Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

Dabigatran versus warfarin major bleeding in practice: an observational comparison of patient characteristics, management and outcomes in atrial fibrillation patients.

Data comparing the patient characteristics, management and outcomes for dabigatran versus warfarin major bleeding in the practice setting are limited. We performed a retrospective single health system study of atrial fibrillation patients with dabigatran or warfarin major bleeding from October 2010 through September 2012. Patient identification occurred through both an internal adverse event reporting system and a structured stepwise data filtering approach using the International Classification of Diseases diagnosis codes. Thirty-five dabigatran major bleeding patients were identified and compared to 70 warfarin major bleeding patients. Intracranial bleed occurred in 4.3 % of warfarin patients and 8.6 % of dabigatran patients. Dabigatran patients tended to be older (79.9 vs. 76 years) and were more likely to have a creatinine clearance of 15-30 mL/min (40 vs. 18.6 %, p = 0.02). Over one-third of dabigatran patients had an excessive dose based on renal function. More dabigatran patients required a procedure for bleed management (37.1 vs. 17.1 %, p = 0.03) and received a hemostatic agent for reversal (11.4 vs. 1.4 %, p = 0.04). Dabigatran patients were twice as likely to spend time in an ICU (45.7 vs. 27.1 %, p = 0.06), be placed in hospice/comfort care (14.3 vs. 7.1 %, p = 0.24), expire during hospitalization (14.3 vs. 7.1 %, p = 0.24), and expire within 30-days (22.9 vs. 11.4 %, p = 0.28). In a single hospital center practice setting, as compared to warfarin, patients with dabigatran major bleeding were more likely to be older, have renal impairment, require a procedure for bleed management and receive a hemostatic agent. Patients with dabigatran major bleeding had an excessive dose for renal function in more than one-third of cases.

Drug-induced thrombocytopenia in critically ill patients.

Thrombocytopenia occurs in 15% to 58% of intensive care unit patients. The incidence varies based upon patient population, timing and frequency of platelet monitoring, and definition of thrombocytopenia. Up to 25% of acutely ill patients develop drug-induced thrombocytopenia. When drug-induced thrombocytopenia is suspected, nondrug related causes must be evaluated and excluded. Establishing the diagnosis of drug-induced thrombocytopenia is challenging, as hundreds of medications have been implicated. Medications commonly associated with drug-induced thrombocytopenia include glycoprotein IIb/IIIa inhibitors, cinchona alkaloids, antibiotics, anticonvulsants, and heparin. Once the diagnosis is suspected, clinicians should identify the start date of medications to assess the timeline of development. The likelihood of each medication causing thrombocytopenia must be evaluated. The risk vs. benefit of discontinuing the suspected medication and availability of alternative medications must be assessed. The role of corticosteroids, immune globulin, and plasmapheresis is uncertain. Once the offending agent has been discontinued, the overall prognosis is excellent. In the case of suspected or confirmed heparin-induced thrombocytopenia, an alternative anticoagulant should be initiated. Drug-induced thrombocytopenia should be documented in the medical record and reported according to institutional and national standards. This review focuses on immune-mediated drug-induced thrombocytopenia from medications commonly utilized in the critically ill patient.

Argatroban dosage requirements and outcomes in intensive care versus non-intensive care patients.

STUDY OBJECTIVE: To compare the outcomes of reduced-dose argatroban therapy in patients in the intensive care unit (ICU) with those of non-ICU patients. DESIGN: Retrospective medical record review. SETTING: Large, academic, tertiary care hospital. PATIENTS: Thirty-eight ICU patients and 43 non-ICU patients who received the institutional protocol of argatroban 0.8 microg/kg/minute and 1.2 microg/kg/minute, respectively, between March 2004 and September 2005. MEASUREMENTS AND MAIN RESULTS: Data on patient demographics, argatroban dosing, heparin-induced thrombocytopenia antibody results, activated partial thromboplastin times (aPTTs), new thrombotic events, and major bleeding events were extracted from medical records. Time-weighted mean +/- SD doses of argatroban were 0.82 +/- 0.3 microg/kg/minute for ICU patients and 1.25 +/- 0.29 microg/kg/minute for non-ICU patients. Mean aPTT ratios were similar between groups: 2.07 +/- 0.53 for ICU patients and 2.00 +/- 0.45 for non-ICU patients. More than 70% of all aPTT ratios were therapeutic. More than 95% of patients in both groups achieved a therapeutic aPTT ratio during therapy. Fewer ICU patients than non-ICU patients had all therapeutic aPTT ratios during argatroban therapy (29% vs 51%, p=0.07). Thrombotic events occurred in six (16%) ICU patients versus none of the non-ICU patients (p=0.009). Thrombotic events occurred in 4 (31%) of the 13 ICU patients with confirmed heparin-induced thrombocytopenia. Major bleeding occurred in four (11%) ICU patients versus none of the non-ICU patients (p=0.04). CONCLUSION: Both ICU and non-ICU patients require less than the manufacturer-recommended initial dosage of argatroban. However, ICU patients appear to be at an increased risk for bleeding and thrombotic events despite their attainment of therapeutic aPTTs.