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

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Each year the coagulation community raises awareness as to the risks and prevention of thrombosis. This occurs on October 13, the birthday of Virchow, who is considered the father of thrombosis. In 1856, Rudolf Virchow postulated a triad of conditions that lead to thrombosis: endothelial injury, circulatory stasis, and abnormalities in blood clotting components (hypercoagulable state). He was the first to describe the occurrence of thrombosis as follows:

New masses of coagulum deposit themselves from the blood upon the end of the thrombus layer after layer. The thrombus is prolonged beyond the mouth of the branch into the trunk in the direction of the current of the blood, shoots out in the form of a thick cylinder farther and farther, and becomes continually larger and larger. It is these prolonged plugs that constitute the source of real danger; it is in them that ensues the crumbling away, which leads to secondary occlusions in remote vessels. Thus we see that as a rule all the thrombi from the periphery of the body produce secondary obstructions and metastatic deposits [emboli] in the lung.¹

What are the statistics? We know that ischemic heart disease and stroke are the top two causes of death globally responsible for more than 16 million deaths in 2021. Most are caused by arterial clots. VTE is the third most common acute cardiovascular condition and affects at least 10 million people globally. The greatest occurrence of VTE is hospital associated (60%), however of those 70% could be prevented with appropriate thromboprophylaxis. This is the leading cause of CV disability in low income and middle-income countries and second in high income countries. In recent years, age-standardized mortality rates from VTE have increased in five years due to factors of vascular inflammation and reduced medical care during COVID-19. This all points to the increased need for awareness and prevention not only to the public but across specialties.^2,3,4

The campaign this year is to dance to the rhythm of thrombosis prevention with "From Head to Toe, Take Control". Think of the song, "Head, shoulders, knees and toes" and know that thrombosis can strike anywhere in the body from top to bottom.

Thrombosis and Cancer:

One of the focuses of this year is awareness of the risk factors of thrombosis and cancer-associated thrombosis (CAT) and how to reduce that risk. It is important to have your risk assessed, be aware of symptoms, to stay active as much as possible and to use anticoagulants as recommended by your physicians.

Cancer will develop in one in of two people and VTE will further complicate this diagnosis in one in 20 people. It comes with a fourfold risk of VTE and in those patients their risk of mortality is threefold higher. Since there are now advanced treatment options, people with cancer are living longer and as a result have increased the number of patients at risk of CAT.⁵

The risk of VTE in hospitalized cancer patients varies in different diagnosis, with some presenting with a much higher risk than others. Hematological malignancies, lung, pancreas, stomach, bowel and brain cancers are associated with a high risk of clot formation. A low risk of thrombosis is seen in prostrate and breast cancers, however since these are two of the most prevalent cancers worldwide, VTE is commonly seen in these populations.⁶

VTE is the second leading cause of death in cancer patients, with the first being the progression of the disease. CAT has characteristics that distinguish it from other VTE, both in pathophysiology mechanisms, risk factors and especially in treatment, which need to be considered.⁶

A study was performed using the National Inpatient Sample (NIS) Database to identify patients admitted with active cancer from 2016 to 2018. Patients were stratified into those with solid malignancies and those with hematological malignancies. The cohorts were matched based on age, gender, race, use of antiplatelets, anticoagulants and actively being treated with chemotherapy, immunotherapy and radiation. A total of 1,233,832 cancer patients were identified and of those 5.1% (63,505) were diagnosed with acute VTE with a higher rate found in females (5.5%) versus males (4.8%). There were also racial disparities seen with black patients having the highest incidence (6.4%), followed by whites (5%), Native Americans and Hispanics (4.9%), and Asians (3.9%). Based on cancer type 78.6% (n=970,405) had solid malignancies and 21.4% (n=263,427) had hematological malignancies. Patients with solid malignancies exhibited a significantly higher incidence of VTE compared to those with hematological malignancies (5.4% vs. 4.1 however non-Hodgkins lymphoma contributed to the highest rate of VTE in hematological malignances (42%). Among solid tumors, gastrointestinal and lung malignancies were the most prevalent, contributing to 28.7% and 25.9% of VTE cases, respectively.⁷

Mechanism of CAT

In the cancer patient, the thrombotic generation process is distinct from the non-cancer population. Tissue factor (TF) is critical to CAT since it is abnormally produced by cancer cells and is the activator of the extrinsic pathway in coagulation. This results in the activation of factor X and the synthesis of fibrin and platelet activation. Cancer cells can also produce other substances such as procoagulant factors that stimulate FXA, inflammatory cytokines that mediate endothelial dysfunction and carcinoma mucins that interfere in the coagulation cascade. The fibrinolytic system is also inhibited by cancer cell synthesized plasminogen activator inhibitor-1. This imbalance leads to CAT.⁸

There are several conditions inherent in cancer patients that put them at a risk for thrombin generation. Treatment often requires multiple surgical procedures along with the placement of long-term catheters and chemotherapy. They may be immobile, reducing blood flow and several types of cancer are associated with increased blood viscosity and acquired thrombophilia. Genetic characteristics of tumors such as K-ras in colon and lung cancer were associated with an increased risk of VTE. This was also seen in myeloproliferative cancer and the JAK2 V617F mutation.⁶

DIAGNOSIS of VTE in Cancer population:

In cancer patients and elevated D-dimer is nonspecific and can be elevated without thrombosis. As a result, in this population the negative predictive value is decreased and can impact clinical prediction rules in these patients based on low, intermediate or high risks, the sensitivity of the assay and age adjusted cutoffs. High risk pretest probability patients computed tomography is performed and the D-dimer test is not warranted. In cancer patients who have a high prevalence of VTE, there is a very low threshold for diagnostic workups or compression ultrasound for DVT and proceeding with imaging is the usual course in patients with malignancy. The rate of DVT in extremities varies from less than 1% to as high as 7% and may be underestimated since systemic assessment of distal veins may not always be performed. The rate of PE is about 3.36% depending on the site of the primary malignancy.⁹

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Take the pledge to prevent thrombosis.
Protect your health

I pledge to take charge of my health and help protect others by taking simple, life-saving steps to prevent blood clots:

• I will learn to recognize the signs and symptoms of blood clots so I can act quickly and seek medical care when it matters most.
• I will understand my personal risk factors —like cancer, heart disease, diabetes, or other health conditions—and discuss them openly with my healthcare provider to make informed decisions about prevention.
• I will stay active and keep moving, especially during long periods of sitting, travel, or recovery—because even small steps help keep blood flowing.
• I will follow my doctor's advice carefully, taking prescribed medications exactly as directed and staying updated on the latest information about blood clot risks.
• I will share what I learn with my family, friends, and community—because raising awareness can save lives.

I'm signing the pledge to prevent thrombosis and protect my health.

https://www.worldthrombosisday.org/wtd-2024-calls-to-action/take-the-pledge-to-prevent-thrombosis-protect-your-health/

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CONCLUSION:

World Thrombosis Day plays an important role in making the public and specialties aware of the risks and outcomes of thrombosis. Educating these populations and having the public be knowledgeable about symptoms and prevention will help to minimize risks as well as enhance treatment efforts.

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REFERENCES:

1. Virchow RC. Cellular Pathology as based upon physiological and pathological history. [Tr. from the 2nd ed. of the original by Frank Chance.] Birmingham; Gryphod Editions, Ltd; 1978.
2. Raskob GE, Zondag MT, Kakkar AK, et al. Thrombosis: A Major Contributor to the Global Disease Burden. Research and Practice in Thrombosis and Haemostasis. 2024. https://vizhub.healthdata.org/gbd-results/
3. Wendelboe AM, Weitz JI. Global Health Burden of Venous Thromboembolism. Arteriosclerosis, Thrombosis, and Vascular Biology. 2024;44(5):1007-1011. https://doi.org/10.1161/ATVBAHA.124.320151
4. Cancer-associated venous thrombosis in adults (second edition)Date: Thursday, 25 April 2024 https://b-s-h.org.uk/guidelines/guidelines/cancer-associated-venous-thrombosis-in-adults-second-edition
5. Caio J. Fernandes Luciana T. K. Morinaga José L. Alves Jr, Cancer-associated thrombosis: the when, how and why, European Respiratory Review 2019 28(151
6. Ghada Araji, Chapman Wei, Varun Chowdhry, Kevin Wu, Zaid Khamis, Tyler Sarkis, Sajan Sah, Salman Khan, Ahmad Mustafa, Muhammad Raphay Niazi Cancer-Associated Venous Thromboembolism Among Solid and Hematological Malignancies: A Comprehensive National Study, Blood (2024) 144 (Supplement 1): 2641.
7. Blann AD, Lip GY. Venous thromboembolism. BMJ 2006; 332: 215–219.
8. Heloni M. Dave, MBBS and Alok A. Khorana, MD, FACP, FASCO
   Management of venous thromboembolism in patients with active cancer Cleveland Clinic Journal of Medicine February 2024, 91 (2) 109-117

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