Hemolytic reaction to a platelet concentrate.
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Biomedical subjects
Publications and source records attributed to B C McLeod.
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A new blood donation procedure for obtaining selectively the proteins in cryoprecipitate consists of sequential automated plasma exchanges, in which the donor's fresh plasma is replaced with the autologous cryoprecipitated supernatant from the previous exchange donation. Fresh plasma is processed into cryoprecipitate and supernatant, both of which are frozen and stored. Six donors have undergone a total of twenty-six exchange donations of 1.5 to 2 litres. No adverse effects have been encountered. The yield of factor VIII per unit of plasma processed decreases during a donation but remains substantial in the last unit of plasma obtained from a 2 litre exchange. The average total yield of factor VIII from a donation was 730 U. The increased yield of factor VIII per donor may reduce the donor exposure, and hence the hepatitis risk, associated with factor VIII replacement therapy.
Two patients with thrombotic thrombocytopenic purpura (TTP) were treated with plasmapheresis procedures in which the replacement fluid included normal plasma. In both cases, the platelet count rose, hemolysis decreased, and neurologic symptoms improved promptly after this therapy. Unfortunately, both patients eventually died, one of complications of end-organ damage and the other of complications of maintenance therapy with prednisone. Plasmapheresis may be an effective treatment for TTP, either by removing a toxic factor or supplying a deficient factor.
Three patients with cryoglobulinemia have been treated with automated plasma exchange procedures in which the replacement fluid was autologous plasma, obtained at a previous plasmapheresis and incubated in the cold to precipitate abnormal protein. All three responded with a reduction in cryoglobulin level and an improvement in clinical manifestations of cryoglobulinemia. The cost of treatment was less than that of conventional plasmapheresis, even though the quality of the replacement fluid was superior. The term "cryoglobulinpheresis" is suggested for this treatment process.
C56 is known to appear in the fluid phase when zymosan is incubated at 37 degrees C with certain acute phase 'reactor' sera. In the present study, C56 was detected bound to the zymosan particle prior to its appearance free in solution. In reactor sera C56 was formed and released with kinetics similar to that of the generation and decay of a C56-binding site formed when zymosan was incubated with normal serum. Bound and fluid phase C56 was detected only in reactor sera, and was generated only by agents known preferentially to activate the properdin pathway. Elution of C56 from zymosan in hypertonic salt solutions proved to be a convenient step in the partial purification of large amounts of this haemolytically active bimolecular complex.
Multiple polyanions and polycations were tested for their ability to influence formation of EC567 from C56, C7, and sheep erythrocytes. Six of 11 polyanions tested, including polyanethol sulfonate, heparin, and dextran sulfate, inhibited this reaction. By contrast, polycations (five or seven tested), including polybrene, protamine, and polyornithine, potentiated formation of EC567. The inhibition was similar to that previously described for anionic serum factors termed C567-INH, while the potentiation seemed to involve neutralization of serum C567-INH. Thus, this step of the complement attack mechanisms seems amenable to modulation by certain polyelectrolytes, and may thereby be susceptible to pharmacologic manipulation.
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In granulocyte donors during centrifugation leukapheresis (CL), total hemolytic complement, Clq, C3, factor B, and properdin decreased, but only to the extent expected from hemodilution. Crossed immunoelectrophoresis showed no C3 conversion in plasma obtained from the leukapheresis appeared during CL or in donor plasma immediately after CL. When serum was incubated with hydroxyethyl starch, total hemolytic complement did not decrease and C3 conversion was not detected by crossed immunoelectrophoresis. This investigation revealed no evidence that complement activation is associated with CL.
Because of their structural similarity to dialysis membranes, six plasma separator membranes were evaluated for the ability to activate complement, as judged by immunoconversion of the third component of complement in crossed immunoelectrophoresis. A polysulfone and two cellulose acetate membranes were relatively strong alternative pathway activators. Polypropylene, poly[vinylidine fluoride] and polyvinyl-chloride derivative membranes were weak activators in some sera. Membrane activation was inhibited in citrate-anticoagulated but not in heparin-anticoagulated plasma. The results of such in vitro screening should be of value in selecting materials and anticoagulation regimens for membrane plasma separators.
Plasma exchange donation accomplishes the selective donation of cryoprecipitate. It facilitates the repeated donation of large quantities of factor VIII by individual donors and reduces donor exposure for recipients. A highly motivated donor is described who has undergone 103 donations between May 1983 and March 1987, producing 359,460 IU of factor VIII and supplying all the factor VIII needed since August 1983 by his severely affected hemophiliac son, now age 14. The donor has remained in good health, and no significant abnormalities have been noted in hematologic, biochemical, immunologic, coagulation, and serum protein testing. Extensive experience with this donor suggests that repeated plasma-exchange donation is safe and can sometimes allow single-donor support of severe hemophiliacs.
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