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

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Throughout history, many cultures have described the heart as the seat of life where it captures emotions. In this month of "hearts", where does that association come from and how does this interplay with the brain and emotions and of course coagulation. Normal variability in heart rate is influenced by sympathetic or parasympathetic dominance, depending on environmental changes¹. Measuring the variability of the heart rate provides information about emotional processing and the heart's response. This leads to the concept of emotions as a risk factor for cardiovascular disease. It has been hypothesized that there is a link between negative emotional triggers and clinical events including autonomic dysfunction, hemodynamic responses, neuroendocrine activation, and inflammatory and prothrombotic responses. Negative and positive emotions have been shown to independently increase or decrease the risk of CVD related events.¹

Role of stress in blood coagulation:

Stress is a contributor to several health issues, everything from headaches to severe conditions including inflammation and heart disease and a possible role in the formation of blood clots. Stress is the body's response to threats or challenges by triggering physiological changes. There are two types of stress, acute stress is short term and can help people stay alert and focused in situations as opposed to chronic stress which is long lasting, persistent and results from pressures from work, finances or relationships.²

During stress our body goes into "fight or flight" response and releases cortisol and adrenaline which prepares the body for increasing heart rate, elevating blood pressure, and redirect blood flow to essential organs and muscles. This process is crucial for survival in acute stress, prolonged activation can impact health. Chronic stress has been linked to hypertension which is a risk for heart disease and stroke.

Stress hormones can also increase factors in the clotting process resulting in an increased risk for thrombosis. Published studies (JAMA) showed that people with high levels of work-related stress had a 43% higher risk of developing blood clots compared to those with low stress levels.² Stress induced hormones can increase the production of platelets and other clotting factors. It can also cause increased inflammation which also contributes to clot formation by activating platelets and clotting factors. Chronic inflammation can also damage the lining of blood vessels allowing susceptibility to clot formation.²

People who present with acute anxiety disorder tend to suffer the highest level of blood clotting in comparison to psychologically healthy population and may be why they are at a greater risk of dying from heart disease. Most initial claims were made based on surveys of subjects. A study was conducted to look at people who are gripped by fears such as panic attacks in crowds or social phobias compared to a healthy control group. To eliminate the confounding variable of age, 31 patients were matched by age and sex with healthy controls. Blood samples showed that when coagulation factors were measured the anxiety group have highly activated coagulation systems versus the healthy controls. The levels did not result in acute danger, however if they were combined with additional risk factors like smoking and obesity, the risk for blood clotting can become a threat.³

Stress and Coagulation Factors:

Stress-induced hyper activation of the autonomic nervous system and hypothalamic–pituitary–adrenal axis can trigger cellular and molecular alterations in platelets, coagulation factors, endothelial function, redox balance, and sterile inflammatory response.⁴

Emotions can impact blood coagulation in the following ways:

• Emotional upset has been identified as a potential trigger of myocardial infarction (MI).
• Intense emotions increase the risk of MI by about 4.7 times.
• Individuals with pre-existent atherosclerosis and impaired endothelial anticoagulant function are most vulnerable to acute coronary events within two hours of intense emotions.
• Patients with blood clots may experience anxiety, grief, and post-traumatic stress disorder.
• Provoked anger and other core negative emotions are associated with an increased risk of cardiovascular disease events.⁴

When cardiovascular (CVD) patients are under acute stress, it is noted that both coagulation and fibrinolysis are enhanced, with procoagulant factors being more increased resulting in a prothrombotic state. Under chronic stress only the procoagulant pathway is upregulated and fibrinolysis impaired. When compared to healthy subjects psychologically acute stress increases plasma filtration with consequent blood hyper viscosity, decrease of plasma volume, increase of hematocrit, and activation of clotting factors. Patients present with an increase in of FVIIa, FVIIIa, FXIIa, fibrinogen, and von Willebrand factor antigen (vWF:Ag); thrombin–antithrombin complex (TAT); and D-dimer. The PT was increased while the aPTT is decreased.⁴

Chronic stress can affect hemostasis differently with elevated levels of fibrinogen, FVIIa, FVIIIa, vWF, D-dimer, and PAI-1. Work related stress reduced t-PA without impacting the PT/aPTT, while caregiver stress increased levels of vWF:Ag, PAI-1:Ag, TAT, D-dimer, and t-PA:Ag and a massive increase in D-dimer which remains higher for up to 30 months after the end of caregiving.⁴

Stressful conditions can also stimulate thrombopoiesis and platelet activation. Due to enhanced expression of glycoproteins, fibrinogen receptors and P-selectin on platelets, aggregation is promoted and interation with leukocytes. This protects against excessive bleeding. During acute stress, in healthy patients the percentage of PLA returns to basal level between 20 and 45 minutes, as opposed to CVD patients in which is it increased until 75 minutes post stress. Hyper-reactivity of platelets has also been enhanced in stable CVD and in post MI patients when compared to normal controls. When exogenous administration of glucocorticoids are given to healthy volunteers, an increase in platelet aggregation and activation is seen as is when altered levels of serotonin levels were induced increasing coronary thrombosis. Also, catecholamines stimulate thrombopoiesis and increased expression of the GP1b and GPIIb-IIIa complex. Combining increased stress levels and the release of hormones can increase platelet activity and put people at risk for thrombosis.⁴

Minimizing Risk:

Managing stress is not easy since people react differently to different situations, so there is no one size fits all. However, certain activities and choices can help to minimize your prothrombic risk and CVD.

A study looked at 7 males who did yoga exercises daily for one hour for a total of four months. Blood samples were taken before and after yoga training. Fibrinolytic activity was increased with a decrease in fibrinogen, aPTT and a prolonged platelet aggregation. Both hemoglobin, hematocrit and platelets were increased. This supports the impact of yoga on the prevention of cardiovascular and thrombotic disorders.⁵

A one third reduction in the risk of cardiovascular disease was seen with dark chocolate. This is due to the flavonoids including flavan-3 including epicatechin which is a micronutrient found in chocolate, green tea and grape. This is known to impact platelet function. A study looked at 10 healthy subjects with normal coagulation profiles to determine if cocoa has an impact on coagulation and fibrinolysis. Platelet aggregation, clot lysis and thrombin generation testing was performed. Epicatechin 100 µmol/L, was found to result in lower maximal aggregation in ADP and collagen 45% versus 73% in control and 67% versus 79% in control. Coagulation was found to be slightly decreased as shown in thrombin generation 1345 (1161 - 1563)nM. min versus 1503 (1262 - 1728)nM. min (in control and fibrinolysis was impaired in subjects with epicatechin 100 µmol/L was significantly lower than without epicatechin with 11,0 (8,0 - 16,0) min versus 15,0 (9,5 - 20,8) min in control (p < 0.01). Further studies will need to confirm these findings.⁶

Healthy subjects were given a cocoa beverage and versus a placebo, 2 hours after ingestion, blood was take and platelets were stimulated with epinephrine and ADP. And both parameters were significantly reduced in patients who had cocoa. This worked by reducing the formation of active platelet microparticles and increasing platelet related function. Another study looked at platelet function in smokers 2 hours after eating 40g of dark chocolate. The study showed a significantly reduced platelet adherence by shear stress by 5%. Similar results were found in heart transplant patients. This was attributed to the antioxidant properties of cocoa flavanols leading to an increase in nitrous oxide (NO) bioavailability attributing to a decrease in platelet reactivity.⁷

What about the cardio-protective impact of wine? It was considered to be a heart healthy contributor in moderation, however new studies may have uncovered more questions than answers. What about the risk of cancer with alcohol? The US surgeon general called for alcoholic beverages to carry a warning label about cancer risk. But is all alcohol the same? Red wine seems to be an outlier possibly due to it's anti-inflammatory and antioxidant resveratrol which may protect against heart disease, aging and cancer. However, several studies that revealed this was said to be biased leading to these positive associations.

Alcohol is a group 1 carcinogen after ingested it is metabolized into acetaldehyde which can damage DNA and research has shown that there is a risk of at least 7 types of cancer: oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A "standard" drink has 14 g of alcohol, which translates to a 5-oz glass of wine.) Heavy drinking, more than 2 drinks per day, has a fivefold increase in these cancers with a 61% increase in breast cancer. A study in JAMA found this risk occurred in people with chronic health conditions including diabetes or HBP.

How people ingest alcohol could make a difference. In wine drinkers, or those who drank only with meals, showed a lower risk for cancer mortality and all cause mortality. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was "substantial" heterogeneity among the studies.

Previous studies have shown that beneficial doses of 30–50 g and 130/250 mL for chocolate and wine, respectively, for women and men. The accumulated evidence indicates that the active ingredients in the products under consideration in this review are phenolic compounds, characterized by anti-inflammatory, antioxidant, and antiplatelet properties. However, there are also some reports of cardioprotective properties of other compounds such as esters, amines, biogenic amines, amino acids, fatty acids, mineral ingredients, and vitamins. Also, the bioactive compounds in chocolate and wine depend on age, sex, body weight as well as medical conditions.⁹

Conclusions:

There is a complex relationship between stress and a prothrombotic state. This includes platelet activation, dysregulation of coagulation, fibrinolysis and endothelial dysfunction and inflammation. Direct causation has not been established, evidence suggests that chronic stress can contribute as a pathological trigger. This is especially important in susceptible patients with pre-existing comorbidities creating a perfect storm. It is important to manage stress for cardiovascular health and for physical and mental well-being. Taking steps to adopt stress reduction strategies including exercise, diet, sleep and stress management can make a difference in health outcomes.

Apparently, chocolate is still a good thing, alcohol is pretty much under fire and you should proceed with caution. It is important to not just be aware of our hearts in February, but all year long. I do believe in finding what makes you happy and allowing yourself to do that. It doesn't hurt to hug someone; I am sure that improves platelet function and contributes to CV health. Happy Valentine's Day!

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REFERENCES:

1. Provenzani, U. (2020). Emotional Processing and Heart Activity. In: Govoni, S., Politi, P., Vanoli, E. (eds) Brain and Heart Dynamics. Springer, Cham. https://doi.org/10.1007/978-3-030-28008-6_15
2. Can Stress Cause Blood Clots? August 18, 2024 https://neurolaunch.com/can-stress-cause-blood-clots/
3. Anxiety Linked To Blood Clots: Fear That Freezes The Blood In Your Veins, March 26, 2008. https://www.sciencedaily.com/releases/2008/03/080325111800.htm
4. Leonardo Sandrini, Alessandro Ieraci, Patrizia Amadio, Marta Zarà, Silvia Stella Barbier, Int J Mol Sci 2020 Oct 22;21(21):7818. doi: 10.3390/ijms21217818 https://pmc.ncbi.nlm.nih.gov/articles/PMC7659944/
5. I S Chohan, H S Nayar, P Thomas, N S Geetha, Influence of yoga on blood coagulation, Thromb Haemost, 1984 Apr 30;51(2):196-7
6. Thomas Sinegre, André Mazur, Marc G Berger, Dragan Milenkovic, Anne-Françoise Sapin, Christine Morand, Aurelien Lebreton, Epicatechin Impact on Primary Hemostasis, Coagulation and Fibrinolysis, Blood, Volume 126, Issue 23, 2015. https://www.sciencedirect.com/science/article/pii/S0006497118516670
7. Galleano M, Oteiza PI, Fraga CG. Cocoa, chocolate, and cardiovascular disease. J Cardiovasc Pharmacol. 2009 Dec;54(6):483-90. https://pmc.ncbi.nlm.nih.gov/articles/PMC2797556/
8. Amy Norton, Red Wine May Not Be a Health Tonic, but Is It a Cancer Risk?, January 13, 2025 https://www.medscape.com/viewarticle/red-wine-may-not-be-health-tonic-it-cancer-risk-2025a10000o5?ecd=WNL_mdpls_250117_mscpedit_wir_etid7168751&uac=477955CG&spon=17&impID=7168751
9. Sperkowska B, Murawska J, Przybylska A, Gackowski M, Kruszewski S, Durmowicz M, Rutkowska D. Cardiovascular Effects of Chocolate and Wine-Narrative Review. Nutrients. 2021 Nov 26;13(12):4269. https://pmc.ncbi.nlm.nih.gov/articles/PMC8704773/

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