Clinics in haematology最新文献

Thrombotic thrombocytopenic purpura (TTP) and the haemolytic-uraemic syndrome (HUS) are caused by platelet thrombi in the microcirculation (i.e. arterioles and capillaries) throughout the body (TTP) or predominantly in the kidneys (HUS). Plasma factors that induce intravascular platelet agglutination have been a focus of investigation into the pathogenesis of these disorders. Von Willebrand factor (vWF) multimeric forms that are larger than those present in normal plasma are found in the plasma of patients with the chronic relapsing form of TTP. These unusually large vWF multimers are similar to those produced by normal human endothelial cells, but never allowed into the normal circulation. Unusually large vWF multimers in chronic relapsing TTP patients are most apparent in plasma during remission. They disappear, presumably in the process of attaching to platelets and inducing the formation of platelet thrombi, during relapses in chronic TTP. The disappearance of the largest plasma vWF multimeric forms during acute episodes of non-relapsing TTP and HUS has also been seen. These syndromes may be the result of damage to systemic or renal endothelial cells. A cofactor which induces the attachment of large vWF multimers to platelets during episodes of TTP has recently been detected, but not yet characterized biochemically. The cryosupernatant (i.e. vWF-depleted) fraction of normal plasma contains an activity that converts, or potentiates the conversion of, unusually large vWF multimers to the somewhat smaller circulating vWF forms as the bloodstream. There is clinical evidence that an autoantibody may prevent the effect of this 'unusually large vWF depolymerase' in some chronic relapsing TTP patients. Transfusions of normal plasma or cryosupernatant as prophylaxis against, or therapy for, episodes of TTP may transiently provide this missing unusually large vWF depolymerase activity, as well as additional plasma proteins to bind and eliminate the vWF cofactor proposed as the inciting agent of TTP episodes. In some patients, partial removal of unusually large vWF multimers (and possibly the inciting vWF cofactor) by plasmapheresis may be required along with the transfusion of normal plasma or cryosupernatant, in order to control in vivo platelet agglutination. Plasma manipulation has greatly improved the survival of patients with relapsing and non-relapsing forms of TTP. Corticosteroids may also be beneficial. The effectiveness of ancillary measures (splenectomy, vinca alkaloids or other immunosuppressive drugs) is not precisely defined. There is no convincing evidence that aspirin, dipyridamole or PGI2 are helpful in TTP.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluating the use of antithrombotic drugs in artery disease has been a long and difficult process, which is far from complete. The aims of treatment have ranged from the primary prevention of myocardial infarction or stroke, through the restoration of blood flow to ischaemic organs in order to salvage threatened tissue, to the prevention of recurrent vascular occlusion. Drugs studied in depth by clinical trial include the oral anticoagulants, antiplatelet drugs (especially aspirin), and thrombolytic agents. Their results are considered under the headings of coronary artery disease, cerebral ischaemia, and peripheral vascular disease. Aspirin, with or without dipyridamole, prevents progression of unstable angina to myocardial infarction or death, probably reduces long-term mortality after myocardial infarction, and prevents aortocoronary bypass graft occlusion. It decreases the risks of stroke or death in patients with transient cerebral ischaemia, diminishes cardiovascular morbidity after a thrombotic stroke, and may improve the outcome after some kinds of surgery for peripheral vascular disease. The benefits of oral anticoagulant treatment to prevent artery occlusion remain poorly defined. Oral anticoagulants prevent systemic embolism in many groups of high-risk patients, and probably reduce the risk of recurrence after embolism has occurred. Whether their long-term use to prevent reinfarction in patients with a previous myocardial infarct can be justified remains uncertain. They are of little or no proven value in patients with transient cerebral ischaemia or thrombotic stroke. On the other hand, there is increasing support for early thrombolytic treatment after myocardial infarction, especially since two multicentre trials have now shown reduced mortality in patients treated with intracoronary streptokinase within 4-6 hours of infarction and a further large multicentre study also demonstrated reduced mortality in patients treated with early intravenous streptokinase. In addition, the local infusion of streptokinase leads to recanalization in a high proportion of patients with a recent peripheral artery occlusion who are poor candidates for surgery.

The discovery of a fast-acting plasminogen activator inhibitor has resulted in the notion that the balance between tissue-type plasminogen activator and its inhibitor determines the net fibrinolytic activity of blood. The inhibitor shows a rapidly fluctuating acute-phase pattern, which may be important in relation to thrombosis in acute disease. Other newly discovered modulators of the fibrinolytic system include histidine-rich glycoprotein, tetranectin and thrombospondin. The role of fibrin as a cofactor in its own dissolution is further elucidated with emphasis on local aspects. Therapeutic inhibition of overactive fibrinolysis by various drugs needs careful monitoring. Prophylactic stimulation of fibrinolysis is possible, e.g. by stanozolol or other drugs that lower inhibitor levels, but its proven value is as yet limited. Results of clinical trials with activators of the fibrinolytic system as thrombolytic agents are discussed in relation to the physiology of the fibrinolytic system.