Saudi Journal of Kidney Diseases and Transplantation

CASE REPORT
Year
: 2011  |  Volume : 22  |  Issue : 4  |  Page : 792--795

ADAMTS-13 deficiency following Hemiscorpius lepturus scorpion sting


Ehsan Valavi1, Mohammad Javad Alemzadeh Ansari2, Sudabeh Hoseini3,  
1 Department of Nephrology, Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Faculty of Medicine, Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Pathology, Ali Asghar Children Hospital, University of Medical Sciences, Tehran, Iran

Correspondence Address:
Ehsan Valavi
Division of Nephrology, Pediatric Department, Abuzar Children«SQ»s Hospital, Pasdaran St, Ahvaz
Iran

Abstract

Hemiscorpius lepturus is a lethal scorpion with potentially cytotoxic venom. Various degrees of local and systemic toxicity have been observed after its envenomation ranging from local erythema to disseminated intravascular coagulation, renal failure and severe pulmonary hemorrhage. In this case report, we report on a seven-year-old patient who developed the hemolytic uremic syndrome (HUS) after being stung by the scorpion H. lepturus. This condition is characterized by microangiopathic hemolytic anemia, thrombocytopenia, increased serum levels of lactate dehydrogenase and uremia. We evaluated the causes of HUS and found that the levels of C3, C4, CH50 and H factors were normal, but the activity of Von Willebrand factor cleaving protease was decreased (less than 5% of the normal activity). The patient improved after administering therapy with plasma exchange.



How to cite this article:
Valavi E, Ansari MA, Hoseini S. ADAMTS-13 deficiency following Hemiscorpius lepturus scorpion sting.Saudi J Kidney Dis Transpl 2011;22:792-795


How to cite this URL:
Valavi E, Ansari MA, Hoseini S. ADAMTS-13 deficiency following Hemiscorpius lepturus scorpion sting. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Dec 8 ];22:792-795
Available from: http://www.sjkdt.org/text.asp?2011/22/4/792/82699


Full Text

 Introduction



Hemiscorpius lepturus is medically the most important scorpion in Iran. This scorpion is endemic in Khuzestan province and other southwestern areas of Iran and south of Iraq. [1],[2] The lethality arising from this scorpion is approximately 60 times higher than the average for the remaining venomous scorpion stings in the region. [3] The prominent and serious feature of the syndrome arising from the envenomation by H. lepturus is the occurrence of disseminated intravascular coagulation (DIC) and microangiopathic hemolytic anemia (MHA) and renal toxicity, which is characterized by hemoglobinuria, proteinuria, renal failure and the hemolytic uremic syndrome (HUS). [3],[4] However, the role of ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) in the pathogenesis of these findings is unknown as enzyme activity following scorpion sting has never been studied previously. Hence, we evaluated the level of ADAMTS-13 in a patient who presented to us with the HUS following H. lepturus scorpion sting.

 Case Report



A seven-year-old boy presented with bloody urine, vomiting and agitation, two days after being stung in the right forearm by the H. lepturus scorpion. The patient's vital signs and physical examination were normal. On admission, the hemoglobin and platelet count were 9.7 g/dL and 110,000/mm 3 , respectively; urine analysis showed 3+ hemoglobinuria and 3+ proteinuria. The serum creatinine (SCr) and blood urea nitrogen (BUN) levels were normal (0.7 and 22 mg/dL, respectively); prothrombin time and partial thromboplastin time were 36 and 75 sec, respectively [Table 1]. The Coomb's test was negative and the glucose-6 phosphate dehydrogenase (G6PD) level and peripheral blood smear were normal. At this time, the patient received polyvalent scorpion anti-venom, cefazoline and 20 meq/L of sodium bicarbonate in dextrose water. During his stay in the hospital, the SCr and BUN levels gradually rose to 1.4 and 61 mg/dL, respectively, but the hemoglobin level and platelet count dropped to 8.8 g/dL and 86,000/mm 3 , respectively. The lactate dehydrogenase (LDH) level increased to >4,000 IU/L. Blood film on day five showed fragmented erythrocytes and burr cells; the prothrombin time and partial thromboplastin time were in normal range. A clinical diagnosis of HUS was made. Blood sampling on day five prior to administration of any blood products showed plasma ADAMTS-13 level of 300 ng/mL (normal range: 630-850 ng/mL, American Diagnostics, Stanford, USA) and ADAMTS-13 autoantibody level was 14 IU/mL (normal range: <9.6 IU/ mL, American Diagnostics, USA). The levels of C3, C4, CH 50 and H factor were in the normal range. Packed cell transfusions were given and daily plasma exchange was performed and the patient was discharged after 15 days with a scar at the sting site and near normal laboratory data. After two months of follow-up, the SCr and BUN were 0.6 and 14 mg/dL respectively, LDH had decreased to 340 IU/L, and the scar had healed.{Table 1}

 Discussion



In 2008, we reported the case of a patient who developed HUS after being stung by H. lepturus.[4] We experienced several such cases in these two years and empirically treated the patients with plasma exchange.

HUS is a part of the disease cluster called thrombotic microangiopathies and is characterized by thrombocytopenia, microangiopathic hemolytic anemia and acute renal impairment. The causes of thrombotic microangiopathies vary widely and they have recently been divided into two groups, based on the understanding of the underlying etiology. Diseases associated with thrombotic microangiopathies where the etiology is not so well defined include HIV, malignancy, drugs (including cytotoxic drugs, immunosuppressive drugs, oral contraceptives and anti-platelet agents), pregnancy, systemic lupus erythematosus, and the anti-phospholipid antibody syndrome. Circumstances where the etiology is well understood include infection (Shiga and verocytotoxin-producing bacteria or Streptococcus pneumoniae), disorders of complement regulation (genetic or acquired disorders of complement regulation), defective cobalamine metabolism, quinine-induced thrombotic microangiopathies and ADAMTS-13 deficiency. [5],[6]

Since 2001, the Von Willebrand Factor (VWF)-cleaving protease has been identified as ADAMTS-13, which is a novel member of the ADAMTS family of metalloproteases. Initially, ADAMTS-13 was reported to be involved in the pathogenesis of thrombotic thrombocytopenic purpura; however, it has recently been reported that the activity of VWF-cleaving protease decreases in a wide variety of conditions, including liver cirrhosis, chronic uremia, HUS, idiopathic thrombocytopenic purpura, DIC, systemic lupus erythematosus, leukemia, pregnancy, snake bite, postoperative state, neonatal period and with advancing age. [7],[8],[9] ADAMTS-13 deficiency sequentially leads to the accumulation of unusually large VWF (ULVWf) multimers, platelet aggregation, and platelet clumping. [10]

Some reports state scorpion sting to be one of the causes of HUS; [4],[11],[12] however, the mechanism underlying HUS that develops after a scorpion sting remains unclear. The findings of histological examinations support the hypothesis that the venom of H. lepturus is primarily cytotoxic. This hypothesis was based on the following observations: dermonecrotic effects and widespread damage to all the nephron segments. [13] DIC and vascular injuries are well-known complications of scorpion stings, and several researchers have reported the occurrence of thrombotic events and development of microangiopathies (i.e., stroke and multiple cerebral and cerebellar infarctions), which explain the increased incidence of vascular injuries after envenomation. [14],[15] On the other hand, red cell fragmentation, MHA, thrombocytopenia, renal impairment and HUS have been reported following brown snake (genus Pseudonaja) and taipan (Oxyuranus scutellatus) envenomation and decreased level of ADAMTS-13 has been found in some of them. [7],[16],[17],[18],[19] However, we presumed that the mechanism underlying DIC and HUS in our patient could be similar to that seen after snake bite.

It is possible that the decrease in the VWF-cleaving protease activity can result through two pathways: destruction of ADAMTS-13 by the components of the scorpion venom and/or stimulation of the immune system to produce auto-antibodies against ADAMTS-13. We obtained good results following treatment with plasma infusion and plasma exchange for DIC and HUS following scorpion sting; however, plasma exchange with fresh frozen plasma (FFP) or cryosupernatant removes auto-antibodies and replaces deficient ADAMTS-13. Furthermore, we always use scorpion anti-venom, sodium-bicarbonate (15-20 mEq/L) and furosemide in these patients.

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