PL4-SN-27 - Freeze-Dried Platelets Decrease Bleeding in Refractory Thrombocytopenic Patients with Hematological Malignancies

Freeze-Dried Platelet-Derived Hemostatic (FPH) have a room temperature shelf life of 3 years, lack immunogenicity and thrombogenicity, and are heat-treated to reduce infection risk. Bleeding patients with hematologic malignancies often experience platelet shortages, and other hemostatic options are needed.

Study

Design/Methods: We conducted a prospective, multicenter, randomized, open-label, Phase 2, multidose, dose-ranging ranging trial (NCT04631211) for bleeding thrombocytopenic patients with hematologic malignancies. Three FPH dose-level groups and one liquid-stored platelets (LSP) group were studied. Treatment success was defined as cessation or decreased bleeding of the most severe bleeding site. Correlative analysis was performed on baseline plasma and serum from 7 clinically refractory patients before infusion of FPH or LSP. Samples were analyzed for anti-HLA and anti-platelet antibody presence and identification, cross matching reactivity and the ability to affect hemostasis ex vivo

Results/Findings: 22 patients were screened for enrollment, 2 failed screenings, and 20 patients were randomized to receive low dose (n=5), medium dose (n=5), high dose (n=7) FPH or LSP (control, n=3). One patient discontinued before receiving treatment. All patients were clinically refractory to LSP and received concomitant blood product transfusions including LSP. At 12 hrs there was a dose-dependent response with increased percentages of patients with improved clinical response and decreased bleeding (Figure A). At the primary bleeding site, 20% of patients had improved bleeding scores at WHO grade 1 at the low dose; 40% had improved/resolved bleeding at the medium dose; and 57.2% had improved/resolved bleeding at the high dose. Three (100%) patients receiving conventional platelets (control) had persistent Grade 2 bleeding at 12 hrs. Treatment success at 24 hrs was achieved for most patients on FPH: Low (60%), Medium (60%), and High Dose (57%) compared with none (0%) in the control LSP group. 

In multiply transfused clinically refractory bleeding thrombocytopenic patients, 28.6% (2/7) were presented with anti-HLA antibodies more reactive to LSP than FPH antigens. FPH retained hemostatic activity independent of reactive antibody status, as judged by thrombin generation assay (TGA) and total thrombus formation analysis system (T-TAS) analyses whereas TGA LSP was  impaired in one specimen. FPH ability to generate thrombin was not affected by abciximab. FPH remained hemostatic in the presence of refractory antibodies offering a potential efficacious alternative in clinically refractory thrombocytopenia.

Conclusions:

24 hours post-administration, approximately 60% of all FPH-treated patients achieved treatment success, while no patient achieved success in the control group. FPH contributed to decreased bleeding in patients with hematologic malignancies and platelet refractoriness.