ISIS 104838 sodium

Chinese origin (female, 4-6 years old)^[1]

30 mg/kg (loading dose on Days 1,4,7); 30 mg/kg twice weekly (Days 10-35); 30 mg/kg once weekly (Days 38-80); total weekly dose of 60 mg/kg

s.c.; loading dose on Days 1, 4, 7; twice weekly from Days 10 to 35; once weekly from Days 38 to 80

Reduced platelet counts relative to baseline by Day 30 (baseline: 396-551 ×10³ cells/μL).
Induced moderate 50% platelet count decrease (to ~150 ×10³ cells/μL, Phenotype 1) in four monkeys and severe thrombocytopenia (as low as 16 ×10³ cells/μL, Phenotype 2) in one monkey.
Increased mean platelet volume most significantly in the severely affected monkey.
Increased platelet sequestration in the liver and/or spleen by 25-45% relative to baseline at Day 55/56.
Increased total serum IgM by 2-4.5-fold, anti-platelet factor 4 (PF4) IgM by 2-5-fold, and anti-platelet IgM by 2-3-fold in all monkeys.
Increased monocyte chemoattractant protein 1 (MCP-1) levels by 2-9-fold and monocyte-derived extracellular vesicles by 2-6-fold in all monkeys.
Increased von Willebrand factor (VWF) antigen by 2-3-fold in all monkeys with no clear decrease in ADAMTS13 activity.
Showed correlation between IL-8 levels and platelet counts, with IL-8 levels decreasing parallel to platelet count reductions and rebounding as platelet counts recovered in the severely affected monkey.
Normalized platelet counts and mean platelet volume in the severely affected monkey after corticosteroid treatment, but had little effect in the four monkeys with moderate thrombocytopenia.