https://doi.org/10.5812/compreped.45829

Intracardiac Thromboembolic Complications in Nephrotic Syndrome

authors:

avatar Sylva Skalova 1 , *

Department of Pediatrics, Medical Faculty in Hradec Kralove, Charles University in Prague
Journal of Comprehensive Pediatrics: Vol.8, issue 1; e45829
published online: February 7, 2017
article type: Review Article
received: January 18, 2017
accepted: February 3, 2017

how to cite: Skalova S. Intracardiac Thromboembolic Complications in Nephrotic Syndrome. J Compr Ped. 2017;8(1):e45829. https://doi.org/10.5812/compreped.45829.

Abstract

Children with nephrotic syndrome are prone to hypercoagulation disorders and thromboembolism. Of these patients, intracardiac thrombus is the most serious and life-threatening complication, which is detectable by echocardiography and can be successfully treated with plasminogen activator. This review deals with the very rare occurrence of intracardiac thrombi in children with nephrotic syndrome.

1. Introduction

Nephrotic syndrome (NS) in children is characterized by proteinuria with resulting hypoalbuminemia, consequent edema, and hypercholesterolemia (1). Furthermore, in some patients, hypercoagulation disorders occur, resulting in thromboembolism, which is the most serious and rare complication of NS (2-5). This review deals with the very rare occurrence of intracardiac thrombi in children with NS.

1.1. Pathophysiology and Incidence of Thrombosis in Nephrotic Syndrome

The hypercoagulation status in NS occurs as a result of Antithrombin III (ATIII) deficiency, increased fibrinogen level, decreased protein C and S activity, increase in platelet number, and increased platalet aggregation. There are several risk factors of thromboembolic complications in patients with NS: hypovolemia, infection, diuretic treatment, immobilization, trauma, glucocorticoid therapy, hypoalbuminemia (< 20 g/L), and proteinuria (> 10 g/L) (2-5). All these factors contribute to the increased risk of thromboembolic complications in NS.

The incidence of thromboembolism in NS differs between children and adults. While reported as relatively high in adults, where the incidence varies between 9% and 70%, it is much lower in pedatric patients (≤ 5.3%). However, the incidence of clinical vascular thromboembolic events may be higher (up to 66%), regarding specific complications (2). Furthermore, pediatric patients with secondary forms of NS have a higher incidence of thrombotic events than those with minimal change disease (2). Thrombi form mostly in deep leg veins, inferior vena cava, rarely in superior vena cava, renal veins, axillary, subclavian, femoral, coronary and mesenteric arteries, and hepatic veins (2-5). Large retrospective studies from Bulgaria included 447 children with NS and the incidence of thromboembolic complications was 2% (9/447), while 16 clinically inapparent thromboembolic complications were recorded in 9 children. The reported incidence of thromboembolic events was 1.5% among patients with steroid-sensitive NS and 3.8% among those with steroid resistant NS (4). In a Turkish study, 16 children (median age of 2.2 years) with various primary diagnoses and confirmed intracardiac thrombus were analyzed. Six patients were newborns and two were infants. The localization was right atrium in 7, right ventricle in 5, left ventricle in 1, pulmonary artery in 1, and superior vena cava in 2 patients. The primary diagnoses were prematurity in 5, cyanotic congenital heart disease in 1, blood culture positivity in 3, malignancy in 4, nephrotic syndrome in 1, indwelling catheters in 10, and acquired or genetic thrombophilia in 6 patients (6).

Intracardiac location of thrombus in NS patients is extremely rare (3-18). To date, intracardiac thrombi have been reported in 15 patients (3, 6-18); in 5 adults (7-11) and 10 children (3, 6, 12-18).

1.2. Clinical Manifestations

Clinical manifestations of intracardiac thrombus include chest pain, shortness of breath, cardiac arrhytmias, heart failure, and acute coronary syndrome with myocardial infarction (14, 16). Such clinical manifestations may be even absent and the patients might be asymptomatic or with a subclinical course (13, 17, 18).

1.3. Diagnosis

Diagnostic tools include imaging procedures and laboratory assessment of several indices of coagulation status.

Echocardiography is the most reliable diagnostic tool in detecting intracardiac thrombus (7-18).

The diagnostic workup should also include complete blood count and laboratory assessment of fibrinogen, antithrombin III, protein C, protein S, International Normalized Ratio (INR) index, Activated Partial Thromboplastin Time (APTT) index, and serum level of homocysteine. The mutational analysis of coagulation factors V, II and Methylene-Tetra-Hydro-Folate-Reductase (MTFHR) is also helpful. Lung perfusion scan can be performed in patients with thrombus or thrombi in the right ventricle and anticipated lung perfusion defect (14).

1.4. Treatment

Treatment of intracardiac thrombus in NS is a medical emergency. Heparin and low-molecular heparin have been employed (16, 17), however, thrombolysis with alteplase, which is a tissue-type plasminogen activator is the most effective therapy, leading to thrombus dissolution within several hours after application (14). Surgical removal of thrombus has also been reported (12, 17). Prophylaxis with low-molecular heparin and consequentely with warfarin should follow for several months (14).

Undoubtly, adequate treatment of NS (corticosteroids, cyclophosphamide, cyclosporine A, levamisole, mycophenolate mofetil, and atorvastatin) is also necessary.

2. Conclusions

Pediatric nephrologists should be aware of thromboembolic complications in patients with NS. Intracardiac location of thrombus is a life-threatening complication of NS and physicians must be aware of this possibility.

References

  • 1.

    Bagga A, Mantan M. Nephrotic syndrome in children. Indian J Med Res. 2005;122(1):13-28. [PubMed ID: 16106086].

  • 2.

    Citak A, Emre S, Sairin A, Bilge I, Nayir A. Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol. 2000;14(2):138-42. [PubMed ID: 10684364]. https://doi.org/10.1007/s004670050029.

  • 3.

    Jarmolinski T, Zachwieja J, Bortkiewicz E, Stachowski J, Maciejewski J. Thrombo-embolic disease as a complication of nephrotic syndrome in children [Article in Polish]. Pediatr Pol. 1996;71(5):437-41. [PubMed ID: 8710427].

  • 4.

    Lilova MI, Velkovski IG, Topalov IB. Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974-1996). Pediatr Nephrol. 2000;15(1-2):74-8. [PubMed ID: 11095017]. https://doi.org/10.1007/s004679900253.

  • 5.

    Zaffanello M, Franchini M. Thromboembolism in childhood nephrotic syndrome: a rare but serious complication. Hematology. 2007;12(1):69-73. [PubMed ID: 17364996]. https://doi.org/10.1080/10245330600940048.

  • 6.

    Cetin ,I, Ekici F, Unal S, Kocabas A, Sahin S, Yazici MU, et al. Intracardiac thrombus in children: the fine equilibrium between the risk and the benefit. Pediatr Hematol Oncol. 2014;31(5):481-7. [PubMed ID: 24933192]. https://doi.org/10.3109/08880018.2014.919546.

  • 7.

    Huang TY, Chau KM. Biventricular thrombi in diabetic nephrotic syndrome complicated by cerebral embolism. Int J Cardiol. 1995;50(2):193-6. [PubMed ID: 7591332]. https://doi.org/10.1016/0167-5273(95)02366-5.

  • 8.

    Mak SK, Wong PN, Lee KF, Fung LH, Wong AK. Intracardiac thrombus in an adult patient with nephrotic syndrome. Nephrol Dial Transplant. 1996;11(8):1627-30. [PubMed ID: 8856224]. https://doi.org/10.1093/oxfordjournals.ndt.a027626.

  • 9.

    Raj M, Ramakrishnan A, Shenoy P, Negi VS, Swaminathan RP. Asymptomatic right atrial thrombus in a case of nephrotic syndrome. J Nephrol. 2006;19(6):825-7. [PubMed ID: 17173258].

  • 10.

    Schwartz JC, Wyrzykowski AD, Dente CJ, Nicholas JM. The nephrotic syndrome: an unusual case of multiple embolic events. Vasc Endovascular Surg. 2009;43(2):207-10. [PubMed ID: 18838397]. https://doi.org/10.1177/1538574408324511.

  • 11.

    Tamura H, Oyamada J, Shimada S, Okazaki M, Tsuchida S, Toyono M, et al. Large intracardiac thrombus in a patient with steroid-responsive nephrotic syndrome. Nephrology (Carlton). 2016;21(1):72. [PubMed ID: 26693847]. https://doi.org/10.1111/nep.12553.

  • 12.

    Bilginer Y, Ozaltin F, Duzova A, Erdogan I, Aki TF, Demircin M, et al. Right atrial thrombosis complicating renal transplantation in a child. Pediatr Transplant. 2008;12(2):251-5. [PubMed ID: 18179641]. https://doi.org/10.1111/j.1399-3046.2007.00857.x.

  • 13.

    Mortazavi F, Samadi M. Asymptomatic intracardiac thrombus in a child with nephrotic syndrome. Arch Iran Med. 2006;9(4):426-8. [PubMed ID: 17061622].

  • 14.

    Skalova S, Lukes A, Vanicek H, Klein T, Hak J, Dedek P, et al. Intracardiac thrombus--a rare complication of the steroid resistant nephrotic syndrome. Bratisl Lek Listy. 2008;109(12):573-5. [PubMed ID: 19348381].

  • 15.

    Ueno K, Nagasako H, Ueno M, Nerome Y, Eguchi T, Okamoto Y, et al. Large intracardiac thrombus in a child with refractory nephrotic syndrome. Pediatr Int. 2010;52(1):e51-3. [PubMed ID: 20158650]. https://doi.org/10.1111/j.1442-200X.2009.02991.x.

  • 16.

    Khan JA, Masood T, Shamsi F. Nephrotic syndrome: a rare cause of acute coronary syndrome in a child. J Coll Physicians Surg Pak. 2012;22(2):123-5. [PubMed ID: 22313655].

  • 17.

    Ekici F, Cakar N. A large intracardiac thrombus in a child with steroid-resistant nephrotic syndrome. Cardiol Young. 2013;23(3):440-2. [PubMed ID: 22813602]. https://doi.org/10.1017/S1047951112000923.

  • 18.

    Weisz W, Kemper MJ, Weil J, Muller-Wiefel DE. Asymptomatic intracardiac thrombus in steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2002;17(4):287-9. [PubMed ID: 11956884]. https://doi.org/10.1007/s00467-002-0831-4.