Solvent/detergent-treated plasma suppresses shear-induced platelet aggregation and prevents episodes of thrombotic thrombocytopenic purpura

Abstract

Two children with congenital chronic relapsing thrombotic thrombocytopenic purpura (TTP) have episodes every 3 weeks. These relapses can be prevented by the infusion of normal fresh-frozen plasma (FFP) without concurrent plasmapheresis. We conducted a study to determine whether the exposure of normal plasma to agents that inactivate human immunodeficiency virus and other viruses destroys the component necessary for the effective treatment of this type of TTP that requires only plasma infusion to prevent or reverse relapses. Clinical responsiveness and von Willebrand factor (vWF)-mediated fluid shear stress-induced platelet aggregation were evaluated before and after the infusion of 10 mL/kg FFP or solvent [tri(n- butyl)phosphate]/detergent (Triton X-100)-treated plasma (S/D plasma). Platelet aggregation at shear stresses of 90 to 180 dyne/cm2 (similar to those in the partially occluded microcirculation) imposed for 30 seconds was excessive using the citrated platelet-rich plasma of both patients, and was associated with the presence of unusually large vWF forms in patient platelet-poor plasma. Infusion with either FFP or S/D plasma at 3-week intervals caused the platelet count to increase to (or above) normal within 1 week (on 12 of 12 occasions); the disappearance or diminution of unusually large vWF forms within 1 hour (on 6 of 10 occasions studied); and the reversal within 1 to 4 hours of excessive shear-induced platelet aggregation (on 8 of 9 occasions studied). We conclude that a component in normal plasma resistant to S/D treatment is responsible for preventing thrombocytopenia and TTP episodes, and for controlling excessive shear-induced aggregation in these patients. Our results suggest that excessive in vivo platelet aggregation in chronic relapsing TTP and excessive in vitro vWF-mediated shear-induced aggregation may be similar phenomena.

Cryoprecipitate prepared from plasma virally inactivated by the solvent detergent method

“…In this study, SDFFP had normal VWF antigen but reduced VWF activity. Moake et al (1994) have previously shown that SDFFP lacks the high molecular weight multimeric forms of VWF:Ag. We have confirmed this observation and, in addition have demonstrated that the VWF:Ag multimeric distribution in SD cryoprecipitate is also abnormal, reflecting that in whole plasma.…”

Plasma exchange with solvent/detergent‐treated plasma of resistant thrombotic thrombocytopenic purpura

“…Previous reports of successful plasma exchange with S/D plasma in TTP have focused on the chronic relapsing form of the disease, usually in childhood (Moake et al, 1994). In this case, the patient failed to enter sustained clinical remission despite standard therapy and was therefore classified as having unremitting TTP, and a spontaneous remission was therefore unlikely.…”

“…Thus cryosupernatant, deficient in higher molecular weight forms of VWF, may benefit patients refractory to standard FFP. S/Dtreated plasma, for unknown reasons, lacks high molecular weight forms of VWF (Moake et al, 1994), and may be beneficial primary plasma replacement in TTP.…”

Cryoprecipitate‐reduced plasma:rationale for use and efficacy in the treatment ofthrombotic thrombocytopenic purpura

“…[42][43][44] The rationale for its specific use is that, for unknown reasons, the highest-molecularweight multimers of vWF are lost in the production process, similar to the reduction seen when CRP was analyzed. 42 One study demonstrated that S/D plasma suppressed shear-induced platelet aggregation in vitro and was effective in preventing disease recurrence in two children with chronic relapsing TTP (via infusion). 42 Like FFP and CRP infusions in chronic relapsing TTP, S/D plasma was associated with the rapid disappearance of unusually large vWF multimers.…”

“…42 One study demonstrated that S/D plasma suppressed shear-induced platelet aggregation in vitro and was effective in preventing disease recurrence in two children with chronic relapsing TTP (via infusion). 42 Like FFP and CRP infusions in chronic relapsing TTP, S/D plasma was associated with the rapid disappearance of unusually large vWF multimers. Another case report described a patient with refractory TTP who achieved a sustained remission upon the use of S/D plasma as an exchange medium.…”