Antiphospholipid Syndrome and Pregnancy - Causes, Symptoms, Risk Factors, and Treatment

What Is Antiphospholipid Syndrome (APS)?

Antiphospholipid Syndrome (APS)- It is an autoimmune disorder in which the immune system attacks phospholipid-bound proteins in blood cells and blood vessel linings. The usual equilibrium between bleeding and clotting is disturbed when APS antibodies inhibit proteins in the blood from attaching to phospholipids. If left untreated, this can result in blood clots and blocking of blood flow, leading to deep vein thrombosis, strokes, and heart attacks. During pregnancy, many complications can arise like preeclampsia, autoimmune thrombocytopenia, thrombosis, fetal growth restriction, and even fetal loss. Antiphospholipid syndrome can be classified as -

• Primary Antiphospholipid Syndrome- It is diagnosed in patients who fit the disease's clinical and laboratory criteria but have no other autoimmune disease.

• Secondary Antiphospholipid Syndrome- It is found in people with other autoimmune diseases such as systemic lupus erythematosus (SLE).

What Are the Risk Factors for Developing Antiphospholipid Syndrome?

Women are more likely than men to develop antiphospholipid syndrome. Antiphospholipid syndrome is more common with other autoimmune diseases like lupus.

The following factors increase the risk of developing antiphospholipid syndrome -

• Pregnancy.

• Surgery.

• People who are immobile for very long periods due to bed rest.

• Women taking hormone replacement theory or oral contraceptive pills.

• High triglycerides and cholesterol levels.

• Smoking.

What Are the Features of Antiphospholipid Syndrome in Pregnancy?

The following features of the antiphospholipid syndrome can be observed during pregnancy -

• Severe preeclampsia before 34 weeks of pregnancy.

• Recurrent pregnancy loss. Three or more spontaneous abortions with no more than one live birth.

• Unexpected fetal death in the second or third trimester.

• Severe fetal growth retardation (unexplained).

• Stillbirth or unexplained fetal death.

• Chorea Gravidarum - A rare illness marked by uncontrollable movements and speech alterations during the first trimester of pregnancy.

• Deep Vein Thrombosis (DVT) - It can lead to pain, swelling, and redness. These clots have the ability to go to the lungs causing pulmonary embolism.

• Rashes and ulcers on the legs.

• Photosensitivity.

• Digital gangrene.

• Digital cyanosis.

• Livedo Reticularis - A reddish-blue netlike pattern of skin discoloration.

To conclude, fetal complications include early delivery, oligohydramnios, neonatal complications (such as prematurity in SLE patients, intrauterine growth restriction (IUGR), fetal distress, and rarely fetal or neonatal thrombosis. Maternal obstetric complications include preeclampsia, eclampsia, HELLP syndrome, hemolytic anemia, elevated liver enzymes, low platelet counts, and arterial or venous thrombosis.

What Are the Causes of Antiphospholipid Syndrome in Pregnancy?

Antiphospholipid syndrome, like other autoimmune illnesses, has an unknown cause. Several theories exist to explain the probable cause. The following hypotheses are given to understand the cause of antiphospholipid syndrome -

• Family history of antiphospholipid syndrome.

• Passive transfer of maternal antibodies.

• The cell membranes are disrupted during infectious diseases, and phospholipids are released, stimulating antiphospholipid antibodies. These infections can be -

  • Viral (human immunodeficiency virus [HIV], Epstein-Barr virus [EBV], cytomegalovirus [CMV], or adenoviruses).

  • Bacterial (bacterial endocarditis, tuberculosis, Mycoplasma pneumonia).

  • Spirochetal (syphilis, leptospirosis, or Lyme disease).

  • Parasitic (malaria infection).

• Epitope mimicry in autoimmune disease.

How Is Antiphospholipid Syndrome Diagnosed in Pregnant Women?

Positive tests for circulating antiphospholipid antibodies, including lupus anticoagulant or anticardiolipin, or both, at medium-high values, identified at least twice in six weeks, are required to classify this syndrome. In addition, the patient must meet at least one clinical and one laboratory criterion to be diagnosed.

• Clinical Criteria-

  • Any tissue or organ with one or more clinical episodes of arterial, venous, or small-vessel thrombosis.

  • Unexpected deaths of morphologically normal fetuses at or after ten weeks of pregnancy.

  • Premature births of morphologically normal fetuses at or before 34 weeks of pregnancy due to eclampsia, severe preeclampsia, or characteristics consistent with placental insufficiency.

  • Three or more unexplained spontaneous miscarriages before the 10th week of pregnancy, with maternal anatomic or hormonal abnormalities, as well as paternal and maternal chromosomal reasons, were ruled out.

• Laboratory Criteria-

  • Lupus anticoagulant (LAC) has been found in the blood on two or more occasions, at least 12 weeks apart.

  • Anticardiolipin Antibodies - Anticardiolipin IgG or IgM antibodies are detected in the blood at moderate or high levels on two or more occasions, separated by at least 12 weeks.

  • Anti-beta2-glycoprotein I antibodies, IgG or IgM, in titers above the 99th percentile for normal, as defined by the laboratory performing the test, on two or more occasions, at least 12 weeks apart.

• Other additional findings in antiphospholipid syndrome during pregnancy -

  • Unexplained transient ischemic attacks.

  • Hemolytic anemia.

  • Positive Coombs test.

  • Chorea gravidarum.

• Tests used for diagnosis of the antiphospholipid syndrome -

  • Immunoassays-

    • Biologic false positive (BFP) syphilis test.

    • Anticardiolipin antibodies (cofactor-dependent assay).

    • Antiphosphatidylserine antibodies.

    • Anti-b2GPI antibodies.

    • Antiprothrombin antibodies.

  • Coagulation Tests-

    • Dilute Russel viper venom time (DRVVT).

    • aPTT (activated partial thromboplastin time).

    • Kaolin clotting time.

    • Plasma clotting time.

What Is the Treatment of Antiphospholipid Syndrome During Pregnancy?

More than 70 % of pregnant women with antiphospholipid syndrome can give birth to a healthy baby with meticulous care. The following steps must be taken for the management and antithrombotic treatment of antiphospholipid syndrome in pregnancy-

• Preconception counseling allows the clinician to educate about the unique circumstances of each patient with the syndrome, as well as the risks of pregnancy and therapy.

• Pregnancy should be avoided in all women with significant pulmonary hypertension and postponed in the case of uncontrolled hypertension or recent thrombotic events, like stroke.

• Before planning a pregnancy, a complete profile of antiphospholipid antibodies, including recurrent anticardiolipin and lupus anticoagulant, should be provided.

• Patients should be advised about thrombosis and thromboembolism symptoms in all cases. They should be educated about and inspected frequently for signs or symptoms of thrombosis or thromboembolism, severe preeclampsia, or decreased fetal movement.

• Treatment for antiphospholipid syndrome in pregnant women aims to enhance maternal and fetal-neonatal outcomes.

Antiphospholipid syndrome in pregnant women can be categorized and treated as follows -

1. Patients Who Have Never Experienced a Thrombotic Event and Have Antiphospholipid Syndrome-Low-dose aspirin, either alone or in combination with unfractionated or low-molecular-weight heparin (LMWH). Postpartum thromboprophylaxis with Warfarin or LMWH is suggested after birth.

2. Those Who Have Had One or More Fetal Deaths (At More Than Ten Weeks’ Gestation) Or Early Deliveries (At Less Than 34 Weeks Gestation) Due to Severe Preeclampsia or Placental Insufficiency- Low dose Aspirin with unfractionated heparin subcutaneously. Following delivery, postpartum thromboprophylaxis with Warfarin or LMWH is recommended.

3. Antiphospholipid Syndrome With Thrombosis- Low dose Aspirin with unfractionated heparin subcutaneously.

• Antithrombotic coverage during the postpartum period is indicated in all women with antiphospholipid syndrome, whether or without previous thrombosis, to lower the risk of postpartum deep vein thrombosis.

• Future Therapies- Several new therapy techniques for the antiphospholipid syndrome are being developed-

  • Combination antiaggregant therapy (low-dose Aspirin with Clopidogrel or Dipyridamole).

  • Direct thrombin inhibitors (Dabigatran).

  • Statins (Fluvastatin or Rosuvastatin).

  • Oral anti factor Xa drugs (Rivaroxaban or Apixaban).

  • B-cell depletion (Rituximab).

  • Hydroxychloroquine.

• However, the majority of these potential therapies are for non-pregnant individuals. Dipyridamole and hydroxychloroquine are the only medications that pregnant women can take.

Conclusion:

Antiphospholipid syndrome is a medical condition in which the immune system produces antibodies that attack body tissues. Due to these antibodies, blood clots can form in the legs, lungs, and other organs like the kidneys and spleen. The blood clots formed in the organs can cause strokes, heart attacks, and other issues. In addition, the antiphospholipid syndrome can cause miscarriage and stillbirth during pregnancy. Unfortunately, some patients with the syndrome have no symptoms or signs. This uncommon illness has no treatment, but drugs can minimize the risk of blood clots and miscarriage.