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ANTIPHOSPHOLIPID ANTIBODY SYNDROME

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A-MOWAFY 2013

DEFINITION:

It is a condition in which antibodies (lupus anticoagulant and anti cardiolipins antibodies) are formed

against vascular endothelium and plattlets leading to vasoconstriction, thrombosis, placental

infarctions and fetal loss

PATHOGENESIS:

Antiphosholipid antibodies

(lupus anticoagulant and anti cardiolipins antibodies)

Antiphospholipid Antibody

syndrome Venous thromboembolism during pregnancy

Thrombosis

blocks the action of

prostacyclin (vasodilator and prevent

plattlets aggregation)

relative excess of

thromboxane E2 (vasoconstrictor substance)

reduces the release of

hCG

inhibits

trophoplastic invasion

vasculopathy of

Spiral Arterioles

uteroplacental insufficiency

Oligohydraminos

Fetal Hypoxia

IUGR

Fetal loss

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ANTIPHOSPHOLIPID ANTIBODY SYNDROME

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A-MOWAFY 2013

EFFECT OF ANTIPHOSPHOLIPID ANTIBODIES ON PREGNANCY:

1. Recurrent pregnancy loss (typically at or beyond 10 weeks)

2. IUGR

3. IUFD

4. Early onset pre-eclampsia (before 20 weeks)

5. Placental abruption

6. Preterm labour

7. Occasionally infertility

DIAGNOSIS:

Criteria for diagnosis should include at least one clinical data + one laboratory data

Clinical criteria: I. Pregnancy morbidity:

i.Any unexplained fetal death of a morphologically normal fetus at or beyond 10 weeks

(normality is determined by direct examination or ultrasound)

ii.Any birth of a morphologically normal neonate before 34 weeks due to SPET or severe

placental insufficiency

iii.At least 3 consecutive spontaneous abortions before 10 weeks after exclusion of

maternal, anatomical, hormonal and chromosomal causes (of both parents)

II. Vascular thrombosis: past or current history of:

i.Recurrent DVT

ii.Peripheral arterial gangrene

iii.Cerebro-vascular stroke

iv.Coronary thrombosis

v.Pulmonary hypertension

III. Associated immune and connective tissue disease:

i.SLE

ii. Thrombocytopenia

IV. Persistent false positive Wasserman’s test

V. Infertility

Laboratory criteria: I. Positive titres of moderate to high dilution of anti-cardiolipin antibody at least 12 weeks apart

(IgG, IgM)

II. Anti-β2 glycoprotein antibody

III. Lupus anti-coagulant antibody (Russell’s Viber Venom test)

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ANTIPHOSPHOLIPID ANTIBODY SYNDROME

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A-MOWAFY 2013

MANAGEMENT:

Lines of management: I. Pre-conception counselling

II. Throboprophylaxis

III. Corticosteroid therapy

IV. Immunologic therapy

V. Prevention of complications

VI. Post-partum care

I. PRE-CONCEPTION COUNSELLING:

Counselling the patient about the possible risk and pregnancy outcome

Patients with antiphospholoipid antibody syndrome secondary to renal disease, SLE,

thrombocytopenia, and hemolytic anemia need a specialized care

Pre-conceptional correction of anemia, thrombocytopenia ….etc

II. THROBOPROPHYLAXIS:

Low dose Aspirin: Aspirin (60 – 80 mg) tablet once daily

Heparin:

Types I. Unfractionated heparin → UFH “Cal-heparin” II. Low molecular weight heparin → LMWH “Clexan”

Onset Within 10 minutes

Half-life 6 hours

Doses I. Unfractionated heparin

Normal body weight → 5000 IU/day

Body weight ˂ 50 kg → 2500 IU/day

Body weight ˃ 90 kg → 5000 IU/12 h

High prophylactic dose→ 100 IU/kg/12h

II. Low molecular weight heparin

Normal body weight → 40 mg/day

Body weight ˂ 50 kg → 20 mg /day

Body weight ˃ 90 kg → 40 mg / 12h

High prophylactic dose→ I mg/kg/12h

Monitoring 1. Activated partial thromboplastin aPPT twice weekly 2. Plattlets concentration monthly 3. Bone mineral density every 3 months

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ANTIPHOSPHOLIPID ANTIBODY SYNDROME

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A-MOWAFY 2013

Advantages 1. No effect on the fetus ( does not cross placental blood barrier )

2. Not secreted on milk ( no effect on lactation ) N.B : advantages of LMWH over UFH

o Fewer side effect o Prolonged half-life o Greater inhibitory effect on factor X o Prophylactic dose once daily o No need for continuous laboratory monitoring

Drawbacks Increase bleeding tendency

Osteoporosis ( improved by adding calcium , hence name “ Cal-heparin “

Fat necrosis at site of injection

Alopecia

Anti-dot Protamine sulphate 1mg/100IU

N.B:

Epidural anesthesia should be avoided in patients under heparin therapy

III. CORTICOSTEROID THERAPY:

Prednisone ( ˃40 mg/day) in combination with low dose aspirin

Complications include: cushenoid manifestation, induced DM, predisposition to

infections

IV. IMMUNOLOGIC THERAPY:

Indications :

a. Failure of 1st line therapy

b. Associated hypertensive disorders

c. Associated IUGR

Immunoglobulins IV 0.4 gm/kg/daily for 5 days and repeated monthly

Immunosuppressive drugs; azathioprine, cyclosporins do not improve success rate

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ANTIPHOSPHOLIPID ANTIBODY SYNDROME

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A-MOWAFY 2013

V. PREVENTION OF COMPLICATIONS:

Continuous monitoring by:

a. ANC weekly

b. NST and ultrasound every 2 weeks

c. Doppler ultrasound for early detection of uteroplacental insufficiency and IUGR

Corticosteroid therapy may be used for lung maturity but it is better to be avoided in

heparinized patients

High risk patients should be fully anticoagulated with LMWH throughout the whole

pregnancy

Low-dose aspirin alone is enough if no complications

VI. POST-PARTUM CARE:

Thromboprophylaxis should be continued for first 6 weeks postpartum

Warfarin can be used to achieve INR values between 2.0 and 3.0 even in breast feeding

woman

Estrogen-containing pills are contraindicated

N.B: Postpartum examination of placenta is important

In complicated cases the placenta appears of low weight, massive infarctions and intravascular thrombosis