Antiphospholipid Antibody Syndrome and

Pregnancy
Last Updated: October 3, 2002
Synonyms and related keywords: lupus, lupus anticoagulant, LAC, antiphospholipid syndrome,
APS, systemic lupus erythematosus, SLE, autoimmune disease, lupus erythematosus, LE, fetal
loss, thrombosis, autoimmune thrombocytopenia, infertility, pregnancy complications, fetal
mortality, fetal morbidity, maternal morbidity, spontaneous abortion, prematurity, stillbirth, fetal
growth restriction, FGR, fetal growth retardation

Author: Stella Nowicki, DDS, Head of Infectious Diseases Laboratory, Assistant

Professor, Departments of Obstetrics and Gynecology, Microbiology and
Immunology, University of Texas Medical Branch at GalvestonBackground:
Antiphospholipid syndrome (APS) is a recently recognized autoimmune condition
that may manifest with fetal loss, thrombosis, or autoimmune thrombocytopenia.
Women with these clinical features should be tested for lupus anticoagulant
(LAC) and anticardiolipin (aCL) antibodies; most patients with APS have both
LAC and aCL immunoglobulin G (IgG) antibodies. The diagnosis of APS requires
the presence of both clinical and biological features.

Systemic lupus erythematosus (SLE) is a chronic systemic disease with diverse

clinical and laboratory manifestations. LAC (and aCL) predisposes to clotting in
vivo, predominantly by interfering with the antithrombotic role of phospholipids
(PLs); therefore, it is associated with clinical thrombosis, not bleeding. The
antiphospholipid (aPL) autoantibodies bind moieties on negatively charged PLs
or moieties formed by the interaction of negatively charged PLs with other lipids,
PLs, or proteins.

aPL antibodies belong to the large family of antibodies that react with negatively
charged PLs, including cardiolipin, phosphatidylglycerol, phosphatidylinositol,
phosphatidylserine, phosphatidylcholine, and phosphatidic acid.

Pathophysiology: The biologic effects mediated by the human aPL antibodies

include (1) reactivity with endothelial structures, which disturbs the balance of
prostaglandin E2/thromboxane production; (2) interaction with platelet PLs, with
consequent up-regulation of platelet aggregation; (3) dysregulation of
complement activation; and (4) interaction of aPL with phosphatidylserine
exposed during trophoblast syncytium formation, which raises the possibility of a
more direct effect of these autoantibodies on placental structures.

In patients with primary APS, the presence of the 3 aCL isotypes plus LAC has
been associated with a higher number of recurrent spontaneous abortions
compared to other possible combinations of aCL isotypes.

The association between aPL antibodies and particular human leukocyte antigen
(HLA) alleles and HLA-linked epitopes has been reported in studies of patients
with lupus erythematous (eg, HLA-DR7, HLA-DR4). The HLA-DR3 phenotypes
seem to predispose to the formation of aCL antibodies and antinuclear antibodies
(ANAs), but this has not been confirmed in patients. However, particular HLA
alleles associated with recurrent miscarriage have not been reported.

Animals immunized with aCL or with the cofactor beta-2 glycoprotein I (b2GPI)
develop clinical manifestations of APS, including fetal loss, thrombocytopenia,
and neurological and behavioral dysfunction, along with elevated levels of aPL
antibodies.

aCL antibodies bind to b2GPI, or a complex formed by this b2GPI is a platelet

adhesin glycoprotein and cardiolipin. Exposure of endothelial cells to anti-b2GPI
antibodies and their corresponding peptides leads to the inhibition of endothelial
cell activation, as shown by decreased expression of adhesion molecules E-
selectin, intercellular adhesion molecule, and vascular cell adhesion molecule
and of monocyte adhesion.

In vivo infusion of each of the anti-b2GPI antibodies into BALB/c mice followed
by administration of the corresponding specific peptides prevents the peptide-
treated mice from developing experimental APS. These fascinating results
suggest that the use of synthetic peptides that focus on neutralization of
pathogenic anti-b2GPI antibodies represents a possible new therapeutic
approach to APS.

Passive transfer into naive mice of inherently heterogeneous aPL antibody

populations, either affinity-purified or as part of whole immunoglobulin fractions,
from humans with APS or autoimmune mice has been shown to induce growth
retardation and fetal loss.

Frequency:

• In the US: SLE occurs in approximately 120 cases per 100,000 population
and causes pregnancy complications in approximately 45 cases per
100,000 pregnant population. The aPL antibodies account for 65-70% of
cases of venous thrombosis. In women with venous thrombosis in unusual
sites (eg, cerebral portal, splenic, subclavian mesenteric veins), aPL
antibodies are detected in approximately 2% of patients with nontraumatic
venous thrombosis. This is a rate similar to that of several inherited
conditions of hypercoagulability such as antithrombin III deficiency and
protein C deficiency. Approximately 22% of women with APS have had
venous thrombosis and 6.9% have had a cerebrovascular incident (over a
median follow-up period of 60 mo); 24% of thrombotic events occurred
during pregnancy or the postpartum period. The rate for thrombosis or
stroke is 5-12%. These observations suggest that women with
documented APS should not take estrogen-progestin combination oral
contraceptives.
Mortality/Morbidity:

• APS increases the risk for maternal and fetal morbidity and fetal mortality
in pregnancy. The rate of fetal loss may exceed 90% in untreated patients
who have APS. Therapy (including aspirin and heparin) can reduce the
rate of fetal loss to 25%, as described by Cowchock et al.

• APS is one of the major causes of thrombosis and its complications in

women. SLE, transient serologic abnormalities, skin lesions, and
congenital heart block are affected by APS. The true neonatal lupus
dermatitis, a variety of systemic and hematologic abnormalities, and
isolated congenital heart block are associated with APS.

• APS is also associated with infertility and pregnancy complications such

as spontaneous abortions, prematurity, and stillbirths. Fetal deaths at or
beyond 20 weeks’ gestation may be attributed to APS involvement, and
aPL antibodies are found in 10-15% of women at high risk for fetal growth
restriction.

Sex: The female-to-male ratio is 9:1.

Age: Newborns of women with SLE may develop lupus syndrome. This
predominantly affects reproductive-aged women (ie, 15-55 y).

Clinical

Physical:

• Obstetric complications related to APS include the following:

o Sporadic miscarriage

o Recurrent pregnancy loss: Positive test results for IgG or

immunoglobulin M (IgM) aCL antibodies may be found in up to 20%
of women with the antibodies, but many positive results are of low
level or only the IgM isotype and therefore are not diagnostic of
APS.

o Recurrent embryonic pregnancy loss or death of the fetus at or

beyond 10 weeks of gestation

o Pregnancy-induced hypertension (PIH) with high risk for preterm

delivery

o Preterm birth
 o Uteroplacental insufficiency

o LAC and medium-to-high positive levels of aCL antibodies (IgG or

IgM): These may be found in 2-4% of otherwise healthy individuals.

• Clinical evidence of glomerulonephritis is found in more than 50% of

cases. However, if biopsies are performed on all patients, the incidence of
some nephritis may be as high as 90%. SLE is associated with
encephalopathy and seizures, to a lesser degree with ischemic stroke,
and, rarely, with subarachnoid hemorrhage.

• Clinical criteria for the diagnosis of APS are as follows:

o Fetal loss: This criterion is defined as 3 or more spontaneous

abortions with no more than one live birth or unexplained second or
third trimester fetal death.

o Thrombosis or stroke: This is unexplained venous or arterial

thrombosis, including stroke and arterial insufficiency due to arterial
thrombosis.

o Autoimmune thrombocytopenia: Other causes of thrombocytopenia

must be excluded.

o Cutaneous manifestations
 These may include digital cyanosis, livedo reticularis, digital
gangrene, and leg ulcers. The cause of these features
remains otherwise unexplained.
 Other features related to cutaneous manifestations, with a
cause that remains unexplained, include transient ischemic
attacks or amaurosis fugax, positive result from the Coombs
test, hemolytic anemia, chorea, and chorea gravidarum.
 Discoid rash (ie, erythematous raised patch with keratotic
scaling and follicular plugging) is a criterion. Older lesions
may be atrophic. Again, the cause remains unexplained.
 Photosensitivity with an unexplained cause is another
criterion.

o Arthritis: Patients may have nonerosive arthritis involving 2 or more

peripheral joints, and the cause cannot otherwise be determined.

o Serositis: This may be (1) pleuritis or pleural effusion or (2)

pericarditis or pericardial effusion, the cause of which cannot be
explained.
 o Renal disorder: Proteinuria of 0.5 g/d or the presence of cellular
casts, without another cause, is a criterion for APS.

o Neurologic disorder: Criteria include seizures in the absence of

other causes or psychosis in the absence of other causes.
o Hematologic disorder: Features, without an otherwise explainable
cause, include (1) hemolytic anemia with reticulocytosis, (2)
leukopenia of less than 4000 cells/mm3 on at least 2 occasions, (3)
lymphopenia of less than 1500 cells/mm3, or (4) thrombocytopenia
of less than 100,000 cells/mm3.
o Immunologic disorder: Again, the cause remains unexplained.

• The clinical manifestations of SLE include the following:

o Skin lesions - 84-71%

o Arthritis - 63-95%
o Nephritis - 46-77%
o Raynaud phenomenon - 10-58%
o Neuropsychiatric features - 0-59%
o Lymphadenopathy - 0-58%
o Pleurisy - 37-56%
o Mucous membrane ulceration - 7-54%
o Pericarditis - 29-45%
o Splenomegaly - 9-18%
o Aseptic necrosis - 0-10%

Causes: Passive transfer of maternal antibodies mediate autoimmune disorders

in the fetus and newborn. The mechanism of excess autoantibody production
and immune complex formation is not well understood, although current
investigation is focused on abnormal regulator functions and the possibility of a
slow virus infection. In addition, certain genetic factors may be important, as
indicated by a number of family and twin studies for SLE and the demonstration
of an increased frequency of HLA-DR2, HLA-DR3, and HLA-DR4 null alleles in
patients with SLE.

Significant controversy still exists regarding the role of oral contraceptives in

inducing SLE. ANA associated with LP were reverted to negative when the drug
was discontinued. Some patients using the intrauterine device complain of
dysmenorrhea and recurrent infections, especially those taking prednisone and
cytotoxic drugs. Although the incidence of SLE in families was initially believed to
be no greater than in the general population, this is no longer thought to be true.

PL molecules are ubiquitous in nature and are present in the inner surface of the
cell (ie, on the inner or outer surface of the cell membrane or intracellular
organelles) and in microorganisms. Therefore, during infectious disease
processes, including viral (eg, HIV, Epstein-Barr virus [EBV], cytomegalovirus
[CMV], adenoviruses), bacterial (eg, bacterial endocarditis, tuberculosis,
Mycoplasma pneumonia), spirochetal (eg, syphilis, leptospirosis, Lyme disease),
and parasitic (eg, malaria infection), the disruption of cellular membranes may
occur during cell damage. PLs release and stimulate aPL antibodies.

The SWISS PROT protein database revealed high homology between the
hexapeptides that bind to ILA-1, ILA-3, and H-3 mAbs and the membrane
particles of different bacteria and viruses. The sequence LKTPRV showed
homology to 8 different bacteria (eg, Pseudomonas aeruginosa) and homologies
to 5 types of viruses (ie, polyoma virus, human CMV, adenovirus). The sequence
TL-RVYK shows homology to 8 different bacteria, including Haemophilus
influenzae, Neisseria gonorrhoeae, and Shigella dysenteriae, and to viruses such
as EBV and HIV. Therefore, data might support the theory predicting that epitope
mimicry is involved in the propagation of the autoimmune status.

• Autoantibodies include the following:

o Antiphospholipid

o Anticardiolipin

o Antiphosphatidylinositol

o Antiphosphatidylserine

o Antiphosphatidylcholine

o Anti–beta-2 glycoprotein I

o Antinuclear antibody

o Anti-DNA (double- or single-stranded)

o Anti-Sjögren syndrome A antibody (Ro)

o Anti-Sjögren syndrome B antibody (Ia)

• Antibodies against microorganism(s) associated with infection or

vaccination include the following:

o Antibacterial PL

o Antibacterial protein

o Antiviral glycoprotein
 o Anti-Sjögren syndrome A antibody (Ro) and anti-Sjögren syndrome
B antibody (Ia): These are associated with neonatal lupus
erythematosus, including congenital complete heart block. These
antibodies are usually present in patients with Sjögren syndrome.

Differential
Preeclampsia
Thymic tumor

Other Problems to be Considered:

Other causes of thrombocytopenia (eg, HIV infection, drug-induced

thrombocytopenia, thrombotic thrombocytopenia, gestational thrombocytopenia,
PIH, other autoimmune disease)

Workup

Lab Studies:

• APS is diagnosed when the patient has LAC IgG or IgM aCL in medium-
to-high levels, or both, on 2 occasions at least several weeks apart.

o APL antibodies are detected by conventional and specific solid-

phase or enzyme-linked immunoassays. Results are measured as
GPL (IgG aCL), MPL (IgM aCL), or aPL (immunoglobulin A [IgA]
aCL) units and reported in semiquantitative terms such as negative,
low-positive, medium-positive, or high-positive.

o Isolated IgA aCL results are also of uncertain clinical significance

and are not diagnostic of APS. An easy and reliable test would
significantly help detection and follow-up of affected patients.

o Autoantibodies include ANA, aCL antibodies, anti-DNA antibodies

(single- or double-stranded), and anti-b2GPI.

• SLE is associated with lower serum complement levels measured either

as total hemolytic complement activity CH50 or as levels of the third and
fourth components of complement C3 and C4, respectively. Decreased
levels of these are indicative of consumption by immune complexes.
However, preeclampsia is associated with an increased serum
complement level.

• Indications for testing for aPL antibodies include the following:

o Obstetric indications are as follows:

 Unexplained fetal death or stillbirth
  Recurrent pregnancy loss (3 or more spontaneous
abortions)
 Unexplained second or third trimester fetal death
 Severe preeclampsia at less than 34 weeks of gestation
 Severe fetal growth restriction

o Nonobstetric indications are as follows:

 Nontraumatic thrombosis or thromboembolism (venous or
arterial)
 Stroke, especially in individuals aged 24-50 years
 Autoimmune thrombocytopenia
 Transient ischemic attacks
 Livedo reticularis
 Hemolytic anemia
 Systemic lupus erythematosus
 False-positive serologic test result for syphilis

• Laboratory criteria for the diagnosis of APS are as follows:

o LAC is detected by PL-dependent clotting assays, without

correction with normal plasma. Results are confirmed by
demonstrating PL dependency. The activated partial thromboplastin
time is prolonged. Sera are screened for anticoagulant activity by
mixing them with platelet-pool normal sera and assaying the
activated partial thromboplastin time. Several laboratory
measurements are available for the assessment of LAC.

o For aCL or anti-b2GPI antibodies, an IgG isotype greater than 12-

20 GPL units (medium- to high-positive) detected in a standardized
assay using standard serum calibrators is indicative.

• Hematologic and serologic manifestations of APS are as follows:

o For antinuclear factor, the range is 0-94.9.

o For lupus erythematosus cells, the range is 75.7-82.

o For leukopenia with 5000 cells/mm3, the range is 0-66.9. For

leukopenia with 4000 cells/mm3, the range is 0-45.7

o For gamma globulin at 1.6 g/dL, the range is 0-77.

o For rheumatoid arthritis latex, the range is 0-57.

o For thrombocytopenia, the range is 7-26.

 o For a positive result from the Coombs test, the range is 0-23.9.

o Patients may have positive results for autoimmune hemolytic

anemia.
o The range for false-positive results from the VDRL test is 8.3-24.

Imaging Studies:

• Appropriate neurologic or imaging studies should be performed based on

clinical findings (ie, in the presence of CNS symptoms, a CT scan or MRI).

Histologic Findings: Histologically, 6 classes of lupus glomerulonephritis have

been recognized by the World Health Organization.

• Class I - Normal glomeruli observed with light microscopy; may show

deposits with immunofluorescence or electron microscopy
• Class II - Mesangial lesions
• Class III - Focal proliferative glomerulonephritis
• Class IV - Diffuse proliferative glomerulonephritis
• Class V - Membranous glomerulonephritis
• Class VI - Diffuse glomerular sclerosis

Human aCL antibodies cause placental necrosis in BALB/c mice.

Treatment

Medical Care: Pregnant women with APS are considered high-risk obstetric
patients, and medical care is instituted with this in mind. If a chromosomal
abnormality is found, genetic counseling is recommended.

• Intravenous immunoglobulin (IVIG): Infused immunoglobulins may

modulate aCL antibodies levels by 3 mechanisms.
o Antiidiotypic antibodies may be present in the IVIG preparation.
These antiidiotypic antibodies may bind autoantibodies to form
idiotype-antiidiotype dimers, resulting in neutralization of
autoantibody effects.
o Antiidiotype antibodies may bind and down-regulate B-cell
receptors, resulting in a decrease in autoantibody production.
o Antiidiotype antibodies might bind receptors of regulatory T cells,
resulting in suppression of lymphokine production and decreased
activation of autoantibody-producing B cells.

• Landry-Guillain-Barré-Strohl syndrome (LGBSS) of acute inflammatory

demyelinating polyradiculoneuropathy
o Patients usually present with progressive bilateral and symmetrical
muscle weakness accompanied by mild sensory symptoms,
 including paresthesia, numbness, and tingling. The disease can
progress to involve the respiratory muscles, resulting in respiratory
failure. Two thirds of the patients have a history of virallike
infections 1-3 weeks prior to the onset of symptoms.
o Recently, CMV infection has been incriminated as a potential
etiologic agent in some pregnant patients presenting with LGBSS.
o Acute inflammatory demyelinating polyradiculoneuropathy is a rare
disease with an incidence of approximately 1-1.5 cases per
100,000 LGBSS cases per year. LGBSS is exceedingly rare in
pregnancy.

• Obstetric care
o Patients should be counseled in all cases regarding symptoms of
thrombosis and thromboembolism and should be educated
regarding and examined frequently for the signs or symptoms of
thrombosis or thromboembolism, severe PIH, or decreased fetal
movement.
o In patients with poor obstetric histories, evidence of PIH, or
evidence of fetal growth restriction, ultrasonography is
recommended every 3-4 weeks starting at 18-20 weeks of
gestation.
o Human chorionic gonadotropin (hCG) values may suggest early
prognosis of the pregnancy outcome in the first trimester. If hCG
levels are increasing normally (ie, doubling every 2 d) in the first
month of pregnancy, a successful outcome is predicted in 80-90%
of cases. However, when the increases are abnormal (ie, slower), a
poor outcome is predicted in 70-80% of cases.
o In patients with uncomplicated APS, ultrasonography is
recommended at 30-32 weeks of gestation (ie, to evaluate
uteroplacental sufficiency).
o Low molecular weight heparin (LMWH) may be used in APS and
pregnancy (replacement of unfractionated sodium heparin).
o Importantly, counsel the patient regarding potential adverse effects
of heparin. Heparin-induced osteoporosis occurs in 1-2% of cases.
o Drugs such as chloroquine and cytotoxic agents are not
recommended during pregnancy, and patients should stop taking
these drugs several months prior to becoming pregnant.
o Warfarin may be substituted for heparin during the postpartum
period to limit further risk of heparin-induced osteoporosis and bone
fracture.
o Splenectomy during the early second trimester or at the time of
cesarean delivery may be considered in patients refractory to
glucocorticoid therapy.

• Nonobstetric care
 o Immunosuppressive agents are recommended for patients with
SLE with secondary APS.
o Thromboprophylaxis is recommended.
o Patients should be evaluated for renal disease, (glomerulonephritis,
N-stage disease), anemia, and thrombocytopenia.

Proposed Management for Women with aPL Antibodies

Management

Feature Pregnant Nonpregnant

APS with prior Heparin in prophylactic Optimal

fetal death or doses (15,000-20,000 U management
recurrent of unfractionated uncertain; options
pregnancy loss heparin or equivalent include no
per d) administered treatment or daily
subcutaneously in treatment with low-
divided doses with low- dose aspirin
dose aspirin daily
Calcium and vitamin D
supplementation

APS with prior Heparin to achieve full Warfarin

thrombosis or anticoagulation (does administered daily
stroke not cross the placenta) in doses to
maintain
International
Normalized Ratio
of 3 or greater

APS without prior No treatment or daily No treatment or

pregnancy loss treatment with low-dose daily treatment with
or thrombosis aspirin or daily low-dose aspirin
treatment with Optimal
prophylactic doses of management
heparin plus low-dose uncertain
aspirin
Optimal management
uncertain

Preeclampsia IVIG at 400 mg/kg/d for Not applicable

5 days monthly
Additional therapy is
heparin plus low-dose
 aspirin

LGBSS High-dose IVIG at 400- IVIG at 400-1500

1500 mg/kg/d for mg/kg/d for several
several days days

aPL antibodies without APS

LAC or medium- No treatment No treatment

to-high level of
aCL IgG

Low levels of No treatment No treatment

aCL IgG, only
aCL IgM, or only
aCL IgA Without
LA, aPL, or aCL

• Note the following:

o The medications shown should not be used in the presence of

contraindications.
o Close obstetric monitoring of the mother and fetus is necessary in
all cases.
o The patient should be counseled in all cases regarding symptoms
of thrombosis and thromboembolism.

Surgical Care:

• Cardiac valvular surgery is recommended in patients with severe aortic

regurgitation as a result of APS.

• Splenectomy is recommended in patients with the chronic form of

idiopathic thrombocytopenic purpura and is associated with remission in
approximately 75% cases.

• Thromboprophylaxis is recommended for any abdominal or orthopedic

surgery.

• Manage thrombotic or hemorrhagic complications. Be aware of associated

thrombocytopenia, and employ laboratory methods of perioperative
anticoagulation monitoring in the setting of prolonged clotting times.

Consultations:
 • The patient should be informed about potential maternal and obstetric
problems, including fetal loss, thrombosis or stroke, PIH, fetal growth
restriction, and preterm delivery.

• In women with APS and one or more prior thrombotic events, lifelong
anticoagulation with warfarin may be advisable to avoid recurrent
thrombosis.

Medication

In women with well-recognized obstetric APS, anticoagulant prophylaxis is

recommended during pregnancy and the postpartum period. Pregnant women
with APS are considered at risk of thrombosis and pregnancy loss. Data suggest
low-dose aspirin and heparin (either unfractionated heparin or LMWH) are the
treatments of choice for prevention of pregnancy loss in pregnant women with
APS and previous pregnancy losses. Pregnant women with APS and a history of
thrombosis but no pregnancy loss only require treatment with heparin. Treatment
is optional for patients with no history of pregnancy loss or thrombosis.

Drug Category: Heparin compounds -- Unfractionated IV heparin and

fractionated SC LMWH are the 2 choices for initial anticoagulation therapy.
Warfarin therapy may be initiated in the postpartum stage.

These are used in the treatment or prophylaxis of clinically evident intravascular

thrombosis. Special precaution should be exercised in obstetrical emergencies or
massive liver failure.

LMWHs may also be used. Similar to unfractionated heparin, LMWHs are a class
of anticoagulants termed glycosaminoglycans. LMWHs are derived from
unfractionated heparin but have smaller, more standard average masses than
heterogeneous unfractionated heparin.

Unlike standard heparin, LMWHs have higher specificity for factor Xa and have
fewer effects on platelet activity. As a result, LMWH may cause bleeding less
often, while still retaining anticoagulant effects. LMWHs may be associated with
less risk of heparin-induced osteoporosis.

Drug Name Heparin, unfractionated (Hep-Lock) --

Indicated to decrease risk of thrombosis
and pregnancy loss in pregnant women
with APS.
Augments activity of antithrombin III and
prevents conversion of fibrinogen to
fibrin. Does not actively lyse but is able to
inhibit further thrombogenesis. Prevents
reaccumulation of clot after spontaneous
 fibrinolysis.
APS with prior fetal death/recurrent
pregnancy loss: 15,000-20,000 U/d SC
divided q12h plus low-dose aspirin
APS with prior thrombosis or stroke:
Adult Dose Adjusted dose heparin SC q12h to
maintain aPTT within target range
APS without prior pregnancy loss or
thrombosis: 15,000-20,000 U/d SC
divided q12h (treatment optional)
Pediatric Dose Adolescents: Administer as in adults
Documented hypersensitivity; subacute
bacterial endocarditis, active bleeding,
Contraindications
history of heparin-induced
thrombocytopenia
Digoxin, nicotine, tetracycline, and
antihistamines may decrease effects;
Interactions NSAIDs, aspirin, dextran, dipyridamole,
and hydroxychloroquine may increase
toxicity
C - Safety for use during pregnancy has
Pregnancy
not been established.
Hemorrhage, monitor aPTT, adjust dose
accordingly; caution in severe
Precautions
hypotension and shock; heparin-induced
osteoporosis
Enoxaparin (Lovenox) -- Indicated to
decrease risk of thrombosis and
pregnancy loss in pregnant women with
APS.
Prevents DVT, which may lead to
pulmonary embolism in patients
Drug Name
undergoing surgery who are at risk for
thromboembolic complications. Enhances
inhibition of factor Xa and thrombin by
increasing antithrombin III activity. In
addition, preferentially increases
inhibition of factor Xa.
Adult Dose APS with prior fetal death/recurrent
pregnancy loss: 40 mg/d SC plus low-
dose aspirin
APS with prior thrombosis or stroke: 1
mg/kg SC q12h
 APS without prior pregnancy loss or
thrombosis: 40 mg/d SC (treatment
optional)
Pediatric Dose Adolescents: Administer as in adults
Documented hypersensitivity; major
Contraindications
bleeding, thrombocytopenia
Platelet inhibitors or oral anticoagulants
such as dipyridamole, salicylates, aspirin,
Interactions
NSAIDs, sulfinpyrazone, and ticlopidine
may increase risk of bleeding
B - Usually safe but benefits must
Pregnancy
outweigh the risks.
If thromboembolic event occurs despite
LMWH prophylaxis, discontinue drug and
initiate alternate therapy; elevation of
hepatic transaminases may occur but is
reversible; heparin-associated
thrombocytopenia may occur with
Precautions
fractionated or LMWH; 1 mg of protamine
sulfate reverses effect of approximately 1
mg of enoxaparin if significant bleeding
complications develop; heparin-induced
osteoporosis; monitor target anti-Xa
levels, adjust dose accordingly

Drug Category: Antiplatelet agents -- Randomized controlled trials

demonstrate improved fetal survival when pregnant women with APS and prior
pregnancy losses are treated with low-dose aspirin plus heparin compared to
low-dose aspirin alone.

Aspirin (Anacin, Ascriptin, Bayer Aspirin,

Bayer Buffered Aspirin) -- Antiplatelet
effect indicated to decrease risk of
thrombosis and pregnancy loss in
pregnant women with APS. Inhibits
Drug Name prostaglandin synthesis, preventing
formation of platelet-aggregating
thromboxane A2. Used in low dose to
inhibit platelet aggregation and improve
complications of venous stasis and
thrombosis.
1-2 mg/d PO for antiplatelet effect; not to
Adult Dose
exceed 325 mg/d (low-dose aspirin)
 Pediatric Dose Adolescents: Administer as in adults
Documented hypersensitivity; liver
damage, hypoprothrombinemia, vitamin K
deficiency, bleeding disorders, asthma;
Contraindications
due to association of aspirin with Reye
syndrome, do not use in children (<16 y)
with flu
Effects may decrease with antacids and
urinary alkalinizers; corticosteroids
decrease salicylate serum levels; additive
hypoprothrombinemic effects and
increased bleeding time may occur with
Interactions coadministration of anticoagulants; may
antagonize uricosuric effects of
probenecid and increase toxicity of
phenytoin and valproic acid; doses >2 g/d
may potentiate glucose-lowering effect of
sulfonylurea drugs
C - Safety for use during pregnancy has
Pregnancy
not been established.
Pregnancy category D in third trimester
with full-dose aspirin; may cause
transient decrease in renal function and
Precautions aggravate chronic kidney disease; avoid
use in patients with severe anemia, with
history of blood coagulation defects, or
taking anticoagulants

Follow up

Further Inpatient Care:

• Institute inpatient care as appropriate for the clinical findings.

Further Outpatient Care:

• Institute outpatient care as appropriate for clinical findings.

• Grief support may be indicated for families who experience perinatal

losses.

Special Concerns:
• Regarding corticosteroid therapy, administer supplementation to cover the
labor or cesarean delivery in patients currently receiving steroids or those
recently treated with these drugs.

• No evidence indicates adverse effects related to breastfeeding, although

breastfeeding is not recommended if high doses of cytotoxic or
immunosuppressive agents are required.

• Pregnancy in itself is not harmful to the mother or the baby unless the
added work related to the newborn and the emotional stress in the family
prove to be too much for a particular patient. Therapeutic abortions are
generally not indicated in pregnant women with autoimmune disease.

• Epidural anesthetic is not recommended if the mother has a marked drop

in the maternal platelet count.

• The use of forceps or the vacuum extractor should be individualized.