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OBJECTIVE: To assess bleeding and activated partial thromboplastin time (APTT) In relation to body mass index (BMI) in patients prescribed weight-based dosing of intravenous unfractionated heparin (UFH) for cardiac indications [...]

Byline: Mitchell Levy (1), Marcel Levi (2), Mark D. Williams (3), Massimo Antonelli (4), Dazhe Wang (3), Mariano Alejandro Mignini (5) Keywords: Severe sepsis; Drotrecogin alfa (activated); Heparin; XPRESS; Clinical trial; Recombinant human activated protein C Abstract: Purpose The safety of using heparin concomitantly with drotrecogin alfa (activated) {DrotAA} was explored in the XPRESS study. No heparin effect on mortality was observed. Safety results from that study are explored in more detail. Methods A randomized, double-blind trial of prophylactic heparin versus placebo in severe sepsis patients treated with DrotAA (24 ug/(kg h) for 96 h) was conducted at 224 sites in 20 countries. Patients were randomized 1:1:2 to receive unfractionated heparin (UFH) (5,000 Units twice daily) (n = 511), low-molecular-weight heparin (LMWH) (enoxaparin, 40 mg per day) (n = 493), or placebo (n = 990) every 12 h during the DrotAA infusion. Results Bleeding events during the DrotAA infusion period (Days 0--6) were higher in the heparin than placebo groups (10.8 vs. 8.1% p = 0.049), but serious bleeding events were similar (heparin 2.3% vs. placebo 2.5% p = 0.72) and central nervous system (CNS) bleeds were rare in both groups (0.3 vs. 0.3%). Fewer heparin patients experienced an ischemic stroke during infusion (0.3 vs. 1.3% p = 0.018) and 28-day period (0.5 vs. 1.8% p = 0.009). Conclusions Coadministration of DrotAA with low-dose heparin in severe sepsis patients did not increase incidence of serious bleeding. Fewer ischemic strokes in the heparin group suggest heparin cessation should be avoided during DrotAA infusion. Author Affiliation: (1) Rhode Island Hospital and Brown University Medical School, 593 Eddy St., Providence, RI, 02903, USA (2) Departments of Vascular Medicine and Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (3) Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, IN, USA (4) Policlinico Universitario A. Gemelli Universita Cattolica del Sacro Cuore, Rome, Italy (5) Medical Department of Eli Lilly SpA, Sesto Fiorentino, Italy Article History: Registration Date: 30/03/2009 Received Date: 01/07/2008 Accepted Date: 27/03/2009 Online Date: 15/04/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1483-7) contains supplementary material, which is available to authorized users. An erratum to this article can be found at http://dx.doi.org/10.1007/s00134-009-1503-7

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2009.01.005 Byline: Eric M. Crespo (a), Gustavo B.F. Oliveira (b), Emily F. Honeycutt (b), Richard C. Becker (b), Peter B. Berger (c), David J. Moliterno (d), Kevin J. Anstrom (b), Charles S. Abrams (e), Neal S. Kleiman (f), Stephan Moll (g), Lawrence Rice (h), Jo E. Rodgers (g), Steven R. Steinhubl (i), Victor F. Tapson (b), Christopher B. Granger (b), E. Magnus Ohman (b) Abstract: Thrombocytopenia and heparin-induced thrombocytopenia (HIT) are potentially devastating paradoxical side effects of heparin therapy. We explored the evaluation, management, and clinical consequences of thrombocytopenia occurring during heparin therapy in diverse clinical settings. Author Affiliation: (a) University of Vermont, Burlington, VT (b) Duke Clinical Research Institute and Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC (c) Geisinger Clinic, Danville, PA (d) University of Kentucky, Lexington, KY (e) University of Pennsylvania School of Medicine, Philadelphia, PA (f) Methodist DeBakey Heart Center, Houston, TX (g) University of North Carolina, Chapel Hill, NC (h) Baylor College of Medicine, Houston, TX (i) The Medicines Company, Zurich, Switzerland Article History: Received 24 September 2008; Accepted 16 January 2009

Byline: Hidesaku Asakura (1), Yoko Sano (2), Tomotaka Yoshida (3), Mika Omote (3), Yasuo Ontachi (1), Tomoe Mizutani (1), Masahide Yamazaki (1), Eriko Morishita (1), Akiyoshi Takami (1), Ken-ichi Miyamoto (2), Shinji Nakao (1) Keywords: Disseminated intravascular coagulation; Lipopolysaccharide; Low molecular weight heparin; Tranexamic acid; Fibrinolysis Abstract: Objective We examined the role of coagulation and fibrinolysis in lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats, studying their contribution to fibrin deposition and organ failure in rats with LPS-induced DIC by concurrent administration of low molecular weight heparin (LMWH) with or without tranexamic acid (TA). Methods DIC was induced in male Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In the LPS+LMWH group LMWH (200u/kg) was administered to rats from 30 min before the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 Aug/kg) and TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS for 4.5 h. Results In the LPS+LMWH group lower plasma levels of TAT, D dimer, creatinine, and alanine aminotransferase were observed, along with less glomerular fibrin deposition and improved survival over rats administered LPS alone. However, these effects of LMWH were completely eliminated and damage beyond that observed in rats administered LPS alone resulted from combined administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels remained lower than in the group administered LPS alone. Conclusions Suppression of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased organ damage in this study, suggesting that depressed fibrinolysis plays a large role in organ failure resulting from LPS-induced DIC, even though hemostatic activation is moderately suppressed by LMWH Author Affiliation: (1) Department of Internal Medicine III, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa, 920-8641, Ishikawa, Japan (2) Hospital Pharmacy, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa, 920-8641, Ishikawa, Japan (3) Department of Laboratory Medicine, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa, 920-8641, Ishikawa, Japan Article History: Registration Date: 25/05/2004 Received Date: 08/01/2004 Accepted Date: 19/05/2004 Online Date: 15/06/2004

Byline: Lorenz Risch (1), Joachim E. Fischer (2), Roberto Herklotz (3), Andreas R. Huber (3) Keywords: Argatroban; Children; Danaparoid; Heparin-induced thrombocytopenia; Thromboembolism; Lepirudin Abstract: Objective: Reports on heparin-induced thrombocytopenia (HIT) in paediatrics are confined to isolated case reports. The objective was to systematically combine the published data. Design and setting: Cases were identified by MEDLINE search and review of bibliographies. Patients: We included subjects reported with HIT, collecting patient demographics, clinical and laboratory characteristics, therapeutic regimens and outcomes. Measurements and results: Reports on 70 patients were retrieved. In a majority of children, HIT occurred during hospitalisation in a paediatric ICU. In most patients, the typical onset pattern was reported, although rapid-onset-pattern HIT occurred in some. The median platelet-count nadir was 54x10.sup.9/l 11% of reported patients had nadirs in the normal range. Clinical symptoms included isolated thrombocytopenia and solitary or combined venous, arterial and intracardiac thromboembolism, sometimes catheter-related. Pulmonary embolism and major bleeding were rarely described. Confirmatory functional or antigenic testing of HIT antibodies showed a similar cumulative sensitivity of about 88%. An unfavourable outcome (death/limb amputation) was reported in 42.1% of patients without therapy and in 18% of patients treated with danaparoid, lepirudin, or argatroban. Conclusions: HIT in children mainly occurs in paediatric intensive care with diagnostic features and outcomes similar to those seen in adults. HIT cannot be ruled out based on normal platelet counts or occurrence after fewer than 5 days of heparin exposure. Children should be presumed to suffer from HIT based on clinical grounds and treated accordingly (immediate heparin withdrawal and alternative anticoagulation). Alternative anticoagulation with danaparoid, lepirudin and argatroban appears to improve outcomes. Author Affiliation: (1) Clinical Decision Making Research Unit, Academic Teaching Hospital, 6800, Feldkirch, Austria (2) Department of Neonatology and Pediatric Intensive Care, University-Children's Hospital, 8032 , Zurich, Switzerland (3) Zentrum fur Labormedizin, Kantonsspital, 5001 , Aarau, Switzerland Article History: Registration Date: 01/04/2004 Received Date: 06/01/2004 Accepted Date: 31/03/2004 Online Date: 19/05/2004 Article note: Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2315-4

ABSTRACT: Increasing evidence indicates that management of 'isolated' heparin-induced thrombocytopenia (HIT) should include substitution of heparin by an alternative anticoagulant, such as danaparoid, lepirudin, or argatroban. Usually, one of these [...]

ABSTRACT: Mild to moderate thrombocytopenia that is complicated by thrombosis is the typical presentation of immune-mediated heparin-induced thrombocytopenia (HIT). Usually, the platelet count begins to fall 5 to 10 days [...]

Byline: Kanwalpreet. Sodhi, Sidhartha. Garg, Bakhshish. Singh, Anupam. Shrivastava, Manender. Singla Hyperkalemia is a potentially life-threatening condition, which may occur in many clinical settings. Heparin-induced hyperkalemia is less well-recognized than [...]

Byline: Dharmesh. Agrawal, Mohammed. Sayeed, Indira Rajani. Roy, K. Somaraja Sir, Heparin-induced thrombocytopenia (HIT) is defined as a decrease in the platelet count during or shortly following exposure to heparin. [...]