Interpreting Blood Tests Part 2 - simplyrevision.org.uk

Interpreting Blood Tests

Part 2

Dr Andrew Smith

OutlinePrevious Talk:• Introduction• Which Tube!?!• FBCs• U+Es

This Week:• LFTs• Clotting• Extras:• D-Dimers• Acute Phase Reactants• TFTs• Calcium, Phosphate and Alk Phos• Immunoglobulins• Batch Tests

Case 13• A 36 year old man is referred to you in AnE because he is noted to

be jaundiced. He has been feeling generally unwell recently, with

some D+V.

• His LFTs show the following: What’s useful to know?

Normal Values

ALP 34 30-150µmol/L

ALT 12 5-35iu/L

AST 7 5-35iu/L

ɣGT 12 <45iu/L

Bil 88 <20µmol/L

Alb 37 35-50g/L

Rest of the bloods are normal

Unconjugated Bili: 70 DAT negative

Conjugated Bili: 18

Isolated hyperbilrubinaemia

Unconjugated

Haemolysis

Gilbert’s Syndrome

Benign Neonatal Jaundice

Drugs

Crigler-Najjar Syndrome

Conjugated

Dubin-Johnson Syndrome

Rotor Syndrome

Glycogen Storage Disease

Case 14• A 40 year old woman presents

to your GP practice with a

history of upper abdominal

pain.

• Her LFTs show the following:

Normal Values


ALT 120 5-35iu/L

AST 78 5-35iu/L

ɣGT 124 <45iu/L

Bil 33 <20µmol/L

Alb 42 35-50g/L

What’s important to know?What might you find on examination?

• Present in cholecystitis • Not typically present in

simple cholelithiasis or ascending cholangitis

Case 14

• The pain worsens and she

becomes nauseous; she

attends AnE.

Normal Values

Amylase 466 <150 iu/L

Lipase 421 <160 iu/L

Both are pancreatic enzymes.

Classically if raised x3 upper

limit of normal it’s indicative of

acute pancreatitis

Case 15

• A 36 year old female’s LFTs:

Normal Values


ALT 1795 5-35iu/L

AST 1029 5-35iu/L

ɣGT 68 <45iu/L

Bil 28 <20µmol/L

Alb 35 35-50g/L

Amylase 110 <120iu/L

4 main causes of transaminitis >1000?

•Acute Viral Hepatitis•Autoimmune Hepatitis• Ischaemic Hepatitis• Drugs (e.g. Paracetamol Overdose, Amiodorone, Methotrexate)

LFTs

ALTAlanine

AminotransferaseThe ‘transaminases’ – intracellular so classically raised in

hepatocellular disorders.Typically ALT>AST. If AST>ALT, suggestive of ETOH disease.

In chronic liver disease transaminases may reduceASTAspartate

Transaminase

ALPAlkaline

Phosphatase

Related to bile ducts so classically raised in cholestasis.Also raised in bone disease (will have normal gGT),children and pregnancy (isoform analysis can help

differentiate)

ɣGTGamma glutamyltranspeptidase

Related to bile ducts.If raised with ALP suggests cholestasis.

If isolated rise, suggest enzyme induction (e.g. Alcohol)

Bil

BilirubinUnconjugated

(indirect)Conjugated

(direct)

Conjugated by liver enzymes and excreted in bile.Can be raised in all types of liver disease and there are extra-

hepatic causes.Ratio of indirect:direct bilirubin helps classify

Alb AlbuminMarker of hepatic synthetic function

(along with clotting factors) but has half life of around 20 days

Anti-thrombin

-

-

Vit. K needed for: VII, IX, X, II

/CONTACT ACTIVATION PATHWAY

/TISSUE FACTOR PATHWAY

PT/INRaPTT

Thrombin Time

Warfarin-

Heparin+

Dabigatran (NOAC)

-

Rivaroxaban (NOAC)

-

PT Prothrombin Time

Test of the extrinsic and common pathways. Clotting initiated in

the presence of Tissue Factor (thromboplastin).

Prolonged in:

• Vitamin K deficiency/antagonism (e.g. Warfarin)

• Deficiencies of factors VII, X, II and I (genetic/liver disease)

• DIC

• Transiently after a bolus of high dose heparin

INRInternational

Normalised Ratio

A standardisation of the PT (above).

Normal is 0.9-1.1. Typical targets:

• 2-3 in AF; venous-thrombolic prophylaxis

• 3-4 with mechanical heart valves; high-risk clotting

(a)PTT

(activated) Partial

Thromboplastin

Time

Test of the intrinsic and common pathways. Clotting initiation in

the absence of Tissue Factor.

Prolonged in:

• Deficiency of all factors apart from VII

• Unfractionated Heparin therapy

(LMWH and warfarin might cause a mild rise but not suitable

for monitoring)

• DIC

•Anti-phospholid antibody/Lupus Anticoagulant (which

paradoxically increases thrombosis due to its effect on platelets)

Coagulation Tests - Part 1 of 2

Coagulation Tests – Part 2 of 2

TTThrombin

Time

Measures the final step of the common pathway (fibrinogen to

fibrin) by adding thrombin to plasma.

Prolonged in:

• Presence of Thrombin inhibitors

(e.g. Direct – Dabigatran; Indirect – Heparin)

• Hypofibrinogenemia (genetic, liver disease, DIC)

• High serum protein (Amyloid, Myeloma)

Bleeding

Time

A test of platelet function.

A cut is made on the forearm and the time until haemostasis is measured.

Prolonged in:

• Thrombocytopaenia

•Aspirin therapy

• Von Willibrand’s disease

• DIC

Specific

Assays

Measurement of quantity/function of specific factors

e.g. Fibrinogen, anti-Xa (LMWH/NOAC Monitoring), VII, IX, VII, vWF,

Factor V Leiden, Protein C, Protein S

Case 16 • A 4 year old boy is referred to you by his GP after concerns

relating to non-accidental injury. He appears to have a number of

bruises which the parents cannot account for.

• You undertake some clotting studies:

Normal Values

(Very variable

between labs!)

PT 11 10-12 secs

INR 1.0 0.9-1.1

(a)PTT 68 30-45 secs

Thrombin

Time

12 12-14 secs

Case 17 a and b • Two 70 year old ladies. Bloods taken at 19:00

In Bed 1 In Bed 2

Normal Values

PT 30 10-12 secs

INR 2.5 0.9-1.1


Thrombin Time 16 12-14 secs

Normal Values

PT 12 10-12 secs

INR 1.1 0.9-1.1



On Warfarin Therapy After treatment dose LMW Heparin.

Case 18• A 16 year old boy is brought in by ambulance after a motorcycle accident. He is

unconscious with an open fracture to his right tibia which is haemorrhaging.

• He undergoes emergency surgery and is then taken to ITU. Post-operatively, he is noted to be bleeding from his wound site, central line site and nose.

Normal Values

PT 60 10-12 secs

INR 5 0.9-1.1


Bleeding Time 15 1-9 mins


Disseminated Intravascular

Coagulopathy/Coagulation

D-Dimers• D-Dimers are degradation products of fibrin, e.g. they occur when

there is venous thromboembolism.• However, they are also raised in infection, malignancy, post-

operatively and in pregnancy!

• If negative, they can help rule out VTE in patients with low risk pre-test probability.

• Nonetheless, a negative D-dimer with high clinical suspicion does not rule out a VTE!

Cardiac Enzymes

• Troponins • Seecautions on the right

• LDH: Lactate Dehydrogenase – found in most cells and rises in tissue damage/inflammation (can be used to differentiate a transudate from an exudate)

• CK: Creatine Kinase –different isoforms exist in cardiac and skeletal muscle

CRP: C-Reactive Protein

Other Acute Phase Reactants:

• Ferritin

• Fibrinogen

• Haptoglobulin

• Compliment Proteins

Inflammation/Acute Phase Reaction

ESR: Erythrocyte Sedimentation Rate

TFTs – 1 of 2

Low TSHRaised FT3

or FT4

Common causes:

Primary hyperthyroidism - Graves' disease,

multinodular goitre, toxic nodule.

Relatively common causes with low radio-

iodine uptake:

Transient thyroiditis (postpartum, post-viral,

De Quervain's thyroiditis).

Rare with a low radio-iodine uptake:

Thyroxine ingestion.

Ectopic thyroid tissue.

Iodine-induced.

Amiodarone therapy.

Rare with a positive pregnancy test:

Gestational thyrotoxicosis with hyperemesis

gravidarum.

Hydatiform mole.

Rare:

Familial TSH receptor mutation.

Low TSHNormal FT3

or FT4

Common causes:

Subclinical hyperthyroidism.

Thyroxine ingestion.

Rare causes:

Steroid therapy.

Dopamine and dobutamine infusion.

Non-thyroidal illness.

Low or

normal TSH

Low FT3 or

FT4

Common causes:

Non-thyroidal illness.

Recent treatment for hyperthyroidism.

Rare causes:

Pituitary disease.

Congenital TSH or TRH deficiencies.

TFTs – 2 of 2

Raised

TSH

Low FT4 or

FT3

Common causes:

Chronic autoimmune thyroiditis.

Following radio-iodine.

Following thyroidectomy.

Transient thyroiditis - hypothyroid

phase.

Rare causes (anti-TPO negative):

Following external beam radiotherapy to the neck.

Drugs - amiodarone, lithium, interferons, interleukin-2.

Iodine deficiency.

Amyloid goitre.

Congenital causes:

Thyroid dysgenesis.

Iodine transport defects.

TSH-receptor defects.

TSH resistance.

Raised

TSH

Normal

FT4 or FT3

Common causes:

Subclinical autoimmune

hypothyroidism.

Rare causes:

Drugs - amiodarone, sertraline, colestyramine.

Recovery phase after non-thyroidal illness.

Heterophile (interfering) antibody.

Congenital causes:

TSH-receptor defects.

TSH resistance.

Normal or

raised TSH

Raised FT4

or FT3

Rare causes:

Amiodarone.

Interfering antibodies.

Familial.

TSH-secreting pituitary tumour.

Acute psychiatric illness.

Parathyroid Hormone, Ca and PO

Ca, PO and Alk Phos DifferentialsCalcium Phosphate Alk Phos

Osteoporosis Normal Normal Normal

Osteomalacia (Vit D Deficiency) Low low High

Paget’s Normal Normal Very high

Myeloma High High/Normal Normal

Bone Metastases High High/Normal High

Primary Hyperparathyroidism High Low/Normal High

Secondary Hyperparathyroidism Low Low/Normal High

Hypoparathyroidism Low High Normal

Pseudo-hypoparathyroidism Low High Normal

Pseudo-Pseudo- hypoparathyroidism Normal Normal Normal

Renal Failure Low High Normal/High

Immunoglobulin Allotypes

Key point:

• IgM tends to signify acute infection

• IgG tends to signify immunity

Auto-antibody vs. Condition

Antinuclear

antibodies

(ANA)

Anti-SSA/Ro autoantibodies

ribonucleoproteins

Systemic Lupus Erythematosus, Neonatal Heart Block,

Primary Sjögren's syndrome

Anti-La/SS-B

autoantibodiesPrimary Sjögren's syndrome

Anti-centromere antibodies centromere CREST syndrome

Anti-neuronal nuclear

antibody-2Ri Opsoclonus

Anti-dsDNA double-stranded DNA SLE

Anti-Jo1 histidine-tRNA ligase Inflammatory Myopathy

Anti-RNP Ribonucleoprotein Mixed Connective Tissue Disease

Anti-Smith snRNP core proteins SLE

Anti-topoisomerase

antibodiesType I topoisomerase Systemic Sclerosis (anti-Scl-70 antibodies)

Anti-histone antibodies histones SLE and Drug-induced LE

Anti-p62 antibodies nucleoporin 62

Primary Biliary CirrhosisAnti-sp100 antibodies Sp100 nuclear antigen

Anti-glycoprotein-210 antibodies nucleoporin 210kDa

Anti-mitochondrial antibody mitochondria

Anti-transglutaminase antibodiesAnti-tTG Coeliac Disease

Anti-eTG Dermatitis Herpetiformis

Anti-ganglioside antibodies

ganglioside GQ1B Miller-Fisher Syndrome

ganglioside GD3 Acute Motor Axonal Neuropathy (AMAN)

ganglioside GM1 Multifocal Motor Neuropathy with Conduction Block (MMN)

anti-CCPcyclic citrullinated

proteinRheumatoid Arthritis

Auto-antibody vs. Condition

Anti-neutrophil

cytoplasmic

antibody

c-ANCA proteins in neutrophil cytoplasm Wegener's Granulomatosis

p-ANCA neutrophil perinuclearMicroscopic Polyangiitis, Churg-Strauss syndrome, systemic

Vasculitides (non-specific)

Rheumatoid factor IgG Rheumatoid arthritis

Anti-smooth muscle antibody smooth muscle Chronic Autoimmune Hepatitis

Anti-SRP

signal recognition particle Polymyositis

exosome complex Scleromyositis

nicotinic acetylcholine receptor Myasthenia Gtavis

muscle-specific kinase (MUSK) Myasthenia Gravis

Anti-VGCC

voltage-gated calcium channel

(P/Q-type)Lambert-Eaton Myasthenic Syndrome

thyroid peroxidase (microsomal) Hashimoto's Thyroiditis

TSH receptor Graves' disease

Hu Paraneoplastic Cerebellar Syndrome

Yo (cerebellar Purkinje Cells) Paraneoplastic Cerebellar Syndrome

amphiphysin Stiff person syndrome, Paraneoplastic Cerebellar Syndrome

Anti-VGKC

voltage-gated potassium channel

(VGKC)

Limbic encephalitis, Isaac's Syndrome (autoimmune

neuromyotonia)

basal ganglia neuronsSydenham's chorea, paediatric autoimmune neuropsychiatric

disease associated with Streptococcus (PANDAS)

N-methyl-D-aspartate receptor (NMDA)Encephalitis

glutamic acid decarboxylase (GAD) Diabetes mellitus type 1, stiff person syndrome

aquaporin-4 Neuromyelitis Optica (Devic's syndrome)

Lupus anticoagulantthrombin Systemic Lupus Erythematosus

phospholipid Antiphospholipid syndrome

Liver kidney microsomal type 1 antibody Autoimmune Hepatitis.

“Do a...”Liver Screen Anaemia Work-up Bone Profile

Septic Screen

Renal Workup


FBC

U+Es

LFTs

gGT

Amylase

Viral Serology Septic Screen

Auto-antibodies

Clotting

Glucose

+/- Ferritin Renal Workup

+/- Ceruloplasmin/Cu

+/- Alpha-fetoprotein

+/- Alpha-1 antitrypsin


FBC FBCs

U+Es Iron Studies

(Fe, TIBC, Transferrin)LFTs

gGT Blood Film

Amylase B12

Viral Serology Ferritin Septic Screen

Auto-antibodies Folate

Clotting Coeliac Serology

Glucose +/- Hb electrophoresis


+/- Ceruloplasmin/Cu

+/- Alpha-fetoprotein

+/- Alpha-1 antitrypsin


FBC FBCs

U+Es Iron Studies

(Fe, TIBC, Transferrin)LFTs

gGT Blood Film

Amylase B12






+/- Ceruloplasmin/Cu Blood Electrolytes and Proteins

+/- Alpha-fetoprotein Auto-antibodies/Complement

+/- Alpha-1 antitrypsin Urinary Electrolytes and Proteins


FBC FBCs Calcium

U+Es Iron Studies

(Fe, TIBC, Transferrin)

Phosphate

LFTs Vitamin D

gGT Blood Film LFTs

(for Alk Phos and Albumin)Amylase B12






+/- Ceruloplasmin/Cu Blood Electrolytes and Proteins

+/- Alpha-fetoprotein Auto-antibodies/Complement

+/- Alpha-1 antitrypsin Urinary Electrolytes and Proteins


FBC FBCs Calcium

U+Es Iron Studies

(Fe, TIBC, Transferrin)

Phosphate

LFTs Vitamin D

gGT Blood Film LFTs

(for Alk Phos and Albumin)Amylase B12


Auto-antibodies Folate FBC, U+Es, LFTs, CRP

Clotting Coeliac Serology Blood Cultures + Lac + U.O.

Glucose +/- Hb electrophoresis Chest Xray

+/- Ferritin Renal Workup Urine Dip (+/- MCS)

+/- Ceruloplasmin/Cu Blood Electrolytes and Proteins +/- Stool MCS

+/- Alpha-fetoprotein Auto-antibodies/Complement +/- Lumbar Puncture

+/- Alpha-1 antitrypsin Urinary Electrolytes and Proteins +/- Sputum MCS and Swabs

What you want

What you get

Thank-you

Any Questions?

Interpreting Blood Tests Part 2 - simplyrevision.org.uk

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