ConditionBlood & immune system
Thrombophilia (Clotting Disorders)
Thrombophilia is an increased tendency for the blood to form clots, usually in the veins, causing deep vein thrombosis (DVT) or pulmonary embolism (PE). It can be inherited, such as factor V Leiden or the prothrombin gene mutation, or acquired, most importantly antiphospholipid syndrome. Many people with an inherited thrombophilia never have a clot. Testing is useful only in selected situations, and treatment depends on clot history rather than the test result alone.
Also called: Hypercoagulable state, blood clotting disorder, increased clotting tendency, hypercoagulability
At a glance
- What it is
- A tendency to form blood clots more easily than usual.
- Inherited types
- Factor V Leiden, prothrombin G20210A, and deficiencies of antithrombin, protein C and protein S.
- Acquired types
- Antiphospholipid syndrome, cancer, pregnancy, estrogen, immobility, myeloproliferative disorders.
- Main problems
- DVT, pulmonary embolism, and, with antiphospholipid syndrome, arterial clots and pregnancy loss.
- Management
- Anticoagulants for clots, preventive treatment during high-risk periods, and avoiding estrogen where advised.
When to get help
Call 911 or go to the ER
- Sudden shortness of breath, sharp chest pain worse on breathing, coughing blood or fainting (possible pulmonary embolism): call 911 or your local emergency number
- Sudden facial drooping, arm weakness, speech difficulty or vision loss (possible stroke)
- Severe headache with vomiting or seizures, especially in pregnancy or on hormones (possible clot in brain veins)
See a doctor within a day or two
- A swollen, painful, warm or red calf or leg
- Severe abdominal pain with known clotting tendency (possible clot in abdominal veins)
Book a routine appointment
- A first clot at a young age, in an unusual place, or without an obvious trigger
- Recurrent miscarriages or late pregnancy loss
- A strong family history of clots before starting estrogen contraception or HRT, or before pregnancy
How blood clotting can tip out of balance
Normal clotting balances clot-promoting factors with natural anticoagulants (antithrombin, protein C and protein S). Thrombophilia tips this balance toward clotting. Clots usually form only when a trigger is added, such as surgery, immobility, pregnancy, estrogen or long travel.
Inherited thrombophilias
| Condition | How common (white populations) | Relative clot risk |
|---|---|---|
| Factor V Leiden (one copy) | About 5% | Mild increase, about 3 to 5 times |
| Prothrombin G20210A mutation | About 2% | Mild increase, about 2 to 3 times |
| Protein C deficiency | Rare | Moderate to high |
| Protein S deficiency | Rare | Moderate to high |
| Antithrombin deficiency | Rare | Highest among inherited types |
Having two copies of factor V Leiden, or combined defects, raises risk further. These variants are less common in people of African and Asian ancestry.
Acquired thrombophilias
- antiphospholipid syndrome: autoantibodies cause venous and arterial clots (including strokes) and pregnancy complications. Often linked to lupus
- cancer and chemotherapy
- pregnancy and the 6 weeks after birth
- estrogen-containing contraceptives and oral HRT
- myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia)
- paroxysmal nocturnal hemoglobinuria
- nephrotic syndrome
- heparin-induced thrombocytopenia
- inflammatory bowel disease
- obesity, immobility, major surgery and trauma
Symptoms
Thrombophilia itself causes no symptoms. Symptoms come from clots:
- DVT: one swollen, painful, warm, red leg
- pulmonary embolism: sudden breathlessness, chest pain, coughing blood, fast heartbeat
- clots in unusual sites: brain veins (headache, seizures), abdominal veins (abdominal pain), arm veins
- arterial clots in antiphospholipid syndrome: stroke, heart attack
- pregnancy complications: recurrent miscarriage, stillbirth, severe preeclampsia (antiphospholipid syndrome)
Who should be tested
ASH 2023 guidelines suggest testing only in specific situations where results would change management, for example:
- after a clot triggered by a minor provoking factor, to help decide on long-term anticoagulation
- family members of someone with a known high-risk thrombophilia, before estrogen therapy or pregnancy
- clots in unusual sites
Antiphospholipid antibody testing is important after unexplained arterial clots, recurrent pregnancy loss, or clots in young people, because it changes which blood thinner is used.
Testing is generally not useful during an acute clot or while on certain blood thinners, because results can be falsely abnormal.
Tests
- factor V Leiden and prothrombin gene tests (DNA tests, unaffected by blood thinners)
- antithrombin, protein C and protein S activity
- antiphospholipid antibodies: lupus anticoagulant, anticardiolipin and anti-beta-2 glycoprotein I, repeated after 12 weeks
- blood count and other tests for acquired causes
Treatment
Treating a clot
- anticoagulants: direct oral anticoagulants (apixaban, rivaroxaban, dabigatran, edoxaban), low-molecular-weight heparin, or warfarin
- usually at least 3 months
- antiphospholipid syndrome: warfarin is preferred over direct oral anticoagulants, especially in high-risk (triple-positive) or arterial cases
How long to treat
Duration depends on whether the clot was provoked, the bleeding risk and the type of thrombophilia. Unprovoked clots often warrant long-term treatment.
Prevention during high-risk times
- preventive heparin after surgery, during hospital stays and in pregnancy for some people
- avoiding estrogen-containing contraception and oral HRT in many thrombophilias. Progestin-only or non-hormonal methods are preferred
- staying mobile on long journeys and keeping hydrated
Pregnancy
ACOG recommends heparin prophylaxis during pregnancy and/or after birth for women with certain thrombophilias and personal or family clot history. Antiphospholipid syndrome with pregnancy loss is treated with low-dose aspirin and heparin.
Outlook
Most people with mild inherited thrombophilia live normal lives and may never have a clot. Awareness of the condition helps reduce risk during surgery, pregnancy and hormone use.
Frequently asked questions
What is thrombophilia?
Thrombophilia is a condition in which the blood clots more easily than normal, raising the risk of clots in veins (DVT and pulmonary embolism) and, in some forms, arteries. It can be inherited or acquired.
What is the most common inherited thrombophilia?
Factor V Leiden is the most common inherited thrombophilia in people of European descent, present in about 5%. It mildly increases clot risk, especially combined with estrogen, pregnancy, surgery or immobility.
Should I be tested for thrombophilia?
Testing is recommended only in specific situations, such as some first clots, clots in unusual places, recurrent pregnancy loss, or a family history of a high-risk thrombophilia before pregnancy or estrogen use. Discuss with your doctor or a hematologist.
Can I take the birth control pill if I have thrombophilia?
Estrogen-containing pills, patches and rings raise clot risk and are usually avoided. Progestin-only pills, hormonal IUDs, the copper IUD and implants are generally safer choices. Your doctor can advise based on your specific condition.
Does thrombophilia mean lifelong blood thinners?
Not necessarily. Many people with thrombophilia never need blood thinners. After a clot, treatment length depends on whether it was provoked and on bleeding risk. Some people, such as those with antiphospholipid syndrome and clots, need long-term treatment.
Sources
This guide was written from current patient and clinical guidance, including:
- American Society of Hematology (ASH): 2023 Guidelines for thrombophilia testing
- ASH: Venous thromboembolism treatment guidelines
- National Heart, Lung, and Blood Institute (NHLBI): Venous thromboembolism
- CDC: Blood clots and thrombophilia
- ACOG: Inherited thrombophilias in pregnancy (Practice Bulletin 197)