Thrombocytopenia severe, treatment

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. 

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. 

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. 

Thrombocytopenia Moderate thrombocytopenia (platelet counts between 100,000/mm and 50,000/mm ) occurred at a rate of 2.9% in patients in orthopedic clinical trials. Severe thrombocytopenia (platelet counts less than 50,000/mm ) occurred at a rate of 0.2% in patients in orthopedic clinical trials. Moderate thrombocytopenia occurred at a rate of 0.5% in patients given the fondaparinux treatment regimen in the DVT and PE treatment clinical trials. Severe thrombocytopenia occurred at a rate of 0.04% in patients given the fondaparinux treatment regimen in the DVT and PE treatment clinical trials. 

As a single agent in the setting of locoregional, recurrent, and metastatic disease, docetaxel is also tolerated fairly well with leukopenia as the primary dose-limiting toxicity (39). Response rates have been favorable at approx 42% when administered docetaxel (100 mg/m2) every 21 d. Hesse et al. reported on significant toxicides encountered in a phase I study of concomitant taxotere (initial dose = 15 mg/m2)/conventional radiation therapy (70 Gy) grade 3/4 radiation dermatitis, neuropathy, and thrombocytopenia at dose level 1 (40). Of five evaluable patients three patients achieved a CR and one patient achieved a PR. Based on the severity of these toxicities, this treatment schedule was not pursued further. 

The toxicities of 5-fluorouracil vary with the schedule and mode of administration. Nausea is usually mild if it occurs at all. Myelosuppression is most severe after intravenous bolus administration, with leukopenia and thrombocytopenia appearing 7 to 14 days after an injection. Daily injection or continuous infusion is most likely to produce oral mucositis, pharyngitis, diarrhea, and alopecia. Skin rashes and nail discoloration have been reported, as have photosensitivity and increased skin pigmentation on sun exposure. Neurological toxicity is manifested as acute cerebellar ataxia that may occur within a few days of beginning treatment. 

It is used in the treatment of pneumocystosis (pulmonary and extrapulmonary disease caused by P. carinii), African trypanosomiasis (disease caused by Trypanosoma brucei) and leishmaniasis. Systemic pentamidine is highly toxic and can lead to severe hypotension, tachycardia, dyspnea, dizziness, hypoglycemia. Other adverse effects are skin rash, metallic taste, gastrointestinal symptoms, thrombocytopenia and cardiac arrhythmias. 

F. Role in therapy According to Micro-medex, treatment of severe chemotherapy-related thrombocytopenia is hmited to platelet transfusions. There is a need for an alternative, especially due to the frequent use of myeloid colony-stimulating factors (G-CSF, GM-CSF) to reduce febrile neutropenia although effective, their use increases the risk of acute and prolonged thrombocytopenia, and the need for platelet transfusions. Other cytokines, such as interleukin-1 and interleukin-6, have been investigated as a means of ameliorating chemotherapy-induced thrombocytopenia, but results have been equivocal. 

Because of its toxicity, plicamycin (mithramycin) is not the drug of first choice for the treatment of hypercalcemia. However, when other forms of therapy fail, 25-50 mcg/kg given intravenously usually lowers serum calcium substantially within 24-48 hours. This effect can last several days. This dose can be repeated as necessary. The most dangerous toxic effect is sudden thrombocytopenia followed by hemorrhage. Hepatic and renal toxicity can also occur. Hypocalcemia, nausea, and vomiting may limit therapy. Use of this drug must be accompanied by careful monitoring of platelet counts, liver and kidney function, and serum calcium levels. 

A 42-year-old woman, treated with octreotide infusion 50 mg/hour for cirrhosis-related gastrointestinal bleeding on two occasions 9 months apart, had an immediate fall in platelet count on both occasions, resolving after octreotide withdrawal (26). The thrombocytopenia was not severe (nadir platelet counts 62 and 55 x 109/1) and did not require specific treatment. 

Interleukin-11 is the first growth factor to gain FDA approval for treatment of thrombocytopenia. It is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by patients who experienced severe thrombocytopenia after a previous cycle of chemotherapy. Although IL-11 has broad stimulatory effects on hematopoietic cell lineages in vitro, it does not appear to have significant effects on the leukopenia or neutropenia caused by myelosuppressive chemotherapy. Interleukin-11 is given by subcutaneous injection at a dose of 50 g/kg/d. It is started 6-24 hours after completion of chemotherapy and continued for 14-21 days or until the platelet count passes the nadir and rises to > 50,000 cells/ L. 

Pancreatic toxicity is common. Hypoglycemia due to inappropriate insulin release often appears 5-7 days after onset of treatment, can persist for days to several weeks, and may be followed by hyperglycemia. Reversible renal insufficiency is also common. Other adverse effects include rash, metallic taste, fever, gastrointestinal symptoms, abnormal liver function tests, acute pancreatitis, hypocalcemia, thrombocytopenia, hallucinations, and cardiac arrhythmias. Inhaled pentamidine is generally well-tolerated but may cause cough, dyspnea, and bronchospasm. 

E3 monoclonal antibody to GPIIb/llla (abciximab) is very useful as an antiplatelet drug in high-risk ACSs and PCI, It can be used in conjunction with reduced levels of heparin and with aspirin (Table I), Patients may uncommonly experience sudden severe thrombocytopenia within the early hours of treatment as a side effect. 

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