Blood clots and cancer

The Link Between Lung Cancer and Blood Clots

Another 2012 study, published in the Journal of Thrombosis and Thrombolysis, reviewed rates of VTE in 7,052 lung cancer patients, including 2,242 who were receiving chemotherapy. The study found that although both groups had a higher-than-average risk of embolism, the people receiving chemotherapy had a 30 percent higher risk than those not receiving chemotherapy. Most cases of VTE occurred within six months of starting chemotherapy.

“Many cancers increase the risk of blood clots,” says Harry Raftopoulos, MD, associate professor of medical oncology at Hofstra North Shore-LIJ School of Medicine in Manhasset, New York. “These include lung cancers, as well as cancers of the pancreas and stomach. Lung cancers called mucinous adenocarcinomas may have the highest risk. Many factors associated with cancer, such as surgery, chemotherapy, and inactivity, can contribute to blood clot risk.”

Why Blood Clots Are More Common With Cancer

“Blood clots are common in all cancers,” says Jacques-Pierre Fontaine, MD, a chest surgeon at Moffitt Cancer Center in Tampa, Florida. “Having lung cancer surgery increases the risk, and we routinely protect patients by giving them blood thinners after surgery.”

Having cancer increases blood clotting in ways we don’t completely understand — but “anything that increases blood clotting increases the risk for DVT and embolism,” says Dr. Raftopoulos.

Here are some ways that cancer and cancer treatment can raise blood clot risk,:

  • Cancer cells may release chemicals that stimulate the body to produce more clots.
  • Chemotherapy may damage blood vessels or reduce the production of proteins that protect against clotting.
  • Some cancers produce substances called mucin, which increases blood clotting risk. Cancers that produce mucin include lung, pancreas, bowel, stomach, and ovary.
  • Pain and fatigue from cancer may lead to less activity. Lack of movement allows for more blood clotting.

Preventing and Managing Blood Clots

The most important thing you can do to protect yourself from blood clots and embolism is to know the symptoms. Blood clot symptoms include pain, redness, swelling, warmth, and tenderness near the clot. Embolism symptoms include shortness of breath, chest pain, and coughing up blood.

If your doctor suspects a DVT, an ultrasound (a type of imaging test of the blood vessel that uses sound waves) may be done. “If a lung cancer patient continues to be short of breath with a normal chest X-ray, a chest CT scan with dye injection should be done, which is the best way to show a pulmonary embolism. People with lung cancer may have shortness of breath already, so you need to be aware of this danger,” Dr. Fontaine says.

Treatment of DVT involves giving blood thinning medications by injection under the skin or directly into the blood. You might also be given oral blood thinners. “It may be necessary to continue blood thinners for six months or longer,” Fontaine adds.

“There is not enough evidence to support giving people with cancer blood thinners to prevent blood clots, except when they are in the hospital, or to prevent blood clots in a person who had already had one,” Raftopoulos says.

Awareness is key to protecting your health. “The best way to prevent blood clots is to get some daily physical activity, like walking. The best way to prevent PE is to be aware of the symptoms of DVT and let your doctor know right away if you’re experiencing these symptoms so you can get started on treatment,” says Fontaine.

A blood clot is a serious condition that needs treatment right away. People with cancer and those receiving cancer treatment have an increased risk for blood clots.

Normal blood clotting, called coagulation, is a complex process. It involves specialized blood cells, called platelets, and different proteins in the blood, called clotting or coagulation factors. These platelets and coagulation factors clump together to heal broken blood vessels and control bleeding. Coagulation factors that promote bleeding and those that promote clotting must be balanced.

Blood clotting disorders occur when some clotting factors are missing or damaged. This causes clots to form inside the body that block normal blood flow and cause serious problems.

Blood clots can occur in and travel to different parts of the body, including:

  • Veins, called a venous thromboembolism (VTE). If the vein is in the leg, thigh, or pelvis, it is called deep venous thrombosis (DVT).

  • The lungs, called a pulmonary embolism (PE).

  • An artery. This is less common but also very serious.

Signs and symptoms of clotting problems

People with clotting problems may experience:

  • Arm or leg swelling on 1 side of the body

  • Pain in the arm or leg where a blood clot is located

  • Trouble breathing or chest pain when breathing

  • Rapid heart beat

  • Low oxygen levels

Relieving side effects is an important part of cancer care and treatment. This is called palliative care or supportive care. Tell your health care team about any of these symptoms immediately. Even people with low levels of platelets can develop a blood clot. Sometimes people do not know they have a blood clot until it is diagnosed during a test.

Causes of clotting problems

People with cancer have a higher risk of blood clots and clotting disorders. This may be caused by the cancer or its treatment. Such risk factors include:

  • Cancers of the lung, kidney, brain, digestive system, female reproductive system such as uterine cancer, and blood such as leukemia and lymphoma

  • Metastatic cancer, which is cancer that has spread to other parts of the body from where it started

  • Cancer treatment, including surgery lasting longer than 1 hour, chemotherapy, radiation therapy, and hormone therapy. Drugs called anti-angiogenic drugs that block the formation of new blood vessels such as thalidomide (Synovir, Thalomid) and lenalidomide (Revlimid) may also raise the risk of blood clots.

  • Treatment with drugs called erythropoiesis stimulating agents that help the body make more red blood cells, such as epoetin (Epogen, Eprex, Procrit) and darbepoetin (Aranesp)

  • Long-term use of an intravenous catheter or port

Blood clots can also be caused by reasons other than cancer and its treatment, such as:

  • Long periods of inactivity, such as a long plane or car ride. This may also include being in the hospital, because most people in the hospital cannot be physically active and need to stay in bed or are unable to get out of bed.

  • Having other diseases or conditions in addition to cancer, such as obesity, infection, kidney disease, lung disease, or a blood clot in a blood vessel called an artery that carries blood away from the heart.

  • Older age.

  • Race/ethnicity. The risk is higher for black people and lower for white and Asian people.

  • A condition that is inherited, meaning it is passed down from parent to child in a family. This includes a factor V Leiden mutation, which is a condition that causes too much blood clotting.

Diagnosing clotting problems

Your doctor may use one or more ways to find a blood clot, including:

  • A Doppler ultrasound. An ultrasound uses sound waves to look at the flow of blood in veins in the arms or legs. It can detect decreased blood flow from a blood clot.

  • A computed tomography (CT) scan. A CT scan takes pictures of the inside of the body using x-rays taken from different angles. A special dye called a contrast medium is injected into a patient’s vein or given as a pill or liquid to swallow before the scan to provide better detail on the image. Doctors commonly use CT scans to diagnose a blood clot in the lungs or a PE.

  • A lung ventilation/perfusion (VQ). This test that can diagnose a PE is made up of 2 different parts:

    • A ventilation scan of the airflow in the lungs

    • A perfusion scan of the blood flow in the lungs

  • An angiogram. This test can detect a blood clot in an artery. During an angiogram, a dye is injected into the artery. And then the artery is examined with a special x-ray device called a fluoroscope.

Preventing and treating clotting problems

Blood clots can be prevented and treated with drugs. Anticoagulants are drugs that stop clots from happening or stop existing clots from getting worse. These drugs may increase a person’s risk of bleeding, but they are safe for most people. Typical anticoagulants include:

Some of these drugs are taken by mouth. Others are given as an injection under the skin, called a subcutaneous injection.

The American Society of Clinical Oncology (ASCO) recommends the following to help prevent blood clots in people with cancer:

  • Some people staying in the hospital may need to take medicine to prevent blood clots. This type of medicine is called an anticoagulant. Whether someone needs to take an anticoagulant may depend on how long their hospital stay is and whether they are at a high risk of blood clots.

  • People with multiple myeloma who are taking an anti-angiogenic along with chemotherapy and/or dexamethasone (multiple brand names) should take heparin or low doses of aspirin.

  • People who will be having a major cancer surgery should receive treatment to prevent blood clots after surgery. Treatment should continue for at least 7 to 10 days or up to 4 weeks, depending on the type of surgery and your risk of blood clots.

  • People who have a high risk of blood clots but are not staying in the hospital may receive apixaban, rivaroxaban, or some form of heparin

Your doctor may also recommend the following methods in addition to taking medicine to prevent blood clots:

  • Graduated compression stockings, which are a type of support hose

  • Intermittent pneumatic compression, which squeezes the legs through a sleeve connected to a machine

  • Mechanical foot pumps

Learn more about these recommendations on a separate ASCO website.

A person with a blood clot needs treatment right away. The most common treatment is an anticoagulant that can be injected under the skin or into a vein. But some people may take a pill that is swallowed. Once the blood is considered thin enough, there is a lower risk of clotting.

People who are receiving blood thinners must be regularly monitored for any increased bleeding. Some people are unable to receive blood thinners because they have low platelet levels or a high risk of bleeding. For these people, a special type of filter can be placed in the body to prevent a blood clot from traveling to the lungs, a condition that can be very dangerous.

Questions to ask the health care team

Talk with your health care team to learn more about your risk of developing a blood clot, how blood clot prevention will be included in your overall treatment plan, and what treatments are available if you develop a blood clot.

Consider asking the following questions:

  • Do I have a higher risk of a blood clot?

  • What can be done to prevent a blood clot before it starts?

  • What are the signs and symptoms of a blood clot?

  • If I have a blood clot or have had them before, what treatment do you recommend?

  • How long will I need this treatment?

  • What is my risk of bleeding with such treatment? Are there other side effects?

  • What health conditions or medications may interfere with the treatment for blood clots?

  • Who should I call if I have concerns about a symptom?

Related Resources

When to Call the Doctor During Cancer Treatment

Traveling with Cancer

A lung cancer patient with deep vein thrombosis:a case report and literature review

DVT is a well-studied cancer complication and the incidence is estimated to be from 4 to 17% in patients presenting underlying malignancies . Cancer patients are predisposed to the development of VTE events with an up to 7% risk, partly due to their considerable exposure to various circumstantial risk factors including surgery, immobilization and medications during the course of their disease. Additionally, cancer is often associated with a prothrombotic state, which might be clinically asymptomatic or lead to VTE that is resistant to anticoagulants . When compared to cancer patients without thrombosis, patients with both thrombotic events and cancer have a lower survival rate. Furthermore, patients with malignancies and concomitant VTE have an increased complication rate from anticoagulation therapy and increased risk of a second VTE episode .

It’s recommended that the risk of VTE should be assessed before the commencement of chemotherapy . Efforts have been made to recognize the predictors of the VTE episode in lung cancer patients and several risk models were established to assign patients to risk classes. Khorana risk score (KRS) is a validated prediction score for cancer-associated thrombosis. The biomarkers concerned in KRS include the site of cancer, platelet counts, leukocyte counts, haemoglobin and body mass index (BMI) (Table 2). Nonetheless, in a review of 719 patients, a high KRS was not associated with VTE compared to an intermediate score in both univariate and multivariable analyses. A high KRS, however, was a mortality predictor . The patient in this case had a KRS of 1, placing him in an intermediate-risk group. Protecht score is an improved risk assessment method where platinum or gemcitabine-based chemotherapy was added to the predictive variables that are already taken into account in the Khorana score. Compared to the Khorana score, Protecht score demonstrated a bettered ability to identify cancer patients who are at high risk for VTE . Based on the original Knorana score, Vienna prediction score added P-selectin and D-dimer, two markers of platelet aggregation and clotting cascade respectively, which considerably improved prediction of VTE (Table 3).

Table 2 Coagulation lab results of the patient Table 3 Khorana risk score

Apart from the biomarkers mentioned in the above risk-evaluation models, it is found that some other individual biomarkers are also correlated with the development of VTE in lung cancer patients. For example, besides surgical interventions and hospitalization, chemotherapy with cisplatin , immunomodulatory drugs (thalidomide analogues) or angiogenic inhibitors increases risk for thrombosis . Advanced stage is confirmed to be a strong predictor of VTE in patients with non-small cell lung carcinoma (NSCLC). It is observed in several studies that there is a direct association between the cancer stage and thrombosis risk, patients with stage III or IV NSCLC being more predisposed to VTE . The tumor grade may help identify patients with cancer who are at high risk of VTE . Yang W et al. demonstrated that platelet-lymphocyte ratio (PLR) at the time of cancer diagnosis could be a useful clinically important, independent risk predictor for VTE in cancer patients, where PLR > 260 could predict a VTE episode .

Guidelines regarding the use of prophylactic anticoagulants in lung cancer patients receiving chemotherapy varies. The American College of Chest Physicians (ACCP) does not recommend the use of thromboprophylaxis ; The European Society for Medical Oncology (ESMO) recommends that in cases of VTE high-risk patients with solid tumors are considered case by case and that the decision be discussed with patients ; the American Society of Clinical Oncology (ASCO) guidelines recommend all hospitalized cancer patients should be considered for VTE prophylaxis with anticoagulants in the absence of bleeding or other contraindications ; the International Society on Thrombosis and Haemostasis (ISTH) recommends the use of thromboprophylaxis in patients with advanced/metastatic cancer of pancreas or lung at low risk of bleeding . There is still a long way to go between guidelines and clinical practice and consensus is needed.

Some factors might reduce the effect of treatment. The lung cancer in this patient was in the late phase, spreading throughout both lungs. Failure to notice the thrombotic event early caused delayed treatment. Additionally, the patient also had many risk factors predisposing VTE, like smoking, bed rest and high coagulability caused by the malignancy. All these factors might explain why treatment did not work. Differential diagnosis includes heparin-induced thrombocytopenia (HIT), Antiphospholipid Syndrome and warfarin necrosis. For HIT to be diagnosed, patients with proven thrombosis must present with a significant fall in platelet 5–10 days after the commencement of heparin treatment . In this case, however, the patient didn’t show a significant fall in platelet, making the diagnosis of HIT less likely. The diagnosis of Antiphospholipid Syndrome, an autoimmune disease, requires the detection of autoantibodies. Although lab tests concerning this disease were not ordered by corresponding physicians, a lack of any history of thrombotic events or autoimmune defects makes Antiphospholipid Syndrome a less likely etiology. The risk of warfarin necrosis is normally reduced by concomitantly administrated heparin, because heparin takes a different mechanism than warfarin.

The anticoagulant therapy was not initiated until the patient developed distending pain of the left lower limb, with venous duplex ultrasonography confirming DVT. Aspirin, warfarin and LMWH were used as the initial treatment in this case. ACCP recommends the use of heparin and vitamin K antagonist to treat patients who are highly suspected of acute DVT while waiting for the results of diagnostic tests. Aspirin was used empirically as an anti-platelet agent. Despite the use of anticoagulants, the outcome was very poor, eventually leading to the last choice of amputation when gangrene developed. Although there are diverse results in the statistical significance in the use of prophylactic anticoagulants , the low complication rates observed with prophylaxis in the major medical trials appear to justify the use of pharmacologic prophylaxis in hospitalized patients with cancer. A better outcome might be had if the anticoagulant therapy were started from the beginning of chemotherapy instead of the moment when DVT symptoms developed.

In conclusion, cancer patients, especially those whose cancer originates in the lung, are predisposed to the development of DVT. Khorana score, Protecht score and Vienna score could be considered in the evaluation of the risk of the VTE episode. Advanced stage, surgery, immobility, chemotherapy and PLR are important predictors for these patients. A prophylactic use of anticoagulants is recommended for patients with advanced lung cancer.

News

This is an excerpt of a story that appeared in Everyday Health. Read the full article here.

Maria De Sancho, M.D.

A cancer diagnosis comes with an array of new health risks to consider, and one of them is deep vein thrombosis (DVT), a potentially life-threatening blood clot that blocks blood flow in the veins, typically in the legs. One in five cancer patients will develop DVT, according to the National Blood Clot Alliance. And research suggests that a number of varieties of cancer — including lung — make patients particularly vulnerable.

A review published in September 2015 in Multidisciplinary Respiratory Medicine found that, among people with lung cancer, those most at risk were people with adenocarcinoma, or non-small-cell lung cancer (compared with small-cell lung cancer), those with advanced disease, and those who had undergone lung cancer surgery or received chemotherapy.

Why the increased risk? No one yet knows for sure. Some possible explanations include:

Tumors can compress blood vessels. Tumors take up space and crowd what’s around them, including blood vessels. If a tumor presses hard enough on a blood vessel, it can slow blood flow and cause blood to stagnate, increasing clotting risk, says, the chief of the benign hematology service at Weill Cornell Medicine in New York City.

Tumors change blood and blood cells. “Blood becomes thicker, cancer cells release substances that can damage the walls of blood vessels, and cells release pro-coagulant substances,” says Dr. De Sancho. Among these chemicals are a protein called mucin, which binds to blood vessel walls and forms the basis of clots.

Chemotherapy changes blood vessels. As chemotherapy kills cancer cells, it may also damage the lining of blood vessels and interfere with the release of chemicals that prevent blood clots. One study, published in the November 2012 issue of the Journal of Thrombosis and Thrombolysis, reviewed rates of DVT in 7,052 lung cancer patients and found that those receiving chemotherapy had a 30 percent higher risk of DVT than those not receiving it.

Inactivity. Pain and fatigue from cancer may lead to less activity. People with lung cancer may find themselves short of breath or bedridden as they recover from surgery. Lack of movement is a known risk factor for blood clots.

Blood Clot Lung

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Patient Education – Lung Cancer Program at UCLA

Educating yourself about lung cancer:

Signs and symptoms: Blood clot – lung

Pulmonary embolus

Definition

A pulmonary embolus is a blockage of an artery in the lungs by fat, air, blood clot, or tumor cells.

Alternative Names

Venous thrombo-embolism; Lung blood clot; Blood clot – lung; Embolus; Tumor embolus

Causes

Pulmonary emboli are most often caused by blood clots in the veins, especially veins in the legs or in the pelvis (hips). More rarely, air bubbles, fat droplets, amniotic fluid, or clumps of parasites or tumor cells may obstruct the pulmonary vessels.

The most common cause of a pulmonary embolism is a blood clot in the veins of the legs, called a deep vein thrombosis (DVT). Many clear up on their own, though some may cause severe illness or even death.

Risk factors for a pulmonary embolus include:

  • Prolonged bed rest or inactivity (including long trips in planes, cars, or trains)
  • Oral contraceptive use
  • Surgery (especially pelvic surgery)
  • Childbirth
  • Massive trauma
  • Burns
  • Cancer
  • Stroke
  • Heart attack
  • Heart surgery
  • Fractures of the hips or femur

Persons with certain clotting disorders may also have a higher risk.

Symptoms

Symptoms of pulmonary embolism may be vague, or they may resemble symptoms associated with other diseases. Symptoms can include:

  • Cough
    • Begins suddenly
    • May produce bloody sputum (significant amounts of visible blood or lightly blood streaked sputum)
  • Sudden onset of shortness of breath at rest or with exertion
  • Splinting of ribs with breathing (bending over or holding the chest)
  • Chest pain
    • Under the breastbone or on one side
    • Especially sharp or stabbing; also may be burning, aching or dull, heavy sensation
    • May be worsened by breathing deeply, coughing, eating, bending, or stooping
  • Rapid breathing
  • Rapid heart rate (tachycardia)

Additional symptoms that may be associated with this disease:

  • Wheezing
  • Clammy skin
  • Bluish skin discoloration
  • Nasal flaring
  • Pelvis pain
  • Leg pain in one or both legs
  • Swelling in the legs (lower extremities)
  • Lump associated with a vein near the surface of the body (superficial vein), may be painful
  • Low blood pressure
  • Weak or absent pulse
  • Lightheadedness or fainting
  • Dizziness
  • Sweating
  • Anxiety

Exams and Tests

Tests to evaluate the function of the lungs:

  • Arterial blood gases
  • Pulse oximetry

Tests to detect the location and extent of embolism:

  • Chest x-ray
  • Pulmonary ventilation/perfusion scan
  • Pulmonary angiogram
  • CT angiogram of the chest

Tests to detect DVT:

  • Doppler ultrasound exam of an extremity blood flow studies
  • Venography of the legs
  • Plethysmography of the legs

An ECG may show abnormalities caused by strain on the heart.

This disease may also alter the results of the following tests:

  • Echocardiogram
  • D-dimer level
  • Chest CT scan
  • Chest MRI scan

Treatment

Emergency treatment and hospitalization may be necessary. In cases of severe, life-threatening pulmonary embolism, definitive treatment may consist of dissolving the clot with thrombolytic therapy. Anticoagulant therapy prevents the formation of more clots and allows the body to re-absorb the existing clots faster.

Clot-dissolving medication (thrombolytic therapy) includes streptokinase, urokinase, or t-PA. Clot-preventing medication (anticoagulation therapy) consists of heparin by intravenous infusion initially, then oral warfarin (Coumadin). Subcutaneous low-molecular weight heparin is substituted for intravenous heparin in many circumstances. Patients who have reactions to heparin or related medications may need other medications.

Patients who cannot tolerate anticoagulation therapy may need an inferior vena cava filter (IVC filter). This device, placed in the main central vein in the abdomen, is designed to block large clots from traveling into the pulmonary vessels. Oxygen therapy may be required to maintain normal oxygen concentrations.

Surgery is sometimes needed in patients at great risk for recurrent embolism.

Outlook (Prognosis)

It is difficult to predict how the patient will do in the future. Often, the outlook is related to the disease that puts the person at risk for pulmonary embolism (for example, cancer, major surgery, trauma). In cases of severe pulmonary embolism, where shock and heart failure occur, the death rate may be greater than 50%.

Possible Complications

  • Heart palpitations
  • Heart failure or shock
  • Severe breathing difficulty
  • Sudden death
  • Hemorrhage (usually a complication of thrombolytic or anticoagulation therapy)
  • Pulmonary hypertension with recurrent pulmonary embolism

When to Contact a Medical Professional

Go to the emergency room or call the local emergency number (such as 911) if you have symptoms of pulmonary embolus.

Prevention

Prevention of deep venous thrombosis (DVT) among at-risk patients is very important. Walking and staying active as soon as possible after surgery or during a prolonged medical illness can reduce the risk for pulmonary embolus. Heparin therapy (low doses of heparin injected under the skin) may be used for those on prolonged bedrest. Other preventive measures include compression stockings (plastic sleeves that fit around the legs and help circulate the blood).

Perrier A, Roy PM, Aujesky D, et al. Diagnosing pulmonary embolism in outpatients with clinical assessment, D-Dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Am J Med. March 2004;116:291-299.

Ramzi DW, Leeper KV. DVT and Pulmonary Embolism: Part II. Treatment and Prevention. Am Fam Physician. June 15 2004;69:2841-2848.

Merli G. Diagnostic assessment of deep vein thrombosis and pulmonary embolism. Am J Med. August 2005;118:3S-12S.

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