What is the management of Antiphospholipid Antibody Syndrome (APAS) in the Emergency Room (ER) setting?

Management of Antiphospholipid Antibody Syndrome (APAS) in the Emergency Room

Immediate Assessment and Risk Stratification

For patients presenting to the ER with suspected or confirmed APAS, immediately assess for acute thrombotic events (arterial or venous), bleeding complications, or catastrophic APAS, as these determine the urgency and intensity of anticoagulation. 1

Critical Initial Evaluation

• Obtain focused history: Document prior thrombotic events, pregnancy losses, known antiphospholipid antibody status (lupus anticoagulant, anticardiolipin antibodies, anti-β2 glycoprotein-I antibodies), current anticoagulation regimen, and recent bleeding 1
• Assess for catastrophic APAS: Look for multi-organ thrombosis developing over days to weeks, often triggered by infection, surgery, or anticoagulation withdrawal 1
• Laboratory workup: CBC with platelet count, PT/INR, aPTT, renal and hepatic function, troponin if chest pain present 1
• Imaging as indicated: CT angiography for suspected pulmonary embolism, ultrasound for deep vein thrombosis, CT head for stroke 1

Management of Acute Thrombotic Events in APAS

Venous Thromboembolism

Initiate therapeutic anticoagulation immediately with unfractionated heparin or low molecular weight heparin, then transition to warfarin with target INR 2.0-3.0 for long-term management. 1, 2, 3

• Initial anticoagulation: Start unfractionated heparin bolus (80 units/kg IV) followed by infusion (18 units/kg/hour), or enoxaparin 1 mg/kg subcutaneously every 12 hours 2
• Overlap with warfarin: Begin warfarin on day 1 at 5-10 mg daily, overlap with heparin for minimum 5 days and until INR ≥2.0 for 24 hours 2
• Target INR: Maintain INR 2.0-3.0 for venous thrombosis 1, 2, 3
• Duration: Plan for indefinite anticoagulation given high recurrence risk (1.30 per patient-year within 6 months of stopping warfarin) 3

Arterial Thrombosis (Stroke, Myocardial Infarction)

For arterial thrombosis in APAS, initiate anticoagulation with higher intensity warfarin (target INR 3.0-4.0) or consider combination therapy with warfarin (INR 2.0-3.0) plus low-dose aspirin 75-100 mg daily. 1, 3

• Higher intensity anticoagulation: Target INR 3.0-4.0 for arterial events, as moderate intensity (INR 2.0-3.0) has recurrence rate of 0.23 per patient-year versus 0.013 per patient-year with high-intensity 3
• Aspirin addition: Consider adding aspirin 75-100 mg daily to warfarin for arterial thrombosis 1
• Avoid DOACs: Do not use direct oral anticoagulants in triple-positive APAS due to increased arterial thrombosis risk, especially stroke 1

Management of Catastrophic APAS

Catastrophic APAS requires aggressive triple therapy: therapeutic anticoagulation plus high-dose glucocorticoids plus plasma exchange or intravenous immunoglobulin. 1

• Anticoagulation: Unfractionated heparin infusion (easier to reverse if bleeding occurs) 1
• Glucocorticoids: Methylprednisolone 1000 mg IV daily for 3 days, then prednisone 1 mg/kg daily 1
• Plasma exchange: 5 exchanges over 7-10 days, or IVIG 0.4 g/kg daily for 5 days if plasma exchange unavailable 1
• Cyclophosphamide: Add IV cyclophosphamide 500-1000 mg/m² if catastrophic APAS occurs with SLE flare 1

Management of APAS Patients with Bleeding Complications

Active Bleeding on Anticoagulation

For APAS patients with active bleeding, prioritize mechanical hemostasis first, then consider temporary anticoagulation reversal only if bleeding is life-threatening, recognizing the high thrombotic risk. 4

• Etiological treatment: Surgical hemostasis, endoscopy, embolization, or tamponade as primary intervention 4
• Supportive care: Vascular filling, vasopressors, red blood cell transfusion, warming measures 4
• Tranexamic acid: Administer 1 gram IV early in severe bleeding (not associated with increased thrombotic risk in trauma/cardiac surgery) 4
• Warfarin reversal: For life-threatening bleeding, give vitamin K 10 mg IV slow infusion plus 4-factor prothrombin complex concentrate 25-50 units/kg 2
• Resume anticoagulation: Restart therapeutic anticoagulation as soon as bleeding controlled, given extremely high thrombotic risk (1.30 per patient-year off warfarin) 3

Intracranial Hemorrhage

For intracranial hemorrhage in APAS patients on anticoagulation, reverse anticoagulation emergently but plan to resume therapeutic anticoagulation within 7-14 days after neurosurgical consultation. 4

• Immediate reversal: 4-factor prothrombin complex concentrate for warfarin, platelet transfusion controversial (may increase mortality despite reducing hematoma expansion) 4
• Neurosurgical consultation: Urgent evaluation for decompression if indicated 4
• Anticoagulation resumption: Balance thrombotic risk (very high in APAS) against rebleeding risk, typically resume within 7-14 days 3

Management of APAS Patients Requiring Urgent/Emergent Surgery

Non-Neurosurgical Procedures

For urgent/immediate non-neurosurgical procedures in APAS patients on anticoagulation, proceed without reversal unless intraoperative bleeding becomes uncontrollable. 4

• Continue anticoagulation: Perform urgent procedures without neutralizing anticoagulation when possible 4
• Intraoperative decision: If bleeding uncontrollable and attributable to anticoagulation, then reverse 4
• Resume anticoagulation: Restart within 24-72 hours post-procedure given high thrombotic risk 4

Neurosurgical Procedures

For urgent/immediate intracranial surgery in APAS patients, neutralize anticoagulation before the procedure. 4

• Warfarin reversal: 4-factor prothrombin complex concentrate 25-50 units/kg plus vitamin K 10 mg IV 2
• Heparin reversal: Protamine sulfate 1 mg per 100 units of heparin given in last 2-3 hours 4

Special Considerations in the ER Setting

APAS with Sepsis

Continue therapeutic anticoagulation in APAS patients with sepsis unless active bleeding or platelet count critically low, as sepsis itself is prothrombotic and synergizes with APAS thrombotic risk. 1

• Monitor coagulopathy: Check platelet count, PT-INR, SOFA score for sepsis-induced coagulopathy 1
• Maintain anticoagulation: Sepsis-induced coagulopathy does not contraindicate anticoagulation in APAS 1
• INR monitoring: May be unreliable due to hepatic dysfunction; consider anti-Xa monitoring if on heparin 1

Thrombocytopenia in APAS

Do not withhold anticoagulation based on thrombocytopenia alone unless platelet count <25,000/mcL or active bleeding, as thrombocytopenia in APAS is prothrombotic, not protective. 1

Pregnancy-Related APAS Presentations

For pregnant APAS patients presenting with thrombosis, use therapeutic-dose low molecular weight heparin (not warfarin) plus aspirin 81 mg daily throughout pregnancy and 6 weeks postpartum. 1

• Avoid warfarin: Teratogenic in pregnancy 1
• LMWH dosing: Enoxaparin 1 mg/kg subcutaneously every 12 hours, monitor anti-Xa levels 1

Critical Pitfalls to Avoid

• Never use DOACs in triple-positive APAS: Increased arterial thrombosis and stroke risk compared to warfarin 1
• Never stop anticoagulation without bridging plan: Recurrence rate 1.30 per patient-year within 6 months of stopping 3
• Never use moderate-intensity anticoagulation for arterial thrombosis: INR 2.0-3.0 has 18-fold higher recurrence rate than INR ≥3.0 3
• Never delay anticoagulation for "complete workup": Start therapeutic anticoagulation immediately for acute thrombosis 1, 3
• Never assume bleeding risk outweighs thrombotic risk: APAS has exceptionally high thrombotic risk requiring aggressive anticoagulation 3, 5