The BRAF inhibitor vemurafenib can cause severe cutaneous reactions, including Stevens-Johnson syndrome, particularly when administered after ipilimumab, which usually prevents further drug administration. We report the case of a patient with Stevens-Johnson syndrome due to vemurafenib, who was retreated with vemurafenib with a program of slow desensitization with dexamethasone and diphenhydramine. Vemurafenib was tolerated at a 50% dose after a 3-week desensitization. Desensitization may be possible in patients who develop Stevens-Johnson syndrome after vemurafenib treatment.

Heparin was administered to 34 normal subjects by intravenous injection (100 mu/kg) and the template bleeding time was significantly increased both 10 min and 120 min following injection. Before heparin the bleeding time was 5-3 +/- 1.0 min (mean +/- 1 SD); 10 min after injection it was 9.8 +/- 5.6 min (P less than 0.001); and 120 min after injection it was 7.2 +/- 3.9 min (P less than 0.001). Increases in the bleeding time were unrelated to changes in platelet count, and independent of heparin's effect on plasma coagulation. In blood drawn 10 min and 120 min following heparin injection, there was significantly less [14C]5-HT released from platelet-rich plasma (PRP) in response to collagen, 0.41 mM epinephrine and 8 micron ADP, although in vitro addition of heparin (0.1 mu/ml, 0.5 mu/ml and 2.5 mu/ml) to baseline PRP of three subjects did not depress [14C]5-HT release. Our experiments suggest that intravenous administration of a therapeutic dose of heparin can cause a significant reversible inpairment of platelet haemostatic properties, possibly by an indirect mechanism.

The initiation of globin synthesis in intact reticulocytes and in reticulocyte lysates is maintained by the addition of hemin. The specificity of this effect, has been studied to determine whether it is restricted to hemoglobin and erythroid cells. In intact reticulocytes, hemin (500 pM) enhances the synthesis of carbonic anhydrase as well as of hemoglobin. Similar enhancement of protein synthesis is observed on addition of hemin (500 pM) to intact Krebs II ascites tumor cells, in cell-free extracts of these cells, added hemin (50 ;&M) increases endogenous protein synthesis and the translation of exogenous rabbit globin messenger RNA. These results provide evidence that the effect of hemin is not restricted to globin, and they suggest that hemin may enhance protein synthesis in at least some nonerythroid cells.The synthesis of globin in immature erythroid cells is promoted by the addition of iron (1-4) or of hemin (5). This effect of added hemin or iron is associated with improved maintenance of the number, size, and activity of polyribosomes (6, 7). When desferrioxamine, a specific chelating agent of iron, is added to the incubation medium, the effect of added iron is abolished, but the effect of added hemin is not impaired (6). These findings and additional studies in reticulocyte lysates have focussed attention on the role of hemin in the initiation of globin synthesis (8)(9)(10)(11)(12)(13)(14). In addition, however, to the question of the mechanism of action of hemin in initiating globin synthesis, there is the closely related question of the specificity of the effect of hemin, i.e., does hemin affect the initiation of other proteins, not only in erythroid cells but in other cells in which hemoglobin synthesis does not occur?In this paper, we report the effect of added hemin on (1) the synthesis of a nonheme protein, carbonic anhydrase, as well as of globin in rabbit reticulocytes; (2) the synthesis of protein in intact Krebs II ascites tumor cells; and (3) the translation of endogenous mRNA and of exogenous rabbit globin mRNA in ah extract of Krebs II ascites tumor cells. The results provide evidence of a role for hemin in the initiation of protein synthesis that is not restricted to globin and may obtain in at least some nonerythroid cells. MATERIALS AND METHODS Preparation of reticulocytesNew Zealand rabbits, 3 months old and 3 kg in weight, were bled by cardiac puncture, 25-35 ml/day for 5 days. On the * This work was presented in part at the meeting of the American Society of Hematology, December 6, 1972 [Blood (1972 fifth day, 0.5 ml of Imferon (an iron dextran preparation) was injected intramuscularly; 2 days later, when the reticulocyte count was elevated to 20% or more, the reticulocyte-rich blood was collected. The blood was heparinized (2 mg/10 ml of blood) and centrifuged at 2000 X g for 10 min. The plasma and buffy coat were removed, and the erythrocytes were washed 3 times by suspension in a saline solution (0.13 M NaCl-5.2 mM KCl-7.5 mM MgCl2) and centrifugation at 2000 X g. Incubati...

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