Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura
Division of Hematology, Cardarelli General Hospital, Naples, Italy.Annals of Hematology (Impact Factor: 2.63). 12/1999; 78(11):521-3. DOI: 10.1007/s002770050549
Vincristine (1.4 mg/m(2) on day 1, followed by 1 mg on days 4 and 7) was given to eight patients with thrombotic thrombocytopenic purpura (TTP) who were refractory to plasma exchange (n=4) or plasma infusion (n=4). Seven of eight patients (87%) achieved a complete response; one was refractory to treatment and died within a few weeks. After a median follow-up of 50 months, all responding patients are alive and well. Two patients relapsed and were successfully retreated with vincristine. Toxicity was mild, consisting of two episodes of leukopenia and one of autonomic neuropathy leading to paralytic ileus in a patient aged 70 years. We conclude that vincristine is highly effective in the treatment of patients suffering from refractory TTP, with negligible toxicity.
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ABSTRACT: Abstract - Abstract - Abstract - Abstract - Background. Vincristin is an important and fre- quently used chemoterapeutic drug in the treatment of ma- lignant lymphoproliferative disease. Among its side effects are well known bone marrow supression and polyneuropathia. But common physicians are not familiar with vincristine bowel peristaltics inhibitory effect. Patient and methods. This study presents 64-years old patient with acute lymphoblastic leukemia (ALL) who was treated with chemotherapy which included vincristine. Two weeks after the treatment started paralytic ileus developed which was la- ter sucessfully treated with laxatives and prokynetic drugs. Secondary causes for ileus development were excluded. Lite- rature data was reviewed and a higher incidence of paraly- tic ileus in vincristine treated patients was found, especially when they are given concomitant itraconazole. Our patient received concommitant itraconazole as a part of antifungal prophylaxis against invasive aspergillosis which is a perceived routine on hematological departments. Conclusions. Vincristine treated patients should be carefully observed regarding bowel peristaltics and obstipation. If ob- stipation or even paralytic ileus developes, we must stop vin- cristine therapy. All patients receiving vincristine must re- ceive fluconazol instead of itraconazol as a part of antifun- gal prophylaxis. Ključne besede: Ključne besede: Ključne besede: Ključne besede: Ključne besede: akutna limfoblastna levkemija; limfoproli- ferativna bolezen; vinkristin; itrakonazol; paralitični ileus Izvleček - Izvleček - Izvleček - Izvleček - Izvleček - Izhodišča. Vinkristin je nepogrešljiv citostatik pri zdravljenju malignih limfoproliferativnih bolezni. Med stran- skimi učinki zdravila sta dobro poznana njegov zaviralni učinek na kostni mozeg in polinevropatija. Navadno pa leče- či zdravniki prezremo njegov zaviralni učinek na črevesno peristaltiko. Bolnik in metode. Predstavljen je 64-letni bolnik z akutno lim- foblastno levkemijo (ALL), zdravljen s kombinirano kemote- rapijo, ki je vključevala tudi vinkristin. Dva tedna po začet- ku zdravljenja je prišlo do nastanka paralitičnega ileusa, ki se je razrešil po dolgotrajnem zdravljenju z odvajali in proki- netiki. S preiskavami smo izključili sekundarni vzrok za na- stanek ileusa. Ob pregledu literature smo ugotovili, da je inci- denca paralitičnega ileusa pri bolnikih, zdravljenih z vinkri- stinom, še posebej visoka, če hkrati prejemajo tudi itrakona- zol. Tudi v našem primeru je bolnik prejemal itrakonazol, ki ga na hematoloških oddelkih pogosto uporabljamo za prepre- čevanje glivičnih okužb, predvsem invazivne aspergiloze. Zaključki. Pri bolnikih, ki prejemajo vinkristin, moramo biti pozorni na pojav zaprtja. Če se pojavi zaprtje ali pa pride celo do nastanka paralitičnega ileusa, potem moramo prene- hati zdraviti z vinkristinom. Vsi bolniki, ki prejemajo vinkri- stin, naj kot protiglivično preventivno zdravljenje prejemajo flukonazol in ne itrakonazol.
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ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are today often regarded as variants of one syndrome denoted as TTP/HUS, characterized by thrombocytopenia caused by intravascular platelet clumping, microangiopathic haemolytic anaemia, fever, renal abnormalities and neurological disturbances. Unusually large von Willebrand factor multimers have been observed in plasma from patients with chronic relapsing forms of TTP. Their appearance in patients with classic TTP is caused by deficiency of a specific von Willebrand factor-cleaving protease. A constitutional deficiency of this protease has consistently been found in familial cases of TTP, whereas in acquired TTP the protease deficiency is caused by the presence of an inhibiting autoantibody. A normal activity of von Willebrand factor-cleaving protease has been established in patients with HUS. In this chapter, we report 23 cases with severe constitutional protease deficiency: about one half of these patients had their first acute episode as children, whereas the other half had their first TTP event at an adult age, several of them during their first pregnancy. Two of these 23 individuals with congenital protease deficiency, both older than 35 years, have never had an acute TTP event. These results indicate that a deficiency of von Willebrand factor-cleaving protease alone is not sufficient to cause acute TTP. Patients with long-lasting dormant protease deficiency have been found to experience multiple relapses of TTP after having had their first acute episode. In one protease-deficient, plasma-dependent patient with chronic relapsing TTP, we estimated that 5% of normal protease activity is sufficient to remove the most adhesive von Willebrand factor multimers and prevent the formation of platelet microthrombi. The deficiency of von Willebrand factor-cleaving protease is a very strong risk factor for TTP, but the development of an acute bout requires a trigger, possibly causing the activation or apoptosis of endothelial cells in the microcirculation. It is unclear whether anti-endothelial cell antibodies, cytokines or other agents are involved in triggering thrombotic microangiopathy. The release of platelet calpain (and/or other proteases), leading to a degradation of von Willebrand factor and to platelet aggregation, has been reported in patients during their acute TTP episode. It is unknown whether calpain directly triggers an acute event or whether it merely reflects its release during the aggregation of platelets by the unusually large von Willebrand factor multimers. With regard to the heterogeneous aetiology of thrombotic microangiopathies, requiring distinct therapeutic measures, a new classification of thrombotic microangiopathy should replace the current, frequently inappropriate clinical discrimination between TTP and haemolytic uraemic syndrome.Bailliè re s Best Practice and Research in Clinical Haematology 07/2001; 14(2):437-54. DOI:10.1053/beha.2001.0142 · 2.12 Impact Factor
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ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are multisystemic disorders that are characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic manifestations, resulting from platelet agglutination in the arterial microvasculature. Until the introduction of plasma-based therapy, TTP was associated with a mortality rate greater than 90%. Current outcomes of TTP and HUS have improved dramatically with the use of plasma exchange, which should be initiated promptly at diagnosis. Recent evidence suggests that deficiency of a specific plasma protease responsible for the physiologic degradation of von Willebrand factor plays a pathogenic role in a substantial proportion of familial and acute idiopathic cases of TTP. Although multiple triggers, such as infection, drugs, cancer, chemotherapy, bone marrow transplantation, and pregnancy, are recognized, knowledge of the pathogenesis of TTP and HUS in relationship to these disorders remains incompletely understood and continues to evolve. While uncommon, TTP and HUS are of considerable clinical importance because of their abrupt onset, fulminant clinical course, and high morbidity and mortality in the absence of early recognition and treatment.Mayo Clinic Proceedings 12/2001; 76(11):1154-62. DOI:10.4065/76.11.1154 · 6.26 Impact Factor
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