Haematology Flashcards
Define anaemia
Low haemoglobin (Hb) concentration due to either a low red cell mass (reduced production or increased loss of RBCs) or increased plasma volume
What are the signs/symptoms of anaemia?
Systemic:
- fatigue
- pallor
- dyspnoea
- anorexia
Head:
- faintness
- headache
- tinnitus
- cognitive dysfunction
Heart:
- palpitations
- angina
- tachycardia
- heart murmurs
Neurological symptoms in B12 deficiency:
- weakness
- neuropathy
- psychiatric
Koilonychia (curved nails)
Angular cheilitis (ulcers in corner of mouth)
List the 4 types of anaemia and their causes
Microcytic anaemia (low mean cell volume - small RBCs):
- iron-deficiency anaemia (most common)
- thalassaemia (decreased Hb production)
Normocytic anaemia (normal MCV and RBC size):
- acute blood loss
- renal disease
- chronic disease
- bone marrow failure
Macrocytic anaemia (high MCV - big RBCs):
- folate deficiency
- B12 deficiency
- alcohol excess/liver disease
Haemolytic anaemias (can be normocytic or macrocytic):
- sickle cell (normocytic)
- bone marrow disorders
- autoimmune
- infection (e.g. malaria)
What are the causes of iron deficient anaemia?
Blood loss (GI, menstrual)
Increased demand (pregnancy)
Impaired absorption (e.g. coeliac disease, IBD, gastrectomy)
Dietary deficiency (rare in adults)
What are the investigations needed for iron-deficiency anaemia?
Blood film: shows microcytic, hypochromic (pale) RBCs
Low MCV
Low ferritin = diagnostic
Low transferrin
High total iron binding capacity
What are the treatments for iron deficiency anaemia?
Investigate/treat source of bleeding or underlying cause
Replace iron - oral (ferrous sulphate) is preferred, but also IV option, continue 3 months after Hb is normal to replenish stores
What are the causes of folate deficiency?
Poor nutrition (found in green veg e.g. poverty, elderly)
Malabsorption (coeliac, Crohn’s)
Increased demand (pregnancy, malignancy)
What are the causes of B12 deficiency?
Dietary (found in meat/dairy e.g. vegans)
Malabsorption (due to reduced intrinsic factor production = pernicious anaemia, ileal resection, Chron’s, or bacterial overgrowth)
What are the investigations needed of folate or B12 deficiency anaemia?
Blood film: macrocytic RBCs, hypersegmented neutrophils (megaloblasts differentiate from other macrocytic causes)
Raised MCV
Serum folate/B12
LFTs
Intrinsic factor antibodies for B12 deficiency
What are the treatments for folate deficiency anaemia?
Asses underlying cause
Oral supplements of folic acid (5mg/day)
*if combined with B12 replacement, start B12 replacement first
What are the treatments for B12 deficiency anaemia?
B12 replacement:
- given frequently, then less as maintenance
- intramuscular if due to malabsorption
- oral if due to dietary causes
*if combined with folate replacement, start B12 replacement first
What are the complications of anaemia?
Cardiopulmonary complications (heart failure)
Cognitive/behavioural impairment in children
Increased morbidity for mother and child in pregnancy
Complications of B12 deficiency: neurological symptoms (paraesthesia, ataxia, neuropathy, cognitive impairment), neural tube defects in pregnancy
Complications of folate deficiency: CVD, prematurity and neural tube defects in pregnancy
Define acute myeloid leukaemia
Cancer of the blood cells characterised by rapid division and arrested maturation of the most immature cells from the myeloid progenitor cell line, which do not resemble the appearance and function of the normal cell (cancer develops more rapidly)
Commonest leukaemia in adults, associated with myelodysplastic syndromes, radiation, and Down’s syndrome
Define chronic myeloid leukaemia
Cancer of the blood cells characterised by rapid division and arrested maturation of slightly developed but still immature cells from the myeloid progenitor cell line, which somewhat resemble the appearance and function of the normal cell (cancer develops more slowly)
More common in men, occurs most often between 40-60 y/o
Define acute lymphoid leukaemia
Cancer of the blood cells characterised by rapid division and arrested maturation of the most immature cells from the lymphoid progenitor cell line (most commonly B-cell), which do not resemble the appearance and function of the normal cell (cancer develops more rapidly)
It is the most common childhood cancer, and is associated with Down’s syndrome and ionising radiation during pregnancy
Define chronic lymphoid leukaemia
Cancer of the blood cells characterised by rapid division and arrested maturation of slightly developed but still immature cells from the lymphoid progenitor cell line, which somewhat resemble the appearance and function of the normal cell (cancer develops more slowly)
It is the commonest leukaemia, mostly affects older people, with strong familial risks
Can transform into lymphoma
What are the signs/symptoms of acute myeloid leukaemia?
Bone marrow failure: anaemia, infection, bleeding
Infiltration: hepatomegaly, splenomegaly, swollen gums
What investigations are needed for acute myeloid leukaemia?
Blood film: blast cells seen (AUER RODS)
FBC: usually low WBC, Hb, RBC, platelets
Cytogenic analysis - FISH (type of mutation)
Molecular testing
Bone marrow biopsy
What is the treatment of acute myeloid leukaemia?
Chemotherapy
Supportive measures (RBC/platelet transfusion, treatment of infection)
Allogenic haemopoietic stem cell transplant
What are the signs/symptoms of chronic myeloid leukaemia?
Mostly chronic and insidious:
Weight loss
Tiredness
Fever
Sweats
Bleeding
Abdominal discomfort
Splenomegaly (often massive)
Hepatomegaly
Anaemia
What are the investigations needed for chronic myeloid leukaemia?
FBC: very high WBC (whole spectrum), low Hb, variable platelets
Cytogenic analysis - FISH (Ph chromosome)
Peripheral blood film and bone marrow biopsy (lost of blast cells seen)
Genetic test for BCR ABL gene
What are the treatments for chronic myeloid leukaemia?
Chemotherapy: tyrosine kinase inhibitors (imatinib)
Allogenic haemopoietic stem cell transplant (if TKI resistant)
What are the signs/symptoms of acute lymphoid leukaemia?
Marrow failure: anaemia, infection, bleeding
Infiltration: hepatomegaly, splenomegaly, lymphadenopathy, swollen testicles, CNS involvement (cranial nerve palsies, meningism)
What investigations are needed for acute lymphoid leukaemia?
Blood film and bone marrow biopsy: >20% lymphoblast cells seen, positive for periodic acid Schiff
FBC: usually low WBC, Hb, and platelets
CXR/CT: look for mediastinal and abdominal lymphadenopathy
Lumbar puncture: look for CNS involvement
Cytogenetic analysis (poor prognosis with Ph gene)
What is the treatment for acute lymphoblastic leukaemia?
Supportive treatments: replacement blood therapy, antibiotics
Chemotherapy
CNS prophylaxis: cranial radiation and intrathecal chemotherapy (methotrexate)
Allogenic stem cell transplant
What are the signs/symptoms of chronic lymphoid leukaemia?
Variable, with insidious onset, often asymptomatic
Susceptible to infection
Fatigue (from anaemia)
Symmetrically enlarged lymph nodes (lymphadenopathy)
Abdominal discomfort (from splenomegaly)
Hepatomegaly
What investigations are needed for chronic lymphoid leukaemia?
FBC: high lymphocytes, low Hb and platelets
Blood film: lots of lymphocytes with SMUDGE CELLS (old, damaged cells)
Bone marrow aspirate: lots of lymphocytes, and confirmation of anaemia
Lymph node biopsy: check for transformation to high-grade lymphoma
Cytogenetics: not usually performed but can show common abnormalities
What are the treatments of chronic lymphoid leukaemia?
Only patient with active or symptomatic disease require therapy
Chemotherapy: monoclonal antibodies + protein kinase inhibitor
Steroids: treat autoimmune complications
Allogenic stem cell transplant
Define multiple myeloma
Malignant proliferation of plasma cells, leading to progressive bone marrow failure, the production of paraprotein (commonly IgG), destructive bone disease (stimulated osteoclasts, inhibited osteoblasts), and kidney failure
Describe the epidemiology of multiple myeloma
Median age at diagnosis = 70
Survival range = a few moths - over 20 years
More common in Afro-Caribbeans
More common in men
Define MGUS
Monoclonal gammopathy of undetermined significance
Asymptomatic, pre-malignant stage, no related organ or tissue impairment
Progresses to multiple myeloma
What are the signs/symptoms of multiple myeloma?
Bone pain (particularly backache)
Pathological fractures
Spinal cord/nerve root compression
Fatigue (due to anaemia)
Dehydration
Recurrent infection
Thirst, constipation, nausea, confusion (due to hypercalcaemia)
Bleeding/bruising
CRAB: hypercalcaemia, renal failure, anaemia, bone pain
What investigations are needed for multiple myeloma?
FBC: anaemia, high ESR
U&E and creatinine (raised)
High calcium
Bone marrow biopsy (DIAGNOSTIC, shows abnormal plasma cells)
Electrophoresis (plasma - shows paraprotein, urine - shows Bence Jones’ protein)
X-rays: pepper-pot skull, vertebral collapse, osteoporosis
Whole body MRI
What is the treatment of multiple myeloma?
Chemotherapy
Autologous stem cell transplantation
Supportive treatments:
- bisphosphonates (e.g. zoledronic acid) and calcium to slow bone loss
- blood transfusions
- analgesia/antibiotics as needed
What are the complications of multiple myeloma?
Hypercalcaemia
Spinal cord compression
Hyperviscosity
AKI
Pathological fractures
Define non-Hodgkin’s lymphoma
A group of lymphoproliferative malignancies characterised by lymphomas without Reed-Sternberg cells, classified by histological type and divided into two prognostic groups:
- low grade: good prognosis, but not curable (only treatable)
- high grade: shorter history, more aggressive but can often be cured with intensive chemotherapy regimens
Describe the epidemiology of non-Hodgkin’s lymphoma
More common than Hodgkin’s lymphomas
Median age at presentation is 50 years
Most common types are diffuse large B-cell lymphoma (high grade) and follicular lymphomas (low grade)
What are the risk factors of non-Hodgkin’s lymphoma?
Immunodeficiency - congenital or acquired
H. pylori infection
EBV (in immunocompromised e.g. HIV)
Autoimmune disorders
What are the signs/symptoms of non-Hodgkin’s lymphoma?
Low-grade: painless, slow growing lymphadenopathy, hepatosplenomegaly, potential bone marrow failure (anaemia, infection, bleeding), systemic symptoms/extranodal involvement in advanced/end-stage
High grade: rapidly growing, bulky lymphadenopathy, common systemic symptoms/extranodal involvement (GI tract, skin, thyroid, CNS), hepatosplenomegaly, bone marrow failure (anaemia, infection, bleeding)
What investigations are needed for non-Hodgkin’s lymphoma?
FBC: anaemia, thrombocytopenia, neutropenia
U&E: look for renal function and hypercalcaemia
LFTs
Bone marrow aspirate and biopsy
Lymph node excision and biopsy
Cytology
CT: for staging - check for enlarged lymph nodes and hepatosplenomegaly
MRI of brain and spinal cord: if CNS lymphoma suspected
What is the treatment for non-Hodgkin’s lymphoma?
Low grade: not needed if symptomless, radiotherapy (palliative but may curative), chemotherapy
High grade: chemotherapy (often multi-agent and high-dose), radiotherapy allogenic stem cell transplant for some types
Define Hodgkin’s lymphoma
Malignant tumour of the lymphatic system originating from B lymphocytes, characterised by the presence of multinucleated giant cells (Reed-Sternberg cells)
Describe the epidemiology of Hodgkin’s lymphoma
Incidence peaks in young adults and elderly
More common in males
What are the risk factors for Hodgkin’s lymphoma?
EBV infection
Mononucleosis
HIV
Immunosuppression
Smoking
Affected siblings
What are the sings/symptoms of Hodgkin’s lymphoma?
Enlarged lymph nodes (most common in neck)
Night sweats, fever, weight loss
Alcohol-induced lymph node pain
Hepatosplenomegaly
Anaemia
Mediastinal mass causing breathlessness
What investigations are needed for Hodgkin’s lymphoma?
Lymph node excision and biopsy
FBC: anaemia, lymphopenia, exclude leukaemia and mononucleosis
ESR
LFT
CT and bone marrow biopsy: for staging
What is the treatment for Hodgkin’s lymphoma?
Low stages: radiotherapy and short-course chemotherapy
High stages: long-course chemotherapy
Relapse: high-dose chemotherapy + autologous stem cell transplant
Define polycythaemia vera
A myeloproliferative disorder where there is an overproduction of red blood cells, white blood cells, and platelets, leading to hyperviscosity and thrombosis, more commonly affecting older patients
What are the signs/symptoms of polycythaemia vera?
Non-specific fatigue
Splenomegaly
Thrombotic events (stroke, MI, DVT, PE)
Pruritis
Bleeding/bruising
Hypertension
What investigations are needed for polycythaemia vera?
FBC: high Hb, Hct, red cell mass, WBC, platelets
EPO: subnormal
Genetic: presence of JAK2 mutation
Ferritin: low
Bone marrow: hypercellular
What is the treatment for polycythaemia vera?
Control cardiovascular risk factors
Phlebotomy
Low-dose aspirin
Chemotherapy (if history of thrombosis and >60)
Define sickle cell anaemia
A group of inherited conditions characterised by abnormally haemoglobin (Hb) causing sickle-shaped red blood cells
Describe the epidemiology of sickle cell disease
Predominantly occurs in people of African and Afro-Caribbean origin
Prevalence follows the pattern of malaria, because the gene mutation is protective against malaria
Describe the pathophysiology of sickle cell anaemia
Abnormal beta-globin chain cause the production of HbS not HbA. HbS polymerises when deoxygenated, distorting the RBC into a sickle shape
The deformed RBCs form clusters which block small vessels, causes vessel damage, get trapped in liver and spleen, and cause anaemia, intense pain (sickle cell crisis), and infection
What are the signs/symptoms of sickle cell anaemia?
Manifest after aged 6 months:
Jaundice
Pallor
Tachycardia
Shock
Swelling of joints
Leucocytosis (in absence of infection)
May present with acute crisis or chronic complication
What are the investigations needed for sickle cell anaemia?
National newborn screening programme
Sickle solubility test
Electrophoresis
What are the treatments for sickle cell anaemia?
Prevention of complications:
- stay warm and hydrated
- vaccinations and antibiotics
Manage chronic symptoms (pain, lung disease, eye problems, leg ulcers, renal disease)
Regular blood transfusion
Hydroxycarbamide (increases production of foetal haemoglobin)
What are the complications of sickle cell anaemia?
Sickle cell crisis (intense pain triggered by cold, infection, dehydration, hypoxia)
Acute chest syndrome (lung damage -> hypoxia -> HbS polymerisation -> reduced blood flow -> lung damage)
Splenic infarction
Liver/kidney failure
Define thalassaemia
A group of recessively autosomal inherited conditions with absent or decreased synthesis of the alpha or beta chains which form haemoglobin, resulting in low Hb and anaemia
What are the sings/symptoms of thalassaemia?
Presentation depends on severity
Thalassaemia trait (only one missing gene): mild anaemia
More severe thalassaemia: severe anaemia, hepatosplenomegaly, jaundice, pallor, exercise intolerance, growth restriction, bone deformities (frontal bossing)
*severe alpha thalassaemia is usually lethal in utero (foetal Hb needs alpha chains)
What investigations are needed for thalassaemia?
FBC: microcytic anaemia, usually high WBC
High ferritin and iron saturation
Haemoglobin electrophoresis: (DIAGNOSTIC)
Genetic testing: specialist only, offered to couples at risk
Imaging: X-ray of skull, long bones, and flat bones to see deformities
What are the treatments for thalassaemia?
- Asymptomatic carriers: no treatment needed, promote fitness and healthy diet
- Blood transfusion to maintain Hb levels (mild cases: only occasionally e.g. times of growth, infection, pregnancy, severe cases: regularly
- Iron chelation to prevent overload (oral - deferasirox)
- Monitor heart, liver, and endocrine organs for iron overload
- Folate supplements
- Bone marrow transplant: curative
What are the complications of thalassaemia?
Iron overload -> organ failure
Endocrine dysfunction -> hypogonadism, short stature, diabetes mellitus
Severe anaemia -> cardiac failure
Osteoporosis
Blood borne disease and infections from repeated transfusions
Define haemophilia
A congenital coagulation disorder with X-linked recessive inheritance, classified as…
- haemophilia A (factor VIII deficiency, more common)
- haemophilia B (factor IX deficiency)
What are the signs/symptoms of haemophilia?
Presentation of haemophilia A depends on severity, haemophilia B tends to be less severe
- haematoma in muscles or joints (haemarthrosis) from delivery, surgery, trauma
- joint deformity (if severe and untreated)
- unexpected bleeding from venepuncture, tooth loss, immunisations
- excessive bruising
- haematuria
- GI bleeds (associated more with haemophilia B)
What investigations are needed for haemophilia?
Activated partial thromboplastin time (APPT) - raised
Factor VII/IX - decreased
Imaging: detect haemorrhages and joint deformity
What is the treatment for haemophilia?
Recombinant factor VIII/IX for major bleeds (can be used prophylactically but risk of inhibitors developing)
Avoid NSAIDs and IM injections
What are the complications of haemophilia?
Degenerative joint disease
Life-threatening haemorrhage
Risk of infection from blood products and transfusions
Define von Willebrand’s disease
A congenital coagulation disorder, caused by the deficiency or abnormality of von Willebrand’s factor (vWF - needed for platelet clotting)
What are the signs/symptoms of von Willebrand’s disease?
Bruising
Epistaxis (nose bleeds)
Menorrhagia
GI bleeding
Increased bleeding after tooth extraction/surgery
Severe types: haemarthrosis
What investigations are needed for von Willebrand’s disease?
Bloods: platelet count and morphology is normal
Activated partial thromboplastin time (APPT) - raised
Increased bleeding time
Plasma levels of vWF - low in type I and III
Factor VIII - low in type II
What are the treatments for von Willebrand’s disease?
Avoid NSAIDs and anti-platelet drugs
Tranexamic acid (antifibrinolytic) and desmopressin (increases release of vWF and factor VIII from endothelial stores) to treat minor bleeding, or prophylactically before surgery
vWF-containing factor VIII concentrates for major bleeding, and prophylactically before surgery
Describe HIV
Human immunodeficiency virus
Uses reverse transcriptase to replicate (retrovirus), replicates within CD4 cells, leading to immunodeficiency
Course: acute infection, clinical latency (asymptomatic, viral load drops, but CD4 count continues to decrease), opportunistic diseases (high viral load, very low CD4 count = AIDS)
What are the signs/symptoms of acute HIV?
Fever
Sore throat
Myalgia
Rash
Lymphadenopathy
Weight loss
What are some common opportunistic diseases in HIV?
PCP = pneumocystis pneumonia (fungal pneumonia, causing fevers, SOB, pleuritic chest pain, exertional drop in O2 sats) - most common
TB (AIDS defining)
Candidiasis (oral/vaginal)
Kaposi’s sarcoma
What investigations are needed for HIV?
HIV serology (antigens and antibody screen)
Rapid point-of-care testing: finger-prick or mouth swab immunoassay, needs serology for confirmation
Infection is monitored by CD4 cell count and HIV viral load
What is the treatment of HIV?
Antiretroviral therapy - reduces viral load to undetectable levels, leads to untransmittable infection (U=U) and good prognosis
How is HIV prevented?
Practicing safe sex
Post-exposure prophylaxis (PEP) - emergency short term ART after potential HIV exposure
Pre-exposure prophylaxis (PrEP) - ART used by those at high risk or acquiring HIV
ART to prevent vertical transmission
