Thrombotic risk in proteinuric renal disease
Research type
Research Study
Full title
Utility of Sonoclot to evaluate thrombotic risk in pregnant patients with proteinuric renal disease.
IRAS ID
264258
Contact name
Matthew Hall
Contact email
Sponsor organisation
Nottingham University Hospitals
Duration of Study in the UK
0 years, 11 months, 31 days
Research summary
Research Summary
Pregnancy is associated with blood clots - pregnant women have a 4.3-fold higher risk of developing a blood clot compared to controls. Protein leak in urine can also increase clot risk as a result of concentrating blood, reduced flow through veins and imbalanced loss of factors that normally control clotting. Outside of pregnancy, there is a proven benefit of blood-thinning treatment for patients with nephrotic syndrome (heavy protein loss, low circulating protein in blood and swelling) caused by membranous nephropathy.
Standard laboratory tests do not predict clotting risk. Furthermore, risk calculators for clotting in pregnancy do not include protein leak in their assessment. Unfortunately, clots remain the most frequent direct cause of maternal death in the UK, affecting approximately 1 in 100000 births (MBRRACE-UK - Saving Lives, Improving Mothers’ Care 2016).
At present there is no accepted standard of care for managing clot risk in pregnant women with protein losing kidney diseases. Consensus guidelines issued in 2018 state that blood thinning treatment should be offered to all women with nephrotic syndrome during pregnancy but there is no agreement on whether to treat women with less severe protein loss. An international survey of doctors working in renal-obstetric clinics revealed widespread differences in approaches to clot prophylaxis. Although treatment with low molecular weight heparin appears safe during pregnancy, daily injections can be uncomfortable, lead to bruising, complicate delivery plans and are undoubtedly inconvenient.There is, therefore, an unanswered question on how best to treat these patients. This proposed study will use established technology - a Sonoclot point of care viscoelastic haemostasis monitor - to explore the coagulation system of pregnant women with kidney disease and varying degrees of proteinuria. The hypothesis is that increasing proteinuria correlates with markers of increased clot formation rate.
Lay summary of study results
Fresh whole and citrated whole blood samples from 13 pregnant women with kidney disease were analysed with Sonoclot at different timepoints in pregnancy (22 samples in all) to observe possible changes in clotting parameters. We aimed to review whether it was possible to recruit participants from routine clinic visits, whether there were significant differences in results between fresh and citrated samples, and whether clotting results were affected by abnormal protein leak in patients' urine.
We found that is was possible to recruit patients from our clinic but not at the rate we had predicted. This was predominantly limited by the number of referrals to the clinic and whether or not patients had already been started on blood-thinning treatments.
We found that results compared between fresh and citrated samples were comparable without proportionate bias.
We did not find any association between protein levels in urine and any of the clotting results Sonoclot analysis reported.
It is unlikely that differences in results would be identified without recruiting hundreds to thousands of participants, so further exploration of this project is not planned.
URL to summary results: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT05108389%253Fterm%253Dsonoclot%2526rank%253D6%2526tab%253Dresults%2FNBTI%2FaSO3AQ%2FAQ%2F3336d948-8db1-4940-b90f-abde01354474%2F1%2Fw_aSgxG8a-&data=05%7C02%7Ccambridgeeast.rec%40hra.nhs.uk%7C42eaee11853a450a84b508dcb568dca2%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638584709189700073%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=PjSiWvZanb3MwILwEV7UrApqZSrx4robtRZq%2BQOyx2I%3D&reserved=0
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
21/EE/0271
Date of REC Opinion
17 Dec 2021
REC opinion
Further Information Favourable Opinion