Management of Disorders of the Phospholipids Pathway
I must clarify that the provided evidence does not contain guidelines or research specifically addressing "disorders of the phospholipids pathway" as a distinct clinical entity requiring management. The evidence primarily discusses antiphospholipid syndrome (APS) in the context of lupus nephritis and general phospholipid biology.
Antiphospholipid Syndrome-Associated Nephropathy (APSN)
For patients with antiphospholipid antibodies causing vascular nephropathy, hydroxychloroquine combined with antiplatelet or anticoagulant therapy should be initiated, with full anticoagulation reserved for those meeting definite APS criteria. 1
Clinical Recognition and Diagnosis
APSN presents with thrombotic microangiopathy and chronic vascular lesions including fibrous intimal hyperplasia, organizing thrombi with recanalization, focal cortical atrophy, and arterial/arteriolar occlusions 1
Histological lesions of APSN are present in 20-30% of patients with SLE and must be distinguished from thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and malignant hypertension 1
Adverse prognostic factors include hypertension, impaired renal function, and interstitial fibrosis 1
Treatment Algorithm
Step 1: Identify antiphospholipid antibodies
- Test for anti-cardiolipin antibodies, anti-β2-glycoprotein I antibodies, and lupus anticoagulant 1
- Patients with moderate to high titers are at increased risk for thrombotic complications 1
Step 2: Initiate hydroxychloroquine
- Hydroxychloroquine should be continued in all patients with antiphospholipid antibodies, including during pregnancy 1
Step 3: Add antiplatelet or anticoagulant therapy
- For APSN without definite APS criteria: consider antiplatelet agents or anticoagulants in combination with immunosuppressive treatment if nephritis is present 1
- For definite APS: anticoagulation treatment is mandatory 1
- Perioperative anticoagulation may be needed in transplant candidates with moderate to high antibody titers 1
Step 4: Add renin-angiotensin-aldosterone system blockade
- RAAS blockade may delay disease progression in APSN 1
- However, these agents are contraindicated in the first trimester of pregnancy due to teratogenicity 1
Special Considerations
Pregnancy management:
- Blood pressure control should avoid RAAS blockers at conception if possible, switching to nifedipine or labetalol 1
- Hydroxychloroquine, prednisone, and azathioprine are acceptable during pregnancy 1
Transplantation:
- Patients with moderate to high antiphospholipid antibody titers require perioperative anticoagulation 1
- Eculizumab's role in APSN remains investigational 1
Critical Pitfall
The absence of controlled studies means treatment recommendations are based on expert consensus rather than randomized trial evidence 1. Despite this limitation, the combination approach of hydroxychloroquine plus antithrombotic therapy represents the current standard based on pathophysiologic rationale and observational data.