# Myelofibrosis Aspirin sits in a different place in **myelofibrosis**, or **MF**, than it does in many other cancer settings. Here, aspirin already has a recognised role in selected patients because **thrombosis risk** is a major issue across the **myeloproliferative neoplasms**, or **MPNs**. It also makes sense to ask whether aspirin may have broader **anti-inflammatory**, **disease-modifying**, or **anti-fibrotic** relevance in MF itself. That is the key split in this topic. ### Overview MF is not only a clonal blood cancer. It is also a disease of **platelet activation**, **cytokine excess**, **bone-marrow fibrosis**, and chronic **JAK-STAT** pathway signalling. That makes aspirin biologically interesting for four reasons: * it suppresses **platelet COX-1** and **thromboxane A2**, or **TXA2** * it may reduce **NF-κB**-driven inflammatory pressure * salicylate biology intersects with **JAK-STAT** and **TGF-β-linked** fibrosis pathways * MPNs create unusually fast **platelet turnover**, which changes how aspirin dosing behaves The strongest current clinical use is still **thrombosis prevention**. The broader anti-fibrotic and disease-modifying story is still **early**. {% hint style="warning" %} MF is not a blanket low-dose aspirin disease. Bleeding risk, thrombocytopenia, acquired von Willebrand disease, portal hypertension, varices, and anticoagulant use can all change the balance. {% endhint %} ### What the human evidence shows #### Why some MF patients already use aspirin Aspirin is already used in MF mainly to reduce **arterial and microvascular thrombotic risk**. There is also growing interest in whether it may matter in other ways. That logic comes from the wider **MPN** literature, where thrombotic events remain a major cause of morbidity and mortality. Aspirin works here through irreversible **COX-1** acetylation in platelets, which suppresses **TXA2** generation and reduces platelet aggregation. [Read the Haematologica review](https://haematologica.org/article/view/haematol.2022.281388) Unlike some solid-tumour aspirin pages, MF is a setting where aspirin may already be used for a standard haematology reason. It still does **not** suit every MF patient. The balance changes quickly when platelet counts fall, bleeding history appears, or anticoagulation is already in place. [Read the Macmillan summary](https://www.macmillan.org.uk/cancer-information-and-support/blood-cancer/myelofibrosis-mf) #### What recent MF data suggest A 2025 **ASH** abstract reported a real-world cohort of **215 consecutive MF patients** and found a **trend toward lower thrombosis risk** in patients receiving aspirin. [Read the ASH abstract](https://ashpublications.org/blood/article/146/Supplement%201/5596/553166/Aspirin-therapy-in-myelofibrosis-Real-world) True MF-specific aspirin datasets are still rare. This was not a randomised trial. It does not prove aspirin improves survival or changes marrow fibrosis. It does support the practical view that aspirin remains relevant in MF because the thrombotic question is real. #### Why dosing can be different in MPNs Standard **once-daily low-dose aspirin** often gives incomplete platelet suppression in **MPNs**. The reason is accelerated platelet production. New platelets enter the circulation without aspirin-mediated **COX-1** acetylation, which means **TXA2** recovery can happen faster than expected. A 2023 study confirmed that **immature platelet fraction**, or **IPF**, and residual **TXA2** output measured as **serum TXB2** are both higher in MPN patients than in controls. [Read the open-access paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC9979736/) That makes MF different from ordinary cardiovascular aspirin use. In MPN pharmacodynamic studies, including the **ARES** programme and later follow-up work, **100 mg twice daily** suppressed **TXA2** more completely than once-daily dosing and improved microvascular symptoms without a major bleeding signal in selected patients. [Read the pharmacodynamic paper](https://pubmed.ncbi.nlm.nih.gov/30012347/) Most of this evidence comes from **ET** and **PV**, not pure MF cohorts. So the dosing lesson is probably relevant to MF biology, but much of it still comes from the wider **MPN** field rather than from large MF-only trials. ### Why aspirin may matter beyond clot prevention #### JAK-STAT and NF-κB overlap MF is strongly driven by **JAK-STAT** pathway activation. That is usually linked to **JAK2**, **CALR**, or **MPL**-driven signalling, plus a chronic inflammatory state that feeds back on the malignant clone and on stromal cells. Aspirin becomes interesting here because salicylate-related signalling can suppress both **STAT3 phosphorylation** and **NF-κB** activity in model systems. That means aspirin touches two pathways that matter deeply in MF biology. [Read the open-access mechanistic paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6202076/) Aspirin is not functioning like a true **JAK inhibitor**. It does, however, touch some of the same inflammatory wiring. #### Cytokine suppression and inflammatory pressure MF is a cytokine-heavy disease. High levels of **IL-6**, **TNF-α**, **TGF-β**, and related mediators help drive constitutional symptoms, marrow remodelling, stromal activation, and progressive fibrosis. Aspirin and salicylates can inhibit **IKKβ** and downstream **NF-κB** signalling. That can reduce production of several of these same inflammatory mediators. [Read the open-access fibrosis paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC5618301/) MF is not only about the malignant clone. It is also about the inflammatory environment the clone creates. That is one reason aspirin remains mechanistically interesting even though direct MF disease-modification data is still missing. #### Anti-fibrotic plausibility This is one of the most interesting areas. It is also where the research is thinnest. Several non-marrow fibrosis models suggest aspirin can reduce fibroblast activation, collagen deposition, and pro-fibrotic signalling through pathways that matter to MF, including: * **MAPK-Erk1/2** and **PI3K-AKT-β-catenin** suppression. [Read the cardiac-fibrosis paper](https://karger.com/cpb/article/45/5/1955/73386/Aspirin-Reduces-Cardiac-Interstitial-Fibrosis-by) * **ROS** and **p38** pathway inhibition. [Read the study](https://www.nature.com/articles/aps2016143) * modulation of **TGF-β**-linked fibrosis signalling by salicylate. [Read the paper](https://www.nature.com/articles/s41598-024-67266-5) * reduced stellate-cell activation and lower **IL-6** and **TNF-α** in fibrosis models. [Read the open-access paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC5618301/) Bone-marrow fibrosis is driven by activated stromal and fibroblast-like cells responding to cytokines such as **TGF-β**, **PDGF**, and inflammatory stress. Clinical studies here have not caught up yet. There is still **no clinical trial** showing aspirin reverses or meaningfully reduces **bone-marrow fibrosis** in MF patients. [Read the review record](https://pubmed.ncbi.nlm.nih.gov/25120015/) #### Aspirin-triggered lipoxins Aspirin may also matter through a more specialised **pro-resolution** pathway. When aspirin acetylates **COX-2**, the pathway can shift toward production of **15-epi-lipoxin A4**, often called an **aspirin-triggered lipoxin**, or **ATL**. These mediators do not just suppress inflammation. They help actively resolve it. [Read the open-access review](https://pmc.ncbi.nlm.nih.gov/articles/PMC5459549/) MF is not simply an inflamed state. It is a chronically dysregulated inflammatory state that fails to switch off cleanly. In lung-fibrosis models, aspirin-triggered lipoxin signalling has shown anti-fibrotic and pro-resolution effects. A randomised study in healthy volunteers also found that **81 mg aspirin** increased circulating ATL levels while lowering **TXB2**. [Read the open-access review](https://pmc.ncbi.nlm.nih.gov/articles/PMC5459549/) This pathway has not yet been shown to change outcomes in MF. That may simply reflect how little direct MF research has been done here. ### Clinical positioning | Setting | Evidence | Position | | ----------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | ----------------------------------------------------- | | **Thrombosis prevention in selected MF patients** | Real clinical use plus supportive MF and wider MPN data. [Read the Haematologica review](https://haematologica.org/article/view/haematol.2022.281388) | Established in selected patients | | **Real-world MF thrombosis reduction** | 2025 cohort showed a trend toward lower thrombosis risk. [Read the ASH abstract](https://ashpublications.org/blood/article/146/Supplement%201/5596/553166/Aspirin-therapy-in-myelofibrosis-Real-world) | Supportive, but not definitive | | **Once-daily low-dose aspirin in MPNs** | Often gives incomplete COX-1 suppression because of platelet turnover. [Read the open-access paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC9979736/) | Pharmacodynamically limited | | **Twice-daily plain aspirin in MPNs** | Better TXA2 suppression and symptom control in pharmacodynamic studies. [Read the pharmacodynamic paper](https://pubmed.ncbi.nlm.nih.gov/30012347/) | Biologically stronger, but still extrapolated into MF | | **Disease modification or marrow-fibrosis reversal** | No direct MF trial evidence. [Read the review record](https://pubmed.ncbi.nlm.nih.gov/25120015/) | Not established | | **JAK-STAT and NF-κB pathway overlap** | Strong mechanistic plausibility only. [Read the open-access mechanistic paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6202076/) | Investigational | | **Anti-fibrotic signalling and aspirin-triggered lipoxins** | Interesting non-MF fibrosis data. [Read the open-access review](https://pmc.ncbi.nlm.nih.gov/articles/PMC5459549/) | Hypothesis-generating | ### What this means in practice In MF, aspirin already matters clinically, mainly for a **haematology** reason rather than a direct anti-cancer one. That is why it helps to keep two ideas separate: * where aspirin is already useful * where aspirin is still promising but unproven Right now: * aspirin has real value in **selected MF patients** for **thrombosis** and microvascular-risk management * **MPN biology** creates a genuine aspirin-dosing problem that may make **twice-daily plain aspirin** more pharmacodynamically rational than once-daily dosing in some patients * aspirin also has credible **JAK-STAT**, **NF-κB**, **cytokine**, and **fibrosis-pathway** overlap with MF biology * there is still **no clinical proof** that aspirin improves marrow fibrosis, spleen response, symptom burden, or survival through disease modification Aspirin is already relevant in MF. The wider disease-modifying story is still early. If aspirin is being discussed, it helps to be clear about the goal. Is the aim **clot prevention**? Or is the aim to explore whether aspirin might also help with inflammation or fibrosis? Those are different conversations. The most useful questions for the haematology team are: 1. Is aspirin being considered because of **thrombotic risk**, **microvascular symptoms**, or both? 2. What is the current **platelet count**, and is there any concern about **bleeding**, **varices**, or **acquired von Willebrand disease**? 3. Is the patient **JAK2-mutant**, previously thrombosed, or otherwise in a subgroup where aspirin logic is stronger? 4. If aspirin is being used, is the goal simple **once-daily prophylaxis**, or does accelerated **platelet turnover** make dosing adequacy a real issue? 5. Are people hoping for **anti-fibrotic** or **disease-modifying** benefit that has not actually been shown yet? The last question matters most. The anti-fibrotic possibility is still unproven. ### References * Haematologica 2022 review — aspirin, thrombosis, and MPN platelet biology. [Read the review](https://haematologica.org/article/view/haematol.2022.281388) * ASH 2025 abstract — real-world aspirin therapy in **215 consecutive MF patients**. [Read the abstract](https://ashpublications.org/blood/article/146/Supplement%201/5596/553166/Aspirin-therapy-in-myelofibrosis-Real-world) * Long-term MPN aspirin pharmacodynamics — twice-daily versus once-daily low-dose aspirin. [Read the paper](https://pubmed.ncbi.nlm.nih.gov/30012347/) * Open-access 2023 paper — residual **TXA2** generation, immature platelet fraction, and aspirin non-responsiveness in MPNs. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC9979736/) * Open-access mechanistic paper — aspirin effects on **STAT3** and **NF-κB** signalling. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC6202076/) * Open-access fibrosis paper — aspirin suppresses **TLR4-MyD88-NF-κB**, **IL-6**, and **TNF-α** in fibrosis models. [Read the paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC5618301/) * Cardiac-fibrosis model — aspirin reduces fibrosis through **MAPK-Erk1/2** and **PI3K-AKT-β-catenin** pathways. [Read the paper](https://karger.com/cpb/article/45/5/1955/73386/Aspirin-Reduces-Cardiac-Interstitial-Fibrosis-by) * ROS and p38-linked anti-fibrotic paper. [Read the study](https://www.nature.com/articles/aps2016143) * Salicylate and **TGF-β** modulation paper. [Read the paper](https://www.nature.com/articles/s41598-024-67266-5) * Aspirin-triggered lipoxins and pro-resolution signalling. [Read the open-access review](https://pmc.ncbi.nlm.nih.gov/articles/PMC5459549/) * MF background and practical caution summary. [Read the Macmillan summary](https://www.macmillan.org.uk/cancer-information-and-support/blood-cancer/myelofibrosis-mf) * Review record on aspirin in MPNs and evidence limits. [Read the record](https://pubmed.ncbi.nlm.nih.gov/25120015/)

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