thromboembolism in patients with nephrotic syndrome is a well - known complication because of hypercoagulable state and many other factors like hemoconcentration , increased blood viscosity , hypoalbuminemia , alteration in platelet function , and possibly administration of steroids and/or diuretics .
the thromboembolic complication of peripheral and deep veins is more common in adults as compared to children though lower incidence in children , it tended to be more severe in children .
cerebral venous sinus thrombosis ( cvst ) in children is a rare complication and only few cases have been reported.[37 ] following two cases demonstrate this rare complication .
sinovenous thrombosis is probably less recognized and the symptoms and clinical course are highly variable . as in the present reported cases , symptoms may be very non - specific like headache , vomiting , drowsiness and altered behavior .
the cvst should be suspected in any patient with nephrotic syndrome who develops any neurologic symptoms like headache , vomiting and cranial nerve palsy , altered sensorium or seizures .
easy availability of imaging techniques like magnetic resonance imaging ( mri ) and magnetic resonance venography ( mrv ) along with increasing awareness of condition should make it more frequently diagnosed , with scope of its reversal with timely treatment .
a 4-year - old boy , weighing 14 kg with steroid - responsive nephrotic syndrome of 1-year duration developed vomiting and drowsiness for 2 days , with fresh re - appearance of edema ( relapse of nephrotic state ) .
he had vomiting , 5 - 6 times a day , after each feeding attempt .
he was on tapered treatment with prednisolone 5 mg per day , but developed fresh relapse . on admission ,
past medical history was negative for migraine headaches , head trauma , febrile illness , substance abuse , vitamin intake or thrombophlebitis .
family history was unremarkable . on admission , his vital signs were normal with pulse rate of 80/min , regular , and blood pressure of 110/80 mmhg .
neurologic examination revealed uncooperative child , conscious but resenting interference with normal cranial nerve examination and good tone and power in all four limbs with normal sensation and normal deep tendon reflexes .
there was no neck rigidity , fundus examination revealed blurring of disc margin with early papilledema .
investigations showed hemoglobin 11.1 gm / dl with packed cell volume of 36% , total leucocytes count of 12,600/mm , platelet count 2.8 lac / mm , serum creatinine of 0.42 mg / dl , blood urea of 18 mg / dl and serum albumin of 2.1 .
coagulation profile showed prothrombin time of 11 s with international normalized ratio ( inr ) of 1.12 and activated partial thromboplastin time of 28 s. protein c and protein s levels were normal .
urine analysis showed 2 + proteinuria , 24 h urine protein excretion was 2.0 gm / day .
computer tomography scan brain without contrast was normal , so mri brain and mr venography was done which demonstrated thrombosis of superior sagittal , left transverse and left sigmoid sinuses .
magnetic resonance imaging brain ( left ) and magnetic resonance venography ( right ) showing thrombosis of superior sagittal sinus , left transverse and left sigmoid sinuses he was treated with daltaparin , a low molecular weight heparin 1000 u ( 75 - 100 u / kg each dose 12 h ) subcutaneous twice daily for 5 days , and oral anticoagulant warfarin was added on fourth day in dose of 0.75 mg twice a day . dose of warfarin was adjusted to keep inr between 2.0 to 2.5 ( in dose range of 0.05 - 0.1 mg / kg ) .
the nephrotic state was treated with 50 ml of 20% human albumin i / v daily for four days with prednisolone 20 mg / day and patient had increased dieresis on 4 day of admission and child had nil proteinuria after 10 days .
the child responded well to treatment , his drowsiness and vomiting improved in 2 days , and he recovered completely in 2 weeks .
repeat mri brain with mrv performed after 2 months showed complete resolution of thrombus from all the cerebral venous sinuses .
his warfarin dose was reduced after resolution , and was continued in lower dose 0.5 mg twice a day for further 6 months , though inr was difficult to keep at two . at present , patient is off anticoagulant treatment without any neurological complaints [ figure 2 ] .
repeat magnetic resonance imaging brain with magnetic resonance venography performed after 2 months showed complete resolution of thrombus from all the cerebral venous sinuses a 3 and a 1/2-year - old boy weighing 12.5 kg with new onset nephrotic syndrome of 15 days duration presented with continuous frontal headache for 3 days at the time of admission .
past medical history and family history was unremarkable . on admission , patient was conscious , cooperative , and well oriented .
his pulse rate was 86/min and blood pressure was 100/60 mmhg . on general examination ,
investigations showed hemoglobin 11.6 gm / dl , total leucocyte count of 11800/mm , platelet 2.3 lac / mm , serum creatinine of 0.50 mg / dl , blood urea of 22 mg / dl , and serum albumin of 1.7 gm / dl , s. serum cholesterol was 537 mg / dl .
coagulation profile showed prothrombin time of 10 s with inr of 1.1 , and activated partial thromboplastin time of 29 s cranial mri and mrv showed thrombosis of superior sagittal , bilateral transverse and bilateral sigmoid sinuses [ figure 3 ] .
magnetic resonance imaging and magnetic resonance venography showed thrombosis of superior sagittal , bilateral transverse , and bilateral sigmoid sinuses his steroid dose was continued at 15 mg per day and daily intravenous human albumin ( 20% ) 50 ml was given for 5 days till his serum albumin rose to 3 gm / dl .
he was started on deltaparin ( lmwh ) 1000 u ( 75 - 100 u / kg each dose 12 h ) subcutaneous twice daily for 5 days and warfarin was added on the fourth day with a dose of 0.75 mg ( in dose range of 0.05 - 0.1 mg / kg ) twice a day .
sixth day onwards , patient was maintained on warfarin only to keep inr between 2.0 and 2.5 .
his mri with mrv done 3 weeks later showed significant dissolution of thrombosis in all affected sinuses .
presently , the boy is on warfarin 1.5 mg for venous thrombosis , prednisolone 15 mg / day , and mycophenolate mofetyl 125 mg twice a day with his nephrotic state in remission .
a 4-year - old boy , weighing 14 kg with steroid - responsive nephrotic syndrome of 1-year duration developed vomiting and drowsiness for 2 days , with fresh re - appearance of edema ( relapse of nephrotic state ) .
he had vomiting , 5 - 6 times a day , after each feeding attempt .
he was on tapered treatment with prednisolone 5 mg per day , but developed fresh relapse . on admission ,
past medical history was negative for migraine headaches , head trauma , febrile illness , substance abuse , vitamin intake or thrombophlebitis .
family history was unremarkable . on admission , his vital signs were normal with pulse rate of 80/min , regular , and blood pressure of 110/80 mmhg .
neurologic examination revealed uncooperative child , conscious but resenting interference with normal cranial nerve examination and good tone and power in all four limbs with normal sensation and normal deep tendon reflexes .
there was no neck rigidity , fundus examination revealed blurring of disc margin with early papilledema .
investigations showed hemoglobin 11.1 gm / dl with packed cell volume of 36% , total leucocytes count of 12,600/mm , platelet count 2.8 lac / mm , serum creatinine of 0.42 mg / dl , blood urea of 18 mg / dl and serum albumin of 2.1 .
coagulation profile showed prothrombin time of 11 s with international normalized ratio ( inr ) of 1.12 and activated partial thromboplastin time of 28 s. protein c and protein s levels were normal .
urine analysis showed 2 + proteinuria , 24 h urine protein excretion was 2.0 gm / day .
computer tomography scan brain without contrast was normal , so mri brain and mr venography was done which demonstrated thrombosis of superior sagittal , left transverse and left sigmoid sinuses .
magnetic resonance imaging brain ( left ) and magnetic resonance venography ( right ) showing thrombosis of superior sagittal sinus , left transverse and left sigmoid sinuses he was treated with daltaparin , a low molecular weight heparin 1000 u ( 75 - 100 u / kg each dose 12 h ) subcutaneous twice daily for 5 days , and oral anticoagulant warfarin was added on fourth day in dose of 0.75 mg twice a day . dose of warfarin was adjusted to keep inr between 2.0 to 2.5 ( in dose range of 0.05 - 0.1 mg / kg ) .
the nephrotic state was treated with 50 ml of 20% human albumin i / v daily for four days with prednisolone 20 mg / day and patient had increased dieresis on 4 day of admission and child had nil proteinuria after 10 days .
the child responded well to treatment , his drowsiness and vomiting improved in 2 days , and he recovered completely in 2 weeks .
repeat mri brain with mrv performed after 2 months showed complete resolution of thrombus from all the cerebral venous sinuses .
his warfarin dose was reduced after resolution , and was continued in lower dose 0.5 mg twice a day for further 6 months , though inr was difficult to keep at two . at present , patient is off anticoagulant treatment without any neurological complaints [ figure 2 ] .
repeat magnetic resonance imaging brain with magnetic resonance venography performed after 2 months showed complete resolution of thrombus from all the cerebral venous sinuses
a 3 and a 1/2-year - old boy weighing 12.5 kg with new onset nephrotic syndrome of 15 days duration presented with continuous frontal headache for 3 days at the time of admission .
his pulse rate was 86/min and blood pressure was 100/60 mmhg . on general examination ,
investigations showed hemoglobin 11.6 gm / dl , total leucocyte count of 11800/mm , platelet 2.3 lac / mm , serum creatinine of 0.50 mg / dl , blood urea of 22 mg / dl , and serum albumin of 1.7 gm / dl , s. serum cholesterol was 537 mg / dl .
coagulation profile showed prothrombin time of 10 s with inr of 1.1 , and activated partial thromboplastin time of 29 s cranial mri and mrv showed thrombosis of superior sagittal , bilateral transverse and bilateral sigmoid sinuses [ figure 3 ] .
magnetic resonance imaging and magnetic resonance venography showed thrombosis of superior sagittal , bilateral transverse , and bilateral sigmoid sinuses his steroid dose was continued at 15 mg per day and daily intravenous human albumin ( 20% ) 50 ml was given for 5 days till his serum albumin rose to 3 gm / dl .
he was started on deltaparin ( lmwh ) 1000 u ( 75 - 100 u / kg each dose 12 h ) subcutaneous twice daily for 5 days and warfarin was added on the fourth day with a dose of 0.75 mg ( in dose range of 0.05 - 0.1 mg / kg ) twice a day .
sixth day onwards , patient was maintained on warfarin only to keep inr between 2.0 and 2.5 .
his mri with mrv done 3 weeks later showed significant dissolution of thrombosis in all affected sinuses .
presently , the boy is on warfarin 1.5 mg for venous thrombosis , prednisolone 15 mg / day , and mycophenolate mofetyl 125 mg twice a day with his nephrotic state in remission .
cerebral sinovenous thrombosis is a rare disorder in children , but increasingly diagnosed now because of greater clinical awareness , sensitive neuroimaging techniques . in follow - up of 700 children with nephrotic syndrome over a period of 17 years , divekar et al .
it is surprising that case 2 in the present study had persistant headache at the time of initial presentation of nephrotic syndrome of 15 days duration .
cvst in nephrotic syndrome is associated with a hypercoagulable state arising due to alteration in blood levels of various factors involved in coagulation , fibrinolytic system , alteration in platelet function , hemoconcentration , increased blood viscosity , and possibly administration of steroids and diuretics .
loss of antithrombin iii ( physiological anticoagulants ) and plasminogen in urine and their low level in blood has been correlated with low serum albumin level .
mri with magnetic resonance venography is the preferred modality over ct scan for diagnosis and follow - up of cerebral venous thrombosis because of its high sensitivity .
in addition to treating relapse of nephrotic state , correction of hypoalbuminemia by intravenous fresh frozen plasma to replace deficient physiologic anticoagulant factors and or i / v human albumin in small aliquots daily till serum albumin is reasonably normalized .
the most commonly used treatment is unfractionated heparin or low - molecular - weight heparin to arrest the thrombotic process for initial few days to a week with overlap of oral anticoagulants in the last 2 days of parentral heparin.[37 ] the optimal duration of oral anticoagulant ( warfarin ) treatment after the acute phase is unknown in this particular situation , but in the absence of recurrent thrombosis , according to the guidelines of seventh accp conference on antithrombotic therapy in children , anticoagulant therapy is to be continued at least for 6 months , using vitamin k antagonists ( warfarin ) with targeted inr range 2.0 - 3.0 fibrinolytic agents have not been fully investigated in nephrotic children .
the signs and symptoms of cerebral venous thrombosis are occasionally non - specific making clinical diagnosis difficult .
hence , a high degree of suspicion is required , and a diagnosis of cvst should be considered in any child of nephrotic syndrome presenting with features of central nervous system involvement .
mri and mr venography is a better way of imaging as compared to ct scan .
prompt treatment with anticoagulation is very useful and should be instituted as early as possible to improve the outcome .
not allowing serum albumin to fall below 2 gm / dl could be a preventive measure to such complications .
 nephrotic syndrome in infancy and childhood can be associated with thromboembolic complications . 
 we describe two cases of nephrotic syndrome who presented with non - specific findings . 
 magnetic resonance imaging brain with magnetic resonance venography showed thrombosis of multiple venous sinuses . 
 patients were successfully treated with anticoagulants and there was complete resolution of thrombosis on repeat imaging . 