Ming-ming Ma, Li-hua Luo, Shu-fei Zeng, Xiao-yi Chen,Fan-na Liu, Bao-zhang Guan, Zhan-hua Chen, Xiang-nan Dong, and Liang-hong Yin

?

A Case Report of Acute Arterial Embolization of Right Lower Extremity As the Initial Presentation of Nephrotic Syndrome with Minimal Changes△

Ming-ming Ma, Li-hua Luo, Shu-fei Zeng, Xiao-yi Chen,Fan-na Liu, Bao-zhang Guan, Zhan-hua Chen, Xiang-nan Dong, and Liang-hong Yin

Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China

acute arterial thrombosis; nephrotic syndrome

Chin Med Sci J 2016; 31(4):261-263

HROMBOEMBOLISM is a well-known complication of nephrotic syndrome. Deep vein thrombosis, pulmonary embolism and renal vein thrombosis are the most common venous thromboembolic diseases in patients with nephrotic syndrome, while arterial thromboembolic complications are observed less frequently, and rarely when it occurs before the diagnosis of nephrotic syndrome.1Here we report a case with minimal change of nephrotic syndrome who presented initially as external iliac artery thrombosis, which may be associated with long sitting while playing Mah-Jong.

CASE DESPRIPTION

A 41-year-old man presented to the emergent unit of the First Affiliated Hospital, Jinan University for sudden severe pain and numbness of the right lower limb. He expe- rienced acute pain of right thigh two days ago, accompanied with paresthesia and paralysis of the lower right limb, for which he was admitted to the local hospital then. Digital subtraction angiography there revealed acute arterial embolization of right lower extremities. Emergent intraarterial thrombolysis, stent angioplasty were performed with Fog- arty balloon catheter for limb salvage. However there was no improvement after the treatment. Therefore, the pa- tient was referred to our hospital. On admission, his right leg was remarkably swelling, high tension and cold, with reduced motor activity as well as sensation. There was no palpable arterial pulse of the leg. Blood pressure was 104/70 mmHg, and temperature was 36.7?C. He was conscious and his general appearance was acutely ill. His heart and lungs ausculations were normal. The patient denied any history of fever, skin rash and chest or abdominal pains. He did not have significant history of medical disease, allergy and surgery. He was a non-smoker and with no alcohol or drug addictions, but had a habit of playing Mah-Jong, the most popular strategy game in some Chinese communities. None of his family members had renal disease.

Laboratory investigation showed elevated white blood cell 13.6×109/L(normally 4-10×109/L) with normal hemoglobin 12.3 g/dl (11-17 g/dl) and platelet count 28.6× 109/L (10-30×109/L), decreased serum total protein 2.55 g/dl (normally 6.5-8.5 g/dl) and albumin 1.27 g/dl (normally 4.0-5.5 g/dl). Serum cholesterol was 250.2 mg/dl (normally 119.8-220.4 mg/dl), and triglyceride was 75.4 mg/dl (normally 49.6-150.6 mg/dl). The coagulation profile showed an activated partial thromboplastin time of 55.8 seconds (normally 28-44 seconds), prothrombin time of 12.3 seconds (normally 11-16 seconds), fibrinogen of 486 mg/dl (normally 200-400 mg/dl). The results of liver and renal functions examinations and electrolytes tests were normal. Laboratory investigation for Systemic lupus erythematosus (SLE) showed nothing special. Urinalysis revealed 3(+) proteinuria. Urine protein excretion of 24 hours reached 9.3g/day. Computed tomography angiography did not find evidence of pulmonary embolism. Lower extremity angiography showed that the right common iliac artery was totally occluded from its origin.

Emergent intra-arterial thrombolysis was applied accordingly. Stent angioplasty and percutaneous transluminal angioplasty (PTA) were performed with the Fogarty balloon catheter for limb salvage. However, the swelling of the right leg got worsen and the pulses of his right dorsal pedis and posterior tibial arteries were unpalpable. Considering the potential high risks of pulmonary thrombosis and cerebral embolism at that moment, the patient finally had to take amputation of right lower extremity unfor- tunately. After the operation, the patient received anticoagulant therapy of low molecular weight heparin (LMWH) at a dose of 5,000 units/day. Percutaneous renal biopsy revealed minimal changes of nephrotic syndrome (Fig. 1 and Fig. 2). The patient was treated with methylprednisolone at a dose of 48 mg/day for eight weeks, with gradually reduced dose afterwards. 35 days after renal biopsy, laboratory data showed serum total protein and albumin regained normal level (5.0 g/dl and 3.45 g/dl respectively). His 24 hour urine protein excretion decreased to 0.093 g/day. No further symptom or sign of arterial thrombosis was shown. The patient has accepted a prosthetic surgery in our hospital.

DISSCUSSION

Most cases of thromboembolism associated with nephritic syndrome occur in the venous system. Arterial thrombosis is unusual but more severe if happens. Several factors that contribute to the hypercoagulative state in nephrotic syndrome might lead to thromboembolic compli- cations, including urinary loss of antithrombin Ⅲ and proteins; increased liver synthesis of procoagulants stimulated by hypoalbuminemia; alteration in levels of coagulation factors; lowered fibrinolytic activity; an increased viscosity of the blood and hemoconcentration; and other iatrogenic factors, such as administration ofimmobilization, multiple venous puncture, and treatment with diureticsand steroids.2,3The patient we report had hypoalbuminaemia and hyperli- pidaemia, the risk factor which may contribute to the thr- omboembolism in this case.

Figure 1. Light microscopy, periodic acid-Schiff staining, ×100. Glomeruli appeared almost normally. The capillary lumina were patent. The basement membranes were intact. A slight increase in the mesangial matrix was observed without increased amount of mesangial cells.Vacuolation in some epithelial cells of renal tubules was demonstrated.

Figure 2. Electron microscopy, ×3000. Diffuse effacement of the podocyte foot processes without electrondense immune deposits in the glomeruli. The width of glo- merular basement membrane presented normally.

Thromboembolic complications have been frequently reported in patients with long-lasting nephrotic syndrome.4Once acute lower limb arterial thrombosis or embolism onset, it develops and deteriorates rapidly. So early diagnosis and early treatment are critically important in order to re-open the blood vessel, restore blood flow and shorten the time of ischemia as far as possible. Thrombosis within 48 hours or less can be treated by interventional thrombolysis , but the chance of re-open is very small. In this case although the patient was diagnosed as lower extremity arterial thrombosis and received thrombolytic therapy within 2 days, it failed to save the limb and the specific situation was unknown. The subsequent interventional treatment performed in our hospital was a failure too because of the delayed time. At last, the right leg was swollen with diminished pulses of the right dorsal pedis and posterior tibial arteries, indicating irreversible necrosis, which warrant an amputation.

It is worth mentioning that in this case the patient had been playing Mah-Jong 4 to 5 hours everyday for 2 weeks before admitted to emergency unit. Zhang5reported a case of deep-vein thrombosis (DVT) associated with Mah-Jong. The possible mechanism of Mah-Jong-related thrombosis is not clear. Playing Mah-Jong may be associated to prolonged immobility of lower limbs, causing blood-flow stasis and incr- eased plasma viscosity. In addition, the author suggested that Mah-Jong-related DVT could be complicated by stress, especially the stress when gambling was involved in the game, and sleep deprivation. So it is distinct from the classic “economy class syndrome”. We speculated that thromboembolism in patients with nephrotic syndrome may be related to motionless of long-term sitting and intensive concentration. Hence, proper activity, relaxation and avoiding stress (especially gambling in Mah-Jong) should be recommended for patients with nephrotic syndrome.

In conclusion, patients with nephrotic syndrome have increased risks of thromboembolic events, especially when combined with other risk factors. Avoiding intensive con- centration while sitting statically for long time should be integrated in prophylactic therapy for thromboembolism in nephrotic syndrome.

1. Hsu HF, Huang SY. Carotid artery thrombosis in a child with membranous nephropathy associated with factor V Leiden mutation. Pediatr Int 2012; 54:573-4.

2. Ekici F, ?akar N. A large intracardiac thrombus in a child with steroid-resistant nephritic syndrome. Cardiol Young 2013; 23 :440-2.

3. Kimura A, Nishimura K, Miyasaka S, et al. A case of acute arterial thrombosis caused by nephrotic syndrome. Ann Vasc Dis 2010; 3:68-70.

4. Bellomo R, Atkins RC. Membranous nephropathy and thro- mboembolism: is prophylactic anticoagulation warranted. Nephron 1993; 63:249-54.

5. Zhang GS, Peng HL, Deng MY, et al. Mah-Jong-related deep vein thrombosis. Lancet 2010; 375:2214.

for publication November 29, 2015.

Tel: 86-13725251458, E-mail: 13725251458@ 126.com

△Funded by Obershi blood purification academician workstation of Guangdong Province (2013B090400004).