Haematology Flashcards
Leukaemias can be:
Myeloid (red cells, platelets, macrophages, neutrophils, eosinophils, monocytes etc.)
Lymphoid (B + T lymphocytes)
How do AML and ALL present?
How are they investigated?
How are they managed?
Presentation
- Generally in similar way:
- Marrow infiltration -> anaemia, thrombocytopenia, neutropenia
- Raised WCC -> leucostasis + microvasc occlusion (SOB, hypoxia, papilledema)
- Tissue infiltration: bone pain, hepatosplenomagaly, lymphadenopathy, CNS - headache, CN palsy
- Tumour lysis
- AML: elderly. Main risk = acutepromyelocytic anaemia –> coagulaopthy –> bleeding —> death (Need to do coag)
- ALL: children (ALL children get leukaemia)–> testicular enlargement, high risk CNS involvement
Investigations
- Full blood count
- Blood film - raised blast cells (immature precursors), Auer rods (AML)
- Marrow aspirate - >20% cells replaced w/ blast cells
- CSF - ? CNS involvement
- Coag - DIC (raised APPT + APT + low fibrinogen) - ? acute promyelocytic leukaemia
- Cytogenetics (helps determine prognosis + guide management)
Managment
- General supportive measures in both
- RBC + platelet transfusion
- FFP + cryoprecipitate (fibrinogen) transfusion
- Treat infection + give prophylaxis (bacteria, fungal, viral)
- AML
<60 + fit = chemo +/- stem cell transplant
>60 or unfit - palliative low dose chemo
(remission = no evidence Ca, cure = remission for 5 years)
- ALL
- once in remission give methorexate + CNS targetted therapy
How do CML and CLL present?
How are they investigated?
How are they managed?
CML
Presentation
- Age: 60-65yo
- Typically slow progression - anaemia, abdo discomfort (spleen), leucostasis - headache, priapism, retinal haemorrhage
- BUT can –> blast crisis w/ transformaiton to ALL, AML or myelofibrosis –> lymphadenopathy of chloroma (skin deposits)
Investigation
- Hb/platelets ok, raised WCC (>100)
- Marrow: neutrophilia + myeloid precursors (if blasts present = crisis)
- Genetics - philadelphia chromosome (t (9:22))
Management
- chronic - tyrosine kinase inhibitor
- blast crisis - stem cell transplant
CLL = old people, not really a problem
Presentation
- Often asymptomatic or inisidiou(as above)
- BUT can undergo Richter’s transformation –> B cell lymphoma
Investigations
Hb/plt ok, raised WCC
Film: lymphocytosis, no blasts, smudge cells (damaged lymphocytes)
Marrow: lymphocytes
Management
- 30% never need treatment.
- Treat if:
- marrow failure
- recurrent infection
- massive splenomegaly/lymphadenopathy
- doubling of lymphocytes in 6/12
- systemic features
- cytopenia or haemolytic anaemia
How does Hodgkin’s lymphoma present?
How is it staged and investigated?
How is it managed?
**Presentation **
- Painless cervical lymphadenopathy +/- B symptoms (worse prog if B sx present)
- B: night sweats, fever >38, weight loss
- In women -> cough
Investigations
- CXR (mediastinal widening)
- CT
- PET
- Marrow biopsy if stage III, IV or B sx
- Blood count/film
- Staging:
1- 1 node region or lymphoid structure involved
2 - 2 or more on same side of diaphragm
3- 2 or more on different sides of diaphragm
4 - extra-nodal organ/tissue involvement
**Treatment **
- Chemo:: ABVD regime
How might the following forms of non-hodgkins lymphoma present?
- Diffuse Large B cell lymphoma (most common)
- Follicular (2nd most common)
- Burkitt’s
- Lymphoplasmacytic
- Primary CNS lymphoma
- Primary gastric lymphoma/MALT
- Primary cutaneous lymphoma
Diffuse large B cell lymphoma
- Rapidly progressive. Painless cervical lymphadenopathy + B symptoms
- Tx: CHOP-R chemo (rituximab = R)
Follicular
- painless cervical lymphadenopathy. B symptoms rare (if present consider transformation to DLBCL)
- Tx: if well - monitor, if not radio/chemotherapy
Burkitt’s
= most rapidly proliferating lymphoma.
Can be Endemic (w/ EBV infection, typically involves maxilla/mandible) OR sporadic (more common in HIV)
Microscopy = starry sky appearance (lymphocyte sheets interspersed w/ macrophages containing dead tumour cells)
Good prognosis w/ chemo/rituximab
Needs rasburicase (high risk tumour lysis)
Lymphoplasmacytic
- Associated w/ IgM paraprotein + marrow infiltration + hyperviscosity
CNS lymphoma
- occurs in immunosupressed (eg post-transplant) - can treat by lowering the immunosupressant dose
Primary gastric/MALT
- H.pylori associated - if low grade can manage w/ H.pylori eradication
Cutaneous
e.g. sezary syndrome - dry scaly eczema OR generalsed erythema ->Can spread to blood
Or cutaneous B cell lymphoma
Tumours that are highly proliferative are at high risk of Tumour Lysis Syndrome when treatment is started.
Presentation
Investigation
Prevention
Management
Lab Values
- High: phosphate, K+, Uric acid
- Low: calcium
Presentation
- Typically in teens/young adults
- Chest pain, syncope, oliguria, arrhythmis, SOB, haematuria
- Low Ca -> weakness/cramps, seizures
- high K+ - arrhythmia
- Uric acid -> renal failure
Prevention
- raised LDH pre-treatment is risk factor
- Allopurinol (prevent new uric acid production)
- IV rasburicase (breaks down existing uric acid)
- Pre-hydration
Management
- ECG, LDH, U&E, Bone profile
- Hydration + diuretics (to maintain u/o)
- Rasburicase + uric acid
- Calcium gluconate (for low ca + high K)
- Insulin-dextrose
-Phosphate binders
If unresponsive to above–> dialysis
Myeloma
- Pathophysiology
- Presentation
- Investigation
- Management
Myeloma
Pathophysiology
Presentation
Investigation
Management
Pathophysiology
- Malignant disease of bone marrow plasma cells (B cells that produce immunoglobulins)
Presentation
- Can be asymptomatic (lab stuff, below)
- If symptomatic (evidence of end organ failure) (CRABBI):
- Hyercalcaemia (bone destruction)
- Renal impairment
- Anaemia (marrow infiltration)
- Bone lytic lesions
- Bleeding (thrombocytopenia)
- Infection (low normal immunoglobulins)
- Diagnostic criteria (one major + one minor OR 3 minor)
Major: plasmacytoma, 30% plasma in bone marrow, raised M protein in blood/urine
Minor: 10-30% plasma in BM, minor elevation of M protein, osteolytic lesions, low Ab
Investigation
- Serum protein electrophoresis: paraprotein (IgG or IgA) + immune paresis (reduction in all other Ig classes)
- Serum free light chain assay (abnormal Kappa:lamda - light chain restriction)
- Bone marrow: plasma cells >30%
- Whole body MRI (plasmacytom)
- X-rays: rain drop skull
N.B. possible differential of paraproteinaemia = MGUS - monitor as can progress to myeloma in 30%
Management
- Supportive/tx of complications
- chemo + stem cell transplant
Give possible causes of microcytic, normocytic and macrocytic anaemia
** Microcytic**
-TAILS
- Thallassaemia (A (lack of A chain, worse prog), B (lack of B chain, B trait = asymptomatic))
- Anaemia of chronic disease (altho normally normocytic)
- Iron Deficiency Anaemia (low iron/ferritin, raised TIBC)
- Lead poisoning
- Sideroblastic (enough iron but cannot use) OR spherocytosis
N.B. Polycythaemic rubra vera can cause microcytosis w/ normal Hb
Normocytic
- Anaemia of chronic disease (iron studies all low EXCEPT ferritin (raised)
- Haemolytic anaemia (autoimmune, marrow failure, transfusion reaction, infection, sickle cell, thalassaemia)
- CKD
- Aplastic anaemia
- Acute blood loss
- Sickle Cell
Macrocytic
FAT Red Blood Cells
F - folate deficiency + foetus (pregnancy)
A - alcohol
T - Thyroid (hypo)
R - reticulocytosis
B - B12 deficiency
C - cirrhosis/chronic liver disease
Give causes and treatment of the following types of anaemia
- Iron Deficiency
- Folate Deficiency
- B12 Deficiency
- Autoimmune Haemolytic Anaemia
Iron defieciency
- Causes: bleeding, reduced intake/absorption, increased requirement (pregnancy, growth spurt)
- Signs: koilonychia, glossitis, angular stomatitis
- Tx: manage cause + PO ferrous sulfate for 3/12 (check levels at 1/12, Hb should have increased by 20) Diet: meat, leafy green veg.
Folate deficiency
- Causes: pregnancy, reduced intake, phenytoin, alcohol, methotrexate
- Often co-exists w/ B12 def so check both
- General treatment: 4/12 of 5mg folic acid
- In pregnancy:
- All women 400mcg OD until 12/52
- High risk: 5mg OD pre-conception until 12/52
- (high risk: either partner, fam Hx or prev preg w/ NTD; on antiepileptics, obese, mum: thalassaemia, DM or coeliac)
B12 Deficiency
- Causes: pernicious anaemia, reduced intake/absorption
- Presentation -> peripheral neuropathy, cognitive change, headache, visual disturbance. If pernicious anaemia may have features of other autoimmune conditions.
- Refer gastro if think is pernicious anaemia (Anti-intrinsic factor antibodies)
- Treatment:
- If neuro features –> refer to haem
- If no neuro feature –> IM hydroxycobalamin injections
- Diet: eggs, cod/salmon, fortified foods, meat, milk/dairy
**Autoimmune Haemolytic Anaemia **
- General features of haemolytic anaemia: Reticulocytosis, Low haptoglobin, raised LDH, raised bilirubin. Film: spherocytes or reticulocytes
- Positive Coomb’s Test
- Warm haemolytic anaemia - common, IgG related, haemolysis extravascular (e.g. spleen) + at body temp
Causes: SLE, neoplasia (lymphoma, CLDD), methyldopa
Responds well to steroids
- Cold haemolytic anaemia - IgM related, intravasc, occurs at 4degrees –> Raynaud’s, acrocyanosis
Causes: Lymphoma, mycoplasma, EBV
Not so responsive to steroids
Sickle Cell Anaemia
Pathophysiology
Potential Crises
Management of Crises
Pathophysiology
- Autosomal recessive
- HbAS = sickle trait, HbSS = sickle cell anaemia
Potential Crises
- Can be triggered by: infection, low O2, dehydration
- Thrombotic (painful) –> infarcts in various organs + bone (avasc necrosis hip, hand-foot syndrome (severe pain/swelling), brain, lung, spleen)
- Sequestration (anaemia w/ raised reticulocytes)
- Aplastic (anaemia w/ low reticulocytes) - can be triggered by parvovirus
- Acute Chest syndrome - SOB, chest pain, pulmonary infiltrates on CXR, low O2
- Haemolytic (rare)
Management of Crises
- Manage cause: abx, IVI, O2
- Analgesia
- Blood transfusion if: severe/symptomatic anaemia, pregnant, pre-operative
- Exchange transfusion (to rapidly reduce % of HbS cells) in any acute vaso-occlusive crisis e.g. stroke, chest syndrome, multiorgan failure OR splenic sequestation
Myeloproliferative = proliferation of haematopoeitic cells. Increased cellular elements in blood BUT normal morphology.
The following are examples of myeloproliferative disorders (that have the potential to transform into each other). Describe each, including presentation, blood results and management.
- Aplastic Anaemia
- Essential Thrombocythaemia
- Polycythaemia
- Myelofibrosis
Aplastic Anaemia
Pancytopenia w/ decreased marrow cellularity (but no abnormal/cancerous cells)
Causes - idiopathic, fanconi anaemia, meds (abx, phenytoin, carbazapine, carbimazole)
Present- anaemia, bleeding, infection
Tx- supportive + treat cause +/- stem cell translant
Essential Thrombocythemia
Platelets >450 wo/reactive cause/haem malig
Present - incidental or thrombolitis or erythromelalgia (burning pain, erythema, warmth of feet/hands)
Tx - hydroxycarbamide
(can transform to PC, MF, AML)
Polycythaemia
Raised RBCs. Primary (rubra vera), Secondary (COPD, altitude, OSA, EPO), Relative (dehydration)
Present - Rubra Vera - insidious, >60yo, fatigue, pruritis (hot bath), visual disturbance, headache, palpable spleen, thromboses or haemorrhage
Lab 95% have JAK2 mutation
Tx - venesection, chemo
(can transform to myelofibrosis or AML)
Myelofibrosis
clonal proliferation of stem/myeloid cells in marrow, spleen + other organs -> marrow scarring
Present- insidious, fatigue, weakness, splenomeg, bone pain, bruising + bleeding
Lab - teardrop cells, anaemia, high or low plts, aspirate often unsuccessful, trephine shows increased fibrosis
Philadelphia chromosome to dx from CML
Tx - supportive, stem cell transplant
When is neutropenic sepsis diagnosed?
What is the treatment?
Diagnosis
- Neutrophils <0.5 in patient on chemo w/ one of the following
- Temp higher than 38C
- Other signs/symptoms consistent w/ sepsis
Prophylaxis
- If anticipated that pt will have neut <0.5 due to their tx then offer fluoroquinolone
Management
- Start abx immediately - Taxocin 1st
- If nil improvement then meropenem +/- vancomycin
- If not improving after 4-6d then assess for fungal infection eg. HRCT
- G-CSF in selected patients
What is mild, moderate and severe neutropenia?
What are possible causes of neutropenia?
Classification
Mild - 1-1.5
Mod - 0.5-1
Sev - <0.5
Causes
Viral: HIV, EBV, hepatitis, COVID
Drugs: cytotoxics, carbimazole, clozapine
Benign ethnic neutropenia (black/afro-carribean - no tx needed)
Haem malig - myelodysplastic, aplastic anaemia
Rheum - SLE, RA
Severe sepsis
Haemodialysis
Paroxysmal Nocturnal Haemoglobinuria
Pathophysiology
Presentation
Investigation
Management
Pathophysiology
- Acquired -> intravascular haemolysis + increased VTE risk
Presentation
- Haemolytic anaemia +/- low plts + WCC/ aplastic anaemia
- Haemoglobinuria (dark coloured urine, typically worse in mornign)
- Thrombosis e.g. budd chiari syndrome
Diagnosis
- Flow cytometry - low CD59 + CD55
- (Ham’s test - less used - acid-induced haemolysis (normal red cells would not)
Management
- Blood product replacement
- Anticoagulation
- Eculizumab (monoclonal antibody)
- Stem cell transplant
What are the different types of bleeding disorders and their general presentation/inheritance/management?
Haemophilia A + B
Pathophys - X-linked recessive, A(8) + B(9).
Presentation - haemarthroses, haematoma, prolonged bleed post traum/surgery
Ix- prolonged APTT BUT normal bleeding time, thrombin time + PT time
Tx- Factor 8/9 conc IV infusion
For mild A can give desmopressin
Von Willebrand’s Disease = most common inherited bleeding disorder
Pathophys - autosomal dominant.
Type 1 (partial reduction in vWF (most patients); 2 (abnormal form vWF); 3 (total lack - autosomal recessive)
Presentation - behaves like plt disorder (epistaxis, menorrhagia)
Ix - prolonged bleeding time, APTT long, factor VIII levels reduced, defective plt aggregation
Tx
- Tranexamic acid - mild bleeding
- Desmopressin (raises vWF levels)
- Factor VIII (often co-existent def)
