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Recently, analyses on inhibitor development according to concentrate in previously untreated patients (PUPs) from two national cohort studies have been published. A similar analysis has been performed on the first 4 years of data collection of the European Haemophilia Safety Surveillance System (EUHASS) project. Together with the initial report from the RODIN study published in 2013 [4], these publications provide data on a very considerable number of patients, almost exclusively originating from Europe. Reporting to multiple registries is common, and a rare disease such as haemophilia is no exception. Although the FranceCoag study, the UKHCDO study and the EUHASS study excluded patients overlapping with the RODIN study from their analyses, the additional overlap between the EUHASS, the FranceCoag and UKHCDO studies has not been previously reported. The analysis of non-overlapping data from the EUHASS study has the potential to contribute to the ongoing discussion about the perceived increased inhibitor risk associated with the use of specific recombinant Factor VIII concentrates. Thus, we hereby provide additional analyses of the data from the EUHASS study., peer-reviewed

International audience; Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 109/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 109/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 109/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients

International audience; Congenital haemorrhagic diseases are the consequences of haemostasis dysfunction or defects. Among primary haemostasis disorders, von Willebrand disease is the most frequent. Hopefully the type 1 von Willebrand disease, which affects 85% of patients, is generally a mild haemorrhagic disorder. However it may induce some troubles during the everyday life. On the other side, haemophilia is the most frequent congenital coagulation disorders. Haemophilia A is due a factor VIII deficiency while haemophilia B is due to a factor IX deficiency. Haemophilia is mainly a musculoskeletal disease. Recurrent joint bleedings may lead to a severe disabling arthropathy. The organization of care for hemophilia is managed by haemophilia treatment centers. Other rare bleeding disorders may lead to the same complications but requires specific treatments.

Background: Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant., Aim: To report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study., Methods: Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95% Confidence Intervals (95% CI) were calculated according to diagnosis and concentrate used., Results: Between 1-10-2008 and 31-12-2012, 68 centres reported on 7969 patients with non-severe haemophilia A and 1863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95% CI 0.30-0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20-80); with 72% occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2149 treatment years, resulting in an inhibitor rate of 0.05/100 years (CI 0.001-0.26). This inhibitor developed at age 6 years, after 6 EDs. The rate of inhibitors appeared similar across recombinant and plasma derived FVIII concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events., Conclusion: Inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of Inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII., peer-reviewed

Recently the French Society of Anaesthesia and Intensive Care (Societe Francaise d'Anesthesie et de Reanimation [SFAR]) issued recommendations for the prescription of routine preoperative testing before a surgical or non-surgical procedure, requiring any type of anaesthesia. Thirty clinical specialists performed a systematic analysis of the literature, and recommendations were then developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. One part of these guidelines is dedicated to haemostatic assessment. The goal of pre-anaesthetic screening for congenital or acquired haemostatic disorders is to prevent perioperative haemorrhagic complications through appropriate medical and surgical management. Preoperative assessment of bleeding risk requires a detailed patient interview to determine any personal or family history of haemorrhagic diathesis, and a physical examination is necessary in order to detect signs of coagulopathy. Laboratory investigation of haemostasis should be prescribed, not systematically, but depending on clinical evaluation and patient history. Standard tests (prothrombin time, activated partial thromboplastin time, platelet count) have a low positive predictive value for bleeding risk in the general population. Patients with no history of haemorrhagic diathesis and no conditions liable to interfere with haemostasis should not undergo pre-interventional haemostasis testing. Conversely, the existence of a positive history or a disease that could interfere with haemostasis should be an indication for clinically appropriate testing.

von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels

Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, web-based study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Forty-one surgical operations (24 'major' and 17 'minor') were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Factor VII (rFVIIa). Bleeding occurred during three major interventions of orthopaedic surgery, but rFVIIa was given at very low dose in each case. An antibody to FVII was observed in one patient who underwent a multiple dental extraction. No thromboses were reported during the 30-d follow up period. Replacement therapy with rFVIIa proved effective when suitable doses were used, which, during the period of maximum bleeding risk (the day of operation), were calculated (Receiver Operated Characteristic analysis) to be of at least 13 μg/kg/body weight per single dose and no less than three administrations. This indication is important especially in the case of major surgery.

Fibrinogen is routinely determined by functional assay on citrated plasma in the hematology department. However, immunoassay can be performed easily with nephelometric analyzer in the clinical chemistry laboratory allowing automatization. The aim of this study was first to compare the clotting von Clauss method (activity assay) with an immunonephelometric method (antigen assay) on the BN ProSpec (Dade Behring). Moreover, we evaluated the possibility of collecting blood samples on heparin to facilitate blood collection for clinicians and reduce required blood collection volumes for dosages.In a first step of experiment, the accuracy of immunonephelometric analytical performance was tested on heparinized and citrated tubes. For comparison studies, fibrinogen activity was then determined on citrated tubes in the hematology department and antigen measurement was performed on both citrated and heparinized plasma from 130 consecutive patients.As a result, the immunonephelometric method shows reliable performance and clinical sample measurements are not affected by the method used, validating the use of heparinized plasma samples for fibrinogen antigen determination with Dade Behring reagents.

A forty-two-year-old man presented with erythema nodosum of undeterminated etiology and pancytopenia. A bone marrow biopsy revealed extensive hairy-cell infiltration. Four months later, the diagnosis of pulmonary tuberculosis was suggested by the appearance of a pulmonary infiltrate in the left upper lobe. Despite antituberculous chemotherapy, the patient died. Post-mortem bacteriologic confirmation was given by sputum culture.

The authors report a case of Ph 1 positive chronic myelocytic leukemia associated with cutaneous mastocytosis, occuring lately in a 75 years old man. 12 similar cases (associations mastocytosis chronic or acute leukemia) are described in the literature.

Eleven partial splenectomies are performed in pigs. Simultaneous section and hemostasis are obtained with continuous 80 W power shoot. There is no hemorrhagic or septic complication and normal splenic weight is recovered in 5 months. Platelets elevation observed in post-operative. Platelets elevation observed in post-operative period returns to normal rate between 20th and 30th day. Acute cellular damage of cut splenic edge does not exceed 3 mm in thickness. Semi-thick and electron microscopic examination reveals at day 10 mitotic figures of lymphocytes (i.e. splenic regeneration) and at day 30 high density of mast cells and plasmocytes i.e. cellular biostimulation).

The main reason for using low molecular weight heparin (LMWH) is its capacity to keep the antithrombotic effect of standard non-fractioned heparin (NFH) while reducing its hemorrhagic power. Various studies comparing LMWH to NFH gave contradictory results, so we carried out a meta-analysis of randomized trials comparing these two treatments in prevention of deep-vein thrombosis (DVT) (and in prevention of deep-vein thrombosis or pulmonary embolism). From a selection of ten trials we could not show any significant difference in the DVT rates, as well as for the whole of surgical indications as for the subgroups of abdominal and orthopedic surgery. The weighted global difference between the DVT rates is so low that, in spite of the use of meta-analysis, the power is clearly insufficient. The hemorrhagic risk is not statistically reduced as well for the whole of surgical indications as for the subgroups.

A case is reported of a 49 years-old man who presented with cutaneous and muscular manifestations revealing periarteritis nodosa. Two years after detection of this disease occured a preleukemic condition and four years later a chronic lymphocytic leukaemia is discovered. In clinical course appeared a tuberous infiltration of the face and a sudden bilateral deafness. Regression of these two abnormalities is obtained after administration of prednisolone. The patient died of generalized infectious process postoperatively. From these clinical and pathological findings relations between periarteritis and CLL, occurence of deafness and cutaneous lesions are discussed. The relationship between the development of CLL and the immunosuppressive treatment is considered.

The variations of FVII, PAI-1, TAT complexes, fibrinopeptide A, D-Dimers and beta thromboglobulin plasma levels were studied on 30 sedentary men, smokers and non-smokers, who were admitted to a 6 months' program of physical training and smoking cessation. After 3 months of intervention, sustained physical training was associated with the decrease of FVII and PAI-1 levels. Mild exercise performed during a second 3-month period could maintain normal FVII and PAI-1 activities but participants who stopped the training increased their FVII and PAI-1 plasma levels. FVII was not influenced by smoking habits. Smoking cessation seemed to slightly potentiate the decrease of PAI-1 levels associated with mild exercise. Overweight, FVII and PAI-1 levels were correlated and the weight reduction induced by training was related to the changes in the factors. In smokers, physical exercise was associated with a significant increase of hemostatic markers. This exercise-induced variation disappeared after 3 months of intervention in participants who stopped smoking and reappeared in those who smoked again after 6 months of intervention. This finding was not influenced by the physical training program.

Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient’s interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention.