Haematology Flashcards
Raised INR + warfarin
Any major bleeding:
- Stop warfarin
- IV vitamin K 5mg
- PTT
Minor bleeding:
- INR > 8.0
- Stop warfarin
- IV vitamin K 1-3mg
- INR 5.0-8.0
- Stop warfarin
- IV vitamin K 1-3mg
No bleeding:
- INR > 8.0
- Stop warfarin
- PO vitamin K 1-3mg
- INR 5.0-8.0
- Withhold 1-3 doses
Warfarin + heparin cover
Upon initiation of warfarin therapy, protein C production is reduced
This causes a temporary pro-coagulant state, requiring LMWH cover
Anticoagulant mechanisms
Streptokinase derivatives e.g. alteplase, duteplase
- Bind plasminogen activator to increase generation of plasmin and therefore fibrin degradation
A2PY antagonists e.g. clopidogrel
- Binds platelet A2PY ADP receptors and inhibits them
- Therefore inhibits platelet aggregation
Glycoprotein IIb/IIIa receptor antagonists e.g. tirofiban, eptifibatide
- Inhibits to prevent fibrinogen-to-platelet binding
Vitronectin receptor inhibition e.g. abciximab
- Binds the vitronectin receptor on platelets, smooth muscle, and endothelial cells
Antithrombin III activators e.g. heparin
- Activates ATIII to inactivate thrombin and other proteases
Vitamin K antagonists e.g. warfarin
- Competitive inhibition of vitamin K binding sites
- Inhibit synthesis of factors II, VII, IX, X and proteins C, S, Z
Factor Xa inhibitors e.g. rivaroxaban, apixaban, edoxaban
Direct thrombin inhibitors e.g. dabigatran
Hodgkin’s disease
Epidemiology:
- Bimodal - 20s, 60s
- Association with EBV
Classical (90%):
- Nodular sclerosing
- Most common
- Lymphocyte-rich
- Best prognosis
- Lymphocyte-deplete
- Mixed cellularity
Non-classical (10%):
- Nodular lymphocyte-predominant
Features:
- B symptoms
- Generalised lymphadenopathy
- Pain on drinking alcohol
Investigations:
- Bloods
- Imaging
- Lymph node biospy
- Classically see Reed-Sternberg cells (owl-eyes)
Complications
- Nephrotic syndrome
- minimal change disease
Haemophilia A
Factor VIII deficiency
- X-linked
- 1/5000 males
Features:
- Prolonged bleeding time
- Spontaneous deep bleeding - haemarthrosis, GI tract, cerebral
Classification:
- Mild (>5% activity)
- Moderate (1-5% activity)
- Severe (<1% activity)
- Present with spontaneous bleeding
Investigations:
- Prolonged APTT, normal PT
- Reduced factor VIII activity on assay, normal vWF
- Genetic testing
Management:
- Preventative
- Factor VIII injections (octocog alfa) ever 48h
- On-demand or pre-procedure
- Desmopressin
- Octocog alfa
Paroxysmal nocturnal haemoglobinuria (PNH)
Genetic condition leading to reduction in cell surface GPI on bone marrow-derived cells, impaired CD55 and CD59 presentation, and therefore inappropriate complement activation and lysis
- X-linked
- PIGA mutation
- Prevents anchoring of CD55/CD59
Features:
- Haemolytic anaemia
- Thrombocytopenia
- Intermittent haemoglobonuria
- Abdominal pain
- Renal dysfunction
- Silent thrombosis
Investigations:
- Bloods
- Haemolytic anaemia
- Thrombocytopenia
- Leucopenia
- Urine
- Haemoglobinuria
- Flow cytometry
- Poor CD55/CD59 expression
Management:
- Eculizumab
- C5 inhibitor
- Requires Abx prophylaxis
- Blood transfusion
- Stem cell transplant
Heparin-induced thrombocytopenia
Aetiology:
- Formation of anti-platelet factor 4 IgG
- A type II hypersensitivity response
- 5% of people exposed to heparin
- Most common with unfractionated heparin
Features:
- A 50% fall in platelet count beginning 5-14 days after initial exposure, or 2-3 days if has had previous exposure
- Thrombotic phenomena
- Haemorrhage (less common)
Management:
- Discontinuation of heparin
- Supplementary anticoagulation e.g. direct antithrombin inhibitors (argatroban)
Myelofibrosis
A chronic myeloproliferative disorder characterised by medullary fibrosis, extramedullary haematopoiesis, anaemia
- Associated with JAK2 mutation
- Presents in 60s
- Insidious onset
Features:
- Splenomegaly secondary to extramedullary haematopoiesis
- Fatigue
- Abdominal fullness
- Hepatomegaly
Investigations:
- Bloods
- Anaemia +/- thrombocytopenia
- Normal WCC
- Blood film
- Leukoerythroblastosis
- Teardrop poikilocytes
- BMAT
- Initially hypercellular, then fibrotic
Management:
- Symptomatic support
e.g. blood transfusion, hydroxyurea
Complications:
- Severe anaemia
- Splenic infarction
- Thrombocytopenia
- Severe bony pain
- Hyperuricaemia
Myelofibrosis - prognostic risk factors
DIPSS criteria
- Age > 65
- Hb < 10 g/dL
- Leucocyte count > 25 x 109 L
- Circulating blasts ≥1%
- Constitutional symptoms
- Requirement for RBC transfusion
- Platelets < 100 x 109 L
- Unfavourable karyotype
Chronic myeloid leukaemia
Malignancy resulting from BCR-ABL fusion oncogene (t 9;22)
3 phases
- chronic (asymptomatic)
- 3-10 years
- accelerated (progression)
- Gradual transformation into acute leukaemia
- 2-15 months
- blast crisis (acute progression)
- 3-6 months, inevitably fatal
- May not go through accelerated phase
Features:
- B symptoms
- Splenomegaly + LUQ discomfort
- Epistaxis
- Arthralgia
Investigations:
- Bloods
- High WCC, low RBCs, high or low PLT
- Elevated LDH, K+, uric acid
- Blood film
- High numbers of mature myeloid cells,
granulocyte left shift
- t(9;22) on cytogenetic analysis/FISH
- BMAT
- Granulocytic hyperplasia
Management:
- Tyrosine kinase inhibitors e.g. imatinib
- Allogenic stem cell therapy
Progression - 5-10% risk in first 2 years, then 10% risk for the following years
Chronic myeloid leukaemia - phase definitions
Chronic phase
- Minimal symptoms
- < 10% circulating blasts
Accelerated phase
- 10-19% circulating blasts
- 20% peripheral basophils
- Persistent thrombocytopenia/cytosis resistant to therapy
- Increasing splenomegaly and WCC resistant to therapy
- Cytogenetic evidence of clonal evolution
Blast crisis
- Blasts 20% of circulating WCC or nucleated bone marrow cells
- Extramedullary blast proliferation
- Large foci of blasts on bone marrow biopsy
Chronic lymphocytic leukaemia
Epidemiology:
- The most common leukaemia in the West
- Predominantly older adults (70+)
Pathophysiology:
- Monoclonal expansion of CD5+CD19+CD23+ B lymphocytes
- Poor prognosis associated with TP53, NOTCH1, ATM, BIRC3, SF3B1 mutations
Features:
- Often asymptomatic and diagnosed on routine blood tests
- B symptoms
- SOB, fatigue, pallor
- Splenomegaly
- Recurrent infections
- Autoimmune pathology e.g. AIHA, ITP
Investigations:
- Bloods
- Raised WCC with lymphocytosis > 5 x 109/L
- Anaemia and thrombocytopenia
- Blood film
- Smear cells
- Flow cytometry
- CD5+, CD19+, CD20+, CD23+
Management:
- Observation if early/asymptomatic
- Chemotherapy
- Fludarabine + cyclophosphamide + rituximab
- Allogenic stem cell transplant
- Esp. if have TP53 mutations
Complications:
- Hypogammaglobulinaemia
- Autoimmune haemolytic anaemia
- Immune thrombocytopenic purpura
- Richter transformation
Multiple myeloma
Malignancy of plasma cells, thought to evolve from MGUS
- MGUS - < 30g/L paraprotein, no organ
damage
- Myeloma - >30g/L paraprotein, >10% clonal
plasma cells in bone marrow, +/- symptoms
Features:
- Back pain - pathological fractures
- Hypercalcaemia - thirst, constipation, confusion
- Renal impairment - oligouria
- Normocytic anaemia - fatigue, pallor
- Weight loss
- Recurrent infections (functionally immunosuppressed)
- Hyperviscosity (esp. IgA disease)
Investigations:
- Bloods incl. FBC, U&Es, electrophoresis, serum free light chains, beta-2-microglobulin
- Imaging - XR for fractures, whole-body MRI
- Bone marrow biopsy
Management:
- Treatment only indicated where symptomatic with aim to slow disease and complications
- Autologous transplantation if tolerated
- Dexamethasone +/- bortezomib or
thalidomide or VAD
- Bone support via bisphosphonates
Alpha-thalassaemia
Reduced or absent production of alpha-globin chains
- Mutations in HBA1 or HBA2
Subtypes:
- 1 mutation - silent
- 2 mutations - alpha-thalassaemia minor
- 3 mutations - HbH disease
- 4 mutations - Hb Barts/hydrops fetalis (fatal)
Features:
- Minor:
- Asymptomatic or mild symptoms
- HbH:
- Anaemia - periodic haemolysis
- Jaundice
- Splenomegaly
- Growth restriction
Beta-thalassaemia
Reduced or absent production of beta-globin chains.
- Mutations in HBB
- Leads to accumulation and precipitation of
alpha-globin chains, damaging RBCs
Subtypes:
- 1 mutation - minor/trait
- 2 mutations - intermedia or major
Features:
- Trait:
- Microcytic anaemia
- Major:
- Anaemia - haemolysis and reduced production
- Jaundice
- Splenomegaly
- Growth restriction
Management:
- Major - RBC transfusion + iron chelation
- Intermedia - occasional transfusions e.g. during stress, pregnancy
Complications:
- Iron overload
IgA deficiency
Features:
- 90% asymptomatic
- Recurrent GI, respiratory, and sinus infections
- Increased frequency allergies and autoimmune disease
IgA deficiency
Features:
- 90% asymptomatic
- Recurrent sinus, respiratory, and GI infections
- Increased incidence of allergies and autoimmune disease
IgG2 deficiency
Features:
- Increased susceptibility to polysaccharide-coated bacteria e.g. Haemophilus
- Recurrent otitis media, respiratory tract
infections
- Absent response to pneumococcal vaccine
IgG3 deficiency
Features:
- Increased susceptibility to Moraxella catarrhalis
- Recurrent sinusitis
Waldenstrom’s macroglobulinaemia
A form of low-grade NHL characterised by B cell malignancy and IgM paraprotein
- Typically 60-70yr, M > F
Features:
- Anaemia
- Generalised muscle weakness
- Serum hyperviscosity - mucosal and retinal bleeding
- Purpura
- Hepatosplenomegaly
- Lymphadenopathy
- Peripheral neuropathy
- Headaches
Investigations:
- Normocytic anaemia
- Rouleaux formation
- Electrophoresis - IgM paraprotein band
- Bone marrow - hypercellularity, plasmacytosis
Management:
- Bendamustine-rituximab therapy +/- plasmapheresis
Complications:
- Cryoglobulinaemia
- Renal failure
- Pancytopenia
Amyloidosis
A group of diseases in which abnormal proteins (amyloid fibrils) build up in tissue and cause organ damage
Aetiology:
- AL
- light chains
- idiopathic or associated with myeloma etc.
- AA
- inflammation
- e.g. RA, IBD etc.
- Aβ2M
- dialysis-related
- Hereditary/old age
Features:
- Kidney deposition -> failure
- 20% AL, 50% AA develop ESRF
- Heart deposition
- cardiomyopathy, heart blocks, heart failure
- Gastrointestinal
- diarrhoea, malabsorption, jaundice, bleeding
- Other:
- Hypothyroidism
- Arthralgia
- Purpura
Management:
- Supportive
- Treat underlying cause
e.g. stem cell transplant for AL amyloidosis
Heyde syndrome
Triad of aortic stenosis, GI bleeding, and acquired von Willebrand syndrome
Pathophysiology:
- Shear stresses + increased velocity across stenotic aortic valve cause unfolding and activation of vWF
- Uses up vWF and so less is available for normal clot formation, in particular predisposing to GI bleeding
Management:
- Aortic valve replacement
Iron-deficiency anaemia
Screening:
- FBC - Hb low, microcytic
- Film - anisocytosis, poikilocytosis, hypochromia,
pencil cells
- Iron studies - low iron, low ferritin, high TIBC
and transferrin, low transferrin saturations
Diagnosis:
- FIT test +/- endoscopy
- Urine dip for haematuria
- Screen for nosebleeds, heavy periods, long-term NSAID/PPI use
Management:
- Oral iron
- Usually OD, sulphate or fumarate
- Aiming for Hb increase of 10 g/dL over 14
days
- IV iron
- If oral iron ineffective or not tolerated
Sideroblastic anaemia
Anaemia with presence of sideroblasts
- perinuclear halo of iron deposition due to
impaired incorporation into Hb
Aetiology:
- Congenital
- Usually X-linked deficiency in heme synthesis
- Acquired
- Myelodysplastic syndromes
- Copper or B12 deficiency
- Lead or Zinc overdose
- Alcohol
