Best practice & research. Clinical haematology
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Best Pract Res Clin Haematol · Jan 2006
ReviewPlasma and plasma components in the management of disseminated intravascular coagulation.
A variety of clinical conditions can cause systemic activation of coagulation that ranges from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of a widespread systemic activation of coagulation, resulting in diffuse fibrin deposition in small and midsize vessels. There is compelling evidence from clinical and experimental studies that DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. ⋯ Recent insight into important pathogenetic mechanisms that might lead to DIC has resulted in novel preventive and therapeutic approaches to patients with sepsis and derangement of coagulation. Supportive strategies aimed at inhibition of coagulation activation might theoretically be justified and have been found beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways.
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Multiple myeloma is a treatable but not necessarily a curable plasma-cell cancer. After decades of minimal progress, two new classes of drugs with novel mechanisms of action - immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib) - have been introduced for the treatment of this disease. Thalidomide and lenalidomide have shown great activity as single agents and in combination with glucocorticoids for the treatment of chemotherapy-refractory myeloma. ⋯ These drugs can easily be combined with other chemotherapeutic agents to potentiate the anti-myeloma effect. The immunomodulatory function of these drugs can be successfully exploited to control residual disease during remission. Thus, both thalidomide and lenalidomide have ushered in a new era of optimism in the management of this incurable cancer.
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Best Pract Res Clin Haematol · Jun 2005
ReviewRole of ferritin and ferroportin genes in unexplained hyperferritinaemia.
A large body of evidence indicates that the level of serum ferritin parallels the concentration of storage iron within the body, regardless of the cell type in which it is stored. Elevated serum ferritin levels, in the absence of inflammation and liver disease, are currently taken to indicate increased iron stores and require further investigation to determine the site of iron overload. Until recently, the only genetic disorder with elevated serum ferritin levels known in Western countries was hereditary HLA-related HFE-related genetic haemochromatosis in Caucasians (HFE, OMIM 235200), and a high serum ferritin in apparently healthy persons was considered suggestive of this disease. ⋯ The second one is haemochromatosis type 4, or HFE4 (OMIM 606069), or ferroportin disease. In this latter condition, reticuloendothelial iron overload and hyperferritinaemia are caused by loss-of-function mutations in the SLC11A3 gene that mainly impair macrophage iron recycling. These genetic disorders should be taken into account in the differential diagnosis of unexplained hyperferritinaemia.
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Anaemia is typically the first clue to iron deficiency, but an isolated haemoglobin measurement has both low specificity and low sensitivity. The latter can be improved by including measures of iron-deficient erythropoiesis such as the transferrin iron saturation, mean corpuscular haemoglobin concentration, erythrocyte zinc protoporphyrin, percentage of hypochromic erythrocytes or reticulocyte haemoglobin concentration. ⋯ The treatment of iron deficiency should always be initiated with oral iron. When this fails because of large blood losses, iron malabsorption, or intolerance to oral iron, parenteral iron can be given using iron dextran, iron gluconate or iron sucrose.
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Best Pract Res Clin Haematol · Jan 2005
ReviewMonoclonal gammopathies of undetermined significance.
The monoclonal gammopathies include multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), primary systemic amyloidosis (AL), and Waldenström's macroglobulinemia (WM). At Mayo Clinic, almost 60% of patients with a monoclonal gammopathy have MGUS. ⋯ To confirm the findings, we conducted a population-based study on MGUS in the 11 counties of southeastern Minnesota from 1960 to 1994. The risk of progression to a malignant plasma-cell disorder was 1% per year.