Interpreting Blood Tests Part 2. Dr Andrew Smith

Transcription

1 Interpreting Blood Tests Part 2 Dr Andrew Smith

2 Outline Previous 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

3 Case 8 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 µmol/L ALT iu/L AST iu/L ɣgt 12 <45iu/L Bil 88 <20µmol/L Alb g/L Rest of bloods are normal Unconjugated Bili: 70 Conjugated Bili: 18

4 Isolated hyperbilrubinaemia Unconjugated Haemolysis Gilbert s Syndrome Neonatal Drugs Crigler-Najjar Syndrome Conjugated Dubin-Johnson Syndrome Rotor Syndrome Glycogen Storage Disease

5 Case 9 A 30 year old woman presents to your GP practice with a one month history of upper abdominal pain. Her LFTs show the following: Normal Values ALP µmol/L ALT iu/L AST iu/L ɣgt 124 <45iu/L Bil 33 <20µmol/L Alb g/L

6 Case 9 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

7 Case 10 A 45 year old woman... Normal Values ALP µmol/L ALT iu/L AST iu/L ɣgt 68 <45iu/L Bil 28 <20µmol/L Alb g/L Amylase 110 <120iu/L 4 main causes of transaminitis >1000? Drugs (e.g. Paracetamol, Amiodorone) Ischaemic Hepatitis Acute Viral Hepatitis Autoimmune Hepatitis

8 LFTs ALT AST ALP ɣgt Bil Alb Alanine Aminotransferase Aspartate Transaminase Alkaline Phosphatase Gamma glutamyl transpeptidase Bilirubin Unconjugated (indirect) Conjugated (direct) Albumin The transaminases intracellular so classically raised in hepatocellular disorders. Typically ALT>AST In chronic liver disease transaminases may reduce 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) Related to bile ducts. If raised with ALP suggests cholestasis. If isolated rise, suggest enzyme induction (e.g. Alcohol) Conjugated by liver enzymes and excreted in bile. Can be raised in all types of liver disease and there are extrahepatic causes. Ratio of indirect:direct bilirubin helps classify Marker of hepatic synthetic function (along with clotting factors) but has half life of around 20 days

9 Vit. K needed for: VII, IX, X, II - - Anti-thrombin

10 Coagulation Tests - Part 1 of 2 PT INR (a)pt T Prothrombin Time International Normalised Ratio (activated) Partial Thromboplastin 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 A standardisation of the PT (above). Normal is Typical targets: 2-3 in AF; venous-thrombolic prophylaxis 3-4 with mechanical heart valves; high-risk clotting 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 doesn t) (Warfarin may also cause a small rise in aptt) DIC Anti-phospholid antibody/lupus Anticoagulant (which paradoxically increases thrombosis due to its effect on platelets)

11 Coagulation Tests Part 2 of 2 TT Bleeding Time Specific Factor Assays Thrombin 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 Dagibatran; Indirect Heparin) Hypofibrinogenemia (genetic, liver disease, DIC) High serum protein (Amyloid, Myeloma) 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 Measurement of specific factors e.g. Fibrinogen, anti-xa (Heparin Monitoring), VII, IX, VII, vwf

12 Case 11 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 secs INR (a)ptt secs Bleeding Time mins Thrombin Time secs

13 Case 12 a and b Two 70 year old ladies. Bloods taken at 18:20 In Bed 1 In Bed 2 Normal Values PT secs INR (a)ptt secs Bleeding Time mins Thrombin Time secs Normal Values PT secs INR (a)ptt secs Bleeding Time mins Thrombin Time secs On Warfarin Therapy After LMW Heparin. If using Unfractionated Heparin, the aptt would be prolonged.

14 Case 13 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 secs INR (a)ptt secs Bleeding Time mins Thrombin Time secs Disseminated Intravascular Coagulopathy/Coagulation

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17 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, postoperatively 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!

18 Cardiac Enzymes Troponins are the most used now But see cautions on the right LDH: Lactate Dehydrogenase found in most cells and rises in tissue damage/inlammation (can be used to differentiate a transudate from an exudate CK: Creatine Kinase different isoforms exist in cardiac and skeletal muscle

19 Inflammation/Acute Phase Reaction ESR: Erythrocyte Sedimentation Rate

20 CRP: C-Reactive Protein Other Acute Phase Reactants: Ferritin Fibrinogen Haptoglobulin Compliment Proteins

21 TFTs 1 of 2 Common causes: Primary hyperthyroidism - Graves' disease, multinodular goitre, toxic nodule. Rare with a low radio-iodine uptake: Thyroxine ingestion. Ectopic thyroid tissue. Iodine-induced. Amiodarone therapy. Low TSH Raised FT3 or FT4 Relatively common causes with low radioiodine uptake: Gestational thyrotoxicosis with hyperemesis Rare with a positive pregnancy test: Transient thyroiditis (postpartum, post-viral, gravidarum. De Quervain's thyroiditis). Hydatiform mole. Rare: Familial TSH receptor mutation. Low TSH Low or normal TSH Normal FT3 or FT4 Low FT3 or FT4 Common causes: Subclinical hyperthyroidism. Thyroxine ingestion. Common causes: Non-thyroidal illness. Recent treatment for hyperthyroidism. Rare causes: Steroid therapy. Dopamine and dobutamine infusion. Non-thyroidal illness. Rare causes: Pituitary disease. Congenital TSH or TRH deficiencies.

22 TFTs 2 of 2 Raised TSH Raised TSH Normal or raised TSH Low FT4 or FT3 Normal FT4 or FT3 Raised FT4 or FT3 Common causes: Chronic autoimmune thyroiditis. Following radio-iodine. Following thyroidectomy. Transient thyroiditis - hypothyroid phase. Common causes: Subclinical autoimmune hypothyroidism. Rare causes: Amiodarone. Interfering antibodies. Familial. TSH-secreting pituitary tumour. Acute psychiatric illness. 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. Rare causes: Drugs - amiodarone, sertraline, colestyramine. Recovery phase after non-thyroidal illness. Heterophile (interfering) antibody. Congenital causes: TSH-receptor defects. TSH resistance.

23 Parathyroid Hormone, Ca and PO

24 Ca, PO and Alk Phos Differentials Calcium Phosphate Alk Phos Osteoporosis Normal Normal Normal Osteomalacia Low low High Pagets Normal Normal Very high Myeloma High High normal Normal Bone Metastases High High normal High Primary Hyperparathyroidism High Low normal Normal High Hypoparathyroidism Low High Normal Pseudo -hypoparathyroidism Low High Normal Pseudo-Pseudo- hypoparathyroidism Normal Normal Normal Renal Failure Low High Normal High OHCM 8 th ed.

25 Immunoglobulin Allotypes Key point: IgM tends to signify acute infection IgG tends to signify immunity

26 Antinuclear antibodies (ANA) Auto-antibody vs. Condition Anti-SSA/Ro autoantibodies Anti-La/SS-B autoantibodies ribonucleoproteins Systemic Lupus Erythematosus, Neonatal Heart Block, Primary Sjögren's syndrome Primary Sjögren's syndrome Anti-centromere antibodies centromere CREST syndrome Anti-neuronal nuclear antibody-2 Anti-dsDNA Anti-Jo1 Ri double-stranded DNA SLE Opsoclonus histidine-trna ligase Inflammatory Myopathy Anti-RNP Ribonucleoprotein Mixed Connective Tissue Disease Anti-Smith Anti-topoisomerase antibodies snrnp core proteins SLE Type I topoisomerase Systemic Sclerosis (anti-scl-70 antibodies) Anti-histone antibodies histones SLE and Drug-induced LE Anti-p62 antibodies nucleoporin 62 Anti-sp100 antibodies Anti-glycoprotein-210 antibodies Anti-mitochondrial antibody Anti-transglutaminase antibodies Anti-ganglioside antibodies anti-ccp Sp100 nuclear antigen Primary Biliary Cirrhosis nucleoporin 210kDa mitochondria Anti-tTG Anti-eTG ganglioside GQ1B ganglioside GD3 ganglioside GM1 cyclic citrullinated protein Coeliac Disease Dermatitis Herpetiformis Miller-Fisher Syndrome Acute Motor Axonal Neuropathy (AMAN) Multifocal Motor Neuropathy with Conduction Block (MMN) Rheumatoid Arthritis

27 Auto-antibody vs. Condition Anti-neutrophil cytoplasmic antibody c-anca proteins in neutrophil cytoplasm Wegener's Granulomatosis p-anca neutrophil perinuclear Rheumatoid factor IgG Rheumatoid arthritis Microscopic Polyangiitis, Churg-Strauss syndrome, systemic Vasculitides (non-specific) Anti-smooth muscle antibody smooth muscle Chronic Autoimmune Hepatitis signal recognition particle Polymyositis Anti-SRP exosome complex Scleromyositis nicotinic acetylcholine receptor Myasthenia Gtavis muscle-specific kinase (MUSK) Myasthenia Gravis voltage-gated calcium channel (P/Q-type) Lambert-Eaton Myasthenic Syndrome thyroid peroxidase (microsomal) Hashimoto's Thyroiditis Anti-VGCC 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) basal ganglia neurons Limbic encephalitis, Isaac's Syndrome (autoimmune neuromyotonia) Sydenham'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 anticoagulant thrombin Systemic Lupus Erythematosus phospholipid Antiphospholipid syndrome Liver kidney microsomal type 1 antibody Autoimmune Hepatitis.

28 Do a... Liver Screen Anaemia Work-up Bone Profile Septic Screen Renal Workup

29 Do a... Liver Screen Anaemia Work-up Bone Profile FBC U+Es LFTs ggt Amylase Viral Serology Septic Screen Auto-antibodies Clotting Glucose +/- Ferritin Renal Workup +/- Ceruloplasmin +/- Alpha-fetoprotein +/- Alpha-1 antitrypsin

30 Do a... Liver Screen Anaemia Work-up Bone Profile FBC U+Es LFTs ggt Amylase FBCs Iron Studies (Fe, TIBC, Transferrin) Blood Film B12 Viral Serology Ferritin Septic Screen Auto-antibodies Clotting Glucose Folate Coeliac Serology +/- Hb electrophoresis +/- Ferritin Renal Workup +/- Ceruloplasmin +/- Alpha-fetoprotein +/- Alpha-1 antitrypsin

31 Do a... Liver Screen Anaemia Work-up Bone Profile FBC U+Es LFTs ggt Amylase FBCs Iron Studies (Fe, TIBC, Transferrin) Blood Film B12 Viral Serology Ferritin Septic Screen Auto-antibodies Clotting Glucose Folate Coeliac Serology +/- Hb electrophoresis +/- Ferritin Renal Workup +/- Ceruloplasmin Blood Electrolytes and Proteins +/- Alpha-fetoprotein Auto-antibodies +/- Alpha-1 antitrypsin Urinary Electrolytes and Proteins

32 Do a... Liver Screen Anaemia Work-up Bone Profile FBC FBCs Calcium U+Es LFTs Iron Studies (Fe, TIBC, Transferrin) Phosphate Vitamin D ggt Blood Film LFTs Amylase B12 (for Alk Phos and Albumin) Viral Serology Ferritin Septic Screen Auto-antibodies Clotting Glucose Folate Coeliac Serology +/- Hb electrophoresis +/- Ferritin Renal Workup +/- Ceruloplasmin Blood Electrolytes and Proteins +/- Alpha-fetoprotein Auto-antibodies +/- Alpha-1 antitrypsin Urinary Electrolytes and Proteins

33 Do a... Liver Screen Anaemia Work-up Bone Profile FBC FBCs Calcium U+Es LFTs Iron Studies (Fe, TIBC, Transferrin) Phosphate Vitamin D ggt Blood Film LFTs Amylase B12 (for Alk Phos and Albumin) Viral Serology Ferritin Septic Screen Auto-antibodies Folate FBC, U+Es, LFTs, CRP Clotting Coeliac Serology Blood Cultures Glucose +/- Hb electrophoresis Chest Xray +/- Ferritin Renal Workup Urine Dip (+/- MCS) +/- Ceruloplasmin Blood Electrolytes and Proteins +/- Stool MCS +/- Alpha-fetoprotein Auto-antibodies +/- Lumbar Puncture +/- Alpha-1 antitrypsin Urinary Electrolytes and Proteins +/- Sputum MCS and Swabs

34 What you want

35 What you get

36 Thank-you Any Questions?