Reviews in clinical and experimental hematology最新文献

{"title":"Autosomal recessive deficiencies of coagulation factors.","authors":"Flora Peyvandi, R. Asselta, P. M. Mannucci","doi":"10.1046/J.1468-0734.2001.00051.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00051.X","url":null,"abstract":"Deficiencies of coagulation factors that cause a bleeding disorder, other than factor VIII and factor IX, are inherited as autosomal recessive traits and are generally rare, with prevalence in the general population varying between 1 in 500 000 and 1 in 2 000 000. In the last few years, the number of patients with recessively transmitted coagulation deficiencies has increased in European countries with a high rate of immigration of Islamic populations where consanguineous marriages are frequent. As a consequence of the relative rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects and the actual management of bleeding episodes are not as well established as for hemophilia A and B. This article reviews these disorders, in terms of clinical manifestations and characterization of the molecular defects. The general principles of management are also discussed.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00051.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57745121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Von Willebrand factor and von Willebrand disease.","authors":"Ulrich Budde, Reinhard Schneppenheim","doi":"10.1046/J.1468-0734.2001.00048.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00048.X","url":null,"abstract":"von Willebrand disease (vWD) is caused by quantitative and/or qualitative defects of the von Willebrand factor (vWF), a multimeric high molecular weight glycoprotein. Typically, it affects the primary hemostatic system, which results in a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (i) by initiating platelet adhesion to the injured vessel wall under conditions of high shear forces, and (ii) by its carrier function for factor VIII in plasma. Accumulating knowledge of the different clinical phenotypes and the pathophysiological basis of the disease translated into a classification that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters, and by analyzing the electrophoretic pattern of vWF multimers. The advent of molecular techniques provided the opportunity for conducting genotype-phenotype studies which have recently helped, not only to elucidate or confirm important functions of vWF and its steps in post-translational processing, but also many disease causing defects. Acquired von Willebrand syndrome (avWS) has gained more attention during the recent years. An international registry was published and recommendation by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis in 2000. It concluded that avWS, although not a frequent disease, is nevertheless probably underdiagnosed. This should be addressed in future prospective studies. The aim of treatment is the correction of the impaired hemostatic system of the patient, ideally including the defects of both primary and secondary hemostasis. Desmopressin is the treatment of choice in about 70% of patients, mostly with type 1, while the others merit treatment with concentrates containing vWF.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00048.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57745053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-induced and drug-dependent immune thrombocytopenias.","authors":"A. Greinacher, P. Eichler, N. Lubenow, Volker Kiefel","doi":"10.1046/J.1468-0734.2001.00041.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00041.X","url":null,"abstract":"Thrombocytopenia is a frequent comorbid condition in many in hospital patients. In some patients, drugs are the cause of low platelet counts. While cytotoxic effects of anti-tumor therapy are the most frequent cause, immune mechanisms should also be considered. This review addresses thrombocytopenias in four groups. Heparin-dependent thrombocytopenia (HIT), by far the most frequent drug-induced immune-mediated type of thrombocytopenia, has a unique pathogenesis and clinical consequences. HIT is a clinicopathological syndrome in which antibodies mostly directed against a multimolecular complex of platelet factor 4 and heparin cause paradoxical thromboembolic complications. The mechanisms through which heparin can enhance thrombin generation are discussed and treatment alternatives for affected patients are presented in detail. It is of primary importance to recognize these patients as early as possible and to substitute heparin with a compatible anticoagulatory drug, such as hirudin, danaparoid or argatroban. Patients seem to benefit from therapeutic doses of alternative treatment rather than from low-dose prophylactic doses. With the increasing use of glycoprotein (GP) IIb/IIIa inhibitors in patients with acute coronary syndromes, thrombocytopenias are increasingly recognized as an adverse effect of these drugs. Up to 4% of treated patients are affected. Most important, pseudothrombocytopenia, a laboratory artefact, is as frequent as real drug-induced thrombocytopenia and must be excluded before changes in treatment are considered. The pathogenesis of these thrombocytopenias is still debated; an immune mechanism involving preformed antibodies is likely. However, since these antibodies are also detectable in a high percentage of normal controls and of patients not developing thrombocytopenia, their impact is still unclear. Patients with real thrombocytopenia are at an increased risk of bleeding; treatment consists of cessation of the GP IIb/IIIa inhibitor and platelet transfusions in cases of severe hemorrhage. Classic immune thrombocytopenia can be induced by some drugs, e.g. gold, which trigger anti-platelet antibodies indistinguishable from platelet autoantibodies found in autoimmune thrombocytopenia. Drug-induced and drug-dependent immune thrombocytopenia is induced by antibodies recognizing an epitope on platelet GP formed after binding of a drug to a platelet glycoprotein. Still unresolved is whether antibody binding is the consequence of a conformational change of the antigen, the antibody, or both. These antibodies typically react with monomorphic epitopes on platelet GP, but only in the presence of the drug or a metabolite. Although several platelet GP have been identified as antibody target (GPIb/IX, GPV, GP IIb/IIIa), antibodies in an individual patient are highly specific for a single GP. Clinically, these patients present with very low platelet counts and acute, sometimes severe, hemorrhage. Treatment is restricted to withdrawal of th","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00041.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of adult immune thrombocytopenia.","authors":"K. Lechner","doi":"10.1046/J.1468-0734.2001.00043.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00043.X","url":null,"abstract":"Immune thrombocytopenia (ITP) is a heterogeneous disease with regard to pathogenesis, severity, spontaneous course and response to treatment. Except in patients with severe bleeding tendency and very low platelet counts (< 10 x 10(9)/L), there are no clear rules on the indications for treatment. The standard initial therapy is corticosteroids, but the optimal dose and duration of therapy is unknown and in practice, some patients may be overtreated by aiming for complete remission (CR). In patients who have no sustained response after steroids, the most effective single therapy is splenectomy. Laparascopic splenectomy has a very low mortality and moderate morbidity. Preoperative prediction of success is difficult. About 50% of patients are in CR or partial remission after 5 years, but there are few data on the long-term outcome. Patients who fail steroids and splenectomy are difficult to treat. The choice may be palliative, with low doses of steroids or aggressive therapy with the intention of sustained remission. In selected patients, high-dose immunoglobulin or anti-D may be useful to temporarily raise the platelet count. Other drugs tried in ITP had either no or very limited clinically meaningful efficacy.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00043.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of immune thrombocytopenic purpura in children.","authors":"H. Gadner","doi":"10.1046/J.1468-0734.2001.00040.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00040.X","url":null,"abstract":"Immune thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder occurring in previously healthy children and can be classified into two major forms. Acute and chronic ITP are benign conditions with a high probability of spontaneous recovery with or without therapy. Rates of 80-90% complete remission can be achieved irrespective of the treatment given. In only 10-20% of children thrombocytopenia persists for more than six months, showing a chronic course, which also has a high probability of remitting over time (up to 80% or more). The variability of the clinical course, and the lack of consistent clinical features, make the decision on whether and how to treat difficult. Most physicians are driven to treat all children with symptoms by concern over life-threatening hemorrhage, although the risk of intracranial hemorrhage (ICH) is only 0.1-0.9%. The commonly used treatment regimens for acute ITP are corticosteroids, intravenous immunoglobulins (IVIgG), or intravenous anti-D immunoglobulin (anti-D). So far, there is no evidence that initial therapy can prevent ICH or a chronic course of the disease. In chronic ITP the same drugs are generally used and it seems that pulses with steroids may be just as effective as IVIgG. Anti-D may also be considered a reliable and cheap alternative for chronic disease. A major problem in the management of chronic ITP is the question of whether repeated infusions of Ig (IVIgG or anti-D) and/or corticosteroids can postpone or ultimately preclude splenectomy, which must be considered only for a small proportion of patients resistant to therapy. In these cases, a laparoscopic approach should be preferred. Children who fail to respond to splenectomy (< 20% of cases) warrant second line treatment with other drugs, like cyclophosphamide or azathioprine and deserve a revisit of diagnosis for exclusion of secondary ITP.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00040.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New aspects in the pathogenesis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.","authors":"T. Raife, R. Montgomery","doi":"10.1046/J.1468-0734.2001.00044.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00044.X","url":null,"abstract":"The thrombotic microangiopathy (TM) syndromes, thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome, are a rare and heterogeneous group of disorders characterized by widespread microvascular thrombosis and end organ injury. Decades of descriptive studies have defined clinical subsets of TM syndromes by clinical and laboratory features. Despite many advances, however, progress towards understanding of the etiology and pathogenesis of TM disorders remains limited. The rarity of occurrence and lack of natural animal models of TM syndromes have hampered progress in experimental and clinical studies. Treatment remains essentially empirical and options are limited. However, recent advances in the genetic and molecular understanding of subsets of TM disorders and the development of relevant animal models offer new resources to explore the pathogenic mechanisms. With these new advances more effective and individualized treatments for TM syndromes can be developed.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00044.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisitation of the clinical indications for the transfusion of platelet concentrates.","authors":"Paolo Rebulla","doi":"10.1046/J.1468-0734.2001.00042.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00042.X","url":null,"abstract":"Platelet transfusion is indicated when the expected benefits of increasing the number of functional platelets in the patient's circulation outweigh the potential risks generated by exposing the patient to allogeneic, manipulated and stored blood products such as platelet concentrates. Although reassuring evidence has been collected indicating that current risks associated with blood transfusion are lower than those of several voluntary and involuntary human activities, balancing benefits and risks of platelet transfusion may not be easy in a proportion of patients and in a number of conditions. To facilitate this task, guidelines have been developed, with particular attention to cancer patients. As witnessed by the most recent guidelines, over the last few years there has been a progressive, although not absolute, consensus on: (i) the routine use of platelets as a tool to prevent hemorrhage in oncohematology (the so called 'prophylactic approach') as opposed to limiting platelet transfusion to actual bleeding episodes (the so-called 'therapeutic approach') and (ii) lowering the trigger for prophylactic platelet transfusion in stable oncohematology recipients from 20 x 109 to 10 x 109 platelets/L. This has been accompanied by a reduction of platelet use per oncohematology patient of about 20%, an important outcome in view of the progressive increase of platelet demand due to more aggressive therapy in cancer patients. In selected clinical conditions, specific triggers ranging from 30 x 10(9) to 100 x 10(9) platelets/L have been recommended, with higher values when surgical procedures are required for the patient's treatment. Indications and trigger values proposed in the guidelines must be considered within the context of careful clinical evaluation of each patient, with a clear appreciation of the power of discrimination of automated platelet counters at low counts, and of the quality and local availability of platelet products for emergency.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00042.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood platelets; progress and problems: Editorial","authors":"P. Mannucci","doi":"10.1046/J.1468-0734.2001.00046.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00046.X","url":null,"abstract":"","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00046.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57745042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet glycoprotein gene polymorphisms and risk of thrombosis: facts and fancies.","authors":"A. Reiner, D. Siscovick, F. Rosendaal","doi":"10.1046/J.1468-0734.2001.00045.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00045.X","url":null,"abstract":"Over the past several years, platelet glycoprotein gene polymorphisms have received increasing attention as possible inherited determinants of prothrombotic tendency. However, their role in genetic susceptibility to thrombotic disease remains controversial. The glycoprotein IIIa Leu33Pro amino acid substitution appears to be associated with a subtle effect on platelet thrombogenicity in vitro, but is not a major risk factor for arterial thrombotic disease among the general population. Evidence suggests that the glycoprotein IIIa Pro33 allele may be associated with increased risk of thrombotic events following coronary re-vascularization and possibly among younger subjects with atherosclerosis. The nucleotide 807T variant of glycoprotein Ia is associated with increased platelet glycoprotein Ia/IIa receptor density, collagen-induced platelet adhesion and an increased risk of early onset myocardial infarction and stroke. Evaluation of the roles of the glycoprotein Ibalpha Thr145Met and variable number of tandem repeat polymorphisms has been complicated by their lack of well-defined effects on platelet adhesive function and the strong linkage disequilibrium between the two sites. Future epidemiologic studies of platelet glycoprotein gene polymorphisms will require larger sample sizes and family based approaches to further elucidate clinically important associations with thrombotic disease, including gene-environment and gene-gene interactions. Other polymorphisms of potential functional significance within genes encoding platelet membrane proteins will undoubtedly be discovered. The challenge will be to integrate advances in platelet biology with molecular and genetic epidemiology to enhance our understanding of the genetic determinants of common, but etiologically complex thrombotic diseases.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00045.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57745031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Results of unrelated umbilical cord blood hematopoietic stem cell transplantation.","authors":"E. Gluckman, V. Rocha, S. Chevret","doi":"10.1046/J.1468-0734.2001.00034.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2001.00034.X","url":null,"abstract":"The number of umbilical cord blood transplants is increasing worldwide. The purpose of Eurocord is to evaluate the results and to compare the outcome of umbilical cord blood transplants with allogeneic bone marrow transplants. Data have been reported to Eurocord by multiple transplant centers. Close links have been established with the cord blood banks through Netcord. Bone marrow transplant data have been provided by transplant centers and also through the European Group for Blood and Marrow Transplantation (EBMT) and International Bone Marrow Transplant Registries (IBMTR). Eurocord has analyzed the outcome of unrelated umbilical cord blood transplants from 121 transplant centers and 29 countries. The results showed that survival with unrelated mismatched umbilical cord blood transplants was comparable to that with unrelated bone marrow transplants. Engraftment with cord blood was delayed, resulting in an increased incidence of early transplant complications. The incidence of acute and chronic graft-vs.-host disease was reduced with cord blood grafts even in human leukocyte antigen (HLA)-mismatched transplants and in adults. In patients with leukemia, the rate of relapse was similar to the rate of relapse after bone marrow transplant. The overall event-free survival with umbilical cord blood transplantation was not statistically different when compared to bone marrow transplants. This large registry study confirms the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2001.00034.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}