AntiPhospholipid Syndrome Flashcards
Antiphospholipid Syndrome
Systemic APS is defined as the presence of:
≥1 clinical manifestations: unexplained repeated spontaneous abortions or vascular thrombosis (e.g., deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction, ±APS nephropathy), and
Antiphospholipid Syndrome
Systemic APS is defined as the presence of:
Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks
Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks
Antiphospholipid Syndrome
Systemic APS is defined as the presence of:
Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks
aPLS are autoantibodies (typically IgG or IgM, but can be IgA) directed against plasma proteins bound to anionic surfaces.
Antiphospholipid Syndrome
Systemic APS is defined as the presence of:
Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks
aPLs of interest: lupus anticoagulant, anti-β2-glycoprotein I, anti-vimentin/cardiolipin, antibodies against cell membranes including phosphatidylserine, phosphotidylinositol, phosphatidylethanolamine, phosphatidic acid
Antiphospholipid Syndrome
Systemic APS is defined as the presence of:
Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks
The prevalence of aPLs is 1% to 5% of general population, but may be as high as 16% to 40% in patients with SLE, and 16% in those with rheumatoid arthritis.
Antiphospholipid Syndrome
The prevalence of APS may be > 20% during long-term follow-up in SLE patients.
Antiphospholipid Syndrome
Renal APS may present with renal artery or vein thrombosis or APS nephropathy.
Antiphospholipid Syndrome
APS nephropathy is a vasoocclusive kidney injury due to TMA and is a subset of renal APS. APS nephropathy per se is not generally considered a clinical manifestation required for the diagnosis of systemic APS.
APS nephropathy has been reported in 10% of patients with LN and in 20% to 30% of those with SLE.
Up to one-third of patients with APS nephropathy does not have systemic APS.
Antiphospholipid Syndrome
Systemic APS may be classified as primary or secondary APS. Primary APS has no associated systemic disease, whereas secondary APS is associated with a systemic disease, typically autoimmune (e.g. SLE).
Antiphospholipid Syndrome
Clinical Manifestations
Renal APS: renal vascular fibrointimal hyperplasia, renal artery or vein thrombosis with or without associated hypertension, cortical ischemia/necrosis, hematuria, kidney injury, tubulointerstitial fibrosis, glomerulosclerosis, and any glomerular lesion.
Antiphospholipid Syndrome
Clinical Manifestations
Histopathology of APS nephropathy
Arterial/arteriolar fibrin thrombi ± fibrin extending into the vascular intima and endothelial cell swelling with narrowed lumens
Antiphospholipid Syndrome
Clinical Manifestations
Histopathology of APS nephropathy
Fragmented red blood cells in vessel lumens, or walls, or in areas of glomerular mesangiolysis
Antiphospholipid Syndrome
Clinical Manifestations
Histopathology of APS nephropathy
Concentric thickening (onion skinning) ± mucoid subendothelial widening of arterial/arteriolar walls
Antiphospholipid Syndrome
Clinical Manifestations
Histopathology of APS nephropathy
Glomerular capillary ischemic wrinkling, sometimes with double contours
Antiphospholipid Syndrome
Clinical Manifestations
Histopathology of APS nephropathy
IF: Fibrin in glomerular capillaries and/or vessel walls and lumens
Antiphospholipid Syndrome
Clinical Manifestations
Histopathology of APS nephropathy
EM: subendothelial electron lucent widening between glomerular capillary basement membrane and swollen endothelium
Antiphospholipid Syndrome
Clinical Manifestations
Glomerular lesions commonly associated with APS:
Primary APS: membranous, MCD, FSGS
Secondary APS: typically LN of any World Health Organization class
Antiphospholipid Syndrome
Pathogenesis
Inciting event is thought to arise from aPL-mediated blood vessel injury, followed by endothelial disruption, formation of β2-glycoprotein I IC, activation of endothelial cells, platelets, and circulating monocytes, all leading to a thrombogenic state.
Antiphospholipid Syndrome
Pathogenesis
Other downstream effects that would favor thrombus formation:
Release of tissue factor, followed by activation of the extrinsic coagulation pathway, and production of vasoconstrictive thromboxane A2
Antiphospholipid Syndrome
Pathogenesis
Other downstream effects that would favor thrombus formation:
Reduction of endothelial nitric oxide production, leading to increased endothelial monocyte adhesion, superoxide generation, and decreased arterial relaxation
Antiphospholipid Syndrome
Pathogenesis
Other downstream effects that would favor thrombus formation:
Activation of classical complement pathway, increased expression of C5a, leading to neutrophil recruitment to area of tissue injury
Antiphospholipid Syndrome
Management
Life-time anticoagulation for APS, even APS nephropathy alone, with goal INR 2-3. Aspirin alone is inadequate therapy.
Antiphospholipid Syndrome
Management
NOTE: Overanticoagulation (INR > 3.0) may be associated with warfarin-related nephropathy (WRN, AKI associated with glomerular hemorrhage and intratubular red blood cell obstruction). Underlying CKD is thought to be a risk factor for WRN
