Haematology Flashcards
Malaria
a parasitic infection caused by protozoa of the genus plasmodium, this infection is almost exclusively sen in tropics & subtropics
Notifiable disease in the UK
NB consider malaria in every febrile travel returning from a malaria endemic area in the last year
Protective factors for malaria
sickle cell trait
G6PD deficiency
HLA-B53
Species of malaria
Plasmodium falciparum
- commonest type
- most severe kind
non falciparum (plasmodium vivax/ovale/malarine)
- plasmodium vivax is most common
- vivax is usually benign
Presentation of malaria
fever
- often recurring
- cyclical, occurring every 48-72h
chills, rigors, headache, cough, myalgia, GI upset
jaundice
hepato/splenomegaly
Severe disease (usually P. falciparum)
- impaired consciousness
- SOB
- bleeding
- fits
- AKI, ARDS, anaemia
Investigations for malaria
Blood smears with Giemsa stain
- gold standard
- presence of parasites within RBCs
FBC
- ↓Hb
- thrombocytopenia
- ↑ reticulocytes
Rapid diagnostic tests (RDIs)
-detect parasite antigens
LFTs
-often abnormal
Management of malaria
Falciparum:
- Artemisinin-based combination therapy (ART) or PO quinine if uncomplicated
- IV quinine in severe disease
Non-falciparum malaria:
- 1st line = chloroquine
- 2nd line = ART (1st line if chloroquine resistance)
- primaquine (as relapse prevention, destroys liver hypnozoites)
Prevention of malaria
reduced chance of being bitten
- misquito nets
- mosquito spray
Chemoprophylaxis
- start 1 week befogging entering malarious area
- chloroquine, proguanil, mefloquine
Hodgkin’s lymphoma
malignant tumour of the lymphatic system characterised histologically by the presence of Reed-Sternberg cells (multinucleate giant cells)
Bi-modal age distribution
- peak age 20-34yrs
- 2nd peak >70yrs
classical Hodgkin’s lymphoma (most common), especially nodular sclerosing kind
NB lymphocyte deplete kind is rare & carries worst prognosis
Risk factors include immunodeficiency, EBV infection & autoimmune disease
Hodgkin’s lymphoma characteristic histological feature
Reed-Sternberg cells (multinucleate giant cells)
Presentation of Hodgkin’s lymphoma
painless non tender asymmetrical lymphadenopathy
- most frequently affects cervical nodes
- may present as mediastinal mass
B symptoms
- weight loss, fever, night sweats
- imply poor prognosis
alcohol induced pain at sites of nodal disease
Investigations for Hodgkin’s lymphoma
FBC
- ↑/↓ WCC
- ↓Hb
- eosinophilia
Lymph node biopsy
- Reed-Sternberg cells
- Hodgkins cells
CXR
- mediastinal mass
- mediastinal lymphadenopathy
ESR (↑), LDH (↑)
CT, Gallium scan, PET-CT
Management of Hodgkin’s lymphoma
chemo+radiotherapy
-ABVD or BEACOPP regimes
autologous stem cell transplant
Non-Hodgkin’s lymphoma
a heterogenous group of malignancies of the lymphoid system, ~5x more common than Hodgkin’s lymphoma
usually seen in >50y/o pts
Subtypes
- B-cell lymphomas (~85%)
- T-cell lymphomas (~15%)
Risk factors include Caucasian origin, EBC infection, FH of lymphoma, immunodeficiency, autoimmune disease
Presentation of Non-Hodgkin’s lymphoma
painless lymphadenopathy
- non tender
- rubbery
- asymmetrical
constitutional/B-symptoms
-fever, weight loss, night sweats, lethargy
splenomegaly, hepatomegaly
Extra-nodal disease (more common than in Hodgkins)
-early satiety, GI bleeding, headache, skin lesions, pruritus
Investigations for Non-Hodgkin’s lymphoma
excision node biopsy
-investigation of choice
CT chest/abdo/pelvis
FBC (↓Hb), ESR (↑), LDH (↑)
PET-CT
Management of Non-Hodgkin’s lymphoma
depends on subtype
generally watch & wait (if low grade), chemo or radiotherapy
Burkitt’s lymphoma
high grade non-hodgkins lymphoma, that is rapidly growing & aggressive
usually seen in children, and is strongly associated with EBV infection
characterised by starry-sky appearance on biopsy (lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells)
managed with chemo
Strongly associated with tumour lysis syndrome
Acute lymphoblastic leukaemia (ALL)
a malignant clonal disease that develops when lymphoid progenitor cells undergo uncontrolled proliferation
most common cancer in children with peak incidence at 2-5yrs
-~80% of leukemias in children)
Presentation of Acute lymphoblastic leukaemia (ALL)
sudden onset & rapid progression
fatigue dizziness, palpations, pallor, weakness
bone & joint pain
headache, neck stiffness
fever without obvious infection
bruising, epistaxis, petechiae, ecchymosis
LUQ fullness, early satiety (due to splenomegaly)
testicular enlargement
lymphadenopathy
Investigations for Acute lymphoblastic leukaemia (ALL)
FBC
- ↓ Hb
- ↓ platelets
- ↓ neutrophils
- ↓/↑WCC
Blood smear
-leukaemic lymphoblasts
Bone marrow aspiration &biopsy
-≥20% blast cells
clotting (may show DIC), LDH (↑), uric acid (↑)
LFTs, U&Es,
Management of Acute lymphoblastic leukaemia (ALL)
Induction (to restore normal haematopoesis)
-corticosteroids + vincristine/cyclophosphamide/doxorubicin
Maintenance
-mercaptopurine + methotrexate
CNS prophylaxis
-intrathecal methotrexate
Stem cell transplant
NB relapses after treatment have very poor prognosis
Acute myeloid leukaemia (AML)
the malignant clinical expansion of myeloid blasts in the bone marrow, peripheral blood or extra medullary tissue
may be primary disease or secondary transformation of other lymphoproliferative disorders
Most common acute leukaemia in adults usually seen age 65yrs
Risk factors for Acute myeloid leukaemia (AML)
aplastic anaemia
myelofibrosis
paroxysmal nocturnal haemoglobulinaemia
polycythaemia rubera vera
Presentation of Acute myeloid leukaemia (AML)
anaemia (pallor, fatigue, weakness) fever petechiae purpura ecchymosis epistaxis frequent infections hepatosplenomegaly leukaemia cutis (nodular skin lesions, gray-blue/purple) gingival hypertrophy gingivitis bleeding gums
Investigations for Acute myeloid leukaemia (AML)
FBC
- ↓ Hb
- ↓ platelets
- ↓ neutrophils
clotting
- DIC common
- ↑PT, ↑aPTT, ↓fibrinogen
LDH (↑)
Bone marrow biopsy
-≥20% blast cells
LFTs, U&Es, blood film/smear
Management of Acute myeloid leukaemia (AML)
induction
-cytarabine + daunorubicin
consolidation
-cytarabine / daunorubicin / mitoxantrone
Stem cell transplant
Acute promyelotic anaemia (APL)
presents younger than other AMLs (~25y/o)
often has DIC/thrombocytopenia at presentation
has Auer-rods on histology
treated with arsenic trioxide (ATO) or all-trans relinoic acid (ATRA)
Epidemiology of leukaemias
ALL = most common leukaemia in children
CLL = most common leukaemia in adults
-often has lymphadenopathy
AML = most common acute leukaemia in adults
CML= only ~15% of adult leukaemias
- rarely has lymphadenopathy
- associated with Philadelphia chromosome
Chronic lymphocytic anaemia (CLL)
malignant monoclonal expansion of B lymphocytes with accumulation of abnormal lymphocytes in blood / bone marrow / spleen / lymphnodes / liver
most common leukaemia in adults, usually diagnosed ~70y/o
Presentation of Chronic lymphocytic anaemia (CLL)
variable presentation with insidious onset, may be symptomatic & incidentally found on blood test
symmetrically enlarged painless lymph nodes (NB CML rarely has lymphadenopathy) susceptibility to infection anorexia, weight loss hepatosplenomegaly, abdo discomfort brusing, petichae
Investigations for Chronic lymphocytic anaemia (CLL)
FBC
- ↓ Hb
- ↑↑ WCC
- ↓ platelets
Blood film
-smear cells & smudge cells
Immunophenotyping
-key investigations
Bone marrow aspirate / lymph node biopsy
T53 gene test
-done before treatment
Management of Chronic lymphocytic anaemia (CLL)
chemotherapy
stem cell transplant
if CD20 +ve
-rituximab
TP53 targeted therapy
-ibrutinib
Chronic myeloid anaemia (CML)
a myeloproliferative disorder of pluripotent haemopoietic stem cells affecting one or all cell lines
usually seen in adults age 60-65 yrs
associated with Philadelphia chromosome in ~95% of pts
Presentation of Chronic myeloid anaemia (CML)
often asymptomatic & incidentally found on blood test, otherwise symptoms have insidious onset
fatigue, night sweats, weight loss abdo fullness, abdo distension LUQ pain splenomegaly & hepatomegaly easy bruising
NB CML only rarely has enlarged lymph nodes, but they are common in CLL = key differentiating factor
Investigations for Chronic myeloid anaemia (CML)
FBC
- ↓ Hb
- ↑ WCC (>100x10^9/L)
- ↓/↑ platelets
Blood film
- all stages of maturation seen
- looks like bone marrow aspire
LDH (↑)
leukocyte alkaline phosphate (↓)
bone marrow aspirate & biopsy
cytogenetics
Fluorescent in situ hybridisation (FISH)
quantitive reverse transcriptase PCR
Myeloma/multiple myeloma
a plasma cell dyscrasia characterised by terminally differentiated plasma cells, infiltration of the bone marrow by plasma cells and presence of a monoclonal immunoglobulin in the serum and/or urine
classified by immunoglobulin type (IgG most common)
2nd most common haematological malignancy
median age of presentation is 70yrs
Epidemiology of Myeloma/multiple myeloma
classified by immunoglobulin type
-IgG most common type
2nd most common haematological malignancy
median age of presentation is 70yrs
Epidemiology of Myeloma/multiple myeloma
classified by immunoglobulin type
-IgG most common type
2nd most common haematological malignancy
median age of presentation is 70yrs
more common in men & afro-carribbeans
Presentation of Myeloma/multiple myeloma
bone pain
-particularly back pain
pathological fractures
lethargy, anorexia, night sweats, weight loss
↑ Ca2+ (constipation, nausea, confusion)
dehydration, thirst, pallor
easy bruising / bleeding
↑susceptibility to infection & repeated infections
Presentation of Myeloma/multiple myeloma
bone pain
-particularly back pain
pathological fractures
lethargy, anorexia, night sweats, weight loss
↑ Ca2+ (constipation, nausea, confusion)
Renal damage (dehydration, thirst, pallor)
easy bruising / bleeding
↑susceptibility to infection & repeated infections
Investigations for Myeloma/multiple myeloma
FBC
- ↓ Hb
- ↓ platelets
U&Es
- ↑ urea
- ↑ creatinine
serum / urine electrophoresis
- ↑ monoclonal IgA / IgG
- Bence-Joyce proteins in urine
Bone marrow aspiration & biopsy
-monoclonal plasma cell infiltration
X-ray
- rain drop skill
- randomly placed dark spots due to bone lysis
Ca2+ (↑)
Whole body MRI
Diagnostic criteria for Myeloma/multiple myeloma
Symptomatic multiple myeloma is defined at diagnosis by the presence of all 3 of the following:
- Monoclonal plasma cells in the bone marrow >10%
- Monoclonal protein within serum / urine (as determined by electrophoresis)
- Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures
Management of Myeloma/multiple myeloma
currently deemed incurable
elderly pts/not suitable for transplant
-Thalidomide + an Alkylating agent + Dexamethasone
suitable for transplant
- Bortezomib + dexamthasone
- followed by stem cell transplant
NB pts should be mounted every 3 months with blood tests & electrophoresis
Polycythaemia
refers to an increased number of Red blood cells in the body
Aetiology of Polycythaemia
Relative causes:
-dehydration, stress (gaissbock syndrome)
Primary:
-polycythaemia vera
Secondary
- COPD
- high altitude
- OSA
- uterine fibroids (cause ↑ EPO)
Polycythaemia vera
myeloproliferative disorder characterised by erythropoietic independent rise in erythrocyte & platelets count
associated with a mutation in the JAK2 gene
Presentation of Polycythaemia vera
maybe be asymptomatic or incidentally found on blood tests
hyper viscosity syndrome
-mucosal bleeding, visual changes, neurological symptoms (dizziness, headache, tinnitus)
Pruritus
-typically after contact with warm water
plethoric appearance
- flushed face with purple hue
- cyanotic lips
erythromyalgia
-warmth, pain, erythema, infarction of distal extremities
thrombosis
-e.g. stroke, MI, PE, DVT, thrombophlebitis
haemorrhage
-from gums, easy bruising, GI bleeds
splenomegaly, hypertension
Investigations for Polycythaemia vera
FBC
- ↑ Hb/RBC
- ↑ haematocrit
- ↑ platelets
- ↑ WCC
- ↓ MCV
Jak2 gene mutation (+ve) LDH (↑) erythropoietin (↓) ferritin (often ↓) LFTs
NB in secondary causes of polycythaemia there is only an isolated ↑ Hb/RBC and no ↑ platelets
Management of Polycythaemia vera
Venesection (1st line)
Myelosuppression (2nd line)
- e.g. with hydroxyurea or phosphorus-32
- ↑ risk of secondary leukaemia
JAK2 inhibitors
-e.g. ruxolitinib
Aspirin
- low dose
- to decrease risk of thromboembolic events
NB ~5% of pts progress to myelofibrosis or acute leukaemia (↑ risk of this with myelosuppression therapy)
Neutropenia
refers ti a low neutrophil count i.e. <1.5x10^9 (normal range (2.0-7.5 x10^9)
important to recognise as it predisposes to infection
Aetiology of neutropenia
Viral
-HIV, EBV, hepatitis
Medications:
-cytotoxics/chemotherapy, carbimazole, clozapine
Benign ethnic neutropenia
- seen in black africans, afro-carribbean individuals
- no treatment required
Haemtological malignacies
- aplastic anaemia
- myelodysplastic malignancy
SLE, RA, haemodialysis
Neutropenic sepsis / Febrile neutropenia
oral temp ≥38.5°C / ≥2 consecutive readings ≥38.0°C with a neutrophil count <0.5 x10^9
often associated with cancer therapy
Investigations for Neutropenic sepsis / Febrile neutropenia
Only investigate after starting Abx
FBC (↓ neutrophils) blood cultures CXR U&Es LFTs
Presentation of Neutropenic sepsis / Febrile neutropenia
fever
tachycardia
hypotension
recent chemo therapy
Thrombocytopenia
a platelets count below the normal range i.e. <150 x10^9/L
Aetiology of thrombocytopenia
Most severe
- immune thrombocytopenia (ITP)
- Disseminated intravascular coagulation (DIC)
- thrombotic thrombocytopenic purpura (TTP)
- haematological malignancies
Others
- heparin induced thrombocytopenia (HIT)
- HELLP syndrome
- Antiphospholipid syndrome
- Medication (quinine, aspirin, thiazides, sulphonamides)
Pseudo thrombocytopenia
can be caused the use of EDTA as an anticoagulant
has low platelet count but without suggestive symptoms
Investigations for thrombocytopenia
FBC Blood film coagulation screen U&Es LFTs consider bone marrow biopsy
NB rapidly falling platelet count even if within normal range is worrying
Management of thrombocytopenia
treat any significant bleeds
consult haematology
consider replacing platelets
-e.g. if anticipated need for urgent surgery, significant bleeding or neurological symptoms
NB rapidly falling platelet count even if within normal range is worrying
Presentation of thrombocytopenia
epistaxis
-usually excessive, prolonged, frequent
bleeding gums ↑ bleeding from tooth extractions spontaneous bruising menorrhagia PPH excessive bleeding after surgery
Immune thrombocytopenia (ITP)
An autoimmune disorder with autoantibodies to platelets causing thrombocytopenia, which may be triggered by viral infections
NB in children it is usually acute, following a viral infection or vaccination but is generally self limiting (lasts 1-2 weeks)
Presentation of Immune thrombocytopenia (ITP)
often asymptomatic & incidentally picked up on FBC
petechiae, bruising, epistaxis
absent splenomegaly
major haemorrhages e.g. intracranial bleeds are uncommon
NB presence of splenomegaly should make you consider other diagnosis
Investigations & Management of Immune thrombocytopenia (ITP)
FBC shows platelet count <100 x10^9/L & blood film shows normal platelets
1st line
-oral prednisolone
if active bleed or urgent need to ↑ platelets use IVIG (human immunoglobulin
Investigations & Management of Immune thrombocytopenia (ITP)
FBC shows platelet count <100 x10^9/L & blood film shows normal platelets
1st line
-oral prednisolone
if active bleed or urgent need to ↑ platelets use IVIG (human immunoglobulin)
Thrombotic thrombocytopenic purpura (TTP)
thrombotic microangiopathic where micro thrombi consisting primarily of platelets occlude microvasculature due to deficiency of ADAMTS13
should be treated as an emergency
most common in adults usually aged ~40 yrs
Investigations for Thrombotic thrombocytopenic purpura (TTP)
FBC
- ↓ platelets
- ↓ Hb
- ↑ reticulocytes
- ↓ haptoglobin
U&Es
- ↑ urea
- ↑ creatinine
urinalysis
-proteinuria ± haematuria
Blood film
-schisticytes (erythrocyte fragements)
LDH (↑↑)
direct coombs test (-ve)
pretreatment ADAMTS13 activity levels & ADAMTS13
Presentation fo Thrombotic thrombocytopenic purpura (TTP)
Fever
Fluctuating neurological signs
- delirium, altered mental status
- stroke, seizures
- headache, dizziness
Microangiopathic haemolytic anemia
- fatigue, dyspnoea, pallor
- jaundice, myalgia, arthralgia
Impaired renal function:
-haematuria, oliguria, proteinuria
Purpura
-non palpable small purpuric spots or petechiae
Direct & indirect Coombs test
Direct
-checks if antibodies are stuck to RBC surface
In-driect
-checks for free antibodies in serum
help to rule out haemolytic anaemia
Management of Thrombotic thrombocytopenic purpura (TTP)
Plasmaphoresis
-IV plasma exchange
Steroids
-high dose prednisolone
Rituximab
-if severe
NB is treated as an emergency
Features of Thrombotic thrombocytopenic purpura (TTP)
Pentad of
- fever
- fluctuating neurological signs
- microangiopathic haemolytic anemia
- thrombocytopenia
- renal failure
Von Willebrand disease (vWD)
The most common hereditary coagulopathy due to the deficiency or abnormal function of von Willebrand factor (vWF)
characteristically behaves like a platelet disorder as vWF promotes platelet adhesion & platelet plug formation + vWF binds factor VIII preventing its clearance
inherited in an autosomal dominant fashion
Von Willebrand disease (vWD)
The most common hereditary coagulopathy due to the deficiency or abnormal function of von Willebrand factor (vWF)
characteristically behaves like a platelet disorder as vWF promotes platelet adhesion & platelet plug formation + vWF binds factor VIII preventing its clearance
inherited mostly in an autosomal dominant fashion
Presentation of Von Willebrand disease (vWD)
often asymptomatic
bleeding tendency from mucosa
- epistaxis
- menorrhagia (common in women)
prolonged bleeding from minor injuries / post surgery
NB haemoarthrosis are rare
Investigations for Von Willebrand disease (vWD)
Coagulation profile
- PT (normal)
- aPTT (may be ↑)
- bleeding time (↑)
FBC (normal) Factor VIII (may be ↓) vWF antigen (↓) ristocetin cofactor assay (defective platelet aggregation)
Management of Von Willebrand disease (vWD)
TXA for mild bleeding
Desmopressin (DDAVP)
-stimulates vWF release
vWF containing factor VIII concentrate
-for severe bleeding or surgical prophylaxis
Thrombocytosis
a platelets count >450 x10^9/L
Aetiology
- reactive (platelets = acute phase reactant_
- e.g. stress, surgery, infection
- malignancy
- e.g. CML
- hyposplenism / post splenectomy
- essential thrombocytosis
Essential thrombocytosis (primary thrombocytosis)
most common myeloproliferative neoplasm due to sustained dysregulates megakaryocytic proliferation, usually seen in pts age 50-60yrs
Essential thrombocytosis presentation
commonly asymptomatic
erythromelalgia
-burning pain & erythema of hands and feet
thrombotic events (stroke/TIA/retinal artery occlusion)
Vasomotor symptoms
-headache, visual disturbance, ocular migraines
splenomegaly/hepatomegaly
bleeding
-primarily GI, simulates duodenal ulcer following duodenal arcade thrombosis
Investigations for Essential thrombocytosis
FBC
-platelets >600 x10^9
Blood smear
-immature precursor cells e.g. myelocytes
Bone marrow aspirate
- hypercellularity
- megakaryocyte hyperplasia
LDH (↑)
CRP/ESR (normal)
Management of Essential thrombocytosis
Hydroxyurea (hydroxycarbamide)
-to ↓ platelet count
low dose aspirin
-↓ thrombotic risk
NB Interferon-alpha is preferred in young pts & pregnant women over hydroxyurea
Haemophilia
an X-linked recessive inherited bleeding disorder resulting in the deficiency of coagulation factors
Genetics of haemophilia
X-linked recessive inheritance
hence only seen in males
Types of haemophilia
Haemophilia A
- deficiency in clotting factor VIII
- accounts for ~80% of cases
Haemophilia B
- deficiency in clotting factor IX
- accounts for ~20% of cases
Haemophilia C
- deficiency of factor XI
- very rare
- seen in Ashkenazi jews
Presentation of haemophilia
repeated haemarthrosis
- especially of knees
- can lead to haemophilic arthropathy
frequent brusing & haematomas
oral mucosal bleeding, epistaxis, excessive bleeding after minor procedures
musculoskeletal bleeding/haematomas
NB female carriers may present with mild symptoms
Investigations for haemophilia
Coagulation screen
- aPTT ↑
- PT normal
- bleeding time normal
Factor VIII/IX assay
- ↓ / absent
joint x-rays
-may show degenerative joint disease
Management of haemophilia A
prophylactic factor VIII
if acute bleeding
-FFP/recombinant factor VIII
Management of haemophilia B
if acute bleeding
- 1st line = recombinant factor IX
- 2nd line = PCC or plasma derived factor IX
Disseminated intravascular coagulation (DIC)
a syndrome characterised by systemic activation of the coagulation cascade resulting in the formation of intravascular thrombi & the depletion of platelets + coagulation factors
Aetiology of Disseminated intravascular coagulation (DIC)
-Sepsis
-trauma (trauma induced coagulopathy)
-malignancy
-obstetric complications (e.g. HELLP syndrome, amniotic fluid embolus)
-organ failure (e.g. pancreatitis, fulminant hepatitis)
transfusion reaction
Presentation of Disseminated intravascular coagulation (DIC)
oliguria, hypotension, tachycardia large bruises spontaneous bleeding at venipuncture sites / soft palate / site of trauma massive haemorrhage organ failure -ARDS -PE -purpura fulminans (DIC + extensive skin necrosis) -Waterhouse-Friedirchsen syndrome
Investigations for Disseminated intravascular coagulation (DIC)
Coagulation screen
- PT ↑
- aPTT ↑
- bleeding time ↑
- Fibrinogen ↓
FBC
-platelets ↓
D-Dimer ↑
Management of Disseminated intravascular coagulation (DIC)
treat underlying cause
blood products as needed
anticoagulation
- if hypercoaguability is the main problem
- therapeutic dose LMWH/UFH
do not use antifibrinolytics e.g. TXA in pts with DIC
Thalassaemia
a group of hereditary haemoglobin disorders characterised by mutations in the alpha or beta global chains
inherited in autosomal recessive pattern
Alpha-Thalassaemia
deficient production of α-globin
2 α genes present on each chromosome 16
Types of Alpha-Thalassaemia
Normal (α,α / α,α)
a+ heterozygous i.e. silent carrier (α,- / α,α)
- i.e. one allele affected
- borderline Hb & MCV
- pt asymptomatic
a+ homozygous (α,- / α,- or α,α / -,-)
- i.e. two alleles affected
- slightly low Hb, slightly low MCV & MCH
- pt asymptomatic
HbH disease (α,- / -,-)
- i.e. three alleles affected
- microcytic hypo chromic anaemia
- splenomegaly & skeletal deformities
α Thalassaemia major / Hb Barts (-,- / -,-)
- i.e. all four alleles affected
- hydrops fettles & intrauterine death
- incompatible with life
- Hb Barts = γ chain tetramere
Investigations for Alpha-Thalassaemia
FBC
- Hb ↓
- MCV ↓
- MCH ↓
- reticulocytes ↑
- RBC count ↑
Iron studies
- iron ↑
- ferritin ↑
Blood film + supra vital stain
-Heinz bodies (HbH inclusion bodies of β-chain tetrameres)
Investigations for Alpha-Thalassaemia
FBC
- Hb ↓
- MCV ↓
- MCH ↓
- reticulocytes ↑
- RBC count ↑
Iron studies
- iron ↑
- ferritin ↑
Blood film + supra vital stain
-Heinz bodies (HbH inclusion bodies of β-chain tetrameres)
Management of Alpha-Thalassaemia
no management for silent carriers or asymptomatic pts
folic acid supplements for most pts
Blood transfusions
-especially in HbH disease
Splenectomy if hyposplenism
Iron chelation
-e.g. desferrioxamine to prevent iron overload
Beta-Thalassaemia
deficient production of β globes
one β global gene on each chromosome 11
Types of Beta-Thalassaemia
Normal (β / β)
β Thalassaemia trait (β / -)
- one functional allele, one non functional
- HbA2 >4%
- slight anaemia, ↓MCV, ↓MCH
- asymptomatic
β Thalassaemia major (- / -)
- absence of β chains
- HbF >90%
- severe haemolytic anemia ↓↓MCV, ↓↓MCH
- hepatosplenomegaly & skeletal deformities
- chronic diffusion dependency
- presents in 1st year of life with failure to thrive
Investigations for Beta-Thalassaemia
FBC
- Hb ↓
- MCV ↓
- MCH ↓
- reticulocytes ↑
Blood film + supra vital stain
- Target cells
- Teardrop cells
Haemoglobin analysis
- minimal/no HbA
- HbF ↑
- HbA2 ↑
LDH (↑)
Management of Beta-Thalassaemia
Repeated transfusions
-risk of iron overload
iron chelation
-e.g. with IV desferrioxamine or PO deferrasirox
Folic acid supplements as required
consider splenectomy
Sickle cell anaemia
Autosomal recessive single gene defect in the β chain of haemoglobin leading to production of sickle haemoglobin (HbS)
more common in people of african descent
most common form of intrinsic haemolytic anaemia
Sickle cell trait
i.e. heterozygous individuals carrying HBSA
people with sickle cell trait are generally asymptomatic but may present with gross haematuria due to renal papillary necrosis
protective against malaria
Presentation of sickle cell disease
symptoms begin age 3-6 months as HbF levels drop
pallor, jaundice, lethargy, growth restriction, weakness
failure to thrive
splenomegaly
further presentations with crisis
Vaso-occlusive crisis
Most common type of sickle cell crisis
due to obstruction of microcirculation by sickle RBCs leading to ischaemia
precipitated by cold, infection, dehydration, hypoxia etc.
causes severe pain, swollen joints, dactylitis, priapism (in men)
may affect major organs e.g. stroke if brain, bowel ischaemia if mesentery, renal papillary necrosis (loin pain &haematuria)
Acute chest syndrome
a type of sickle cell crisis
essentially a vast-occlusive crisis of the lung vasculature
presents with dyspnoea, hypoxia, chest pain, tachypnoea & new infiltrates on CXR
symptoms + new infiltrates = diagnostic
Aplastic crisis
temporary cessation of erythropoiesis leading to severe anaemia in sickle cell pts
usually due to parvovirus B19 infections
leads to rapid ↓Hb (~1 week), due to bone marrow suppression the reticulocyte count is ↓
FBC (↓Hb, ↓reticulocytes)
requires transfusions
Sequestration crisis
mainly seen in babies/young children, sickling in organs e.g. spleen/lungs cause blood pooling and worsening of anaemia
presents with splenomegaly, LUQ pain, shock (tachycardia, hypotension)
FBC (↓Hb, ↑reticulocytes)
NB recurrent spleen sequestration is an indication for splenectomy
Hyperhaemolytic crisis
rare sickle cell crisis
↓Hb due to ↑ rate of haemolysis
Investigations for sickle cell disease
FBC
- Hb ↓
- reticulocytes ↑ (if ↓ indicates aplastic crisis)
Blood smear
- presence of sickle cells
- Howell-Jolly bodies
- nucleated RBCs
- target cells
Haemoglobin electrophoresis
- gold standard
- no HbA
- ~90% HbSS
- ~10% HbF
U&Es, Lung function tests, LFTs
Screening for sickle cell disease
heel prick blood spot test on day 3-10 after birth
OR
pre-conceptual screening in high risk groups
Management of sickle cell disease
Crisis
- high dose analgesia e.g. opiates
- O2, IV fluids
- blood transfusions / exchange transfusion
- Abx if signs of infection
folic acid supplements
oral penicillin prophylaxis from diagnosis
unconjugated pneumococcal vaccine from age 2yrs
-repeat every 5 years
exchange transfusions
- as required
- should be done if a stroke occurs
hydroxycarbamide (hydroxyurea)
- to ↑ HbF levels
- helps ↓ frequency of crisis
NB most pts have crisis plan which includes analgesic regiments, this should be followed, these pts are often deemed to be opiate seeking and left in pain
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
most common RBC enzyme defect leading to ↑ susceptibility to oxidative stress
X-linked recessive inheritance i.e. male only
usually seen in mediterranean & african people
generally managed by avoiding triggers for crisis & blood transfusion if necessary
Presentation of Glucose-6-phosphate dehydrogenase (G6PD) deficiency
often asymptomatic
recurring haemolytic crisis
-sudden onset back/abdo pain, jaundice, dark urine, transient splenomegaly, pallor
precipitants include fava beans. chlorquine, isoniazid, NSAIDs, sylph-group drugs
Investigations for Glucose-6-phosphate dehydrogenase (G6PD) deficiency
FBC
- Hb ↓
- reticulocytes ↑
Urinalysis
-haemoglobinuria
Blood smear
-Heinz bodies & bite cells
G6PD enzyme assay
-3 month after acute episodes
Indirect bilirubin (↑) LDH (↑)
Hereditary spherocytosis
hereditary abnormality of RBCs caused by defects in structural membrane proteins leading to ↓ lifespan of RBCs
inherited in autosomal dominant fashion
most common cause of hereditary haemolytic anaemia in people of northern european descent
Presentation of Hereditary spherocytosis
failure to thrive jaundice splenomegaly LUQ pain black pigmented gallstones pallor anaemia
Investigations for Hereditary spherocytosis
FBC
- Hb ↓
- reticulocytes ↑
Blood smear
-spherocytes
EMA binding test
-↓ binding of dye to RBC membranes
Unconjugated bilirubin (↑)
LDH (↑)
direct antiglobulin test (-ve)
NB direct antiglobulin test is +ve in other haemolytic anaemias
Management of Hereditary spherocytosis
folate replacement
splenectomy
transfusions if necessary
Haemolytic anemia
a group of disorders that result in premature destruction of RBCs leading to a normocytic anaemia
Types:
- Intrinsic: due to abnormalities in the RBCs
- Extrinsic: due to external causes e.g. mechanical damage or immune mediated
Mechanism
- Intravascular: due to complement fixation, trauma or other extrinsic factors e.g. G6PD/TTP/DIC/ABO mismatch
- Extravascular: most common type, RBCs removed by phagocytic system due to intrinsic defects e.g. spherocytosis
Aetiology of Haemolytic anemia
Hereditary
-G6PD, spherocytosis, sickle cell anaemia
Acquired immune:
-autoimmune haemolytic anaemia, transfusion reactions, haemolytic disease of the new born, drugs e.g. penicillin
Acquired non immune:
-DIC, TTP, HUS, malignancy, pre-eclampsia, prosthetic heart valves, paroxysmal nocturnal haemoglobinuria
Presentation of Haemolytic anemia
may be sudden with tachycardia, dyspnoea, angina, weakness and mild jaundice
gallstones (due to ↑ bilirubin)
haematuria (if intravascular)
Investigations for Haemolytic anemia
FBC
- Hb ↓
- Reticulocytes ↑
- MCV/MCH normal
direct antiglobulin test (direct coombs test)
- if +ve suggests immune aetiology
- if -ve non immune aetiology
blood smear
- abnormal forms
- fragments
LDH (↑)
haptoglobin (↓)
bilirubin (↑)
urinalysis (haematuria)
Haemolytic uraemia syndrome (HUS)
Triad of AKI, microangiopathic haemolytic anaemia (combs -ve) and thrombocytopenia
generally seen in young children, ~90% of cases are due to shiga-toxin producing E.coli (0157:H7)
presents with diarrhoea illness preceding onset of thrombocytopenia, microangiopathic haemolytic anaemia and AKI
Investigations include Hb ↓, haptoglobin ↓, bilirubin ↑, LDH ↑, reticulocytes ↑, platelets ↓, urea ↑, creatinine ↑ & ↑ schistocytes
management is supportive (IV fluids, blood transfusions), with consideration for plasma exchange or eculizumab
Aplastic anaemia
a condition defined by pancytopenia with hypo cellular bone marrow and absence of abnormal cells
diagnosis requires ≥2 of
- Hb <100g/L
- platelets <50x10^9 /L
- neutrophil count <1.5x10^9 /L
Aetiology of Aplastic anaemia
~75% of cases are idiopathic
congenital e.g. Flaconi syndrome, drugs e.g. cytotoxics/phenytoin/sulphonamides, radiation, parovirus
Presentation of Aplastic anaemia
fatigue, malaise, pallor, dyspnoea
ankle oedema
purpura, petechiae
mucosal bleeding, retinal haemorrhage
no lymphadenopathy
no hepatosplenomegaly
Investigations for Aplastic anaemia
FBC
- Hb <100g/L
- platelets <50x10^9 /L
- neutrophil count <1.5x10^9 /L
- reticulocytes ↓
- MCV normal
Bone marrow biopsy
- hypocellular bone marrow
- no abnormal cells
Management of Aplastic anaemia
removal of underlying causes e.g. if drug induced
haemopoietic stem cell transplant (HSCT)
immunsuppression e.g. ATG + ciclosporin
supportive care including blood/platelet transfusion
Normocytic anaemia
a low level of haemoglobin with a normal MCV
Mechanism includes ↓blood volume and/or ↓erythropoiesis
Aetiology of Normocytic anaemia
Haemolytic anaemias
-sickle cell, HUS, G6PD, hereditary spherocytosis, pyruvate kinase deficiency, TTP, DIC, malaria, mechanical destruction
Aplastic anaemia
-idiopathic, Falconi syndomre
Acute blood loss
anaemia of chronic disease
anaemia of CKD (falls under anaemia of chronic disease)
Aetiology of Normocytic anaemia
Haemolytic anaemias
-sickle cell, HUS, G6PD, hereditary spherocytosis, pyruvate kinase deficiency, TTP, DIC, malaria, mechanical destruction
Aplastic anaemia
-idiopathic, Falconi syndomre
Acute blood loss
anaemia of chronic disease (most common normocytic anaemia)
anaemia of CKD (falls under anaemia of chronic disease)
Anaemia of chronic disease
anaemia secondary to chronic inflammation, 2nd most common anaemia overall
aetiology include chronic infections e.g. TB, malignancy, inflammatory conditions e.g. RA/SLE
Investigations include FBC (normocytic, normochromic anaemia), serum iron (↓), total iron binding capacity (↓), ferritin (↑), reticulocyte count (↓), ESR/CRP (↑)
management include treatment of underlying cause, blood transfusion or use of recombinant human erythropoietin/NESP e.g. darbepoetin e.g. in CKD
Microcytic anaemia
a condition with ↓Hb & ↓MCV due to insufficient Hb production
Aetiology
- iron deficiency anaemia (most common)
- lead poisoning
- late phase anaemia of chronic disease
- Thalassaemia
- sideroblastic anaemia
Iron deficiency anaemia (IDA)
most common type of anaemia
due to a deficiency in iron
Aetiology of Iron deficiency anaemia (IDA)
excessive blood loss e.g. menorrhagia, GI bleeding
dietary inadequacy (e.g. vegans/vegetarians)
malabsorption (e.g. coeliac disease, IBD)
increased demand (e.g., pregnancy)
NB GI bleeding is the most common cause in men & post menopausal women and should prompt consideration of colon cancer
Presentation of Iron deficiency anaemia (IDA)
often found incidentally
fatigue, SOB on exertion, pallor, palpitations koilonychia (spoon nails) atrophic glossitis angular stomatitis changes in hair / hair loss brittle nails angular chelitis
dysphagia due to oesophageal webs (Plummer-Vinson syndrome)
Investigations for Iron deficiency anaemia (IDA)
FBC
- microcytic hypo chromic anaemia
- reticulocytes ↓
iron studies
- serum iron ↓
- total iron binding capacity ↑
- transferrin ↑
- transferrin saturation ↓
- ferritin ↓
Blood film
- anisopoikilocytosis (red blood cells of different sizes and shapes)
- target cells (hypo chromic RBCs)
- ‘pencil’ poikilocytes
Management of Iron deficiency anaemia (IDA)
Treat underlying cause
PO ferrous sulfate/ferrous salts
-side effects include constipation, dark stools, nausea, diarrhoea, abdo pain
Parenteral iron supplements are reserved for severe cases
Iron rich diet
-e.g. dark green leafy veg, meat, iron fortified bread
NB consider urgent referral if pt with new IDA age >60yrs or <50yrs presenting with rectal bleeding (?colon cancer)
Macrocytic anaemia
a condition with ↓Hb & ↑MCV due to insufficent nucleus maturation reactive to cytoplasmic expansion due ti defective DNA synthesis or defective DNA repair
Aetiology
- Megaloblastic anaemia (characterised by hyperhsegmented neutrophils)
- Vit B12 deficiency
- Folate deficiency
- normoblastic anaemia
- alcohol abuse, liver disease, pregnancy, myelodysplasia, hypothyroidism
Pernicious anaemia
autoimmune disorder causing Vit B12 deficiency due to autoantibodies against intrinsic factor* ± gastric parietal cells
accounts for ~80% of megaloblastic anaemias
NB ↑ risk of gastric cancer
Presentation of Pernicious anaemia
fatigue, lethargy, palpitations, faintness, dyspnoea
pallor + jaundice (gives lemon twinge)
peripheral neuropathy
-typical symmetrical affecting arms & legs
subacute combined degeneration of the spinal cord
- progressive weakness, ataxia, parasthesia
- can progress to spasticity, paraplegia
neuropsychiatric features
-memory loss, poor concentration, confusion, depression, irritability
Investigations for Pernicious anaemia
FBC
- Hb↓
- MCV↑
Blood smear
- hypersegmented neutrophils
- megakaryocytes
Serum Vit B12 (↓)
Folate (normal or ↓)
anti intrinsic factor antibodies (+ve)
anti parietal cell antibodies (may be +ve)
transfusion thresholds
Hb levels <70g/L
Hb levels <80g/L in ACS
ongoing haemorrhage & chronic anaemia requiring transfusions do not have to meet these thresholds
Non haemolytic febrile transfusion reaction
thought to be due to leaked cytokines that accumulate during storage
presents with fever, chills and flushing
managed with temporarily stopping infusion, paracetamol, restarting transfusion at slower rate with increased monitoring
Minor allergic reaction to transfusions
due to foreign plasma proteins
presents with urticaria, pruritus (i.e. only cutaneous symptoms)
managed by temporarily stopping infusion, antihistamines, restarting transfusion at slower rate with increased monitoring
Anaphylactic transfusion reaction
pt presents with SOB, dyspnoea, wheezing, angioedema, hypotension and respiratory distress
managed by stopping transfusion, 500mcg adrenaline IM (0.5ml 1:1000) & supportive measures
Acute haemolytic transfusion reaction
due to ABO incompatibility (this is a never event)
presents within minutes of starting transfusion with fever, abdo pain, hypotension, tachycardia, dyspnoea, chills & flushing
management
-STOP transfusion, supportive care, fluid resuscitation
NB blood should be returned to lab for confirmation i.e. direct coombs test & repeat crossmatch
Acute haemolytic transfusion reaction
due to ABO incompatibility (this is a never event)
presents within minutes of starting transfusion with fever, abdo pain, hypotension, tachycardia, dyspnoea, chills & flushing
can lead to DIC & renal failure
management
-STOP transfusion, supportive care, fluid resuscitation
NB blood should be returned to lab for confirmation i.e. direct coombs test & repeat crossmatch
Transfusion associated circulatory overload (TACO)
fluid overload secondary to excessive rate of transfusion or pre-existing HF
presents with hypertension, extended JVP S4 heart sound, peripheral oedema, pulmonary oedema (on CXR) and dyspnoea
managed by stopping/slowing transfusion & IV diuretics e.g. furosemide
Transfusion related acute lung injury (TRALI)
non cardiogenic pulmonary oedema due ↑ vascular permeability secondary to neutrophil activation
presents with hypoxia, dyspnoea, hypotension, fever, no signs of fluid overload, SOB & pulmonary infiltrates on CXR
managed by stopping transfusion, giving O2
-consider mechanical ventilation if required
Delayed transfusion reaction
24h - 28 days post infusion
generally mild symptoms including mild fever, jaundice, anaemia, chest/abdo/back pain
generally self limiting and do not need treatment
Fluid resuscitation
500ml bolus of crystalloids (usually NaCl 0.9%) over 15 min
-consider 250ml bolus if elderly or known HF
if no response then can repeat boluses to a maximum of 2000ml
- juniors should get senior help at 1000ml
- ITU support is needed at 2000ml
Routine maintenance fluid requirements
Daily requirements over 24h
- 25-30ml/kg of fluid
- 1mmol/kg of K+/Na+/Cl-
- 50-100g of glucose
Nb weight based K+ should be rounded to the nearest common fluid available so in 67kg person give 60mmol (one 40mmol & one 20mmol)
K+ replacement rate should not exceed 10mmol/h
Maximum rate of K+ infusion outside ITU
K+ replacement rate should not exceed 10mmol/h
Calculating fluid rate
flow rate = drip factor X (volume (ml)/minutes)
drip factor is found on the giving set packaging
flow rate is in drops/min`
Tumour lysis syndrome
an oncological emergency resulting from the rapid destruction of tumour cells leading to a massive release of intracellular components generally associated with the introduction of combination chemotherapy
Tumour lysis syndrome
an oncological emergency resulting from the rapid destruction of tumour cells leading to a massive release of intracellular components generally associated with the introduction of combination chemotherapy
associated with high grade lymphomas & leukemias especially Burkitts lymphoma
Characteristic features of Tumour lysis syndrome
Hyperkalaemia (K+ ↑)
hyperuricaemia (uric acid ↑)
hyperphosphataemia (Phosphate ↑)
hypocalcaemia (Ca2+ ↓)
Presentation of Tumour lysis syndrome
typically within 1-5 days of staring chemo
Renal failure
-oedema, lethargy, oliguria
Hyperkalaemia
-arrhythmias (syncope, palpitations, chest pain) nausea, vomiting
Hypocalcaemia
-seizures, tetany, muscle cramps, perioral paraesthesia
Investigations of Tumour lysis syndrome
uric acid > 475umol/l or 25% ↑ potassium > 6 mmol/l or 25% ↑ phosphate > 1.125mmol/l or 25% ↑ calcium < 1.75mmol/l or 25% ↓ serum creatinine ≥1.5x upper limit of normal LDH ↑ FBC U&Es
Management of Tumour lysis syndrome
Prevention is key
- High risk pt = IV allopurinol or IV rasburicase + ↑ hydration
- low risk pts = PO allopurinol
- meds to be given when chemo commences
Treatment:
- IV fluids & hydration
- IV Rasburicase (do not combine with allopurinol as ↓ activity of Rasburicase)
- cardiac monitoring
- IV calcium gluconate (if symptomatic ↓ Ca2+)
Heparin induced thrombocytopenia (HIT)
an immune mediated prothrombotic disorder characterised by a sudden drop in platelet count in a pt receiving heparin containing products
due to antibody formation against heparin platelet factor 4 (PF4)
usually occurs within 5-10days of initiating heparin
NB although platelet levels are low its a prothrombotic condition (platelet levels are low as they are activated & used up)
Presentation of Heparin induced thrombocytopenia (HIT)
Thrombotic manifestations
- mainly DVT, PE
- less commonly acute limb ischaemia, MI, stroke
localised skin necrosis at heparin injection sites
NB venous thrombosis is more common than retail thrombosis
NB bleeding is very uncommon
Investigations and management of Heparin induced thrombocytopenia (HIT)
Investigations
-FBC (↓platelets >50%)
Mangement
- stop heparin
- address need for ongoing coagulation with argabotran/fondaparinux/danaparoid
NB there should be lifetime avoidance of heparin
Factor V Leiden
i.e. activated protein C resistance =i most common inherited thrombophilia,
affects ~5% of UK population
leads to ↑ risk of VTEs, but usually not screened for
