Antiphospholipid syndrome

Syndrome caused by antibodies called antiphospholipids (APL) that can cause clotting. Not everyone with these antibodies gets blood clots but risk is increased. They usually manifest in 3 ways:

• Miscarriages
• Leg blood clot (Deep vein thrombosis, DVT)
• Lung blood clot (pulmonary embolism, PE)

Lab

3 Phospholipid antibodies usually tested for :

• Cardiolipin antibody
• Lupus anticoagulant
• Beta-2-glycoprotein antibody

Other APL abs:

• Phosphatidyl serine antibody

Diagnostic criteria/ classification criteria

Saporro criteria. One clinical plus one lab criterion = APS. 

Management of APL Scenarios

APL positive confirmed after 12 weeks. Test incidental.

Small increased risk of thrombosis in patients with APL and no thrombus history. <1%. More in lupus or with high risk profiles. Cochrane review 2018 conclusion could not recommend any management. Guidelines say treat primary prevention with low dose ASA if "high risk" profile. Others, case by case decision on ASA. [1]

Management of OB APL without history of thrombus

Long-term use low dose ASA and not warfarin. Risk of DVT long-term is low. 
Thrombotic APS in pregnant woman. Continue therapeutic anticoag with LWM Heparin. Warfarin is teratogenic. Add low dose ASA. LMW Heparin does not cross placenta. [1]

Management of microvascular manifestations

Usually don't respond to ASA or anticoagulants. Immunomodulatory measures might help. [1]

• Hydroxychloroquine can reduce ab titers. Reduces thrombosis. Study in APL ab and events in 57 hydroxychloroquine patients. 
• Rituximab. Open label trial showed improvement in skin, heart
• Sirolimus might help APL nephropathy
• Eculizumab for microangiopathic hemolysis

Manage DVT and pos APL tests

Warfarin indefinitely. Standard therapy for APS = warfarin. LMWH initially x >3-5 days transition to warfarin. Heparin prevents warfarin induced skin necrosis and blocks complement.  TRAPS trial. Rivaroxaban vs warfarin. 19% events on rivaroxaban vs 3% on warfarin. Study stopped. [2] 2022 in Blood Advances. Apixaban vs warfarin for secondary prevention. 48 patients randomized. 26% had primary outcome compared to 0 in warfarin group. Both trials cancelled prematurely. 2022 Khairani et al in JAC. DOAC vs warfarin in APS. 472 patient meta-analysis. DOAC had increased odds 5.43 arterial event. "Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with vitamin K antagonists (VKAs) appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding." [1] [3]

Image from V Pengo et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. Sep 27, 2018. 

Intensity of warfarin/duration of therapy. Crowther NEJM 2003 randomized APS 2.0-3.0 vs 3.1-4.0. 10.7% clots in high intensity vs 3% moderate group. So 2-3 INR is the goal. Duration should be indefinite. [1]

Lupus anticoag withdrawal study in France. 30 patients withdrew after 6 mos. 7.3% relapsed in 4 yrs vs 1%. [1]

Arterial thrombus in APS. 

Catastrophic APL Syndrome (CAPS)

Most severe form of APS. Life-threatening. 37% mortality. Thrombosis large and small in short time in presence of APL ab. Small vessel occlusion causes microvascular disease.

Define

3 or more major organ systems one week histopathology of small vessel occlusion with APL abs. Only 1% of all APS.[1]

Triggers

• lupus flare
• preganancy
• drugs
• malignancy
• infection

Lab CAPS

Differential

Treatment of CAPS

Guidelines 2018. Triple therapy

• Plasmapheresis or IV Ig both support lower mortality
• Steroid
• Heparin therapeutic

Plasmapheresis

x 5 days

IV Ig

2 grams per kg. Avoid in renal disease. 

Pulse steroids

Rituximab also mentioned in guidelines. For refractory disease.