March 2022: Migraines & Coagulation Factors

by Donna Castellone, MS, MT (ASCP) SH • March 14, 2022



The interpretations below are provided by Donna Castellone, MS, MT (ASCP) SH for Aniara Diagnostica.


What do Napoleon, Robert E. Lee, Elvis Presley and Serena Williams and I all have in common? We are all migraine sufferers. For those of you who are part of this club it is quite large. I have always wondered - Is there a connection between these awful occurrences and coagulation factors? Do they play a causal role?

 

History of Migraines:

Believe it or not, the history of migraines goes back to as early as 7000 BC. An early explanation of migraines was believed to be due to the release of demons and evil spirits, which seems to be reasonable. Just ask anyone who has experienced one! Trepanation was a practice in which the removal of a segment of bone from the skull was performed possibly to release demons and evil spirits from the head. In 1200 BC the Ebers Papyrus mentions migraine, neuralgia and shooting head pains. Their relief came from binding a clay crocodile holding grain in its mouth to the head of the patient using a strip of linen, which actually may have helped their pain by collapsing distended vessels that were causing the pain. Whatever works! In 400 BC Hippocrates was the first to describe the visual symptoms of migraine including a shining light, followed by violent pain in the temples and radiating to the entire head and neck.(1)

After several different theories throughout time, in 1888 Dr. William Gowers known as the founder of modern neurology published a treatment of migraines which included a healthy diet and treatment including nitroglycerin and alcohol as well as marijuana. He noted the importance of continuous treatment with drugs to make attacks less frequent. (1)

 

Migraines with Aura

Up to 15% of the US population experience migraines. A migraine with aura (MA) is a subtype in which individuals see flashing lights, blind spots or jagged lines prior to the start of their headaches. Patients with MA also have a heightened risk of stroke up to two-fold and cardiovascular disease.(2) This risk increase is most pronounced in young women and is thought to be multicausal.

Migraine with aura has also been associated with endothelial dysfunction which also causes a prothrombotic and proinflammatory state and impaired vascular reactivity which in turn can lead to clot initiation.(3)

 

Hypercoaguability and Migraines:

Traditional thrombogenic factors, such as VWF (von Willebrand factor) and, aPL (antiphospholipids) were found to be elevated in migraine patients, though results were conflicting.(3) Hypercoagulability has been found in patients with migraines. Levels of prothrombin factor 1.2 (F 1.2) were measured in patients with migraines. This is a specific marker of ongoing thrombin generation and an indicator for hypercoagulability. Levels were measured in 35 patients with migraines and compared to 24 healthy controls. Of those patients, 22 presented with aura and 13 without aura. Elevated F1.2 levels were found in 11/22 patients with aura while none of the patients with migraine without aura or healthy controls had elevated F1.2 levels. These findings suggests that there is activation of the clotting system in certain patients with migraine with aura.(4)

One theory suggests that MA patients have an increased risk for ischemic stroke not due to enhanced atheroschlerosis but that micro-emboli induced ischemia provokes cortical spreading depression but transient ischemic attacks in others highlights a potential role for hypercoagulability as a link between migraine (with aura) and stroke. This may be due to acquired or inherited thrombophilic states included elevated estrogen levels, antiphospholipid antibodies and the presence of genetic polymorphisms.(5)

There is some evidence that links migraine and in particular MA to increase levels of estadiol, pregnancy, VWF, fibrinogen, TPA, and endothelial microparticles but are conflicting for aPL homocysteine, Protein S and MTHFR.(5)

A study looked at the association of the factor V Leiden and the prothrombin G20210A gene polymorphism and its possible association to migraine. The prevalence of the FV allele was found to be similar between both cases and controls at 4.9% and 4.7% respectively. The cumulative prevalence of the FII allele was also found to be similar between cases and controls at 4.2% and 4.5% respectively. The sub-analysis revealed the polymorphisms were not associated with migraine in adults but they were two-fold more prevalent in children with migraine than in those without. The role of the FV Leiden and FII 20210 allele in children may play a role in migraine headache.

 

Coagulation Factors and Migraines

A study out of Brigham and Women’s Hospital used a technique in genetic analysis called Mendelian randomization to examine 12 coagulation parameters to determine what coagulation factors may be associated with migraines. They found only an association in patients that had migraine with aura and found that there were four coagulation parameters that had a causal role in that hemostatic risk factors that may play a role in contributing to a MA.(2)

This study included 59.674 participants with migraines and 315,078 controls. Subgroups included one group with 4837 MA patients and 49,174 controls and another consisted of 4833 patients with migraine without aura (MO) and 106,834 controls. Using Mendelian randomization investigators found a strong association between four coagulation factors and migraine susceptibility. Genetically increased levels of Factor VIII, von Willebrand factor and phosphorylated fibrinopeptide A and genetically decreased levels of fibrinogen were all associated with migraine susceptibility however this association was not found in individuals that have migraines without aura. These findings support coagulation and thrombosis as a potential etiology for migraine susceptibility. There may also be a potential connection between MA and stroke.(2)

 

Conclusion:

Based on a review of the literature, there appears to be an association between four coagulation factors and the occurrence of migraine with aura. This also appears to have an increased risk in the incidence of stroke in this cohort of migraine patients. There are many processes that are associated with migraines that link to coagulation activities such as platelet hyperactivity and inflammation.

I am sure that the added stress that a migraine adds on the body creates an entire activation of many physical and psych systems- many of which include a dark room, quiet, and no movement. To those of you who suffer from them I hope they are few and far between, and to those of you who do not, you are lucky and have patience with those who do!

 


REFERENCES:

  1. https://headacheaustralia.org.au/what-is-headache/history-of-headache/
  2. Guo Y, Rist PM, Sabater-Lleal M, et al. Association between hemostatic profile and migraine: a Mendelian randomization analysis. Neurology. Published online April 1, 2021.
  3. Hendrikus J A van Os 1, Marieke J H Wermer 1, Frits R Rosendaal 2, José W Govers-Riemslag 3, Ale Algra 4, Bob S Siegerink 2 5 Intrinsic Coagulation Pathway, History of Headache, and Risk of Ischemic Stroke Stroke 2019 Aug;50(8):2181-2186
  4. R Hering-Hanit, Z Friedman, I Schlesinger, Evidence for Activation of the Coagulation System in Migraine with Aura, First Published March 1, 2001 https://doi.org/10.1046/j.1468-2982.2001.00181.x
  5. Gretchen E. Tietjen MD,Stuart A. Collins PhD, Hypercoagulability and Migraine Headache Currents: The Journal of Head and Face Pain, 09 February 2017
  6. Lippi G1, Mattiuzzi C, Cervellin G Meta-analysis of factor V Leiden and prothrombin G20210A polymorphism in migraine Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis, 01 Jan 2015, 26(1):7-12.