Haematology Flashcards
ITP definition?
Immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
ITP in children vs. adults?
- Children = acute post infection/vaccination
- Adults = chronic
ITP presentation?
- Incidentally following routine bloods
- Symptomatic = petechiae, purpura, bleeding, catastrophic bleeding uncommon
ITP Rx?
- Oral prednisolone
- IVIG (raises plts quickly, use if active bleeding or urgent invasive procedure)
- Splenectomy rarely
Evan’s syndrome?
ITP + AIHA
Blood product transfusion complications x5?
- Immune
- Infective
- TRALI
- TACO
- Other = hyperkalaemia, iron overload, clotting
Immunological transfusion reactions?
- Acute haemolytic
- Non-haemolytic febrile
- Allergic/anaphylaxis
Acute haemolytic reaction mushkies?
- ABO incompatible blood e.g. human error
- Fever, abdominal pain, hypotension
- Rx = stop transfusion, confirm Dx, send blood for Coombs, repeat typing and cross matching, supportive care with fluid resuscitation
Non-haemolytic febrile reaction mushkie?
- White blood cell HLA antibodies, often the result of sensitization by previous pregnancies or transfusions
- Fever, chills, red cells (1%), platelets (10-30%)
- Rx = slow or stop transfusion, paracetamol, monitor
Anaphylaxis reaction mushkies?
- Patients with IgA deficiency who have anti-IgA antibodies
- Stop transfusion, IM Adrenaline, ABC
Minor allergic reaction mushkies?
- Foreign plasma proteins
- Pruritis, urticaria
- Temporarily stop the transfusion, antihistamine, monitor
TACO mushkies?
- Excessive rate of transfusion, pre-existing heart failure
- Pulmonary oedema, hypertension
- Rx = Slow or stop the transfusion, consider loop diuretic and oxygen
TRALI mushkies?
- Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood, within 6 hours of transfusion
- Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension
- Rx = stop the transfusion, oxygen and supportive care
Differentiating between TACO and TRALI?
TACO = hypertension
Critical mediator of DIC?
TF (Tissue factor) = TF binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation
DIC causes?
- Sepsis
- Trauma
- Obstetric complications (amniotic fluid embolism, haemolysis, HELLP)
- Malignancy
DIC bloods Dx?
- Low platelets and fibrinogen
- Raised PT, APTT and fibrinogen degradation products
- Schistocytes due to MAHA
Warfarin clotting effect?
Prolonged PT
Aspirin clotting effect?
Prolonged bleeding time
Heparin clotting effect?
APTT prolonged (although PT ay be prolonged)
Warfarin antidote?
Vitamin K
Dabigatran antidote?
Idarucizumab
Heparin antidote?
Protamine sulphate
Dabigatran mushkies?
- MOA = direct thrombin inhibitor
- Excretion = majority renal
Rivaroxaban mushkies?
- MOA = direct factor Xa inhibitor
- Excretion = majority liver
- Antidote = andexanet alfa
Apixaban mushkies?
- MOA = direct factor Xa inhibitor
- Excretion = majority faecal
- Antidote = andexanet alfa
Edoxaban mushkies?
- MOA = direct factor Xa inhibitor
- Excretion = majority faecal
- Antidote = none
Sickle cell crises types x5?
- Thrombotic (painful)
- Sequestration
- Acute chest syndrome
- Aplastic
- Haemolytic
Sickle cell thrombotic crisis mushkies?
- AKA Painful/vaso-occlusive crises
- Precipitated by infection, dehydration, deoxygenation
- Clinical diagnosis
- Infarcts in various organs e.g. Hip AVN, hand-foot syndrome in children, lungs, spleen, brain
Sequestration crises mushkies?
- Sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
- Associated with an increased reticulocyte count
Acute chest syndrome mushkies?
- Vaso-occlusion within the pulmonary microvasculature → infarction in the lung parenchyma
- Fx = dyspnoea, chest pain, CXR pulmonary infiltrates, low pO2
- Rx = analgesia, oxygen, Abx, transfusion (improves oxygenation)
- Most common cause of death after childhood
Aplastic crisis mushkies?
- Parvovirus infection causes sudden fall in Hb
- Bone marrow suppression causes a reduced reticulocyte count
Sickle cell haemolytic crisis mushkies?
- Rare, fall in Hb due to increased rate of haemolysis
Microcytic anaemia causes?
TAILS
1. Thalassaemina
2. ACD
3. IDA
4. Lead poisoning
5. Sideroblastic anaemia
New onset microcytic anaemia in elderly pt Rx?
2ww
Microcytosis disproportionate to anaemia?
Beta thalassaemia minor
Most common inherited bleeding disorder?
Von Willebrand’s Disease
Von Willebrand’s Disease inheritance?
Usually AD
vWF role?
- Large glycoprotein which forms massive multimers
- Promotes platelet adhesion to damaged endothelium
- Carrier molecule for factor VIII
VWD Types?
- Type I = partial reduction of vWF (80%)
- Type II = abnormal form of vWF
- Type III = total lack of vWF (AR)
vWD clotting?
- Prolonged bleeding time
- APTT may be prolonged, Factor VIII levels may be moderately reduced
- Defective platelet aggregation with ristocetin
vWD Rx?
- Tranexamic acid for mild bleeding
- DDAVP = raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
- Factor VIII concentrate
What is PCC?
Concentrate of the four vitamin K dependents factors
Causes of massive splenomegaly?
- Haem = CML, myelofibrosis
- Infection = VL, Malaria
- Metabolic = Gaucher’s
CML pathophysiology?
Philadelphia chromosome in 95%. It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal
CML presentation?
- Splenomegaly
- Increase in granulocytes at different stages of maturation +/- thrombocytosis
- Decreased leukocyte alkaline phosphatase
- May undergo blast transformation (AML in 80%, ALL in 20%)
CML Rx?
- Imatinib 1st line = inhibitor of tyrosine kinase associated with BCR-ABL, very high response rate in chronic phase CML
- Hydroxyurea
- IFN-a
- Allogenic bone marrow transplant
Multiple myeloma definition?
A haematological malignancy characterised by plasma cell proliferation. It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells. MM is the second most common haematological malignancy.
Multiple myeloma features?
CRABBI
1. Calcium = hypercalcaemia due to increased osteoclast activity in bone
2. Renal = light chain deposition in renal tubules, causes renal damage
3. Anaemia
4. Bleeding
5. Bone pain and fractures
6. Infection
Multiple myeloma Ix?
- Bloods = anaemia, thrombocytopenia, raised urea and creatinine, raised calcium
- Peripheral blood film = Rouleaux
- Serum/urine protein electrophoresis = raised concentrations of monoclonal IgA/IgG proteins will be present in the serum. In the urine, they are known as Bence Jones proteins
- Bone marrow aspiration and trephine biopsy = confirms the diagnosis if the number of plasma cells is significantly raised
- Whole body MRI = Skeletal survey for bone lesions
Multiple myeloma X-ray finding?
Raindrop skull
Symptomatic multiple myeloma diagnosis?
- Monoclonal plasma cells in the bone marrow >10%
- Monoclonal protein within the serum or the urine (as determined by electrophoresis)
- Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures
Multiple myeloma prognosis?
A chronic relapsing and remitting malignancy which is currently deemed incurable. Management aims to control symptoms, reduce complications and prolong survival.
Multiple myeloma Rx?
Induction therapy
1. For patients who are suitable for autologous stem cell transplantation = Bortezomib + Dexamethasone (typically younger patients)
2. For patients who are unsuitable for autologous stem cell transplantation, induction therapy consists of Thalidomide + an Alkylating agent + Dexamethasone
Multiple myeloma Rx after induction?
- Monitored 3m with bloods and electrophoresis –> many will achieve remission and will not need further therapy for some time
- Many patients do relapse after initial therapy. If this occurs the 1st line recommended treatment is Bortezomib monotherapy. Some patients may also be suitable for a repeat autologous stem cell transplant but this is decided on a case-by-case basis
Multiple myeloma complications and management?
- Pain = analgesia
- Pathological fracture = Zoledronic acid
- Infection = Annual influenze vaccine, sometimes Ig replacement therapy
- VTE prophylaxis
- Fatigue = if symptoms persist then EPO
Sickle cell crisis general management?
- Analgesia e.g. opiates
- Rehydrate
- Oxygen
- Consider Abx if infection
- Blood transfusion = severe/symptomatic anaemia, pregnancy, pre-operative (+ do not rapidly reduce % of HbS containing cells)
- Exchange transfusion = indications include: acute vaso-occlusive crisis (stroke, acute chest syndrome, multiorgan failure, splenic sequestration crisis) (+rapidly reduce the percentage of HbS containing cells)
What blood product has the highest rate of bacterial contamination?
Platelet transfusions
Platelet transfusion for active bleeding?
- Offer platelet transfusions to patients with a platelet count of <30 x 10 9 with clinically significant bleeding
- Platelet thresholds for transfusion are higher (maximum < 100 x 10 9) for patients with severe bleeding (World Health organisation bleeding grades 3&4), or bleeding at critical sites, such as the CNS.
Platelet level aims before surgery/invasive procedure?
- > 50 for most
- 50-75 if high risk of bleeding
- > 100 if surgery at critical site
Platelet transfusion if no active bleeding or planned invasive procedure?
A threshold of 10 x 10^9 except where platelet transfusion is contradindicated or there are alternative treatments for their condition
Transfusion threshold for pts with ACS?
80, target 80-100
Transfusion threshold for pts without ACS?
79, target 70-90
Sickle cell definition?
An autosomal recessive condition that results for synthesis of an abnormal haemoglobin chain termed HbS. Sickle-cell anaemia is an autosomal recessive condition that results for synthesis of an abnormal haemoglobin chain termed HbS
Sickle cell anaemia presentation time?
Develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin
Hb SS pO2 at which they sickle?
5-6
Hb AS pO2 at which they sickle?
2.5-4
Sickle cell disease Ix?
Hb electrophoresis
Polycythaemia vera definition?
A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has a peak incidence in the sixth decade, with typical features including hyperviscosity, pruritus and splenomegaly
Polycythaemia vera management>
- Aspirin
- Venesection
- Chemotherapy = hydroxyurea, phosphorus-32 therapy
- Ruxolitinib
Polycthaemia vera prognosis?
- Thrombotic events significant cause of M&M
- 5-15% progress to myelofibrosis
- 5-15% progress to acute leukaemia
Haemophilia inheritance?
X-linked recessive
Haemophilia A deficiency?
Factor VIII
Haemophilia B deficiency?
Factor IX
Haemophilia features?
- Haemarthroses
- Haematomas
- Prolonged bleeding after surgery or trauma
Haemophilia clotting?
- Prolonged APTT
- Bleeding time, thrombin time, PT normal
Haemophilia A Factor VIII treatment complication?
Up to 10-15% develop Abs to Factor VIII treatment
Compression stockings to all pts with DVT?
No
Post-thrombotic syndrome mushkies?
Venous outflow obstruction and venous insufficiency after DVT result in chronic venous hypertension
1. Painful, heavy calves
2. Pruritis, sweating
3. Varicose veins, venous ulceration
Post-thrombotic syndrome Rx?
- Compression stockings
- Keep leg elevated
When should COCP be stopped before an operation?
4 weeks before, to reduce risk of PE
Most common inherited thrombophilia?
Factor V Leiden
Acquired cause of thrombophilia?
- Antiphospholipid syndrome
- COCP
Inherited causes of thrombophilia
- Gain of function polymorphisms
- Deficiencies of naturally occurring anticoagulants
Gain of function polymorphism thrombophilia causes?
- Factor V Leiden (Activated Protein C resistance) = most common cause
- Prothrombin gene mutation = 2nd most common cause
Deficiencies of naturally occurring anticoagulants thrombophilia causes?
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
Thrombophilia with greatest relative risk of VTE?
Antithrombin III deficiency
Pathophysiology of pregnancy DVT?
- Increase in factors VII, VIII, X and fibrinogen
- Decrease in Protein S
- Uterus presses on IVC causing venous stasis in legs
Pregnancy DVT Rx?
S/C LMWH
Neutropenia thresholds?
- Mild = <1.5
- Moderate = <1
- Severe = <0.5
Neutropenia causes?
- Viral = HIV, EBV, Hepatitis
- Drugs = cytotoxics, carbimazole, clozapine
- Benign ethnic neutropenia = Black African
- Haematological malignancy
- Rheum = SLE, RHA
- Sepsis, haemodialysis
Most common cause of recurrent tonsillitis in a young person?
Glandular fever
Laboratory tumour lysis syndrome Dx?
Cairo-Bishop scoring system: 2 or more of the following within 3 days before or 7 days after chemotherapy:
1. Raised uric acid, potassium, phosphate
2. Low calcium
Tumour lysis syndrome prophylaxis?
- Allopurinol
- Rasburicase
Clinical tumour lysis syndrome Dx?
Laboratory tumour laboratory syndrome + one of:
1. Increased serum creatinine
2. Cardiac arrhythmia or sudden death
3. Seizure
Who has the highest prevalence of IDA?
Preschool age children
IDA causes?
- Blood loss
- Inadequate dietary intake
- Poor intestinal absorption
- Increased iron requirements (children, pregnancy)
IDA nail change?
Koilonychia
IDA iron study?
- Low ferritin, low serum iron, low transferrin saturation
- Raised TIBC
IDA Blood films?
- Target cells
- Pencil cells
- Anisopoikilocytosis
IDA ferrous sulfate replacement duration?
Continue for 3m after correction in order to replenish iron stores
Ferrous sulphate s/e?
- Nausea, abdominal pain
- Constipation, diarrhoea
Iron rich diet?
- Dark-green leafy vegetables
- Meat
- Iron-fortified bread
Hereditary spherocytosis mushkies?
- AD defect of RBC cytoskeleton, RBC survival reduced as destroyed by spleen
- Most common hereditary haemolytic anaemia in people of northern European descent
Hereditary spherocytosis presentation?
- Failure to thrive
- Jaundice, gallstones
- Splenomegaly
- Aplastic crisis precipitated by parvovirus infection
- Degree of haemolysis variable
- MCHC elevated
Hereditary spherocytosis diagnosis?
- Clinical
- If equivocal, EMA binding test and cryohaemolysis test
- For atypical presentations, electrophoresis analysis of erythrocyte membranes
- Osmotic fragility test no longer recommended
Hereditary spherocytosis Rx?
- Acute = supportive, transfusion if necessary
- Longer term = folate replacement, splenectomy
G6PD mushkies?
- X-linked recessive, only affects males
- African + Mediterranean descent
- Neonatal jaundice, infection/drugs precipitate haemolysis, gallstones
- Blood film = Heinz bodies
- Test = G6PD enzyme activity
Heinz bodies?
G6PDD
Hereditary spherocytosis mushkies?
- AD (Male + Female)
- Northern European descent
- Neonatal jaundice, chronic symptoms with haemolytic crises precipitated by infection, gallstones, splenomegaly
- Spherocytes = round, lack of central pallor
- EMA binding test
Neutropenic sepsis definition?
Neutrophil < 0.5 in pt having anticancer treatment and has one of:
1. Temp > 38
2. Other S&S consistent with clinically significant sepsis
Neutropenic sepsis prophylaxis?
If anticipated that neut < 0.5 then offered fluoroquinolone
Neutropenic sepsis prophylaxis?
If anticipated that neut < 0.5 then offered fluoroquinolone
Neutropenic sepsis Rx?
- Tazocin immediately, dont wait for WBC
- If febrile and unwell after 48h then meropenem +/- vancomycin
- If not responding after 4-6 days –> Ix for fungal infection e.g. HRCT
- May be a role for G-CSF in selected patients
Most common form of acute leukaemia in adults?
AML
AML aetiology?
- Primary disorder
- Secondary transformation of a myeloproliferative disorder
AML poor prognostic features?
- > 60 y/o
- > 20% blasts after first course of chemo
- Cytogenetics = deletions of chromosome 5 or 7
Acute Promyelocytic Leukaemia M3 mushkies?
- t (15;17)
- Fusion of PML and RARA genes
- Presents younger than other types of AML (25 y/o on average)
- Auer rods (seen with myeloperoxidase stain)
- DIC or thrombocytopenia often at presentation
- Good prognosis
Polycythaemia causes?
- Relative
- Primary = PRV
- Secondary
Relative polycythaemia causes?
- Dehydration
- Stress: Gaisbock syndrome
Secondary polycythaemia causes?
- COPD
- Altitiude
- OSA
- Excessive EPO = cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids
How to differentiate between relative and true polycythaemia?
Red cell mass studies (elevated in ture)
How to differentiate between relative and true polycythaemia?
Red cell mass studies (elevated in ture)
CLL treatment agents?
Fludarabine and cyclophosphamide
Rituximab MOA?
mAB anti-CD20, a lymphocyte marker
Hodgkin’s lymphoma definition?
A malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades
4 types of Hodgkin’s lymphoma?
- Nodular sclerosing = most common (70%), women, lacunar cells
- Mixed cellularity = large number of Reed-Sternberg cells
- Lymphocyte predominant = best prognosis
- Lymphocyte depleted = rare, worst prognosis
Main poor prognosis markers in Hodgkin’s Lymphoma?
B symptoms = Weight loss >10% in 6m, Fever >38, night sweats
Beta thalassaemia trait definition?
- An autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia. It is usually asymptomatic.
- Microcytosis disproportionate to the anaemia
- HbA2 raised >3.5%
