Eculizumab in a pregnant patient with laboratory onset of catastrophic antiphospholipid syndrome

Abstract

Rationale:Hypercoagulability and pregnancy morbidity are hallmarks of the antiphospholipid syndrome (APS). Catastrophic antiphospholipid syndrome (CAPS) is a potentially life-threatening omplication of APS, with widespread acute thrombotic microangiopathy (TMA) that can be precipitated by pregnancy and delivery and result in multiorgan damage. Unrestrained activation of the complement cascade is involved, favoring endothelial activation, tissue factor expression by leukocytes, and platelet aggregation. The complement block, which interrupts this amplification cycle, could prevent CAPS in patients with early TMA who face precipitating events.Patient concerns:We present a nulliparous pregnant woman with APS at the 30+6 week of gestation who has developed thrombocytopenia, intravascular hemolysis, elevated creatinine, proteinuria, and hematuria.Diagnoses:These featurs were compatible with the diagnosis of CAPS. Consensually, serum C3 protein levels were rapidly decreasing, reflecting complement consumption.Interventions:She was treated with eculizumab, a humanized monoclonal antibody against C5 that prevents the formation of the complement membrane attack complex.Outcomes:Laboratory parameters improved and the patient did not develop thrombosis or detectable organ/tissue damage. The patient safely delivered by cesarean section at week 32 of gestation a healthy 1640 g male infant. After 5 days, she received additional eculizumab, with complete resolution of the clinical condition. Low complement activity was detectable in the infant blood for a week after delivery. No infectious complication occurred.Lessons:Inhibition of the terminal complement activation is safe and might be effective in patients with APS developing early TMA, enabling safe delivery and preventing thrombotic events both in the mother and in the newborn.

Prevention of Pregnancy Complications in Antiphospholipid Syndrome

“…37 A recent study confirmed this finding and histologic examinations showed vasculopathy and intervillous thrombi as the most common finding in OAPS placentae. 38 Furthermore, treatment of catastrophic, multiorgan thrombi in APS with eculizumab, a complement blocking agent, 39,40 supports the role of complement activation in APS and will have implication on therapeutic perspectives especially in women who fail standard of care 41 and other therapies may emerge in the future. 33 The scientific discussion is still ongoing 42 and could result in additional therapeutic concepts.…”

The immunology of the fetal–placental unit comes of age

“…see [15]). Complement activation plays an important role in the pathogenesis, and molecular interventions targeting the pathway hold promise for prevention of the uncommon but life-threatening complication, the catastrophic APS (e.g.…”

“…Complement activation plays an important role in the pathogenesis, and molecular interventions targeting the pathway hold promise for prevention of the uncommon but life-threatening complication, the catastrophic APS (e.g. see [15]). Proteins that physiologically curb the activation of complement, such as decay accelerating factor (DAF, CD55) and the membrane co-factor protein (MCP, CD46) are expressed in the placenta.…”

Peripartum hyperhemolysis prophylaxis and management in sickle cell disease: A case report and narrative review

“…47,49,50 It has also been suggested that low complement levels may be related to prematurity associated with the underlying disease. 51,52 Further data are needed to conclusively determine whether this drug is safe to be used during pregnancy. Although there are published cases of HS complicating pregnancy, ours is the first published case of hyperhemolysis prophylaxis in a pregnant patient.…”