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Journal of Thrombosis and Haemostasis: JTH

M Menegatti, R Palla, P Bucciarelli, F Peyvandi
We thank Dr. Dorgalaleh et al. for their interest in our report regarding the minimal Factor XIII (FXIII) activity level to prevent major spontaneous bleedings [1] and for describing their experience using a low dose prophylaxis in patients with severe FXIII deficiency [2]. As reported by the authors, primary prophylaxis is mandatory for all patients with severe congenital FXIII deficiency, since the diagnosis, to prevent spontaneous life-threatening bleeding. It is well known that the main cause of death or disability in these patients is intracranial haemorrhage (ICH), occurring either spontaneously or after minor trauma, therefore an early prophylaxis is crucial [3]...
September 19, 2017: Journal of Thrombosis and Haemostasis: JTH
Robert L Medcalf
We all know about classical fibrinolysis, how plasminogen activation by either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) promotes fibrin breakdown, and how this process was harnessed for the therapeutic removal of blood clots. While this is still perfectly true and still applicable to thromboembolic conditions today, another dimension to this system came to light over two decades ago that implicated the plasminogen activating system in a context far removed from the dissolution of blood clots...
September 19, 2017: Journal of Thrombosis and Haemostasis: JTH
J M L Halton, M Albisetti, B Biss, L Bomgaars, M Brueckmann, S Gropper, R Harper, F Huang, M Luciani, H Maas, I Tartakovsky, L G Mitchell
BACKGROUND: The current standard-of-care treatments for pediatric venous thromboembolism (VTE) have limitations. Dabigatran etexilate (DE), a direct thrombin inhibitor, may offer an alternative therapeutic option. OBJECTIVES: To assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of DE oral liquid formulation (OLF) in pediatric patients with VTE. PATIENTS/METHODS: Patients who had completed planned treatment with low-molecular-weight heparin or oral anticoagulants for VTE were enrolled in two age groups (2-<12 and 1-<2 years) and received DE OLF based on an age- and weight-adjusted nomogram...
September 16, 2017: Journal of Thrombosis and Haemostasis: JTH
Carlo Zaninetti, Federica Melazzini, Giorgio A Croci, Emanuela Boveri, Carlo L Balduini
Most commonly located in liver and spleen, extramedullary hematopoiesis (EMH) is the presence of hematopoietic tissue outside the bone marrow. MYH9-related thrombocytopenia (MYH9-RD) and ANKRD26-related thrombocytopenia (ANKRD26-RT) are two of the most frequent form of inherited thrombocytopenia (IT). Until recently, EMH has been associated with neoplastic and non-neoplastic hematologic conditions in which ITs were not included. We describe a case of mass-like EMH in the presacral space in a patient affected with ANKRD26-RT, comparing it with another case of paravertebral EMH we recently described in a subject with MYH9-RD...
September 16, 2017: Journal of Thrombosis and Haemostasis: JTH
A B Pedersen, J Vandenbroucke, E Horváth-Puhó, H T Sørensen
BACKGROUND: It is unknown whether venous thromboembolism (VTE) in rheumatoid arthritis (RA) patients can be marker of occult cancer. OBJECTIVES: To examine cancer risk subsequent to VTE among RA patients compared with cancer risk in RA cohort without VTE and in a general population without RA and without VTE. PATIENTS/METHODS: All RA patients with a first-time diagnosis of VTE (index date) during 1978-2013 and comparison cohorts were identified from population-based registries in Denmark...
September 15, 2017: Journal of Thrombosis and Haemostasis: JTH
D J Rabbolini, M-C Morel-Kopp, Q Chen, S Gabrielli, L C Dunlop, L P Chew, N Blair, T A Brighton, N Singh, A P Ng, C M Ward, W S Stevenson
BACKGROUND: Mutation of the GFI1B fifth DNA-binding zinc-finger domain causes macrothrombocytopenia and α-granule deficiency leading to clinical bleeding. The phenotypes associated with GFI1B variants disrupting non-DNA-binding zinc-fingers remain uncharacterized. OBJECTIVES: To determine the functional and phenotypic consequences of GFI1B variants disrupting non-DNA-binding zinc-finger domains. METHODS: The GFI1B C168F variant and a novel GFI1B c...
September 7, 2017: Journal of Thrombosis and Haemostasis: JTH
H-J Tsai, K-Y Chien, H-R Liao, M-S Shih, Y-C Lin, Y-W Chang, J-C Cheng, C-P Tseng
Essentials Disabled-2 (Dab2) phosphorylation status in thrombin signaling of human platelet was investigated. Ser723 was the major Dab2 phosphorylation site in human platelets stimulated by thrombin. Dab2 S723 phosphorylation (pS723) caused the dissociation of Dab2-CIN85 protein complex. Dab2-pS723 regulated ADP release and integrin αIIbβ3 activation in thrombin-treated platelets. SUMMARY: Background Disabled-2 (Dab2) is a platelet protein that is functionally involved in thrombin signaling in mice...
September 6, 2017: Journal of Thrombosis and Haemostasis: JTH
Laurent Bertoletti, Philippe Robin, Luis Jara-Palomare, Cécile Tromeur, Jean Pastre, Nathalie Prevot-Bitot, Thomas Mouneh, Grégoire Le Gal, Pierre-Yves Salaun
BACKGROUND: Most recent trials evaluating extensive screening strategies for occult cancer in patients with unprovoked venous thromboembolism failed, among other explanations because of an overall low rate of occult cancer. The RIETE investigators recently proposed a score aiming to identify a sub-group at higher risk. METHODS: We retrospectively computed the RIETE score for all patients included in the MVTEP study, which evaluated the accuracy of FDG-PET in the screening of occult cancer in patients with unprovoked venous thromboembolism...
September 6, 2017: Journal of Thrombosis and Haemostasis: JTH
Akbar Dorgalaleh, Shadi Tabibian, Majid Safa, Mahmood Shams, Majid Naderi
In a recent publication by Menegatti et al. on patients with congenital factor XIII (FXIII) deficiency, an effort was made to suggest a cut-off to start prophylaxis in order to prevent spontaneous major bleeds, including central nervous system (CNS) bleeding, gastrointestinal (GI) bleeding, hematoma and hemarthrosis (grade III bleeding according to EN-RBD classification) (1). Fifteen IU/dL FXIII coagulant activity (FXIII:C) was proposed as a cut-off for this purpose. Surprisingly, in this study, ~50% of patients with FXIII:C between the lower detection limit and 29 IU/dL, experienced these bleeds and 36% of those with FXIII:C ≥ 30% had minor spontaneous bleeding (1)...
September 4, 2017: Journal of Thrombosis and Haemostasis: JTH
S Barco, F Pomero, M N D Di Minno, E Tamborini Permunian, A Malato, S Pasca, G Barillari, L Fenoglio, S Siragusa, G Di Minno, W Ageno, F Dentali
BACKGROUND: Studies of long-term thromboembolic complications and death following acute isolated superficial vein thrombosis (iSVT) of the lower extremities are scarce. OBJECTIVES: To investigate the course of iSVT in the setting of an observational multicenter study. METHODS: We collected longitudinal data of 411 consecutive outpatients with acute, symptomatic, objectively-diagnosed iSVT previously included in the cross-sectional ICARO study...
September 4, 2017: Journal of Thrombosis and Haemostasis: JTH
Yan Song, Zhaoqing Wang, Itay Perlstein, Jessie Wang, Frank LaCreta, Robert J A Frost, Charles Frost
BACKGROUND: Currently, there is no approved reversal agent for direct factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). OBJECTIVE: This open-label, randomized, placebo-controlled, 3-period crossover study assessed the effect of two 4-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. METHODS: Subjects received apixaban 10 mg twice daily for 3 days...
August 28, 2017: Journal of Thrombosis and Haemostasis: JTH
A Greinacher, Kathleen Selleng, T E Warkentin
Autoimmune heparin-induced thrombocytopenia (aHIT) indicates patients with anti-PF4/polyanion antibodies that are able to activate platelets strongly even in the absence of heparin (heparin-independent platelet activation). Nevertheless, as seen with serum obtained from patients with otherwise typical HIT, serum-induced platelet activation is inhibited at high heparin concentrations (10-100 IU/mL heparin). Further, upon serial dilution, aHIT serum will usually exhibit heparin-dependent platelet activation. Clinical syndromes associated with aHIT include: delayed-onset HIT, persisting HIT, spontaneous HIT, fondaparinux-associated HIT, heparin "flush"-induced HIT, and severe HIT (platelet count <20×10(9) /L) with associated disseminated intravascular coagulation (DIC)...
August 28, 2017: Journal of Thrombosis and Haemostasis: JTH
Bradford J Kim, Ryan W Day, Catherine H Davis, Nisha Narula, Michael H Kroll, Ching-Wei D Tzeng, Thomas A Aloia
BACKGROUND: The incidence of venous thromboembolism remains high after liver surgery. OBJECTIVE: To evaluate the safety and efficacy of extended pharmacologic thromboprophylaxis in liver surgery for the prevention of venous thromboembolism (VTE). PATIENT/METHODS: From August 2013 to April 2015, 124 patients who underwent liver resection for malignancy were placed on an extended pharmacologic thromboprophylaxis protocol. Intraoperative VTE prophylaxis included Thrombo-Embolic Deterrent hose and sequential compression devices...
August 28, 2017: Journal of Thrombosis and Haemostasis: JTH
Marilyn J Manco-Johnson, Bjorn Lundin, Sharon Funk, Charles Peterfy, David Raunig, Michael Werk, Christine L Kempton, Mark T Reding, Stefcho Goranov, Liana Gercheva, Luminita Rusen, Valentina Uscatescu, Marta Pierdominici, Sylvia Engelen, Jennifer Pocoski, Dale Walker, Walter Hong
BACKGROUND: Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. OBJECTIVES: This analysis describes 3-year bleeding, joint, health-related quality-of-life (HRQoL), and other outcomes from the open-label, randomized, multinational SPINART study. PATIENTS/METHODS: Males aged 12-50 years with severe hemophilia A, ≥150 FVIII exposure days, no inhibitors, and no prophylaxis for >12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII (rFVIII-FS) prophylaxis or on-demand therapy (OD)...
August 24, 2017: Journal of Thrombosis and Haemostasis: JTH
D Spirk, A K Stuck, A Hager, R P Engelberger, D Aujesky, N Kucher
Essentials Venous thromboembolism (VTE) prophylaxis in hospitalized medical patients remains inconsistent. We implemented an electronic alert system featuring a validated risk assessment model for VTE. In this randomized controlled study, the e-alert system did not improve VTE prophylaxis. Many electronic alerts were ignored by ordering physicians. SUMMARY: Background The use of thromboprophylaxis among acutely ill hospitalized medical patients remains inconsistent. Objective To improve thromboprophylaxis use by implementing a computer-based alert system combined with a Geneva Risk Score calculation tool in the electronic patient chart and order entry system...
August 24, 2017: Journal of Thrombosis and Haemostasis: JTH
M Nagler, A Angelillo-Scherrer, M Méan, A Limacher, C Abbal, M Righini, J H Beer, J Osterwalder, B Frauchiger, M Aschwanden, C M Matter, N Kucher, J Cornuz, M Banyai, M Husmann, D Staub, L Mazzolai, O Hugli, N Rodondi, D Aujesky
BACKGROUND: The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear. OBJECTIVES: We examined the association between CYP2C9/VKORC1 variants and long-term clinical outcomes in a prospective cohort study of elderly patients treated with vitamin K antagonists for venous thromboembolism (VTE). METHODS: We followed 774 consecutive patients aged ≥65 years with acute VTE from nine Swiss hospitals for a median duration of 30 months...
August 22, 2017: Journal of Thrombosis and Haemostasis: JTH
Y Hisada, C Ay, A C Auriemma, B C Cooley, N Mackman
BACKGROUND: Pancreatic cancer patients have a high rate of venous thromboembolism. Human pancreatic tumors and cell lines express high levels of tissue factor (TF) and release TF-positive microvesicles (TF+MVs). In pancreatic cancer patients, tumor-derived TF+MVs are present in blood and increased levels are associated with venous thromboembolism and decreased survival. Previous studies have shown that mice with orthotopic human or murine pancreatic tumors have circulating tumor-derived TF+MVs, an activated clotting system, and larger clots than controls in an inferior vena cava stenosis model...
August 22, 2017: Journal of Thrombosis and Haemostasis: JTH
Katherine I Bridge, Lize Bollen, Jim Zhong, Mark Hesketh, Fraser L Macrae, Anne Johnson, Helen Philippou, D Julian Scott, Ann Gils, Robert A S Ariёns
BACKGROUND: Intra-luminal thrombosis is a key factor in Abdominal Aortic Aneurysms (AAA) growth. Patients with AAA form dense clots that are resistant to fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) has been shown to influence AAA development in murine models. OBJECTIVE: The aim of this study is to characterise the role of TAFI in human AAA. METHODS: Plasma levels of TAFI, TAFI activation peptide (TAFI-AP), activated/inactivated TAFI (TAFIa/ai) and plasmin-α2-antiplasmin complex were measured by ELISAs in patients with AAA (n=202) and controls (n=188)...
August 21, 2017: Journal of Thrombosis and Haemostasis: JTH
L Martorell, E Luce, J L Vazquez, Y Richaud-Patin, S Jimenez-Delgado, I Corrales, N Borras, S Casacuberta-Serra, A Weber, R Parra, C Altisent, A Follenzi, A Dubart-Kupperschmitt, A Raya, F Vidal, J Barquinero
BACKGROUND: The royal disease (RD) is a form of hemophilia B that affected many descendants of Queen Victoria in the 19(th) and 20(th) centuries. It was found to be due to the mutation F9 c.278-3A>G. OBJECTIVE: To generate a physiological cell model of the disease and to study F9 expression at the RNA level. METHODS: Using fibroblasts from skin biopsies of a previously identified hemophilic patient bearing the F9 c.278-3A>G mutation and his mother, we generated induced pluripotent stem cells (iPSCs)...
August 21, 2017: Journal of Thrombosis and Haemostasis: JTH
C E A Dronkers, Y M Ende-Verhaar, P A Kyrle, M Righini, S C Cannegieter, M V Huisman, F A Klok
No abstract text is available yet for this article.
August 20, 2017: Journal of Thrombosis and Haemostasis: JTH
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