Primary and rescue immune tolerance induction in children and adults: a multicentre international study with a VWF‐containing plasma‐derived FVIII concentrate

Most studies on immune tolerance induction (ITI) therapy in haemophilia A patients are focused on primary ITI in children. Here we report on the ITI outcome in a large retrospective cohort, including adults and patients with rescue ITI, treated with a pdFVIII/VWF concentrate. Retrospective data from haemophilic patients (FVIII< 2%) with inhibitors from 22 centres in Spain, Italy and Germany, who underwent primary or rescue ITI with pdFVIII/VWF concentrate, were collected. Complete success (CS), partial success (PS) and failure were defined based on the criteria of the consensus recommendations of the 2006 International ITI Workshop. A total of 41 cases of primary ITI (32 children and 9 adults) and 19 cases of rescue ITI (17 children and 2 adults) were evaluated. Success (CS+PS) rate of 87% was achieved in primary ITI and 74% in the higher risk profile of rescue ITI. Eight of nine (85%) patients with poorest prognosis (three or more of the known risk factors of poor response to ITI) achieved success (CS+PS). CS of 100% was observed in eight primary ITI patients with titre at start of ITI ≤2.5 BU and inhibitor peak ≤25 BU. The favourable response rates in primary and rescue ITI in children and in adult patients, even in the presence of poor prognostic factors, should be encouraged for broadening the indication of immune tolerance therapy in haemophilia A patients with inhibitors.     

Extra-Venous Use of Autologous Platelet Concentrate: Beginning of a New Era of Therapy of Transfusion Medicine?

Autologous infusion of blood platelets to induce healing of injured tissue is reported in several recent journals. The presence of many ‘platelet-derived-factors’ forms the basis of these studies. These studies have demonstrated improvement in 70–80% patients over a period of up to several months. We have identified the lapses in their techniques. We decided to undertake a small pilot study to test our use of “platelet concentrate” (U. S. P.) in patients of tendon injuries and also to establish a protocol for the extra-venous use of autologous blood platelets. We present, here, an improved technique of autologous platelet therapy in three groups of patients. Our results are compared with four earlier studies. Enhancement in clinical recovery of patients was achieved in shorter interval of time. We have concluded that use of “Platelet Concentrate” with its quality control tests, seems to be better in place of PRP and/or ‘uncontrolled’ platelet injection. Further, selection of patients for this therapy is crucial. Patients with acute bursitis do not appear ideal for this kind of therapy. However, chronic tendon injuries that are likely to worsen on corticosteroid injections can be treated with autologous platelets with excellent results. This appears to pave a new path for mesodermal regeneration and healing by extra venous use of platelet concentrate.     

A study of reported factor VIII use around the world

Summary.  The effect of replacement therapy has significantly improved the morbidity and mortality of people with haemophilia A in high income countries, a recent socio-economic development as the availability of safe concentrates has been matched by a willingness for their provision through reimbursement. In the developing world, however, this state has not been achieved, primarily because of the low visibility of haemophilia coupled with its expense, leading to inadequate treatment with its sequelae of severe pain, joint deformities, arthropathy, disabilities, and even death in childhood or early adult life. The objective of this paper was to study the reported factor VIII (FVIII) use on a country-by-country basis. Data on the reported FVIII use for 104 countries were obtained from the Marketing Research Bureau, Inc. and the World Federation of Hemophilia. The results show that FVIII use varies considerably among countries, even among the wealthiest of countries. The use of FVIII concentrate increases as economic capacity increases; in addition, consumption of FVIII has been increasing at a greater rate in high income countries. Given these trends, there probably will be a global increase in FVIII concentrates usage. Such information is critical for national healthcare agencies to determine realistic budget priorities in planning for an increased allocation of resources required to improve the treatment of patients with haemophilia A. This information is also important for pharmaceutical manufacturers to adequately plan for increased production of FVIII concentrates.     

不同杀螺剂现场灭螺效果比较

目的比较25％氯硝柳胺乙醇胺盐悬浮剂（SCNE）、50％氯硝柳胺乙醇胺盐可湿性粉剂（WPN）、40％密达利、50％荣宝的现场灭螺效果,为选择安全、高效的灭螺药物提供依据。方法选择4处螺情相似的有螺环境,分别用上述4种药物喷洒灭螺,于施药后3、7、15d开展钉螺调查,比较不同药物的灭螺效果。结果施药后3、7、15d,SCNE灭螺现场的钉螺校正死亡率为93．13％、91．85％、85．28％,WPN为89．82％、86．97％、77．66％,密达利为85．26％、89．47％、8t．25％,荣宝为77．23％、73．28％、78．15％。结论SCNE杀螺效果较好,值得进一步推广应用。     

Obesity in haemophilia patients: effect on bleeding frequency,clotting factor concentrate usage,and haemostatic and fibrinolytic parameters

The prevalence of obesity in patients with haemophilia (PWH) is increasing. We investigated the effect of obesity on bleeding frequency and clotting factor concentrate (CFC) usage in PWH and assessed whether prothrombotic changes observed in obesity differ between controls and PWH. Number of bleeds and CFC usage were compared between obese (N = 51) and non‐obese (N = 46) haemophilia A patients. Markers of haemostasis and fibrinolysis were compared between PWH, and gender‐, age‐ and body mass index (BMI)‐matched non‐haemophilic controls (N = 91). Median number of bleeds/patient‐month was comparable between obese and non‐obese patients with severe haemophilia (P = 0.791). Obese patients with severe haemophilia used 1.4 times more CFC/patient‐month than non‐obese patients (P = 0.036). When adjusting for weight this difference disappeared (P = 0.451). von Willebrand factor plasma concentration (VWF:Ag), factor VIII activity and endogenous thrombin potential were higher in obese than in non‐obese controls. Obesity did not influence these markers in PWH. Plasminogen activator inhibitor type 1 levels were higher in obese vs. non‐obese PWH (P < 0.001), whereas levels were comparable between PWH and controls (P = 0.912). Plasmin‐α2‐antiplasmin complex (PAP) levels appeared to be lower in obese vs. non‐obese subjects, both within controls (P = 0.011) and PWH (P = 0.008). However, in PWH, PAP levels were higher than in controls (P < 0.001). Obesity is associated with an increase in net CFC usage in PWH, but has no effect on bleeding frequency. In addition, obesity attenuates hyperfibrinolysis in PWH. Future research investigating whether obese PWH need CFC treatment dosed on weight or whether a lower dosage would suffice to prevent and treat bleedings is needed.     

26%四聚杀螺胺悬浮剂现场灭螺效果-成本分析

目的 了解26%四聚杀螺胺悬浮剂 （MNSC） 现场灭螺效果和应用成本, 评价其推广应用价值。 方法 选择河滩和湖滩为试验现场, 评价MNSC喷洒法灭螺效果与使用成本; 设50%氯硝柳胺乙醇胺盐可湿性粉剂 （WPN） 作为对照。结果 喷洒MNSC后15 d, 河滩钉螺死亡率为89.40%, 钉螺密度下降了92.35%; WPN组钉螺死亡率为88.08%, 钉螺密度下降了91.67%。在湖滩, MNSC组钉螺死亡率为86.59%, 钉螺密度下降了90.05%; WPN组钉螺死亡率为87.01%, 钉螺密度下降了91.71%。2个试验现场2种药物杀螺效果差异均无统计学意义 （P均＞0.05）。MNSC 每应用100 m2 的综合成本为15.03 元, WPN每应用100 m2 的综合成本为16.29元。结论 MNSC杀螺效果好、 使用成本低、 对环境影响小, 是一种值得推广应用的杀螺药物。     

The effects of selective serotonin reuptake inhibitors on platelet function in whole blood and platelet concentrates

Several studies report that patients who are treated with selective serotonin reuptake inhibitors (SSRIs) for depression may have increased risk of bleeding, particularly from the gastrointestinal tract. This may be related to low intraplatelet serotonin concentrations. Several blood banks do not store platelets from donors using SSRIs for transfusion, although the possible effects of SSRIs on platelet storage are not documented. We conducted a case-control pilot study of apheresis platelet concentrates prepared from donors using SSRIs (n?=?8) and from donors without medication (n?=?10). The platelet concentrates were stored for 5 days. Light transmission aggregometry (LTA), thrombelastography (TEG), and flow cytometric analyses were preformed for in vitro measurements of platelet function. Platelet function and platelet serotonin content were investigated in whole blood and in platelet concentrates stored for up to 5 days. LTA, TEG, and flow cytometric analysis of glycoprotein expression did not reveal any significant differences between the two groups. All 18 platelet concentrates performed well according to the standards set for platelet quality in relation to transfusion. Blood donors using SSRIs had significantly lower platelet serotonin compared to blood donors without medication. The results from our pilot study indicate that platelets from donors using SSRIs may be suitable for transfusion after storage for 5 days, but further laboratory and clinical studies are necessary to confirm this.     

Treatment of ischaemic heart disease in haemophilia patients: an institutional guideline

Summary.  Since the introduction of clotting factor concentrates, life expectancy of haemophilia patients is increasing and now approaches that of the general male population. Increasingly, haemophilia patients are confronted with age-related co-morbidity, including ischaemic cardiovascular disease. Treatment of stable angina pectoris and the acute coronary syndrome with antithrombotic therapy and percutaneous coronary intervention in haemophilia patients is feasible, but requires a tight co-operation between all specialists involved. As evidence-based guidelines are lacking, we developed a protocol on how we will treat haemophilia patients with ischaemic heart disease.     

Platelet concentrates produced from whole blood using the Atreus processing system

Background  The Atreus 2C+ system automates whole blood (WB) processing into a red cell concentrate, plasma and buffy coat (BC) suitable for platelet concentrate (PC) manufacture. This study compared the quality of PC made from BC using the Atreus, with those made by a manual method.
Study design and methods  WB was collected into Atreus disposables or standard bottom and top processing packs and held without active cooling for 26 h at 22 ± 2°C before processing, either with the Atreus, or using a centrifuge and press. BC were rested for 3 h and then 4 BC were pooled with one unit of plasma, mixed, centrifuged and pressed to make a pooled PC. The PC were analysed for quality markers to day 9 of storage.
Results  Platelet quality was good in both Atreus 2C+ derived PC and control units throughout storage. Metabolic markers (pH, ATP and HSR) and activation markers (CD62P, sCD62P, annexin V binding, microparticles, GP IIb/IIIa) did not differ between the Atreus and control units. Atreus-derived PC had significantly lower platelet yields (302 ± 59 × 10⁹ platelets/unit; mean ± standard deviation, n  = 8) than control PC (411 ± 76 × 10⁹ platelets/unit; P  < 0·01), but met the UK guidelines for platelet yield
Conclusion  From these in vitro data, PC produced from buffy coats prepared using the Atreus appear suitable for clinical use, and WB may be held at ambient temperature overnight without the use of active cooling devices. Optimizing the secondary processing conditions to handle Atreus 2C+ derived BC may increase the platelet yield.     

Warfarin and intracranial haemorrhage

SUMMARY: Spontaneous intracerebral haemorrhage is one of the most feared complications of long-term anticoagulation. Warfarin therapy not only increases the likelihood of suffering an intracranial haemorrhage, but also increases the mortality associated with it. This review aims to examine the incidence, pathogenesis, and outcome following a warfarin associated intracranial haemorrhage. It also evaluates the available evidence regarding optimal management of these patients, including timing and strategies for reversal of the coagulopathy, the role of neurocritical care and surgery, and indications for re-anticoagulation once the acute phase has past. The specific management of patients with prosthetic heart valves is also discussed. A summary of current societal guidelines is also included, as are some key practice points.