Haematology Flashcards
MCV?
Average cell size
RDW?
Red cell distribution width - measure of the range of variation of red blood cell volume
Reticulocytes?
Immature red cells
TIBC?
Total iron binding capacity - blood’s capacity to bind iron with transferrin
Haematocrit?
How many red cells in blood volume (% red cells) - if it decreases with Hb then it suggests decrease is dilutional
Mnemonic for remembering absorption?
DUDE IS JUST FEELING ILL BRO
Duodenum = iron Jejunum = folate Ileum = B12
Causes of micro, normo and macro-cytic anaemias
Micro = iron, thalassaemia Normo = chronic disease, sickle cell Macro = B12/folate, ETOH, pregnancy
Signs of IDA?
Pallor
Severe –> hyperdynamic circulation (tachy, flow murmurs, cardiac enlargement, rectal bleeding)
Chronic –> koilonychia, atrophic glossitis, angular stomatitis, post-cricoid webs
Investigations in IDA?
High = TIBC (clinging on to iron) Low = Hb, MCV, ferritin, serum iron, transferrin saturation
Ferritin = acute phase reactant
Management of IDA?
Ferrous sulphate/ferrous fumerate TDS
3 wks to 1 month - should increase Hb by 20 - continue for 3 months
SEs = constipation, black stools, abdo pain, nausea
Causes of macrocytic anaemia?
DIETARY
Lack of intake, alcohol
MALABSORPTION
Stomach - pernicious anaemia –> no intrinsic factor. Also post gastrectomy.
Terminal ileum - Crohn’s disease
PREGNANCY
ANYTHING THAT KNACKS UP BONE MARROW
Signs in macrocytic anaemia?
Lemon tinge to skin (pallor + haemolysis)
Glossitis, angular stomatitis
Complications of macrocytic anaemia?
Neuropsychiatric - irritability, depression, psychosis, dementia
Neurological - paresthesia, peripheral neuropathy, subacute combined generation of spinal cord
Investigations in macro anaemia?
High = MCV Low = Hb, WCC, platelets, serum B12, reticulocytes (because production is impaired)
Intrinsic causes of haemolytic anaemias?
RBC membrane - hereditary spherocytosis/elliptocytosis
Hb synthesis - sickle cell disease, thalassaemia
RBC enzymes - G6PD deficiency, pyruvate kinase deficiency
Extrinsic causes of haemolytic anaemia?
Immune - incompatibility (newborn, transfusion), AI haemolytic anaemia
Non-immune - infections (malaria, black water fever, Clostridium welchii), chemicals (lead, drugs, toxins)
Investigations in haemolytic anaemia?
High = reticulocytes, bilirubin, LDH
Low = Hb, haptoglobin (what Hb binds to)
Others = Coomb’s test (AI causes)
Management of haemolytic anaemia
HAEMATOLOGY
Folic acid, steroids, rituximab, IVIG (IV immunoglobulins)
Transfusion therapy
EPO
Pathophysiology of sickle cell disease?
Normal Hb = 2 alpha 2 beta –> 1 deficient beta chain
Autosomal recessive - heterozygotes = sickle cell trait
homozygotes = SC disease
Investigations in sickle cell?
Hb = 60-90
MCV normal
RBC breakdown –> high reticulocytes and bilirubin
Presentation of SC disease?
Anaemia + vaso-occlusive crisis (precipitated by hypoxia, infection, dehydration, cold)
Pain crisis, splenic infarct, stroke, priapism
Management of sickle cell crisis?
O2, morphine, treat cause (fluid/abx)
Pathophysiology of thalassaemia?
Normal globin chains, but not enough - autosomal recessive
Alpha/Beta, Trait/Major
Homozygous = major (disorder) - 2 chains deleted Heterozygous = trait (healthy carrier) - 1 chain deleted
Alpha major = death in utero (b/c only have fHb)
Beta major = severe anaemia
Presentation of thalassaemia?
Trait = often asymptomatic
B major = severe anaemia at 4-6 months (babies have HbF)
Characteristic facial features, splenomegaly, pallor, failure to thrive, stunted growth, HF
Presentation and treatment of haemochromatosis?
Iron overload (symptoms develop in middle age, later in females because of periods)
Bronze diabetes –> bronze deposits in skin, hepatic dysfunction, diabetes, gonadal dysfunction, cardiac problems
Treatment = venesection (once a week –> every few months)
Too little and too many white cells?
Too little = leucopenia (99% neutropenia)
Too many = leucocytosis
Definitions of neutropenia?
<1.5 = neutropenia <1 = infection <0.5 = immediate review
Causes of neutropenia?
REDUCED PRODUCTION
Marrow aplasia/infiltration, viral infections, TB, drugs (antimetabolites, sulphonamides, carbimazole, sulfasalazine)
INCREASED CONSUMPTION
Septicaemia (neutrophils used up), hypersplenism (neutrophils destroyed), autoimmune destruction of neutrophils (SLE, Felty’s syndrome)
Presentation of neutropenic sepsis?
7-10 days post-chemo
Fevers, rigors, malaise, hypothermia, hypotension, tachycardia, dizziness, reduced urine output
What is the MASCC risk score?
Assesses risk of complications during febrile neutropenic episode
What is involved in a neutropenic sepsis screen?
Bloods - FBC, LFT, U+E, CRP, lactate Cultures - line and peripheral cultures Swabs, viral swabs Sputum culture Urine analysis and culture Stool analysis and culture CXR
Management of neutropenic sepsis?
Empirical antibiotic therapy - TAZOCIN or VANC/AZTREONAM
?G-CSF
Differentials for leucocytosis?
Primary haem problem (cancer) or a secondary response (infection)
NEUTROPHILIA
Infection (rarely >30), CML (>200, really high), others (steroid use, post-op, MI, DKA)
LYMPHOCYTOSIS
Viral (infectious mono), CLL/ALL/NHL
LEUCOSTASIS
Emergency –> ischaemia
Too little and too many platelets?
Too little = thrombocytopenia
Too many = thrombocytosis
Definition of thrombocytopenia?
<100
in reality…
For surgery - should be over 100
>30 asymptomatic
<10 worrying
Causes of thrombocytopenia?
IMMUNE - ITP, drug induced (HEPARIN - 5-10 days after), SLE, post-transfusion
Dilutional Haemolytic uraemic syndrome Cancer DIC Decreased production (low numbers megakaryocytes - radiation)
Presentation of thrombocytopenia?
Bleeding tendency - spontaneous purpura/ecchymoses, mucous membrane bleeding, nose bleeds, menorrhagia, PPH
Rare (< 30) - retinal/subconjunctival haemorrhage, GI bleeding, intracranial bleeding
Thrombocytosis?
Differentiate between primary cause or secondary reactive cause
Primary = myeloproliferative neoplasm Secondary = acute phase reactant (rarely >1000)
Rough definition of leukaemias, lymphomas, myeloma?
Leukaemia = malignant cells in marrow
Lymphoma = malignant cells in LNs
Myeloma = plasma cell malignancy
Myelodysplasias = not enough cells, Myeloproliferative = too many cells
Acute myeloid leukaemia?
Older adults (65-70) - 80% under 50 get complete remission, 30% cure with chemo post-remission
Symptoms of anaemia, thrombocytopenia, neutropenia
Infections (bacterial/fungal)
Fever
DIC
Infiltration of extramedullary sites (lymphadenopathy, hepatosplenomegaly, CNS involvement, gingival infiltration)
Acute lymphoblastic leukaemia?
Kids (most commonly) - Philadelphia chromosome (Ph1) –> poor outcome. Good remission/cure rates.
Acute illness over several days, tiredness or non-specific aches over several weeks/months.
BONE MARROW FAILURE –> anaemia, thrombocytopenia (bleeding), bacterial infection
ACCUMULATION OF LEUKAEMIC CELLS –> bone/joint pain, hyperleukocytosis –> CNS involvement; tissue deposits of leukaemic cells –> gum hypertrophy, stomatitis; hepatosplenomegaly, lymphadenopathy, bone tenderness
Chronic myeloid leukaemia?
Median age 65 yrs. 95% have philadelphia chromosome.
Usually remains stable for years then transforms to more malignant fatal disease. Only bone marrow transplantation is curative.
REALLLY high WCC; splenomegaly, weight loss, sweats, anaemia, bleeding.
Chronic lymphocytic leukaemia?
Median age 69 years
Insidious onset - when symptoms present disease is advanced
‘B’ symptoms - lethargy, weight loss, fever, night sweats
Infections, anaemia, thrombocytopenia
Symmetrical, non-tender lymphadenopathy
Hepatosplenomegaly
Skin lesions (HZV, pruritis)
Histology and spread of Hodgkin’s lymphoma?
Histology = polymorphic - Reed-Steenberg cells diagnostic
Spread = predictable - step by step to contiguous LNs, starting in neck usually.
Histology and spread of Non-Hodgkin’s lymphoma?
Histology = monomorphic - malignant cells most numerous.
Spread = random
Aetiology and epidemiology of Hodgkin’s/Non-Hodgkins?
Hodgkins = unknown aetiology; bimodal distribution (many are young)
Non-Hodgkins = unknown aetiology (EBV, h.pylori, HIV, hep C); median age = 50, increasing with age.
What are B symptoms?
Indicate poor prognosis in lymphoma
Fever, night sweats, weight loss
Lymphadenopathy in Hodgkin’s?
Painless - single group of nodes (cervical/supraclavicular)
Lymphadenopathy in non-Hodgkin’s?
Painless (generalised; visceral) - typically disseminated at presentation
Symptoms in Hodgkin’s
B symptoms (25%) Pruritis Chest discomfort/cough/dyspnoea Anaemia Immune dysfunction
ETOH-induced LN pain
Symptoms in non-Hodgkin’s
B symptoms
Anaemia
Infections
Purpura
Staging system in Lymphoma?
Ann Arbor System
Investigations in lymphoma?
LN biospsy
Blood - film, FBC/ESR, U+E, LFT, bone profile, LDH (worse prog in non-hodgkin’s), HIV serology
Chest radiography
Staging with contrast (CT neck to pelvis or PET/CT)
Bone marrow biopsy
Management of Hodgkin’s?
Localised = RTx
Disseminated = high-dose chemotherapy (+/- stem cell transplantation)
Management of Non-Hodgkin’s?
INDOLENT
Local RTx = first line; watchful waiting if asymptomatic, rituximab, chemo
AGGRESSIVE
Usually HIV +ve; R-CHOP regimen; chemo/radioT; bone marrow/stem cell transplantation
What is myeloma?
Malignant proliferation of plasma cells
Presence of paraproteins in blood or urine
Associated organ dysfunction
What are paraproteins?
Abnormal immunoglobulin light chains –> damage kidneys by forming protein casts in renal tubules
How does myeloma cause bone pain/hypercalcaemia?
Abnormal plasma cells screte factors which activate osteoclasts
Lytic lesions, bone pain, hypercalcaemia
Risk factors for myeloma?
Age, male, afro-caribbean, +ve FH, obesity, diet
Mneominc for myeloma?
CRAB
HyperCalcaemia
Renal failure
Anaemia
Bone lesions
Presentation of myeloma?
Bone pain (spine, ribs, pepper pot skull)
Anaemia/thrombocytopenia (normocytic normochromic)
Renal failure (uraemic symptoms, itching/muscle cramps, SoB/oedema)
Infection
Neurological (hypercalcaemia, hyperviscosity, peripheral neuropathy)
Bloods in myeloma?
FBC - anaemia, neutropenia, thrombocytopenia
U+E - creatinine, hypercalcaemia
ESR - persistently raised
Blood film - Rouleaux formation
Protein electrophoresis –> bence jones protein (blood and urine)
Imaging in myeloma?
Skeletal survey –> x-rays of skull, axial skeleton and proximal long bones (lytic lesions)
What is the intrinsic pathway and what measures its time?
XII, XI, IX, VIII
aPTT
What is the extrinsic pathway and what measures its time?
TF + VII
PT
What is haemophilia A/B deficiency of?
A = FVIII B = FIX
What is prolonged in haemophilia?
aPTT
How is haemophilia inherited?
X-linked recessive (only affects males - can have female carriers)
How does haemophilia present?
Haemarthroses and soft tissue bleeds after trauma or spontaneously
What is vWD? How is it inherited?
Congenital deficiency of vWF
Autosomal dominant
What does vWF do? How does vWD present?
Is a cofactor essential for platelet adhesion and transport of factor VIII
Prolonged APTT, low levels of factor VIII and IX
Asymptomatic usually, and diagnosed following perioperative bleeding.
Haemarthroses, soft tissue haematomas, epistaxis and menorrhagia.
What can liver disease do to bleeding?
Increase INR, low platelets
What can renal disease do with bleeding?
Uraemic bleeding –> affects platelet function
Causes of DIC?
Malignancy, infection, obstetric complications
How does DIC happen?
Trigger –> release of THROMBIN –> activation of platelets and clotting factors –> these are used up and form microthrombi
Fibrinolytic system activates in response to thrombi –> unregulated fibrinolysis
THROMBOTIC AND HAEMORRHAGIC FEATURES
What is antithrombin III deficiency?
AT III inhibits thrombin, fXa, fXIIa, fXIIIa and fIXa
Autosomal dominant deficiency of this –> recurrent thrombosis and thromboembolism
What is protein C deficnecy?
Protein C = vit K dependent protease which inactivates fVIII and fV and stimulates fibrinolysis
deficiency —> THROMBOPHILIA
What is protein S deficiency?
Protein S = regulates protein C on surface of endothelial cells (needs Ca2+ as cofactor)
deficiency –> THROMBOPHILIA
Packed red cells - how much do they increase Hb and how long over?
1 unit lasts 4 hours
1 unit –> Hb increased by 10-15, given over 3 hours
Platelets - how much do they increase by and how long over?
1 unit –> plts increase by 20, given over 30 minutes.
lasts 24-48 hours in body
What are the special requirements for blood?
Hep E negative -
CMV negative - transplant patients
Irradiated blood - chemo/prego/immunosuppressed
ALWAYS ASK WHETHER PATIENT HAS ANY SPECIAL REQUIREMENTS
Additional treatments in transfusion?
Furosemide (if overloaded)
K+ treament –> can increase K+ because is intracellular and can damage cells
Name some acute transfusion reactions?
Febrile non-hemolytic transfusion reaction (FNHTRs)
Bacterial contamination
Transfusion related acute lung injury (TRALI)
Transfusion-related circulatory overload (TACO)
Allergic/anaphylactic reaction
Management of FNHTR?
Slow or temporarily stop transfusion
PCM
Monitor closely
Can occur up to 2 hours after. Less common now due to leucodepleted blood.
Management of bacterial contamination?
Stop transfusion
Urgent supportive care - IV abx
Call haem - send unit back to lab
Presentation of TRALI?
Antibodies in donor blood react with patients neutrophils, monocytes or pulmonary endothelium
Within 2 hours of transfusion
Severe breathlessness, cough + frothy sputum
Hypotension, fever, rigors
Management of TRALI?
Stop transfusion
Supportive managment - O2, ICU if required
Remove donor from panel
Presentation of TACO?
Acute pulmonary oedema
Acute resp distress, tachycardia, hypertensive, positive fluid balance
Managment of TACO?
Stop/slow transfusion
Oxygen/diuretic therapy
Careful monitoring and critical care if required
Management of allergic reaction?
Slow transfusion
Antihistamine (oral/IV) - chlorphenamine
Monitor closely
Management of anaphylaxis transfusion reaction?
STOP TRANSFUSION
Anaphylaxis algorithm
