Essential Hematology Book Pdf
Stefania Sholar
Hoffbrand's Essential Haematology is widely regarded as the most authoritative introduction to the subject available, helping medical students and trainee doctors understand the essential principles of modern clinical and laboratory haematology for nearly four decades. Now in its eighth edition, this market-leading textbook introduces the formation and function of blood cells and the diseases that arise from dysfunction and disruption of these processes.
Hoffbrand's Essential Haematology outlines the basic principles of clinical and laboratory haematology and shows how manifestations of blood diseases can be explained by new knowledge of the disease processes. It is an indispensable resource for students and trainees and an essential read for all specialists who are interested in updating their knowledge.
Children with hematologic and oncologic health conditions are at risk of impaired skeletal muscle strength, size, and neuromuscular activation that may limit gross motor performance. A comprehensive assessment of neuromuscular function of these children is essential to identify the trajectory of changes in skeletal muscle and to prescribe therapeutic exercise and monitor its impact. Therefore, this review aims to (a) define fundamental properties of skeletal muscle; (b) highlight methods to quantify muscle strength, size, and neuromuscular activation; (c) describe mechanisms that contribute to muscle strength and gross motor performance in children; (d) recommend clinical assessment measures; and (e) illustrate comprehensive muscle assessment in children using examples of sickle cell disease and musculoskeletal sarcoma.
The last four years have seen an explosion in our understanding of the myeloproliferative neoplasms. Important and often unexpected insights into the molecular mechanisms responsible for these disorders have been accompanied by the development of new diagnostic tests and by an improved understanding of the relationship between the different disease entities. This review will focus on recent developments in the pathogenesis and management of essential thrombocythemia with a particular emphasis on its phenotypic overlap with polycythemia vera and primary myelofibrosis.
The second randomized study was the Medical Research Council (MRC) primary thombocythemia-1 (PT-1) trial,2 in which high-risk patients (prior thrombosis, age > 60 years or platelets > 1000 109/L) were randomized to receive hydroxyurea plus aspirin or anagrelide plus aspirin. With over 800 patients randomized and with central clinical and histological review of end-points, it is the largest and most comprehensive study of essential thrombocythemia performed to date. The results demonstrate several major differences between the two arms. Compared to hydroxyurea plus aspirin, treatment with anagrelide plus aspirin was associated with increased rates of arterial thrombosis, major hemorrhage, myelofibrotic transformation and treatment withdrawal, but a decreased rate of venous thromboembolism.
In marked contrast to arterial thrombosis, the rate of venous thrombosis was significantly lower in the anagrelide plus aspirin arm. The incidence of venous thrombosis in untreated patients with high-risk essential thrombocythemia is unknown and so it is not clear whether this rate is increased by hydroxyurea plus aspirin or decreased by anagrelide plus aspirin. The optimal management of a patient with prior venous thrombosis will depend on individual circumstances, remembering that arterial thrombotic events are > 3 fold more common than venous thrombotic events in ET.
Taken together the results of the PT-1 trial suggest that hydroxyurea plus aspirin should remain first-line therapy for patients with essential thrombocythemia at high risk of developing vascular events. For other patients at a lower risk of thrombosis, the situation is less clear. The decision whether or not to use a cytoreductive agent requires balancing two opposing risks, both of which are small: the risk of a thrombotic event and the risk of a significant drug-related side effect. Unfortunately, the frequency of these two types of events is not clear from existing data. Some studies suggest that patients aged < 60 years and with no prior thrombosis do not exhibit an increased frequency of thrombosis compared to controls.35 However, the number of patients studied was small, the number of events very small and the choice of an appropriate control population is difficult. Moreover, other studies have found that such patients do have a significant risk of thrombosis.36 With respect to the risks of treatment, these differ for the different agents. The most commonly used drugs are hydroxyurea, anagrelide and interferon.
Median survival in essential thrombocythemia exceeds 20 years and clinical course is usually indolent with a minority of patients experiencing thrombohemorrhagic complications. Leukemic, polycythemic, or fibrotic disease transformation in essential thrombocythemia is an infrequent occurrence with a 15-year cumulative risk of approximately 5% or less in each instance. The major incentives for this review have been the recent description of an activating JAK2 tyrosine kinase mutation (JAK2V617F) in essential thrombocythemia, related myeloproliferative disorders, and the impact on clinical practice from the publication of a major treatment trial.
Several studies have reported on the occurrence of JAK2V617F in approximately 50% of patients with essential thrombocythemia and its presence has been associated with advanced age at diagnosis, higher hemoglobin and leukocyte levels, and increased rate of polycythemic transformation. In contrast, the mutation did not appear to affect the incidence of thrombotic, leukemic, or fibrotic events. There is increasing evidence regarding the thrombogenic role of neutrophils in essential thrombocythemia and this might partly explain the superior overall performance by hydroxyurea, compared with anagrelide, in a recent randomized study.
Although it is in vogue to consider essential thrombocythemia as more than one disease in terms of both molecular phenotype (presence or absence of JAK2V617F) and putative pattern of myelopoiesis (monoclonal versus polyclonal), it is yet to be shown that such differences influence either the natural history of the disease or current therapy. From a treatment standpoint, hydroxyurea is now confirmed to be the drug of choice for high-risk patients with essential thrombocythemia.
The Indiana University School of Medicine Cooperative Center of Excellence in Hematology (IU-CCEH) brings together investigators whose research activities are focused on various aspects of nonmalignant hematology. The center supports three biomedical research cores that are essential to these investigators' research efforts. The center also sponsors a robust enrichment program to advance the development of students and early career members.
The Experimental Mouse Resources Core provides advanced resources for studies using mice for murine and human transplantation models. The core maintains on-site breeding colonies of essential mice to study human and murine hematopoiesis in vivo such as NSG and NRG mice and provides specialized services including irradiations, transplantations, serial sampling, and compound dosing. The core serves as an educational resource and works closely with the Flow and Tissue Cytometry and the Hypoxia Cores.
The Flow and Tissue Cytometry Core supports investigators with critical flow cytometric techniques and procedures and allows investigators to extend their interrogation of hematopoietic cells to include quantitative analyses of the spatial distribution of HSC with other cells during different conditions of nonmalignant hematopoiesis. Using the core, investigators across the country can apply an integrated and economical approach to their studies in nonmalignant hematology.
The Hypoxia Core supports and enhances research efforts in nonmalignant hematology for better in vivo understanding of phenotypic and functional cellular, molecular, and biochemical aspects of hematopoietic and Immune cells. This involves regulation of normal hematopoiesis and pre-leukemia in the context of their lowered oxygen environment in vivo. Collection and processing of stem cells in the core will prevent cells from exposure to Extra Physiological Shock/Stress (EPHOSS) that is detrimental for their survival and function.
In hematology, essential thrombocythemia (ET) is a rare chronic blood cancer (myeloproliferative neoplasm) characterised by the overproduction of platelets (thrombocytes) by megakaryocytes in the bone marrow.[3] It may, albeit rarely, develop into acute myeloid leukemia or myelofibrosis.[3] It is one of the blood cancers wherein the bone marrow produces too many white or red blood cells, or platelets.[3]
Most people with essential thrombocythemia are without symptoms at the time of diagnosis, which is usually made after noting an elevated platelet level on a routine complete blood count (CBC).[4] The most common symptoms are bleeding (due to dysfunctional platelets), blood clots (e.g., deep vein thrombosis or pulmonary embolism), fatigue, headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting, and numbness in the extremities; the most common signs are increased white blood cell count, reduced red blood cell count, and an enlarged spleen.[4][5][6]
In 2013, two groups detected calreticulin mutations in a majority of JAK2-negative/MPL-negative patients with essential thrombocythemia and primary myelofibrosis, which makes CALR mutations the second most common in myeloproliferative neoplasms. All mutations (insertions or deletions) affected the last exon, generating a reading frame shift of the resulting protein, that creates a novel terminal peptide and causes a loss of endoplasmic reticulum KDEL retention signal.[9][10]
The following revised diagnostic criteria for essential thrombocythemia were proposed in 2005.[11] The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6.[12] The criteria are as follows:[12]
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