Haematology Flashcards
What is anisocytosis
Variation in size of RBCW
Causes of anisocytosis
- Myelodysplastic syndrome
- Many types of anaemia, e.g. iron deficiency, pernicious, autoimmune haemolytic anaemia
What are target cells
RBC with central pigmented area surrounded by pale area, surrounded by ring of thicker cytoplasm on the outside
Causes of target cells
- Iron deficiency anaemia
- Post splenectomy
- Sickle cell/thalassaemia
- Liver disease
What are Heinz bodies
Individual blobs (inclusions) seen inside RBC - denatured haemoglobin
Causes of Heinz bodies
- G6PD deficiency
- Alpha thalassaemia
What are Howell-Jolly bodies
Individual blobs of DNA material seen inside RBC
Causes of Howell-Jolly bodies
- Splenectomy or non-functioning spleen
- Severe anaemia
What are reticulocytes
Immature RBC - larger than normal RBC, and still have RNA material in them
Cause of high retic %
Rapid turnover of RBC, e.g. haemolytic anaemia
What are schistocytes
Fragments of RBC
Causes of schistocytes
- Microangiopathic haemolytic anaemia (small blood clots obstruct small blood vessels)
- Metallic heart valve replacement
Causes of microangiopathic haemolytic anaemia
- Haemolytic uraemic syndrome
- Disseminated intravascular coagulation
- Thrombotic thrombocytopenic purpura
What are sideroblasts
Immature red blood cells with a nucleus surrounded by iron blobs, seen in sideroblastic anaemia
What is sideroblastic anaemia
When bone marrow cannot incorporate iron into the haemoglobin molecules
Causes of sideroblastic anaemia
- Genetic defect
- Myelodysplastic syndrome
What are smudge cells?
Ruptured WBC, occur when preparing blood film when cells are aged or fragile
Causes of smudge cells
Chronic lymphocytic leukaemiaW
What are spherocytes
Sphere shaped red blood cells without bi-concave disk shape
Causes of spherocytes
Autoimmune haemolytic anaemia
Hereditary spherocytosis
Causes of tear drop poikilocytes
Myelofibrosis
Causes of basophilic stippling
- Lead poisoning
- Thalassaemia
- Sideroblastic anaemia
- Myelodysplasia
Causes of pencil poikilocytes
Iron deficiency anaemia
Causes of Burr cells (echinocytes)
Uraemia
Pyruvate kinase deficiency
Causes of acanthocytes
Abetalipoproteinaemia
Causes of hypersegmented neutrophils
Megaloblastic anaemia
Causes of microcytic anaemia
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemiaC
Causes of normocytic anaemia
Acute blood loss
Anaemia of chronic disease
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism
Causes of megaloblastic macrocytic anaemia
B12 deficiency
Folate deficiency
Most common acute leukaemia in adults
AML
Features antiphospholipid syndrome
- Predisposition to arterial and venous thromboses
- Recurrent fetal loss
- Thrombocytopenia
Most common condition antiphospholipid syndrome occurs secondary to
SLE
Complications antiphospholipid syndrome in pregnancy
Recurrent miscarriage
IUGR
Pre-eclampsia
Placental abruption
Pre-term delivery
VTE
Management antiphospholipid syndrome in pregnancy
Low dose aspirin once pregnancy confirmed on urine testing
LMWH once fetal heart seen on USS, discontined at 34 weeks
Investigation findings haemolytic anaemia
Anaemia
Reticulocytosis
Low haptoglobin
Raised LDH and indirect bili
Spherocytes and reticulocytes on blood film
Investigation findings specific to autoimmune haemolyic anaemia
Positive direct antiglobulin test (Coombs’ test)
Where does haemolysis occur warm AIHA
Extravascular sites, e.g. spleen
Causes warm AIHA
Idioapthic
Autoimmune disease, e.g. SLE
Neoplasia - lymphoma, CLL
Drugs, e.g. metyldopa
Management warm AIHA
Treatment of underlying disease
Steroids +/- rituximab
What temp does warm AIHA occur best at
Body temp
What temp does cold AIHA occur best at
4 c
What antibody usually involved in warm AIHA
IgG
What antibody usually involved in cold AIHA
IgM
Where does haemolysis occur in cold AIHA
Intravascular
Features cold AIHA
Symptoms of Raynaud’s and acrocyanosis
Causes cold AIHA
Neoplasia, e.g. lymphoma
Infections, e.g. mycoplasma, EBV
Presentation beta thalassaemia major
Presents in first year of life
Failure to thrive
Hepatosplenomegaly
Blood results beta thalassaemia major
Microcytic anaemia
HbA2 and HbF raised
HbB absent
Management beta thalassaemia major
Repeat transfusion
Prevention of iron overload caused by repeated transfusion in beta thalassaemia major
Iron chelation, e.g. desferrioxamine
Typical blood film hyposplenism
Howell-Jolly bodies
Pappenheimer bodies
Siderotic granules
Acanthocytes
Typical blood film iron deficiency anaemia
Target cells
Pencil poikilocytes
Blood film iron deficiency anaemia combined with B12/folate deficiency
Dimorphic film - mixed microcytic and macrocytic cells
Typical blood film myelofibrosis
Tear drop poikilocytes
Typical blood film intravascular haemolysis
Schistocytes
Typical blood film megaloblastic anaemia
Hypersegmented neutrophils
Features non-haemolytic febrile reaction to blood transfusion
Fever
Chills
Management non-haemolytic febrile reaction to transfusion
Slow or stop transfusion
Paracetamol
Monitor
Features minor allergic reaction to blood transfusion
Pruritis
Urticaria
Management minor allergic reaction to blood transfusion
Temporarily stop transfusion
Antihistamine
Monitor
Features anaphylaxis to blood transfusion
Hypotension
Dyspnoea
Wheezing
Angioedema
Management anaphylaxis blood transfusion
Stop transfusion
IM adrenaline
ABC
Features acute haemolytic reaction to blood transfusion
Fever
Chest and abdominal pain
Hypotension
Agitation
Management acute haemolytic reaction to transfusion
Stop transfusion
Confirm diagnosis - check matching details, send blood for direct Coombs, repeat typing and x match
Supportive care - fluid resus
Complications acute haemolytic transfusion reaction
Disseminated intravascular coagulation
Renal failure
Features transfusion associated circulatory overload
Pulmonary oedema
Hyertension
Treatment transfusion associated circulatory overload
Slow or stop transfusion
Consider IV loop diuretic and oxygen
What is transfusion related acute lung injury
Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
Features transfusion related acute lung injury
Hypoxia
Pulmonary infiltrates on CXR
Fever
Hypotension
Symptoms develop within 6 hours of transfusion
Management transfusion related acute lung injury
Stop transfusion
Oxygen and supportive care
Antibody involved in acute haemolytic transfusion reaction
IgM
What kind of pathogens are RBC most at risk of transmitting
Viral - HIV, HBV, HCV
What kind of pathogens platelets most at risk of transmitted
Bacteria (stored at room temp, increasing risk of bacterial proliferation)
Most common bacterial contaminants platelets
Staphylococcus epidermidis
Bacillus cereus
Measures taken to reduce risk of vCJD transmission from blood transfusion
All donations undergone removal of white cells to reduce any vCJD infectivity
Plasma derivatives have been fractionated from imported plasma rather than being sourced from UK donors
Recipients of blood components excluded from donating blood
Use of packed red cells
- Chronic anaemia
- Cases where infusion of large volumes of fluid may result in cardiovascular compromise
Use of platelet rich pplasma
Thrombocytopaenia and bleeding or requiring surgery
Use of platelet concentrate
Thrombocytopenia
What does FFP contain
Clotting factors
Albumin
Immunoglobulin
How much is unit of FFP
200-250ml
Dose FFP
12-15ml/kg
Use FFP
- Clinically significant but not major haemorrhage in patients with prothrombin time ratio or APTT ratio of >1.5
- Prophylaxis in patients undergoing major surgery with risk of significant bleeding
Universal donor FFP
AB (lacks any anti-A or anti-B antibodies)
What does cryoprecipitate contain
Concentrated factor VIII, von Willebrand factor, fibrinogen, factor XIII, and fibronectin
Use cryoprecipitate
-Patients with clinically significant but not major haemorrhage and fibrinogen concentration <1.5g/L
E.g.;
DIC
Liver failure
Hypofibrinogenaemia secondary to massive transfusion
- Prophylaxis in patients undergoing invasive surgery where risk of significant bleeding and fibrinogen <1.0
- von Willebrand disease
- Emergency treatment haemophiliacs when specific factors not available
What is SAG-mannitol blood
Blood with all plasma removed and replaced with a solution of;
- Sodium chloride
- Adenine
- Anhydrous glucose
- Mannitol
How much SAG-M blood can be given
4 units
Which blood components must be cross matched
Packed red cells
FFP
Cryoprecipitate
Whole blood
Which blood componenets can be ABO incompatible in adults
Platelets
Use of cell saver devices
Avoid the use of infusion of blood from donors into patients, e.g. Jehovah’s witnesses
May reduce risk of blood borne infection
Contraindication cell saver devices
Malignant disease (may facilitate dissemination)
How long does IV vitamin K take to reverse warfarin
4-6 hours
How long does oral vitamin K take to reverse warfarin
24 hours
Dose of FFP in warfarin reversal
30ml/kg
Limitations of FFP
Need to give at least 1L fluid in 70kg person - not appropriate in fluid overload
Need blood group
Only use if human prothrombin complex not available
How long does human prothrombin complex take to reverse warfarin
1 hour
Limitation human prothrombin complex
Short half life - give with vitamin K
Purpose of irradiated blood
Depleted of T lymphocytes - avoid transfusion-associated graft versus host disease caused by engraftment of viable donor T lymphocytes
Requirements CMV negative blood
Granulocyte transfusions
Intra-uterine transfusions
Neonates up to 28 days post EDD
Elective transfusions during pregnancy (not during labour or delivery)
Requirements irradiated blood
Granulocyte transfusions
Intra-uterine transfusions
Neonates up to 28 days EDD
Bone marrow/stem cell transplants
Immunocompromised, e.g. chemo, congenital
Current or previous Hodgkin’s lymphoma
Hb transfusion threshold
70g/L
80g/L if ACS
Hb target after transfusion
70-90g/L
80-100g/L in ACS
What is Burkitt’s lymphoma
High grade B cell neoplasm
Major forms Burkitts’ lymphoma
Endemic form
Sporadic form
Where does endemic form Burkitt’s lymphoma typically involve
Maxilla or mandibleW
Where does sporadic form Burkitt’s lymphoma affect
Abdominal (ileo-caecal)
Risk factors sporadic Burkitt’s lymphoma
HIV
What is associated with the development of endemic form Burkitt’s lymphoma
EBV
Microscopy findings Burkitt’s lymphoma
‘Starry sky’ appearance - lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
Management Burkitt’s lymphoma
Chemotherapy
Complication chemo in Burkitt’s lymphoma
Tumour lysis syndrome
Prevention of tumour lysis syndrome in Burkitt’s lymphoma
Rasburicase given before chemo
Complications tumour lysis syndrome
- Hyperkalaemia
- Hyperphosphataemia
- Hypocalcaemia
- Hyperuricaemia
- Acute renal failure
Most common leukaemia in adults
CLL
Complications chronic lymphocytic leukaemia
Anaemia
Hypogammaglobulinaemia → recurrent infections
Warm autoimmune haemolytic anaemia
Richter’s transformation
What is Richter’s transformation
When leukaemia cells enter the lymph node and change into high grade fast growing non-Hodgkins lymphoma
Symptoms Richter’s transformation
Lymph node swelling
Fever without infection
Weight loss
Night sweats
Nausea
Abdominal pain
Pathophysiology CLL
Monoclonal proliferation of well-differentiated lymphocytes, almost always B-cells
Presentation CLL
Often asymptomatic, picked up with incidental finding of lymphocytosis
Constitutional - anorexia, weight loss
Bleeding
Infections
Lymphadenopathy
FBC CLL
Lymphocytosis
Anaemia (due to marrow replacement or AIHA)
Thrombocytopenia (due to marrow replacement or ITP)
Blood film CLL
Smudge cells
Key investigation CLL
Immunophenotyping
Genetics CML
Philadelphia chromosome present in more than 95% of patients
What is Philadelphia chromosome
Translocation between long arm of chromosome 9 and 22
Presentation CML
Anaemia - lethargy
Weight loss
Swelling
Splenomegaly → abdo discomfort
Blood film CML
Increase in granulocytes at different stages of maturation +/- thrombocytosis
May undergo blast transformation
First line treatment CML
Imatinib
Other treatments CML
Hydroxyurea
Interferon alpha
Allogenic BMT
What is cryoglobulinaemia
Presence of immunoglobulins which undergo reversible precipitation at 4 degrees C and dissolve when warmed to 37
Antibodies type I cryoglobulinaemia
Monoclonal - IgG, IgM
Associations type I cryoglobulinaemia
Multiple myeloma
Waldenstrom macroglobulinaemia
Antibodies type II cryoglobulinaemia
Mixed monoclonal and polyclonal, usually with rheumatoid factor
Associations type II cryoglobulinaemia
Hepatitis C
Rheumatoid arthritis
Sjorgen’s
Lymphoma
Antibodies type III cryoglobulinaemia
Polyclonal, usually with rheumatoid factor
Associations type III cryoglobulinaemia
Rheumatoid arthritis
Sjorgen’s
Presentation cryoglobulinaemia
Vascular purpura
Distal ulceration
Arthralgia
Diffuse glomerulonephritis
Raynaud’s in type I
Investigation findings cryoglobulinaemia
Low complement, esp C4
High ESR
Management cryoglobulinaemia
Treatment of underlying condition
Immunosuppression
Plasmapheresis
Use DOACs
Prevention of stroke in non-valvular AF
Prevention of VTE following hip/knee surgery
Treatment of DVT and PE
Reversal agent dabigatran
Idarucizumab
Reversal agent rivaroxiban
Andexanet alfa
Reversal agent apixaban
Andexanet alfa
Reversal agent edoxaban
No authorised reversal agent
Coag results DIC
Low platelets
Low fibrinogen
High PT and APTT
High fibrinogen degradation products
Coag results warfarin
Prothrombin time increased
APTT normal
Bleeding time normal
Platelet count normal
Coag results aspirin
Prothrombin time normal
APTT normal
Bleeding time prolonged
Platelet count normal
Coag results heparin
Prothrombin time often normal, may be prolonged
APTT prolonged
Bleeding time normal
Platelet count normal
What is factor V leiden
Inherited thrombophilia - gain of function mutation of factor V leiden protein → activated factor V is inactivated 10x more slowly by activated protein C than normal
Inheritance G6PD deficiency
X-linked recessive
Factors precipitating crisis in G6PD deficiency
Drugs
Fava beans
Drugs precipitating crisis in G6PD deficiency
Anti-malarials - primaquine
Ciprofloxacin
Sulph- group drugs - sulphonamides, sulphasalazine, sulfonylureas
Features G6PD deficiency
Neonatal jaundice
Intravascular haemolysis
Gallstones
Splenomegaly
Blood film G6PD deficiency
Heinz bodies
Bite and blister cells
Diagnosis G6PD deficiency
G6PD enzyme assay
When should G6PD deficiency assay be performed for the diagnosis of G6PD deficiency
Around 3 months after acute episode of haemolysis, otherwise may get false negative results
Ethnicity G6PD deficiency
African
Mediterranean
Inheritance haemophilia
X-linked recessive
Cause haemophilia A
Deficiency factor VIII
Cause haemophilia B
Deficiency factor IX
Features haemophilia
Haemoarthroses
Haematomas
Prolonged bleeding after surgery or trauma
Blood results haemophilia
Prolonged APTT
Bleeding time, thrombin time, prothrombin time normal
Inheritance hereditary angioedema
Autosomal dominant
What is hereditary angioedema
Low plasma levels of C1 inhibitor protein → uncontrolled release of bradykinin → oedema of tissues
Presentation hereditary angioedema
Attacks may be preceded by painful macular rash
Painless, non-pruritic swelling of subcutaneous/submucosal tissues
May affect upper airways, skin, or abdominal organs (can present as abdo pain)
Acute management hereditary angioedema
IV C1-inhibitor concentrate
FFP if this is not available
Prophylaxis hereditary angioedema
Danazol (anabolic steroid)
Investigation findings hereditary angioedema
C1-INH level low during attach
Low C2 and C4 levels seen, even between attacks
Inheritance hereditary spherocytosis
Autosomal dominant
Presentation hereditary spherocytosis
- Failure to thrive
- Jaundice, gallstones
- Splenomegaly
- Aplastic crisis precipitated by parvovirus infection
Bloods hereditary spherocytosis
MCHC elevated
Spherocytes
Increase in reticulocytes
Diagnosis hereditary spherocytosis
If family history of HS, typical clinical features, and lab investigations, do not need any other tests
If diagnosis equivocal, EMA binding test and cryohaemolysis test
For atypical presentations, electrophoresis analysis of erythrocyte membranes
Management acute haemolytic crisis in hereditary spherocytosis
Treatment usually supportive
Transfusion if necessary
Longer term treatment hereditary spherocytosis
- Folate replacement
- Splenectomy
Ethnicity hereditary spherocytosis
Northern European
What is Hodgkin’s lymphoma
Malignant proliferation of lymphocytes characterised by presence of Reed-Sternberg cells
Best prognosis Hodgkins lymphoma subtype
Lymphocyte predominant
Worst prognosis Hodgkin’s lymphoma subtype
Lymphocyte depletedM
Most common Hodgkin’s lymphoma subtype
Nodular sclerosing
Cells associated with nodular sclerosing Hodgkin’s lymphoma
Lacunar cells
Cells associated with mixed cellularity Hodgkin’s lymphoma
Large number of Reed-Sternberg cells
B symptoms in Hodgkin’s lymphoma
Weight loss >10% in last 6 months
Fever >38
Night sweats
Factors associated with poor prognosis Hodgkin’s lymphoma
B symptoms
Age >45
Stage IV
Haemoglobin <10.5
Lymphocyte count <600
Male
Albumin <40
WCC >15
Staging system Hodgkin’s lymphoma
Lugano classification
Management Hodgkin’s lymphoma
Chemo (mainstay) +/- radiotherapy
Haematopoietic cell transplantation - may be used for relapsed or refractory classic Hodgkin lymphoma
ITP in children vs adults
In children, acute thrombocytopenia may follow infection or vaccination
Adults tend to have more chronic condition
Presentation ITP
May be incidental following routine bloods
- Petechiae, purpura
- Bleeding
Catastrophic bleeding e.g. intracranial is uncommon
First line treatment ITP
Oral prednisolone
Treatment ITP in active bleeding/needs urgent procedure
Pooled normal human immunoglobulin
What is Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia
Main causes iron deficiency anaemia
Excessive blood loss
Inadequate dietary intake
Poor intestinal absorption
Increased iron requirements
Features iron deficiency anaemia
Fatigue
SOBOE
Palpitations
Pallor
Nail changes - koilonychia
Hair loss
Atrophic glossitis
Post-cricoid webs
Angular stomatitis
FBC IDA
Hypochromic microcytic anaemia
Ferritin IDA
Low
Can be falsely normal/high if co-existing inflammation as is acute phase reactant
TIBC/transferrin IDA
High
Transferrin saturation will be low
Blood film IDA
Anisopoikilocytosis (RBC different sizes and shapes)
Target cells
Pencil poikilocytes
Hb cut offs for endoscopy investigation within 2 weeks
Post-menopausal women ≤10
Men ≤11
Management IDA
Oral ferrous sulphate - continue for 3 months after iron deficiency corrected to replenish stores
SEs iron supps
Nausea
Abdominal pain
Constipation/diarrhoea
Features lead poisoning
Abdominal pain
Peripheral neuropathy, mainly motor
Neuropsychiatric features
Fatigue
Constipation
Blue lines on gum margin
Lead levels in blood considered significant
> 10mcg/dl
FBC lead poisioning
Microcytic anaemia
Blood film lead poisioning
Red cell abnormalities, inc basophilic stippling and clover-leaf morphology
Management lead poisoning
Various chelating agents;
- DMSA
- D-penicillamine
- EDTA
- Dimercaprol
Megaloblastic causes of macrocytic anaemia
- Vitamin B12 deficiency
- Folate deficiency
Normoblastic causes of macrocytic anaemia
- Alcohol
- Liver disease
- Hypothyroidism
- Pregnancy
- Reticulocytosis
- Myelodysplasia
- Cytotoxics
Causes microcytic anaemia
- Iron deficiency anaemia
- Thalassaemia
- Congenital sideroblastic anaemia
- Anaemia of chronic disease (but more common normocytic)
- Lead poisoning
Causes normal haemoglobin with microcytosis
- Thalassaemia
- Polycythaemia rubra vera
Types of monoclonal gammopathy of undetermined significance
Non-IgM MGUS
IgM MGUS
Light chain MGUS
Non-IgM MGUS may progress too…
Multiple myeloma
AL amyloidosis
IgM MGUS may progress too…
Waldenstrom macroglobulinaemia
Lymphoma
Light chain MGUS may progress too…
Renal disease
AL amyloidosis
Features MGUS
Usually asymptomatic
10-30% have demyelinating neuropathy
MGUS vs myeloma
MGUS has:
- Normal immune function
- Normal beta-2 microglobulin levels
- Lower level of paraproteinaemia than myeloma (<30g/L IgG or <20g/L IgA)
- Stable level of paraproteinaemia
- No clinical features of myeloma, e.g. lytic lesions, renal disease
What is myelofibrosis
A myeloproliferative disorder caused by hyperplasia of abnormal megakaryocytes → stimulation of fibroblasts → fibrosis of bone marrow
Where does haematopoiesis occur in myelofibrosis
Liver and spleen
Presentation myelofibrosis
- Anaemia
- Massive splenomegaly
- Hypermetabolic symptoms - weight loss, night sweats
FBC myelofibrosis
Anaemia
High WCC and platelets early in disease
Film myelofibrosis
Tear drop poikilocytes
Bone marrow biopsy myelofibrosis
Unobtainable - dry tap - trephine biopsy needed
Other blood tests myelofibrosis
High urate
High LDH
What is multiple myeloma
Haematological malignancy characterised by plasma cell proliferation
Features multiple myeloma
- Hypercalcaemia
- Renal damage - dehydration and increased thirst
- Anaemia
- Bleeding (thrombocytopenia)
- Bone pain and pathological fractures
- Increased risk of infection
- Amyloidosis
- Carpal tunnel syndrome
- Neuropathy
- Hyperviscosity
Causes renal impairment in myeloma
- Monoclonal production of immunoglobulins → light chain depositions within renal tubules
- Amyloidosis
- Nephrocalcinosis
- Nephrolithiasis
Where is bone pain most common in myeloma
Back
Blood film myeloma
Rouleaux formation
Protein electrophoresis findings myeloma
Raised concentrations of monoclonal IgA/IgG proteins
X-ray findings myeloma
Rain drop skull
Diagnostic criteria multiple myeloma
One major + one minor, or 3 minor with signs/symptoms
Major:
- Plasmacytoma
- 30% plasma cells in bone marrow sample
- Elevated levels of M protein in blood or urine
Minor:
- 10-30% plasma cells in bone marrow sample
- Minor elevations in level of M protein in blood or urine
- Osteolytic lesions
- Low levels of antibodies in the blood
Viral causes neutropenia
HIV
EBV
Hepatitis
Drug causes neutropenia
Cytotoxics
Carbimazole
Clozapine
Other causes neutropenia
Benign ethnic neutropenia
Haematological malignancy - myelodysplastic malignancies, aplastic anaemia
Rheumatological conditions
SLE
Rheumatoid arthritis
Severe sepsis
Haemodialysis
Timeline neutropenic sepsis
Most commonly occurs 7-14 days after chemo
Diagnostic criteria neutropenic sepsis
Neuts <0.5 in patient having anti-cancer therapy and:
- Temp >38 or
- Other signs/symptoms consistent with clinically significant sepsis
Most common bacteria causing neutropenic sepsis
Coag negative, gram +ve bacteria, particularly staph epidermidis
Prophylaxis neutropenic sepsis
If anticipated that patients likely to have neutrophil count <0.5, should be offered a flouroquinolone
First line antibiotics neutropenic sepsis
Tazocin.
Management neutropenic sepsis if still febrile and unwell after 48h IV Abx
Meropenum +/- vanc
Management neutropenic sepsis ongoing after 4-6 days IV Abx
Fungal infection investigations, e.g. HRCT
Causes normocytic anaemia
Anaemia of chronic disease
Chronic kidney disease
Aplastic anaemia
Haemolytic anaemia
Acute blood loss
What is paraproteinaemia
A haematological condition characterised by abnormal overproduction of a single type of immunoglobulin or immunoglobulin fragment
Causes of benign paraproteinaemia
Monoclonal gammopathy of undetermined significance
Transient paraproteinaemia, e.g. following infection
Causes of malignant paraproteinaemias
- Multiple myeloma
- Waldenstrom macroglobulinaemia
- Primary amyloidosis
- B-cell lymphoproliferative disorders, e.g. CLL, non-Hodgkin lymphoma
Clinical features paraproteinaemia
- Hyperviscosity syndrome
- Neuropathy, e.g. sensory, motor, or autonomic dysfunction
- Renal dysfunction
- Haematologic abnormalities, e.g. anaemia, thrombocytopenia, leukopenia
What is paroxysmal noctural haemoglobinuria
An acquired disorder leading to haemolysis (mainly intravascular) of haematological cells
Features paroxysmal noctural haemoglobinuria
- Haemolytic anaemia
- RBC, WBC, platelets, or stem cells may be affected - can be pancytopenia
- Haemoglobinuria
- Thrombosis
- Aplastic anaemia in some patients
Diagnostic test paroxysmal noctural haemoglobinuria
Flow cytometry of blood to detect low levels of CD59 and CD55
Management paroxysmal noctural haemoglobinuria
Blood product replacement
Anticoagulation
Eculizumab
Stem cell transplant
Platelet threshold for transfusion pre-surgery/invasive procedure
> 50 for most patients
50-75 if high risk of bleeding
100 if at critical site, e.g. CNS
Platelet threshold for transfusion if no active bleeding
10
Conditions contraindicating platelet transfusion
- Chronic bone marrow failure
- Autoimmune thrombocytopenia
- Heparin induced thrombocytopenia
- Thrombotic thrombocytopenic purpura
Platelet threshold for transfusion clinically significant bleeding
<30
Lower threshold if severe bleeding or bleeding at critical sites, e.g. CNS
Causes relative polycythaemia
Dehydration
Stress - Gaisbock syndrome
Causes primary polycythaemia
Polycythaemia rubra vera
Secondary causes polycythaemia
COPD
Altitude
OSA
Excessive erythropoietin
Causes of excessive erythropoietin → polycythaemia
Cerebellar haemangioma
Hypernephroma
Hepatoma
Uterine fibroids
How to differentiate between true (primary/secondary) polycythaemia and relative polycythaemia
Red cell mass studies - in true, total red cell mass >35 in males and >32 in women
What is polycythaemia vera
Myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to increase in red cell volume, often accompanied by overproduction of neutrophils and platelets
Features polycythaemia vera
- Pruritis, typically after a hot bath
- Splenomegaly
- Hypertension
- Hyperviscosity - arterial thrombosis, venous thrombosis
- Haemorrhage
ESR in polycythaemia vera
Low
First line investigations in polycythaemia vera
FBC/film
JAK2 mutations
Serum ferritin
Renal and liver function tests
Findings FBC in polycythaemia vera
Raised haematocrit
Neutrophils, basophils and platelets raised in half of patients
Management polycythaemia vera
- Aspirin
- Venesection
- Chemotherapy
Complications polycythaemia vera
Thrombotic events
Myelofibrosis
Acute leukaemia
Features post-thrombotic syndrome
- Painful, heavy calves
- Swelling
- Varicose veins
- Venous ulceration
Treatment post-thrombotic syndrome
Compression stockings
Keep legs elevated
Why increased risk of DVT/PE in pregnancy
- Increase in factors VII, VIII, X, fibrinogen
- Decrease in protein S
- Uterine presses on IVC causing venous stasis in legs
Management DVT/PE in pregnancy
SC LMWH
Age of onset homozygous sickle cell
4-6 months (abnormal HbSS molecules take over from fetal haemoglobin)
Diagnostic investigation sickle cell anaemia
Haemoglobin electrophoresis
Prophylactic management of sickle cell
Hydroxyurea - increases HbF levels
Vaccination sickle cell
Pneumococcal polysaccharide vaccine every 5 years
Precipitants thrombotic (painful) crises
- Infection
- Dehydration
- Deoxygenation, e.g. high altitude
Complications thrombotic crises sickle cell
Infarcts in various organs;
- Avascular necrosis of hip
- Hand-foot syndrome in children
- Lung infarct
- Splenic infact
- Brain infarct
What is acute chest syndrome sickle cell
Vaso-occlusion in pulmonary microvasculature → infarction in lung parenchyma
Presentation acute chest syndrome in sickle cell
- Dyspnoea
- Chest pain
- Pulmonary infiltrates on CXR
- Low pO2
Management acute chest syndrome in sickle cell
- Pain relief
- Resp support, e.g. oxygen
- Antibiotics
- Transfusion
Purpose antibiotics in acute chest syndrome
Infection may precipitate acute chest syndrome
Clinical findings can be difficult to distinguish from pneumonia
Purpose transfusion in acute chest syndrome
Improves oxygenation
Cause aplastic crises in sickle cell
Infection with parvovirus
Investigation findings aplastic crises in sickle cell
- Sudden fall in Hb
- Reduced retic count (due to BM suppression)
What is sequestration crises sickle cell
Sickling within organs, e.g. spleen and lungs, causing pooling of bloods with worsening of anaemia
Retic count in sequesteration crises
High
Indications for transfusion in sickle cell
- Severe or symptomatic anaemia
- Pregnancy
- Pre-op
Indications for exchange transfusion in sickle cell
Acute vaso-occlusive crisis (stroke, acute chest syndrome, multiorgan failure, splenic sequesteration)
Causes of massive splenomegaly
Myelofibrosis
CML
Visceral leishmaniasis
Malaria
Gaucher’s syndrome
Causes of non-massive splenomegaly
- Portal hypertension
- Lymphoproliferative disease, e..g CLL, Hodgkin’s
- Haemolytic anaemia
- Infection - hepatitis, glandular fever
- Infective endocarditis
- Sickle cell, thalassaemia
- RA
Causes of thrombocytosis
- Reactive
- Malignancy
- Essential thrombocytosis
- Hyposplenism
What is essential thrombocytosis
Myeloproliferative disorder - megakaryocyte proliferation results in overproduction of platelets
Features essential thrombocytosis
- Platelet count >600
- Thrombosis (venous or arterial) or haemorrhage can be seen
- Burning sensation in hands
Genetics essential thrombocytosis
JAK2 mutation found in 50% of patients
Management essential thrombocytosis
- Hydroxyurea
- Interferon-alpha in younger patients
- Low dose aspirin to reduce thrombotic risk
Use tranexamic acid
- Menorrhagia
- Trauma
Role of tranexamic acid in trauma
Benefit when administered in the first 3 hours
Given as IV bolus → infusion
Prevention tumour lysis syndrome
- IV fluids
- Rasburicase if high risk, allopurinol if lower risk
Underlying conditions increasing risk of VTE
Malignancy
Thrombophilia
Heart failure
Antiphospholipid syndrome
Behcet’s
Polycythaemia
Nephrotic syndrome
Sickle cell
Paroxysmal noctural haemoglobinuria
Hyperviscosity syndrome
Homocystinuria
Thrombophilias eg
Activated protein C resistance
Protein C deficiency
Protein S deficiency
Subclavian vs femoral CVC for VTE risk
Femoral higher risk than subclavian
Medications increasing VTE risk
COCP
HRT (combined>oestrogen only)
Raloxifene, tamoxifen
Antipsychotics, esp olanzapine
What is required for absorption of vitamin B12
Binding to intrinsic factor
Where is intrinsic factor secreted from
Parietal cells in stomach
Where is intrinsic factor absorbed
Terminal ileum
Causes B12 deficiency
- Pernicious anaemia (most common)
- Post gastrectomy
- Vegan/poor diet
- Disorders/surgery of terminal ileum, e.g. Crohn’s (disease activity or post-resection)
- Metformin (rare)
Features of B12 deficiency
- Macrocytic anaemia
- Sore tongue and mouth
- Neurological symptoms
- Neuropsychiatric symptoms, e.g. mood disturbance
Features neurological symptoms of B12 deficiency
Dorsal column usually affected first (joint position, vibration) prior to distal parasthesia
Treatment B12 deficiency with no neuro involvement
1mg IM hydroxycobalmin 3/week for 2 weeks, then once every 3 months
Treatment B12 deficiency if also deficient in folic acid
Important to treat B12 def first, to avoid precipitating subacute combined degeneration of cord
Inheritance von Willebrands
Autosomal dominant
Common types of bleeding in vWD
Epistaxis and menorrhaga
Type 1 vWD = ?
Partial reduction in wVF
Type 2 vWD = ?
Abnormal form of vWF
Type 3 vWD = ?
Total lack of vWF
Autosomal recessive
Coag results vWD
Prolonged bleeding time
APTT may be prolonged
Factor VIII may be mod reduced
Defective platelet aggregation with ristocetin
