In one line
SLE and antiphospholipid syndrome (APS) are placental and multi-system diseases in which outcome is decided before conception by disease quiescence, antibody profile and drug optimisation — the consultant's job is to risk-stratify on the antibody profile, continue hydroxychloroquine and aspirin ± heparin, and not mistake a lupus flare for pre-eclampsia.
This chapter assumes the diagnostic and first-line groundwork in recurrent pregnancy loss, pre-eclampsia & HELLP basics and hypertension in pregnancy; the consultant-level content is the antibody-driven risk stratification, the subtype-specific regimens, and the judgement calls.
Aetiology & pathophysiology — the subtypes a consultant must separate
That APS is an antibody-mediated prothrombotic/placental disease and that SLE is a multi-system autoimmune disease is assumed. The discriminating step is recognising that "SLE/APS in pregnancy" is not one disease but a family of phenotypes, each with a different dominant mechanism and a different management consequence. Get the phenotype wrong and you give the wrong drug.
- Thrombotic APS (prior venous and/or arterial thrombosis). Mechanism: aPL antibodies activate endothelium, platelets and complement and inhibit natural anticoagulant pathways, producing a systemic thrombotic tendency that the placenta merely shares. Consequence: this woman needs therapeutic anticoagulation lifelong and in pregnancy — her risk is maternal thrombosis first, fetal loss second.
- Obstetric APS (clinical criterion is pregnancy morbidity — recurrent early loss, one fetal death ≥10 weeks, or delivery <34 weeks for pre-eclampsia with severe features/placental insufficiency — without thrombosis). Mechanism here is less about large-vessel thrombosis and more about a direct antibody effect on trophoblast: aPL bound to β2-glycoprotein-I on the syncytiotrophoblast surface impairs trophoblast proliferation, invasion and hCG secretion, and drives complement activation (C5a) and a local inflammatory placentopathy. This is why heparin's benefit in obstetric APS is plausibly anti-complement and anti-inflammatory, not just anticoagulant — and why prophylactic, not therapeutic, dosing is the standard.
- Non-criteria / seronegative obstetric APS. Persistent clinical picture with low-titre or "non-criteria" antibodies (e.g. IgA anti-β2GPI, anti-phosphatidylserine/prothrombin), or recurrent morbidity with negative standard assays. A real entity but a diagnostic trap — do not anticoagulate on a single weak result; repeat and involve rheumatology.
- Catastrophic APS (CAPS). A rare (<1% of APS) thrombotic storm — multi-organ small-vessel thrombosis evolving over days, often triggered by infection, surgery, the puerperium or anticoagulation withdrawal. Mortality historically ~50%, now ~25–30% with early triple therapy. Pregnancy and the puerperium are recognised triggers; CAPS mimics severe HELLP/pre-eclampsia and TTP and must be in the differential of the deteriorating multi-organ APS mother.
- SLE phenotypes that change obstetric risk, chiefly lupus nephritis (the dominant driver of loss, growth restriction and superimposed pre-eclampsia — and the group excluded from the reassuring PROMISSE data) and anti-Ro/La positivity, which is an antibody trafficking problem rather than a thrombotic one: IgG anti-Ro/SSA crosses the placenta from ~16 weeks and binds fetal cardiac conduction tissue, causing inflammation, fibrosis and congenital heart block (CHB) — independent of whether the mother has any symptoms or even meets criteria for SLE (a Sjögren or asymptomatic anti-Ro carrier can have an affected baby).
The unifying principle: the antibody profile predicts the phenotype, and the phenotype dictates the drug. A positive aPL with thrombosis → therapeutic anticoagulation; the same aPL with only obstetric morbidity → aspirin + prophylactic heparin; anti-Ro/La → hydroxychloroquine + fetal cardiac surveillance, not anticoagulation; lupus nephritis → disease control before conception above all.
Assessment
The core skill is pre-pregnancy risk stratification, then distinguishing the three things that mimic each other in the third trimester: flare, pre-eclampsia and APS-driven placental insufficiency.
- Conception readiness. Aim for ≥6 months of clinical and serological quiescence on pregnancy-compatible drugs. Active disease at conception — especially active lupus nephritis — is the dominant driver of fetal loss, prematurity and growth restriction.
- Antibody panel (the load-bearing test). Full antiphospholipid panel — lupus anticoagulant (LAC), anticardiolipin (aCL) IgG/IgM, anti-β2-glycoprotein-I IgG/IgM — plus anti-Ro/SSA and anti-La/SSB, anti-dsDNA, and C3/C4. LAC is the single antibody that predicts late obstetric morbidity; triple positivity (LAC + aCL + anti-β2GPI) is the highest-risk phenotype. Anti-Ro/La drive congenital heart block (CHB) and neonatal lupus regardless of maternal symptoms.
- Organ baseline. Baseline BP, urine protein:creatinine ratio (uPCR), creatinine, FBC. A booking uPCR and platelet count are essential — without them you cannot later separate nephritis/flare from pre-eclampsia.
- Flare vs pre-eclampsia vs HELLP. Falling C3/C4, rising anti-dsDNA, active urinary sediment (red-cell casts), arthritis or rash point to flare; normal/raised complement with rising uric acid, transaminases and new hypertension after 20 weeks points to pre-eclampsia/HELLP. The two coexist, and APS adds early, severe, placentally-mediated disease — see pre-eclampsia and HELLP basics and hypertension in pregnancy.
- Fetal surveillance. Serial growth and umbilical artery Doppler from ~24 weeks (earlier if APS/prior loss); in anti-Ro/La pregnancies, weekly fetal echo/PR-interval monitoring across the 16–26-week vulnerable window for emerging heart block.
Obstetric APS classification requires a clinical event (≥3 consecutive losses <10 weeks; ≥1 loss ≥10 weeks; or delivery <34 weeks for pre-eclampsia with severe features/placental insufficiency) plus a persistently positive aPL ≥12 weeks apart — distinct from the recurrent loss covered in recurrent pregnancy loss.
The atypical presentations and the judgement calls
The textbook presentation rarely arrives clean. The consultant-level discriminations are:
- The "pre-eclampsia at 24 weeks" that is actually a nephritis flare. New hypertension and proteinuria before the usual pre-eclampsia window, with an active urinary sediment, falling complement and rising anti-dsDNA, is lupus nephritis until proven otherwise — and it needs immunosuppression and delivery planning, not delivery alone. Uric acid and sFlt-1/PlGF help (the angiogenic axis is driven by pre-eclampsia, not lupus), but the booking baseline you took at first contact is what makes the call possible. A booking uPCR that was already 0.5 reframes a third-trimester "new" proteinuria entirely.
- The thrombocytopenia with three causes. A low platelet count in this woman may be lupus-related immune thrombocytopenia (chronic, present from booking), consumption in HELLP (acute, with haemolysis and transaminitis), or the first sign of evolving CAPS or TTP. The trend and the company it keeps — not a single value — make the diagnosis.
- The asymptomatic anti-Ro carrier. Severity here is fetal, not maternal: an entirely well mother (normal BP, no rash, even labelled "Sjögren" or "incidental ANA") can be carrying a fetus heading for irreversible complete heart block. Maternal wellbeing is no reassurance.
- Antibody profile beats clinical "activity score". Two women with identical, quiescent disease but different antibody profiles (one LAC-positive/triple-positive, one aCL-low-titre only) are not the same risk. The stratification is on the antibody, weighted by LAC and triple positivity, layered on top of organ involvement — which is exactly what the 2023 ACR/EULAR criteria formalised (see Investigations).