Recurrent early (pre-embryonic or embryonic) miscarriage: Despite the general recommendation of combined therapy with aspirin and heparin for all women with obstetric APS, data from observational studies in this subgroup of women have reported 79% to 100% pregnancy success rates with low-dose aspirin.25 Therefore, the option of monotherapy with aspirin may be a valid option in selected cases within the subgroup of women with recurrent early miscarriages.
Fetal death (>10 weeks’ gestation) or prior early delivery (<34 weeks’ gestation) due to severe pre-eclampsia or placental insufficiency: Combination therapy with aspirin and heparin in this category of patients is recommended. Aspirin is best started before conception, and then unfractionated heparin or low–molecular weight heparin (LMWH) can be given once pregnancy has been confirmed.25
Antiphospholipid syndrome with thrombosis: In patients with APS who have suffered a previous thrombosis, low-dose aspirin and therapeutic dose heparin or LMWH at anticoagulant doses are recommended.25 The change from warfarin to heparin should be achieved prior to six weeks’ gestation to avoid exposing the mother to the potential teratogenic effects of vitamin K-antagonists.
Postpartum period: Heparin should be continued intrapartum and postpartum until the patient is ready to start therapy with vitamin K-antagonists. Both warfarin and subcutaneous heparin are compatible with breastfeeding. Antithrombotic coverage of the postpartum period is also recommended in women with aPLs who have not had a previous thrombosis. Prophylactic-dose heparin or LMWH is recommended. The duration is variable, ranging from one to six weeks, and should be tailored according to the presence of additional risk factors.
Novel Oral Anticoagulants
The novel oral anticoagulants, dabigatran etexilate and rivaroxaban, are rapidly absorbed and have been shown to be effective in the management of venous thromboembolism. They may be considered as potential new therapies for the management of thrombosis in APS without the need for laboratory monitoring.26,27 A clinical trial with rivaroxaban is currently underway to elucidate its safety and efficacy in the prevention of thrombosis in APS.28
Statins
The recent consensus guidelines advocate the use of statins as adjuvant therapy. This rationale is based on their pleiotropic effects; in addition to lowering lipid levels, they also have antiinflammatory and antithrombotic effects.17,29 For example, a recent study by Lopez-Pedrera et al revealed that fluvastatin modulates a chain of events involving the downregulation of tissue factors, adhesion molecules, and downstream signaling and transcription factors in monocytes.30 This may attenuate the procoagulant state seen in APS.
Hydroxychloroquine
Hydroxychloroquine (HCQ) is an antimalarial drug commonly used in the management of SLE due to its antiinflammatory and antithrombogenic properties. The consensus guidelines recommend the use of HCQ as an alternative treatment modality in patients with recurrent APS.17
Rituximab
Rituximab is a CD-20 monoclonal antibody commonly used in the treatment of rheumatoid arthritis. In a recent uncontrolled and nonrandomized pilot study to evaluate the safety of rituximab in aPL-positive patients with non-criteria manifestations of APS, Erkan et al suggested that the safety of rituximab in aPL-positive patients is consistent with the general safety profile of this drug.31 Despite the lack of observing any substantial change in aPL profiles, rituximab may be effective in controlling some, but not all, non-criteria manifestations of APS.
Conclusion
Since its first description three decades ago, APS is now recognized as a common autoimmune disorder, linking immunology with thrombovascular disease. Ongoing research into the pathogenesis, diagnosis, and management of APS has significantly contributed to the understanding of this syndrome, and introduced the concept that some individuals with connective tissue diseases require anticoagulation, rather than steroids or antiinflammatory treatments.
