aggregation in microvasculature due to a reduction in ADAMSTS13 protease enzyme
Consumption of platelets
RBC fragments - Schistocytes
Schistocytes
RBC fragments
Haematology - most likely exam topics
CML Rituximab Hodgkin's lymphoma Myeloma Anaemia
CML
FBC - High WCC Blood film - Basophilia Splenomegaly Slow onset 40-60 yo Key diagnostic feature - Philadelphia chromosome (t9:22) - Abnormal tyrosine kinase leads to abnormal proliferation of WBCs Treatment (targeted) - Imatinib (TKI)
Rituximab
MAb
Targets CD20 expressed on surface of B cells (targets and reduces B cells)
Chimeric mouse-human protein (only SEs are related to the mouse proteins - allergy)
Hodgkin’s lymphoma - age group
Young adults
Elderly
Myeloma
Skeletal survey - lytic lesions
Production of osteoclast-activating factors
Sclerotic vs lytic lesions
Sclerotic - Regrowth
Lytic - Dissolved with no regrowth
Normocytic anaemia
Combined haematinic disease
Sickle cell anaemia
Chronic haemolytic anaemia - with jaundice
Raised reticulocyte count
Haemoglobinopathy
Reticulocyte count
Production failure - Low levels
Increased removal - Raised
Neutrophilia
Physiological response to bacterial infections
Aspirin - Antiplatelet effect
Irreversible inhibitor of cyclooxygenase enzyme