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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_958_Библиотеки_им_академика_М_И_Перельмана
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von Willebrand disease
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• Bruising
• Prolonged bleeding
• Mucosal bleeding – epistaxis, menorrhagia
Chapter 5: Haematology 75
von Willebrand factor:
• facilitates platelet adhesion
• carrier protein for factor VIII
preventing its degradation
Mild APTT, normal platelets & INR
For any acute bleeds: elevation, compression & tranexamic acid
• Mild (10–50%): PO/IV tranexamic acid ± SC or nasal desmopressin (DDAVP)
• Moderate/severe: recombinant vWF
Most common inherited bleeding disorder
Thrombophilias
1. Inherited:
• Factor V Leiden and prothrombin mutations (most common
in north Europe)
• Protein C/S deficiency
2. Acquired:
• Antiphospholipid syndrome
• FBC & clotting
• Protein C & S levels, homocysteine
• Antiphospholipid Abs (lupus anticoagulant, anticardiolipin, B2-glycoprotein
antibodies)
• ± Factor V Leiden and prothrombin mutations
Consider thrombophilia screen if:
• Arterial thrombosis <50y
• Venous thrombosis <40y & no RFs
• Recurrent, unexplained V TE
• Familial VTE
• Recurrent miscarriage
• Unusual site of thrombosis
e.g. mesenteric veins
Medicine
76 Chapter 5: Haematology
auma
brin clot
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Performing clotting studies:
Blue-topped bottle
(2nd in draw order after blood cultures)
in both PT & APTT =
a) common path problem (CF II, V, X) OR
b) global CF deficiency (e.g. vit K antagonism
affecting CF II, VII, IX, X)
History & examination
• Symptoms: bleeding/bruising/menorrhagia; where, how much, associated Sx
• PMHx/FHx: bleeding/clotting disorders, liver dysfunction, autoimmune
• DHx: anticoagulants, NSAIDs, ABX
• SHx: alcohol, smoking
Ask if ever happened before
e.g. with operations / dental work
Coagulation testing
INTRINSIC PATHWAY
1. FBC & blood film: plt
number & morphology
2. Other: vWF assays, plt
func. (not routine)
1. Clotting screen
• PT = extrinsic pathway
(CF 7 & 10)
• APTT = intrinsic
pathway (CF 8-12)
• Thrombin time = time
for fibrinogen to make
fibrin
2. Mixing studies: patient
plasma + FFP
• Full correction indicates
CF deficiency
• No correction indicates
CF inhibition (i.e. antibody against CF)
3. Fibrinogen and fibrinogen degradation products / d-dimers
4. CF assays: measure individual CF levels (depending on mixing
studies / othertests)
Damaged
Surface
Kininogen
Kallikrein
XII
XI
APPT
FINAL COMMON
PATHWAY
EXTRINSIC PATHWAY
XII
a
IX
XI
a
IX
a
X
Prothrombin
(II)
Fibrinogen
VIII
a
(I)
X
a
VII
V
a
Thrombin
Trauma
a
Tissue
factor
)
(II
a
Cross-linked
Fig. 5.7 Coagulation cascade.
X
Fibrin
PT
VII
Tr
)
(I
a
XIII
a
Medicine
Types of anticoagulant
Heparins: act on CFs II & X – cause prolonged APTT → reverse with protamine sulphate
Warfarin: vitamin K antagonist affects CFs II, VII, IX, X to cause prolonged APTT & PT →
DOACs: reversible inhibitors of CF Xa → NB: they have poor correlation with APTT & PT →
Blood groups
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• Blood group determined by antigens on RBCs → encoded by A, B & O genes
on chromosome 9
• From 3 months old we produce natural IgM antibodies against the A or B
antigens that we don’t have
• Receiving ABO incompatible blood can cause massive transfusion reaction
& death
Group UK prevalence Antigens Antibodies
O 47% None
A & B
A 42% A B
B 8% B A
AB 3% A & B None
Rhesus antigen
Chapter 5: Haematology 77
Universal donor blood is O Rh −ve
Alleles / inheritance of blood group:
O = OO → recessive
A = AA, AO → co-dominant
B = BB, BO → co-dominant
AB = AB → co-dominant
• Encoded by 2 genes (D gene & CcEe gene)
1 unit blood increases Hb by 10g/L
(repeat Hb measurement 30min
• Rh −ve individuals will produce IgG antibodies (anti-D) if exposed to d-antigen
post-transfusion)
Transfuse 1U over 2h if non-urgent
Blood products
Product Indication
RBC Acute anaemia <70g/dL*, blood loss (haemorrhage), bone marrow failure, SCD/thalassaemia
Platelets
FFP Clotting defects (e.g. DIC, liver disease, TTP), major haemorrhage
Cryoprecipitate Fibrinogen / factor VIII replacement (e.g. haemophilia, vWD, DIC with bleeding)
Human albumin solution Protein replacement (e.g. ascitic tap)
Alternatives to blood transfusion:
• Cell savers (recycle & clean patient’s own blood during operations)
• Iron infusion (if iron-deficient) or B12/folate replacement (if folate-deficient)
• EPO
Process of blood transfusion
Bleeding or Plt count <10 × 109 due to DIC with bleeding or chemotherapy → must not give if ITP or TTP
8
Do not transfuse patients with
very low B12 or folate
• CAREFULLY LABEL samples for cross-match to ensure no mistakes
• Explain risks and benefits to patient & document their verbal consent →
give patient info leaflet
• Assess & document TACO risk in patient
• Complete prescription including special requests**
• Go through pre-collection checklist incl. any previous transfusion reactions
• Prep patient: record obs & insert wide-bore cannula
8
British Society for Haematology (2017) The administration of blood components
Medicine
78 Chapter 5: Haematology
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• Patient ID & consent
• Component prescription – correct type, compatibility, correct rate,
signed by doctor
• Expiry date & appearance of unit – any discolouration/damage
• Document date & time of start → complete & stick pink sticker on prescription
chart & return blue sticker to blood bank
(temp., pulse, RR, BP)
Massive blood transfusion
Indications: trauma, ruptured AAA, GI bleed, cardiac surgery etc.
Complications: dilution of platelets & clotting factors → triad: acidosis,
Major transfusion protocol: triggered if SBP <80mm/Hg → combine RBCs with
FFP & cryoprecipitate
Temp ≥39°C or ≥2 from baseline = stop
transfusion & senior r/v
Complications of blood transfusion
Pathogenesis: mismatched ABO group = complement activation & intravascular
haemolysis
Symptoms: temp, BP, HR, abdo/chest pain, anxiety
Complications: shock, renal failure, DIC & death
Management: stop transfusion → ABCDE, saline, check identity of unit
*** Tell blood bank, repeat G&S sample, do haemolysis and coag screen, and send
this with blood unit to blood bank ***
Symptoms: shivering & fever 1.5h post-transfusion
Management: slow/stop transfusion + antipyretic
Mild allergy: urticaria, itch
Severe anaphylaxis: bronchospasm, wheeze/stridor, cyanosis
*** Tell blood bank and check IgA (may be IgA-deficient and so have made
antibodies to IgA = 1 in 700) ***
More common with platelet transfusion
Symptoms: rigors, fever, hypotension → shock
Management: stop transfusion & start Sepsis 6
*** Tell blood bank & culture the blood unit ***
Medicine
Pathogenesis: due to Abs in donor plasma vs. host neutrophils, FFP or platelets
(FFP & platelets contain more antibodies so greater risk of reaction)
Symptoms: SOB, cough, hypoxia, white-out on CXR (2–6h post-transfusion)
Management: stop transfusion, ABCDE, 100% O
*** Tell blood bank and screen the donor unit for antibodies → they may have
donated other units ***
2
Chapter 5: Haematology 79
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Symptoms: within 6h post-transfusion
• Dyspnoea, hypoxia
• Tachycardia, hypertension
• Basal crepitations (pulm. oedema)
Pathogenesis:
• Only seen in immunosuppressed, as normal immune systems kill lymphocytes
transfused in units of blood
• In TA-GVHD, lymphocytes from the transfused blood attack the recipient’s skin,
bone marrow, and gut
Symptoms: rash, fever, diarrhoea, BM failure 1–3w post-transfusion
Pathogenesis:
• Slower antibody response to a foreign antigen on transfused blood than with
ABO mismatch
• Causes extravascular haemolysis, and progressive anaemia
Symptoms: fever, haemolysis (jaundice), dark urine & falling Hb
Tests:
1. Haemolysis screen: LDH, unconjugated bilirubin, haptoglobin
2. Direct Coombs test: positive
3. Antibody identification – to ensure patient doesn’t receive a unit expressing
that antigen again
Treatment: symptomatic Tx (paracetamol) + avoid future transfusions containing
the implicated RBC antigen
Management:
• Slow/stop transfusion
• O2 – may need ventilation
• Consider exchange transfusion
Risk factors for TACO:
• >70y
• Low weight / child
• Cardiac failure
rare
Cannot give blood again
if have received a blood transfusion
• Renal
impairment / low
albumin
Pathogenesis:
• Host produces antibodies against donor platelets which destroy both the
transfused platelets & patient’s own platelets
• Results in severe, persistent thrombocytopenia
Symptoms: thrombocytopenia → purpura, bleeding
Treatment: IV immunoglobulins ± steroids
Medicine
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inhibitor
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cell-mediatedcytotoxicity
81
assay
ofunknown significance
immunodeficiency
82 Chapter 6: Immunology and allergy
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Common allergens:
• nuts, shellfish, eggs, sesame seeds
• pollen, dust mites, animal fur
• insect stings
Denitions
hypotension, HR, oedema, wheeze/stridor
e.g. radioactive dyes
due to direct mast cell damage
Classifying allergic disorders
Type 1 IgE crosslinking via allergen triggers mast cell degranulation Asthma, food allergies
Type 2 IgG binds cell-surface antigen (ADCC) triggering complement reaction & cell lysis MG, Goodpasture’s
Type 3
Type 4
IgG binds free antigen → immune complexes deposit in tissues
Cell-mediated – T cells activate macrophages → inflammatory mediators & B cell activation (delayed reaction)
SLE, HSP
Contact dermatitis
Investigations
Symptoms of allergies:
• Rash
• Pruritus
• Swelling/angioedema
• Sneezing/rhinorrhoea
• Dyspnoea, wheeze, tachypnoea
• Nausea, vomiting, diarrhoea
Long-term management of allergies:
1. Avoid allergen
2. Prescribe 2x EpiPens
3. EpiPen training & education
4. Medi-Bracelet / alert device
5. Antihistamines if appropriate
6. Good asthma control if have it
1. Detailed history (most important)
• Symptoms – timing, type, previous experience
• Potential allergen identification – what? when? how much eaten?
• DHx, PMHx, FHx – other atopies
2. Skin prick test: prick with antigen of allergen/s & measure size of rash
• Positive control: histamine – may be negative if on antihistamines
• Negative control: saline – only have reaction if dermographism
(skin reaction to trauma → not allergy)
3. IgE testing: if skin prick not conclusive
• Total IgE: not specific to allergen
• Specific IgE
4. Challenge tests: last resort / to prove negative → ONLY UNDER CLOSE
MEDICAL SUPERVISION
Can measure
suspect mast cell disorder (often
associated with insect sting reactions)
baseline tryptase
if
*chronic urticaria = rarely allergic aetiology
DDx of anaphylaxis:
• ACEi angioedema (no urticaria)
• Hereditary angioedema
• Vasovagal episode
• Inducible laryngeal obstruction (ILO)
• Phaeochromocytoma
• Panic disorder
• Septic shock
Management of allergic rhinitis
Mild/intermittent
• Antihistamines
Medicine
Severe/persistent
• Antihistamines
• Intranasal steroid
• Chromone eyedrops
Specic reactions
Urticaria Angioedema
Causes Acute (<6w)
• Idiopathic/spontaneous
• Concurrent infection
• Allergic or
anaphylactoid reaction
Management Acute:
• Consider oral corticosteroids
Long-term:
1. Avoid triggers
2. Antihistamines (if allergic cause)
Chronic (>6w)*
• Idiopathic/
spontaneous
• Pressure, cold
• Dermographism
• ACEis
• Hereditary
• Viral infection
• Exercise, stress
Acute:
1. Stop ACEis (if taking)
2. Oral corticosteroids
3. TXA (may help)
Long-term:
Avoid triggers ±
antihistamines
Investigations
albumin
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• PMHx or FHx: autoimmune disorders / immunodeficiency / multisystem
disease
• Symptoms: constant fatigue, arthralgia, myalgia
• DHx: penicillamine
• Female
Normally have equal levels
of each globulin
Chapter 6: Immunology and allergy 83
α1 α2
Fig. 6.1 Serum electrophoresis.
β
γ
Autoimmune disease Immunodeficiency
• Urinalysis & BP
• FBC: anaemia, leukopenia,
thrombocytopenia
• CRP/ESR (ESR may be raised but not CRP)
• U&Es, LFTs
• Coagulation screen
• Complement & Ig levels: C3/C4
( in SLE, immune-complex diseases &
some infections)
• Autoantibodies
(tested for with ELISA/immunofluorescence)
• Blood-borne virus screen: HIV, HBV &
HCV serology
• FBC: lymphocyte subsets (T cells, B cells,
NK cells)
→ recognise immunodeficiencies
• Complement & Ig levels: C3/C4
( in SLE, immune-complex diseases &
some infections)
• Antibody levels: IgG/A/M
( in myeloma & Ig deficiencies)
• Functional antibody testing: shows how
well Igs function
(measure Ig levels pre- & post-vaccination)
• Serum protein electrophoresis:
(abnormal levels in myeloma & Ig disorders)
• Urine protein electrophoresis: Bence
• Organ biopsy
• C XR / joint X-ray
• ECG
Jones protein
• Blood-borne virus screen: HIV, HBV &
HCV serology
Examples of Ig disorders:
• CVID
• Hyper IgM
• Hyper IgE
• MGUS
• Hypogammaglobulinaemia
Cryoglobulinaemia = disorder where abnormal Igs
become insoluble at cold temperatures
Medicine
84 Chapter 6: Immunology and allergy
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Summary of autoantibodies in dierent autoimmune
disorders
Condition Autoantibodies
Thyroid Graves’: TSI (thyroid-stimulating immunoglobulin)
Hashimoto’s: anti-TPO, anti-thyroglobulin
Addison’s disease Anti-21 hydroxylase
Pernicious anaemia Anti-intrinsic factor
Type 1 diabetes mellitus Insulin, GAD (glutamic acid decarboxylase) & islet cell
autoantibodies (associated with HLA-DR3/4 alleles)
Coeliac Anti-transglutaminase
Goodpasture’s syndrome Anti-type IV collagen (anti-basement membrane)
Autoimmune hepatitis ANA, anti-SM, anti-LKM
Primary biliary cholangitis Anti-mitochondrial
Primary sclerosing cholangitis ANCA
Rheumatoid arthritis RF, anti-CCP, anti-IgG
Systemic lupus erythematosus ANA, RNP, dsDNA, anti-SM, anti-Ro, anti-La
Anti-phospholipid syndrome Anti-lupus anticoagulant, anti-cardiolipin
Sjögren’s syndrome Anti-Ro (SSA), anti-La (SSB)
Scleroderma Anti-centromere
Pemphigoid Anti-desmoglein
Medicine
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