Can sticky blood stoke a migraine?

Frequently Asked Questions about Natural Migraine Relief: Episode # 114

Several weeks ago (late March 2026) we all watched long, long lines of weary souls wend their way through the TSA security lines at various airports. Four plus hours of “shuffle your luggage two more feet, wait, then repeat X 250...” It also triggered memories of the many DVTs (episodes of deep vein thrombosis-also called VTE, or venous thromboembolism)) I have seen in my 25 years of part-time ER work. Many of those cases were related to long hours of standing or sitting involved in travel, although work situations were often contributors. I also reflected on the nature of circulatory micro-clots and their relationship to migraine headaches, especially in those who experience some form of “aura” preceding the headache pain. From those musings, I put together this post, where I’ll review:

-how microemboli and migraine are connected.

-what circumstances and situations can put you at risk.

-preventive and therapy measures for this root cause contributor to the migraine mix.

When we consider what could be fixable factors for migraine, we want to know if any one of them contributes meaningfully to “overflowing your migraine cup”. A migraine typically has multiple contributing factors, with rarely the same list for any two migraineurs. For more on this essential concept and the “full cup theory of migraine”, see FAQ #89 Why individualized treatment of Migraine is essential.

In the search for contributory root cause factors, the questions we want to answer are:

1) Which hidden in plain sight factors may be adding to your “causes my migraine” list?

2) What are the focused action steps to achieve prevention and management?

In this FAQ post we will focus on the role of micro clots in the promotion of migraines, especially the 25-30% which have an associated aura event. If you are unsure if you have an associated aura, review the first footnote at the end of this article, and if needed, discuss them with your personal physician.¹

The first principle of diagnosis: understanding the underlying pathophysiology

I’ve always found the clotting cascade to be one of the body’s more elegant and improbable features. Blood is designed to clot… or not clot, at exactly the right time and place. There are thirteen main clotting factors, along with several task specific regulatory proteins, plus platelets that daisy-chain their way through a dance that makes the clot ‘band-aid’ which seals down leaks in the circulatory system. This process keeps blood from leaking while our bodies do routine or acute damage repair.

If we have too little clotting capacity, we get the potential for fluid leak or blood loss.

However, too much can produce more serious clots in major veins, or a potentially fatal embolic block if it travels up to the lungs or brain.

But what about the ‘just enough’ stickiness for ongoing micro clots, but not enough for the larger ones that give notable symptoms, or cause serious damage? You could cycle in and out of a stage of low-grade hypercoagulability for months or years and not know it.

So, how does this relate to migraines?

One popular mainstream model of migraine describes how 1) endothelial dysfunction induces 2) an inflammatory response which results in 3) oxidative stress and 4) a hypercoagulable state marked by increased platelet reactivity, altered erythrocyte morphology and metabolism, and increased fibrinogen levels. This goes on to cause 5) changes in blood vessels, 6) hypoperfusion disorders, and 6) microembolization. The result of this can be 7) neurovascular dysfunction and the provocation of the evoke cortical spreading depression (CSD), an event widely thought to underlie migraines, especially those with preceding aura symptoms.²³

Wow. That’s a lot of pathophysiology in two run-on sentences. The fundamental concept for this discussion is the endothelial dysfunction part. This inner layer of a blood vessel is the direct interface with potentially hyper viscous blood. It assists in directing blood flow volume and, in the process, the downstream oxygen delivery. If there is less oxygen delivery, we get reduced aerobic energy production in our mitochondrial power plants. The brain is an energy hog, and when it “browns out”, it kicks the aura and then migraine vicious cycle into gear.

It has been demonstrated that the occurrence of migraine provoking cortical spreading depression (CSD) is related to the magnitude and duration of blood flow reduction. Also, the migraine triggering mechanism may be in the range where you can get decreased brain perfusion without clinically obvious sustained tissue damage.⁴ Keep in mind that just because it’s not “clinically obvious” does not mean that cumulative damage that affects neurological function, including general cognitive function, is not occurring.

How micro-embolisms do their dirty work

The details under each heading can get into the deep weeds of the relevant biochemistry. I finish each one with a summary line about the consequences of the related biochemical dysfunction.

1. Micro clots increase the viscosity of blood flow. And vice versa as well. Think of pulling water up through a straw, and then compare that to moving a milkshake through the same straw…more work, slower flow, right? Some elegant research at the Institute of Neurological Sciences in Ankara, Turkey showed that the selective thrombosis of a single penetrating arteriole (about one-fifth the width of a human hair) in a mouse brain could induce spreading depression and ischemic injury as a trigger for migraine.⁵ Multiply that by dozens of sluggish arterial feeders and a resulting headache might be hard to avoid.

2. They can cause direct mechanical injury to small vessels

   When micro thrombi lodge in capillaries and arterioles, they physically compress the endothelium and obstruct luminal flow. The resulting ischemia-reperfusion injury, which occurs when flow is intermittently restored, generates reactive oxygen species (ROS) that oxidize membrane lipids and damage endothelial tight junctions. Glycocalyx degradation follows, which strips the endothelium of its primary anti-thrombotic and permeability-regulating layer. This perpetuates recurring micro-emboli and can have long term cognitive implications if it persists.

3. They lead to a reduction of nitric oxide signaling

   Healthy endothelium tonically releases nitric oxide (NO) via eNOS, which suppresses platelet aggregation, promotes vasodilation, and inhibits leukocyte adhesion. Micro clots disrupt this in multiple ways:

   -Fibrin and platelet-derived thromboxane A₂ directly antagonize prostacyclin-mediated NO release

   -Asymmetric dimethylarginine (ADMA), elevated in ischemic endothelium, competitively inhibits eNOS

   -Oxidized LDL and ROS uncouple eNOS, causing it to produce superoxide instead of NO.

   Bottom line: when small arterioles lose the ability to dilate as required, you get less oxygen to the brain.

4. They activate a cascade of inflammation

   Clot-trapped platelets degranulate, releasing PDGF, TGF-β, serotonin, and P-selectin, which together upregulate endothelial ICAM-1 and VCAM-1. This triggers leukocyte rolling and transmigration, amplifying local inflammation. NFκB activation follows, driving cytokine release (IL-6, IL-1β, TNF-α) that further suppresses endothelial barrier integrity. Chronic inflammation is one of the most potent promotors of recurrent migraine.

5. Further promotion of coagulation feedback loops

   Damaged endothelium loses thrombomodulin expression, reducing activated protein C generation, which is normally a key brake on coagulation. Tissue factor is simultaneously upregulated on the endothelial surface. The result is a prothrombotic phenotype that propagates further micro clot formation downstream. This becomes a self-reinforcing cycle that is particularly relevant in hypercoagulable states like migraine with aura.

6. Disruption and heightened permeability of the blood-brain barrier (BBB)

   Clot-associated thrombin directly cleaves PAR-1 receptors on endothelial cells, triggering cytoskeletal reorganization via Rho-kinase. Tight junction proteins (occludin, claudin-5, ZO-1) are phosphorylated and internalized, increasing paracellular permeability. In cerebral microvasculature this is especially consequential, as it represents a partial breach of blood-brain barrier integrity. If prolonged, these occlusion events will cause tissue microinfarction and progressive neurological damage. Loss of BBB integrity is a root cause factor in most every chronic neurological disorder.

7. This process has mitochondrial and metabolic consequences

   Sustained ischemia downstream of micro clots shifts endothelial metabolism toward anaerobic glycolysis, which depletes the ATP needed for ion pump function and cytoskeletal maintenance. Mitochondrial ROS release further oxidizes eNOS cofactors (BH₄) and inactivates antioxidant enzymes (SOD, catalase), deepening the oxidative burden. Underperforming mitochondria are one of the most important contributors to recurrent migraine attacks.

Who gets ‘sticky blood’, and how?

There are several migraine promoting micro-clot factors that can be identified and addressed. Let’s first ID them, then we’ll review proactive management for each.

1. Prolonged immobility during travel is the most common source of serious clot formation. One study of 8,755 adults aged 18 to 71 found that even four-hour flights can triple your risk of getting deep vein thrombosis formation.⁶

   Sitting without regular muscular contraction lets blood pool in the lower extremities. Some seat configurations compress veins and impede blood from returning upward. This isn’t just a travel concern. Consider your daily routine. Hours per day at a desk job. Or, two to three hours at a time on the couch binging Netflix. You might not get a full-blown thrombotic clot, but the resulting micro clot condition can persist for hours after those events.

2. Dehydration. Many of us are chronically dehydrated, which is often accentuated during travel conditions. This adds to excess blood viscosity. Make plans to bolster your hydration while traveling, working outside or with prolonged exercise or recreation.

3. Smoking. Although most migraineurs have quit the habit, smoking and even vaping can significantly amplify migraine frequency and intensity, especially when you have an associated aura, with hypercoagulability being a key factor. If you have migraines, quit you must!

4. Excess iron stores. Although most people have heard of anemia, most of us don’t worry about having too much blood! That’s also true of iron stores, but an excess of both iron and red cells can promote inflammation and be a pro-coagulant. Most women at premenopause are “donating blood” every monthly cycle. But despite this, if you have a habit of taking iron in a multivitamin, post pregnancy, this could promote excess iron stores, even before menopause. There is also a low chance (1/300) of having an iron storage disorder called hereditary hemochromatosis, which can become more problematic at menopause. If your family history is positive for this problem, have your doctor check your CBC and ferritin level.

5. There are several hypercoagulable conditions that are inheritable traits:

   • Factor V Leiden: This most common coag mutation makes factor V resistant to activated protein C (APC), a natural anticoagulant, leading to excessive clotting. Seen most often in individuals of European and Mediterranean descent (approx. 5% prevalence), it is rarer in Asian, African, and Native American populations, where it occurs in roughly 1%–2%.

   • Prothrombin G20210A Mutation: The second most common inheritable trait, with a carrier frequency of roughly 1.5% to 3% in Caucasians. This is a “gain of function” mutation that leads to increased production of prothrombin, increasing blood clotting potential.

     Both this variant as well as Factor V Leider are found in ~15-20% of patients diagnosed with venous thromboembolism (VTE).

     If you have been diagnosed with a major VTE and also have migraine with aura, ask your doctor about testing for both of these variants.

   • Antithrombin Deficiency: A deficiency of this natural anticoagulant that inhibits thrombin and Factor Xa, often leading to severe clotting disorders.

   • Protein C and Protein S Deficiency: Deficiencies in these natural anticoagulants impair the inactivation of clotting Factors V and VIIIG

   • MTHRF methylation deficits. This can result in an elevated homocysteine level, secondary inflammation and potential hypercoagulability.

6. Excess fibrinogen levels. Fibrinogen is a clotting protein made in the liver. When it's elevated it signals two things simultaneously: 1) the coagulation system is primed, and 2) there's systemic inflammation. A high level is both a marker of inflammation as well as an active contributor to pathology. It’s not just a passive bystander. When it’s elevated, it becomes a feed-forward loop, where inflammation drives fibrinogen up, and then the elevated fibrinogen amplifies neuroinflammation and endothelial vulnerability, which worsens a migraine vicious cycle.

7. Patent Foramen Ovale. This might be one of the “most common heart conditions you’ve never heard about.” Before we were born, we all had a connection between the two upper chambers of our heart, allowing maternal blood to bypass the lungs. After birth when the lungs begin ventilating, this connection, known as the foramen ovale, should close completely, as is does in some 75% of us. Sometimes this can remain as a residual opening, called a patent foramen ovale (PFO), which persists into adult life for ~one out of four people and is the most common congenital cardiac anomaly in adults. A PFO can cause additional oxidative stress on our platelets. This can cause additional wear and tear on the cells which can initiate platelet aggregation (clumping). When this happens, micro clots can develop and become a factor in brain vascular problems like migraines or strokes. I wrote an entire lesson on this for my Natural Migraine Relief course and have opened this lesson to all readers for this post. Find it at: Lesson 22: PFOs as a Root Cause factor in Migraine with aura.

   The prevalence of a PFO in patients with migraine with aura has been found to be 46.3–88%, compared with 16.2–34.9%, or two to three times more common in migraine patients without an aura. On the other hand, those with migraine without aura do not appear to have a significantly higher prevalence of PFO compared to the general population.⁷ So, if you:

   -have migraine with an aura

   -have been told that you have “an innocent heart murmur”. or

   -have undergone sclerotherapy for varicose veins in the legs that resulted in a migraine with aura episode (where a PFO could allow microemboli from the procedure to circulate to the brain.)

   you should read Lesson 22 to consider your options.

Testing for the hypercoagulable state

If you have a migraine with an aura, or chronic intractable migraines you almost certainly have some of the elements described above. Unfortunately, there is not a simple blood test for micro clots. Here are a few tests worth considering to provide clues to the inflammatory-thrombotic burden that can lead to a low grade but still meaningful hypercoagulable state:

-fibrinogen level: (normal 200-400 mg/dl): Fibrinogen is the soluble precursor to fibrin, the structural backbone of blood clots, and its elevation is a signal of systemic inflammation, as well as a pro-coagulation entity of its own. Comments on therapy for this in the next section.

-an elevated homocysteine level (greater than 15) indicates a functional inability to methylate B6, B12 and folate optimally. It could also be aggravated by too high a red meat protein diet. Keep that in mind all of you keto and carnivore devotees… Homocysteine elevation can promote inflammation and hypercoagulation. You may want to follow any elevation in this blood work with genetic testing for the variants of gene sets C677T and A1298C. If you have used 23&me or Ancestry, they usually have this information, or you can derive it from their raw data (see my FAQ Episode 3: Using genomic tests like 23andme to learn about your methylation genetics and their role in migraine for details on this.)

-CBC and ferritin: for women, a hemoglobin should be less than 15, and the ferritin in the ~70-90 range. If higher than those, and you are a suitable candidate, you might want to consider donating a unit of whole blood at the local community blood bank. Your personal physician can advise you further on this.

-a D-dimer test measures fibrin degradation products in the blood. It can be elevated in patients with chronic migraine, signaling a state of hypercoagulability and increased inflammation compared to healthy individuals. Studies show higher d-dimer levels during migraine attacks and in individuals with specific risks, like Patent Foramen Ovale (PFO). Elevation of this test would be a strong indicator of a hypercoagulable state (and possibly a current DVT.)

-cardiac ultrasound to assess for PFO, if you have migraine with an aura, especially if you have been told that you have “an innocent heart murmur.”

Practical management of micro-clots as a potential migraine provocateur

1. Keep moving! Stagnant, sludgy blood is sticky blood. Whether traveling, working or binging Netflix, get up and move every 45-60 minutes (and not just to the refrigerator and back! Been there myself, so not judging…).

2. Avoid crossing your legs at rest, it unduly compresses superficial veins.

3. Consider using knee length compression socks for those days when you know some immobility is unavoidable. (great for those cold weather days, too.)

4. Hydrate well, especially on a day of prolonged travel or sitting at work.

5. Avoid (quit) smoking of vaping. Kind of non-negotiable if you would like to not have migraines.

6. Whether at a desk or flying the friendly skies, fit in some stretches every 15-30 minutes, such as:

   -ankle circles (twirling your feet lifted off the ground)

   -foot pumps (raising your toes while keeping your heel on the floor and vice versa

   -shoulder rolls (hunching your shoulders and moving them in a circle for 30 seconds in each direction)

   -arm curls (putting your elbows on your armrests and moving your hands to your chests and back).

   By the way, did you know that these kind of motions, which your mom called fidgeting (a.k.a. “Non-Exercise Activity Thermogenesis”), can burn an extra 100 to 800 calories/day, with some studies suggesting an average of 350 extra calories per day. (350 cal/day X 10 days = 1 lb of fat!! As good or better than a GLP-1.)

7. If you have had both a venous thromboembolism and migraine with aura, you have roughly a ~20% chance of having either the Factor V Leiden or the Prothrombin G20210A mutation. If so, ask your doctor to check for these. If they are positive, much of the therapy includes the preventive measures mentioned here.

8. Have your homocysteine checked. If elevated, see FAQ Episode 39: Is there a relationship between Migraine and Alzheimer’s type dementia? where I go into detail on non-drug therapy to manage this.

9. Reduce excess fibrinogen with nattokinase. A clinical trial with nattokinase (non-rx) of 4,000 FibrinUnits/day for two months reduced fibrinogen ~10%. ⁸ Because of this benefit, be aware that nattokinase could increase bleeding risk when combined with anticoagulant, antiplatelet, or fibrinolytic drugs. If you need more aggressive therapy, the fibrate prescription meds for lipid management, like bezafibrate, can cut fibrinogen levels by anywhere from 15-40 %.

   Remember also that elevated fibrinogen is your body’s yellow flag marking excess inflammation from somewhere. Undiagnosed early adult diabetes? Excess refined grains, seed oils, sugar, trans fats, and processed foods in the diet? Liver congestion die to obesity or alcohol use? There are many suspects. Plan to give this concern further investigation.

10. Be cautious with estrogen. Oral contraceptives or high dose estrogen replacement therapy can increase the risk of blood clots on their own, which also worsen with every co-factor on this list. I always recommend that if taking post-menopausal HRT that you: 1) combine the more potent estradiol form of estrogen with estriol (this requires a compounded topically applied version) and 2) check serum levels of the estradiol component to make sure that its “the least amount needed to manage the symptoms.” Usually a blood level in the 20-75 pg/ml range. Also, pair it with USP progesterone (whether or not you still have your uterus.)

11. If you have excess red cells, iron or ferritin, and have no other contraindications, consider donating a unit of blood. But in general, keep the Hb (hemoglobin) level at ~12 or greater. Donating one unit of blood will drop the hemoglobin reading 1 point. So consider not donating unless the hemoglobin is in the upper 12 range or higher.

12. If you have migraine with an aura, especially if you have been told that you have “an innocent heart murmur”, you may want to talk with your personal physician about getting a screening cardiac ultrasound to assess for a physiologically meaningful PFO. If this is positive for PFO, also consider a D-dimer test to see if there are active fibrin degradation products in the blood. That would be an additional sign that considering PFO correction might be worthwhile.

Optimal flow of blood and oxygen fuels brain functionality. ‘Sticky blood’ and micro clots impede this process as well as promoting chronic small vessel inflammation and injury. If you have migraines, particularly if you have an associated aura, pursue the optimal management of this root cause factor as if your brain depends on it, because it really does.

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1. A migraine aura is a set of temporary focal neurological symptoms, usually visual, that precede or accompany a headache. Common characteristics include gradually spreading zigzag lines, bright spots, blind spots (scotomas), numbness, or speech difficulties, typically developing over 5–60 minutes and resolving completely.

Key Characteristics of Migraine Aura:

• Duration and Onset: Symptoms tend to develop slowly (over 5-20 minutes) and last less than 60 minutes. They usually occur immediately before the headache, but can happen during it or, rarely, without any headache (silent migraine).

• Visual Aura (Most Common - 90%):

  • Positive Symptoms: Shimmering spots, sparks, flashes of light, or colored zig-zag lines (fortification spectra) that float or spread across the field of vision.

  • Negative Symptoms: Temporary blind spots (scotomas) or partial vision loss.

• Sensory Aura: Tingling or numbness that often starts in one hand and travels up the arm, sometimes affecting the face, lips, or tongue.

• Dysphasic Aura (Speech/Language): Difficulty speaking, finding words, or understanding speech.

• Motor Aura: Less common, involving temporary weakness or paralysis on one side of the body (known as hemiplegic migraine).

• Reversibility: A key feature is that all symptoms are fully reversible, meaning they go away completely without permanent damage

2. “A Possible Role of Amyloidogenic Blood Clotting in the Evolving Haemodynamics of Female Migraine-With-Aura: Results From a Pilot Study” Sulette de Villiers, et.al. Front. Neurol., 25 November 2019 Sec. Headache and Neurogenic Pain Volume 10 - 2019 | https://doi.org/10.3389/fneur.2019.01262

3. “Migraine aura pathophysiology: the role of blood vessels and microembolisation” Turgay Dalkara, et.al. Lancet Neurol. 2010 Mar;9(3):309-17. doi: 10.1016/S1474-4422(09)70358-8 https://pubmed.ncbi.nlm.nih.gov/20225282/

4. “Microemboli may link spreading depression, migraine aura, and patent foramen ovale.” Ala Nozari, et. al. Ann Neurol. 2010 Feb;67(2):221-9. doi: 10.1002/ana.21871. https://pubmed.ncbi.nlm.nih.gov/20225282/

5. “Microembolism of single cortical arterioles can induce spreading depression and ischemic injury; a potential trigger for migraine and related MRI lesions.” Buket Dönmez-Demir, et. al. Brain Res. 2018 Jan 15:1679:84-90. DOI: 10.1016/j.brainres.2017.11.023 https://pubmed.ncbi.nlm.nih.gov/29183666/

6. “The Absolute Risk of Venous Thrombosis after Air Travel: A Cohort Study of 8,755 Employees of International Organisations” Saskia Kuipers, et. al. PLoS Med. 2007 Sep 25;4(9):e290. doi: 10.1371/journal.pmed.0040290 https://pmc.ncbi.nlm.nih.gov/articles/PMC1989755/

7. “Right-to-left shunt is common in chronic migraine.” Nahas, SJ. et. al. Cephalalgia. 2010 May;30(5):535-42. doi: 10.1111/j.1468-2982.2009.02002.x. Epub 2010 Feb 11. PMID: 19732069.

8. “Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.” Chien-Hsun Hsia et. al. Nutrition Research Volume 29, Issue 3, March 2009, Pages 190-196bbhttps://doi.org/10.1016/j.nutres.2009.01.009