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Liv Path > Haem - Non-Malignant > Flashcards

Haem - Non-Malignant Flashcards

1
Q

Anaemia - General

A

Hb <135 g/L in males and <115 g/L in females

Causes: decreased production, increased destruction, dilution

Classified based on MCV: microcytic (<80 fL), normocytic (80-100 fL), macrocytic (>100 fL)

Arise from disease processes affecting synthesis of haem, globin or porphyrin

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2
Q

Microcytic Anaemia - Key Differentials and Ix

A 
Key differentials (FAST):
Fe deficiency anaemia
Anaemia of Chronic disease 
Thalassaemia
Sideroblastic anaemia

Key investigations:
Peripheral blood smear
Iron studies

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3
Q

Iron Deficiency Anaemia - Causes

A

Commonest cause is blood loss - bleeding until proven otherwise

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4
Q

Iron Deficiency Anaemia - Key Features

A

Key features
Peripheral blood smear – pencil cells. Also microcytic, hypochromic anisocytosis and poikilocytosis.
Iron studies – ↓iron, ↓ferritin, ↑transferrin, ↑TIBC
FBC – reactive thrombocytosis

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5
Q

Iron Deficiency Anaemia - Rx

A

Investigate underlying cause, iron supplementation

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6
Q

Thalassemia General

A

α-thalassaemia, β-thalassaemia, thalassaemia trait

Key features
Peripheral blood smear – basophilic stippling, target cells
Iron studies – all normal

Management – iron supplementation, regular transfusions, iron chelation

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7
Q

Sideroblastic Anaemia - Causes

A

Congenital or acquired (myelodysplastic disorders, post chemo, irradiation, ALCOHOL EXCESS, lead excess, anti-TB drugs, myeloproliferative disease)

Ineffective erythropoiesis –> iron loading in the bone marrow –> haemosiderosis.

Results in endo, liver and cardiac damage due to iron deposition.

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8
Q

Sideroblastic Anaemia - Key Features

A

Iron studies – ↑iron, ↑ferritin, ↓transferrin, ↓TIBC
Peripheral blood smear – basophilic stippling
Bone marrow – ringed sideroblasts

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9
Q

Sideroblastic Anaemia - Rx

A

Treat underlying cause, regular transfusions. Pyridoxine (vit B6 promotes RBC production).

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10
Q

Macrocytic Anaemia - Key Differentials and Ix

A 
FATRBC
Foetus (pregnancy)
Antifolates (e.g. phenytoin)
Thyroid (hypothyroidism)
Reticulocytosis (e.g. with haemolysis)
B12/Folate Deficiency
Cirrhosis (alcohol excess or liver disease)
Myelodysplastic syndromes

Key differentials:
Megaloblastic anaemia - vitamin B12 deficiency, folate deficiency
Alcohol
Hypothyroidism

Key investigations:
Peripheral blood smear
LFTs
TFTs

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11
Q

Macrocytic Anaemia - Megaloblastic

A

Vitamin B12 or folate deficiency

How to differentiate?
Duration – months for folate deficiency, years for vitamin B12 deficiency (we have stores for 6months for folate but 1-2 years for B12)

Clinical findings – vitamin B12 deficiency associated with neurological changes

Serum methylmalonic acid – elevated in vitamin B12 deficiency

Schilling test – positive in vitamin B12 deficiency 2º to pernicious anaemia

Drug history – phenytoin inhibits folate absorption

Management – vitamin supplementation (need to supplement B12 BEFORE folate otherwise may mask B12 deficiency –> neuro damage)

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12
Q

B12 Def - Causes

A

Dietary - often vegans (found in meat and dairy products)

Malabsorption
Stomach - pernicious anaemia
Terminal ileum - ileal resection, Crohn’s, bacterial overgrowth, tropical sprue, tapeworms

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13
Q

Folate Def - Causes

A

Poor diet
Increased demand: pregnancy, or increased cell turnover (haemolysis, malignancy, inflammatory disease, renal dialysis)
Malabsorption: coeliac, tropical sprue
Drugs: alcohol, anti-epileptics (phenytoin), methotrexate, trimethoprim

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14
Q

B12 Def - Rx

A

IM hydroxocobalamin

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15
Q

Folate def - Rx

A

Oral folate

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16
Q

Macrocytic Anaemia - Non-megaloblastic

A

Alcohol, hypothyroidism, pregnancy

How to differentiate?
History – features of hypothyroidism
Clinical findings – hepatomegaly, gynaecomastia, abdominal veins, ascites, jaundice
LFTs – ↑AST, ↑ALT, ↑GGT, AST:ALT >2:1
TFTs – ↑TSH, ↓T3/T4, anti-thyroid peroxidase antibodies

Management – treat underlying cause

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17
Q

Normocytic Anaemia - Key Differentials and Ix

A 
Acute blood loss
Anaemia of chronic disease
Bone marrow failure
Renal failure
Hypothyroidism
Haemolysis
Pregnancy

Key differentials
Haemolytic: inherited or acquired (immune-mediated, non-immune-mediated)
Non-haemolytic: anaemia of chronic disease, failure of erythropoiesis

Key investigations
Peripheral blood smear
DAT
CRP, ESR

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18
Q

Anaemia of Chronic Disease

A

Infection, inflammation, malignancy

Key features
Inflammatory markers – raised CRP, ESR
Iron studies – ↑iron, ↑ferritin, ↓transferrin, ↓TIBC

Management – treat underlying cause

Ferritin high as Fe sequestered in macrophages to deprive invading macrophages of Fe.

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19
Q

Haemolytic Anaemia - Causes

A

INHERITED
Membrane defect: hereditary spherocytosis, hereditary elliptopcytosis

Enzyme defect: G6PD deficiency, pyruvate kinase deficiency

Haemoglobinopathies: sickle cell, thalassemias

ACQUIRED
Immune:
Auto-immune - warm or cold
Allo-immune - haemolytic transfusion reactions

Non-Immune:
Microangiopathic - paroxysmal nocturnal haemoglobinuria, MAHA
Macroangiopathic - mechanical e.g. metal valves, trauma
Infections i.e. malaria/Drugs

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20
Q

Hereditary Spherocytosis

A

AD inheritance
Defect in the vertical interaction of the red cell membrane
Spectrin/ankyrin deficiency

Key features
Peripheral blood smear: spherocytes, polychromasia
Positive osmotic fragility test
Positive eosin-5-maleimide (most sensitive test)
(will have -ve DAT test as not autoimmune mediated)

Management – folate supplementation, splenectomy

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21
Q

Hereditary Elliptocytosis

A

AD inheritance
Spectrin mutations
Defect in the horizontal interaction of the red cell membrane

Severity ranges from hydro foetalis to symptomatic

Erythrocytes are elliptical in shape on blood film

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22
Q

G6PD

A

X-linked recessive

G6PD generates NADPH via pentose phosphate pathway

Key features
Episodes of acute haemolysis (anaemia and jaundice) following exposure to oxidative stress (e.g. fava beans, mothballs, drugs- sulfonamides, aspirin etc)
Peripheral blood smear: Heinz bodies, bite cells
Intravascular haemolysis: ↑unconjugated bilirubin, ↓haptoglobin, haemoglobinuria

Management – avoidance of triggers, supportive care, transfuse if severe

Diagnosis - enzyme assay 2-3 months after attack

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23
Q

Pyruvate Kinase Deficiency

A

Autosomal recessive
Clinical features: may present with severe neonatal jaundice, splenomegaly, haemolytic anaemia

Rx- most don’t require treatment (but can include blood transfusion/splenectomy)

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24
Q

Haemoglobinopathies - general

A

Genetic disorders of globin chain synthesis

Haemoglobin
HbA (α2β2) – late foetus, infant, child and adult
HbA2 (α2δ2) – infant, child and adult
HbF (α2ɣ2) – foetus, infant

Diagnosis made with Hb electrophoresis

Disorders – thalassaemia, sickle cell disease

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25
Q

Sickle Cell Disease - Genetics

A 
Autosomal recessive (chromosome 7)
Glu --> Val mutation at codon 6 on the β globin chain --> HbS

HbSS (full sickle cell), HbAS (trait), HbSC (one sickle gene, one defective B), HbSβ (sickle from one parent, beta thal trait from other)

SS manifests at 3-6 months –> coincides with decreasing HbF

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26
Q

Sickle Cell Disease - Key Features & Diagnosis

A

Key features
Haemolytic crisis, sequestration crisis, aplastic crisis, infection (Streptococcus pneumoniae – sepsis, Salmonella – osteomyelitis)

Peripheral blood smear: sickle cells, target cells
Sickle solubility test positive in HbSS and HbAS
Hb electrophoresis
Guthrie test at birth

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27
Q

Sickle Cell Disease - Rx

A

Management – vaccination, folate supplementation, hydroxyurea (increases % HbF), supportive for acute crisis

Chronic - all should be on penicillin V, pneumovax, HIB vaccine

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28
Q

Beta Thalassemia - Genetics

A

Reduced synthesis of β globin chain (Chromosome 11)

Major (homozygous), intermedia and minor (heterozygous)

Β0 – no expression of the gene
Β+– some expression of the gene
Β – normal gene

β- thalassaemia minor (e.g. or β+/ β or β0/ β )
β- thalassaemia intermedia (e.g. β+/ β+ or β0/ β+)
β- thalassaemia major (β0/ β0)

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29
Q

Beta Thalassemia - Key Features

A

Major – severe anaemia requiring regular blood transfusions
Intermedia – genetically complex, moderate reduction in β globin chain production
Minor – benign but important genetically

Clinical presentation: Skull bossing, maxillary hypertrophy, hairs on end skull x-ray. Hepatosplenomegaly.

Diagnosis - Hb electrophoresis

30
Q

Beta Thalassemia - Rx

A

Regular blood transfusions, iron chelation (desferrioxamine), folate supplementation

31
Q

Alpha Thalassemia

A

Reduced synthesis of α globin chain (Chromosome 16) (excess B chains)

Hb Barts (x4), HbH (x3), trait (x2), silent (x1)

Key features
Hb Barts – fatal in utero, hydrops foetalis
HbH – severe anaemia in childhood, hepatosplenomegaly
Trait – mild anaemia
Silent – asymptomatic

Management – regular blood transfusions, iron chelation (desferrioxamine), folate supplementation

32
Q

Autoimmune Haemolytic Anaemia

A

Immune-mediated destruction of red blood cells, DAT positive

Warm
Mediated by IgG
Associated with CLL, SLE, methyldopa
Extravascular haemolysis

Cold
Mediated by IgM
Associated with Mycoplasma, EBV, hepatitis C
Intravascular haemolysis

Management – treat underlying cause, steroids, rituximab

33
Q

Paroxysmal Nocturnal Haemoglobinuria

A

Acquired loss of protective surface GPI markers on RBCs (platelets + neutrophils) → complement-mediated lysis → chronic intravascular haemolysis especially at night.

Morning haemoglobinuria, thrombosis (+Budd- Chiari syndrome – hepatic v thromb).

Diagnosis: immunophenotype shows altered GPI or Ham’s test (in vitro acid-induced lysis).

Treatment: iron/folate supplements, prophylactic vaccines/antibiotics. Expensive monoclonal antibodies (eculizumab) that prevents complement from binding RBCs

34
Q

Microangiopathic Haemolytic Anaemia

A

Non-immune-mediated, small vessel disease

Damage to endothelial cells within the vasculature –> fibrin deposition and platelet aggregation –> fragmentation of red blood cells

Key features
Peripheral blood smear: schistocytes, thrombocytopenia
Disorders – HUS, TTP, DIC
Distinguish from DIC with normal APTT, PT, fibrinogen (DIC would make you consume all of your clotting factors. DIC can cause MAHA but they are separate entities. DIC causing MAHA is consumptive but MAHA itself is not consumptive_

Management – treat underlying cause, supportive

35
Q

Haemolytic Uraemic Syndrome

A

Commonly caused by Escherichia coli O157:H7 – Shiga-like toxin

More frequent but less severe in children

Key features
Symptoms occur after a diarrhoeal illness – do not give antibiotics to treat
Triad of MAHA, thrombocytopenia, acute renal failure (self-limiting in children)
Features of MAHA on peripheral blood smear

Management – supportive care

36
Q

Thrombotic Thrombocytopenic Purpura

A

Deficiency of ADAMTS13 (ABs against it) –> decreased break down of multimers of vWF (stay in vessels like cheese wire and chop up RBCs)

Can be inherited or acquired

Key features
Pentad of MAHA, thrombocytopenia, acute renal failure, neurological symptoms, fever
High mortality rate

Management – supportive care, plasma exchange

37
Q

Haemostasis and Thrombosis - Background

A

Disorders of primary or secondary haemostasis
Primary – platelet adhesion and aggregation (quantitative and qualitative defects)
Secondary – coagulation cascade (inherited and acquired)

Disorders of thrombosis occur as a result of Virchow’s triad
Inherited – factor V Leiden, anti-thrombin deficiency, protein C/S deficiency
Acquired – HIT, malignancy, immobilisation

38
Q

Which pathway is used to monitor heparin therapy?

A

Intrinsic - APTT

39
Q

Which pathway is used to monitor warfarin therapy (INR)

A

Extrinsic - PT

40
Q

Haemostasis

A

Dysfunction in primary haemostasis –> bleeding disorders (superficial bleeding)
Qualitative defect in platelets – von Willebrand disease
Quantitative defect in platelets – ITP, HIT

Dysfunction in secondary haemostasis –> coagulation disorders (deep bleeding)
Inherited disorders – haemophilia A, haemophilia B
Acquired disorders – liver disease, vitamin K deficiency

41
Q

von Willebrand Disease Subtypes

A

Subtypes
Type I – autosomal dominant, quantitative defect
Type II – autosomal dominant, qualitative defect
Type III – autosomal recessive, quantitative and qualitative defects

42
Q

von Willebrand Disease - Key Features

A

Mucocutaneous bleeding
↓platelet adhesion, ↓factor VIII, abnormal ristocetin
↓platelet count, ↑bleeding time, ↑APTT, normal PT

Differentials include Bernard-Soulier disease (large platelets) and Glanzmann’s thrombasthaenia (normal ristocetin)

43
Q

von Willebrand Disease - Rx

A

Desmopressin, vWF and factor VIII concentrates

44
Q

Acute Immune Thrombocytopenia

A

Predominantly children, M:F 1:1
Preceding infection
Self-limiting, treatment with steroids and IVIG if platelet count ↓↓↓, major bleeding

Sudden onset generalised petechiae and purpura. Bleeding from the gums/mucous membranes.

45
Q

Chronic Immune Thrombocytopenia

A

Commonly adults, M:F 1:3
No trigger
Long-term relapsing-remitting, treatment with steroids, IVIG or splenectomy

46
Q

Haemophilia A

A

X-linked recessive

Factor VIII deficiency

Key features
Spontaneous, deep bleeding, haemarthrosis
Normal platelet count, normal bleeding time, ↑APTT, normal PT
More common than Haemophilia B

Management – factor VIII concentrate

47
Q

Haemophilia B

A

X-linked recessive

Factor IX deficiency

Key features
Spontaneous, deep bleeding, haemarthrosis
Normal platelet count, normal bleeding time, ↑APTT, normal PT

Management – factor IX concentrate

48
Q

DIC

A

Acquired coagulation disorder

Widespread activation of coagulation. Clotting factors and platelets are consumed → ↑ risk of bleeding

Causes: Malignancy, sepsis, trauma, obstetric complications, toxins.

Low plts, low fibrinogen, high FDP/D-Dimer, long PT/INR.

Rx- Treat the cause and give transfusions, FFP, platelets, cryo etc.

49
Q

Liver disease

A

Acquired coagulation disorder

↓ synthesis of II, V, VII, IX, X, XI and fibrinogen
↓ absorption of vitamin K
Abnormalities of platelet function

50
Q

Vitamin K Deficiency

A

Vitamin K necessary for synthesis of factors II, VII, IX and X, protein C/S

Secondary to malabsorption, warfarin, antibiotic therapy

Key features
Factor VII first factor to be depleted
Normal platelet count, normal bleeding time, ↑APTT, ↑PT
Differentials include liver disease (↓platelet count), scurvy (corkscrew hair)

Management – vitamin K replacement, prothrombin complex concentrate (PCC), FFP

51
Q

Virchow’s triad

A

VTE RFs

Vessel wall injury, blood hypercoagulability, blood stasis.

52
Q

Factor V Leiden

A

Autosomal dominant – most common inherited prothrombotic disorder

Present in 5% of caucasian population

Key features
Resistance to protein C –> failure to degrade factor V –> hypercoagulable state
Predisposition to venous thromboembolism (arterial thromboembolism rare)

Management – long-term anti-coagulation

53
Q

Antithrombin deficiency

A

Autosomal dominant

Key features
Carries highest risk of thrombosis
Develop thromboembolism in unusual locations (e.g. splenic or mesenteric veins)
Anti-thrombin assay used to make diagnosis
Key differentials include protein C/S deficiency

Management – long-term anti-coagulation with warfarin and argatroban

54
Q

Protein C/S Deficiency

A

Autosomal dominant

Key features
Predisposition to venous thromboembolism (arterial thromboembolism rare)
Associated with warfarin-induced skin necrosis – initial pro-coagulant state –> ischaemia of skin vessels
Protein C/S assay

Management – long-term anti-coagulation with argatroban

55
Q

DVT Prophylaxis

A

Daily subcutaneous LMWH (prophylactic dose), TED stockings

56
Q

DVT Management

A

LMWH (treatment dose) followed by Warfarin or Apixaban/Rivaroxaban/Edoxaban (DOACs)

57
Q

Investigation based on Wells Score for VTE

A

High Wells score – Ultrasound affected limb for DVT / CTPA for PE
Intermediate Wells score – D-DIMER: if high, ultrasound/CTPA; if low, rule out
Low Wells score – consider other diagnosis

58
Q

Obstetric Haem - Background

A

Volume expansion –> ↑cardiac output, dilutional anaemia

Thrombocytopenia – returns to normal post-partum

Hypercoagulable and hypofibrinolytic state –> ↑risk of venous thromboembolism. Highest risk of VTE is postpartum.

59
Q

Haemolytic Disease of the Newborn

A

Prior sensitisation of Rh-negative women from previous pregnancy (make anti-D ABs to D antigen on foetal RBCs)

Key features
IgG-mediated
Foetal anaemia, hydrops foetalis, neonatal jaundice, kernicterus
Monitor foetus for anaemia with MCA doppler ultrasound

Management – prevent sensitisation with anti-D Ig routinely at 28 weeks and within 72 hours of sensitising event, intra-uterine transfusion

Always transfuses Rh-ve blood to Rh-ve women of childbearing age

60
Q

HELLP Syndrome

A

Haemolysis, elevated liver enzymes, low platelets

Life-threatening complication associated with pregnancy (only happens in PET)

Key features
MAHA, ↑↑AST, ↑↑ALT, ↓platelets, normal APTT, PT
Differentials include DIC (↑APTT, ↑PT, ↓fibrinogen), AFLP (marked transaminitis)

Management – supportive, delivery of foetus

61
Q

Acute Transfusion Reactions - Anaphylaxis

A

Symptoms occur within minutes

Risk increases in patients with IgA deficiency

62
Q

Acute Transfusion Reactions - ABO incompatibility

A

Symptoms occur within minutes to hours

Intravascular haemolysis – IgM-mediated

63
Q

Acute Transfusion Reactions - Bacterial Contamination

A

Symptoms occur within minutes to hours

More commonly occurs with platelet transfusion

64
Q

Acute Transfusion Reactions - Febrile Non-Haemolytic Transfusion Reaction

A

Rise in temperature of ≤1ºC without circulatory collapse

Caused by release of cytokines by leukocytes and prevented by leukodepletion

65
Q

Acute Transfusion Reactions - Transfusion Associated Circulatory Overload (TACO)

A

Symptoms of pulmonary oedema/fluid overload occur within hours
Look for signs of heart failure: ↑JVP, ↑PCWP (pulmonary capillary wedge pressure)

66
Q

Acute Transfusion Reactions - Transfusion-Related Acute Lung Injury

A

Symptoms similar to TACO
Caused by interaction with anti-HLA antibodies in donor blood with recipient
Absence of heart failure

67
Q

Delayed Transfusion Reactions - Delayed-haemolytic transfusion reaction

A

Occurs within 1 week

Extravascular haemolysis – IgG-mediated

68
Q

Delayed Transfusion Reactions - Graft vs Host Disease

A

Symptoms include diarrhoea, liver failure, skin desquamation and bone marrow failure
Donor lymphocytes recognise recipient’s HLA as foreign and attack gut, liver, skin and bone marrow
Prevent by irradiating blood components for immunosuppressed recipients

69
Q

Warfarin Reversal

A

INR ≤5 – lower or omit next dose

INR 5-9 – either omit next dose or oral vitamin K

INR >9 – omit next dose + oral vitamin K

Any bleeding – omit next dose + IV vitamin K + PCC or FFP

(the higher the INR, the more likely the pt is to bleed)

70
Q

Reversing Anticoagulants

A

Heparin/LMWH: Protamine

Rivaroxaban, apixaban: Prothrombin complex concentrate (PCC)

Dabigatran: Antibody (Idarucizumab - expensive) or PCC

Aspirin / clopidogrel: platelet transfusion

Liv Path (24 decks)

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