Blood Clot risks in Neuroendocrine Neoplasms (NENs)

I have a personal interest in this subject because I had pulmonary emboli (PE) diagnosed in January 2011 around 6 weeks after I had major surgery. I got a phone call from the hospital to go down that day and meet with a nurse who would teach me to self inject ‘Clexane'(Enoxaparin) and then take away a stock which was to be issued in future via the normal prescription system. The PE soon cleared up shortly after being found but my Oncologist advised me to keep taking blood thinners to reduce risk. After many years of these daily injections, I was moved onto an easier oral tablet twice a day (Apixaban, brand name Eliquis). I still take medication today without any drama. When I read my own research below, it’s likely my PE was surgery related rather than tumour related.

This subject often comes up in my private group and to answer it properly I carried out some research – I do this for many questions in my private group. I decided to add it to my website (see disclaimer below). But also see some high quality references below. My advice is to ask about these risks when you have meetings with Surgeons/Oncologists.

Blood clots (venous thromboembolism, VTE) are a recognised complication of many cancers. Neuroendocrine neoplasms (NENs) are no exception — but the pattern of clotting in NENs is distinctive, possibly under‑recognised, and perhaps different from other solid tumours. This summary brings together what we know about which NENs carry the highest risk, why clots occur, how surgery contributes, and why splanchnic thrombosis is unusually common in this patient group.

1. Which NENs Carry the Highest Risk of Blood Clots?

Across multiple cohorts, one message is consistent: Pancreatic neuroendocrine tumours (PanNENs) have the highest VTE risk of all NEN subtypes. Large NET cohorts show 70–82% of all NET‑related VTEs originate from pancreatic primaries. For Small intestine (midgut) NETs, 20–35%. Lung NETs account for only 4–6%.

Stage matters: Up to 87% of NET‑related VTEs occur in stage IV disease, regardless of grade.

Grade matters less: VTE occurs across G1, G2, and G3 almost evenly.

2. Why Do NENs Sometimes Cause Clots? (Tumour‑Driven Mechanisms)

NENs create a pro‑thrombotic environment through several biological pathways: • Tissue factor and microparticles – Especially prominent in pancreatic NETs.• Hormonal syndromes- Functional tumours can increase clot risk through: Serotonin → endothelial fibrosis e.g. mesenteric, retroperitoneal, Hedinger Syndrome ACTH → cortisol excess → hypercoagulability VIP/glucagon → dehydration → haemoconcentration • High vascularity and angiogenesis: NENs are highly vascular tumours; this increases local clot activation.• Liver metastases: Compression or distortion of the portal system increases splanchnic clot risk.

3. Splanchnic Thrombosis: The Distinctive NEN Pattern

Unlike most cancers, where leg DVT and pulmonary embolism dominate, NENs show a more unique pattern:

Up to 48–61% of all clots in NENs occur in the splanchnic veins, including:
– Splenic vein
– Portal vein
– Superior mesenteric vein (SMV)
– Inferior mesenteric vein (IMV)

This is driven by tumour location (especially pancreatic NETs), hormonal effects, liver metastases, and surgery.

Why this matters? Splanchnic thrombosis can be silent or present with vague abdominal symptoms. It may also lead to: Splenomegaly, Varices, Portal hypertension, Post‑operative complications.

4. Surgery as a Major Cause of Clots in NENs

Surgery is one of the strongest triggers of VTE in NEN patients — especially pancreatic NET surgery. Post‑operative VTE rates Pancreatic NET surgery: 3.3–3.4%, non‑pancreatic abdominal NET surgery: 1.1–1.7%. Looks low but these figures exceed thresholds used in other cancers to justify extended prophylaxis.

Why surgery increases risk? Surgery activates all three components of Virchow’s Triad:
1. Vessel injury – manipulation of pancreas, liver, mesentery
2. Stasis – long operations, reduced mobility
3. Hypercoagulability – cancer + surgical inflammation

Extended prophylaxis – Evidence suggests pancreatic NET patients may benefit from extended (4‑week) prophylaxis, whereas non‑pancreatic NET patients generally do not unless other risk factors are present.

5. Treatment‑Related and Patient‑Related Causes of Clots

The tumour‑driven figures do not include these additional contributors:

Treatment‑related

– Surgery
– Hospitalisation and immobility
– Central venous lines (ports, PICCs)
– Chemotherapy (especially in NECs)
– Targeted therapies
– PRRT (low risk but not zero – however – this is multifactorial, stemming primarily from the underlying advanced cancer, but potentially exacerbated by the treatment itself)

Patient‑related

– Age
– Obesity
– Infection
– Long‑haul travel
– Dehydration (especially in functional NETs)
– Prior VTE

When combined with tumour‑driven risk, these factors raise the true all‑cause VTE risk beyond the tumour‑only numbers.

6. Summary Table: VTE Risk Across NEN Subtypes

7. Why This Matters for Patients and Clinicians

Understanding the distinctive clotting profile of NENs helps with:
– Early recognition of symptoms
– Appropriate imaging (especially portal/splenic veins)
– Post‑operative planning
– Decisions around prophylaxis
– Managing functional syndromes
– Monitoring high‑risk subgroups (PanNENs, stage IV disease) N

NENs don’t behave like typical solid tumours when it comes to clotting. Recognising this pattern can prevent complications and improve outcomes.

8. Sources

1. Gervaso L, Laffi A, Gaeta A, Gandini S, Boldrini L, Meneses-Medina MI, Rubino M, Benini L, Borghesani M, Algeri L, Curigliano G, Spada F, Cella CA, Fazio N. Venous thromboembolism in pancreatic neuroendocrine neoplasm: a cohort study. Res Pract Thromb Haemost. 2024 Mar 15;8(3):102381. doi: 10.1016/j.rpth.2024.102381. PMID: 38617046; https://pubmed.ncbi.nlm.nih.gov/38617046/ PMCID: PMC11015488

2. Massironi, S.; Gervaso, L.; Fanizzi, F.; Preatoni, P.; Dell’Anna, G.; Fazio, N.; Danese, S. Venous Thromboembolism in Patients with Neuroendocrine Neoplasms: A Systematic Review of Incidence, Types, and Clinical Outcomes. Cancers2025, 17, 212. https://www.mdpi.com/2072-6694/17/2/212 https://doi.org/10.3390/cancers17020212

3. Van Beek DJ, Van Den Heede K, Borel Rinkes I, Norlén O, Van Slycke S, Stålberg P, Nordenström E. Surgery for advanced pancreatic neuroendocrine neoplasms: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES). Br J Surg. 2024 Jan 31;111(2):znae017. doi: 10.1093/bjs/znae017. https://pubmed.ncbi.nlm.nih.gov/38364061/ PMID: 38364061

4. Springer Nature. Laura Prakash, Jeffrey E. Lee, James Yao, Priya Bhosale, Aparna Balachandran, Huamin Wang, Jason B. Fleming, Matthew H.G. Katz, Role and Operative Technique of Portal Venous Tumor Thrombectomy in Patients with Pancreatic Neuroendocrine Tumors, Journal of Gastrointestinal Surgery, Volume 19, Issue 11, 2015, Pages 2011-2018, https://pubmed.ncbi.nlm.nih.gov/26282850/ ISSN 1091-255X,

5. https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e24155 ASCO Annual Meeting Abstracts. Venous thromboembolism in neuroendocrine tumours: incidence, risk factors, and outcomes.

6. Nicholas J. Skertich, Justin Gerard, Jennifer Poirier, Martin Hertl, Sam G. Pappas, Erik Schadde, Xavier M. Keutgen, Do All Abdominal Neuroendocrine Tumors Require Extended Postoperative VTE Prophylaxis? A NSQIP Analysis, Journal of Gastrointestinal Surgery, Volume 23, Issue 4, 2019, Pages 788-793, ISSN 1091-255X, https://www.sciencedirect.com/science/article/abs/pii/S1091255X23021054 National Surgical Quality Improvement Program (NSQIP). Postoperative venous thromboembolism after abdominal surgery for neuroendocrine tumours.

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

Thanks for reading.