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The fabrication of a novel in situ forming hydrogel composed of a multifunctional poly(ethylene glycol) (PEG) N-hydroxysuccinimide ester (NHS) and poly(allylamine hydrochloride) (PAA) was investigated. FTIR confirmed that PAA formed the hydrogel matrix (i.e., the formation of a PAA-like hydrogel). A factorial experiment was conducted to identify the key parameters that controlled gelation time, gel content, and swelling properties. The type of PEG (e.g., 4- and 6-arm) appeared to play a major role in determining all three performance parameters, with the greatest effect on gelation time. Other influencing factors include (a) the PEG concentration, which contributes to the gelation time and gel content; (b) pH of the buffer used for dissolving each polymer, which can affect the gelation time; and (c) PAA molecular weights, which contribute to the gel content and swelling. The concentration of PAA solution had no significant effects on hydrogel formation and properties within the investigated range, presumably due to negligible changes in the crosslinking density of the hydrogels. The PAA buffer pH influenced the gel content as well. Finally, thromboelastography was used to examine the effects of each polymer and their in situ gelation on blood coagulation in vitro. All individual polymers tested reduced clot strength, while the gelation of the polymers enhanced overall procoagulant effects. These results suggest that the biomaterial can be optimized to provide a combination of rapid gelation and swelling properties suitable for hemorrhage control and thus warrant further studies in animal bleeding models.

Background: Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain., Objective: To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy., Design: Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment., Setting: 14 anticoagulant therapy clinics in Canada, the United States, and Italy., Patients: Nonbleeding patients with INR values of 4.5 to 10.0., Intervention: Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed)., Measurements: Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes)., Results: 56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, -0.5 percentage point [95% CI, -6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, -0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, -1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001)., Limitation: Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed., Conclusion: Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0., Funding: Canadian Institutes of Health Research and Italian Ministry of Universities and Research.