Haematology Flashcards
How is anaemia defined?
- lower than normal concentration of haemoglobin/RBCs
- Hb <130 in men
- Hb <120 in women
What are the different types of anaemia?
- haemolytic = increased breakdown of RBCs
- aplastic = decreased RBC, WBC, platelets
- microcytic = reduced MCV
- macrocytic = raised MCV
- normocytic = normal MCV
What is MCV?
mean corpuscular volume
- average size of RBCs
General symptoms of anaemia
- fatigue
- headache
- dizziness
- dyspnoea esp on exertion
General signs of anaemia
- tachycardia
- skin pallor
- conjunctiva pallor
- intermittent claudication
What are signs of iron deficiency?
- koilonychia = spoon-shaped nails
- angular stomatitis
What are signs of B12 deficiency?
- angular stomatitis
- lemon-yellow skin
What are signs of haemolytic anaemia?
- jaundice
- dark urine
What are the causes of microcytic anaemia?
- iron deficiency
- anaemia of chronic disease
- sickle cell
- thalassemia
- sideroblastic anaemia
Investigations for iron deficiency microcytic anaemia
FBC → low Hb/MCV
Iron studies
- low ferratin unless active inflammation
- low serum iron
- low transferrin saturation
- raised transferrin
blood film → small, hypochromic cells
Causes of iron deficiency microcytic anaemia
reduced absorption
- low intake
- malabsorption
- drugs eg PPIs and tetracyclines
increased utilisation → pregnancy
blood loss
- stools
- urine
- trauma
- surgery
- menorrhagia
Investigations for chronic disease microcytic anaemia
FBC
- low Hb
- low/normal MCV
- high ESR
Iron studies
- normal/raised ferratin
- low serum iron
- low transferrin saturation/transferrin
Causes of chronic disease microcytic anaemia
- chronic infection
- chronic inflammation → connective tissue diseases
- neoplasia
What is thalassemia?
- inherited alpha or beta globin mutations
- varied presentation
- generally microcytic, hypochromic cells
What is sideroblastic anaemia?
- iron levels normal
- body cannot insert iron into Hb
- microcytic
- increased iron, transferrin, ferratin
- ringed sideroblasts on blood film
Causes of normocytic anaemia
- acute blood loss
- bone marrow failure
- pregnancy
- haemolytic anaemia
Presentation of haemolytic anaemia
- jaundice
- dark urine
Investigations for haemolytic anaemia
- raised reticulocytes (chronic)
- raised bilirubin
- raised urobilinogen
- schistocytes on blood film
Causes of haemolytic anaemia
- autoimmune
- sepsis
- DIC
- sickle cell
- thalassemia
What is the main cause of macrocytic anaemia?
B12 deficiency
Causes of B12 deficiency in macrocytic anaemia
- pernicious anaemia
- malabsorption → coeliac, IBD, bowel resection, ileostomy
- decreased dietary intake
- chronic NO use
Investigations for B12 deficiency in macrocytic anaemia
bloods
- raised MCV
- low Hb, B12
Signs and symptoms of B12 deficiency in macrocytic anaemia
- general anaemia presentation
- range of neurological symptoms
presents as megaloblastic anaemia
- cell changes on blood smear
- oval shaped RBCs
- hypersegmented neutrophils
Causes of macrocytic anaemia
- B12 deficiency
- diseases of the liver and spleen
- haematological malignancy
- alcohol → chronic consumption affects bone marrow
What is neutrophilia?
too many neutrophils
causes
- infection
- inflammation
- CML
What is neutropenia?
not enough neutrophils
causes
- Abs
- chemo
- marrow failure
- liver disease
What is thrombocytosis?
too many platelets
causes
- infection
- inflammation
- tissue injury
- splenectomy
- essential thrombocythemia
What is thrombocytopenia?
not enough platelets
causes
- production failure → marrow failure, congenital
- increased removal → ITP, TTP, DIC
What is lymphocytosis?
too many lymphocytes
causes
- EBV
- cytomegalovirus
- hepatitis
- malignancy → CLL, ALL, lymphoma
- stress
What is lymphocytopenia?
not enough lymphocytes
causes
- steroids
- HIV
- post viral
- marrow failure
- chemo
What is haemostasis?
process that stops bleeding
primary haemostasis
- initiation and formation of platelet plug
- platelet activation
secondary haemostasis
- formation of fibrin clot
- intrinsic and extrinsic coagulation cascade
What are the effects of platelet activation?
- platelet shape change
- dense granule release
- alpha granule release
Inheritance of sickle cell
- autosomal recessive
- gene on Cr11 → glutamic acid substitution with valine → B-globin polymerisation
What is sickle cell disease
- sickled cells
- endothelial damage
- reduced O2 carrying capacity
Acute presentation of sickle cell (7)
- bone and joint pain
- infection
- dyspnoea
- cough
- hypoxia
- stroke
- sequestrian crisis → blood outflow from spleen is blocked → blood accumulates → splenomegaly
Risk factors of sickle cell
- low O2
- cold weather
- parvovirus B19
- exertion
Chronic complications of sickle cell
- avascular necrosis of joints
- silent CNS infarcts
- retinopathy
- nephropathy
- ED
Investigations for sickle cell
- FBC → low MCV, Hb
- blood smear → sickled erythrocytes
- sickle solubility test → detects HbS → does not distinguish trait from disease
- Hb electrophoresis → band of Hbs
Management of sickle cell
acute
- morphine
- O2
- IV fluids
- transfusion exchange
chronic
- hydroxycarbamide → decreases DNA synthesis
What is HIV?
- human immunodeficiency virus
- leads to AIDS
- RNA retrovirus
- virus enters and destroys CD4 T helper cells
How is HIV transmitted?
- unprotected anal, vaginal, oral sex
- mother to child during pregnancy or breastfeeding → vertical transmission
- exposure to blood or bodily fluids
What are AIDS-defining illnesses?
occur when CD4 count drops to level that allows unusual infections and malignancies to appear
- Kaposi’s sarcoma
- PCP
- cytomegalovirus
- candidasis
- lymphomas
- TB
Who should be screened for HIV
- everyone admitted to hospital with an infectious disease should be tested
- patients with risk factors
- test initially then 3 months after exposure
Investigations for HIV
- antibody test
- p24 antigen → quicker
- PCR testing for HIV RNA gives viral load
Monitoring HIV
- CD4 count
- viral load
Treatment for HIV
- antiretroviral therapy ART
- aim is normal CD4 count and undetectable viral load
Natural progression of HIV
- acute primary infection → acute seroconversion illness
- asymptomatic phase
- early symptomatic HIV
- AIDS
Additional management of HIV
- if AIDS, prophylactic septrin to protect against PCP
- monitor and reduce CVD risk
- annual cervical smears for women
- up to date vaccines, but avoid live vaccines
What is HAART?
- highly active ART
- 2 nucleotide reverse transcriptase inhibitors and 1 non-nucloetide reverse transcriptase inhibitor
- 2 NRTIs and 1 protease inhibitor
What is PEP?
- post exposure prophylaxis
- must be started within 72 hours
- combination of ART therapy for 28 days
What is PrEP?
- pre exposure prophylaxis
- Take ART before exposure as prevention
- highly effective
What is leukaemia?
cancer of the bone marrow
- immature blast cells uncontrollably proliferate
- take up space in bone marrow
- then infiltrate into other tissues
lack of space in bone marrow → fewer healthy cells can mature and be released into blood
What are the 4 types of leukaemia
- acute lymphoblastic
- acute myeloid
- chronic lymphoblastic
- chronic myeloid
Features of ALL
- most common leukaemia in children → 0-4
- proliferation of immature lymphoblasts
Presentation of ALL
- general anaemia symptoms
- bleeding/bruising
- infections
- hepatosplenomegaly
- lymphadenopathy
- CNS infiltration → headaches, CN palsies
Diagnosis of ALL
- FBC → anaemia, thrombocytopenia, neutropenia
- blood film
- bone marrow biopsy
- CT/chest xray → lymphadenopathy
lumbar puncture in cases of CNS involvement
Management of ALL
- blood/platelet transfusions
- chemo → methotrexate
- steroids
- stem cell/bone marrow transplant
- Abs
Features of AML
- mostly elderly
- proliferation of immature myeloblasts
Presentation of AML
- general anaemia symptoms
- bleeding/bruising
- infections
- hepatosplenomegaly
- gum hypertrophy
Diagnosis of AML
- FBC → anaemia, thrombocytopnenia
- blood film
- bone marrow biopsy → auer rods
Management of AML
- blood and platelet transfusions
- chemo
- stem cell/bone marrow transplant
- Abs
Features of CLL
- mostly 60+
- most common type of leukaemia in adults
- proliferation of B lymphocytes
Presentation of CLL
- often asymptomatic
- lymphadenopathy
- may have night sweats and weight loss
Diagnosis of CLL
- FBC → anaemia, thrombocytopenia, leukocytosis
- blood film → smudge cells
- bone marrow biopsy
Management of CLL
- watch and wait in early stages
- chemo → rituximab
- stem cell/bone marrow transplant
Features of CML
- most common in 40+
- proliferation of myeloid blood cells
- associated with philadelphia chromosome
Presentation of CML
- general anaemia symptoms
- bleeding/bruising
- infections
- hepatosplenomegaly
- weight loss, night sweats
- gout
Diagnosis of CML
- FBC → anaemia, thrombocytopenia, leukocytosis
- bone marrow biopsy
- blood film
- genetic testing
Management of CML
- chemo
- stem cell/bone marrow transplant
- tyrosine kinase inhibitors → imatinib
Features of hodgkin lymphoma
- proliferation of lymphocytes in lymph nodes
- associated with EBV, immunosuppression
- bimodal distribution → early 20s then 70s
Presentation of hodgkin lymphoma
- lymphadenopathy → painful upon drinking alcohol
- B symptoms → fever, night sweats, weight loss
Diagnosis of hodgkin lymphoma
- ESR raised
- CT/chest xray for staging
- lymph node biopsy → Reed Sternberg cells
Management of hodgkin lymphoma
- ABVD chemo
- radiotherapy
- steroids
- stem cell/bone marrow transplant
What is ABVD chemo?
- adriamycin
- belomycin
- vinblastine
- decarbazine
Features of non-hodgkin lymphoma
- predominantly adults 40+
- associated with EBV, immunosuppression
Presentation of non-hodgkin lymphoma
- painless lymphadenopathy
- B symptoms
- can get hepatosplenomegaly
Diagnosis of non-hodgkin lymphoma
- CT/chest xray for staging
- lymph node biopsy → no Reed sternberg
Management of non-hodgkin lymphoma
- RCHOP chemo
- radiotherapy
What is RCHOP chemo?
- rituximab
- cyclophosphamide
- hydroxy-danorubicin
- oncovin
- prednisolone
What staging is used for lymphoma staging?
Ann Arbor staging
What is Ann Arbor staging
- disease in only one area
- disease in 2 or more areas on same side of diaphragm
- disease in 2 or more areas on both sides of diaphragm
- disease spread beyond lymph nodes
Features of multiple myeloma
- predominantly 40+
- close link to MGUS
What is MGUS
- monoclonal gammopathy of undetermined significance
- too much immunoglobulin released by abnormal plasma cells
- 1% develop into myeloma
Presentation of multiple myeloma
CRAB
- calcium elevation → polydipsia
- renal impairment
- anaemia
- bone lesions → bone pain
Diagnosis of multiple myeloma
- FBC → anaemia
- ESR raised
- blood film → Rouleaux formation
- serum and urine electrophoresis → Bence Jones protein in urine
- bone marrow biopsy
- CT/xray → bone lesions
Management of multiple myeloma
- chemo
- stem cell transplant
- analgesia
- bisphosphonates → zoledronic acid
- blood transfusions
Common chemo combinations for multiple myeloma
- VCD
- VTD
- MTP
What is polycythaemia
- high concentration of erythrocytes in the blood
- 2 types → absolute and relative
What is relative polycythaemia?
- normal number of erythrocytes
- reduction in plasma
causes
- obesity
- dehydration
- excessive alcohol
What is absolute polycythaemia?
- increased number of erythrocytes
- 2 types → primary and secondary
What is primary polycythaemia?
- abnormality in the bone marrow
- AKA polycythaemia vera
What is secondary polycythaemia?
- disease outside bone marrow causing overstimulation of bone marrow
causes
- COPD
- sleep apnoea
- PKD
- renal artery stenosis
- kidney cancer
Features of polycythaemia vera
- myeloproliferative neoplasm
- most people have JAK2 mutation
- affected bone marrow can also produce excessive platelets, WBCs
Presentation of polycythaemia vera
- headaches
- dizziness
- fatigue
- blurred vision
- red skin → hand, face, feet
- HTN
- itching esp after conact with warm water
- hepatosplenomegaly
Diagnosis of polycythaemia vera
- FBC → raised Hb, haematocrit, WCC, platelets
- genetic testing
- serum erythropoietin → decreased (raised/normal in other polycythaemias)
Management of polycythaemia vera
- venesection
- low dose aspirin daily
- hydroxycarbamide → if high risk of thrombus
What is pernicious anaemia?
- lack of intrinsic factor
- usually produced by parietal cells in stomach
- allows B12 absorption in terminal ileum
- low B12 = B12 deficiency macrocytic anaemia
Pathophysiology of TTP
- dysfunctional vWF cleaving protease
- can’t break clumps of vWF into useful monomers
3 microvascular clots form - problem with primary haemostasis
Presentation of TTP
- fatigue
- fever
- jaundice
- petechiae
- purpura
- neurological deficit
Investigations for TTP
FBC
- raised WCC
- low Hb, platelets
blood smear → schistocytes
other → raised bilirubin, creatinine
normal clotting
Treatment of TTP
- plasma exchange
- IV methylprednisolone
- monoclonal Abs
Pathophysiology of ITP
- autoimmune
- IgG destruction of GpIIb/IIIa
- platelets cannot activate
- problem with primary haemostasis
Presentation of ITP
same as TPP
Investigations for ITP
- FBC → raised WCC, low Hb and platelets
- clotting normal
- blood smear normal
Treatment of ITP
- steroids
- IV IgG
What is DIC
- disorder of primary and secondary haemostasis
- widespread activation of coagulation cascade and platelet activation
Presentation of DIC
- bleeding
- ARDS
Investigations for DIC
bloods
- low platelets
- low fibrinogen
- high d-dimer
- long PT
- long APTT
blood smear → schistocytes
Treatment for DIC
- treat underlying cause
- low fibrinogen → cryoprecipitate
- low platelets → transfusion
Causes of DIC
- sepsis
- crush injury
- malignancy
What is haemophilia
A
- factor VIII deficiency (intrinsic)
- secondary haemostasis
- X linked recessive
B
- factor IX deficiency (intrinsic)
Presentation of haemophilia
soft tissue bleeding pattern → into muscles, joints, haematoma formation
Investigations for haemophilia
- APTT long
- PT may be normal
- genetic testing
- factor VIII/IX testing
Treatment for haemophilia
- recombinant factor VIII or IX
- depends on type
What is Von Willebrand’s disease?
- defect in quantity or quality of vWF
- many subtypes
- varied inheritance
- primary haemostasis disorder
What is the most common type of Von Willebrand’s disease?
- type 1
- autosomal dominant
- quantitative disease
Presentation of Von Willebrand’s disease
mucocutaneous bleeding
- epistaxis
- GI bleeds
- menorrhagia
- easy bruising
Investigations for Von Willebrand’s disease
- plasma vWF
- APTT can be prolonged if FVIII low
How does Von Willebrand’s disease cause factor VIII deficiency?
- vWF protects FVIII from liver protein C destruction
- FVIII deficiency occurs is vWF affected
Treatment for Von Willebrand’s disease
- type 1 responds to desmopressin
- tranexamic acid → reduces acute bleeding
What is alpha thalassemia
gene deletion of one or both alpha chains
4 gene deletion
- incompatible with life
- infants often stillborn
3 gene deletion
- moderate anaemia
- splenomegaly
- not transfusion dependent
2 gene deletion
- microcytosis
- carrier presentation
Diagnosis of alpha thalassemia
FBC
- microcytic anaemia
- raised serum iron
Hb electrophoresis
Treatment of alpha thalassemia
- transfusion during crises
- desferrioxamine → iron excretion
- folic acid
What is beta thalassemia?
- decreased/absent beta chains
- excess alpha chains
- point mutations in gene
Presentation of minor beta thalassemia
- mild anaemia
- hypochromic RBCs
- often asymptomatic
Presentation of intermedia beta thalassemia
- infections
- gallstones
- recurrent leg ulcers
- bone deformities
Presentation of major beta thalassemia
- failure to thrive
- severe anaemia from 3-6 months
- thalassemic faces
- bone abnormalities
Diagnosis of beta thalassemia
blood film
- reticulocytosis
- microcytic anaemia
- nucleated RBCs in circulation
Treatment of beta thalassemia
regular life long
- transfusions
- iron-chelating agents → deferipone
- ascorbic acid
- folic acid
What is malaria?
- parasitic infection Plasmodium
- spread by female mosquito
- most common in Africa
What are the species of Plasmodium?
- p.falciparum → most common
- p.vivax
- p.ovale
- p.malariae → least common
Signs and symptoms of malaria
non-specific symptoms
- fever, chills
- headache
- cough
- splenomegaly
severe disease in p.falciparum
- SOB
- fits and hypovolaemia
- AKI and nephrotic syndrome
Investigations for malaria
- travel history
- thick and thin blood smears → 3 over 48hrs
- rapid diagnostic tests → detect parasitic antigens
- PCR
- bloods
- chest xray
- lumbar puncture
Treatment for malaria
non-falciparum malaria
- chloroquine
falciparum malaria
- oral quinine sulphate
- IV quinine dihydrochloride for severe disease
do not treat those with G6PD deficiency
What is tumour lysis syndrome?
collection of metabolic disturbances occurring with rapid destruction of neoplastic cells
Signs of tumour lysis syndrome
following chemo, rapid development of:
- hyperuricaemia, hyperkalaemia, hyperphosphatemia
- hypocalcemia
- AKI
Risk factors of tumour lysis syndrome
occurs more frequently with aggressive treatment of
- non-Hodgkin lymphoma
- leukaemia
Treatment for tumour lysis syndrome
allopurinol alongside chemo
What is G6PD?
- glucose-6-phosphate dehydrogenase
- role in pentose sugar metabolism
- protects RBCs from damage
What is G6PD deficiency?
RBCs exposed to more oxidative stress → haemolysis
Risk factors for G6PD deficiency
- X linked
- west africa, middle east, asia
Presentation of G6PD deficiency
- haemolytic anaemia
- splenomegaly
Investigations for G6PD deficiency
bloods
- anaemia
- increased LDH and reticulocytes → markers of haemolysis
blood smear → Heinz bodies
Treatment for G6PD deficiency
- blood transfusion
- stop exacerbating drugs
What is antiphospholipid syndrome?
- type of inherited thrombophilia
- AP antibodies bind to cell surfaces
Risk factors for antiphospholipid syndrome
- SLE
- females
- diabetes
- HTN
- obesity
Presentation of antiphospholipid syndrome
- unexplained thrombosis
- recurrent miscarriage
- Livedo reticularis
CLOT
What is heparin-induced thrombocytopenia
- heparin administration
- antibodies bind to drug
- prothrombotic state
problem with primary haemostasis
Presentation of heparin-induced thrombocytopenia
- onset of emboli → PE, DVT, CSVT
- suspect in any patient on heparin who’s platelets fall >50%
- bloods → low platelets, high D-dimer
Treatment of heparin-induced thrombocytopenia
- stop heparin
- anticoagulate
What is myelodysplasia
- heterogenous group of conditions
- defined by cell dysplasia
- often manifests as anaemia and bone marrow failure
- haemopoietic tissue is displaced by dysplastic cells
Presentation of myelodysplasia
- signs and symptoms of anaemia
- neutropenia → frequent infections
Investigations for myelodysplasia
- histological diagnosis
- wide variety of abnormalities
