Whitney J. Palmer
June 13, 2019
EULAR has issued new treatment guidelines for antiphospholipid syndrome, a disorder of the immune system that causes blood clots. Among the recommendations, high risk individuals who carry the antiphospholipid antibody should take low-dose aspirin, even if they are asymptomatic. This also applies to systemic lupus erythematosus patients and women with a history of obstetric antiphospholipid syndrome.
The guidelines were recently published in the Annals of the Rheumatic Diseases. Here, we highlight the treatment recommendations.
Overarching principles
Identifying the presence of factors associated with high risk for thrombotic and obstetric events is critical in-patient management.
The guidelines for cardiovascular disease prevention in the general population should be followed. Screening for and management of venous thrombosis risk factors are also recommended.
All patients treated with vitamin K antagonists should receive counseling about treatment adherence, the need for close international normalized ratio monitoring, especially in newly initiated treatment settings or bridging with heparin, the protocol of perioperative bridging therapy with heparin, and drug and food interactions.
Recommendations for primary thromboprophylaxis in antiphospholipid antibody-positive patients
In asymptomatic carriers of the antiphospholipid antibody (aPL) (not fulfilling vascular or obstetric antiphospholipid syndrome classification criteria) with a high-risk profile with or without traditional risk factors, prophylactic treatment with low-dose aspirin (75-100 mg daily) is recommended.
In patients with lupus and no thrombosis history or pregnancy complications:
With high-risk aPL profile, prophylactic treatment with low-dose aspirin is recommended.
With low-risk aPL profile, prophylactic treatment with low-dose aspiring may be considered.
In non-pregnant women with a history of obstetric antiphospholipid antibody only (with or without lupus), prophylactic treatment with low-dose aspirin after adequate risk/benefit evaluation is recommended.
Recommendations for secondary thromboprophylaxis
In patients with definite antiphospholipid syndrome and first venous thrombosis:
Treatment with vitamin K antagonists with a target international normalized ratio of two to three is recommended.
Rivaroxaban should not be used in patients with triple antiphospholipid antibody positivity due to the high risk of recurrent events. Consider direct oral anticoagulants in patients unable to achieve a target international normalized ratio despite good adherence to vitamin K antagonists or in those with contraindications to vitamin K antagonists.
In patients with unprovoked first venous thrombosis, anticoagulation should be continued long-term.
In patients with provoked first venous thrombosis, therapy should be continued for a duration recommended for patients without antiphospholipid syndrome according to international guidelines. Consider longer anticoagulation in patients with high-risk antiphospholipid antibody profile in repeated measurements or other risk factors for recurrence.
In patients with definite antiphospholipid syndrome and recurrent venous thrombosis despite treatment with vitamin K antagonists with a target international normalized ratio of two to three:
Investigation of, and education on, adherence to vitamin K treatment, along with frequent international normalized ratio testing, should be considered.
If the target international normalized ratio of two-to-three had been achieved, addition to low-dose aspirin, increase the international normalized ratio target to three to four or changed to low molecular weight heparin may be considered.
In patients with definite APS and first arterial thrombosis:
Treatment with vitamin K antagonists is recommended over treatment with low-dose aspirin only.
Treatment with vitamin K antagonists with an international normalized ratio of two to three or three to four is recommended, considering the individual’s risk of bleeding and recurrent thrombosis. Treatment with vitamin K antagonists with an international normalized ratio of two to three plus low-dose aspiring may also be considered.
Rivaroxaban should not be used in patients with triple antiphospholipid antibody positivity and arterial events. Based on the current evidence, it is not recommended to use direct oral anticoagulants in patients with definite APS and arterial events due to the high risk of recurrent thrombosis.
In patients with recurrent arterial thrombosis despite adequate treatment with vitamin K antagonists, after evaluating for other potential causes, an increase of an international normalized ratio target to three to four, adding low-dose aspirin or switching to low-molecular weight heparin can be considered.
Obstetric antiphospholipid syndrome
In women with a high-risk antiphospholipid antibody profile, but no history of thrombosis or pregnancy complications (with or without lupus), treatment with low-dose aspirin (75-100 mg daily) during pregnancy should be considered.
In women with a history of obstetric antiphospholipid syndrome only (no prior thrombotic events), with or without lupus:
With a history of more than three recurrent spontaneous miscarriages at less than the 10th week of pregnancy, and in those with a history of fetal loss at more than the 10th week of pregnancy, combination treatment with low-dose aspirin and heparin at prophylactic dosage during pregnancy is recommended.
With a history of delivery at less than 34 weeks gestation due to eclampsia or severe pre-eclampsia or due to recognized features of placental insufficiency, treatment with low-dose aspirin or low-dose aspirin and heparin at prophylactic dosage is recommended after considering the individual’s risk profile.
With clinical “non-criteria” obstetric antiphospholipid syndrome, low-dose aspirin treatment alone or in combination with heparin might be considered based on the individual’s risk profile.
With obstetric antiphospholipid syndrome treated with prophylactic dose heparin during pregnancy, continuation of heparin at prophylactic dose for six weeks after delivery should be considered to reduce the risk of maternal thrombosis.
In women with “criteria” obstetric antiphospholipid syndrome with recurrent pregnancy complications despite combination treatment with low-dose aspirin and heparin at prophylactic dosage, increasing the heparin dose to a therapeutic dose or adding hydroxychloroquine or low-dose prednisolone in the first trimester may be considered. Use of intravenous immunoglobulin might be considered in highly selected cases.
In women with a history of thrombotic antiphospholipid syndrome, combination treatment of low-dose aspirin and heparin at therapeutic dosage during pregnancy is recommended.
Catastrophic antiphospholipid syndrome
Early diagnosis and management of infections and minimization of discontinuation or low-intensity anticoagulation, especially perioperatively, are recommended.
Heparin and plasma exchange or intravenous immunoglobulin is recommended over single agents as the first-line treatment of patients with catastrophic antiphospholipid syndrome.
Concurrent treatment of precipitating factors is also recommended.
For refractory catastrophic antiphospholipid syndrome, B cell depletion (e.g., rituximab) or complement inhibition (e.g., eculizumab) therapies may be considered based on data from case reports.
REFERENCE:
Tektonidou M, Andreoli L, Limper M, et al. “EULAR recommendations for the management of antiphospholipid syndrome in adults," Annals of Rheumatic Diseases (2019), DOI: 10.1136/annrheumdis-2019-215213.
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