Heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a growing complication of a common medication used to prevent deep vein thrombosis (DVT) in hospitalized patients. The purpose of this article is to review the mechanism that causes paradoxical thrombus formation in HIT and ways to recognize this important complication with various testing modalities and to discuss the approaches to treatment once a diagnosis has been made. HIT is a clinical diagnosis that can be further supported by utilizing the "4 Ts": thrombocytopenia, timing of platelet count fall, thrombosis or other complications, and other causes for thrombocytopenia. Diagnosis of HIT can be established using an HIT antibody test. Once a drop in platelet count is observed in a patient, it is important to rule out HIT. When HIT is first suspected, it is important to discontinue all heparin products. The gold standard in diagnosing HIT is the 14C-serotonin release assay (14C-SRA) assay, which has high sensitivity and specificity but is technically demanding and more time consuming than other antibody-detecting immunoassays. Anticoagulation in HIT patients is essential due to the increased risk of thrombosis. Treatment consists of utilizing alternative, nonheparin anticoagulants like lepirudin, argatroban, bivalirudin, or fondaparinux (although fondaparinux is not formally approved by the US Food and Drug Administration for this condition). Each of these agents should be individually formulated based on the patient and the presence/absence of liver or renal failure. Treatment duration has yet to be determined. However, in patients requiring long-term anticoagulation (pulmonary embolism, DVT, stroke), the transition to warfarin can be made once the platelet count recovers and there has been at least 5 days of overlap with a nonheparin anticoagulant.

Improving frontline treatment for chronic myeloid leukemia: emerging evidence for use of nilotinib and dasatinib.

The approval of imatinib in 2001 changed the landscape of chronic myeloid leukemia (CML) management, becoming the standard of care and improving the survival rates of patients. With the prevalent use of imatinib worldwide, it was observed that up to one-third of patients are resistant to or intolerant of imatinib therapy, fueling the search for safer and more effective agents. The newer and more potent tyrosine kinase inhibitors nilotinib and dasatinib were first indicated for the treatment of imatinib-resistant/-intolerant patients, for whom these agents are both safe and efficacious. More recent clinical studies have examined nilotinib and dasatinib in the frontline setting in newly diagnosed patients. Data reported from the phase III ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) study and the DASISION (Dasatinib versus Imatinib in Patients with Newly Diagnosed Chronic-phase CML) trial support the use of nilotinib and dasatinib as potential new standards for frontline care of newly diagnosed patients with CML in chronic phase. Furthermore, both agents have received regulatory approval for use as frontline agents. These agents have demonstrated significantly superior efficacy compared with imatinib, as measured by complete cytogenetic response and major molecular response rates. In addition, progression to advanced disease was significantly lower for nilotinib, and a trend toward lower progression was observed with dasatinib. Although both nilotinib and dasatinib are generally well tolerated in the frontline setting, they have different safety profiles that may affect their selection as treatment. Understanding the efficacy, safety profiles, and patterns of resistance to various BCR-ABL1 mutations of these newer agents, as well as implementing management strategies to treat adverse events, will help physicians to provide the best therapy options for their patients with CML.