Molecular pathogenesis and clinical significance of driver mutations in primary myelofibrosis: a review

Primary myelofibrosis [PMF] is a rare chronic BCR-ABL1-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and shortened survival. The clinical manifestations of PMF include splenomegaly, consequent to extramedullary hematopoiesis, pancytopenias, and an array of potentially debilitating constitutional symptoms. The diagnosis is based on bone marrow morphology and clinical criteria. Mutations in the JAK2 [V617F], MPL [W515], and CALR [exon 9 indel] genes are found in approximately 90% of patients whereas the remaining 10% are so-called triple negatives. Activation of the JAK/STAT pathway results in overproduction of abnormal megakaryocytes leading to bone marrow fibrosis. These mutations might be accompanied by other mutations, such as ASXL1. The commonly used prognostication scoring for PMF is based on the International Prognostic Scoring System. The subsequently developed Dynamic International Prognostic Scoring System-plus employs clinical as well as cytogenetic variables. In PMF, CALR mutation is associated with superior survival and ASXL1 with inferior outcome. Patients with triple-negative PMF have a higher incidence of leukemic transformation and lower overall survival compared with CALR - or JAK2 -mutant patients. The impact of genetic lesions on survival is independent of current prognostic scoring systems. These observations indicate that driver and passenger mutations define distinct disease entities within PMF. Accounting for them is not only relevant to clinical decision-making, but should also be considered in designing clinical trials

Vitamin and mineral supplements: do we really need them?

In the United States, 40-50% of the men and women 50 years of age or older regularly use multivitamin/mineral [MVM] supplements, making the annual sales of these supplements over $11 billion. However, the question remains whether using MVM supplements is beneficial to health. This article reviews the results of randomized studies of MVM supplements and individual vitamins/mineral supplements in relation to overall mortality and incidence of chronic diseases, particularly cancer and ischemic heart disease. The results of large-scale randomized trials show that, for the majority of the population, there is no overall benefit from taking MVM supplements. Indeed, some studies have shown increased risk of cancers in relation to using certain vitamins

Management of acquired thrombophilic disorders in 2011: focus on heparin-induced thrombocytopenia, antiphospholipid syndrome, myeloproliferative neoplasms and paroxysmal nocturnal hemoglobinuria

Arterial and venous thrombosis are interrelated disorders at the interplay of platelets and fibrin. Arterial thrombi are platelet-rich and occur at sites vulnerable to atherosclerotic plaque rupture where blood shear rates are high; on the contrary, venous thrombi occur in association with slow blood flow and shear rates. These differences may underlie why anti-platelet agents are more effective in prevention of arterial thrombosis, while anticoagulants are preferred for venous thrombosis. Although some common thrombophilic disorders [e.g., Factor V Leiden, prothrombin gene mutation, etc.] are almost exclusively associated with venous thromboembolism, there are several disorders that are important to consider when caring for patients with both arterial and venous thromboembolism. This article will review the evidence-based management of heparin induced thrombocytopenia with thrombosis, anti-phospholipid antibody syndrome and catastrophic anti-phospho-lipid antibody syndrome, thrombohemorrhagic manifestations of Philadelphia chromosome-negative chronic myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia and primary myelofibrosis, as well as paroxysmal nocturnal hemoglobinuria

Diagnosis aim management of venous thromboembolism: an update a decade into the new millennium

Venous thromboembolism refers to thrombotic events in the venous system that are most commonly manifested as deep vein thromboses in the upper or lower extremity and/or pulmonary embolism. Venous thromboembolism is a common disorder that is associated with significant mortality, morbidity and health care-related cost. An array of hereditary and acquired risk factors are associated with venous thromboembolism. In recent years, a number of pivotal studies have expanded our understanding of the pathophysiology of venous thromboembolism, and served as the basis for evidence-based guidelines on prevention, diagnosis and treatment of venous thromboembolism. Furthermore, several novel therapeutic agents with different pharmacokinetics, pharmacodynamics and safety profiles have recently become available for treatment and prevention of venous thromboembolism. The purpose of the current paper is to review the pathogenesis and epidemiology of venous thromboembolism as well as an evidence-based approach to the diagnosis and management of venous thromboembolism