In this episode of Hospital Medicine Unplugged, we sprint through antiphospholipid syndrome (APS)—spot it early, anticoag fast, prevent recurrence, never miss CAPS.

We open with the do-firsts: assess for acute thrombosis (venous/arterial/microvascular), pregnancy history, triggers (infection, surgery, anticoagulant interruption), and extra-criteria clues (thrombocytopenia, livedo, valvular disease, neuro). Send aPL panel—LAC, aCL, anti-β2GPI—knowing diagnosis requires ≥1 clinical event + persistent antibody positivity ≥12 weeks. Flag high-risk phenotypes: triple-positive and coexisting SLE.

Call the diagnosis when the clinical picture (thrombosis and/or pregnancy morbidity) pairs with persistent aPL. Support with imaging (US/CTPA/brain MRI), TTE for valves/emboli, and exclude mimics (HIT, DIC, TTP, endocarditis, inherited thrombophilia).

Risk-stratify admission: new/worsening thrombosis, organ dysfunction, pregnancy, suspected CAPS, severe thrombocytopenia, or complex comorbidity. In-house: daily CBC/chemistry, INR/anti-Xa as appropriate, renal/hepatic checks, and watch for microangiopathy.

Treatment—build the anticoagulation backbone:
• Acute VTE/arterial thrombosis: therapeutic UFH or LMWH → transition to warfarin (INR 2–3) for secondary prevention. Higher-intensity warfarin (INR 3–4) isn’t superior and bleeds more.
• Arterial events (e.g., stroke): VKA (INR 2–3) generally preferred over antiplatelet alone; consider adding low-dose aspirin in select atherothrombotic profiles.
• DOACs: avoid in high-risk APS (especially triple-positive) due to inferior efficacy; consider only in carefully selected low-risk scenarios when VKAs are truly not feasible.
• Pregnancy: LMWH (prophylactic or therapeutic) + low-dose aspirin; add hydroxychloroquine when SLE is present. Avoid warfarin (teratogenic) except in rare late-gestation valve indications with specialist input.

If the backbone buckles (recurrent events despite therapeutic INR, intolerance, or special phenotypes):
• Confirm adherence/drug interactions and time-in-therapeutic range; consider LMWH as alternative long-term.
• For inflammatory/non-criteria disease: hydroxychloroquine; refractory selected cases: rituximab for hematologic/valvular/skin disease.
• Complement-targeted therapy (e.g., eculizumab) in refractory CAPS or severe complement-driven phenotypes—case-by-case.

CAPS—don’t miss it: rapid ≤1 week multiorgan small-vessel thrombosis (≥3 organs), thrombocytopenia/MAHA, precipitated by infection/surgery or anticoagulant withdrawal. Action: start “triple therapy” now—heparin + high-dose IV steroids + plasma exchange or IVIG. Add eculizumab or rituximab in refractory cases. Manage in ICU; send biopsies/hemolysis labs; culture aggressively; monitor for DIC.

Monitoring & tapering that stick:
• Warfarin: target INR 2–3; check frequently; manage interactions (antibiotics, diet, antiepileptics).
• Heparins: prefer anti-Xa monitoring when LAC confounds aPTT, pregnancy, renal dysfunction, obesity, or CAPS.
• Track platelets, renal/hepatic function; echo for valve disease; re-test aPL ≥12 weeks to document persistence (not to decide acute care).

Pitfalls you don’t want to meet:
• Calling APS on a single positive test (transient aPL are common).
• Using DOACs in triple-positive APS (↑ recurrence).
• Under-anticoagulating arterial APS or stopping VKAs after an unprovoked event (indefinite therapy is usually indicated).
• Misreading aPTT on heparin in LAC-positive patients—use anti-Xa.
• Delaying CAPS therapy while waiting for labs.

Etiology plays (treat the cause/trigger):
• Infection/surgery/estrogen exposure: remove/optimize; bridge perioperatively with LMWH; resume VKA promptly.
• SLE: tight disease control; HCQ benefits thrombotic risk.
• Pregnancy care: maternal-fetal medicine + hematology; plan delivery/neuraxial timing around LMWH.

We close with the system moves—an APS inpatient bundle that: (1) auto-orders LAC/aCL/anti-β2GPI with reflex repeat plan at 12 weeks; (2) defaults to UFH/LMWH → warfarin (INR 2–3); (3) hard-stops DOACs in triple-positive/high-risk; (4) flags CAPS triggers and fires a triple-therapy pathway; (5) embeds anti-Xa monitoring when LAC present; (6) routes pregnant/SLE patients to co-managed tracks with LMWH+ASA±HCQ; (7) builds discharge plans for indefinite anticoagulation, drug-interaction counseling, and follow-up aPL testing.

Fast recognition, heparin-first, VKA-anchored, steroid-sparing unless CAPS—treat triggers, protect pregnancies, and never miss catastrophic APS.