Thrombotic thrombocytopenic purpura treatment

Ticlopidine inhibits the P2Yj2 platelet ADP receptor, thus inhibiting ADP-dependent activation of the GP Ilb/IIIa receptor. It has a slow onset of action and takes 3-7 days to reach its maximal antiplatelet effect. It is inactive in vitro and must undergo activation by the hepatic cytochrome p450 enzyme system. Secondary prevention trials have found that ticlopidine-treated patients have an estimated RRR of 33% for the composite endpoint of stroke, myocardial infarction, or vascular death after ischemic stroke. Significant adverse effects include bone marrow depression, rash, diarrhea, and thrombotic thrombocytopenic purpura. No clinical trials have studied ticlopidine for the treatment of stroke in the acute phase. 

Sequential determination of platelet counts in patients receiving vincristine during early studies unexpectedly occasionally revealed thrombocytosis, which could not be accounted for by systemic response to treatment alone 10,11). Ultimately shown to most likely be the result of increased megakaryocytic endomitosis II), the observation led to the use of vincristine, and later vinblastine, both alone and bound to platelets, in a variety of thrombocytopenic disorders. These include idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, and chemotherapy-induced microangiopathic hemolytic anemia. 

The use of vincristine to treat thrombotic thrombocytopenic purpura has also been reported to be successful 14,18). This rare disease of sporadic thrombosis of small vessels with consequent intravascular hemolysis has been successfully treated recently with both plasma exchange and plasma infusion. However, there are obvious disadvantages to plasma infusion, including volume overload, transmission of infection, and cost and scarcity of plasma. Several patients have been successfully treated with vincristine alone or in association with plasma therapy. At present, however, this treatment should probably not be used alone because of the high success rate of plasma infusion and/or exchange. 

TTP thrombotic thrombocytopenic purpura (rash due to low platelets) TTS transdermal therapeutic system Tx treatment UC ulcerative colitis... 

Adverse effects of ticlopidine include nausea, dyspepsia, and diarrhea in up to 20% of patients, hemorrhage in 5%, and, most seriously, leukopenia in 1%. The leukopenia is detected by regular monitoring of the white blood cell count during the first 3 months of treatment. Development of thrombotic thrombocytopenic purpura has also been associated with the ingestion of ticlopidine. The dosage of ticlopidine is 250 mg twice daily. It is particularly useful in patients who cannot tolerate aspirin. Doses of ticlopidine less than 500 mg/d may be efficacious with fewer adverse effects. 

Hematological adverse effects can occur during treatment with both simvastatin and atorvastatin, according to a brief review (23). They include thrombotic thrombocytopenic purpura and severe thrombocytopenic purpura. 

Sundram F, Roberts P, Kennedy B, Pavord S. Thrombotic thrombocytopenic purpura associated with statin treatment. Postgrad Med J 2004 80(947) 551-2. 

In addition to the risk of bleeding, which will be detailed in the different studies, thienopyridines are able to cause skin disorders (rashes or prurit) and gastrointestinal disorders (diarrhea). In the CLASSICS study, these side effects were observed in 8.2% of patients treated with ticlopidine and in 3.5% of those taking clopidogrel treatment. The most serious problem was related to hematologic disorders neutropenia or thrombocytopenia. These disorders are much less frequent with clopidogrel than with ticlopidine 0.04% of neutropenia in the CAPRIE study and 0.05% in the CURE trial, Thrombotic thrombocytopenic purpura are exceptional one for 200,000 patients. 

Leach JW, Pham T, Diamandidis D, George JN. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) following treatment with deoxycoformycin in a patient with cutaneous T cell lymphoma (Sezary syndrome) A case report. Am J Hematol 1999 61(4) 268-70. 

Thrombotic thrombocytopenic purpura is a possible complication of interferon alfa in patients with chronic myelogenous leukemia, and can develop even after a successful prolonged (2-3 years) treatment (234). Complete recovery is expected after prompt medical management with plasma exchange and glucocorticoids. 

Intensive plasma exchange has been studied in the treatment of numerous diseases, above all in Waldenstrom s macroglobulinemia, hypercholesterolemia, hyperviscosity syndrome, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, myasthenia... 

Various other hematological complications have been observed during ticlopidine treatment (5). They include neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, pancytopenia, and thrombotic thrombocytopenic purpura (6). These reactions are potentially severe and some are fatal. Major bleeding is rare. Among 188 cases of hematological comphcations associated with ticlopidine and reported to the US Food and Drug Administration, 36 (19%) resulted in death (7). 

In 43 322 patients treated with coronary stents and ticlopidine for 1 year there were 9 cases of thrombotic thrombocytopenic purpura (0.02%) (18). The risk of thrombotic thrombocjdopenic purpura during the use of ticlopidine after coronary stenting was 50-fold higher than in the general population. Ten other cases of thrombotic thrombocytopenic purpura related to ticlopidine were identified from the participating centers. Four of the 19 patients died, and all four deaths occurred in patients who were not treated with plasmapheresis. The authors stressed that early recognition and treatment is crucial for minimizing mortality. 

Fresh frozen plasma contains the components of the coagulation system and is indicated for the replacement of deficient coagulation factors II, V, VII, X, XI, and XIII. Factor VIII and IX deficiencies are treated with specific factor concentrates. Fresh frozen plasma is also used for the rapid reversal of warfarin anticoagulation and in the treatment of disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura is treated by means of therapeutic plasma exchange with fresh frozen plasma as the replacement fluid. Cryo-precipitate, which contains factor VIII, von Willebrand s factor, and fibrinogen, is indicated for the treatment of von Willebrand s disease that does not respond to desmopressin acetate, and for fibrinogen replacement (see Chap. 100). 

Tsai HM (2003) Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J Am Soc Nephrol, 14 1072-1081. 

Niaudet P, Habib R (1994) Cyclosporine in the treatment of idiopathic nephrosis. J Am Soc Nephrol 5 1049-1056 Niaudet P, Habib R (1998) Methylprednisolone pulse therapy in the treatment of severe forms of Schoenlein-Henoch purpura nephritis. Pediatr Nephrol 12 238-243 Noris M, Ruggenenti P, Perna A et al (1999) Hypocomple-mentemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura Role of factor H abnormalities. J Am Soc Nephrol 10 281-293... 

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