Understanding Antiphospholipid Syndrome (APS) and Thrombophilia Test Results

APS and thrombophilia test results can be difficult to understand.

You may receive results containing terms such as DRVVT, lupus anticoagulant, anticardiolipin antibodies, beta-2 glycoprotein antibodies, Factor V Leiden, prothrombin mutation, MTHFR, Protein C, Protein S or antithrombin and understandably wonder what they mean for your health, miscarriage risk or future pregnancy.

The most important point is that an abnormal thrombophilia result does not automatically mean that it caused a miscarriage, that you have antiphospholipid syndrome, or that you need aspirin or heparin.

This guide explains the common APS and thrombophilia results, what an abnormal result may mean and when repeat testing or specialist interpretation may be appropriate.

Read about Specialist Miscarriage Consultation at Innermost Healthcare

Read: Understanding Recurrent Miscarriage

APS and inherited thrombophilia are not the same thing

This distinction is important.

Antiphospholipid syndrome (APS) is an acquired autoimmune condition associated with blood clots and recognised pregnancy complications, including recurrent miscarriage.

Inherited thrombophilias are genetic conditions that alter the body’s tendency to form blood clots. Examples include:

  • Factor V Leiden
  • prothrombin G20210A mutation
  • Protein C deficiency
  • Protein S deficiency
  • antithrombin deficiency.

These inherited conditions are primarily important because of their association with venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

Their association with recurrent early miscarriage is much less clear.

RCOG does not recommend routine inherited-thrombophilia testing for every woman with recurrent early miscarriage, whereas testing for APS is an established part of recurrent miscarriage assessment.

RCOG: Recurrent Miscarriage – Patient Information

ESHRE: Recurrent Pregnancy Loss Guideline

Quick guide to common APS and thrombophilia results

Result What it usually means Important point
DRVVT / lupus anticoagulant positive May indicate a lupus anticoagulant Does not diagnose APS on its own
Anticardiolipin IgG/IgM raised An antiphospholipid antibody is present Level, persistence and clinical history matter
Beta-2 glycoprotein I antibody raised Another APS-associated antibody Persistent positivity is more important than one isolated result
Factor V Leiden heterozygous One copy of the Factor V Leiden variant Mainly affects VTE risk; does not prove a cause of miscarriage
Factor V Leiden homozygous Two copies of the variant Greater thrombosis risk than heterozygosity
Prothrombin G20210A heterozygous One copy of the prothrombin variant Primarily relevant to thrombosis risk
MTHFR variant A common genetic polymorphism Usually not clinically useful for miscarriage or thrombosis decisions
Protein S low Reduced Protein S activity or level Protein S normally falls during pregnancy
Protein S high Level above laboratory range Usually not considered a thrombophilia
Protein C low May indicate reduced Protein C activity Illness, thrombosis and some medicines can alter results
Protein C high Level above laboratory range Usually not clinically significant as a thrombophilia
Antithrombin low May indicate antithrombin deficiency A genuinely persistent low result can be clinically important

Reference ranges vary between laboratories, so numerical results should always be interpreted using the reference range on your own laboratory report.

What does a positive DRVVT mean?

DRVVT stands for dilute Russell’s viper venom time.

It is one of the laboratory tests used to detect a lupus anticoagulant.

Despite the name, having a lupus anticoagulant does not mean that you have lupus.

A DRVVT result is usually interpreted as part of a sequence of laboratory testing involving:

  • a screening test
  • mixing studies
  • phospholipid confirmation
  • the overall laboratory ratio or interpretation.

A prolonged screening result by itself is therefore not enough to diagnose a lupus anticoagulant.

The laboratory will usually report the overall pattern as something such as:

  • lupus anticoagulant not detected
  • lupus anticoagulant detected
  • indeterminate or borderline.

Does a positive DRVVT mean I have APS?

No.

A positive lupus anticoagulant is one of the laboratory criteria used when assessing APS, but APS is a clinical diagnosis, not simply a blood-test result.

The diagnosis requires:

  1. an appropriate clinical history; and
  2. persistent antiphospholipid antibodies.

In recurrent miscarriage assessment, RCOG advises that positive antiphospholipid antibody results should be confirmed on two occasions at least 12 weeks apart, with testing performed at least 6 weeks after a miscarriage.

Anticoagulant medicines can also interfere with lupus-anticoagulant testing, particularly direct oral anticoagulants and, depending on the assay, heparin.

Innermost Healthcare: Lupus Anticoagulant / DRVVT Test

What do raised anticardiolipin antibodies mean?

Anticardiolipin antibodies are antiphospholipid antibodies usually measured as:

  • IgG anticardiolipin
  • IgM anticardiolipin.

A raised result means that one of these antibodies has been detected.

However, interpretation depends upon:

  • whether IgG or IgM is positive
  • the level of positivity
  • whether the result remains positive when repeated
  • whether other antiphospholipid antibodies are present
  • the person’s clinical history.

A weakly or transiently positive result is not the same as persistent clinically significant APS.

Antibodies can occasionally become temporarily positive following infection or inflammation.

This is why one abnormal anticardiolipin result should not automatically be labelled APS.

Innermost Healthcare: Anticardiolipin Antibody Test

What do raised beta-2 glycoprotein antibodies mean?

Anti-beta-2 glycoprotein I antibodies are another recognised group of antiphospholipid antibodies.

They are commonly measured as:

  • IgG anti-beta-2 glycoprotein I
  • IgM anti-beta-2 glycoprotein I.

As with anticardiolipin antibodies, their clinical significance depends upon level, persistence and clinical history.

Someone who repeatedly tests positive for several antiphospholipid antibodies may have a different risk profile from someone with a single low-level result.

Innermost Healthcare: Beta-2 Glycoprotein Antibody Test

What does “triple-positive APS” mean?

You may hear the term triple positivity.

This means that all three principal antiphospholipid antibody groups are persistently positive:

  • lupus anticoagulant
  • anticardiolipin antibodies
  • anti-beta-2 glycoprotein I antibodies.

Triple positivity is generally considered a higher-risk antiphospholipid antibody profile than isolated low-level positivity.

Interpretation and treatment should therefore be based upon the whole clinical picture rather than simply whether a result is marked abnormal on a laboratory report.

What does heterozygous Factor V Leiden mean?

Factor V Leiden is an inherited change in the Factor V gene.

The term heterozygous means that you have:

  • one copy of the Factor V Leiden variant; and
  • one normal copy of the gene.

Factor V Leiden produces resistance to activated Protein C, one of the body’s natural anticoagulant mechanisms.

Is heterozygous Factor V Leiden dangerous?

Most people who are heterozygous for Factor V Leiden will never develop a blood clot.

However, it increases the risk of venous thrombosis compared with someone who does not carry the variant.

The actual risk depends upon other factors such as:

  • previous DVT or pulmonary embolism
  • family history
  • pregnancy
  • Caesarean birth
  • obesity
  • immobility
  • surgery
  • oestrogen-containing medication
  • other thrombophilias.

Does heterozygous Factor V Leiden cause miscarriage?

Factor V Leiden has been extensively studied in pregnancy, but an association does not necessarily mean causation.

Current recurrent miscarriage guidance does not recommend routine Factor V Leiden testing simply because a woman has experienced recurrent early miscarriage.

A heterozygous Factor V Leiden result should therefore primarily be considered in terms of maternal thrombosis risk, rather than automatically being labelled as the cause of miscarriage.

What does homozygous Factor V Leiden mean?

Homozygous means that both copies of the Factor V gene carry the Factor V Leiden variant.

This is much less common than heterozygous Factor V Leiden and is associated with a greater risk of venous thrombosis.

Pregnancy management may therefore differ considerably from someone who is heterozygous.

Specialist assessment is appropriate because the decision about thromboprophylaxis depends upon the individual’s complete risk profile.

What does Activated Protein C Resistance mean?

Activated Protein C Resistance — often abbreviated APCR — means that Factor V is less responsive than expected to the anticoagulant effect of activated Protein C.

The commonest inherited cause is Factor V Leiden.

An abnormal APCR screen may therefore prompt genetic Factor V Leiden testing.

However, APCR assays can be affected by other laboratory and clinical factors, so interpretation depends upon the testing method used.

What does a prothrombin G20210A mutation mean?

The prothrombin G20210A variant is an inherited genetic change associated with increased prothrombin production and a higher risk of venous thrombosis.

Most people identified with the variant are heterozygous, meaning that they have one affected and one normal copy.

As with Factor V Leiden, the finding is primarily relevant to blood-clot risk.

It does not by itself prove that a previous miscarriage was caused by thrombophilia.

The significance depends upon previous thrombosis, family history and other risk factors.

What does an MTHFR result mean?

MTHFR stands for methylenetetrahydrofolate reductase.

The MTHFR gene is involved in folate and homocysteine metabolism.

Two commonly reported variants are:

  • C677T
  • A1298C.

Reports may describe someone as:

  • heterozygous
  • homozygous
  • compound heterozygous.

Is MTHFR a thrombophilia?

Common MTHFR polymorphisms are not regarded as clinically useful inherited thrombophilias in modern thrombosis guidance.

They are common in the general population.

Being heterozygous or homozygous for an MTHFR variant does not by itself establish:

  • increased thrombosis risk
  • a cause of miscarriage
  • infertility
  • implantation failure
  • a need for aspirin
  • a need for heparin.

What about homocysteine?

Certain MTHFR variants can influence homocysteine metabolism, particularly in the presence of nutritional factors such as folate deficiency.

If there is a genuine clinical concern about homocysteine, it can be measured directly.

The presence of an MTHFR variant by itself is considerably less informative than the person’s actual clinical and biochemical picture.

Do I need methylfolate because I have MTHFR?

Not simply because an MTHFR variant has been identified.

Most women should follow established preconception and pregnancy recommendations for folic acid unless there is a separate clinical indication for a different dose or preparation.

An MTHFR result alone is not a reason to start anticoagulation.

What does low Protein S mean?

Protein S is one of the body’s natural anticoagulants.

It works as a cofactor for activated Protein C.

A genuinely reduced Protein S level can occur in inherited Protein S deficiency and may increase venous-thrombosis risk.

However, Protein S is one of the most difficult thrombophilia results to interpret during pregnancy.

Is low Protein S normal in pregnancy?

Protein S levels normally fall during pregnancy.

Therefore, a low Protein S result during pregnancy does not necessarily mean that you have inherited Protein S deficiency.

Protein S can also be affected by:

  • oestrogen
  • acute illness
  • recent thrombosis
  • liver disease
  • vitamin K status
  • anticoagulant medication
  • the timing of the test.

If inherited Protein S deficiency is suspected, repeat testing at an appropriate time outside pregnancy may be required.

What does high Protein S mean?

A Protein S result above the laboratory reference range is generally not regarded as a thrombophilic disorder.

In clinical thrombophilia assessment, concern is usually about deficiency, not an elevated Protein S level.

A high Protein S value by itself does not normally indicate a need for treatment.

What does low Protein C mean?

Protein C is another natural anticoagulant.

Persistently reduced Protein C activity can indicate inherited Protein C deficiency, which is associated with an increased risk of venous thrombosis.

However, Protein C levels can also be reduced by acquired factors.

These include:

  • warfarin therapy
  • severe illness
  • liver disease
  • vitamin K deficiency
  • disseminated intravascular coagulation
  • recent thrombosis in some circumstances.

An unexpected low result may therefore require repeat testing when these factors are no longer present.

What does high Protein C mean?

A Protein C result above the laboratory reference range is generally not considered a thrombophilia.

High Protein C levels are usually much less clinically important than a persistently low level.

A high result alone would not normally indicate anticoagulant treatment.

What does low antithrombin mean?

Antithrombin is an important natural anticoagulant that inhibits thrombin and other activated clotting factors.

True inherited antithrombin deficiency is uncommon but can carry a significant risk of venous thrombosis.

For that reason, a persistently low antithrombin result can be more clinically significant than some of the more common low-risk thrombophilia findings.

However, antithrombin can also fall because of:

  • acute thrombosis
  • heparin therapy
  • severe illness
  • liver disease
  • nephrotic syndrome
  • disseminated intravascular coagulation.

A low result should therefore be interpreted in context and may require confirmation.

A persistently low antithrombin level, particularly in someone with previous thrombosis or a strong family history, warrants specialist assessment.

What does high antithrombin mean?

A high antithrombin level is generally not regarded as a thrombophilic disorder.

As with Protein C and Protein S, clinical concern is primarily focused on significant deficiency rather than values above the reference range.

Can pregnancy affect thrombophilia results?

Yes.

Pregnancy changes the haemostatic system considerably.

Some tests are unaffected by pregnancy because they assess DNA. These include:

  • Factor V Leiden
  • prothrombin G20210A
  • MTHFR.

Other tests can change during pregnancy, particularly:

  • Protein S
  • some coagulation assays.

The timing of thrombophilia testing is therefore important.

Where the result is not urgently required, repeat testing outside pregnancy may sometimes provide more reliable information.

Can blood-thinning medication affect the results?

Yes.

Anticoagulants can interfere with some thrombophilia tests.

This is particularly important for lupus anticoagulant testing.

Potentially interfering medicines include:

  • low-molecular-weight heparin
  • unfractionated heparin
  • warfarin
  • rivaroxaban
  • apixaban
  • dabigatran
  • other anticoagulants.

Always tell your clinician and the laboratory which medication you are taking.

Do not stop prescribed anticoagulant medication simply to obtain a blood test without medical advice.

Does an abnormal thrombophilia result mean I need aspirin?

Not necessarily.

Aspirin is an antiplatelet medication rather than an anticoagulant.

It has important evidence-based uses in pregnancy, including:

  • treatment regimens for appropriate women with APS
  • prevention of pre-eclampsia in women who meet established risk criteria.

However, finding heterozygous Factor V Leiden, an MTHFR variant or a borderline Protein S result does not automatically mean that aspirin is required.

Treatment should be based upon the diagnosis and overall clinical risk.

Does an abnormal result mean I need heparin?

Again, not necessarily.

Heparin may be recommended for different reasons.

These include:

  • APS associated with recurrent miscarriage
  • previous venous thrombosis
  • certain higher-risk inherited thrombophilias
  • combinations of thrombosis risk factors during pregnancy or after delivery.

For inherited thrombophilia, the purpose of heparin may be to protect the mother from venous thrombosis, rather than to prevent miscarriage.

That distinction is important.

Does thrombophilia cause recurrent miscarriage?

This depends upon which condition is being discussed.

APS

APS has an established association with recurrent miscarriage and other pregnancy complications.

For women who fulfil diagnostic criteria for APS and recurrent miscarriage, treatment with low-dose aspirin and heparin can improve pregnancy outcome.

Inherited thrombophilia

The relationship between inherited thrombophilias and recurrent early miscarriage is considerably less clear.

Current RCOG and ESHRE guidance does not recommend routine hereditary thrombophilia testing simply because someone has recurrent early pregnancy loss.

Read: Understanding Recurrent Miscarriage

What if more than one thrombophilia result is abnormal?

The significance of combined abnormalities can be different from an isolated low-risk result.

Examples include:

  • Factor V Leiden together with prothrombin G20210A
  • an inherited thrombophilia plus previous DVT
  • multiple persistent antiphospholipid antibodies
  • antithrombin deficiency plus a strong family history.

This is one reason why thrombophilia reports should be interpreted as a whole profile rather than as individual red or green laboratory values.

When should I have my results reviewed?

Specialist review may be particularly useful if you have:

  • a positive lupus anticoagulant or DRVVT
  • persistently raised anticardiolipin antibodies
  • persistently raised beta-2 glycoprotein antibodies
  • Factor V Leiden homozygosity
  • more than one inherited thrombophilia
  • low antithrombin
  • persistently low Protein C or Protein S
  • a previous DVT or pulmonary embolism
  • a strong family history of thrombosis
  • recurrent miscarriage
  • a previous later pregnancy loss
  • severe or early placental complications
  • uncertainty about whether aspirin or heparin is appropriate.

Understanding your results at Innermost Healthcare

At Innermost Healthcare, APS and thrombophilia results can be reviewed alongside your complete clinical and pregnancy history.

We can discuss:

  • what each result actually means
  • whether an abnormal result is likely to be clinically significant
  • whether repeat testing is required
  • whether pregnancy or medication may have affected the result
  • whether the result changes your thrombosis risk
  • whether it is relevant to previous pregnancy loss
  • whether treatment is indicated
  • what should happen in a future pregnancy.

Specialist Miscarriage Consultation at Innermost Healthcare

Miscarriage and Recurrent Miscarriage Care

APS and thrombophilia tests available at Innermost Healthcare

Individual tests and broader profiles are available depending upon the clinical question.

APS testing

Lupus Anticoagulant / DRVVT

Anticardiolipin Antibodies

Beta-2 Glycoprotein Antibodies

Extended thrombophilia testing

Extended Thrombophilia Screen

A broad thrombophilia screen is not necessarily the most appropriate investigation for every person with recurrent miscarriage.

Where there is uncertainty, clinical assessment can help identify which investigations are likely to provide useful information.

Frequently asked questions about APS and thrombophilia results

Is heterozygous Factor V Leiden serious?

It increases venous-thrombosis risk compared with not carrying Factor V Leiden, but many heterozygous carriers never develop a blood clot.

Its significance depends upon your personal and family history and other thrombosis risk factors.

Does heterozygous Factor V Leiden mean I need heparin in pregnancy?

Not automatically.

RCOG regards isolated heterozygous Factor V Leiden as a lower-risk thrombophilia. Treatment decisions depend upon the complete VTE risk assessment rather than the genetic result alone.

Does MTHFR cause miscarriage?

Common MTHFR variants are not considered an established cause of recurrent miscarriage.

An MTHFR result alone does not indicate aspirin or heparin treatment.

Is MTHFR a clinically important thrombophilia?

Current thrombophilia guidance does not recommend MTHFR genetic testing as part of routine thrombophilia assessment.

What does low Protein S in pregnancy mean?

Protein S normally falls during pregnancy.

A low result during pregnancy therefore does not necessarily mean that you have inherited Protein S deficiency.

Is high Protein C or Protein S dangerous?

Usually not.

Thrombophilia assessment is primarily concerned with significant deficiency of these natural anticoagulants rather than elevated levels.

What does a positive DRVVT mean?

A positive DRVVT may support the presence of a lupus anticoagulant.

It does not by itself diagnose APS, and interpretation can be affected by anticoagulant medication.

Does a positive DRVVT mean I have lupus?

No.

The term lupus anticoagulant describes a laboratory phenomenon. Many people with a lupus anticoagulant do not have systemic lupus erythematosus.

Does one positive anticardiolipin result mean I have APS?

No.

APS requires the appropriate clinical history together with persistent laboratory positivity.

If my APS test is positive, when should it be repeated?

In recurrent miscarriage assessment, RCOG advises confirmation on two occasions at least 12 weeks apart, with testing at least 6 weeks after miscarriage.

Can APS be treated in pregnancy?

Yes.

For women with recurrent miscarriage who fulfil diagnostic criteria for APS, treatment with low-dose aspirin and heparin can improve pregnancy outcome.

Should everyone with recurrent miscarriage have a full thrombophilia screen?

No.

APS testing is an established part of recurrent miscarriage investigation. Routine inherited-thrombophilia screening is not recommended for every woman with recurrent early miscarriage.

Key points

APS and inherited thrombophilia are not the same thing.

APS is an acquired autoimmune thrombophilia and has an established association with recurrent miscarriage.

A positive DRVVT, anticardiolipin or beta-2 glycoprotein result does not by itself diagnose APS.

APS laboratory abnormalities need to be persistent and interpreted alongside the clinical history.

Heterozygous Factor V Leiden mainly affects venous-thrombosis risk and does not automatically explain recurrent miscarriage.

Homozygous Factor V Leiden and antithrombin deficiency generally carry greater thrombotic significance and warrant appropriate specialist assessment.

MTHFR polymorphisms are common and are not considered useful routine thrombophilia tests for miscarriage or VTE assessment.

Low Protein S can be physiological during pregnancy.

Persistently low Protein C, Protein S or antithrombin results require interpretation in the context of pregnancy, medication, illness and previous thrombosis.

High Protein C, Protein S or antithrombin values are generally not considered thrombophilic abnormalities.

An abnormal thrombophilia result does not automatically mean that aspirin or heparin is required.

The most useful interpretation comes from considering the laboratory result together with your complete medical and pregnancy history.

Further information

For independent evidence-based guidance:

RCOG: Recurrent Miscarriage – Patient Information

RCOG Green-top Guideline No. 17: Recurrent Miscarriage

RCOG Green-top Guideline No. 37a: Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium

ESHRE: Guideline on Recurrent Pregnancy Loss

British Society for Haematology: Guidelines for Thrombophilia Testing

For Innermost Healthcare:

Understanding Recurrent Miscarriage

Miscarriage Care and Specialist Miscarriage Consultation

Lupus Anticoagulant / DRVVT Test

Anticardiolipin Antibody Test

Beta-2 Glycoprotein Antibody Test

Extended Thrombophilia Screen

Written and medically reviewed by Dr Bryan Beattie MD FRCOG, Consultant in Fetal and Maternal Medicine.

Last medically reviewed: August 2026.

This information is intended to support rather than replace individual medical assessment. APS and thrombophilia results should be interpreted in the context of your medical history, pregnancy history, medication, thrombosis risk and the reference ranges used by the laboratory.

 

author avatar
Bryan Beattie Lead Consultant in Fetal Medicine
Dr Robert Bryan Beattie MB BCh BAO MD FRCOG Dr Beattie qualified in 1983 from Queen’s University Belfast and is sub-specialty trained in Fetal and Maternal Medicine. He also holds the RCOG/RCR Joint Diploma in Obstetric Ultrasound. He was a founder member of the British Maternal and Fetal Medicine Society and is an internationally recognised pregnancy expert who is regularly called upon to speak at conferences and events. Dr Beattie is the founding Chairman and Trustee of the Innermost Academy, a registered charity dedicated to improving education in pregnancy care.
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