Thrombocytopenia, treatment

Hematological toxicity was analysed in 199 patients treated with a high-dose intravenous bolus aldesleukin regimen for metastatic melanoma or renal cell carcinoma (60). Anemia requiring transfusions was noted in 14% of all treatment courses and severe thrombocytopenia occurred in 2.2%, with three patients suffering from serious hemorrhages. Severe leukopenia was infrequent and not associated with infectious episodes. Early transient lymphopenia (93% reduction) was followed by rebound lymphocytosis up to 198% above baseline values. Except for severe thrombocytopenia, treatment withdrawal was... 

Inadequate blood clotting may result from vitamin K deficiency, genetically determined errors of clotting factor synthesis (eg, hemophilia), a variety of drug-induced conditions, and thrombocytopenia. Treatment, therefore, involves administration of vitamin K, preformed clotting factors, or an-tiplasmin drugs. Thromhocytopenia may be treated by administration of platelets. 

Dacarbazine is the most active compound used for treating metastatic melanoma. It is also combined with anthracyclines and other cytostatics in the treatment of different sarcomas and Hodgkin s disease. Dacarbazine may cause severe nausea and vomiting. Myelosuppres-sion results in leukopenia and thrombocytopenia. Alopecia and transient abnormalities in renal and hepatic function also occur. 

The most common adverse effects are myelosuppression, with leukopenia and thrombocytopenia appearing 7-10 days after treatment, as well as mild nausea. Liver toxicity with jaundice has been reported in rare cases. 

Decitabine is specifically indicated for the treatment of multiple types of myelodysplastic syndromes and chronic myelomonocytic leukemia. As anticipated, use of decitabine is associated with bone marrow suppression including neutropenia and thrombocytopenia which are the most frequently observed serious adverse effects. 

In general, systemic treatment with ASON is well-tolerated and side effects are dose-dependent. Among those, thrombocytopenia, hypotension, fever, increasing liver enzymes, and complement activation were most frequently seen. 

Figure 24.4 The decision-analytic model shows the three strategies that were examined by Arnold and researchers [22] to evaluate the financial implications of the direct thrombin inhibitor argatroban for early treatment (<48 hours after thrombocytopenia onset), compared with delayed treatment, of heparin-induced thrombocytopenia (HIT) with or without thrombosis.

Arnold R, Kim R, Zhou Y, Tang B. Budgetary impact of heparin-induced thrombocytopenia with thrombosis and treatment with the direct thrombin inhibitor Argatroban (P401E). ASHP 39th Midyear Clinical Meeting. Orlando, FL, 2004. 

Arnold R, Kim R, Tang B. The cost-effectiveness of argatroban treatment in heparin-induced thrombocytopenia the effect of early versus delayed treatment. Cardiol Rev 2005 14 7-13. 

Doses and contraindications to glycoprotein Ilb/IIIa receptor blockers are described in Table 5-2. Major bleeding and rates of transfusion are increased with administration of a glycoprotein Ilb/IIIa receptor inhibitor in combination with aspirin and an anticoagulant,30 but there is no increased risk of intracranial hemorrhage in the absence of concomitant fibrinolytic treatment. The risk of thrombocytopenia with tirofiban and eptifibatide appears lower than that with abciximab. Bleeding risks appear similar between agents. 

IgG autoantibody-coated platelets induce Fey receptor-mediated phagocytosis by mononuclear macrophages, predominantly in the spleen and liver. Thrombocytopenia develops as a consequence of megakaryocyte inability to increase platelet production and maintain a normal number of circulating platelets. Currently used treatments are directed at different aspects of the antibody production, platelet sensitization, and the clearance and production cycle.30... 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

Thrombocytopenia is another dose-limiting side effect of chemotherapy. The primary treatment for thrombocytopenia is platelet transfusions. The risk of bleeding is significant when platelet counts are less than 10,000/mm3 (10 x 109/L) ... 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

Contraindications to heparin therapy include hypersensitivity to the drug, active bleeding, hemophilia, severe liver disease with elevated prothrombin time (PT), severe thrombocytopenia, malignant hypertension, and inability to meticulously supervise and monitor treatment. 

J Heparin-associated thrombocytopenia is a benign, transient, and mild phenomenon that usually occurs within the first few days of treatment. Platelet counts rarely drop below 100,000/mm3 and recover with continued therapy. 

These agents interact directly with thrombin and do not require antithrombin to have antithrombotic activity. They are capable of inhibiting both circulating and clot-bound thrombin, which is a potential advantage over UFH and the LMWHs. They also do not induce immune-mediated thrombocytopenia and are widely used for the treatment of HIT. 

Mycophenolate mofetil (CellCept) inhibits DNA and RNA synthesis and has been shown to have a specific lymphocyte antiproliferative effect. Although not FDA approved for this indication, oral mycophenolate mofetil appears effective in the treatment of moderate to severe plaque psoriasis. The usual dose is 500 mg orally four times a day, up to a maximum of 4 g/day. Common adverse effects include GI toxicity (diarrhea, nausea, vomiting), hematologic effects (anemia, neutropenia, thrombocytopenia), and viral and bacterial infections. Lymphoproliferative disease or lymphoma has been reported. 

Hydroxyurea inhibits cell synthesis in the S phase of the DNA cycle. It is used selectively in the treatment of psoriasis, especially in those with liver disease who would be at risk of adverse effects with other agents. However, it is less effective than methotrexate. The typical dose is 1 g/day, with a gradual increase to 2 g/day as needed and as tolerated. Adverse effects include bone marrow toxicity with leukopenia or thrombocytopenia, cutaneous reactions, leg ulcers, and megaloblastic anemia. 

Initial treatment goals include (1) adequate fluid resuscitation, (2) correction of coagulopathy and thrombocytopenia, (3) control of bleeding, (4) prevention of rebleeding, and (5) preservation of liver function. 

Sirolimus is a potent immunosuppressive agent. To prevent thrombocytopenia and hypercholesterolemia, optimize efficacy, and reduce organ rejection, assays were developed to monitor concentrations of sirolimus in the whole blood of patients under treatment.40"12 Wallemacq et al.43 developed and validated a simple high-throughput HPLC-MS/MS method to routinely monitor sirolimus... 

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