Fig. 4: In vivo SPAs inhibit histone-induced tissue injury, thrombocytopenia, anemia, and DVT.

a Mice injected i.p. with SPA and heparin (Hep) doses (as indicated) 10 min prior to i.v. injection of histones (50 mg kg⁻¹), had blood collected 4 h post histones for assessment of liver (alanine aminotransferase, ALT), kidney (creatinine), and general tissue (lactate dehydrogenase, LDH) damage. Data pooled from 15 separate experiments, with n = 2–50 mice per treatment. b Mice (n = 5/group), treated as above but receiving one SPA dosage (100 mg kg⁻¹), had their blood and spleens collected 10 min post histones for assessment of circulating platelets and RBC and splenic hemoglobin (Hb). c Impact of CBS and MTS on a mouse model of histone-induced DVT (n = 7–10 mice per group). All data, except LDH values, are presented as mean ± s.e.m. and analyzed by one-way ANOVA with Dunnett’s correction for multiple comparisons. LDH values at or above the detection limit of 3325 U l⁻¹ are reported in the LDH data of panel a. For some of these samples, sufficient material was available for dilution to obtain accurate LDH levels. The LDH data are presented as median with 95% confidence intervals, instead of the mean that may be biased by the values at the detection limit. The data above the detection limit was set to 3325 U l⁻¹ prior to performing a non-parametric Kruskal–Wallis test with Dunn’s correction for multiple comparisons. Source data are provided as a Source Data File.