| Abstract|| |
A 4-year-old boy with idiopathic steroid responsive nephritic syndrome developed bilateral sixth-nerve palsy and lethargy secondary to cerebral sinus thrombosis. Treatment with heparin, fresh frozen plasma as source of antithrombin III and vitamin K inhibitors may have prevented further sequels. However, anti-coagulation, as assessed by partial thromboplastin and prothrombin time, was difficult to achieve. Despite these problems the child made a complete neurological recovery.
Keywords: Nephrotic syndrome, Cerebral sinus thrombosis, Anti-thrombin III deficiency.
|How to cite this article:|
Al Fakeeh KN, Al Rasheed SA. Cerebral Venous Thrombosis in the Nephrotic Syndrome. Saudi J Kidney Dis Transpl 2000;11:59-63
|How to cite this URL:|
Al Fakeeh KN, Al Rasheed SA. Cerebral Venous Thrombosis in the Nephrotic Syndrome. Saudi J Kidney Dis Transpl [serial online] 2000 [cited 2020 Sep 19];11:59-63. Available from: http://www.sjkdt.org/text.asp?2000/11/1/59/36695
| Introduction|| |
Thromboembolism in patients with the nephrotic syndrome is a well known complication.  Clinically significant thromboembolism is more common in adults than children.  Cerebral venous thrombosis in children with the nephrotic syndrome is extremely rare and only few cases have been reported. ,, It has been reported in idiopathic as well as in congenital nephrotic syndrome.  The following case demonstrates this rare complication.
| Case Report|| |
A 4-year-old boy with idiopathic nephrotic syndrome was successfully treated with a course of steroids. Seven and ten months later he had two relapses, which were also steroid responsive. Four months after the second relapse, and while the patient was on 20 mg prednisone every other day, he was hospitalized because of generalized edema, vomiting and lethargy. Physical examination revealed generalized edema with blood pressure of 120/75 mm Hg, temperature 37 0 C, respiratory rate 20 per minute, weight 22 kg and height 111 cm. Neck stiffness and bilateral sixth nerve paresis were noted. The rest of the examination was unremarkable.
Blood investigations showed leukocyte count 10,000 cells/µL, hemoglobin 155 g/L, platelets 500,000 /µL, hematocrit 45%, serum creatinine 39 µmol/L, serum albumin 7 g/L, total protein 32 g/L and blood urea 3 mmol/L. Coagulation profile showed prothrombin time 11 sec, partial thromboplastin time 35 sec, activated protein C resist 2.4% (normal 2.3-4.6%), functional protein C 79% (normal 70-130%) and free protein S 73% (normal 65-140%). Urine dipstick test showed protein 4+, blood 3+. The collection of 24 hours urine for protein revealed a total excretion of four grams per day. Serum complement C3 and C4 were normal. Serum antinuclear antibodies (ANA) and anti DNA antibodies were negative.
Because of neck stiffness and sudden onset of sixth nerve paresis, a cranial computed tomography (CT) was performed. It showed a fresh clot in the straight sinus as well as in the medial part of the transverse sinus bilaterally. Magnetic resonance imaging (MRI) of the head and cerebral magnetic resonance angiography (MRA) showed thrombosis of the right internal cerebral vein, the straight sinus and the entire right transverse sinus extending into sigmoid sinus. Part of the left transverse sinus and the lower parts of the superior sagittal sinus were also thrombosed, [Figure - 1],[Figure - 2].
A renal ultrasonogram with Doppler flow revealed normal-sized kidneys with normal flow in the renal veins.
Treatment of cerebral venous thrombosis was started immediately with administration of intravenous heparin. A loading dose of heparin of 50 IU/kg was given followed by continuous infusion of heparin, aiming for APTT of 60-85 seconds. This level of anticoagulation was difficult to achieve despite daily infusion of fresh frozen plasma (FFP) as a source of anti-thrombin III (ATIII). A total of 30 ml/kg of (FFP) was given. Warfarin up to 0.3 mg/kg per day was added aiming for International normalized ratio (INR) of 2-3 and heparin infusion was gradually decreased. The nephrotic syndrome remitted within a period of 10 days and cyclophosphamide 2.5 mg/kg was added. Warfarin was continued for one year. One year later the child was still free from neurological complications with normal cranial CT scan findings.
| Discussion|| |
Incidence of clinically evident venous and arterial thrombosis is low in idiopathic nephrotic syndrome in children, and only few cases have been reported in the literature [Table - 1]. Subclinical episodes of thromboembolism are more common.  Risk factors for thrombosis in children includes dehydration, elevated hematocrit, trauma and steroid therapy.  MRI and MRA are more sensitive and specific in diagnosing cerebral venous thrombosis.  A negative CT scan does not rule out the diagnosis.  This was confirmed in our patient where the extent of thrombosis was more delineated by MRI and MRA.
The more severe coagulation abnormalities in children, compared to adult patients is probably due to the more pronounced hypoalbuminemia that is often encountered.  Plasma deficiencies of plasminogen and ATIII, which result from urinary excretion of these factors, and increased concentration of vitamin K-dependent factors resulting from compensatory increase in protein synthesis, all contribute to a hypercoagulable state in the nephrotic syndrome. 
Despite this significant prothrombotic tendency in the nephrotic syndrome, the simultaneous elevation of the natural anticoagulants, protein C and protein S, as well as the increased fibrinolytic activity in children, both seem to have major preventive mechanisms against thromboembolism. 
Loss of ATIII and heparin in nephrotic urine may contribute to the difficulties in anticoagulation in nephrotic patients.  Use of FFP as a source of ATIII or use of ATIII concentrates may help to achieve adequate anticoagulation. Anticoagulation can be maintained by using warfarin. We have been able to achieve INR of 2-3 using warfarin up to 0.3 mg/kg/day for few days. However, in spite of administering the same dose of warfarin INR was always <2 in remission.
The mechanism of warfarin failure in remission is not clear to us. Low molecular weight heparin has longer plasma half-life, better bioavailability and lower hemorrhage risk than standard heparin. It may have additional potential benefit in preventing thrombosis in the nephrotic syndrome and can be used as an alternative therapy.  Fibrinolytic agents have not been fully investigated in nephrotic patients.
Our patient made complete neurological and radiological recovery. Early recognition and treatment with heparin and warfarin may reduce the risk of neurological complications.
| References|| |
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Khalid N Al Fakeeh
Department of Pediatrics, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426
[Figure - 1], [Figure - 2]
[Table - 1]