Protocol Version 2.0 was approved on 16 Jul 2012 and applied to all study centers in the US. Major changes included: • Removing age restriction of ≥3 years old to comply with Pediatric Research Equity Act Requirements. • Removing the weight restriction of <20 kg. • Modifying the Preliminary Part (I) of the study to randomize subjects into the FS Grifols or Surgicel treatment groups, providing the investigators an opportunity to become familiar with using the FS Grifols and Surgicel products in a variety of bleed types and to also generate data to corroborate the Primary Part (II) effect size assumptions. • Excluding mild bleeding subjects from the Preliminary Part (I) of the study to further increase the relevance of the experience gained in the Preliminary Part (I). In addition, the exclusion aligned the study to the intra-operative inclusion criteria of a TBS with moderate bleeding intensity. • Adjusting sample size calculations due to the change in the randomization ratio from 2:1 to 1:1 to FS Grifols or Surgical treatment groups. • Removing drip application of FS Grifols because the usage is unlikely for the designated surgery type. • Disallowing FS Grifols and Surgicel application after the primary endpoint assessment (T4) or at sites other than the TBS to reduce/minimize confounding factors in the assessment of efficacy and safety. • Reducing intraoperative vital signs measurements to alleviate the number of procedures performed in a short period without adding substantial benefit in terms of safety monitoring. • Adding a procedure for handling missing data for the primary efficacy endpoint. Missing hemostatic assessment would be treated as a failure or as not achieving hemostasis at TBS at T4. • Adding sensitivity analysis adjusted for the study center. • Addition of the testing method and multiplicity adjustment for secondary efficacy endpoints. • Adjusting blood sampling requirements for pediatric subjects <30 kg .

Protocol Version 2.1 was approved on 24 Oct 2012 and applied to all study centers in the US. The major change included: • Addition of TStart2 and TEnd2 time points due to the FDA’s request to capture times of study drug re-application, if applicable.

Protocol Version 3.0 was approved on 23 Aug 2013 and applied to all study centers in the US. Major changes included: • Clarification that females who were pregnant or nursing a child at baseline (within 24 hours prior to surgical procedure) were excluded from the study. Laboratory testing for determination of subject’s eligibility was to be performed locally at the study center. • Removing exclusion criterion #5 (Known [documented] previous exposure to thrombincontaining [bovine, human or recombinant] products) to allow testing of FS Grifols in subjects who were previously exposed to other thrombin products. The collection of safety information in those subjects would help determine the safety profile of FS Grifols in a broader subject population. • Clarification that the maximum total volume of FS Grifols allowed to be applied at the TBS would be approximately 12 mL (equivalent to the full content of 2 FS Grifols kits). Reducing the number of Post-Operative Visits by removing visits on Post-Operative Days 1 and 3. • Shifting the following procedures from Post-Operative Days 1 and 3 to Post-Operative Day 2: coagulation panel (INR and aPTT ratio), CBC, and serum clinical chemistry. • Clarification of laboratory panels for pediatric sampling. In pediatric subjects weighing <30 kg, pediatric tubes must have been utilized for CBC, blood coagulation parameters,and serum clinical chemistry. Virology and immunogenicity sampling was eliminated. In pediatric subjects weighing ≥30 kg, pediatric or adult tubes could be utilized for CBC, blood coagulation parameters, and serum clinical chemistry. Virology and immunogenicity sampling may or may not have been performed according to the judgement of the investigator.

Protocol Version 4.0 was approved on 16 Jan 2014. The key update to this protocol amendment was the addition of approximately 6 study centers in 2 new countries, Hungary and Serbia. Major changes included: • Removing the Month 6 Visit for virus safety testing after study drug administration. Removing the Month 6 Visit shortened the observation period from 6 months to 3 months and also shortened the subject’s expected length of participation period from 7 months to 4 months. • Clarification that concurrent interventions on the pancreas, gall bladder, bile duct, or intestines were allowed.

Protocol Version 4.1 was approved on 25 Mar 2014 and applied only to study centers in Hungary. This country-specific protocol amendment was implemented to include the exclusion criteria (listed below) required by Hungary’s national competent authority. • Have known (documented) history of thrombophilia. • Have known (documented) history of IgA deficiency

Protocol Version 5.0 and Version 5.1 were approved on 16 Dec 2014. The key update to these protocol amendments were the addition of approximately 2 study centers in a new country, Russia. Version 5.0 applied to study centers in the US and Serbia; Version 5.1 applied to all study centers in Hungary. The major changes included: • Decreasing the Hgb levels criterion from ≥9.0 g/dL to ≥8.0 g/dL at baseline (within 24 hours prior to surgical procedure) to allow the enrollment of subjects with lower Hgb levels (eg, subjects receiving chemotherapy prior to surgery or pediatric subjects) that otherwise would be screening failures. Laboratory testing for determination of subject’s eligibility was performed locally at the investigative study center. Updating the FS Grifols shelf-life from 1 year to 2 years when stored at a temperature of ≤-18ºC (≤-0.40ºF). • Clarification that baseline central laboratory samples could be drawn shortly after anesthesia but before the start of surgery.

Protocol Version 5.2 was approved on 31 Mar 2015 and applied only to study centers in Russia. The major change included: • Removal of pediatric subject participation in the study.