Recurrent thrombosis prevention with intravenous immunoglobulin and hydroxychloroquine during pregnancy in a patient with history of catastrophic antiphospholipid syndrome and pregnancy loss

Abstract

We report a case of a 36-year old patient with prior history of thrombosis in a setting of antiphospholipid antibody syndrome (APS) as well as pregnancy-associated catastrophic antiphospholipid syndrome (CAPS), resulting in multi-organ infarction and pregnancy loss. The episode of CAPS occurred while she was receiving antepartum low-dose aspirin and therapeutic-dose enoxaparin. This patient presented again at 6 weeks gestation and ultrasounds were consistent with fetal growth restriction, concerning for placental insufficiency and thrombosis. This time, hydroxychloroquine and monthly intravenous immunoglobulin (IVIG) infusions were added to her prophylaxis regimen, resulting in a successful delivery. Platelet count and antiphospholipid antibody titers were routinely monitored throughout pregnancy as markers of disease activity for APS. Current thromboprophylaxis guidelines do not address therapeutic options to prevent further pregnancy morbidity in women who develop recurrent episodes of thrombosis or CAPS despite receiving adequate anti-thrombotic treatment. Use of hydroxychloroquine and IVIG has been associated with good outcomes in this subset of patients.

The role of hydroxychloroquine in catastrophic antiphospholipid syndrome case: Series of two case reports and review of literature

“…Eventually, the patient was able to deliver successfully. 12 HCQ was able to prevent CAPS in combination with IVIG, which ultimately led to successful treatment. It was difficult to tell in our cases whether HCQ had solely resulted in the dramatic improvement; nevertheless, its antithrombotic synergy effect with corticosteroids, aspirin, plasmapheresis, anticoagulants and IVIG was undeniably recognized.…”

Additional Treatments for High-Risk Obstetric Antiphospholipid Syndrome: a Comprehensive Review

“…Mar et al [26] 2014 Case report 0.5 mg kg −1 month −1 from week 8 (7 total doses) Favourable Watanabe et al [27] 2014 Case series 400 mg kg −1 day −1 for 5 days from week 6 or 7 Live birth rate 100 % Rose et al [28] 2014 Case report 1 g kg −1 week −1 from week 9 IUGR, stillbirth at 21 weeks IVIG intravenous immunoglobulins, LDA low-dose aspirin, IUGR intrauterine growth restriction Table 2 Effect of apheresis procedures administered in addition to other treatments in high-risk pregnancies of patients with antiphospholipid syndrome…”

“…Whilst steroids and aphaeresis procedures are currently considered additional therapies [72,73], data on the usefulness of IVIG in obstetric APS are conflicting [18][19][20][21][22][23][24][25][26][27][28][74][75][76]. The use of IVIG in pregnant APS women is rare and is generally considered a second-line treatment when other more standardized therapies have failed [77].…”

“…In addition, IVIG infusion was shown to prevent obstetric complications in APS animal models, possibly preventing the binding of antiphospholipid antibodies to the trophoblast [84]. It is interesting that IVIG resulted beneficial in most cases [18][19][20][21][22][23][24][25][26][27]78] when administered in addition to the first-line therapy, but it had only a slight [74] or no effect at all [75,76] when used alone as the first-line treatment. However, as the literature shows heterogeneous data with respect to IVIG dosing, timing of administration and concomitant treatment used (heparin, aspirin or steroids), it is difficult to draw well definite conclusions about IVIG benefits in obstetric APS.…”

“…The protocols outlined above fail in about 20 % of pregnant APS women [17], and additional treatments including intravenous immunoglobulins (IVIG) [18][19][20][21][22][23][24][25][26][27][28] (Table 1), low-dose prednisolone [29], or aphaeresis procedures such as plasma exchange or immunoadsorption [30][31][32][33][34][35][36][37] have, at times, been combined with conventional therapies (Table 2). Due to the low number of treated cases, the efficacy of these protocols is at present not well established.…”