OVERVIEW

What is Thrombophilia?

Thrombophilia refers to a pathological state where blood clots form easily in blood vessels, leading to embolism. This condition arises from abnormalities in clotting factors or the presence of high-risk factors for thrombosis in the patient's body.
It is classified into hereditary thrombophilia and acquired thrombophilia.

SYMPTOMS

Why does pulmonary embolism occur with deep vein thrombosis in the lower limbs?

Because thrombi often form in veins, when a thrombus develops in the deep veins of the lower limbs, it can travel through the bloodstream from the lower limb veins to the heart, and then be pumped by the heart into the pulmonary artery. When the thrombus reaches the small branches of the pulmonary artery, it can block the artery, causing pulmonary embolism, which is the leading cause of death following venous thrombosis.

Pulmonary embolism has three main clinical symptoms: hemoptysis, chest pain, and dyspnea. However, in many cases, the patient's symptoms are not obvious and may only manifest as chest tightness, shortness of breath, hemoptysis, sudden fainting, pneumonia, pleural effusion, chest pain, or other discomforts.

What are the symptoms of deep vein thrombosis in the lower limbs?

After deep vein thrombosis forms in the lower limbs, there are three main symptoms:

• Swelling of both lower limbs: The degree of swelling is often uneven (a difference of more than 1 cm in circumference at the same location).
• Pain: Especially when the lower limb is straightened and the foot is dorsiflexed, there is deep pain in the calf muscles.
• Superficial varicose veins in the lower limbs: Visible bulging veins resembling earthworms under the skin, caused by collateral circulation forming in superficial veins due to deep vein blockage.

Can thrombi form in both arteries and veins?

Yes. Thrombi commonly occur in veins, but an increase in procoagulant substances can promote thrombus formation in both veins and arteries. Additionally, factors such as aging, obesity, and hyperlipidemia not only increase the risk of arterial atherosclerosis and thrombosis but also make venous thrombosis more likely.

What conditions might suggest thrombophilia?

Thrombophilia can cause thrombi to form in arteries or veins anywhere in the body, with varied symptoms. The following situations should raise suspicion of thrombophilia:

• No identifiable trigger for thrombus formation.
• Thrombi forming in uncommon venous sites, such as the inferior vena cava, mesenteric veins, hepatic veins, or renal veins.
• A history of thrombosis with recurrence.
• First occurrence of arterial or venous thrombosis before the age of 50.
• Venous thrombosis occurring after taking contraceptives or post-menopause.
• Family history of venous thrombosis.
• Recurrent venous thrombosis during anticoagulant therapy.
• Habitual miscarriage or intrauterine fetal death.

CAUSES

What causes thrombophilia?

Thrombophilia can be caused by various factors, such as deficiencies in substances that inhibit blood clot formation, defects in substances involved in clot dissolution, or a patient being in a state prone to thrombosis.

Is thrombophilia hereditary?

There are many causes of thrombophilia, and not all cases are hereditary.

• Hereditary: For example, deficiencies in substances that inhibit clot formation (protein C deficiency, protein S deficiency, etc.).
• Acquired: Such as aging, prolonged limb immobilization (e.g., after a fracture), or pregnancy.

What is the most common type of hereditary thrombophilia?

There are many types of hereditary thrombophilia, some of which are rare. In Asians, deficiencies in protein C, protein S, and antithrombin—three substances that inhibit clot formation—are the most common hereditary forms.

Are deficiencies in clot-inhibiting substances always hereditary?

No, deficiencies in these substances are not always due to reduced production. They can also result from destruction, leading to lower levels in the body.

For example, autoimmune diseases can produce antibodies that target and destroy the body's own substances, resulting in reduced quantities.

What acquired factors can cause thrombophilia?

• Certain diseases, such as cancer, diabetes, myeloproliferative disorders, nephrotic syndrome, antiphospholipid syndrome, or acquired increases in clotting factor levels.
• Conditions that predispose the body to clot formation, such as paralysis, prolonged flights, trauma, surgery, pregnancy, or oral contraceptive use—all of which are acquired factors.

Is thrombophilia related to blood type?

Yes, studies have found that ABO blood type is associated with venous thrombosis. Non-O blood types are more prone to venous thrombosis than O blood types, likely due to higher levels of pro-thrombotic substances in non-O individuals.

Can thrombophilia be caused by elevated homocysteine?

Yes, thrombosis caused by elevated homocysteine is a hereditary form of thrombophilia.

It occurs due to defects in enzymes that metabolize homocysteine, leading to increased levels in the blood and a higher risk of thrombosis (e.g., stroke, heart attack). Taking folic acid, vitamin B6, and vitamin B12 can lower homocysteine levels and reduce clotting risk.

Why are older adults more prone to thrombophilia?

This is due to multiple factors, including:

• Reduced physical activity;
• Weaker muscle contractions;
• Slower blood circulation;
• Aging blood vessels;
• Increased chronic diseases;
• Higher clotting factor activity.

Why are post-surgical patients more prone to thrombophilia?

This is related to the body's response to surgical stress.

For example, tissue damage during surgery releases pro-thrombotic substances (e.g., tissue factor), surgery can damage blood vessel linings, and post-surgical patients often remain immobile for extended periods.

Why does prolonged air travel increase thrombophilia risk?

Blood clots formed during long flights are also called "economy class syndrome."

If these clots break loose, they can travel to the lungs, causing pulmonary embolism or even sudden death. This is due to inactivity during flights, impaired blood flow, mild hypoxia in the cabin, and other high-risk clotting factors in some individuals.

DIAGNOSIS

What tests are needed to diagnose thrombophilia?

Complete blood count, liver and kidney function tests, coagulation function (including clotting time, endogenous prothrombin time), antithrombin activity, protein C activity, protein S activity, homocysteine levels (fasting), antiphospholipid antibodies (including lupus anticoagulant, anticardiolipin antibodies), etc.

Can reduced anticoagulant protein levels in test results diagnose hereditary anticoagulant protein deficiency?

No. Because reduced anticoagulant protein levels may be due to decreased production or excessive consumption.

Anticoagulant proteins are synthesized by the liver and depend on vitamin K. Liver disease, vitamin K deficiency, or taking warfarin can affect anticoagulant protein production, leading to reduced levels. During the acute phase of thrombosis, excessive consumption of anticoagulant proteins may also result in reduced test levels, but this does not confirm hereditary anticoagulant protein deficiency.

What is antiphospholipid antibody syndrome?

Antiphospholipid antibodies are a group of autoantibodies, including anticardiolipin antibodies and lupus anticoagulant. Antiphospholipid antibody syndrome refers to a series of clinical manifestations caused by these autoantibodies, which may include thrombosis in various parts of the body, recurrent miscarriages, thrombocytopenia, and neuropsychiatric symptoms.

Can a single positive antiphospholipid antibody test confirm antiphospholipid antibody syndrome?

No.

Healthy individuals or those taking certain medications (such as penicillin) may temporarily test positive for antiphospholipid antibodies. Therefore, a single positive result cannot confirm the diagnosis. The test must be repeated at least 8 weeks apart. Only if both tests are positive can the diagnosis be confirmed.

Can a negative antiphospholipid antibody test rule out antiphospholipid antibody syndrome?

No.

Antiphospholipid antibodies mainly include lupus anticoagulant, anticardiolipin antibodies, and β₂-glycoprotein I. There are also many unrecognized or routinely undetectable antiphospholipid antibodies. Therefore, a negative test does not exclude antiphospholipid antibody syndrome.

TREATMENT

Can long-term use of warfarin anticoagulation therapy cause bleeding?

Yes, it is possible. Since warfarin inhibits blood clot formation, excessive dosage may lead to bleeding.

Therefore, during warfarin treatment, regular coagulation function tests are necessary to adjust the dosage and maintain the International Normalized Ratio (INR) between 2 and 3, which is relatively safe.

Can thrombolytic therapy be used for cancer patients with thrombosis?

Prophylactic anticoagulation therapy is generally recommended for cancer patients. Once thrombosis occurs, treatment becomes more challenging, and thrombolytic therapy is not advised.

Thrombolytic therapy may promote tumor metastasis, increase the risk of bleeding, and lead to recurrent thrombosis.

Do anticoagulant drugs affect the fetus?

Heparin and low-molecular-weight heparin cannot cross the placenta and are safe for the fetus. However, warfarin can cross the placenta, potentially causing birth defects and fetal bleeding. Therefore, pregnant women can use heparin or low-molecular-weight heparin for anticoagulation but should avoid warfarin.

Do women on long-term prophylactic anticoagulation need to adjust their medication when planning pregnancy?

Since warfarin can cross the placenta and has teratogenic effects, women on prophylactic anticoagulation should switch to low-molecular-weight heparin before conception. In case of unplanned pregnancy, warfarin should be discontinued immediately and replaced with low-molecular-weight heparin.

Do pregnant women with a history of thrombosis require prophylactic anticoagulation?

Yes.

Pregnancy increases the risk of thrombosis due to a hypercoagulable state. Prophylactic anticoagulation with low-molecular-weight heparin is recommended, typically at a daily dose of 40 mg. If ultrasound shows reduced placental perfusion, the dose may be increased to 80 mg daily. Anticoagulation should continue for 4–6 weeks postpartum.

Do women with positive antiphospholipid antibodies require treatment during pregnancy?

Yes. For women with positive antiphospholipid antibodies and a history of recurrent miscarriages, low-dose prednisone (10 mg daily) can be administered during pregnancy until 37 weeks of gestation.

DIET & LIFESTYLE

Can breastfeeding be done while taking anticoagulant medication after childbirth?

Yes, postpartum prophylactic anticoagulants include heparin and warfarin. Heparin is not secreted into breast milk, and warfarin, which binds to proteins, is also rarely secreted into breast milk. Therefore, breastfeeding is possible while taking anticoagulant medication postpartum.

PREVENTION

How to prevent thrombosis after diagnosis of hereditary thrombophilia?

If you have experienced two thrombotic events or have risk factors for thrombosis, long-term anticoagulation therapy is required. Infusion of anticoagulant substances such as protein C, protein S, or antithrombin may be administered. For anticoagulant drug therapy, heparin is typically used for 3–7 days initially, followed by oral warfarin treatment.

Can thrombophilia caused by surgery be prevented?

Yes, thrombosis is prone to occur after surgery. Low-molecular-weight heparin can be used for anticoagulation therapy, usually lasting 7–10 days post-surgery. Specific usage should be tailored to the patient's individual condition.