Haematology Flashcards
Causes of the following blood film findings - Burr cells Target cells Tear drop Pencil poikilocytes Heinz bodies Howell Jolly bodies Reticulocytosis Schistocytes Sideroblasts Smudge cells Spherocytes
- Burr cells - uraemia
- Target cells – iron deficiency anaemia, post-splenectomy, sickle cell
- Tear drop poikilocytes - myelofibrosis
- Pencil poikilocytes: iron deficiency
- Heinz bodies – G6PD, alpha thalassaemia
- Howell-Jolly bodies – post-splenectomy, severe anaemia
- High number of reticulocytes – haemolytic anaemia
- Schistocytes – HUS, DIC, TTP, metallic heart valves, haemolytic anaemia
- Sideroblasts – myelodysplastic syndrome
- Smudge cells – chronic lymphocytic leukaemia
- Spherocytes – autoimmune haemolytic anaemia, hereditary spherocytosis
Causes of microcytic anaemia
TAILS Thalassaemia Anaemia of chronic disease Iron deficiency Lead poisoning Sideroblastic anaemia
Causes of normocytic anaemia
Acute blood loss
Anaemia of chronic disease (eg. renal failure)
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism (can be normocytic or macrocytic)
Pregnancy
Causes of megaloblastic macrocytic anaemia (megaloblastic = impaired DNA synthesis)
Folate deficiency
B12 deficiency
Pernicious anaemia
Causes of normoblastic macrocytic anaemia
Alcohol Reticulocytosis Hypothyroidism Liver disease Drugs (eg. azathioprine)
Specific signs and symptoms caused by iron deficiency anaemia
Koilonychia – spoon shaped nails
Angular chelitis/stomatitis – inflammation of the corners of the mouth
Atrophic glossitis – smooth tongue due to atrophy of the papillae
Brittle hair and nails
Pica – dietary cravings to abnormal things (eg. dirt)
Hair loss
Investigations for anaemia
FBC: haemoglobin, MCV B12 Folate Ferritin Blood film Further Ix: OGD or colonoscopy to investigate for a GI cause of iron deficiency anaemia, bone marrow biopsy if cause is unclear
Causes of iron deficiency anaemia
Blood loss (eg. menorrhagia, oesophagitis, gastritis, GI cancer, IBD)
Dietary insufficiency
Increased requirements during pregnancy
Poor iron absorption: coeliac/Crohns cause inflamm of duodenum/jejunum which is where iron is absorbed. Stomach acid is required to keep iron in the ferrous form, reduced stomach acid changes iron into insoluble ferric form. Drugs which reduce stomach acid (eg. PPI) reduce iron absorption
Iron tests
Iron travels in blood as ferric irons (Fe3+), bound to a carrier protein called transferrin
Ferritin – reliable marker. Low in iron deficiency anaemia, high in inflammation/ infection/ cancer (released from cells)
Serum iron - unreliable to use on its own as it varies throughout the day
Total iron binding capacity (TIBC) is the total amount of space on a transferrin molecule for iron to bind to
TIBC – a marker for how much transferrin is in the blood. Increases in iron deficiency and decreases in iron overload
Transferrin saturation (%) = serum iron / TIBC
Transferrin saturation gives a good indication of the total iron in the body (30% is normal in adults, will be reduced in iron deficiency and raised in iron overload)
Management of iron deficiency anaemia
Oral ferrous sulphate TDS – slowly corrects iron deficiency (Hb rises by 10g/L every week). Causes constipation and black stools. Unsuitable in malabsorption.
Iron infusions – small risk of anaphylaxis but quickly corrects iron deficiency. Avoid during sepsis as it worsens sepsis.
Blood transfusion – immediately corrects the anaemia but carries risks
OGD and colonoscopy required for new iron deficiencies in adults without clear underlying cause to look for cancer of GI tract
Causes of B12 deficiency anaemia
Insufficient dietary intake of B12 (animal products) Pernicious anaemia (autoantibodies against parietal cells or intrinsic factor -> intrinsic factor deficiency -> unable to absorb vit B12 in ileum)
Clinical features of B12 deficiency anaemia
Peripheral neuropathy (numbness, paraesthesia) Loss of vibration sense or proprioception Visual changes Mood or cognitive changes
Investigations fo pernicious anaemia
FBC, B12 levels, Intrinsic factor antibody (first line for pernicious anaemia), gastric parietal cell antibody (less helpful)
Management of pernicious anaemia/ B12 deficiency
Dietary deficiency can be treated with oral replacement with cyanocobalamin
Pernicious anaemia can be treated with IM B12 (hydroxycobalamin)
If there is also folate deficiency, B12 deficiency must be treated before folate deficiency otherwise it can lead to subacute combined degeneration of the cord
Causes of haemolytic anaemia
Inherited: hereditary spherocytosis, hereditary elliptocytosis, thalassaemia, sickle cell disease, G6PD deficiency
Acquired: autoimmune haemolytic anaemia, alloimmune haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, microangiopatic haemolytic anaemia, prosthetic valve related haemolysis, drugs (methyldopa, penicillin)
Features of haemolytic anaemia
Anaemia, due to reduction of circulating RBC: tiredness, SOB, headache, dizziness, palpitations, pallor
Splenomegaly as the spleen becomes filled with destroyed RBCs
Jaundice as bilirubin is released during RBC destruction
Intravascular vs extravascular haemolytic anaemia
Intrinsic – RBC destruction within the blood vessels due to abnormal RBCs
Extrinsic – RBC destroyed in spleen/ liver/ BM/ lymph
Investigations for haemolytic anaemia
FBC – normocytic anaemia, high reticulocytes, MCHC increased in autoimmune haemolytic anaemia and spherocytosis
LFTs – bilirubin high
LDH – high
Haptoglobin – low in intravascular haemolysis (haptoglobin binds to free Hb, so if there is increased Hb release from RBCs there will be more binding of haptoglobin to Hb and therefore less haptoglobin in the circulation)
Blood film – schistocytes (fragments of RBCs), spherocytes, reticulocytes
Direct Coombs test – positive in autoimmune haemolytic anaemia
Hereditary spherocytosis - Inheritance Presentation Ix Mx
Autosomal dominant -> causes sphere-shaped RBCs which are fragile and break down when passing through the spleen
Jaundice, gallstones, splenomegaly, aplastic crisis in the presence of parvovirus
Ix: family history, spherocytes on blood film, raised MCHC, raised reticulocytes
Mx: folate supplementation and splenectomy, cholecystectomy may be required if gallstones are troublesome
G6PD deficiency inheritance crisis triggers presentation investigations Mx
X-linked recessive
Crises triggered by infections, medications (primaquine, ciprofloxacin, sulphonylureas, sulfasalazine), broad beans
Jaundice (usually neonatal), gallstones, anaemia, splenomegaly
Ix: Heinz bodies on blood film, G6PD enzyme assay
Mx: avoid triggers, and transfuse if severe
Warm vs cold autoimmune haemolytic anaemia
Warm type AIHA – more common, haemolysis occurs at body temp, usually idiopathic, usually extravascular. Examples: SLE, lymphoma, CLL, methyldopa
Cold type AIHA – haemolysis at 4 degrees, haemolysis usually intravascular, often causes raynauds and acrocynaosis. Often secondary to lymphoma, leukaemia, SLE, mycoplasma, EBV, CMV and HIV. Responds less well to steorids.
Management of autoimmune haemolytic anaemia
Blood transfusions
Prednisolone
Rituximab
Splenectomy
Alpha thalassaemia inheritance defect presentation diagnosis management
Autosomal recessive
Defects in alpha globin chains
If all 4 alpha globin alleles are affected -> death in utero
Diagnosis: FBC (microcytic anaemia), haemoglobin electrophoresis, DNA testing
Management: monitor FBC, monitor complications, blood transfusions (risk of iron overload), splenectomy, BM transplant
Beta thalassaemia inheritance defect presentation diagnosis management
Autosomal recessive
Defects in beta globin chains (minor, intermedia or major depending on the type)
Beta thalassaemia major causes failure to thrive in first year of life, severe microcytic anaemia, splenomegaly and bone deformities (eg. pronounced forehead due to enlarging BM in order to produce more RBCs)
Diagnosis: FBC (microcytic anaemia), haemoglobin electrophoresis, DNA testing
Management: regular transfusions (risk of iron overload), iron chelation, splenectomy, BM transplant
Sickle cell disease - pathophysiology and relation to malaria
Autosomal recessive mutation of beta globin gene -> Haemoglobin S
One copy of mutated gene -> sickle-cell trait (asymptomatic)
Two copies of mutated gene -> sickle-cell disease
Sickle RBCs are fragile and easily destroyed -> haemolytic anaemia
Prone to sickle cell crises
Patients with a sickle cell trait aren’t affected by malaria as much as other people, so survive and pass on the gene, therefore there is a selective advantage to having sickle cell in areas of malaria
Complications of sickle cell disease
Anaemia Increased risk of infection Stroke Avascular necrosis Pulmonary hypertension Painful persistent erection CKD Sickle cell crises Acute chest syndrome
Management of sickle cell disease
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Abx prophylaxis with pen V
Hydroxycarbamide stimulates production of foetal haemoglobin which does not leas to RBC sickling (protective effect against sickle cell crises)
Blood transfusions for severe anaemia
Bone marrow transplant
Types of sickle cell crises
Painful crisis – thrombi in capillaries -> distal ischaemia. Associated with dehydration and raised haematocrit
Splenic sequestration crisis – RBCs block blood flow within spleen-> acutely large painful spleen. Pooling of blood in spleen -> severe anaemia and hypovolaemic shock. Emergency -> transfusions, fluid, splenectomy if recurrent
Aplastic crisis – loss of RBC production due to parvovirus B19 -> significant anaemia
Acute chest syndrome – fever or resp symptoms with new infiltrates on CXR. Either due to infection or non-infective causes. Emergency -> supportive Mx, abx/antivirals, transfusions, incentive spirometry, NIV or intubation
Triggers of sickle cell crises
Infection, dehydration, cold, significant life events
Management of sickle cell crises
Hospital admission, treat any infection, do a septic screen, keep warm, oxygen if required, keep hydrated with IV fluids, appropriate analgesia, blood transfusion if required, treat underlying cause
Causes of neutropenia
Viral infections
Drugs: chemo, cytotoxics, carbimazole, sulphonamides
Severe sepsis
Neutrophil antibodies (SLE, haemolytic anaemia) -> increased destruction
Bone marrow failure (reduced production)
Causes of neutrophilia
Bacterial infections Inflammation Myeloproliferative disorders Drugs (eg. steroids) Disseminated malignancy Stress (eg. trauma, burns, haemorrhage, seizure)
Causes of lymphopenia
Steroid therapy (SLE, uraemia, HIV, marrow infiltration, chemo, radiotherapy)
Causes of lymphocytosis
Acute viral illness
Chronic infection (TB, hepatitis, syphilis)
Leukaemia (esp chronic lymphocytic leukaemia)
Lymphoma
Haemophilia A Inheritance Deficiency Presentation Ix Mx Complication of treatment
Factor VIII deficiency
X-linked recessive
Usually presents in neonates or early childhood -> intracranial haemorrhage, haematomas, cord bleeding
Bleeding into joints -> crippling arthropathy
Bleeding into muscles-> haematomas (neuropathy, compartment syndrome)
Ix: Increased APTT, reduced factor VIII assay
Mx: Avoid NSAIDs and IM injections. For minor bleeds can give pressure and elevation of body part, plus desmopressin to increase factor VIII levels. If more severe bleeding give recombinant factor VIII. Genetic counselling
Complications: some patients develop antibodies to factor VIII treatment making it ineffective
Haemophilia B deficiency inheritance presentation Ix Mx
Factor IX deficiency
X linked recessive
Presentation same as haemophilia A: haemorrhage (spontaneous or a result of minor trauma) -> into muscle (nerve compression, compartment syndrome), or into joints (crippling arthropathy). Often presents as neonate (ICH, bleeding into cord, haematomas)
Ix: raised APTT, reduced factor IX assay
Mx: recombinant factor IX. Avoid IM injections and NSAIDs
Immune thrombocytopenia
Autoantibodies against platelets
Acute or chronic
Acute - usually in children, 2wks after infection, self-limiting purpura
Chronic – usually in women, bleeding, purpura, epistaxis, menorrhagia
No splenomegaly
Ix: Increased megakaryocytes in BM, antiplatelet autoantibodies
Mx: aim to keep platelets >30. prednisolone if symptomatic or platelets <20, IV immunoglobulin (temp raises platelet levels), rituximab, splenectomy
Abnormal coagulation (effect on APTT, PT, bleeding time)
Haemophilia
vWF disease
Vit K deficiency
Haemophilia: APTT increased, PT normal, bleeding time normal
Von Willebrand disease: APTT increased, PT normal, bleeding time increased
Vit K deficiency: APTT increased, PT increased, bleeding time normal
Abnormal coagulation (factors affected) Heparin Warfarin DIC Liver disease
Heparin: prevents activation factors 2, 9, 10, 11
Warfarin: affects synthesis of factors 2, 7, 9, 10
DIC: factors 1, 2, 5, 8, 11
Liver disease: factors 1, 2, 5, 7, 9, 10, 11
What is APTT and what does it test
What is normal APTT
What causes prolonged APTT
Partial thromboplastin time
Tests clotting factors involved in the intrinsic and common pathways of coag cascade: fibrinogen (I), thrombin (II), X, XI, XII, co-factors V and VIII
A normal blood sample should clot in 30-40s
Prolonged APTT: deficiency in the tested factors, DIC, heparin
What is PT What does it test What is a normal PT How INR works Causes of prolonged PT
Prothrombin time, tests extrinsic pathway
Factors: fibrinogen (I), thrombin (II), VII, IX, X
Normal PT is 11-13s
PT measures factors II, VII, IX, X which are all vit K dependent so will be reduced when taking warfarin -> can therefore be used to monitor warfarin levels. Calculates as patient PT compared to PT or population -> INR value
Prolonged PT: severe liver disease, vit K deficiency, warfarin, DIC, sepsis
Causes of thrombocytopenia
Low production: sepsis, B12 or folate deficiency, liver failure, leukaemia, myelodysplastic syndrome
High destruction: alcohol, ITP, TTP, HIT, HUS, drugs (sodium valproate, methotrexate, isotretinoin, antihistamines, PPI)
Thrombotic thrombocytopenic purpura
what happens
management
Either genetic mutation or autoimmune
Tiny blood clots throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues
Due to a deficiency in the protein responsible for inactivating vWF -> causes overactivity of vWF, increased platelet adhesion and clot formation
The clots in the small vessels break up RBCs -> haemolytic anaemia
Mx: plasma exchange, steroids, rituximab
Von Willebrand disease
- inheritance
- typical presentation
- three types
- ix
- mx
Most common inherited cause of abnormal bleeding
Most are autosomal dominant
Epistaxis, menorrhagia, bleeding gums
Three types:
- partial reduction in vWF (most common)
- abnormal form of vWF
- total lack of vWF (autosomal recessive)
Ix: prolonged bleeding time, APTT may be prolonged, factor VIII may be reduced
Mx: tranexamic acid for mild bleeding, desmopressin raises vWF levels, factor VIII concentrate
Presentation and management of acute haemolytic reaction
Presentation: agitation, rapid onset fever, hypotension, flushing, abdo/chest pain, oozing venepuncture sites, DIC
Mx: stop transfusion, tell blood bank and haematologist, sent the unit of blood + UE + FBC + clotting + cultures + urine to labs, give IV saline, treat DIC
Presentation and management of anaphylaxis as a response to blood transfusion
Presentation: bronchospasm, cyanosis, hypotension, soft tissue swelling
Mx: stop transfusion, maintain airway, give oxygen, contact anaesthetist, give IM adrenaline, chlorphenamine, hydrocortisone
Presentation and management of TRALI
Presentation: dyspnoea, cough, CXR shows ‘white out’
Mx: stop transfusion, give 100% O2, treat as ARDS (resp and circulatory support)
Presentation and Mx or non-haemolytic febrile transfusion reaction
Presentation: shivering and fever usually half hour/1 hour after starting transfusion
Mx: slow or stop the transfusion, give an antipyretic (paracetamol), monitor closely, if recurrent use WBC filter
Allergic reactions to blood transfusion presentation and management
Presentation: urticaria, itch
Mx: slow or stop transfusion, chlorphenamine 10mg slow IV/IM, observe closely, restart transfusion if symptoms resolve
Fluid overload transfusion reaction presentation and management
Presentation: dyspnoea, hypoxia, tachycardia, raised JVP, basal crepitations
Mx: slow or stop transfusion, give O2 and diuretic, consider CVP line
Management of high INR
Major bleed: Stop warfarin, give IV vit K 5mg, prothrombin complex concentrate (or FFP)
INR >8, minor bleed: stop warfarin, give IV vit K 1-3mg, restart warfarin when INR <5
INR >8, no bleed: stop warfarin, give vit K 1-5mg PO, restart when INR<5
INR 5-8, minor bleed: stop warfarin, give IV vit K 1-3mg, restart when INR<5
INR 5-8, no bleed: withhold 1 or 2 doses, reduce subsequent maintenance dose
Factors that may potentiate warfarin
liver disease, P450 inhibitors, cranberry juice, drugs which displace warfarin from albumin (NSAIDs), inhibits platelet function (NSAIDs)
Acute lymphoblastic leukaemia
- epidemiology
- features
- Ix
Affects children, 2-5years of age, boys>girls
Usually affects B lymphoblasts
Associated with Down’s syndrome
Features: BM failure (anaemia, neutropenia, thrombocytopenia) -> lethargy, pallor, frequent severe infections, easy bruising, patechiae Bone pain (secondary to BM infiltration) Splenomegaly Hepatomegaly Fever Testicular swelling
Ix: FBC, blood film, bone marrow biopsy
Consider immunophenotyping, cytogenetics, lymph node biopsy, LP, CT, CXR
ALL poor prognostic factors
<2 or >10 WBC >20 at diagnosis T or B cell surface markers Non-Caucasian Male
Age presentations of ALL, CLL, CML, AML
ALL: <5
CLL: >55
CML: >65
AML: >75
Differential diagnoses of patechiae (non-blanching rash caused by bleeding under the skin)
Leukaemia Meningococcal septicaemia Vasculitis HSP ITP NAI
Investigating leukaemia
FBC with differential
Blood film
Lactate dehydrogenase (raised, but not specific)
BM biopsy: aspiration looks at cells in the liquid bone marrow, BM trephine looks at the cells and structure of the solid BM
ALL investigations and management
Ix:
FBC with differential shows high WCC, anaemia, thrombocytopenia, neutropenia
Blood film shows blast cells
CXR and CT may show mediastinal and abdo lymphadenopathy
LP to look for CNS involvement
Mx:
Supportive: blood/platelet transfusions, IV fluids, allopurinol, hickman line
May have BMT
Chemo: 3 phases
Induction of remission – vincristine, steroids (dex) and L-asparaginase
Intensification/ consolidation – add new chemo agents
Maintenance (for 2 yrs) – immunosuppressants and more chemo
Chronic lymphocytic leukaemia
- how common
- what is it
- who does it affect
- presentation
- transformation
- ix
- mx
Commonest leukaemia
Over proliferation of a single type of small well differentiated lymphocyte (usually B lymphocytes)
Usually affects adults >55
Often asymptomatic but can present with infections, anaemia, bleeding, weight loss, warm AIHA, ITP, sweating
Can transform into high-grade lymphoma (Richter’s transformation)
Ix: FBC with differential shows lymphocytosis, anaemia, neutropenia, thrombocytopenia, autoimmune haemolysis (later)
Blood film: smear or smudge cells
Immunophenotyping
Mx:
Watchful waiting is asymptomatic
If symptomatic -> combination chemo regimen (ibrutinib, steroids, cyclophosomide, rituximab, etc)
Chronic myeloid leukaemia
- cause
- presentation
- ix
- mx
Philadelphia chromosome (9:22 translocation) -> BCR-ABL gene
Presentation: 60yrs+, anaemia (lethargy), may have hyperviscosity due to raised WCC, weight loss, sweating, splenomegaly, thrombocytosis, reduced leukocyte ALP, blast transformation may occur (AML, ALL)
Ix: significantly raised WCC (high neutrophils, monocytes, basophils, eosinophils), anaemia, platelets variable, high urate, high B12
BM is hypercellular
Cytogenetic analysis of blood or BM for philadelphia chromosome
Management: imatinib first line (tyrosine kinase inhibitor), hydroxyurea, interferon-alpha, allogeneic BMT
Acute myeloid leukaemia
- epidemiology and causes
- presentation
- ix
- mx
Commonest acute leukaemia in adults
Middle age onwards
May be a result of transformation from a myeloproliferative disorder
Progresses rapidly BM failure (anaemia, infection, bleeding), DIC, hepatomegaly, splenomegaly, gum hypertrophy, skin involvement
Ix: WCC raised (or normal, or low), blast cells in BM biopsy, immunophenotyping, cytogenetic analysis, blood film shows blast cells (auer rods differentiated ALL from AML)
Mx: intensive chemotherapy or allogeneic bone marrow transplant, with supportive care
What are the differences in clinical features and lab results, between Hodgkin’s and Non-Hodgkin’s lymphoma?
Hodgkin’s has characteristic Reed-Sternberg cells
Hodgkins has alcohol-induced lymph node pain
Hodgkins get B symptoms earlier on compared to Non-Hodgkins
Non-Hodgkins are more likely to get extra-nodal disease compared to Hodgkins
Hodgkins lymphoma risk factors and age group
Bimodal age distribution (20s and 60s) HIV Epstein-Barr virus Autoimmune conditions (RA, sarcoidosis) Family history
Signs and symptoms of Hodgkin’s lymphoma
Enlarged, painless, asymmetrical, non-tender rubbery superficial lymph node
B symptoms (poor prognosis): weight loss, night sweats, fever
Alcohol-induced lymph node pain
Other systemic features: pruritus, cough, fatigue, SOB, abdo pain, recurrent infection
Signs: lymphadenopathy, cachexia, anaemia, hepatosplenomegy
Investigations for Hodgkin’s lymphoma
Lymph node excision biopsy is diagnostic test: Reed-sternberg cells (large B cells with multiple nuclei)
Bloods: FBC (normocytic anaemia, eosinophilia), raised LDH, blood film, raised ESR, LFT, urate, calcium
Imaging: CXR, CT/PET chest abdo pelvis
CT CAP used for staging
Staging for lymphomas
Ann-Arbor staging
- Confined to one region of lymph nodes
- More than one region but same side of diaphragm
- More than one region of lymph nodes, both sides of diaphragm
- Extra-lymphatic infiltration (lungs, liver, etc)
Each stage is either A (no systemic symptoms other than pruritus) or B (B symptom involvement)
Management of Hodgkin’s lymphoma
Combination chemoradiotherapy
Subtypes of Hodgkin’s lymphoma
Nodular sclerosing Hodgkin lymphoma (most common)
Mixed-cellularity Hodgkin lymphoma
Lymphocyte-depleted Hodgkin lymphoma (worst prognosis)
Lymphocyte-rich classical Hodgkin lymphoma (best prognosis)
Poor prognostic factors of Hodgkin lymphoma
Age >45, stage IV disease, low Hb, low lymphocyte (lymphocyte depleted subtype), male, low albumin, high WCC
What is lymphoma
Malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs
Non-Hodgkin Lymphoma
- incidence
- risk factors
More common than Hodgkin’s lymphoma
Typically affects the elderly
Risk factors: elderly, caucasian, Hx of EBV, FHx, chemical agents, Hx of chemo/radiotherapy, immunodeficiency (transplant, HIV, DM), autoimmune disease (SLE, sjögrens, coeliac)
Presentation of Non-Hodgkin’s lymphoma
Painless, non-tender, rubbery, asymmetrical lymphadenopathy
B symptoms: fever, weight loss, night swears, lethargy
Extra-nodal disease: gastric (dyspepsia, dysphagia, weight loss, abdo pain), bone marrow (pancytopenia, bone pain), lungs, skin, CNS (nerve palsies)
Signs: weight loss, lymphadenopathy, palpable abdo mass (hepatomegaly, splenomegaly, lymph nodes), testicular mass, fever
Investigations for Non-Hodgkin’s lymphoma
Excisional node biopsy is diagnostic investigation of choice
CT CAP for staging
FBC and blood film (normocytic anaemia) ESR (raised = poor prognosis) LDH (raised) LFTs (?liver mets) PET CT or BM biopsy (?bone involvement) LP (if neuro symptoms) HIV test (risk factor for NHL)
Management of Non-hodgkin lymphoma
Depends on subtype Watchful waiting if low grade High grade: Chemotherapy Monoclonal antibodies (rituximab) Radiotherapy Stem cell transplantation
Flu and pneumococcal vaccinations
If neutropenia -> prophylactic abx
Subtypes of Non-Hodgkin lymphoma
B cell low grade: follicular, waldenström’s macroglobulinaemia
B cell high grade: diffuse large B cell (most common), Burkitts lymphoma, mantle cell lymphoma
T cell - rare
Chronic lymphocytic leukaemia can undergo Richter’s transformation into a high grade non-Hodgkin lymphoma
Burkitt’s lymphoma
- what is it
- two forms
- associated conditions
- microscopic finding
- management
High-grade B cell non-Hodgkins lymphoma
Two forms: endemic (typically africa, involving maxilla/ mandible), or sporadic (abdo tumours most common, in HIV)
Associated with EBV, malaria and HIV
Microscopic finding: starry sky appearance
Management: chemotherapy and rasburicase due to high risk of tumour lysis syndrome
Multiple myeloma features
CRAABBI
Calcium raised (increased osteoclast activity -> constipation, nausea, anorexia, confusion)
Renal damage (due to immunoglobulin deposition -> dehydration, thirst)
Anaemia (BM crowding suppresses erythropoiesis -> fatigue and pallor)
Amyloidosis
Bleeding (BM crowding -> thrombocytopenia -> bleeding and bruising). May also get hyperviscosity.
Bone pain/fragility fractures (BM infiltration and osteoclast overactivity -> lytic bone lesions)
Infection (reduction in proliferation of normal immunoglobulins)
What is multiple myeloma and what is it’s incidence
Haematological malignant proliferation of plasma cells
Usually produces a monoclonal immunoglobulin (eg. IgA, IgG), a monoclonal light chain, or both (paraproteins)
Common in elderly (median age at presentation is 70)
Risk factors: older age, male, black african ethnicity, FHx, obesity
Investigations for myeloma
Consider myeloma in anyone >60 with persistent bone pain (esp back pain), or unexplained fractures
FBC (pancytopenia), calcium (raised), ESR (raised), U+E (high urea and creatinine due to kidney injury), plasma viscosity (raised)
Urgent serum protein electrophoresis shows monoclonal Ig protein band
Bone marrow aspiration and trephine biopsy (raised plasma cells)
Urine Bence-Jones protein test
Skeletal survery shows lytic ‘punched-out’ lesions
Management of myeloma
Chronic relapsing and remitting malignancy so management aims to control symptoms, reduce complications and prolong survival
In young, healthy patients: stem cell transplant and rigorous chemotherapy regimes, and 3-monthly monitoring
For others: chemo
Complications of multiple myeloma treatment and management of complications
Pain: analgesia
Pathological fractures: zolendronic acid (bisphosphonate)
Infection: annual flu vaccines and immunoglobulin replacement therapy
VTE prophylaxis
Fatigue
Types of myeloproliferative disorders
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia, Chronic myeloid leukaemia
Primary myelofibrosis
- what is it
- gene mutations
- typical presentation
- investigations
- management
- transformation
Hyperplasia of abnormal megakaryocytes -> platelet derived growth factor release -> BM fibrosis and haematopoiesis in liver and spleen
50% have JAK2 mutation
Presentation: elderly patient with anaemia symptoms
Massive splenomegaly
Hypermetabolic symptoms (weight loss, night sweats, fever, etc)
Investigations:
FBC (anaemia, high WCC, high PLT in early disease)
Blood film (tear-drop poikilocytes)
BM biopsy unobtainable (‘dry tap’) as it has turned into scar tissue- trephine biopsy needed
High urate and high LDH (increased cell turnover)
Mx: allogeneic stem cell transplant, chemo, splenectomy, supportive
May transform into acute myeloid leukaemia
Polycythaemia vera
- what is it
- genetic mutation
- age
- features
Myeloproliferative disorder caused by clonal proliferation of marrow stem cell -. increase in RBC volume, often accompanied by overproduction of neutrophils and platelets
JAK2 mutation in majority
Typically in 50yrs+
Features: hyperviscosity (headache, dizziness, tinnitus, visual disturbance, stroke, ischaemia, VTE), pruritus after a hot bath, splenomegaly, haemorrhage (due to abnormal platelets), plethora, HTN
Polycythaemia vera
- investigations
- management
- transformation
Ix: FBC and blood film (raised Hb, haematocrit, neutrophils, basophils, platelets) JAK2 mutation Serum ferritin U+Es, LFTs Low ESR BM biopsy shows hypercellularity with erythroid hyperplasia Reduced serum erythropoietin
Normal haematocrit: 0.48 (female), 0.52 (male)
Management:
Aspirin 75mg OD
Venesection (first line)
Hydroxyurea (may cause secondary leukaemia)
Phosphorous-32 chemotherapy
May transform to acute myeloid leukaemia or myelofibrosis
Essential thrombocythaemia
- what is it
- features
- ix
- mx
Clonal proliferation of megakaryocytes -> high platelets with abnormal function -> bleeding, arterial/venous thrombosis, microvascular occlusions
Ix: platelet count»_space;600, JAK2 in 50%
Mx: aspirin 75mg OD, hydroxyurea if high risk
Causes of thrombocytosis
Reactive thrombocytosis (raised platelets in response to infection, surgery, iron deficiency anaemia)
Malignancy
Essential thrombocythaemia
Hyposplenism
Causes of polycythaemia
Relative polycythaemia (reduce plasma volume, normal RBC mass - acute due to dehydration or chronic due to obesity and HTN)
Absolute polycythaemia:
Primary: polycythaemia vera
Secondary: hypoxia, chronic lung disease, cyanotic heart disease, increased erythropoietin
Types of thrombophilia
Antiphospholipid syndrome Antithrombin deficiency Protein C or S deficiency Factor V leiden etc
Antiphospholipid syndrome
- Features
- Diagnosis
- Mx
- Associated condition
Features: CLOTS
Coagulation defect, Livedo reticularis, Obstetric (recurrent miscarriage), Thrombocytopenia
Dx: persistent antiphospholipid antibodies with clinical features
Paradoxical rise in APTT
Mx: anticoagulation, and advice re pregnancy
Associated with SLE
Aplastic anaemia
- peak incidence
- features
- causes
- diagnosis
- management
Peak incidence = 30 years
Features: Normochromic, normocytic anaemia Leukopenia Thrombocytopenia (pancytopenia) Hypoplastic bone marrow, majority fat cells within BM Raised erythropoietin
Causes: Idiopathic Congenital (Fanconi anaemia) Drugs (cytotoxics, chloramphenicol, sulphonamides, phenytoin) Toxins (benzene) Infections (parvovirus, hepatitis) Radiation
Often diagnosed by excluding other marrow diseases
Mx: stop causative agent, supportive treatment (transfusions), BM transplant, immunosuppressive agents
Disseminated Intravascular Coagulation
- what happens
- causes
- features
- diagnosis
- management
Dysregulation between coagulation and fibrinolysis, release of tisue factor -> widespread clotting with resultant bleeding
Causes: sepsis, trauma, obstetric complications (amniotic fluid embolism, haemolysis, HELLP), malignancy
Features:
Haemorrhages (petechiae, ecchymoses, epistaxis, bleeding from mouth, vagina, urinary and GI tract, pituitary gland, liver, adrenals and brain)
Signs of widespread thrombi (digital gangrene, ARDS, stroke, renal failure)
Mild hypotension
Diagnosis: low platelets, prolonged APTT, prolonged PT, prolonged bleeding time, fibrin degradation products are often raised
Blood film shows schistocytes due to microangiopathic haemolytic anaemia
Management: remove cause (eg. deliver baby, stop drug), transfusion of blood, FFP, and platelet concentrations
Factor V leiden
- incidence
- mutation
- VTE risk
Commonest inherited thrombophilia
Mutation in the factor V leiden protein -> activated factor V (clotting factor) is inactivated 10 times more slowly than usual due to activated protein C resistance
Heterozygotes have a 4-5x increased risk of VTE, homozygotes have a 10x increased risk
Two types of BM transplant
- processes
- indications
- complications
Autologous: patients own stem cells. Patient is primed with G-CSF and chemo, patient’s own stem cells are harvested, pt is given high dose chemo, stem cells are reintroduced. Risk of reinfusing malignant cells. Indicated in relapsed Hodgkins, or in young patients with non-hodgkins or myeloma
Allogeneic: uses HLA-matched donor’s stem cells. Patient is given high dose chemo then infused with donor stem cells.
Complications of allogeneic: Infection due to immunosuppressive agents post transplant, cytomegalovirus (from donor), Graft vs. host disease
Graft-vs-host disease
- what is it
- cause
- two types
Multi-system complication of allogeneic BMT
T cells in the donor tissue mount an immune response towards the recipient’s cells
Severity is related to degree of HLA matching and number of donor T cells in the transplant
Acute GVHD: onset within 100 days of transplant, usually affects the skin, liver and GI tract, multi-system involvement carries worse prognosis
Chronic GVHD: may occur following acute disease, or arise on its own, >100 days after transplant, has a more varied clinical picture
Acute GVHD features
Painful maculopapular rash, may progress to erythroderma or TEN Jaundice Watery or bloody diarrhoea Persistent N+V Culture-negative fever
Chronic GVHD features
Poikiloderma, scleroderma, vitiligo, lichen planus
Keratoconjunctivitis sicca, corneal ulcers, scleritis
Dysphagia, odynophagia, oral ulcers, ileus
Obstructive or restrictive lung disease
Worse prognosis than acute
Investigations for GVHD
LFTs
Abdo USS
Lung function tests
Biopsy of affected tissue
Often clinical diagnosis
Management and prevention of GVHD
Mx: Immunosuppression and supportive measures
IV steroids, anti-TNF, etc
Prevention: prophylactic ciclosporin after transplantation (and/or MMF or methotrexate)
Graft vs leukaemia effect
The T cells within the graft have been shown to have a direct anti-tumour effect on the recipients cells, aiding in treatment of the malignancy
However the T cells also increase the risk of GVHD
Balance the risk of GVL effect and GVHD
