Thrombotic thrombocytopenic

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. 

ACE, angiotensin-converting enzyme aPTT, activated partial thromboplastin time ARB, angiotensin receptor blocker BP, blood pressure CBC, complete blood count ECC, electrocardiogram HR, heart rate INR, International Normalized Ratio RR, respiratory rate SCr, serum creatinine, TTP, thrombotic thrombocytopenic purpura. 

Ticlopidine is slightly more beneficial in stroke prevention than aspirin in both men and women.31,32 The usual recommended dosage is 250 mg orally twice daily. Ticlopidine is costly, and side effects include bone marrow suppression, rash, diarrhea, and an increased cholesterol level. Neutropenia is seen in approximately 2% of patients. Thrombotic thrombocytopenic... 

Identify basic clinical features of thrombotic thrombocytopenic purpura (TTP). 

Thrombotic thrombocytopenic purpura (TTP) is a severe systemic disorder characterized by the thrombi formation within the circulation that result in the platelet consumption and subsequent thrombocytopenia. The inherited sub-type is chronic and relapsing and generally occurs in childhood. Acute idiopathic TTP, which occurs in adults, is more common and harder to treat. The estimated annual incidence of TTP is 3.7 cases per million.33... 

EHEC are the pathogenic subgroup of Stx-producing E. coli (STEC). Acute hemorrhagic colitis has been associated mainly with the 0157 H7 serotype. This serotype has been responsible for larger outbreaks of infection, has higher rates of complications, and appears to be more pathogenic than non-EHEC STEC strains. The spectrum of disease associated with E. coli 0157 H7 includes bloody diarrhea, which is seen in as many as 95% of patients, nonbloody diarrhea, hemolytic-uremic syndrome (HUS), and thrombotic thrombocytopenic purpura. 

Acyclovir 200 mg PO q4hour x 7-/0 days 400 mg PO 3 times daily x 7-10 days3 200 mg PO q12hour x 7-1 0 days6 Headache, confusion, nausea, vomiting, thrombocytopenia, renal insufficiency, rash, pruritus, fever, arthralgias, myalgia, thrombotic thrombocytopenic purpura, hallucinations, somnolence, depression... 

Thrombotic thrombocytopenic purpura Condition characterized by formation of small clots within the circulation resulting in the consumption of platelets and a low platelet count. 

Mortality Rate (untreated) <0.5% overall <15% hemolytic uremic syndrome <99% for thrombotic thrombocytopenic purpura. 

Suggested Alternatives for Differential Diagnosis Malaria, typhoid fever, shigellosis, meningococcemia, salmonella infection, other tick-borne diseases, rickettsial infections, leukemia, lupus, disseminated intravascular coagulation, hemolytic uremic syndrome, leptospirosis, thrombocytopenic purpura, and idiopathic or thrombotic thrombocytopenic purpura. 

Intrinsic Vascular damage Hypercalcemia Hepatorenal syndrome Vasculitis Polyarteritis nodosa Hemolytic uremic syndrom thrombotic thrombocytopenic purpura Emboli Atherosclerotic Thrombotic... 

Another type of autoantibody leading to thrombocytopenia that is induced by ti-clopidine is directed against von Willebrand factor metalloproteinase [45 ]. This prevents the normal clearance of large multimers of von Willebrand this can lead to platelet aggregation, and in some cases, to thrombotic thrombocytopenic purpura, commonly referred to as TTP. Many other drugs have been implicated as cases of TTP, but the mechanism is unclear and appears to differ with different drugs [46],... 

Tsai, H.M. et al., Antibody inhibitors to von Willebrand factor metalloproteinase and increased binding of von Willebrand factor to platelets in ticlopidine-associated thrombotic thrombocytopenic purpura, Ann. Intern. Med., 132, 794, 2000. 

Medina, P.J., Sipols, J.M., and George, J.N., Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, Curr. Opin. Hematol., 8, 286, 2001. 

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. 

Ticlopidine can cause life-threatening hematological adverse reactions, including neutropenia/agranulocytosis and thrombotic thrombocytopenic purpura (TTP). Neutropenia/agranulocytosis Neutropenia defined as an absolute neutrophil count (ANC) less than 1,200 neutrophils/mm occurred in 50 of 2048 (2.4%) stroke patients who received ticlopidine in clinical trials. Neutropenia is calculated as follows ANC = WBC x % neutrophils. In 17 patients (0.8%) the neutrophil count was less than 450/mm. ... 

Thrombotic thrombocytopenic purpura (TTP) TTP has been reported rarely following use of clopidogrel, sometimes after a short exposure (less than 2 weeks). It is... 

Thrombotic thrombocytopenic purpura (TTP) A single case of TTP was reported with risperidone. The relationship to therapy is unknown. 

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) TTP/HUS which has resulted in death, has occurred in immunocompromised patients receiving acyclovir therapy. 

Among the adverse events that were reported at a rate of 3% or more and less than 20%, the following were more prominent in patients maintained on sirolimus 5 mg/day vs 2 mg/day Epistaxis, lymphocele, insomnia, thrombotic thrombocytopenic purpura (hemolytic-uremic syndrome), skin ulcer, increased LDH, hypotension, facial edema. 

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

Clopidogrel is indicated for prevention of vascular ischaemic events in patients with symptomatic atherosclerosis. It is also used, along with aspirin, for the prevention of thromboembolism after placement of an intracoronary stent. Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so that a loading-dose is usually administered. Although rare, severe neutropenia and also thrombotic thrombocytopenic purpura may occur. 

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