APS — Module 2
Clinical Diagnosis & Classification
Thrombotic & obstetric criteria, 2023 ACR/EULAR classification, and clinical decision-making
Thrombotic Manifestations
Board Pearl
APS causes clotting despite thrombocytopenia — if a patient has both low platelets and clots, think APS.| Category | Key Manifestations | Board Tip |
|---|---|---|
| Venous | DVT (most common), PE, cerebral sinus thrombosis, Budd-Chiari, renal vein thrombosis | DVT/PE in young patient without risk factors → test aPL |
| Arterial | Stroke/TIA (most common arterial), MI, peripheral arterial occlusion | Stroke <50 years without risk factors → APS until proven otherwise |
| Microvascular | Livedo reticularis, digital ischemia, renal thrombotic microangiopathy | Livedo + clots → think APS (also SLE overlap) |
| Catastrophic (CAPS) | ≥3 organs in ≤1 week, small-vessel thrombosis | Mortality ~30%; treat: anticoagulation + steroids + IVIG/plasmapheresis |
“Clots everywhere, platelets nowhere — APS is the name of the game” — Arterial, venous, micro; thrombocytopenia doesn’t protect from clotting in APS.
Obstetric Manifestations
| Criterion | Definition | Notes |
|---|---|---|
| Recurrent early loss | ≥3 unexplained miscarriages <10 weeks | Exclude chromosomal, anatomic causes first |
| Fetal loss | ≥1 morphologically normal fetal death ≥10 weeks | Normal fetal morphology must be documented |
| Premature birth | <34 weeks due to pre-eclampsia, eclampsia, or placental insufficiency | High aPL burden association |
Key Nuance
Obstetric APS can exist without thrombosis — don’t require clots to diagnose obstetric APS.“Three early or one late — obstetric APS won’t wait” — 3 early losses OR 1 fetal loss ≥10 weeks qualifies.
Hematologic & Other Features
H
Thrombocytopenia in APS
Low platelets + clotting = APS paradox
- Classified: Persistent thrombocytopenia (<100k) • Not classified: Mild/transient thrombocytopenia
“Platelets low but clots still flow — APS paradox, now you know” — Thrombocytopenia in APS means clotting risk, not bleeding risk.
2023 Classification Framework
1
Entry: At least one positive aPL test within 3 years of event
2
Score Clinical: Pick highest-weighted item per domain (D1–D6)
3
Score Lab: LA assays + aCL/anti-β2GPI ELISA titers (weighted by titer level and test type)
4
Classify: Clinical ≥3 AND Lab ≥3 = APS
“Three-and-Three to Get the Key” — ≥3 clinical AND ≥3 lab points to classify as APS.
Key Nuance
The 2023 criteria are highly specific (99%) but less sensitive (84%) — designed to ensure only true APS is classified in clinical trials and research.2023 Clinical Scoring Domains
Six clinical domains, each weighted. Take the highest-weighted item per domain only. Maximum clinical score = sum of highest items across D1–D6.
D1
Macrovascular — Venous TE
DVT, PE, other venous events
Unprovoked proximal DVT/PE: +3 | Provoked proximal DVT/PE: +1 | Distal DVT: +1
Mnemonic: “Unprovoked = more points” — the less explained the clot, the more it points toward APS.
D2
Macrovascular — Arterial TE
Stroke, TIA, MI
Stroke/TIA: +4 | Other arterial: +3 | MI: +3
Mnemonic: “Strokes score highest” — Arterial domain is weighted more heavily than venous.
D3
Microvascular
Small vessel disease
Livedoid vasculopathy: +3 | APS nephropathy: +2 | Livedo racemosa: +2
D4
Cardiac Manifestations
Valve disease, intracardiac thrombus
Valvular thickening/vegetation: +4 | Intracardiac thrombus: +4
Mnemonic: “Libman-Sacks = APS + SLE” — nonbacterial thrombotic endocarditis on aortic/mitral valves.
D5
Hematologic
Thrombocytopenia
Platelet 20–130k: +2
D6
Obstetric
Pregnancy morbidity
≥3 early losses: +1 | Fetal death ≥10w: +3 | Preeclampsia/insufficiency <34w: +3
Mnemonic: “Late loss = more points” — fetal death is more specific than early recurrent losses.
Key Clinical Pearls
- Young stroke (<50) without risk factors = test aPL
- Obstetric APS can exist without thrombosis
- Classification requires ≥3 clinical AND ≥3 lab points (“Three-and-Three to Get the Key”)
- CAPS = ≥3 organs in ≤1 week — treat with combination therapy
- 2023 criteria: 99% specific, 84% sensitive (traded sensitivity for specificity)
High-Yield Board Fact
Lupus anticoagulant prolongs PTT in vitro but causes thrombosis in vivo — this is the classic APS paradox tested on boards.