AntiPhospholipid Syndrome

Question 1

Antiphospholipid Syndrome

Systemic APS is defined as the presence of:

Answer 1

≥1 clinical manifestations: unexplained repeated spontaneous abortions or vascular thrombosis (e.g., deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction, ±APS nephropathy), and

Question 2

Antiphospholipid Syndrome

Systemic APS is defined as the presence of:

Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks

Answer 2

Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks

Question 3

Antiphospholipid Syndrome

Systemic APS is defined as the presence of:

Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks

Answer 3

aPLS are autoantibodies (typically IgG or IgM, but can be IgA) directed against plasma proteins bound to anionic surfaces.

Question 4

Antiphospholipid Syndrome

Systemic APS is defined as the presence of:

Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks

Answer 4

aPLs of interest: lupus anticoagulant, anti-β2-glycoprotein I, anti-vimentin/cardiolipin, antibodies against cell membranes including phosphatidylserine, phosphotidylinositol, phosphatidylethanolamine, phosphatidic acid

Question 5

Antiphospholipid Syndrome

Systemic APS is defined as the presence of:

Positive antiphospholipid antibodies (aPLs) detected on ≥2 occasions separated by several weeks

Answer 5

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.

Question 6

Antiphospholipid Syndrome

Answer 6

The prevalence of APS may be > 20% during long-term follow-up in SLE patients.

Question 7

Antiphospholipid Syndrome

Answer 7

Renal APS may present with renal artery or vein thrombosis or APS nephropathy.

Question 8

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.

Answer 8

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.

Question 9

Antiphospholipid Syndrome

Answer 9

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).

Question 10

Antiphospholipid Syndrome

Clinical Manifestations

Answer 10

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.

Question 11

Antiphospholipid Syndrome

Clinical Manifestations

Histopathology of APS nephropathy

Answer 11

Arterial/arteriolar fibrin thrombi ± fibrin extending into the vascular intima and endothelial cell swelling with narrowed lumens

Question 12

Antiphospholipid Syndrome

Clinical Manifestations

Histopathology of APS nephropathy

Answer 12

Fragmented red blood cells in vessel lumens, or walls, or in areas of glomerular mesangiolysis

Question 13

Antiphospholipid Syndrome

Clinical Manifestations

Histopathology of APS nephropathy

Answer 13

Concentric thickening (onion skinning) ± mucoid subendothelial widening of arterial/arteriolar walls

Question 14

Antiphospholipid Syndrome

Clinical Manifestations

Histopathology of APS nephropathy

Answer 14

Glomerular capillary ischemic wrinkling, sometimes with double contours

Question 15

Antiphospholipid Syndrome

Clinical Manifestations

Histopathology of APS nephropathy

Answer 15

IF: Fibrin in glomerular capillaries and/or vessel walls and lumens

Question 16

Antiphospholipid Syndrome

Clinical Manifestations

Histopathology of APS nephropathy

Answer 16

EM: subendothelial electron lucent widening between glomerular capillary basement membrane and swollen endothelium

Question 17

Antiphospholipid Syndrome

Clinical Manifestations

Answer 17

Glomerular lesions commonly associated with APS:

Primary APS: membranous, MCD, FSGS

Secondary APS: typically LN of any World Health Organization class

Question 18

Antiphospholipid Syndrome

Pathogenesis

Answer 18

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.

Question 19

Antiphospholipid Syndrome

Pathogenesis

Other downstream effects that would favor thrombus formation:

Answer 19

Release of tissue factor, followed by activation of the extrinsic coagulation pathway, and production of vasoconstrictive thromboxane A2

Question 20

Antiphospholipid Syndrome

Pathogenesis

Other downstream effects that would favor thrombus formation:

Answer 20

Reduction of endothelial nitric oxide production, leading to increased endothelial monocyte adhesion, superoxide generation, and decreased arterial relaxation

Question 21

Antiphospholipid Syndrome

Pathogenesis

Other downstream effects that would favor thrombus formation:

Answer 21

Activation of classical complement pathway, increased expression of C5a, leading to neutrophil recruitment to area of tissue injury

Question 22

Antiphospholipid Syndrome

Management

Answer 22

Life-time anticoagulation for APS, even APS nephropathy alone, with goal INR 2-3. Aspirin alone is inadequate therapy.

Question 23

Antiphospholipid Syndrome

Management

Answer 23

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