Blood clot in the context of Frostbite

Coumarin (/ˈkuːmərɪn/) or 2H-chromen-2-one is an aromatic organic chemical compound with formula C₉H₆O₂. Its molecule can be described as a benzene molecule with two adjacent hydrogen atoms replaced by an unsaturated lactone ring −(CH)=(CH)−(C=O)−O−, forming a second six-membered heterocycle that shares two carbons with the benzene ring. It belongs to the benzopyrone chemical class and is considered a lactone.

Coumarin is a colorless crystalline solid with a sweet odor resembling the scent of vanilla and a bitter taste. It is found in many plants, where it may serve as a chemical defense against predators. While coumarin is not an anticoagulant, its 3-alkyl-4-hydroxy derivatives, such as the fungal metabolite dicoumarol, inhibit synthesis of vitamin K, a key component in blood clotting. A related compound, the prescription drug anticoagulant warfarin, is used to inhibit formation of blood clots, deep vein thrombosis, and pulmonary embolism.

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

Side effects of progestogens include menstrual irregularities, headaches, nausea, breast tenderness, mood changes, acne, increased hair growth, and changes in liver protein production among others. Other side effects of progestogens may include an increased risk of breast cancer, cardiovascular disease, and blood clots. At high doses, progestogens can cause low sex hormone levels and associated side effects like sexual dysfunction and an increased risk of bone fractures.

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

Side effects of estrogens include breast tenderness, breast enlargement, headache, nausea, and edema among others. Other side effects of estrogens include an increased risk of blood clots, cardiovascular disease, and, when combined with most progestogens, breast cancer. In men, estrogens can cause breast development, feminization, infertility, low testosterone levels, and sexual dysfunction among others.

Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol is widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

The general side effects of ethinylestradiol include breast tenderness and enlargement, headache, fluid retention, and nausea among others. In males, ethinylestradiol can additionally cause breast development, feminization in general, hypogonadism, and sexual dysfunction. Rare but serious side effects include blood clots, liver damage, and cancer of the uterus.

Thrombosis (from Ancient Greek θρόμβωσις (thrómbōsis) 'clotting') is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus. Thrombosis can cause serious conditions such as stroke and heart attack.

Thrombosis may occur in veins (venous thrombosis) or in arteries (arterial thrombosis). Venous thrombosis (sometimes called DVT, deep vein thrombosis) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery (ischemia and necrosis). A piece of either an arterial or a venous thrombus can break off as an embolus, which could then travel through the circulation and lodge somewhere else as an embolism. This type of embolism is known as a thromboembolism. Complications can arise when a venous thromboembolism (commonly called a VTE) lodges in the lung as a pulmonary embolism. An arterial embolus may travel further down the affected blood vessel, where it can lodge as an embolism.

Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing in, and coughing up blood. Symptoms of a blood clot in the leg may also be present, such as a red, warm, swollen, and painful leg. Signs of a PE include low blood oxygen levels, rapid breathing, rapid heart rate, and sometimes a mild fever. Severe cases can lead to passing out, abnormally low blood pressure, obstructive shock, and sudden death.

PE usually results from a blood clot in the leg that travels to the lung. The risk of blood clots is increased by advanced age, cancer, prolonged bed rest and immobilization, smoking, stroke, long-haul travel over 4 hours, certain genetic conditions, estrogen-based medication, pregnancy, obesity, trauma or bone fracture, and after some types of surgery. A small proportion of cases are due to the embolization of air, fat, or amniotic fluid. Diagnosis is based on signs and symptoms in combination with test results. If the risk is low, a blood test known as a D-dimer may rule out the condition. Otherwise, a CT pulmonary angiography, lung ventilation/perfusion scan, or ultrasound of the legs may confirm the diagnosis. Together, deep vein thrombosis and PE are known as venous thromboembolism (VTE).

Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts of the body. As clotting factors and platelets are used up, bleeding may occur. This may include blood in the urine, blood in the stool, or bleeding into the skin. Complications may include organ failure.

Relatively common causes include sepsis, surgery, major trauma, cancer, and complications of pregnancy. Less common causes include snake bites, frostbite, and burns. There are two main types: acute (rapid onset) and chronic (slow onset). Diagnosis is typically based on blood tests. Findings may include low platelets, low fibrinogen, high INR, or high D-dimer.

Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of birth control and as a part of menopausal hormone therapy. It is also used to treat endometriosis, abnormal uterine bleeding, paraphilia, and certain types of cancer. The medication is available both alone and in combination with an estrogen. It is taken by mouth, used under the tongue, or by injection into a muscle or fat.

Common side effects include menstrual disturbances such as absence of periods, abdominal pain, and headaches. More serious side effects include bone loss, blood clots, allergic reactions, and liver problems. Use is not recommended during pregnancy as it may harm the baby. MPA is an artificial progestogen, and as such activates the progesterone receptor, the biological target of progesterone. It also has androgenic activity and weak glucocorticoid activity. Due to its progestogenic activity, MPA decreases the body's release of gonadotropins and can suppress sex hormone levels. It works as a form of birth control by preventing ovulation.

Macrovascular disease (also known as macroangiopathy) is a disease of any large (macro) blood vessels in the body. It is a disease of the large blood vessels, including the coronary arteries, the aorta, and the sizable arteries in the brain and in the limbs.

This sometimes occurs when a person has had diabetes for an extended period of time. Fat and blood clots build up in the large blood vessels and stick to the vessel walls.

Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enlarged veins in the affected area, but some DVTs have no symptoms.

The most common life-threatening concern with DVT is the potential for a clot to embolize (detach from the veins), travel as an embolus through the right side of the heart, and become lodged in a pulmonary artery that supplies blood to the lungs. This is called a pulmonary embolism (PE). DVT and PE comprise the cardiovascular disease of venous thromboembolism (VTE).

Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate. CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.

Side effects of CEEs include breast tenderness and enlargement, headache, fluid retention, and nausea among others. It may increase the risk of endometrial hyperplasia and endometrial cancer in women with an intact uterus if it is not taken together with a progestogen like progesterone. The medication may also increase the risk of blood clots, cardiovascular disease, and, when combined with most progestogens, breast cancer. CEEs are estrogens, or agonists of the estrogen receptor, the biological target of estrogens like estradiol. Compared to estradiol, certain estrogens in CEEs are more resistant to metabolism, and the medication shows relatively increased effects in certain parts of the body like the liver. This results in an increased risk of blood clots and cardiovascular problems with CEEs relative to estradiol.

Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication. Its use now rare, in the past, it was widely used for a variety of indications, including pregnancy support for those with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency, treatment of prostate cancer and breast cancer, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported adverse reproductive health outcomes linked to DES, including infertility, miscarriage, ectopic pregnancy, preeclampsia, preterm birth, stillbirth, infant death, menopause prior to age 45, breast cancer, cervical cancer, and vaginal cancer. While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.

DES is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol. It is a synthetic and nonsteroidal estrogen of the stilbestrol group, and differs from the natural estrogen estradiol. Compared to estradiol, DES has greatly improved bioavailability when taken by mouth, is more resistant to metabolism, and shows relatively increased effects in certain parts of the body like the liver and uterus. These differences result in DES having an increased risk of blood clots, cardiovascular issues, and certain other adverse effects.