The molecular biology of von Willebrand disease

von Willebrand disease is the most common inherited bleeding disorder in humans, with the general population prevalence estimated to be as high as 1% in some studies. This condition exhibits extensive heterogeneity with over 20 distinct subtypes distinguished based on subtle clinical and laboratory differences in presentation. Recent research laboratory advances have shed considerable new light on the molecular basis of this disorder. Specific mutations within the von Willebrand factor gene have been identified in many of the qualitative variants of von Willebrand disease, providing important new insight into the structure and function of this central clotting protein. However, the complex genetic factors determining the clinical severity of type 1 von Willebrand disease, the most common variant, still remain largely unknown and are the subject of current investigation.     

Intravascular papillary endothelial hyperplasia of the mouth: report of six cases and literature review

OBJECTIVE: Oral intravascular papillary endothelial hyperplasia (IPEH) is an uncommon, reactive vascular lesion with no specific clinical features. Microscopically two subtypes have been described: a pure and a mixed form. The importance of IPEH is in its resemblance to angiosarcoma. The aim of this study was to evaluate both the prevalence of IPEH in a consecutive series of oral vascular malformations and the clinico-pathological features. MATERIALS AND METHODS: Histological sections of 103 consecutive cases filed as vascular malformations were reviewed for histopathological criteria of IPEH. RESULTS AND CONCLUSION: We found six cases of oral IPEH, of which three were diagnosed previously. Five of these cases were in males, and the mean age was 58 years. It was usually described as a blue or reddish nodule. The lower lip mucosa was the most common site followed by the tongue and the upper lip. Histologically, thrombi were always present and five out of the six lesions appeared in a mixed form, while only one was in a pure form. Three cases were diagnosed at an early stage and in the other three, the lesions were well-established. In this series, IPEH associated with vascular malformation was more common than reported in previous studies. Lesions at early stages, especially in the mixed form, may be unnoticed.     

肝硬化静脉曲张出血患者门静脉血栓的临床特征

目的 探讨肝硬化伴食管胃静脉曲张出血（GVB）患者门静脉血栓（PVT）的发生情况及临床特征。方法 回顾性分析2015至2017年复旦大学附属中山医院收治的肝硬化伴GVB患者的临床资料，根据门静脉CT检查结果，将纳入的患者分为PVT组和无PVT组。比较两组实验室检查指标、肝静脉压力梯度（HVPG）和胃镜特征等。采用多因素logistic回归分析评估PVT的独立相关因素。结果 共纳入356例患者，其中117例（32.9%）有PVT。与无PVT组相比，PVT组脾切除率、白细胞计数、血小板计数和D-二聚体水平更高，血红蛋白水平更低（P<0.05）;PVT组重度食管静脉曲张和伴有红色征的食管静脉曲张发生率更高（P<0.05）。两组HVPG差异无统计学意义。多因素logistic分析显示，白细胞计数增加、D-二聚体水平升高和重度食管静脉曲张与PVT发生独立相关（P<0.05）。结论 肝硬化伴GVB患者PVT发生率较高；该类PVT患者机体炎症和促凝水平更高，伴有更严重的门静脉高压。     

Superior vena caval thrombosis in a child: An uncommon presentation of idiopathic dilated cardiomyopathy

A nine year old girl who presented with a thrombosis of the right internal jugular vein and superior vena cava was found to be in cardiac failure and to have a dilated cardiomyopathy. After transient improvement she deteriorated and was accepted for cardiac transplantation. Following transplantation her condition has been much improved.     

蚓激酶溶栓作用的实验研究

目的　研究蚓激酶在兔动 静脉旁路血栓形成模型中的溶栓作用。方法　将实验动物随机分为 6组 :模型组 ,生理盐水对照组 ,蚓激酶小剂量组 (2 5 μg kg) ,中剂量组 (5 0 μg kg) ,大剂量组 (10 0 μg kg) ,尿激酶阳性对照组 (2×10 4 U kg)。采用家兔颈动 静脉旁路模型 ,测定蚓激酶的溶栓作用 ;心脏取血 ,测定蚓激酶对血浆纤维蛋白原 (FIB)、血浆优球蛋白溶解时间 (ELT)、纤维蛋白裂解产物 (FDP)等生化指标的影响。结果　蚓激酶中剂量组与大剂量组可使ELT缩短 ,使血栓重量减轻 ;蚓激酶大、中、小剂量组可使FDP显著增多 ;蚓激酶对FIB影响不明显。结论　蚓激酶有抑制血栓形成 ,激活纤溶活性的作用 ,具有较好溶栓效力。     

A case in which danaparoid sodium was effective for portal venous thrombosis developed after endoscopic injection sclerotherapy for esophageal varices

We report a case of hepatitis C type liver cirrhosis with portal venous thrombosis in which danaparoid sodium was very effective. The patient developed portal venous thrombosis, esophageal ulcer, and esophageal stenosis at the same time after sclerotherapy. Since it was confirmed by abdominal computed tomography that there was no portal venous thrombosis before sclerotherapy, development of the thrombosis was considered to be associated with sclerotherapy. The patient was treated with balloon dilation therapy for esophageal stenosis, and with anticoagulation therapy using danaparoid sodium for portal venous thrombosis. The portal venous thrombosis disappeared 4 weeks after the treatment. Despite the condition of esophageal ulcer being caused by sclerotherapy, the patient was safely treated without any adverse effects and complications, and the clinical course has been good. It was indicated that danaparoid sodium was an anticoagulant unlikely to cause adverse effects such as hemorrhage and might be an effective drug for treatment of portal venous thrombosis.     

The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy

Summary. Background: The metabolism of estrogen contained within hormone replacement therapy (HRT) is influenced by the route of administration, and this may affect the risk of venous thromboembolism. Thrombin generation, a global coagulation assay, is a marker of hypercoagulability and is of potential use in determining the thrombotic risk associated with particular HRT administration routes. Objectives: To determine whether any effect of oral and transdermal HRT on thrombin generation is related to the plasma estrogen profile. Methods: We investigated the effects of oral, transdermal and no HRT (controls) in 52, 39 and 52 postmenopausal women, respectively, on thrombin generation, standard markers of thrombophilia, estradiol level and estrone level. Results: All parameters of thrombin generation were altered in women using oral HRT as compared with controls (P < 0.001 for all comparisons). No such differences were found in women using transdermal HRT. Estrone levels correlated with peak thrombin generation (R = 0.451, P < 0.001) in women using oral HRT, but there was no correlation in women using the transdermal route. Conclusions: Thrombin generation is significantly increased in women who use HRT administered by the oral route. This is probably mediated by the hepatic first‐pass metabolism of estrone, the main metabolite of oral estradiol, which is avoided by the transdermal route. The effect of estrone on thrombin generation may provide the explanation for the higher thrombotic risk seen in women using oral rather than transdermal HRT.     

成人脑深静脉系统血栓形成

目的：探讨脑深静脉系统血栓形成的病因、临床表现及影像特征和在非急性期局部溶栓治疗的效果。方法：回顾性分析了5例经DSA检查确诊为DCVT患的病因、临床表现及影像特征和在非急性期溶栓治疗的结果。结果：患男3人，女2人，年龄22-49岁，病程1-7月，以发烧为诱因2例，原因不明3例，伴有颅内静脉窦4例。经介入放射局部溶栓和全身抗凝治疗后，神经系统症状和体征明显减轻，未见明显副作用。结论：在诊断DCVT上，DSA比MRI要精确和敏感，且对治疗可进行评估；介入放射局部溶栓和全身抗凝治疗不仅在急性期对DCVT是安全、有效，而且在非急性期亦为一种积极治疗措施。     

Central venous catheter-related complications in children with oncological/hematological diseases: an observational study of 418 devices.

BACKGROUND: The use of indwelling central venous catheters (CVCs) has become commonplace in the management of children undergoing anticancer treatment. Several types of CVC are available, while information on complications observed in children is scarce. We describe the experience of two tertiary care centers in Italy that prospectively followed up three types of CVC used at both institutions over a 30-month period. PATIENTS AND METHODS: Between January 2000 and May 2002, double-lumen (DL) or single-lumen (SL) Hickman-Broviac (HB) catheters, and single-lumen pressure-activated safety valve (PASV) catheters were used and prospectively evaluated. Four types of possible complication were defined a priori: mechanical, thrombotic, malfunctioning and infectious. RESULTS: Four hundred and eighteen CVCs (180 SL-HB, 162 DL-HB and 76 PASV) were inserted in 368 children, for a total of 107 012 catheter days at risk of complication. At least one complication occurred while using 169 of the devices (40%): 46% of the DL-HB, 46% of the PASV and 33% of the SL-HB (P=0.02) catheters. Subjects with hematological malignancies or non-malignant diseases had significantly more complications than those with solid tumors (P <0.0001). Overall, 234 complications were documented: 93 infectious [complication rate per 1000 catheter days at risk (CR)=0.87], 84 malfunctioning (CR=0.78), 48 mechanical (CR=0.45) and nine thrombotic (CR=0.08). SL-HB had statistically fewer infectious complications, while PASV had more mechanical complications. In a multivariate regression model, the most significant risk factors for having a CVC complication were hematological disease [relative risk (RR)=3.0; 95% confidence interval (CI) 1.8-4.8] and age <6 years at CVC insertion (RR=2.5; 95% CI 1.5-4.1). As for the type of CVC, compared with SL-HB, the DL-HB catheter had a statistically significant two-fold increased risk of any complication (RR=2.1; 95% CI 1.2-3.6), while the PASV catheter had a borderline RR of 1.8 (95% CI 1.0-3.6). Analysis by tumor type showed a higher risk of any kind of complication in patients with solid malignancies who had received a DL-HB catheter as compared with an SL-HB catheter (RR=7.2; 95% CI 2.8-18.7). CONCLUSIONS: CVCs may cause complications in up to 40% of patients, with type of CVC, underlying disease and patient age being the three main factors that affect the incidence of CVC-related complications. SL-HB catheters have the best performance.     

Sonographic evaluation of upper extremity deep venous thrombosis.

OBJECTIVE: The purpose of this presentation is to review the techniques of performing an upper extremity Doppler examination, in addition to illustrating the sonographic appearances of acute and chronic upper extremity deep venous thrombosis (UEDVT). METHODS: The risk factors and complications of UEDVT are discussed, and the anatomy of the upper extremity deep venous system as well as examination techniques are described. Cases of acute and chronic deep venous thrombosis were also chosen to illustrate the spectrum of sonographic appearances. RESULTS: Color Doppler sonography is accurate in the diagnosis of UEDVT. However, in cases of equivocal Doppler findings, or when the sonographic findings are normal but clinical suspicion for central venous thrombosis is high, magnetic resonance or contrast venography is necessary for further evaluation. CONCLUSIONS: Color Doppler sonography is a rapid and noninvasive technique in the evaluation of venous disease in the upper extremity and is the modality of choice in screening for UEDVT.