Complement activation and histamine release following administration of roentgen contrast media.

Anaphylactoid reactions following administration of reontgen contrast media (CM) have occasionally been described. In this investigation, blood samples for nonallergic human volunteers were exposed to the CM iodixanol (Visipaque), iohexol (Omnipaque), ioxaglate (Hexabrix) and metrizoate (Isopaque 350). The degree of activation of the complement cascade and the amount of free histamine in the samples were estimated. By using a hemolytic assay, a dose-independent complement consumption was detected when salt-free dilutions of the CM were added to human serum. Very little complement consumption was detectable when the concentrations, indicating that in the CM solutions were adjusted toward normal plasma concentrations, indicating that the lack of salts in the CM formulations was responsible for causing the consumption of complement rather than the CM molecules themselves. By using ELISA assay for determination of the terminal complement complex (TCC), no increase in TCC level was detected following the addition of iodixanol to human serum. The results indicate that iodixanol does not activate the complement cascade when added to human serum, and that it is unlikely that anaphylactoid reactions observed in man after CM administration are caused by CM-induced anaphylatoxins. No histamine release was observed following the addition of ioxaglate, metrizoate, iohexol or iodixanol to blood from nonallergic individuals.

The effect of pretreatment with thio-TEPA and cytosine arabinoside on megakaryocytopoiesis in rats given a sublethal dose of thio-TEPA.

The present study was performed on rats, mainly to examine the so-called priming effect on megakaryocytopoiesis. One group of animals received 2 or 4 mg thio-TEPA or 200 mg cytosine arabinoside/kg body weight (the pretreatment) 2.5 days or 8 days prior to a dose of 10 mg thio-TEPA/kg body weight (the challenge dose). Another group received a pretreatment dose of 1 mg melphalan/kg body weight 2.5 days prior to a challenge dose of 3 mg melphalan/kg body weight. The number of bone marrow megakaryocytes, blood platelet production, mean platelet volume, blood platelet counts, leucocyte and granulocyte counts were examined on days 2, 4, 7, 10, 13, 16 and 20 after the challenge dose. The gut mucosa (number of mucosal crypts in terminal jejunum) and survival were studied in animals receiving pretreatment 2.5 days prior to a challenge dose of about LD100 for thio-TEPA and melphalan. No systematic differences were observed whether the animals received pretreatment prior to the challenge dose or not. Thus, no priming effect was observed.

Transient vinblastine-induced thrombocytopenia during chemotherapy with vinblastine, cis-platinum and bleomycin.

An early, transient drop in peripheral blood platelets to a mean nadir value of 49% (range 31-83%) of the pretreatment value was seen in 31 patients during chemotherapy with cis-platinum, vinblastine and bleomycin (PVB). The mean number of platelets dropped by 22% during the first 24 h after the start of chemotherapy, nadir value was seen after 3 d, with recovery to 107% of pretreatment level on d 14-15. Platelet survival studies during PVB chemotherapy showed shortened platelet survival time and indicated increased destruction of platelets. Identical patterns of early, transient thrombocytopenia were seen in 6 patients treated with vinblastine only. The early fall in circulating platelets did not predict subsequent serious thrombocytopenia. There were no bleeding episodes in the 37 patients studied here, but the early thrombocytopenia seen after vinblastine therapy may possibly be of clinical importance in critically ill patients at risk for bleeding episodes. In rats, an early drop in circulating platelets occurred after a high dose of vinblastine, but not after bleomycin. Addition of bleomycin to vinblastine did not increase the vinblastine-induced thrombocytopenia. It is concluded that the early drop in peripheral blood platelets during chemotherapy with PVB is due to vinblastine.

The effect of splenectomy on platelet formation and megakaryocyte DNA content in rats.

The DNA content of rat bone marrow megakaryocytes (MK) was studied by Feulgen photometry following splenectomy and sham operation, respectively. The DNA measurements were preceded by acetylcholinesterase staining for identification of the 2N-8N MK. The number of 2N-8N MK decreased to minimum values, while the number of 16N-64N MK increased to maximum values about 4 days following both splenectomy and sham operation. However, the changes were somewhat more pronounced following splenectomy than sham operation. The total MK number did not change significantly. Platelet production, measured by 35S incorporation into platelets, increased during the first 2 days and remained high for 6-7 days, increasing the platelet counts. All values were about normal 30 days after surgery, except for a minor thrombocytosis following splenectomy. The early, highly significant thrombocytosis, following both splenectomy and general surgery, is caused by increased production of platelets due to the surgical trauma. This is caused by a direct action on bone marrow MK by transforming 2N-8N MK into higher ploidy classes. Lack of splenic platelet pooling may influence the grade and duration of the early thrombocytosis after splenectomy. The late, long-lasting, minor thrombocytosis, which occurs after splenectomy but not after sham operation, can be explained by the removal of the splenic platelet pool.