Antiphospholipid syndrome(APS)

Antiphospholipid syndrome(APS)
(Acgurred thrombophilia)

Main and The Obgyn Clinic of Hvidovre (danish)

Definition: Criteria for the classification of the APS:
At least one of the following clinical criteria and one of the following paraclinical/laboratorial criteria should be met:

Clinical Criteria:

Unexplained death of a morphologically normal fetus at or beyond 10 weeks.
One or more premature deliveries before 34 week of gestation because of severe preeclampsia/eclampsia or severe IUGR.
Three or more unexplained consecutive abortions before 10 weeks of gestation (controversial, if no fetal heart has been seen, as some believe that very early abortion is not caused by APS)

Paraclinical/laboratory Criteria:

The presence of Antiphospholipid antibody (aPL) on two or more occations at least 12 weeks apart
Antiphospholipid (aPL) antibodies:

Lupus anticoagulant (LA) directed against phospholipidbinding plasm proteins prolonged activated partial thromboplastin time.
Beta 2- glycoprotein-1 antibodies, ß2-GP >99th percentile
Anticardiolipin (aCL) antibody

Medium titer: 20 - 50 anticardiolipin IgG and 20 -80 anticardiolipin IgM.

Secondary Antiphospholipid Syndrome: When antibodies is found in association with systemic lupus (SLE) (see also page 63 ), other rheumatic disease, autoimmune disorders, infections and medicine.

Prevalence: 2 - 5% of all pregnant women have cardiolipin antibodies or lupus anticoagulant but very few have antiphospholipid syndrome.
30% of women with severe early onset preeclampsia may have antiphospholipid antibodies.

Background: Anticardiolipin antibodies react with proteins bound to phospholipids in the cell membrane such as cardiolipin. Different isotypes and subclasses are associated with aCL including IgA, IgM, and IgG subclasses 1 to 4. Elevated levels of IgG anticardiolipin antibodies (particularly IgG2) incur a greater risk.

Risks:
Maternal thromboembolism is highly variable and exacerbated by co-existent hereditary coagulopathies. In one study thrombosis during pregnancy was 5% among women with known antiphospholipid syndrome.

Preeclampsia:
Occurs in one third of women with severe preeclampsia before 34 weeks. The relative risk is about 10 for developing preeclampsia in case of antiphospholipid syndrome.
Recurrent abortion and fetal loss, especially among women with a history of thrombosis and high titers.

Evaluation:
Who should be evaluated for antiphospholipid syndrome? Bad Obstetric History:

more than >= 3 abortions
Unexpected fetal death after 16 weeks
Severe IUGR
Severe preeclampsia/eclampsia before 34 weeks

Indication for investigation:

Pregnancy complication as above
Major abruption of the placenta
Big placental infarction
False positive syphilis serologies

Medical Conditions:

Non-traumatic thromboembolism, stroke, Systemic lupus erythematosus, Hemolytic anemia, transient ischemic attacks, amaurosis fugax, and libido reticularis.
Unexplained prolongations of the activated partial thromboplastine time (aPTT) or PT
Unexplained thrombocytopenia.

Treatment: Women with APS and history of thrombosis should already be permanently anticoagulated (most are given Warfarin, INR 2-3) Low-dose aspirin, preconception and during pregnancy.

If permanently anticoagulated:
Heparin, LMWH in therapeutical dosis and low dose asperin.
If not on permanent anticoagulation:

Prophylactic dose of LMWH and low dose asperin. Same treatment if obstrical complications and lupus anticoagaulant (LA) or high anticardiolipin antibodies
Low molecular heparin (LMWH) or Heparin when pregnancy is confirmed (before 6 weeks to avord Wafarin induced emhyopathy) and stop 6 weeks postpartum in case of previous thrombosis or 5 days after birth if no previous thrombosis.
Heparin stopped once labour has begun and restarted 6 hours post delivery.
See also prophylactic dose and therapeutic dose of Heparin under thrombophilia and thromboembolism and prophylaxis in pregnancy
Consider discontinuing heparin at 20 weeks gestation if uterine artery waveforms are normal and the indication for Heparin is not very strong.

Osteoporosis prevention in Heparin treated women: Vitamin D 800 mg 1500 mg Ca carbonate and weight bearing active i.e: walking are recommended.

References:

(1) Catherine Nielsen-Piercy. Handbook of Obstetric Medicine. 2001 Edition
(2) Regan L, Rai R. Thrombophilia and pregnancy loss. J Reprod Immunol 2002; 55:163-180.
(3) UpToDate 2007
(4) Wilson, WA, Gharavi AE, Koike T et Al: International concensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthr Rehum 1999; 42;1309-11.