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#16
03.04.2007, 02:35
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В продолжение...
"Волшебный аспирин" (навеяно след. публикацией):
J Thromb Thrombolysis. 2007 Mar 31; The thrombolytic effect of aspirin in animal model. Karmohapatra SK, Kahn NN, Sinha AK. Sinha Institute of Medical Science & Technology, Garia, Calcutta, 700084, India. BACKGROUND: The aspirin induced platelet aggregation has been reported to be mediated through the inhibition of platelet prostaglandin synthesis. This compound has also been recently reported to stimulate nitric oxide synthesis in platelets. Since nitric oxide has been reported to produce fibrinogen/fibrinolytic effect, investigation was carried out to determine fibrinolytic effect of in vivo exposure of platelets to aspirin in normal volunteers on the fibrinolysis of the clotted platelet-rich plasma in vitro. The thrombolytic effect of aspirin in situ was also carried out by injecting aspirin solution in the mice with ADP induced formed thrombi in the coronary artery. METHODS AND RESULTS: It was found that the clotted platelet-rich plasma prepared from the volunteers (n = 10, F = 5, M = 5) who ingested 150 mg aspirin, began to undergo spontaneous and progressive fibrinolysis for 200 min at 37 degrees C with the generation of fibrin degradation products in the lysate. No such fibrinolysis could be seen in control experiments. When platelet thrombi were produced in the coronary artery of mice by injecting ADP, and these animals subsequently received intravenous injection of aspirin (4 muM final), they not only survived (P < 0.0001, n = 10) the thrombogenic assault but the lysis of the platelet thrombi was also noted in the post mortem examination. The thrombolytic effect of aspirin was found to be comparable to that of streptokinase in these animals. CONCLUSIONS: Aspirin, through the stimulation of NO synthesis, may produce thrombolysis in vivo. 
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#19
06.04.2007, 00:35
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Потенциальные гематологические проблемы при назначении клопидогреля и их лечение:
Hematologic adverse effects of clopidogrel.
Am J Ther. 2007 Jan-Feb;14(1):106-12. Patients treated with clopidogrel should be carefully monitored for hematologic adverse effects especially in the first 2 to 3 months after initiation of therapy. Early recognition and prompt initiation of treatment can be life saving in patients who have hematologic adverse effects to clopidogrel. NEUTROPENIA Neutropenia is an uncommon adverse effect of clopidogrel with an incidence of 0.04% to 0.10%. Neutropenia was reported in 26 patients in the CAPRIE trial; 10 were due to clopidogrel and the remaining 16 cases were due to aspirin with a 0.10% incidence of clopidogrel-induced neutropenia. However, the differences between the clopidogrel and aspirin groups was not statistically significant.3 Eight patients developed neutropenia in the aspirin and clopidogrel limb and 5 patients developed neutropenia in the aspirin and placebo limb of the CURE trial.4 Even though the risk of myelotoxicity induced by clopidogrel is low, patients need to be evaluated for this potentially life-threatening condition if they develop fever, sore throat, or other signs of infection.9 The onset of clopidogrel-induced neutropenia is between 2 weeks and months after drug initiation. A case of clopidogrel-induced neutropenia was reported in a patient with end-stage renal disease where the neutropenia resolved in 2 weeks, the same time period taken in patients with normal renal function.10 Overall, clopidogrel has been shown to have a lesser incidence of neutropenia when compared with ticlopidine based on a meta-analysis that includes CAPRIE, CURE, CREDO, and the MATCH trials.11 Irreversible myelosuppression with clopidogrel has not been reported so far and the mechanism of leucopenia by clopidogrel is not known. TREATMENT When a diagnosis of clopidogrel-induced neutropenia is made, prompt withdrawal of the drug should be initiated and a follow-up with periodic blood count should be performed. The leucopenia usually resolves in 2 weeks after the discontinuation of clopidogrel.12 If there is persistent neutropenia granulocyte macrophage-colony stimulating factors can be considered. AUTOIMMUNE THROMBOCYTOPENIA Autoimmune thrombocytopenia is an extremely rare adverse effect of clopidogrel therapy. There are 5 cases reported so far on clopidogrel-induced isolated thrombocytopenia. It may be associated with other autoimmune hematologic disorders like autoimmune hemolytic anemia. The autoantibodies to platelets have not been identified. Autoimmune thrombocytopenia is usually symptomatic with bruises or soft tissue bleeding with rapid decline of the platelet count. The disease is attributed to clopidogrel if there is no other previous autoimmune disease or prior drug-induced autoimmune disorder.19 TREATMENT The thrombocytopenia should resolve after discontinuation of clopidogrel. Severe thrombocytopenia can be treated with methylprednisone. Platelet transfusions should be considered if there is a bleeding episode associated with platelet counts less than 50,000.20 No fatal cases have been reported so far.21 TTP (Thrombotic Thrombocytopenic Purpura) This is the most reported and studied hematologic, although uncommon, adverse effect of clopidogrel. There is a 1 in 15,000 occurrence reported by Bennet et al.22 A causal relationship has not been established between the development of TTP and clopidogrel. The FDA has estimated the incidence of TTP as 1 in 8500 to 26,000 patients treated with clopidogrel. TTP is a syndrome with a pentad of fever, thrombocytopenia, neurologic abnormalities, renal dysfunction, and microangiopathic hemolytic anemia.23 Drug-induced TTP usually does not have all the components of the above-mentioned pentad.24 Several drugs have been associated with TTP.25 The most likely cause is autoantibodies against a metalloprotease that degrades von Willebrand factor, leading to impaired proteolysis of this factor, resulting in the binding of unusually large sized multimers to platelets that result in formation of platelet microthrombi.26-28 The disease develops 3 to 14 days after the initiation of clopidogrel and presents with thrombocytopenia, microangiopathic hemolytic anemia with shistocytes on peripheral smear, and a decrease in the hematocrit to an average of 27%.22 Therapy with clopidogrel preceding TTP, recovery from TTP after cessation of the drug and reexposure to clopidogrel causing recurrent TTP were some of the criteria suggested by Majhail et al for the diagnosis of clopidogrel-induced TTP.24 The preferred mode of treatment is plasma exchange; a median of 8 sessions of plasma exchange is required for the complete resolution of the disease.22,29,30 Early diagnosis of this disorder is important. TREATMENT Discontinuation of clopidogrel and early initiation of plasmapheresis is the treatment of choice and can dramatically improve survival. The reported mortality may range from 0% to 24% in patients with drug-induced TTP undergoing early plasmapheresis versus 50% to 60% who do not get plasmapheresis.31-33 The survival rate for clopidogrel-associated TTP was 71.2% and the receipt of therapeutic plasma exchange within 3 days of onset of TTP increased the likelihood of survival by 73%.34 TTP WITH HUS (hemolytic uremic syndrome) More than 50 drugs can cause this syndrome including clopidogrel. Few cases have been reported in literature so far on clopidogrel-associated TTP-HUS. Clopidogrel causes TTP-HUS most likely by an immune-mediated reaction.36 A similar syndrome has been reported in a patient who underwent simultaneous kidney and pancreas transplant. There was rejection of the pancreatic transplant after4 months of clopidogrel therapy followed by the development of TTP-HUS 1 week after surgical removal of the rejected pancreas. A similar syndrome has also been reported in patients with disseminated malignancy, and after bone marrow transplantation.25,37 TREATMENT The disease resolved after clopidogrel was discontinued.37 Though plasma exchange has not been shown as a definitive treatment strategy for TTP-HUS, it can still be attempted considering the high mortality rate of this syndrome.
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#20
06.04.2007, 11:26
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Цитата:
2 года назад только каждый третий пациент с подозрением на коронарный синдром и с ОИМ с элевацией ST получал аспирин на догоспитальном этапе (собственное наблюдение), сейчас вроде лучше..... и еще.. может ,что нибудь и сдвинется с этой работы в проблеме аспирин-резистентности, (если она существует конечно)) 
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Линейный вид
