TDL Update: June 2024

2C19 Clopidogrel genetic test

Patients to be prescribed Clopidogrel to reduce their risk of stroke recurrence should first be offered genotype testing to determine whether the drug will be effective, according to draft guidance from NICE.

The test detects variations in the CYP2C19 gene which determine whether a patient may be resistant to Clopidogrel. Certain CYP2C19 gene variations may affect the effective metabolism of Clopidogrel, reducing its ability to lower the risk of a further stroke, TIA or myocardial infarction. These patients may benefit from an alternative antiplatelet therapy.

Test: Cytochrome P450 2C19

Utility: Provides information as to how effectively a person can metabolise the antiplatelet drug Clopidogrel and be used to guide antiplatelet treatment.

Background: Clopidogrel is a prodrug that can be converted to an irreversible P2Y12 inhibitor with antiplatelet properties. The CYP2C19 gene encodes a protein that is needed to metabolise Clopidogrel to its active form. Clopidogrel may be less effective in patients with particular variants of this gene and these patients may benefit from management using an alternative antiplatelet therapy. CYP2C19 genotyping enables identification of variants in the CYP2C19 gene.

People who have had a stroke are at much greater risk of further occlusive vascular events such as secondary stroke or myocardial infarction. For those with non-cardioembolic ischaemic stroke or TIA, clopidogrel can be considered as an antiplatelet agent to reduce this risk.

Alternative names

• Clopidogrel resistance testing
• CYP2C19 Genotyping
• Cytochrome P450 2C19

Platelet studies are available for cases where efficacy rather than resistance is in question. They require prior arrangement with the Haemostasis Laboratory. Samples for platelet studies have a very short stability time and must be collected by special arrangement. Please contact Deepak Singh (Haemostasis Head of Department) to arrange additional anti-platelet testing if required. Email Deepak.singh@tdlpathology.com

Ziwig Endotest®

A decision to pause the service for Endotest was made in November 2023 following extended delays with reporting times for this referred service. This service for testing for endometriosis is now reinstated (June 2024).

TDL will provide sample taking kits: to order, or for further information about the test please contact endotest@tdlpathology.com.

For more information about Ziwig Endotest click here

Stockholm3 test for Prostate Cancer 

Stockholm3 is a blood test that helps to predict risk of clinically significant prostate cancer in men aged 45–74 years with a PSA level of at least 1.5 ng/ml and no previous diagnosis of prostate cancer.

Stockholm3 combines genetic markers, proteins and clinical data in an algorithm to help identify clinically significant prostate cancer. It allows for screening in primary or secondary care settings and is equivalent across diverse ethnicities.

Stockholm3 has been prospectively validated in more than 90,000 men with results published in more than 30 peer reviewed articles. It provides clear, interpretable results (High risk, Normal risk, Low risk) and treatment recommendations.

Key characteristics

• Increased early detection – increased sensitivity
• Increased specificity reduces over testing, unnecessary biopsies by 50% and treatment
• Higher accuracy compared to PSA, PSAD and prostate cancer risk calculator
• PSA testing cannot distinguish between aggressive and benign tumours
• Validated in combination with MRI and in multiple ethnicities
• Shown to detect clinically significant prostate cancers in PSA levels of 1.5–2.9 ng/ml
• Reduces healthcare costs

Stockholm3 : diagnostic patient pathway

A Stockholm3 risk score of >11 is considered to be an indicator of clinically significant prostate cancer risk and referral to a urologist for further investigations is recommended.

To order the Stockholm3 test, take and send 2 x EDTA tubes, which must be received by the laboratory within 24 hours of sample taking.

TDL will provide sample taking kits/request forms – to order, or for further information about the test, please contact stockholm3@tdlpathology.com. Please do not post samples to TDL – these packs do not include a reply-paid envelope. The timing for receipt of samples is important.

Webinars are arranged for the following dates and times (see below). For those who would like to attend please contact stockholm3@tdlpathology.com to register.

Cardiovascular Risk – Apolipoprotein A1, Apolipoprotein B, Lipoprotein(a) with Lp-PLA2 (PLAC) test

The Lipoprotein(a) test measures the level of lipoprotein(a) in blood. High levels of lipoprotein(a) are indicative of higher risk for heart disease and stroke.

The two main groups of lipoproteins are HDL (high-density lipoprotein) (‘good’ cholesterol) and LDL (low-density lipoprotein) (‘bad’ cholesterol). Lipoprotein(a) is a type of LDL. High levels of LDL particles can create plaque - with associated risks of coronary or peripheral artery disease, narrow or blocked arteries, heart attack, stroke, other blood vessel disease.

Testing for lipoprotein(a) may provide a more accurate understanding of risk than a routine cholesterol or lipid profile that measures total LDL cholesterol level only. A raised lipoprotein(a) level may indicate a higher risk for heart and blood vessel disease, even if cholesterol levels are normal. Lipoprotein(a) levels usually change little over time - and genes control levels of lipoprotein(a). By the age of 5 years one’s lipoprotein(a) levels have been achieved and this tends to remain about the same for the rest of life. For that reason, repeat testing is not considered to be helpful, and diet and exercise may not change a person’s lipoprotein(a) levels. If the level is known to be high, it becomes all the more important to manage patients in an attempt to improve heart health.

ApoA1 and ApoB might be additionally used alongside other routine lipid tests to help determine an individual’s risk of developing CVD – rather than as a general population screen but better positioned where patients have a family history of heart disease and/or hyperlipidaemia to help determine the cause (especially in situations in which the LDL cholesterol cannot be calculated).

Levels of Lipoprotein(a), ApoA1, ApoB and ApoA/ApoB ratio are independent cardiovascular risk factors and using these results in clinical practice may provide more accurate markers of myocardial infarction risk.

The Lp-PLA2 (PLAC) test measures Lp-PLA2 activity quantitatively. This assists with the prediction of risk caused by the thickening, or hardening, of the arteries caused by the build-up of plaque.

Both the methodology and reagent manufacturer changed for this test in mid-February, with resultant changes to reporting ranges, and units of measurement. The new reporting ranges are as follows:

• Reduced risk < 225 nmol/min/ml
• Increased risk = or > 225 nmol/min/ml

TDL NIPT (Non-invasive Prenatal Testing)

Changes were made in September 2023 from Harmony to NIPT testing, using Illumina VeriSeq NIPT Solution v2. The Illumina VeriSeq NIPT Solution v2 includes options for fetal sex and sex chromosome aneuploidies. The Illumina VeriSeq NIPT is used worldwide, and includes the English, Welsh and Scottish National Screening Programmes as well as other European screening programmes. TDL Genetics is UKAS accredited and is one of the three nominated NHS English laboratories approved for the National Fetal Aneuploidy Screening Programme.

TDL NIPT benefits:

• Fast processing time of 2-3 working days from sample receipt.
• NIPT sample reception from Monday to Saturday
• Daily collections (Mon–Sat) with same or next day rapid delivery from UK and Ireland
• Single blood tube required
• Low redraw rate of < 1%
• Suitable for IVF pregnancies including those with donor eggs, donor egg status is not required to be disclosed.
• TDL NIPT is performed by TDL Genetics whose laboratory team have extensive expertise in prenatal diagnosis (invasive and non-invasive).
• TDL Genetics is UKAS ISO:15189 accredited for NIPT.
• TDL Genetics’ NIPT service is selected for the National Fetal Anomaly Screening Programme in England.
• No additional charge for re-test if indicated.
• Clinical advice and support from consultant clinical geneticists.
• TDL Genetics is the largest NIPT provider in the UK.

TDL Genetics does not offer whole genome NIPT. The International Society for Prenatal Diagnosis does not currently recommend using NIPT to look at the whole genome (https://obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.6357).

Please direct service enquiries for TDL NIPT to NIPT@tdlpathology.com.

Click here to find out more information about TDL NIPT

Laboratory testing for COVID-19

• The Roche Total Antibody test (TCOV) has been discontinued.
• The Roche Spike Antibody test (SCOV) is run daily (antibody levels to vaccine or virus).
• COVID-19 by PCR (NCOV) is run daily (8am – 8pm Monday to Friday and 9am – 5pm at weekends).
• COVID-19 by PCR is no longer processed as a standard night service. Results that need to be confirmed will be run next day.

Discontinued tests

Laboratory tests may be discontinued at short notice for a variety of reasons such as changes with reagent manufacturers, analyser development, supply chain, suspension or regulatory review.

Depending on the reason, tests may be discontinued for the short or long term, or even permanently, and sometimes with very little notice. Whilst every effort is made to look for a comparable alternative accredited service this is not always possible.

Where an alternative is available, the turnaround times, normal values and methodology may be different. When there is no suitable alternative, the laboratory will notify as it may not be possible to store samples for the long term and it may be necessary to discard them or return them to the referrer.

Click here to view current discontinued tests

Digestive diagnostics

There has been a significant increase in gastrointestinal investigations being undertaken for gastrointestinal conditions. The most commonly investigated digestive disorders include (from top to bottom):

• Gastro-oesophageal reflux disease
• Gallstones
• Coeliac disease/Gluten intolerance
• Crohn's disease
• Ulcerative colitis
• Irritable bowel syndrome (IBS)
• Haemorrhoids
• Diverticulitis

If requesting more than one stool test please use multiple pots as this speeds up sample handling, processing and reporting. Do not overfill, but please ensure that each stool pot is always half-filled.