CRP is the preferred biomarker of inflammation: its concentration rises earlier and changes more acutely than ESR. 

The exceptions to this are to aid in the diagnosis, and monitoring response to therapy, of certain chronic conditions including temporal arteritis, polymyalgia rheumatica, multiple myeloma, systemic vasculitis and rheumatoid arthritis.

In primary care, it is unlikely that useful clinical information will be obtained by testing both ESR and CRP on the same sample. Do not request both CRP and ESR unless you can be sure doing so will benefit the patient.

Please consider NOT routinely testing ESR

Routine monitoring of vitamin D levels is not required or recommended.  

Do test:

Patients with bone disease such as osteomalacia or osteoporosis that is amenable to treatment with vitamin D

Patients about to start treatment with a potent antiresorptive agent (zoledronate or denosumab) or patients with Paget’s disease, prior to use of a bisphosphonate

Patients with musculoskeletal symptoms (generalised bone or muscle pain, proximal myopathy) that may be attributable to vitamin D deficiency

When investigating abnormalities of corrected calcium levels

Do not test:

Asymptomatic high-risk individuals. 

These patients should instead be offered lifestyle advice about sun exposure, diet and over the counter supplements.

Examples of risk factors for vitamin D-deficiency include:

Reduced sunlight exposure

Black or ethnic minority with darker skin

Living in residential care, or prison

Taking medications that affect vitamin D metabolism (such as phenobarbital, carbamazepine, phenytoin, valproate)

Suspected malabsorption states e.g. IBD, coeliac disease, cystic fibrosis, previous gastric bypass surgery

Patients with CKD (people with CKD stage 4 & 5 should have supplements as per the low clearance clinic advice

After vitamin D supplementation, measure corrected calcium levels within 1 month of completing the loading regimen, in case primary hyperparathyroidism has been unmasked. 

There is no need to measure PTH unless the calcium is abnormal (see PTH section 2.3, below).

Vitamin D levels should be retested 6 months after supplementation only if the cause of deficiency was malabsorption and this remains a concern.

Inappropriate testing of vitamin D

Vitamin D is an extensively requested test, often for patients with non-specific symptoms such as tiredness, fatigue, malaise, exhaustion, 'off-legs', general decline, frailty, dizziness.

The results are rarely helpful and much less testing of vitamin D would not cause clinical harm.

The appropriate indications for testing parathyroid hormone are:

Hypercalcaemia:

PTH high > refer to endocrinology

PTH low  > investigate for malignancy

Hypocalcaemia and normal vitamin D

A common inappropriate indication for testing PTH is monitoring after vitamin D replacement. Only a serum calcium is needed, one month after high-dose vitamin D replacement.

Request PTH only if the calcium level is abnormal.

There is no need to test PTH for patients with CKD at any stage.

In order to monitor diabetes and its complications and associated conditions, including fatty liver, dyslipidaemia and thyroid problems, the following order sets have been developed.

Type 1 diabetes

Annual review

• U&Es, ALT^[1], HBA1c, standard lipid profile, urine ACR, TSH^[2]

Type 2 diabetes

New diagnosis

• U&Es, ALT, HBA1c, standard lipid profile, TSH, urine ACR

Annual review

• U&Es, ALT, HBA1c, standard lipid profile, urine ACR 

Long-term use of metformin is associated with biochemical B12 deficiency. Consider measuring vitamin B12 levels in metformin-treated patients, especially if they have anaemia.

Hba1c and haemaglobinopathy

Fructosamine should only be used to monitor glycaemic control in patients who have already been diagnosed with diabetes and who have a haemoglobinopathy which the laboratory has advised interferes with the measurement of HbA1c.

[1] Where this is available to order as a single test. An AST will be automatically requested (‘reflexed’) if the ALT is abnormal to help diagnose fatty liver. Where this functionality is not available, the order set may trigger a full LFT panel.

[2] Where this is available to order as a single test. A free-T4 will be automatically requested (‘reflexed’) if the TSH is abnormal.

A series of test groups have been agreed to simplify pathology requesting for certain cardiovascular conditions at diagnosis and for the annual reviews of established CVD conditions including ischaemic heart disease, peripheral vascular disease, stroke, hypertension and heart failure.

Suspected heart failure diagnosis

FBC, U&E, LFTs, NT-pro-BNP, standard lipid profile, HbA1c, TSH.  

A urine dipstick should also be performed. Proceed to urine ACR if proteinuria is found. 

Suspected hypertension

U&Es, LFTs, HbA1c, standard lipid profile

Urine dipstick, protein found → urine ACR 

CVD annual review 

U&Es, HbA1c, standard lipid profile

Urine dipstick, protein found → urine ACR

Starting statins (if none of these tests have been done in the last 3 months)

U&Es, full lipid profile, ALT, HbA1c, TSH

Monitoring a statin at 3 and 12 months

Standard lipid profile, ALT

If a 40% reduction in non-HDL cholesterol is achieved, there is no need to continue repeating the full lipid profile in primary prevention. 

Statins do not require liver enzyme monitoring if stable at 12 months unless clinically indicated.

Measuring lipids

To estimate cardiovascular risk a standard lipid profile is required. The total cholesterol and the HDL are measured. From this, the non-HDL cholesterol can be derived.

A full lipid profile, including triglycerides should be checked before starting lipid-lowering therapy. This does not need to be repeated after a normal result has been found once.

Standard Lipid Profile

Total Cholesterol, HDL Cholesterol, TChol / HDL ratio, Non-HDL Cholesterol

Full Lipid Profile

Total Cholesterol, HDL Cholesterol, TChol / HDL ratio, Non-HDL Cholesterol, Triglycerides and calculated LDL Cholesterol

Patients do not need to fast for either test.

CKD 3a (A1 or A2) Annual

U&Es / eGFR, urine ACR

CKD 3a A3 / CKD 3b 6-monthly 

U&Es / eGFR, urine ACR

CKD 3b Annual 

U&Es / eGFR, urine ACR, FBC, standard lipid profile, HBA1c

For new onset CKD 3b, especially if there is proteinuria and raised calcium, please think of myeloma.

If anaemia is found, request haematinics.  These can usually be obtained from the existing sample if requested within three days.

Tumour markers usually perform badly as diagnostic or screening tests. In particular, false reassurance can be obtained by tests that may have poor sensitivity.

These tests will be removed from the standard lists available by electronic ordering systems, but since they are an important part of surveillance, they can be arranged on request.

The RTRT group has agreed that the only tumour markers expected to be requested by GPs are:

CA-125 (ovarian)

PSA (prostate) 

Serum protein and urine (Bence Jones protein) electrophoresis (myeloma screen)

B-HCG can be requested as a pregnancy test.

Order sets for use in the event of abnormal liver function tests and suspected viral hepatitis.

This information does not replace the detailed pathways that are available to guide clinicians on the management of abnormal LFTs.

Case finding hepatitis B and C

• Hb Surface Ag, HCV Ab

 Hepatitis B surface Ag positive

• FBC, INR, LFT (including AST), HBV viral load, Hepatitis C Ab, Hepatitis D Ab, HIV, AFP

Hepatitis C Ab positive

FBC, INR, LFT, AST, TFT, HCV viral load, HCV genotype, Hepatitis B sAg, HIV.

Extended LFT Screen (ALT repeated after 1 month is still raised)

FBC, INR, LFT (including GGT and AST), HB sAg, HCV Ab, autoantibodies, ferritin/iron studies, caeruloplasmin (only for patients <40yr), immunoglobulins, alpha-1 antitrypsin.

ALT>300: an acute hepatitis screen 

Hepatitis A IgM                                – Acute hepatitis screen

Hepatitis B core antibody, IgM         – Acute hepatitis screen

Hepatitis B surface #Ag                     – Acute hepatits screen

Hep C Ab                                         – Acute hepatitis screen

Liver autoantibodies, immunoglobulins, FBC, LFT, AST, GGT

Consider also drug induced injury.

Fatty liver on ultrasound

FBC, LFT, AST

Calculate Fib-4

Fib-4 > 3.25 → high risk of advanced fibrosis → refer to secondary care.

If ELF test is available

Fib-4 1.3-3.25 → Request ELF test

For fatty liver (aka NASH):

ELF > 9.8 → High risk of advanced fibrosis → refer to secondary care.

For those drinking harmful amounts of alcohol and at risk of fibrosis:

ELF > 10.5 → High risk → refer to secondary care.

If low risk of fibrosis, repeat LFTs and calculate Fib-4 annually.

Immunodeficiency

Repeated bacterial infections (≥4 infections in one year), particularly with encapsulated organisms, may suggest antibody or complement deficiency.

Useful initial investigations are IgG, IgA and IgM levels, C3 and C4.

Allergy

An allergy-focused clinical history is essential to the diagnosis of allergy and in many cases no blood testing is required in primary care. 

The review group has decided not to provide allergy testing order sets. 

Children should not be subjected to blanket IgE testing looking for a possible cause of their symptoms. Children can be referred to the paediatric allergy clinic for skin prick tests +/- specific IgE tests if this is required to help make a diagnosis.

Further guidance on diagnosis and assessment of allergy can be found in the references below.

Rheumatology

Autoimmune rheumatological testing should only be done in the context of a patient where there is a higher clinical suspicion.

Do not use these tests as ‘screens’: If an autoimmune condition is likely, specific autoantibody tests can help to narrow a differential diagnosis but are not essential for referral.

Refer patients early if they have a history or examination findings consistent with an inflammatory rheumatological condition.

Early Inflamatory Arthritis (EIA):

• CRP, Rheumatoid Factor, Anti-cyclic citrullinated peptide antibodies (CCP)

Anti-cyclic citrullinated peptide (anti-CCP):

• High specificity, low sensitivity (a negative result does not exclude disease)
• Presence early in disease
• Identifies those at higher risk for more severe disease

Rheumatoid factor:

• Cannot be used to exclude RA, 32% of patients who go on to develop RA have a negative RhF result when first testing.
• Poor sensitivity: It is detectable in 15% of the population without RA following chronic inflammation or infection, and in the elderly.

ANA:

• ANA is positive in 98% of patients with SLE and systemic sclerosis and 80% with Sjogren’s disease.
• ANA testing in low pre-test probability of rheumatological disease is likely to result in high numbers of false positive results.  ANA has been found to be positive in low-titre in up to 15% of the healthy population.
• Poor specificity: A negative result should not rule out a specialist referral if CTD is suspected on clinical grounds.

Anti-ENA tests (Ro,La, Sm, RNP, Scl70, CENP, Jo1, Ku, Mi2):

• Usually used in secondary care only – these should not be requested directly, but will be added to the ANA test profile if indicated by the diagnostic laboratory.
• Used to aid diagnosis and differentiation of various CTD.
• Poor sensitivity: Cannot be used as a rule out test for CTD.

Infertility pre-referral (Female)

• FSH – (day 2-4 of a 28 day cycle)
• LH – (day 2-4 of a 28 day cycle)
• Oestradiol – (day 2-4 of a 28 day cycle)
• Progesterone (Measure it 7 days before expected period i.e. on day 21 of a 28 day cycle or day 28 of a 35 day cycle)
• Rubella Ab 
• FBC
• HIV Ab 
• Hepatitis B surface Ag 
• Hepatitis C Ab
• Haemoglobinopathy screen
• Chlamydia (self swab)

If irregular cycles add:

Prolactin, TSH, testosterone, SHBG and US pelvis

Depending on the timing of menstrual periods, serum progesterone may need to be measured later (for example on day 28 of a 35-day cycle) to confirm ovulation, and repeated weekly thereafter until the next menstrual cycle starts.

Suspected PCOS 

If not already done as part of investigating abnormal periods, consider:

• FSH, LH, TSH, testosterone, SHBG and HBA1c
• Refer adults for ultrasound scan to look for the classic picture of polycystic ovaries (unless the diagnosis of PCOS is obvious on clinical and biochemical grounds).

Erectile dysfunction

1. HBA1c, standard Lipids, U&E

Consider PSA testing if >40 years of age.Consider SHBG / testosterone (If testosterone <12, please check FSH, LH, TSH, prolactin, FBC).

Oligomenorrhoea / Secondary amenorrhoea

• TSH, FSH, LH, oestradiol, testosterone, prolactin

Osteoporosis (secondary causes screen)*

• FBC, ESR, serum protein electrophoresis, calcium, phosphate, LFT, U&E, TSH and coeliac screen

*Secondary causes of osteoporosis are present in 30% of women and 55% of men with vertebral crush fractures

In men with vertebral fractures, serum testosterone should be measured to exclude hypogonadism

In primary osteoporosis, no blood tests are needed.

Consider this order set when an underlying disease affecting bone metabolism is suspected.

Tired All The Time (TATT) No bundle on system

Testing should only be carried out if tiredness has persisted for 1 month or longer and there is no obvious lifestyle reason apparent.  Consider:

• FBC, CRP, LFTs, U&E, TSH, HBA1c and coeliac screen