since pierre rayer first reported renal vein thrombosis associated with nephrotic syndrome in 1837 , thrombosis is known to be one of the main complications of nephrotic syndrome with the renal vein being the most frequent site ( 1 - 5 ) . also since fishberg first drew general attention to the arterial thrombi in 1954 , both venous and arterial thrombosis have been observed in nephrotic patients . although arterial thrombosis has rarely been reported and is mainly observed in children , it is a potentially serious problem in nephrotic patients . therefore awareness of its pathogenesis and assessment of the risk factors for arterial thrombosis are required to allow appropriate prophylactic management . up to now , however , there are no reliable risk factors to suggest anticoagulation therapy in patients with nephrotic syndrome and prophylactic anticoagulants remains controversial . we report a case of cerebral infarction in a 53-yr - old man with nephrotic syndrome with a review of cerebral infarction in adults associated with nephrotic syndrome in english and korean literatures to identify predictive risk factors and to reveal potential benefits of prophylactic anticoagulants . a 53-yr - old man was hospitalized in april 2002 because of a sudden motor weakness in his left extremities , dysarthria , right eye visual disturbance , and headache . a diagnosis of nephrotic syndrome had been made elsewhere in 3 weeks before admission , based on clinical manifestation , blood , and urinary abnormalities and focal segmental glomerulosclerosis was confirmed by percutaneous renal biopsy . also he had been diagnosed with alcohol - associated liver cirrhosis ( child - pugh classification a ) from abdominal ultrasonography and healthy hbv carrier in 7 months before admission . after diagnosis of focal segmental glomerulosclerosis , he had been treated with diuretics , angiotensin converting enzyme ( ace ) inhibitor , prednisolone 1 mg / kg / day , and lamivudine with a dosage of 100 mg / day for the prevention of flare up of viral hepatitis . he had been a 30-pack year smoker and a heavy alcoholic , but quitted smoking and alcohol several months before . on admission , his general appearance revealed that he was acutely ill with bilateral pedal edema . his blood pressure was 120/80 mmhg , pulse rate 120/min , respiratory rate 24/min , and body temperature 37. cardic examination showed normal findings . he had no evidence of systemic thromboembolism , deep vein thrombosis , or cervical bruit . neurological examination revealed drowsy mentality with a left - side motor weakness , and decreased sensory perception on the left side . the initial mr and mr angiography of the brain showed a recent infarction in the right middle cerebral artery territory and the head of the caudate nucleus , no blood flow signal intensity in the right internal carotid artery ( fig . 1 , 2 ) . laboratory data showed leukocytosis ( 2.4910/l ) and hematocrit of 31.9% with hemoglobin of 10.9 g / dl , and platelet of 23010/l . meq / l , potassium 4.1 meq / l , blood urea nitrogen 33 mg / l , serum creatinine 1.0 mg / l , and total serum protein 3.3 g / dl with albumin 1.2 g / dl . the liver function tests , prothrombin time , and activated partial thromboplastin time were normal . the fibrinogen concentration and the negative hbe ag , undetectable hbv dna , and hbs ag seroconversion after lamivudine therapy were demonstrated . anticardiolipin ( igm ) was 4.9 mpl unit / ml ( normal < 12 mpl unit / ml ) . after the admission , supportive care for the cerebral infarction was initiated and he received anticoagulation therapy later . hospital course was uneventful with a mild degree of residual left - side motor weakness at discharge . two months after discharge , remission of nephrotic syndrome occurred on medication with steroid , angiotensin ii receptor blocking agent . at present , 1 yr after discharge , serum albumin level is 4.6 g / dl with serum cholesterol 158 mg / dl and negative albuminuria on tapered dose of prednisolone 7.5 mg every other day ( qod ) . thromboembolic complication has been well known as a clinically important sequelae and its risk is higher in patients with nephrotic syndrome than in any other condition encountered in internal medicine ( 1 ) . although its accurate pathogenesis remains unclear , hypercoagulability is regarded as a major factor for thrombosis in nephrotic patients ( 1 - 8 ) . a disequilibrium between the clotting activator system and the inhibitor system may be important in the hypercoagulability of nephrotic syndrome . ( 5 ) and kendall et al . ( 2 ) demonstrated a reduction in the concentration of low molecular weight coagulation factors ( factor ix , xi ) , probably resulting from increased urinary loss . this is accompanied by an elevated level of high molecular procoagulatory cofactors ( factor v , vii , viii , and x ) and the fibrinogen level . reported low plasma antithrombin iii levels below 70% of normal in eight of the nine patients studied and a significant negative correlation between the antithrombin iii concentraion and the urinary protein excretion . this depletion of antithrombin iii has been confirmed and shown to be the result of urinary losses of this low - molecular weight protein ( 3 ) . however , high concentrations of antithrombin iii have also been reported ( 2 ) as well as high and low levels in other series . meanwhile , andrassy et al . noted that only patients with a serum albumin level below 2.0 g / dl showed low level of antithrombin iii , and that thromboembolic complications occurred in some patients with normal antithrombin iii levels ( 1 ) . plasminogen levels have been generally reported as low because of urinary losses of protein , while 2-antiplasmin and 2-macroglobulin are increased ( 5 ) . observed low level of free protein s in patients with nephrotic syndrome as a result of urinary loss of low molecular weight free protein s. this precludes formation of activated protein c - protein s complexes required for inhibition of thrombin activity resulting in a hypercoagulable state ( 9 ) . in patients with nephrotic syndrome , increased adenosine diphosphate ( adp ) , collagen - induced platelet aggregation , and increased spontaneous platelet aggregation were observed . platelet dysfunction correlated significantly with the degree of proteinuria and hypercholesterolemia ( 5 ) . besides the above described reasons in favor of a hypercoagulable state in nephrotic syndrome , ozsolylu et al . found that steroids raise the concentration of several clotting factors , principally factor viii ( 10 ) . described that steroids decreased the fibrinolytic activity by incomplete breakdown of the thrombus ( 11 ) . and diuretics would favor the development of thrombotic complications with their volume depleting effects leading to hemoconcentration . these include plasma lipid abnormalities , hypovolemia , hypertension , circulating immune complexes , and susceptibility to infections ( 12 , 13 ) . though adult arterial thrombosis is much less common than venous thrombosis in patients with nephrotic syndrome , it is a significant and potentially serious problem due to its high morbidity and mortality . despite the seriousness , there are few reliable predictors of the individual risk . in addition a propensity for arterial thrombosis may be difficult to demonstrate in adults because of a high baseline incidence and the presence of complicating factors ( hypertension , smoking , etc ) . in any case , up to now , prophylactic anticoagulation is a difficult problem and remains controversial . reported that the most important predictive factor for the thrombogenic risk in nephrotic syndrome was the histologic evidence of membranous nephropathy ( 14 ) . andrassy et al . suggested that anticoagulation therapy should be administered as long as the patient has a serum albumin level below 2.0 g / dl ( 1 ) . concluded that nephrotic patients with membranous nephropathy should receive prophylactic anticoagulation ( 15 ) . in 1994 sarasin and schifferli suggested that the benefits of prophylactic administration of oral anticoagulants outweigh the risks in nephrotic patients with membranous nephropathy by the markov - based decision analysis model ( 16 ) . our experience with a case of cerebral infarction in a 53-yr old man with nephrotic syndrome reminded us of prophylactic anticoagulation to reduce the risk of serious arterial thrombosis and suggested that reliable risk factors should be identified . we reviewed cerebral infarction in adults associated with nephrotic syndrome published by english literature ( table 1 ) . twelve cases of cerebral infarction in adult nephrotic patients , including this case , have been reported . the underlying renal disease was membranous nephropathy in three patients , membranoproliferative glomerulonephropathy in three , minimal change disease in three , focal segmental glomerulosclerosis in one and iga in one , and unknown in one . steroids and/or diuretics were used in 8 of 11 patients . the mean serum albumin level was 1.45 g / dl ( 0.7 to 2.7 g / dl ) . the serum fibrinogen , antithrombin iii , free protein s level in sequence available in 9 of 12 , in 11 of 12 , and in 7 of 12 of the adult nephrotic patients with cerebral infarction , respectively . increased fibrinogen levels appeared in six patients and a normal level in three . six patients showed decreased antithrombin iii and serum free protein s was low in four . importantly a review of the literature revealed that serious complications such as death occurred in 4 of 12 relatively young patients . also membranous nephropathy was not predominant ; almost all of the cases showed a serum albumin below 2.1 g / dl and arterial thrombosis was more common on steroid and/or diuretics therapy . in korean literature , 3 cases of cerebral infarction associated with nephrotic syndrome in adults have been published . there were two patients with minimal change disease , and one with focal segmental glomerulosclerosis . in all cases , steroids and/or diuretics were used and serum albumin levels were below 2.0 g / dl ( 26 - 28 ) . in conclusion , if nephrotic patients have risk factors such as severe hypoalbuminemia and are on diuretics or steroid treatment , even they are young patients with other types of nephrotic syndrome besides membranous nephropathy , prophylactic anticoagulants can be considered to reduce the risk of the serious cerebral infarction . also , we suggest that reliable risk factors should be further assessed and the potential benefit of prophylactic anticoagulation therapy be examined by decision analysis in nephrotic patients .
arterial thrombosis is relatively rare compared with venous thrombosis in nephrotic syndrome . 
 however , the assessment of its pathogenesis and risk factors in individual patient with nephrotic syndrome is necessary to allow appropriate prophylactic management because it is a potentially serious problem . 
 hereby , with review of the literature , we report a case of a 53 yr - old man with cerebral infarction associated with nephrotic syndrome due to focal segmental glomerulosclerosis during the course of treatments with diuretics and steroid . 
 it reveals that the hypercoagulable state in nephrotic syndrome can be associated with cerebral infarction in adults . 
 prophylactic anticoagulants can be considered to reduce the risk of serious cerebral infarction in nephrotic patients with risk factors such as severe hypoalbuminemia and on diuretics or steroid treatment , even in young patients regardless of types of underlying glomerular diseases .