Transient protein S deficiency with deep venous thrombosis during Salmonella typhimurium infection.

A patient with deep venous thrombosis and low protein S activity during the course of Salmonella typhimurium infection is presented. Although protein S deficiency has been reported in patients with disseminated intravascular coagulation, it was not present in this patient and his protein S activity was normal after the findings of infection and deep venous thrombosis disappeared.     

Anticardiolipin and acquired protein S deficiency in early childhood

A 27 month old child presented with left hemiplegia and was found to have deep cerebral venous thrombosis. The deep cerebral venous thrombosis resolved on warfarin. Elevated and fluctuating anticardiolipin antibodies as well as protein S deficiency were detected.     

Mesenteric venous thrombosis in a child with type 2 protein S deficiency

A 5-year-old girl presented with abdominal pain and bloody stools 2 weeks after suffering from influenza A infection. Enhanced computed tomographic scan showed widespread splanchnic venous thrombosis and small intestine necrosis. She recovered after the necrotic bowel was resected. The patient continues to receive anticoagulant therapy. Thrombophilia screening after the complete resolution consistently showed mildly decreased protein S (PS) activity with normal PS antigen levels. Sequence analysis detected a heterozygous K196E mutation in the PROS1 gene. Type 2 PS deficiency was diagnosed. This is the first report of mesenteric vein thrombosis in a child with a type 2 PS deficiency.     

RADIOLOGICAL FINDINGS OF ATYPICAL EXTRASKELETAL EWING SARCOMA

Vaso-occlusive crisis is the most common cause of morbidity in patients with sickle cell anemia (SCA). Central nervous system involvement that leads to hemiplegia is the most frequent neurological complication in those patients. Peripheral deep venous thromboembolism was not reported in SCA patients. Activated protein C resistance is associated with an increased risk of thrombophilia. The authors report an SCA patient with recurrent cerebrovascular accident and deep venous thrombosis. Activated protein C resistance due to factor V Leiden heterozygous and heterozygocity for the methylenetetrahydrofolate reductase were diagnosed and suspected to be the risk factors that contribute to the development of the deep vein thrombosis in this SCA patient.     

VENOUS THROMBOEMBOLISM, FACTOR V LEIDEN, AND METHYLENETETRAHYDROFOLATE REDUCTASE IN A SICKLE CELL ANEMIA PATIENT

Vaso-occlusive crisis is the most common cause of morbidity in patients with sickle cell anemia (SCA). Central nervous system involvement that leads to hemiplegia is the most frequent neurological complication in those patients. Peripheral deep venous thromboembolism was not reported in SCA patients. Activated protein C resistance is associated with an increased risk of thrombophilia. The authors report an SCA patient with recurrent cerebrovascular accident and deep venous thrombosis. Activated protein C resistance due to factor V Leiden heterozygous and heterozygocity for the methylenetetrahydrofolate reductase were diagnosed and suspected to be the risk factors that contribute to the development of the deep vein thrombosis in this SCA patient.     

遗传性易栓症5例临床特征及基因分析北大核心CSCD

目的:分析遗传性易栓症(IT)患儿的临床表现、遗传学特点及诊治情况。方法:回顾性研究。纳入2016年10月至2021年8月首都医科大学附属北京儿童医院呼吸一科收治的IT患儿进行研究,并随访。结果:符合IT诊断标准的患儿5例,其中男3例,女2例;确诊年龄为7岁~13岁6个月。5例患儿中,2例先天性蛋白C缺陷症,先天性蛋白S缺陷症、抗活化蛋白C抵抗、先天性纤维蛋白原异常血症各1例。5例患儿均有肺栓塞,2例有下肢深静脉血栓,1例有心脏血栓和动脉栓塞。易栓症实验室检测1例蛋白C水平明显减低,1例蛋白S水平明显减低;2例患儿急性期抗磷脂抗体阳性,但3~6个月后复查为阴性。遗传学分析2例为 PROC基因变异,1例 PROSI基因变异,1例 F5基因变异,1例 FGA基因变异。患儿均行长期抗凝治疗,其中4例行华法林治疗,1例行利伐沙班治疗。随访时间3个月~5年,随访中,1例患儿自行停用抗凝药物1个月后在感染诱因下出现血栓复发。 结论:IT患儿的临床表现与成人一样,主要表现为静脉血栓栓塞(VTE);易栓症实验室检测存在局限性,基因分析具有重要意义。IT患儿需长期抗凝治疗,以减少VTE复发。     

Genotypes and phenotypes of protein S deficiency in Thai children with thromboembolism

The prevalence of protein S (PS) deficiency in Asian patients with venous thromboembolism is around 8–30%, higher than that in Caucasian populations. The present study reports the genotypes (including one novel mutation) and phenotypes of children with PS deficiency at a tertiary care institute. A total of six patients were included, three with arterial ischemic stroke, two with cerebral venous sinus thrombosis, and one with deep vein thrombosis. PS mutations were identified in four patients: p.R355C, p.G336D, p.E67A, and p.N188KfsX9. p.N188KfsX9 is a novel mutation with less than 20% PS activity noted in heterozygotes.     

Deep vein thrombosis in an adolescent

We report an unusual case of deep vein thrombosis following minor trauma in an adolescent who presented with a swollen, tender, lower extremity. Work-up consisted of a venogram which demonstrated occlusion of the deep venous system in the proximal leg. The patient was hospitalized for intravenous heparin followed by oral anticoagulation therapy. The problem of deep venous thrombosis in adolescents and the approach to diagnosis are discussed.     

Neonatal cerebral venous thrombosis coexisting with bilateral adrenal hemorrhage

We report a case of severe perinatal asphyxia with both cerebral venous thrombosis and adrenal hemorrhage who survived with severe sequela including multicystic encephalomalasia, acquired microcephaly and blindness. Hematological investigations showed normal levels of anticardiolipin antibodies, protein C and S levels and activity, antithrombin III levels. Factor V Leiden mutation was negative. The adrenal hemorrhage resolved within three months with glucocorticoid therapy, the cerebral venous thrombosis resolved within two months without treatment. The literature on neonatal cerebral venous thrombosis is also reviewed.     

Postinfection purpura fulminans in a patient heterozygous for prothrombin G20210A and acquired protein S resistance

Purpura fulminans usually consists of large, often symmetrical, spreading ecchymosis, which may later develop into extensive areas of skin necrosis and peripheral gangrene. Postinfectious purpura fulminans associated with an autoantibody directed against protein S has been described. The interaction and the contribution of recently described mutations such as factor V Leiden and prothrombin G20210A to the development and progression of postinfectious purpura fulminans and venous thrombosis is not known. The authors describe a patient heterozygous for prothrombin G20210A who developed purpura fulminans and extensive venous thrombosis secondary to acquired protein S deficiency.     

Deep venous thrombosis in a child with nephrotic syndrome associated with a circulating anticoagulant and acquired protein S deficiency.

Thromboembolic events occur with a frequency of 3-5% in children with nephrotic syndrome (NS). Although numerous abnormalities in all phases of coagulation have been described in NS, the pathogenesis of clotting abnormalities remains poorly understood in this group of patients. We describe a child with long-standing NS in whom a severe deep venous thrombosis and pulmonary embolism secondary to acquired protein S deficiency and a strong lupus-type circulating anticoagulant developed. In addition, this patient had a markedly decreased plasma level of C4b binding protein. Although acquired protein S deficiency has been described in various clinical disorders including NS, our patient is unusual in having C4bBP deficiency, and his is the only reported pediatric case of NS complicated by thromboembolism in which a circulating anticoagulant has been implicated, to our knowledge.     

Neonatal renal vein thrombosis and prothrombotic risk

A case of extensive deep venous thrombosis in a four a day old infant was presented. Unusually this patient was shown to be heterozygous for three thrombophilia genes; Factor V Leiden, prothrombin and antithrombin gene mutations, the latter being novel. Conclusion:  There are no randomized controlled trials to guide management in deep venous thrombosis in the newborn but knowledge of the prothrombotic risk factors may help direct treatment.     

儿童肺炎支原体相关凝血功能障碍与血栓形成

肺炎支原体感染引起凝血功能障碍与血栓形成,主要累及深静脉、肺和脑等器官。中心静脉置管是发生深静脉血栓形成最重要的危险因素。肺炎支原体肺炎肺实变范围超过肺组织2/3是发生肺动脉栓塞的高风险。血液D-二聚体(>5 mg/L)升高是预测血栓风险的独立危险因子,敏感性较高。彩色多普勒超声和CT血管成像等检查是确定血栓形成的主要方法。肺炎支原体感染相关深静脉血栓形成或肺动脉栓塞宜采用个体化的抗凝与溶栓治疗。     

An adolescent with lower-extremity swelling

Lower-extremity swelling is an uncommon presentation in a pediatric emergency department. Deep venous thrombosis is one of the common differential diagnoses in a patient with an underlying predisposing factor. We report a case of a previously healthy adolescent without any risk factor for thromboembolism presented with deep venous thrombosis. The pertinent literature is reviewed.     

以肺栓塞起病的遗传性蛋白S缺乏症家系并文献复习

目的:探讨以儿童肺栓塞起病的PROS1基因相关遗传性蛋白S缺乏症（PSD）的临床特征和基因变异特点。方法:回顾性分析北京大学第一医院儿科于2020年诊断的以肺栓塞起病的PSD 1个家系2例患儿的临床表现、实验室检查、影像学、遗传学等资料,并对其家系成员进行蛋白S活性和PROS1基因的筛查。以“PROS1”“蛋白S缺乏症...     

Prothrombotic abnormalities in children with venous thromboembolism

PURPOSE: The aim of this study was to determine the frequency of acquired or inherited prothrombotic disorders in a pediatric population with venous thromboembolism (VTE). PATIENTS AND METHODS: From May 1992 to April 1998, 56 consecutive children with VTE were prospectively studied at a single center. RESULTS: The median age was 8.4 years (range, 0.1-18 years). There was a male predominance. Fifty (89%) children had thrombosis in the lower venous system. Risk factors were detected in 54 (96%) children. Twenty-one (38%) thrombotic episodes were related to central venous lines. Family history of thrombosis was positive in 13 (23%) patients. In 26 (46%) patients, a prothrombotic disorder was detected. Nine of them had inherited disorders (protein C deficiency, 5 patients; protein S deficiency, 3 patients; Factor V Leiden mutation, 1 patient), and 13 children had acquired disorders (antiphospholipid antibodies, 5 patients; antithrombin deficiency, 8 patients). The remaining four showed combined abnormalities (Factor V Leiden mutation associated with inherited protein S deficiency, 1 patient; acquired antithrombin deficiency, 2 patients and inherited antithrombin deficiency, 1 patient). CONCLUSIONS: In the series, a high percentage of prothrombotic disorders was detected; thus, a complete hemostatic evaluation should be performed in all of the children with VTE whether the patients have one or more risk factors.     

Deep venous thrombosis complicating myelomeningocele: report of three cases

Deep venous thrombosis is a frequent, well-recognized complication of spinal cord injury. Patients with myelomeningocele often have similar weakness of the lower extremities. Following orthopedic surgery, they may also be immobilized at a time when they are hypercoagulable. In addition, as with patients with spinal cord injury, patients with myelomeningocele are prone to urinary tract infection, which may cause local inflammation in the pelvic veins. For the first time, three patients with myelomeningocele complicated by deep venous thrombosis are described. The differential diagnosis (deep venous thrombosis vs osteomyelitis vs fracture) is also discussed in a child with myelomeningocele and a warm, swollen leg, as are the diagnostic methods available. Finally, the issue of antithrombotic prophylaxis in patients with myelomeningocele who are to undergo extensive orthopedic surgery is discussed.     

Cerebral venous thrombosis and Escherichia coli infection in neonates

AIM: To present a possible association between cerebral venous thrombosis (CVT) and infection with Escherichia coli. METHODS: Four neonates with deep CVT occurring during an E. coli infection are presented. RESULTS: In these patients the thrombotic disease was found by Doppler ultrasonography. The thrombosis involved at least the sagittal sinus and the transverse sinus according to subsequent MRI scans. The E. coli strains did not produce verotoxin or haemolysin. Disseminated intravascular coagulation was not demonstrated. Three patients presented with seizures. At discharge, all of the patients had signs of neurological damage, but two of them have improved significantly since then. None of the patients has had recurrent (venous) thrombosis. CONCLUSION: E. coli infections in neonates may predispose to CVT, a finding that has clinical implications.     

Deep venous thrombosis in a child associated with an abnormal inferior vena cava

Congenital anomalies of the inferior vena cava (IVC), such as absence or atresia, although well documented, are uncommon and result from aberrant development during embryogenesis. Absence or atresia of the IVC is usually discovered accidentally. Patients are typically asymptomatic of the condition itself. Many concurrent cardiovascular-associated abnormalities have been described. We report a 10-y-old boy admitted to the emergency room with painful swelling of his right lower limb without previous trauma or surgery. After 3 d, swelling also involved the left lower limb. A Doppler ultrasound of the lower limbs revealed bilateral thrombosis of the vena iliaca communis, vena iliaca externa, femoral vein communis and superficial extending to the IVC. Magnetic resonance imaging (MRI) of the abdomen was performed. On MRI, we demonstrated a hypoplastic IVC. The results of blood coagulation studies, including levels of antiphospholipid antibodies, proteins C and S, and antithrombin III, were normal. The patient was treated with intravenous heparin for 8 d and discharged with oral warfarin therapy, which has been recommended for life.
Conclusion: Therapy against deep venous thrombosis must be focused on its prevention in the future. An abnormal inferior vena cava should be considered in young patients with deep venous thrombosis without apparent cause.     

Prolonged bacteremia with catheter-related central venous thrombosis

Infection of a central venous thrombus is a serious but rarely recognized complication of the use of central venous catheters in children. We report the cases of seven children with persistent bacteremia or fungemia in which central venous thrombosis was demonstrated by ultrasonography after removal of the catheter. All patients had signs and symptoms of infection, but only one had clinical evidence of central venous stasis. Bacteremia persisted from 6 to 35 days. Infection did not resolve in any patient prior to catheter removal, and five patients had positive blood cultures for 5 or more days after removal of the catheter. Six patients, including all who survived, were treated parenterally with antibiotics for more than 28 days. Two patients died; neither death was directly attributable to infection. Central venous thrombosis should be suspected in patients with persistent catheter-related bacteremia. Optimal treatment of this problem is not yet known.