Von Willebrand disease: diagnosis and management

Von Willebrand Disease is a common cause of excessive bruising and bleeding in children. This short article gives advice on diagnosis and management for paediatricians. Given its prevalence and presenting symptoms, VWD should always be considered in the assessment of children suspected of non-accidental injury. Its diagnosis can be challenging, not only because of the various subtypes of the disorder but because of the considerable overlap between VWD and normal individuals. Laboratory diagnosis requires a range of quantitative and qualitative tests of the VWF protein, with targeted gene analysis increasingly used to confirm the diagnosis of type 2 and type 3 VWD. Bleeding Assessment Tools may be helpful in directed laboratory testing but are often less so in young children who have had limited haemostatic challenges. Treatment for VWD includes the use of antifibrinolytic drugs, vasopressin or VWF-containing clotting factor concentrates. Treatment is often on-demand for individual bleeding episodes but there are specific indications for the use of prophylactic treatment in children.     

Utilization of recombinant activated factor VII in southern Ontario in 85 patients with and without haemophilia

Recombinant activated factor VII (rFVIIa) is licensed for the treatment of bleeding in individuals with haemophilia and inhibitors. The use of rFVIIa appears to be increasing, and an increase in unlicensed use is suspected. There are currently few data about the specific indications for its use. The aim of this study was to describe the patterns of utilization of rFVIIa. We performed a retrospective cohort study using rFVIIa infusion data collected prospectively and clinical data collected retrospectively. Patients were identified using a tracking system designed to account for use of all coagulation factor concentrates issued in southern Ontario. Between 1 January 2001 and 31 December 2005, 85 patients received rFVIIa. 1164 infusions were given (8246.4 mg). Haemophilia patients with inhibitors accounted for 82.9% of rFVIIa infused and represented 8.2% of patients. The total amount of rFVIIa used increased each year from 2001 to 2004 and then decreased in 2005. The total number of infusions of rFVIIa administered annually increased. Both on-label and off-label use of rFVIIa increased. The number of patients with haemophilia receiving rFVIIa remained small and constant. The number of patients receiving rFVIIa for off-label indications increased markedly. Most rFVIIa infusions were given for licensed indications; however, these infusions represented <10% of patients treated. Overall, the utilization of rFVIIa is increasing, mostly for approved indications; however, the number of patients being prescribed rFVIIa for off-label indications has increased. The tracking system used in this study is a valuable tool to describe ongoing utilization patterns of rFVIIa.     

The effect of fibrin sealant haemostasis on post-operative pain in tonsillectomy

Pain following tonsillectomy is an important problem. It is caused by the surgical trauma of excision and haemostasis. Numerous surgical and pharmacological solutions have been tried, with disappointing results. Fibrin sealant is a widely used atraumatic haemostatic agent. This study aims to determine whether tonsillectomy with fibrin sealant haemostasis results in less post-operative pain than that with the conventional technique of diathermy. Fifty consecutive adult patients undergoing tonsillectomy were prospectively studied. They were randomized to receive either fibrin sealant or diathermy haemostasis. Other pain variables were controlled. Pain was measured by a visual linear analogue scale and inter-incisor distance on both the day of operation and the first post-operative day. The patients and pain measurer were blind to the randomization. The results showed that tonsillectomy with fibrin sealant haemostasis was significantly (P < 0.05) less painful than that with diathermy on both days studied and by both methods of pain measurement     

Biological coagulation findings in third-generation oral contraceptives

An increased risk of venous thrombosis has been demonstrated in women receiving oral contraceptives (OCs). This risk has been primarily associated with the oestrogen content, but recent studies showed that the progestogen may also play a role. A higher risk was found with the so-called third-generation (desogestrel, gestodene) as compared with the second-generation progestogens (levonorgestrel). The risk was approximately two-fold. These unexpected results have been the subject of many debates, and bias--such as selection bias--has been suggested. The existence of bias cannot be completely excluded, but the thrombotic risk seems however to be slightly higher with the third-generation progestins. Haemostatic changes have been observed during OC intake. Both coagulation and fibrinolytic activity are increased: the beneficial profibrinolytic effect may counterbalance the deleterious procoagulant effect. This may explain that the absolute risk of venous thromboembolism is low during OC treatments. Some women who have pre-existing haemostatic abnormalities such as deficiency in antithrombin or activated protein C resistance with factor V Leiden, may be at a higher risk. The biological plausibility of the increased risk related to the third-generation progestogens has been explored. Theoretically, this could be due to an increased coagulation or to a lack of increased fibrinolysis as compared with second-generation progestogens. The only difference presently reported with third-generation OCs is a decreased sensitivity to activated protein C, possibly resulting in a hypercoagulability of greater magnitude. The selection bias suggested in epidemiological studies may also exist for the latter study, as women taking third- or second-generation OCs were not randomized. The possible increased risk related to third-generation OCs should not change the known general contra-indications. Practical guidelines are proposed for women with personal or family history of venous thromboembolism, and for those with a congenital cause of thrombophilia.     

Thromboelastography, whole-blood haemostasis and recurrent miscarriage

BACKGROUND: Some cases of recurrent miscarriage have a thrombotic basis. Thromboelastography is a rapid, reproducible test of whole-blood haemostasis. METHODS: Thromboelastography was performed in 494 consecutive, non-pregnant women (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range 20-41) with no history of pregnancy loss. The prospective outcome of untreated pregnancies amongst 108 women with recurrent miscarriage was studied. RESULTS: The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5-7.8) significantly lower amongst women with recurrent miscarriage compared with controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P = 0.01). The pre-pregnancy MA was significantly higher amongst women who subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA >or=64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage. CONCLUSIONS: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.     

急性早幼粒细胞型白血病止血凝血检测及其临床意义

目的：探讨争民性早幼粒细胞型白血病的止血凝血变化及其对临床意义的影响。方法：应用放射免疫法、单抗酶联免疫法和发色底物法,对21例初入院的急性早幼粒细胞型白血病（APL）患者于化疗前和获得完全缓解后,进行血浆血栓烷（TXB2）、血管性假血友病因子抗原（VWF：Ag)、抗凝血酶原-Ⅲ（AT-Ⅲ）以及纤维蛋白原（Fg)、凝血酶原时间（PT）等检测,并与正常对照观察。结果：化疗前21例患者血浆TXB2、WVF：Ag、AT-Ⅲ、PT、Fg水平与正常对照比较有明显不同（分别P＜0.05,P＜0.01,P＜0.01,P＜0.01,P＜0.01),经治疗后获得完全缓解的13例患者血浆TXB2、VWF：Ag、AT-Ⅲ、PT、Fg水平与化疗前对照亦有明显不同（分别P＜0.05,P＜0.01,P＜0.01,P＜0.01,P＜0.01)。结论：APL患者的止血凝血障碍由多种因素形成,而且患者止血凝血障碍的 病理变化是普遍存在的。     

Early Experiences of Haemostasis on Brain Tumour Surgery with Argon Plasma Coagulation (APC)

Summary  Objective. We first applied a novel haemostatic strategy involving Argon Plasma Coagulation (APC), an innovative no-touch electrocoagulation technique in which a high-frequency alternating current is delivered to the tissue through ionized argon gas, to brain tumour surgery, and report its usefulness and limitations.  Methods. The APC system we used comprised an APC 300 developed by ERBE Elektromedizin GmbH, Germany. We applied APC to 13 brain tumours in 12 patients (5 meningiomas, 4 sarcomas, 2 glioblastomas, and 2 pituitary adenomas). To avoid unnecessary thermal injury to the tissue as much as possible, power/gas flow settings of 20 and 40 W were used. The impact time was varied individually but was around several seconds per one impact. The argon jet (1.5–4.5 L/min) clears a field of pooled blood and evenly conducts electrical energy to the target tissue. A thin and flexible probe particularly increased the usefulness of APC for haemostasis on deep-seated skull base tumour operations under a microscope.  Conclusion. All patients were successfully treated and satisfied with the surgical results without any complications due to APC. APC appears to be an excellent alternative strategy for achieving haemostasis on vascular-rich brain tumour surgery, and may be valuable for the management of patients with coagulation defects.     

敛溃散抗溃疡病机制分析和急性毒性试验

目的探讨敛溃散抗溃疡病机制并初步评价其安全性.方法抗酸作用采用酸碱滴定法,抑制胃蛋白酶活性和胃酸分泌作用分别采用Mett玻管法和大鼠插管法,镇痛作用采用小鼠扭体法,并观察敛溃散对出、凝血时间,以及胃肠蠕动和中枢神经系统的影响.结果 1g敛溃散能中和7.14mmol盐酸,显著降低大鼠胃液总酸度和胃蛋白酶活性;减少醋酸引起的小鼠扭体次数,缩短兔股动脉出血时间而不影响凝血时间,延长异戊巴比妥钠对小鼠的催眠时间.对大鼠胃酸分泌和小鼠胃肠蠕动未见明显影响.小鼠对敛溃散的最大耐受倍数为171倍.结论临床使用敛溃散是安全的,抗酸、抑制胃蛋白酶、局部止血和黏膜保护以及镇痛等作用是其抗溃疡病的主要机制.     

Endoscopic haemostasis: An overview of procedures and clinical scenarios

Acute gastrointestinal bleeding is among the most urgent situations in daily gastroenterological practise. Endoscopy plays a key role in the diagnosis and treatment of such cases. Endoscopic haemostasis is probably the most important technical challenge that must be mastered by gastroenterologists. It is essential for both the management of acute gastrointestinal haemorrhage and the prevention of bleeding during high-risk endoscopic procedures. During the last decade, endoscopic haemostasis techniques and tools have grown in parallel with the number of devices available for endotherapy. Haemostatic powders, over-the-scope clips, haemostatic forceps, and other emerging technologies have changed daily practise and complement the standard available armamentarium (injectable, thermal, and mechanical therapy). Although there is a lack of strong evidence-based information on these procedures because of the difficulty in designing statistically powerful trials on this topic, physicians must be aware of all available devices to be able to choose the best haemostatic tool for the most effective procedure. We herein present an overview of procedures and clinical scenarios to optimise the management of gastrointestinal bleeding in daily practise.