AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Recognized for its associated thrombosis in the 1950s, antiphospholipid syndrome (APS) and lupus anticoagulant (LAC) are associated with pregnancy complications that include fetal loss, fetal growth restriction, preeclampsia, thrombosis, and autoimmune thrombocytopenia. It is characterized by an autoimmune process that is separate in many women from systemic lupus erythematosus (SLE) and other connective tissue diseases. Diagnosis requires clinical and laboratory findings with the clinical criteria being the primary method of diagnosis. Women with the clinical features should be tested for LAC and anticardiolipin (aCL) antibodies; most patients with APS have both LAC and aCL immunoglobulin G (IgG) antibodies.

APS is classified as primary or secondary depending on its association with other autoimmune disorders. Primary antiphospholipid syndrome is diagnosed in patients demonstrating the clinical and laboratory criteria without other recognized autoimmune disease. Secondary antiphospholipid syndrome is diagnosed in patients with other autoimmune disorders such as SLE.

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

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

For related information on pregnancy, see Medscape's Pregnancy Resource Center.

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 with 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 neurologic 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.

See Medscape's CME activity, Mechanisms of Disease: Antiphospholipid Antibodies -- From Clinical Association to Pathologic Mechanism.

Frequency

United States

Women have been reported to account for approximately 80% of patients with APS.

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 and mesenteric veins). The aPL antibodies are detected in approximately 2% of patients with nontraumatic venous thrombosis. 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.

SLE occurs in approximately 120 cases per 100,000 population and causes pregnancy complications in approximately 45 cases per 100,000 pregnant population. 

Mortality/Morbidity

APS is one of the major causes of thrombosis and its complications in women. Arterial and venous thrombosis are both reported. Coronary artery occlusions are reported in patients with APS. Previous thrombosis in the face of the diagnosis of APS has been documented to have a rate of recurrence of 25% per year if untreated.

Maternal morbidity

Thrombosis, especially in patients with APS and a history of thrombosis is a major concern. Morbidity may also be associated with anticoagulation in patients treated with heparin or low molecular weight heparins in pregnancy. Women with APS have an increased incidence of preeclampsia, which is frequently prior to 34 weeks’, and severe preeclampsia requiring premature delivery. 

APS is also associated with infertility and pregnancy complications such as spontaneous abortions, prematurity, and stillbirths.

Maternal mortality

Mortality rates during pregnancy are not well characterized. Multiorgan failure has been described during pregnancy by Asherson¹ and during postpartum by Kochenour.² 

Perinatal Morbidity

aPL antibodies are found in 10-15% of women at high risk for fetal growth restriction. Neonatal morbidity and mortality may be influenced by indicated preterm delivery for maternal severe preeclampsia or fetal growth restriction.

Neonatal lupus dermatitis, a variety of systemic and hematologic abnormalities, and isolated congenital heart block have been associated with APS and SLE.

Perinatal Mortality

Fetal deaths at or beyond 20 weeks' gestation may be attributed to APS involvement. 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.³

Sex

Most cases of APS (80%) are in women.

Age

APS is predominantly diagnosed in reproductive-aged women (ie, 15-55 y). This is similar to other autoimmune states.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

See Medscape's CME activity, Mechanisms of Disease: Antiphospholipid Antibodies -- From Clinical Association to Pathologic Mechanism.

History

The “International consensus statement for the diagnosis of antiphospholipid syndrome” was published in 1999 by Wilson et al.⁴ This serves as a set of criteria similar to the criteria for the diagnosis of other autoimmune disorders. Diagnosis of antiphospholipid syndrome (APS) requires at least 1 clinical and 1 laboratory criterion.

Clinical criteria

Vascular thrombosis 

• One or more clinical episodes of arterial, venous, or small-vessel thrombosis, occurring within any tissue or organ

Complications of pregnancy

• One or more unexplained deaths of morphologically normal fetuses at or after 10 weeks’ gestation
• One or more premature births of morphologically normal fetuses at or before 34 weeks’ gestation
• Three or more unexplained consecutive spontaneous abortions before 10 weeks’ gestation

Laboratory criteria

• Anticardiolipin antibodies - Anticardiolipin IgG or IgM antibodies present at moderate or high levels in the blood on 2 or more occasions at least 6 weeks apart
• Lupus anticoagulant - Lupus anticoagulant antibodies detected in the blood on 2 or more occasions at least 6 weeks apart, according to the guidelines of the International Society on Thrombosis and Hemostasis

Physical

APS is primarily a diagnosis based on clinical history and laboratory data. Some physical findings may be associated with primary APS, but patients with secondary APS are more likely to have findings on physical examination.       

•  Thrombosis or stroke - Possible residual neurologic findings
• 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.

The following are physical findings that should be considered secondary to other autoimmune disorders and an appropriate evaluation should be undertaken.

• Arthritis: Patients may have nonerosive arthritis involving 2 or more peripheral joints, and the cause cannot otherwise be determined.
• Serositis: This may be (1) pleuritis or pleural effusion or (2) pericarditis or pericardial effusion, the cause of which cannot be explained.
• Renal disorder: Proteinuria of 0.5 g/d or the presence of cellular casts, without another cause, is a criterion for APS.
• Neurologic disorder: Criteria include seizures in the absence of other causes or psychosis in the absence of other causes.
• 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.
• Immunologic disorder: Again, the cause remains unexplained.

The clinical manifestations of SLE include the following:  

• Skin lesions - 84-71%
• Arthritis - 63-95%
• Nephritis - 46-77%
• Raynaud phenomenon - 10-58%
• Neuropsychiatric features - 0-59%
• Lymphadenopathy - 0-58%
• Pleurisy - 37-56%
• Mucous membrane ulceration - 7-54%
• Pericarditis - 29-45%
• Splenomegaly - 9-18%
• Aseptic necrosis - 0-10%
• 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.

Causes

Like other autoimmune disorders, APS does not have a known etiology.

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 systemic lupus erythematosus (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. Antinuclear antibodies (ANAs) 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:  
• • Antiphospholipid
  • Anticardiolipin
  • Antiphosphatidylinositol
  • Antiphosphatidylserine
  • Antiphosphatidylcholine
  • Anti–beta-2 glycoprotein I
  • Antinuclear antibody
  • Anti-DNA (double- or single-stranded)
  • Anti-Sjögren syndrome A antibody (Ro)
  • Anti-Sjögren syndrome B antibody (Ia)
• Antibodies against microorganism(s) associated with infection or vaccination include the following:  
• • Antibacterial PL
  • Antibacterial protein
  • Antiviral glycoprotein
  • 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.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

In women meeting the clinical criteria of early pregnancy loss, care must be taken to assure that the evaluation of spontaneous abortions prior to the 10 weeks’ gestation has included the appropriate evaluation to be considered unexplained.

Other causes of thrombocytopenia such as HIV infection, drug-induced thrombocytopenia, thrombotic thrombocytopenia, gestational thrombocytopenia, and preeclampsia should be considered. Other autoimmune disease should be ruled out in patients with thrombocytopenia.

Many manifestations of SLE can be seen in women with APS. A complete evaluation to exclude SLE as a primary disorder is appropriate if symptoms are present.

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Antiphospholipid syndrome (APS) is diagnosed when the patient has lupus anticoagulant (LAC) or IgG or IgM anticardiolipin (aCL) in medium-to-high levels, or both, on 2 occasions at least several weeks apart.  
• • Antiphospholipid (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 (IgA aCL) units and reported in semiquantitative terms such as negative, low-positive, medium-positive, or high-positive.
  • 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.
  • Autoantibodies include antinuclear antibodies (ANAs), 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:  
• • Obstetric indications
  • • Unexplained fetal death or stillbirth
    • Recurrent pregnancy loss (3 or more spontaneous abortions with no more than 1 live birth)
    • Unexplained second or third trimester fetal death
    • Severe preeclampsia at less than 34 weeks’ gestation
    • Unexplained severe fetal growth restriction
    • Chorea gravidarum
  • Nonobstetric indications 
  • • Nontraumatic thrombosis or thromboembolism (venous or arterial)
    • Stroke, especially in individuals aged 24-50 years
    • Unexplained transient ischemic attack
    • Unexplained amaurosis fugax 
    • Autoimmune thrombocytopenia
    • Autoimmune hemolytic anemia
    • Unexplained prolongation of a clotting assay
    • Transient ischemic attacks
    • Livedo reticularis
    • SLE or other connective tissue disorder
    • False-positive serologic test result for syphilis
• Laboratory criteria for the diagnosis of APS are as follows:  
• • 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 (aPTT) is prolonged. Sera are screened for anticoagulant activity by mixing them with platelet-pool normal sera and assaying the aPTT. Several laboratory measurements are available for the assessment of LAC.
  • 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 values of APS are as follows:  
• • Lupus anticoagulant 
  • • Prolonged clotting times with any of the following:  
    • • aPTT
      • Kaolin clotting time
      • Dilute Russell viper venom time
      • Plasma clotting time
    • These prolongations should be confirmed with one of the following:
    • • Mixing studies with normal plasma, clotting time will remain prolonged with LA
      • Platelet neutralization test (recommended by some authorities
  • Anticardiolipin antibodies: Many aCL antibodies correlate poorly with the clinical manifestations of APS. At present, only IgG and IgM in moderate and high levels are recommended to be used in the diagnosis of APS.
  • False-positive results from the VDRL test may be present.
  • All studies need to be repeated in at least 6 weeks for confirmation before the diagnosis of APS is appropriate.

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

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical Care

Pregnant women with antiphospholipid antibody syndrome (APS) are considered high-risk obstetric patients, and medical care is instituted with this in mind.

• Obstetric care
• • 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 preeclampsia, or decreased fetal movement.
  • In patients with poor obstetric histories, evidence of preeclampsia, or evidence of fetal growth restriction, ultrasonography is recommended every 3-4 weeks starting at 18-20 weeks’ gestation.
  • Human chorionic gonadotropin (hCG) values in the first trimester can be followed to evaluate the viability of the pregnancy. 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. Initiation of heparin in the face of a failing pregnancy should be undertaken with caution due to bleeding risks.
  • In patients with uncomplicated APS, ultrasonography is recommended at 30-32 weeks’ gestation to assess fetal growth. Lagging fetal growth may reflect uteroplacental insufficiency in patients with APS.
  • Anticoagulation with heparin is recommended in APS and pregnancy. Low molecular weight heparin (LMWH) may be used in these patients.
  • Importantly, counsel the patient regarding potential adverse effects of heparin. Heparin-induced osteoporosis occurs in 1-2% of cases.
  • 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.
  • Warfarin may be substituted for heparin during the postpartum period to limit further risk of heparin-induced osteoporosis and bone fracture.
  • Splenectomy during the early second trimester or at the time of cesarean delivery may be considered in patients with thrombocytopenia refractory to glucocorticoid therapy.
  • Bone density studies should be considered in patients receiving anticoagulation with heparin or LMWH due to the risks of osteopenia. This may be most important in women who have been treated in a previous pregnancy or are planning pregnancy.
• Intravenous immunoglobulin (IVIG): Infused immunoglobulins may modulate aCL antibodies levels by 3 mechanisms.
• • 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.
  • Antiidiotype antibodies may bind and down-regulate B-cell receptors, resulting in a decrease in autoantibody production.
  • 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 can be seen in patients with APS and lupus.  
• • 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 viral-like infections 1-3 weeks prior to the onset of symptoms.
  • Recently, CMV infection has been incriminated as a potential etiologic agent in some pregnant patients presenting with LGBSS.
  • 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.
• Nonobstetric care  
• • Immunosuppressive agents are recommended for patients with SLE with secondary APS.
  • Thromboprophylaxis is recommended.
  • Patients should be evaluated for renal disease, (glomerulonephritis, end-stage renal disease), anemia, and thrombocytopenia.

Table. Proposed Management for Women With aPL Antibodies

Note the following:

• The medications shown should not be used in the presence of contraindications.
• Close obstetric monitoring of the mother and fetus is necessary in all cases.
• The patient should be counseled in all cases regarding symptoms of thrombosis and thromboembolism.

Surgical Care

Patients with APS, especially secondary APS, may require surgical interventions for long-standing complications of their autoimmune disorder.

• Cardiac valvular surgery is recommended in patients with severe aortic regurgitation due to the noninfectious vegetations that are seen 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 use 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. Consultation with specialists in Maternal-Fetal Medicine and Rheumatology should be considered.
• In women with APS and one or more prior thrombotic event, lifelong anticoagulation with warfarin may be advisable to avoid recurrent thrombosis. An assessment by a Rheumatologist or Hematologist may also be helpful.

MEDICATION

Section 7 of 11  

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• Introduction
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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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 for 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 intravenous (IV) heparin and fractionated subcutaneous (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 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 with low-dose aspirin alone.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Stella Nowicki, DDS; Gregory Locksmith, MD; and Bogdan Nowicki, MD, PhD to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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12. Branch DW, Silver R, Pierangeli S, et al. Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome. Obstet Gynecol. Apr 1997;89(4):549-55. [Medline].
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Article Last Updated: Aug 11, 2008