Table 1.
Main features of pregnancy-specific TMAs and pregnancy-associated TMAs.
| TMA syndromes in pregnancy | Epidemiology | Key-elements for diagnosis | Physiopathology | Treatment modalities | ||
|---|---|---|---|---|---|---|
| Context/timing | Most discriminating clinico-biological symptoms | Impact of delivery | ||||
| PE with renal dysfunction | 1.7% of all HDP 15% of all PE |
From 20 weeks gestation to 4 weeks PP | new-onset HT andAKI Δ Ratio of sFLT1/PlGF > 85 |
Improvement in 48-72 h PP. Proteinuria may persist >1 year | Abnormal placentation with release of antiangiogenic markers, mediated primarily by sFlt-1 and sEng | Delivery, supportive care |
| HELLP | 0.2–0.6% of all pregnancy | Previous PE (80% of HELLP)/T3 to early PP | Elevated liver enzymes AST or ALT > 70 IU/L |
Improvement in 48-72 h PP | Few understood: Abnormal placentation (continuum with PE); Complement AP dysregulation; DIC | Delivery, supportive care |
| TTP | 5.10−3 to 10−4% of all pregnancy | TTP history/iTTP: T3, early PP; cTTP: from T1 | ADAMTS-13 < 10% platelets < 30.109/L |
No | Congenital or acquired ADAMTS-13 deficiency leading to accumulation of large VWF multimers | PEX, caplacizumab*, IS (iTTP), plasma infusion (cTTP) |
| CM-HUS | 4.10−3% of all pregnancy | HUS history/from T3 to 3-months PP (80%) | Severe AKI Congenital or acquired abnormalities of complement system |
No | Dysregulated activation of complement alternative pathway | PEX, C5 blocker |
| CAPS | 1% of all APS/8% of all CAPS | Context of known APS or criteria +/within 4 weeks PP (80%) | ± anti-cardiolipin ± anti-β2GPI antibodies ±lupus anticoagulant | No | Few understood: direct endothelial injury by aPL; dysregulated complement activation | Anticoagulation, PEX, IS |
| SLE | TMA in 17–24% of all lupus nephritis | Context of known SLE or LN | ± Positive antinuclear ± anti-native DNA (anti-Ro/SSA) | No | Few understood: ADAMTS-13 activity deficiency (TTP-like syndrome); dysregulated complement activation; secondary APS | IS |
| DIC | 0.03 to 0.35% of all pregnancy | Context of obstetrical complications | DIC (prolonged PT, thrombocytopenia, low fibrinogen) | No | DIC activates coagulation and triggers fibrinolysis | Cause-based treatment, supportive care |
AID, auto-immune diseases; APS, antiphospholipid syndrome; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GIT, gastrointestinal tractus; HT, hypertension; HDP, Hypertensive disorders of pregnancy; IS, immunosuppression; TI, topoisomerase; PEX, plasma exchange; PlGF, placental growth factor; PP, postpartum; SLE, Systemic lupus erythematosus; SRC, Scleroderma renal crisis; T1, first trimester of pregnancy; T3, third trimester of pregnancy.
ΔThe definition used in these reports is based on a serum creatinine 0.90 mmol/L and/or a 0.25% increase compared with baseline values.
*caplacizumab is not approved for ongoing pregnancy (small molecular size, transplacental transfer). Nevertheless, it has shown success in pregnant women with acquired TTP, resulting in favorable outcomes (35, 36).