Autoimmune hypercoagulable disorder · KIMS Secunderabad
Antiphospholipid Syndrome — When Autoantibodies Cause Clots and Kidney Damage
Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder characterised by the persistent presence of antiphospholipid antibodies (aPL — lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2-glycoprotein I antibodies) and a clinical manifestation of thrombosis (arterial or venous) or pregnancy morbidity (recurrent miscarriage, foetal loss, preeclampsia). APS may be primary (occurring alone) or secondary (occurring in association with SLE — the most common secondary cause). The kidney is one of the most important target organs in APS — renal involvement occurs through multiple vascular mechanisms that collectively constitute APS nephropathy.
APS nephropathy is frequently underrecognised because the renal manifestations — hypertension, proteinuria, and declining eGFR — are non-specific and can be attributed to other causes. Kidney biopsy is the definitive diagnostic investigation that identifies the specific vascular lesions of APS in the kidney. At KIMS, Dr. Susmitha Chandragiri's women's nephrology programme specifically addresses APS and its renal implications in women with recurrent pregnancy loss, SLE, or unexplained thrombosis.
Renal manifestations of APS
APS nephropathy (chronic)
The most common renal lesion — characterised on kidney biopsy by: thrombotic microangiopathy (TMA) of the small renal vessels, fibrous intimal hyperplasia of interlobular arteries, arteriolar hyalinosis, focal cortical atrophy, and focal cortical infarcts. These lesions reflect repeated episodes of small vessel thrombosis causing ischaemia and infarction of renal parenchyma. Clinical presentation: hypertension (often severe, renovascular in mechanism), proteinuria (usually non-nephrotic), and slowly progressive CKD. Nephrotic syndrome is uncommon unless concurrent lupus nephritis (Class V) is present.
Renal vein thrombosis
APS is an important cause of renal vein thrombosis — particularly in patients with nephrotic syndrome from concurrent lupus nephritis (where the combined thrombotic risk from APS antibodies and the prothrombotic state of nephrotic syndrome is very high). Presents with sudden flank pain, haematuria, and worsening AKI.
Renal artery thrombosis or stenosis
Arterial thrombosis affecting the renal arteries causes renal infarction (acute loin pain, elevated LDH, AKI) or — with repeated small vessel involvement — renal artery stenosis with renovascular hypertension.
Catastrophic APS (CAPS)
A rare, life-threatening variant — multiple organ thrombosis developing simultaneously or within days, affecting the kidneys, lungs, brain, and other organs. AKI is present in above 70% of CAPS cases. Treatment: anticoagulation (heparin) + plasma exchange + steroids + IVIG. Rituximab or eculizumab for refractory cases. CAPS mortality remains approximately 30 to 50% despite treatment.
Diagnosis
Antiphospholipid antibody testing — the serological criteria
All three aPL tests must be performed: lupus anticoagulant (LA — a coagulation test, not an antibody test directly), anticardiolipin antibody (aCL — IgG and IgM), and anti-beta-2-glycoprotein I (anti-B2GP1 — IgG and IgM). A positive result must be confirmed on a second test at least 12 weeks later to exclude transient positivity from infection. Triple positivity (positive LA + aCL + anti-B2GP1) carries the highest thrombotic risk.
Kidney biopsy with LM, IF, and EM at KIMS
Identifies the specific vascular lesions of APS nephropathy. Key LM findings: TMA lesions (fibrin-platelet thrombi in glomerular capillaries and arterioles), fibrous intimal hyperplasia, focal cortical atrophy, organised thrombi in vessels. IF may show non-specific or absent immunoglobulin staining (distinguishing APS from immune complex-mediated lupus nephritis where IgG, C3, and C1q are prominent). EM helps characterise the vascular lesions and confirms the TMA pattern.
Renal imaging
Renal Doppler and CT angiography for renal artery stenosis or renal vein thrombosis assessment.
Treatment
Long-term anticoagulation — the cornerstone
Warfarin (target INR 2.0 to 3.0 for venous thrombosis; 3.0 to 4.0 for recurrent arterial thrombosis or CAPS) is the standard for confirmed APS with thrombotic events. DOACs (rivaroxaban, apixaban) are not recommended as first-line therapy for APS with arterial thrombosis or triple antibody positivity — the RAPS, TRAPS, and Riete registry data show higher recurrence rates with DOACs vs warfarin in these high-risk groups.
Hydroxychloroquine
For all APS patients with concurrent SLE and for primary APS — reduces thrombotic risk through antiplatelet and anti-inflammatory mechanisms.
Low-dose aspirin
For primary prevention in asymptomatic aPL-positive individuals with high-risk profiles (triple positivity, prior obstetric APS).
Blood pressure control
ACE inhibitors or ARBs for APS nephropathy — reduce proteinuria and slow CKD progression through their antiproteinuric and kidney-protective mechanisms.
Book a Women's Nephrology Consultation for Antiphospholipid Syndrome at KIMS
Frequently Asked Questions — Antiphospholipid Syndrome
Yes — obstetric APS is characterised by: recurrent miscarriage (3 or more consecutive early pregnancy losses below 10 weeks), foetal loss (one or more unexplained foetal deaths above 10 weeks), or placental insufficiency causing premature birth below 34 weeks (from severe preeclampsia or foetal growth restriction). APS is the most important treatable cause of recurrent pregnancy loss — identified in approximately 15 to 20% of women with recurrent miscarriage. Treatment during pregnancy: low-molecular-weight heparin (LMWH) combined with low-dose aspirin throughout pregnancy significantly reduces miscarriage and foetal loss rates in APS. Every woman with recurrent miscarriage should be tested for APS antibodies at KIMS.
Lupus anticoagulant is a misnomer — it does not cause bleeding, and it is not specific to lupus. It is a laboratory phenomenon: aPL antibodies interfere with the phospholipid components of the coagulation assay, prolonging the APTT (activated partial thromboplastin time) in the test tube. This prolongation is falsely interpreted as an anticoagulant effect — hence the name. In the body, however, these antibodies promote thrombosis (clotting) — by interfering with natural anticoagulant proteins. A patient with a positive lupus anticoagulant is at significantly higher risk of blood clots — not bleeding. The misleading name prevents patients and sometimes clinicians from appreciating the true thrombotic risk.
APS nephropathy from repeated small vessel thrombosis causes progressive focal cortical infarction and interstitial fibrosis — permanent nephron loss that accumulates with each thrombotic episode. The damage can be slowed or halted by adequate anticoagulation (preventing further thrombotic episodes) and kidney-protective therapy (ACE inhibitors). The kidney function at the time of APS nephropathy diagnosis reflects the cumulative damage from past thrombotic episodes — which are not reversible. This is why early diagnosis of APS and early anticoagulation are critical for long-term kidney outcomes.
For most APS patients — particularly those with arterial thrombosis, triple antibody positivity (positive LA + aCL + anti-B2GP1), or a history of recurrent thrombosis — warfarin (INR 2–3) remains the recommended anticoagulant. Multiple clinical trials comparing DOACs (rivaroxaban, apixaban) vs warfarin in APS have shown higher rates of arterial thrombotic events (stroke) with DOACs in high-risk APS patients. DOACs may be considered for low-risk APS (isolated venous thrombosis with single antibody positivity) in patients who cannot maintain a stable INR on warfarin. The decision is made individually at KIMS based on the thrombotic history, antibody profile, and practical factors.
KIMS Secunderabad — Dr. Susmitha Chandragiri (women's nephrology, APS in pregnancy and SLE), comprehensive aPL testing (lupus anticoagulant, aCL IgG/IgM, anti-B2GP1 IgG/IgM) with 12-week confirmation, kidney biopsy for APS nephropathy, warfarin INR management, LMWH + aspirin for obstetric APS, hydroxychloroquine, ACE inhibitor kidney protection. NABH and NABL accredited. Call 040-4488-5000.