Sodium morrhuate stimulates granulocytes and damages erythrocytes and endothelial cells: probable mechanism of an adverse reaction during sclerotherapy.
Stimulated by a patient with dyspnea, thrombocytopenia, and leukopenia after sodium morrhuate sclerotherapy, we studied the effect of this agent on the plasma coagulation and complement systems, the formed elements of the blood, and cultured human endothelial cells. The addition of sodium morrhuate to citrated plasma did not cause clotting or shorten the prothrombin time or partial thromboplastin time. Incubation of a 1:100 dilution of the clinical sodium morrhuate preparation in heparinized plasma led to a modest rise in [C3a]. The addition of the drug (dilutions 1:50 to 1:300) to granulocytes caused prompt aggregation (and, at the higher concentrations, granulocyte cytotoxicity [trypan blue exclusion; lactate dehydrogenase release]), but the same dilutions failed to aggregate platelets. However, 0.05% morrhuate added to washed red blood cells caused a prompt 84.0% (+/- 0.8% SEM) hemolysis, rendering the supernatant buffer a potent platelet aggregant. Not only was this sclerosing agent toxic to granulocytes and red cells, but a 1:1000 dilution of the drug also caused the destruction of 35.5% (+/- 6.6%) of cultured endothelial cells as measured by chromium 51 release. Three other agents in current use (ethanolamine oleate, sodium tetradecyl sulfate, and polidocanol) were studied and found to cause effects qualitatively similar to those of sodium morrhuate. We conclude that these drugs cause phlebosclerosis not primarily through induction of plasma coagulation, but by directly damaging endothelium and red cells, triggering platelets, and aggregating granulocytes at the venous wall endothelium. These effects likely derive from the surfactant properties of sodium morrhuate as well as its high arachidonate content.(ABSTRACT TRUNCATED AT 250 WORDS)
D001777:Blood Coagulation / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects*; D005227:Fatty Acids / Q000009:adverse effects*; D006098:Granulocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009829:Oleic Acids / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000494:pharmacology; D012976:Sodium Morrhuate / Q000009:adverse effects* / Q000494:pharmacology; D012981:Sodium Tetradecyl Sulfate / Q000494:pharmacology
D005227:Fatty Acids; D009829:Oleic Acids; D000077423:Polidocanol; D011092:Polyethylene Glycols; D012976:Sodium Morrhuate; D012981:Sodium Tetradecyl Sulfate; C033343:ethanolamine oleate