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Research: Scientists May Study Thrombosis Without Use Of Animal Models

A novel apparatus that resembles a human vein might be useful for blood clot research and could replace the use of animals in some tests. Researchers at the University of Birmingham have created the vein-on-a-chip model, which may be applied in studies to better comprehend the mechanics underlying blood clot development.

The gadget is a tiny canal with 'valves' that ensure proper blood flow, as detailed in recent research published in Frontiers in Cardiovascular Medicine. The innovative device was developed by Drs. Daniele Vigolo and Alessio Alexiadis from the School of Chemical Engineering at the University of Birmingham in collaboration with Dr. Alexander Brill from the Institute of Cardiovascular Sciences. Since the valves may open and close, simulating the process seen in a genuine vein, the gadget is more sophisticated than earlier iterations, according to Dr. Brill. The interior of the vessel is lined with a single layer of cells known as endothelial cells. This vein-on-a-chip offers a practical substitute for employing animal models in studies that concentrate on how blood clots form as a result of these two developments. It replicates blood flow in a realistic manner and is biologically accurate to a real vein.

"Organ-on-a-chip devices, such as ours, are not only created to help researchers move away from the need for animal models, but they also advance our understanding of biology as they are more closely representative of how the human body works." Researchers at the University of Birmingham were able to demonstrate one of the basic mechanisms underlying venous clot formation using their newly developed model. Namely, the role of a bridge between a molecule called von Willebrand Factor and a surface receptor on platelets called glycoprotein Ib-alpha.

Deep vein thrombosis is the development of blood clots in veins, usually in the legs. It is a serious condition because the clot can detach and travel to the lungs, where it may block blood vessels, causing difficulty in breathing that may be fatal. Deep vein thrombosis is the third most common cardiovascular disease after myocardial infarction and stroke, with tens of thousands of people in the UK developing this condition every year. Mechanisms of deep vein thrombosis require further research to improve clinicians' understanding and ability to treat or prevent the condition. Dr Alexander Brill said, "The principles of the 3Rs - to replace, reduce and refine the use of animals in research - are embedded in national and international legislation and regulations on the use of animals in scientific procedures. But there is always more that can be done. Innovations such as the new device created for use in thrombosis research are a step in the right direction." (ANI)

(This story has not been edited by Devdiscourse staff and is auto-generated from a syndicated feed.)


What To Know About Deep Vein Thrombosis (DVT)

Deep vein thrombosis (DVT) is when blood clots form, typically in a deep vein in the leg or the pelvis. A pulmonary embolism (PE) can occur if part of a clot breaks off and travels to the lungs. DVT needs urgent medical attention as a PE can be life-threatening.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two parts of the disease known as venous thromboembolism.

DVT is a medical urgency. The Centers for Disease Control and Prevention (CDC) say that 10–30% of people who develop DVT in the leg experience fatal complications within a month of diagnosis.

In this article, we define DVT, explain how to recognize it, and ways to treat it.

DVT is blood clotting that develops with deep veins, often in the leg or pelvis.

If the thrombus, or clot, breaks off, doctors call this an embolus. Emboli can make their way to the lung, causing a PE.

Clots may also form in the veins of the arm, such as in people with Paget-Schoetter disease.

According to a 2017 review, DVT is the most common cause of maternal death in the developed world.

DVT is extremely rare in children. According to a 2016 article, the most recent figures suggest that 0.30 in every 100,000 children under 9 years of age, and 0.64 in every 100,000 children aged between 10 and 19 years develop DVT.

Some people may develop DVT without noticing symptoms. However, if symptoms develop, they may resemble the following:

  • pain in the affected limb that begins in the calf
  • swelling in the affected limb
  • a warm feeling in the swollen, painful region of the leg
  • red or discolored skin
  • In most people, DVT only develops in one leg. However, on rare occasions, both legs may have DVT.

    If a clot dislodges and travels to the lung, the following symptoms may indicate PE:

  • slow breathing or sudden breathlessness
  • chest pain, usually more severe while breathing deeply
  • rapid breaths
  • a faster heart rate
  • There are two possible complications:

    Pulmonary embolism

    PE is the most common complication of DVT and can be life threatening. It happens when a piece of a blood clot becomes dislodged and makes its way through the bloodstream into the lungs.

    The clot becomes stuck and disrupts the flow of blood in one of the blood vessels in the lung. In mild PE, an individual may not be aware.

    A medium sized clot may cause breathing problems and chest pain. In more severe cases, the lung might collapse. PE can lead to heart failure and can be fatal.

    Post-thrombotic syndrome

    This is more common among people with recurrent DVT. According to a 2016 review, a person with post-thrombotic syndrome might experience the following symptoms, although they vary between individuals:

  • a persistent swelling in the calf
  • a feeling of heaviness in the leg
  • a pulling sensation in the leg
  • an excessively tired leg
  • fluid buildup in the affected leg
  • redness of the skin
  • new varicose veins
  • thickening skin around the area of the DVT
  • leg ulcers for people with severe post-thrombotic syndrome
  • Some doctors call this condition post-phlebitic syndrome.

    An individual may develop DVT when there is no clear cause. However, according to the National Heart, Lung, and Blood Institute (NHLBI), most people with DVT develop the condition due to one or several risk factors and underlying conditions.

    Inactivity

    If the human body is inactive for long periods, blood can build up in the lower limbs and pelvic area.

    This situation is not a problem for most people. As soon as physical activity levels return to normal, blood flow speeds up. The vein and arteries redistribute blood around the body.

    However, prolong inactivity means that blood in the legs may slow a person's blood flow, increasing the risk of clots forming.

    A person might be inactive for long periods due to a range of causes, including:

  • an extended hospital stay
  • being immobile at home
  • remaining seated during a long journey, such as a flight
  • a disability that restricts movement
  • Injury or surgery

    An injury or surgery that damages veins can slow the flow of blood. This increases the risk of blood clots. General anesthetics can also widen the veins, making it more likely that blood pools and clots may form.

    While this risk may affect anyone having major surgery, the NHLBI suggest that people receiving knee and hip surgery, particularly, have a high risk of developing DVT.

    Genetics

    A person may have an inherited disorder that makes blood clots more likely, such as Factor V Leiden thrombophilia.

    However, even though having this condition increases the risk, only around 10% of people with it go on to develop unusual blood clots, according to Genetics Home Reference.

    Pregnancy

    As a fetus develops inside the uterus, pressure against a woman's veins in the legs and pelvis increases. A woman has an increased risk of DVT during pregnancy until six weeks after delivering their baby.

    Females with some inherited blood disorders, such as hereditary antithrombin disorder, have a higher risk of DVT during pregnancy compared with other women.

    Cancer

    Some cancers have links to a higher risk of DVT, including late stage colon, pancreatic, and breast cancers.

    Cancer therapies and procedures can also increase a person's risk of DVT, including chemotherapy, a central venous catheter, and certain cancer surgeries.

    Read more about cancer and its treatments here.

    Irritable bowel disease

    People with irritable bowel disease (IBD) have a higher risk of DVT. A 2018 study found that the risk may be three to four times higher than that of a person without IBD.

    Learn all about IBD here.

    Heart problems

    Any condition that affects how well the heart moves blood around the body can cause problems with clots and bleeds.

    Conditions such as heart attacks or congestive heart failure may increase a person's risk of developing a blood clot.

    Find out more about heart disease here.

    Hormone-based medications

    Females who take hormone-based birth control or are on a course of hormone replacement therapy (HRT) for menopause have a higher risk of DVT than those who do not take these medications.

    Discover everything you need to know about HRT here.

    Obesity

    People with obesity experience more pressure on their blood vessels, especially those in the pelvis and legs.

    For this reason, they may have an increased risk of DVT.

    Smoking

    People who smoke tobacco regularly are more likely to develop DVT than people who have never smoked or have stopped.

    People finding it difficult to quit smoking might find these tips helpful here.

    Varicose veins

    Varicose veins are enlarged and misshapen veins. While they often do not cause health problems, particularly overgrown varicose veins may lead to DVT unless a person receives treatment for them.

    Learn more about varicose veins here.

    Age

    Even though DVT may develop at any age, the risk increases as a person's age advances.

    According to the NHLBI, the risk of DVT doubles every 10 years after people reach 40 years of age.

    Sex

    A person's sex can affect their DVT risk.

    Females are more likely than males to experience DVT around childbearing age. However, females have a lower risk after menopause than men do at the same age.

    If a person suspects that they may have DVT, they should seek immediate medical attention. The doctor will ask questions about symptoms and medical history before carrying out a physical examination.

    A doctor will usually not be able to diagnose DVT through symptoms alone and may recommend tests, including:

  • D-dimer test: D-dimer is a protein fragment that is present in blood after a blood clot fibrinolysis degrades a blood clot. A test result revealing more than a certain amount of D-dimer indicates a possible blood clot. However, this test may not be reliable in individuals with certain inflammatory conditions and after surgery.
  • Ultrasound: This type of scan can detect clots in veins, alterations in blood flow, and whether the clot is acute or chronic.
  • Venogram: A doctor may request this scan if the ultrasound and D-dimer tests do not provide enough information. The doctor injects a dye into a vein in the foot, knee, or groin. X-ray images can track the dye as it moves to reveal the location of a blood clot.
  • Other imaging scans: MRI and CT scans may highlight the presence of a clot. These scans may identify blood clots while testing for other health conditions.
  • DVT treatment aims to:

  • stop the growth of a clot
  • prevent a clot from becoming an embolism and moving into the lung
  • reduce the risk that DVT might come back after treatment
  • minimize the risk of other complications
  • A doctor may recommend several methods to manage DVT, as follows:

    Anticoagulant medications

    These are drugs that prevent the clot from growing, as well as reducing the risk of embolism. Two types of anticoagulants support the treatment of DVT: Heparin and warfarin.

    Heparin has an immediate effect. For this reason, doctors usually administer it first through a brief course of injections lasting less than a week.

    With warfarin, the doctor is likely to recommend a 3–6-month course of oral tablets to prevent recurrence of DVT.

    People with recurrent DVT may need to take anticoagulant medication for the rest of their lives.

    Thrombolysis

    People with more severe DVT or PE require immediate medical attention. The doctor or emergency team administers drugs called thrombolytics, or clot busters, that break down clots.

    Tissue plasminogen activator (TPA) is an example of a thrombolytic drug.

    Excessive bleeding is a side effect of these drugs. As a result, medical teams only administer TPA or similar interventions in emergency situations.

    Healthcare professionals administer TPA through a small catheter, or tube, directly into the site of the clot. Patients undergoing catheter-directed thrombolysis will be in the hospital for several days and have intermittent "lysis checks" to make sure the clot is breaking down appropriately.

    Inferior vena cava filter

    A surgeon inserts a very small device, resembling an umbrella, into the vena cava, which is a large vein. The device catches blood clots and stops them moving into the lungs while allowing blood flow to continue.

    Compression stocking

    People wear these to help reduce pain, limit swelling, and prevent ulcers from developing. Stockings can also protect the individual from post-thrombotic syndrome.

    Someone with DVT will have to wear stockings at all times for at least 24 months.

    This is a relatively new technique that surgeons may use to treat a blood clot that occurs with DVT or PE.

    The procedure involves using a catheter and a clot-removing device, which may be an aspiration catheter, a retrieval stent, or a pump.

    Using imaging techniques for guidance, the surgeon:

  • inserts the catheter toward the area where the clot is
  • directs the clot-removing device through the catheter
  • removes the clot, using aspiration or a stent, and reestablishes blood flow
  • The authors of a 2019 review conclude that mechanical thrombectomy is safe and effective at treating DVT and reducing the risk of recurrence.

    There is no available method for screening people for DVT. However, doctors recommend three ways for people with one or several risk factors, such as recent surgery, to prevent the first occurrence of DVT.

    These are:

  • Regular movement: A doctor might recommend staying highly mobile after surgery to stimulate blood flow and reduce the risk of a clot.
  • Maintaining pressure on the at-risk area: This can prevent blood pooling and clotting. Medical professionals may recommend wearing compression stockings or a boot that fills with air to increase pressure.
  • Anticoagulant medication: A doctor may prescribe blood-thinning medication to reduce the risk of clotting before or after surgery.
  • As smoking and obesity are also key risk factors, it may be advisable to quit smoking and engage in regular physical activity.

    According to the American Heart Association (AHA), 150 minutes of moderate-to-high intensity exercise every week is the amount they recommend.


    'Vein-on-a-chip' Could Help Scientists Study Thrombosis Without Animal Models

    Blood clot researchers could benefit from a new device that mimics a human vein, replacing the need for animals for some studies.

    The vein-on-a-chip model has been developed by scientists at the University of Birmingham and can be used in experiments to understand mechanisms of blood clot formation.

    The device, described in a recent paper published in Frontiers in Cardiovascular Medicine, is a tiny channel, which includes structures called 'valves' that ensure the correct direction of blood flow.

    Dr. Alexander Brill from the Institute of Cardiovascular Sciences together with Drs Daniele Vigolo and Alessio Alexiadis from the School of Chemical Engineering at the University of Birmingham, led the development of the new device. Dr. Brill said,

    "The device is more advanced than previous models because the valves can open and close, mimicking the mechanism seen in a real vein. It also contains a single layer of cells, called endothelial cells, covering the inside of the vessel. These two advances make this vein-on-a-chip a realistic alternative to using animal models in research that focuses on how blood clots form. It is biologically reflective of a real vein, and it also recapitulates blood flow in a life-like manner.

    "Organ-on-a-chip devices, such as ours, are not only created to help researchers move away from the need for animal models, but they also advance our understanding of biology as they are more closely representative of how the human body works."

    Researchers at the University of Birmingham were able to demonstrate one of the basic mechanisms underlying venous clot formation using their newly developed model. Namely, the role of a bridge between a molecule called von Willebrand Factor and a surface receptor on platelets called glycoprotein Ib-alpha.

    Deep vein thrombosis is the development of blood clots in veins, usually in the legs. It is a serious condition because the clot can detach and travel to the lungs, where it may block blood vessels, causing difficulty in breathing that may be fatal. Deep vein thrombosis is a third most common cardiovascular disease after myocardial infarction and stroke, with tens of thousands of people in the UK developing this condition every year. Mechanisms of deep vein thrombosis require further research to improve clinicians' understanding and ability to treat or prevent the condition.

    Dr. Alexander Brill said, "The principles of the 3Rs—to replace, reduce and refine the use of animals in research—are embedded in national and international legislation and regulations on the use of animals in scientific procedures. But there is always more that can be done. Innovations such as the new device created for use in thrombosis research are a step in the right direction."

    More information: Hosam Alden Baksamawi et al, Platelet accumulation in an endothelium-coated elastic vein valve model of deep vein thrombosis is mediated by GPIbα—VWF interaction, Frontiers in Cardiovascular Medicine (2023). DOI: 10.3389/fcvm.2023.1167884

    Citation: 'Vein-on-a-chip' could help scientists study thrombosis without animal models (2023, April 27) retrieved 27 April 2023 from https://medicalxpress.Com/news/2023-04-vein-on-a-chip-scientists-thrombosis-animal.Html

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