CRA32 ENZYMATIC STABILITY OF CRYOPRESERVATION RT-PA IN PLEURAL INFECTION

Melvinder Singh Jasbinder, Wen Hui Xin, Noor Izyani Zakaria, Wan Jen Lye, Shivanand Letcheminan.

Respiratory Department, Selayang Hospital, Selangor, Malaysia

Introduction
MIST-2 trial concluded the effectiveness of combination both intrapleural recombinant tissue plasminogen activator (rt-PA) and DNase therapy improved fluid drainage in pleural infection, reduced frequency of surgical referral and shortened hospital stay. Here we present a case of complex pleural infection which showed positive outcome post fibrinolysis using combination ‘cryofreeze rt-PA’ and DNAse therapy.

Case Report
A 77-year-old Chinese man with hypertension, and a 40 pack-year smoking history presented with a month-long cough and fever. He was septic on presentation. Examination and imaging showed a complex left pleural collection (4.2 × 1.2 × 6.1 cm) with a split pleural sign. Cultures grew Stenotrophomonas maltophilia and Pseudomonas aeruginosa. The pleural collection was drained, and intravenous Amoxicillin-Clavulanic Acid was initiated. Due to slow clinical improvement, intrapleural fibrinolysis with Alteplase 5 mg and DNase 5 mg was administered for 3 days. To reduce wastage, Hospital Selayang Pharmacy prepared cryofrozen Alteplase in 5 mg/5 mL syringes by reconstituting a 50 mg vial with 50 mL sterile water (1 mg/mL) using aseptic technique. Withdraw 5 mL of reconstituted solution into a sterile syringe, seal, and store at -35 °C to -18 °C (mean -23 °C) in a Dometic MF 290 SG freezer. Storage stability set at 6 months from reconstitution date. Post fibrinolysis and antibiotics for total of 6 weeks, patient showed significant clinical and radiological improvement.

Conclusion
Study has showed that cryofreeze Alteplase solution able to retain greater than 91% enzymatic activity regardless the thawing method compared to freshly prepared control. In our case, cryofreeze Alteplase usage in our case showed significant clinical and radiological improvement. However more clinical studies needed to look into reliability of cryofreeze rt-PA and its cost effectiveness.