Question of Prophylactic Anticoagulation in Steroid Sensitive Nephrotic Syndrome – Rare Complication in Pediatrics

Case Report

J Pediatr & Child Health Care. 2017; 2(1): 1013.

Question of Prophylactic Anticoagulation in Steroid Sensitive Nephrotic Syndrome – Rare Complication in Pediatrics

Orosz P¹, Durányik M¹, Bíró E¹, Körhegyi I¹, Balogh I² and Szabó T¹*

¹Department of Pediatrics, University and Clinical Center of Debrecen, Hungary

²Department of Laboratory Medicine, University and Clinical Center of Debrecen, Hungary

*Corresponding author: Szabó T, Department of Pediatrics, University and Clinical Center of Debrecen, 4032 Debrecen, Nagyerdei krt. 98, Hungary

Received: February 02, 2017; Accepted: April 12, 2017; Published: April 21, 2017

Abstract

Nephrotic syndrome occasionally may be associated with complications of acquired hypercoagulable state. An eight-year-old boy with steroid responsive nephrotic syndrome developed his fourth relaps after nearly 15 months of remission. Acute neurological symptoms developed on the third day of his hospital stay. Cranial MRI demonstrated severe superior sagital bilateral transverse and rectal sinus thrombosis. Unfractionated heparin was switched to LMWH on the 6th day of treatment as progression-hemiparesis and seizures in the neurologic state were observed. Repeated MRI revealed new hyperacute vascular lesions. Besides the well known acquired prothrombotic state, we decided to search for inherited factors of procoagulant activity. We detected the activated Protein C rate below the lowest normal value. Furthermore, mutational analysis revealed heterozygous FV Leiden mutation in combination with prothrombin 20210A polymorphism (heterozygous mutation). LMWH followed by warfarin therapy led to successful complete recanalisation and neurological recovery. Warfarin was discontinued after 18 months follow up period. Lack of evidence based therapeutic protocols highlights the importance of sharing case reports where multiple aquired and/or genetical causes are detected.

Keywords: Nephrosis; Thrombosis; Pediatric; Leiden; Prothrombin; LMWH

Case Presentation

An eight-year-old boy with Steroid Sensitive Nephrotic Syndrome (SSNS) developed his fourth relaps after nearly 15 months of remission phase. He was diagnosed with Nephrotic Syndrome (NS) at the age of 4 and had experienced three steroid responsive relapses Family history is unremarkable.

On admission the patient was hospitalized with relapse of nephrotic syndrome and was treated with oral steroid at a dose of 60 mg/m2/day.

On the third day of his hospital stay he acutely developed severe headache, somnolent state followed by vomiting and seizures.

Coagulation studies showed the following parameters: Prothrombin Time (PT) of 8.2 sec (controll: 8.8 sec), an Activated Partial Thromboplastin Time (APTT) of 25, 2 sec (controll: 29, 2 sec), a Thrombin Time (TT) of 24.3 sec (controll: 18.2 sec), an INR of 0.97, a D-dimer of 33.85 mg/L FEU, a positive fibrin monomer test, an FDP of higher than 20 mg/L, and a platelet count of 224 G/L.

Cranial MRI demonstrated superior sagittal, bilateral transverseand rectal sinus thrombosis (Figure 2).

A loading dose of Un-Fractionated-Heparin (UFH) of 75 U/kg was given IV, followed by a continous infusion of 15-25 U/kg/hour. We attempted to maintain the APTT between 70 to 90 sec, with a control of 32 sec.

On the 6th day of his treatment the boy developed new symptoms: left sided hemiparesis with faciobrachial dominance, transient visual disturbance, repeatedly occuring seizures. Repeated MRI revealed new hyperacute vascular lesions on territories supplied by the right anterior and medial cerebral artery. The previously detected sinus thrombosis showed unchanged spread.

Anticoagulant therapy was immediately changed to LMWH administration (2mg/kg/day). 11 days after the admission, on reaching the desired level of anticoagulation warfarin was added with successful control of PT while LMWH was withdrawn Warfarin administration was discontinued after 18 months of problem free period.

The child gradually made a complete clinical recovery, proteinuria ceased by the end of the second week of steroid treatment, with no relapse occuring after withdrawal of steroid therapy. Cranial MRI performed 11 months later showed complete recanalisation with regularly filling sinuses (Figure 3).

Besides the well known acquired prothrombotic state, we decided to search for inherited causes of increased procoagulant activity. With functional tests we detected Protein S and ATIII activity within the reference range, however Protein C activity and activated Protein C rate remained below the lowest normal values. Further molecular genetic investigation, using nucleic acid hybridization assays, confirmed the diagnosis of heterozygous FV Leiden mutation that was suspected by previous APC resistance testing method. Prothrombin 20210A polymorphism analysis verified heterozygous mutation (Figure 1), but the presence of lupus “anticoagulant” was excluded.