Haematology Flashcards
What is anaemia?
Reduced red cell mass +/- haemoglobin concentration
Three main causes of microcytic anaemia:
MCV <80
- Iron deficiency
- Chronic disease
- Thalassemia
Three main causes of normocytic anaemia:
MCV 80-100
- Acute blood loss
- Anaemia of chronic disease
- Combined haematinic deficiency
Three main causes of macrocytic anaemia?
MCV >100
- B12 deficiency
- Folate deficency
- Alcohol excess/liver disease
Specific symptoms of Fe deficiency?
- Brittle nails and hair
- Tongue inflammation
- Angular stomatitis
What tests are carried out of Fe deficiency?
- Ferritin
- Reticulocyte count
- Iron studies
- FBC
What can cause Fe deficiency?
- Cancer
- Parasites (LCWW)
- Menorrhagia
- Pregnancy
Treatment for Fe deficiency?
Ferrous sulphate
Can cause black stools
General signs of anaemia?
Pale skin
Pale mucous membranes
Tachycardia
General symptoms of anaemia?
Fatigue Lethargy Dyspnoea Palpitations Headache
Causes of folate deficiency?
Poor folate diet
Malabsorption
Pregnancy
Antifolate drugs, methotraxate
Investigations of folate deficiency?
Blood film: macrocytyic anaemia
Erythrocyte folate level: indicated reduced blood stores
Treatment for folate deficiency?
Folic acid
How is vitamin B12 absorbed?
B12 is absorbed in the terminal ileum bound to intrinsic factor secreted by parietal cells
Causes of vitamin B12 deficiency?
Caused by the destruction of parietal cells or something effecting absorption in the terminal ileum
Investigations for B12 deficiency?
Blood film: macrocytic red blood cells
Autoantibody screen: check of IF antibiodyes
Treatment for B12 deficiency?
B12 tablets/injection
What is haemolytic anaemia?
RBCs usually removed by macrophages in red pulp of spleen after 120 days > haemolytic anaemia occurs when this happens before 120 days
Signs of haemolytic anaemia?
Gallstones Jaundice Leg ulcers Splenomegaly Signs of underlying disease e.g. malar rash
Inherited causes of haemolytic anaemia?
Membranopathies
Enzymopathies
Haemoglobinopathies
Aquired causes of haemolytic anaemia?
Autoimmune
Infections
Secondary to systemic disease
Investigations of haemolytic anaemia?
FBC - reduced haemoglobin
Reticulocyte count - increased
Blood film - presence of SCHISTOCYTES
Treatments for haemolytic anaemia?
Folate and iron supplementation
Immunosurpressives
Splenectomy
Describe anaplastic anaemia?
(bone marrow failure) occurs when there is a reduction in the number of pluripotent stem cells causing a lack of haemopoiesis - reduced number of RBCs to replace old ones causes anaemia
What are the specific signs of anaplastic anaemia?
Increased susceptibility to infection
Increased bruising
Increased bleeding (especially from nose and gums)
What investigations would be carried out for anaplastic anaemia?
FBC - pancytopenia
Reticulocyte count - low
Bone marrow biopsy
What is the treatment for bone marrow failire (anaplastic anaemia)
Removal of causative agent
Blood/platelet transfusion
Bone marrow transplant
Immunosuppressive therapy
Describe sickle cell anaemia?
Autosomal recessive disease, point mutation of the B globin chain (valine to glutamine) resulting in a Hs variant
Carriers are protected against falciparum malaria
What causes the symptoms of sickle cell anaemia?
Chronic haemolysis produced stable Hb so patients often dont have symptoms, if Hb suddenly falls then there are symptoms! Possible causes
- Splenic sequestration/infarction
- Bone marrow aplasia
- Further haemolysis
- Gallstones, leg ulcers, AVN femoral head
What happens to sickle cells under stress?
Under stress e.g. cold, infection, dehydration, hypoxia the RBCs deoxygenate and the Hs polymerises causing the cells to become rigid and sickled
What are the complications of sickle cells anaemia?
Acute: painful crisis, sickle chest crisis, mesenteric ischaemia
Chronic: renal impairment, pulmonary HTN, joint damage
Investigations for sickle cell anaemia?
Screen neonates: BLOOD/HEEL TEST
FBC: reticulocyte count
Blood film: SICKLED erythrocytes
Hb ELECTROPHORESIS for diagnosis: HbSS present and HbA absent
Management of sickle cell anaemia?
Supportive: aggressive analgesia, treat underlying cause (e.g. antibiotics) fluids, folic acid, transfuse with falling Hb
Disease modifying: hydroxycarbamide, transfusion, stem cell transplant
If hyposplenic: prophylactic antibiotics, pneumococcal and meningococcal vaccinations
Describe thalassemia?
Autosomal recessive - decreased production of one or more globin chains in the red cell precursors/mature cells
Precipitation of the globin chains red cell precursors causes ineffective erythropoiesis
Precipitation of the globin chain in mature red cells causes haemolysis
What are the types of thalassemia?
a. Alpha thalassemia (decreased a chain synthesis)
b. B thalassemia (decreased b chain synthesis)
Describe alpha thalassemia?
Varies from mild to severe
4 deletions - no a chain synthesis (incompatible with life)
3 deletions - severe haemolytic anaemia
2 deletions - asymptomatic with possible mild anaemia
1 deletion - blood picture normal
Describe beta thalassemia?
B thal minor - mild/absence anaemia, low MCV, Fe stores normal Hetrozg
B thal intermediate - doesnt require transfusions, moderate anaemia, splenomegaly and bone abnormalities
B thal major = severe anaemia, failure to thrive, chronic infection, Homozg
Investigations for thalassemia?
FBC and film - hypochromic and microcytic anaemia
Irregular and pale RBCs
Diagnosis by Hb electrophoresis - shows HbF + low HbA
Treatment for thalassemia?
Blood transfusions (2-4 per week) \+ Risk of iron overload so give iron chelation & ascorbic acid
Long term folic acid
Bone health, endocrine supplements and psych support
Describe membranopathy?
Autosomal dominant conditions, causes a deficiency in a protein that is used to make red cell membrane = deformed cells that get trapped in the spleen
Spherocytosis - vertical
Elliptocytosis - horizontal
Symptoms of membranopathy?
Neonatal jaundice and haemolytic anaemia exacerbated during infection (splenomegaly)
Excess bilirubin
What investigations would you carry out for membranopathy?
FBC and reticulocyte count
Blood film: osmotic fragility tests (RBC = fragility in hypotonic solutions)
Treatment for membranopathy?
Folic acid and splenectomy
Describe glucose 6 phoshphate deficiency?
X linked - can effect women
Mainly effects males in mediterranean, Africa and middle/far east
May get oxidative crisis
+ preciptated by drugs or illness
+ in attacks: rapid haemolysis - jaundice - anaemia
Diagnosis for glucose 6 phosphate deficiency?
Blood film: bite and blister cells
Diagnosis: enzyme essay
Management of glucose 6 phosphate deficency?
Avoid precipitants e.g. HENNA
Transfuse if severe
What kinds of patients might be over anticoagulated?
Vit K antagonists - WARFARIN
NOACs e.g.apixaban (do not need regular review, cannot be reversed
Why might patients be over anticoagulated?
Bad patient compliance
Artificial valves
New/interacting drugs
Symptoms of over antigcoagulated?
Bruising Bleeding Melena Epistaxis Hamatemesis Haemoptysis
Assessments for bleeding?
APTT = intrinsic pathway PTT = extrinsic pathway
Describe disseminated intravascular crisis?
Rare but life threatening disease
Generation of FIBRIN WITHIN the blood vessels also consumption of platelets/coagulation factors causing secondary activation of fibrinolysis
ie. there will be an initial thrombosis followed by bleeding tendency
Causes of disseminated intravascular crisis?
Malignancy Septicaemia Obstetric causes Trauma Infections Haemolytic transfusion reactions Liver disease
Treatment of disseminated intravascular disease?
Treat underlying cause: maintain blood volume and perfusion
May need transfusions
Activated protein C
Causes of thrombocytopenia? (both types)
- Reduced platelet production in the bone marrow
- Excessive peripheral destruction of platelets
- Problem of an enlarged spleen
ITP more common than TTP
Physiology of thrombotic thrombocytopenic purpura?
Extensive microvascular clots form in small vessels in the body resulting in a low platlet count and organ damage
Clinical features of thrombocytopenia? (both types)
Easy bruising
Purpura
Epistaxis/mennorragia
Investigation of thrombocytopenia?
Reduced platelets so normal/increased megakaryocytes
ITP = may have detection of platelet autoantibodies
Treatment for thrombocytic thrombocytopenic purpura?
Plasma exchange and immunosupression
Physiology of immune thrombocytopenic purpura?
Often triggered by VIRAL INFECTION OR MALIGNANCY
Due to autoimmune destruction of platelets, the antibodies coat the platelets which are then removed by binding to Fc receptors on macrophages
Is autoimmune so may be associated with other autoimmune diseases
Treatment for immune TP?
Corticosteriods
Splenectomy
IV Ig
Anti D
What are the two types of haemophilia?
Haemophilia A - factor 8 deficiency: treatment is IV factor 8
Haemophilia B - factor 9 deficiency: treatment is IV factor 9
Describe haemophilia?
X linked recessive disorders, females rarely severely affected
Haemophilia A is more common
Symptoms are anything associated with excess bleeding
Normal PTT (extrinsic) but prolonged APTT (intrinsic)
What is polycythaemia?
Defined as an increase in haemoglobin, PCV and RBCS
What are the primary causes of polycythaemia?
Increases sensitivity of the bone marrow to EPO
Polycythaemia rubra vera - genetic mutation in the JAK2 gene
Primary familial and congenital polycythaemia - mutation in the EPOR gene
What are the secondary causes of polycythaemia?
The are more RBCs due to more circulating EPO
Due to: chronic hypoxia, poor oxygen delivery (e.g. high altitude), abnormal RBC structurea and tumours which release high levels of RPO
Symptoms of polycythaemia?
May present with no symptoms
May have: easy bleeding /brusing, fatigue, dizziness, headaches etc
Investigations for polycythaemia?
FBC
Bone marrow biopsy
Genetic testing for JAK2 gene
Treatment for polycythaemia?
Polycythaemia rubra vera - bloodletting, aspirin
Secondary - treat the cause
What is acute lymphoblastic leukemia?
Neoplasm within the bone marrow, systemically unwell - B symtoms
Generalised cytopenia - infection and bleeding
Progenitors cant mature - too many blasts
Risk factors for acute lymphoblastic leukemia?
Epi: 2-5 years
Chromosomal abnormalities
Downs sydrome
Radiation
Presentation of acute lymphoblastic leukaemia?
Bone marrow failure
Neutropenia - infections
Anaemia - fatigue, pallor
Thrombocytopenia - brusing
Infiltration of Acute lymphoblastic leukaemia?
LYMPHADENOPATHY, HSM, orchidomegaly
CNS INVOLVEMENT
Bone pain
Systemic features of ALL?
Fever, weight loss
Epidemiology of acute myeloid leukaemia?
60-70 years
Risk factors of AML?
Chromosomal abnormalities
Chemotherapy
Myelodysplastic/proliferative disorders
Presentation of acute myeloid leukaemia?
Bone marrow failure
Neutropenia - Infection
Anaemia - fatigue pallor
Thrombocytopenia - brusing - DIC WITH ANPL
Infiltration with AML?
GUM INFILTRATION
HSM
Bone pain
Systemic features of AML?
Leukaemia
What is acute promyeleocytic leukaemia?
Subtype of AML, translocation t15;t17
Good prognosis but associated with DIC, add all-trans retinoic acid to standard management
Investigations for acute leukaemia? ALL and AML
FBC: White cell count = increased Polymorphonuclear leukocytes = decreased RBCs = decreased Platelets = decreased
BONE MARROW ASPIRATION AND IMMUNOPHENOTYPING & CYTOGENETICS
Lumbar puncture is also indicated in ALL to check for CNS involvement
What is the name given to the cell that is diagnostic of AML if seen on bone marrow aspiration?
Auer rods
Management of acute leukaemia?
Chemotherapy (ATRA in APML)
Bone marrow transplant
Supportive:
+ Anaemia/thrombocytopenia: blood products
+ Infections: prophylactic abc
+ Allopurinol: tumour lysis syndrome
Side effects of chemotherapy - immediate?
\+ alopecia \+ neutropenia \+ anaemia/fatigue \+ thrombocytopenia - bruising/bleeding \+ N&V/ mucosistis/loss of appetite
Side effects of chemotherapy - late?
\+ cardiotoxicity \+ nephrotoxicity \+ pulmonary fibrosis \+ infertility \+ increased risk of other malignancy \+ psychological
Describe chronic lymphocytic leukaemia?
Proliferation of B lymphocytes
Arrested in G0/G1 - do not develop into B plasma cells
Presentation of chronic lymphocytic leukaemia?
Epi: eldery 70+
ASYMPTOMATIC in 50%
Symmetrical painless lymphadenopathy
Bone marrow infiltration (anaemia/infection)
Systemic B symptoms
Investigation of chronic lymphocytic leukaemia?
FBC - increased white cell count
Ig - HYPOGAMMAGLOBULINEMIA
Blood film - SMUDGE/SMEAR celd
Immunophenotyping - distinguish from NHL
Management of CLL?
If symptomatic
Supportive - abx/blood products
RT - lymphadenopathy
Chemotherapy
Bone marrow transplant
Presentation of chronic myeloid leukaemia?
Slow onset/incidental finding
Systemic symptoms
Abdominal discomfort/ SPLENOMEGALY
Investigation of CML?
<5% blasts - chronic phase
>10% blasts - accelerated phase
>20% blasts - blast phase (AML)
With bone marrow aspiration and cytogenetics what would you find in chronic myeloid leukemia?
PHILIDELPHIA CHROMOSOME
Management of chronic myeloid leukaemia?
1st line = TYROSINE KINASE INIHIBITORS e.g. imatinib
Stem cell transplant if TK resistant or blast crisis
What is tumour lysis sydrome
Chemotherapy given >
Cancer cell broken down >
Released contents - hyperkalaemia and nucleic acids >
Produce crystals that get deposited in the kidneys >
Damage and loss of function
Prevention: allopurinol
Treatment: IV fluid and correct electrolytes
Describe the presentation of non Hodgkins lymphoma?
Epi - elderly
Lymphadenopathy
+ painless
+ symmetrical
+ discontinuous spread
Extranodal
+ skin/cns/lymphomas
+ BM: pancytopenia
+ spenomegaly
B symtoms
Describe the presentation of Hodgkins lymphoma?
Epi - bimodal 20s and 60s
Lymphadenopathy
+ painless but pain with alcohol
+ asymmetrical
+ continuous spread
Other
+ itch
+ pel ebstein fever
+ splenomegaly
B symptoms
What would be seen in a lymph node biopsy of hodgkins lymphoma?
Reed Sternberg cells in histology
What investigations would be carried out for a lymphoma?
FBC U&E LFT Ca Blood film LN biopsy
Staging using CT and ann arbor classificaition
Describe the ann arbor classification?
- Singular lymph node region
- > 2 nodal areas on the same side of diaphragm
- Nodes on both sides of diaphragm
- Disseminated e.g. liver, BM
Management of non Hodgkins lymphoma?
Low grade - follicular: watch and wait
High grade - large diffuse b cell: chemo, BMT
Management of Hodgkins lymphoma?
Chemo +/- radiotherapy
Bone marrow transplant for relapse
Describe multiple myeloma?
Neoplastic proliferation of bone marrow plasma cells, IgG is most common
Characterised by monoclonal protein in the serum or urine and CRAB - calcium, renal, anaemia, bone
Aetiology of multiple myeloma?
Clone of B plasma cells in the body
Monoclonal antibodies, repeat infections as no other Ig
Bence jones protein deposition in the urine
Cancer symptoms - confusion, repeat infection, pathological fractures e.g. slipped in garden and fractured L1 and L2, bone pain, renal impairment
Common presenting features of multiple myeloma?
Tiredness and malaise
Bone/back pain +/- fractures
Recurrent infection
Laboratory - anaemia/abnormal FBC, renal failure, hypercalcaemia, raised globulins, raised ESR, serum urine/urine paraprotein
Diagnosis of multiple myeloma?
Monoclonal band on protein electrophoresis
BM aspiration shows excess plasma cells
Xray = pepperpot skull, lyses in long bones, pelvis and spine
Treatment of multiple myeloma?
Radiotherapy - spot welding
Chemotherapy
BMT in some
Management of multiple myeloma?
C - Ca - hydration/bisphosphates
R - renal - hydration/dialysis
A - anaemia - transfusion +/- EPO
B - bone - analgesia + bisphosphates
Complications of multiple myeloma?
Hypercalaemia
AKI
Cord compression
Amyloid
Describe malarial infection?
+ protazoa infection transmitted by plasmodia falciparum
+ transmitted by female anopheles mosquito
+ stages are:
1. exo-erythrocytic
2. endo-erythrocytic
3. hypnozoite
What are the symptoms of a malarial infection?
FEVER + EXOTIC TRAVEL = MALARIA
Chills, sweats, jaundice, hepatosplenomegaly, anaemia, fatigue, black urine
Pathogenesis of malaria?
Parasite matures in RBC - knobs in RNC surface - infected cells bind to eachother and receptors on endothelial walls
Sequestration in small vessels becoming trapped
Microcirculation obstruction = tissue hypoxia
Cerebral malaria, ARDS, hypoglycaemia, renal failure shock
Investigation of malaria?
+ Thick and thin film ( thick - if you havent) (thin - what type)
+ RDT rapid diagnostic test: detects plasmodium antigens in the blood
+ RULE OUT MENIGITIS
+ PREGNANCY TEST
Management of malaria?
Quinine and doxycycline
Risk factors for deep vein thrombosis?
+ Age, obesity, varicose
+ Surgery, immobility, leg fracture, post op
+ OC pil, HRT, pregnancy - high oestrogen state
+ Long haul flights/ travel (rare)
+ Inherited thrombophilia - genetic predisposition
DVT diagnosis?
Symptoms and signs - non specfic, clincial diagnosis unreliable
Symptoms - pain, swelling, (usually in calves)
Signs: tenderness, warmth, discolouration, pitting oedema
Investigation of DVT?
D-dimer: normal excludes diagnosis - positive DOES NOT CONFIRM
Ultrasound compression test in proximal veins
Venogram calf, recurrence uncertain
Treatment for DVT?
LMW heparin s/c od for minimum of 5 days > short acting injectable
Oral warfarin, INR 2-3 for 6 months > long acting but takes a while to get up a therapeutic range
DOAC > dont have to give an injectable component so can be treated as an outpatient
Compression stockings
Treat/seek underlying cause
Spontaneous DVT more likely to recur 10% per year
Prevention of DVT?
Mechanical - hydration early mobilisation, compression stocking, foot pumps
Chemical - LMW heparin
Describe thromboprophylaxis?
Low risk <40 yrs, surgery <30 min, early mobilisation and hydration
High risk: hip, knee and pelvis malignancy, prolonged immobility
Describe pulmonary embolisms?
+ Massive = haemodynamically significant
+ Hypotension, cyanosis, severe dyspnoea , right heart strain/failure
+ Near death experience/medical emergency
+ Rare
+ Consider embolectomy/thrombolysis
Symptoms of PE?
Breathlessness
Pleuritic chest pain
Signs of PE?
Tachycardia
Tachypnoea
Pleural rub
No signs of alternative diagnosis
Prevention of PE?
+ Same as DVT
+ Early mobilisation and hydration
+ Mechanical
+ Chemical: LMW heparin s/c OD
PE initial investigations?
CXR usually normal
ECG sinus tachy - (QI, SI, TIII)
Blood gases - type 1 resp failure, decreased O2 and CO2
Mainly done to exclude alternative causes
PE further investigations?
D dimer: normal excludes diagnosis > if abnormal then CTPA imaging
V/Q scan
CTPA spiral with contrast - visualise major segmental thrombi
Treatment for PE?
+ As for DVT
+ Ensure normal Hb, platelets, renal function, baseline clottning
+ LWM hepatic and weight adjusted warfarin for 6 months (2-3 INR)
+ DOAC outpatient only with minor PE
+ If cannot anticoagulate then consider IVC filter
What is neutropenic sepsis?
Temperature >38 degrees and absolute neutrophil count = 1x10^9
Treatment for acute sickle cell crisis?
Pain relief and IV fluid
Treatment for chest crisis?
IV fluid and abx
Treatment for spinal cord compression?
Steroids and MRI
Which of the following is NOT a complication of sickle cell anaemia?
A. Mesenteric ischaemia
B. Sequestration crisis
C. Acute chest sydrome
D. Acute lateral degloblanation
D. Acute lateral degloblanation
Which of the following is not a cause of secondary polycythaemia?
A. Endogenous EPO
B. High altitude
C. JAK-2
D. COPD
C. JAK-2
Patient has myeloma with side of the diaphragm and weight loss - which stage?
3b
Which of the following is an innappropriate investigation for lymphoma?
PET
Histology
FBC
PR
PR
Inappropriate test for malaria?
Pregnancy
RDT
Thick and thin film
Laprarotomy
Lapraotomy
Which of the following is a sign of iron deficiency anaemia?
Fatigue
Pale mucous membranes
Dysponea
Palpitations
Pale mucous membranes
Where in the GI tract is vitamin B12 absorbed?
Terminal ileum bound to intrinsic factor
In which type of anaemia would you fine a raised reticulocyte count?
Haemolytic
In histology which cells are seen in glucose 6 phosphate deficiency?
Bite and blister
Histology in Hodgkins lymphoma will show which cell?
Reed sternberg
Lady with DVT suddenly has chest pain, what is the most likely diagnosis?
Pulmonary embolism
What does virchows triad contain?
Hypercoagulability
Hemodynamic changes
Endothelial injury/dysfunction
