Safety And Field Evaluation of Plasma Lyophilized for Acute and Surgical Management Applications

• Freeze-Dried Plasma (Biological), also known as EZPLAZ, FDP, Lyophilized plasma: Single-donor human plasma supplied in freeze-dried form and reconstituted with sterile water before transfusion. Administered by intravenous or intraosseous infusion as prescribed by the treating physician and in accordance with institutional transfusion policies. Dose is determined by clinical need.
• Conventional Plasma (Biological), also known as FFP, PF24, PF24RT24: Conventional plasma products selected, prepared, and administered according to each institution's standard of care. The protocol does not restrict the types of conventional plasma used. The treating physician determines the dose based on clinical need.

Primary outcomes

• Proportion of participants with a thrombotic/thromboembolic event, or death [Within 7 days after the start of plasma transfusion.]: Proportion of participants experiencing at least one thrombotic event, thromboembolic event, or death.

Secondary outcomes

• Proportion of participants with serious adverse events [Within 24 hours, 7 days, and 28 days after plasma infusion]: Proportion of participants experiencing at least one serious adverse event, including acute and delayed reactions, evaluated at each specified time point.
• Proportion of participants with treatment emergent adverse events [Within 24 hours after the start of plasma infusion]: Proportion of participants experiencing at least one treatment emergent adverse event
• Proportion of participants with unexpected adverse events [Within 28 days after plasma infusion]: Proportion of participants experiencing at least one unexpected adverse event, as defined in the protocol
• Proportion of participants with acute transfusion reactions [Within 24 hours post infusion]: Proportions of participants experiencing any acute transfusion reactions and bloodstream infection
• Proportion of participants who die [Within 6 hours and 24 hours after the start of the Index Transfusion Episode]: Proportion of participants who die after the start of the Index Transfusion Episode
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels [Pre-transfusion and 7 days post-transfusion]: AST and ALT values obtained during routine clinical care, when available, summarized by laboratory parameter and time point
• Creatinine Levels [Pre-transfusion and 7 days post-transfusion]: Creatinine values obtained during routine clinical care, when available, summarized at each timepoint
• Blood Urea Nitrogen (BUN) [Pre-transfusion and 7 days post-transfusion]: BUN values obtained during routine clinical care, when available, summarized at each time point.
• Volume of Blood Components and Crystalloid Fluids Administered at infusion [From start to complete of plasma infusion]: Total volume of each blood component and crystalloid fluid administered during the plasma infusion period, normalized by participant body weight
• Systolic and Diastolic Blood Pressure [Pre-infusion and 1-hour post-infusion]: Change in blood pressure, summarized separately for systolic and diastolic measurements. Mean change from baseline is calculated when paired measurements are available
• Heart Rate [Pre-infusion and 1 hour post-infusion]: Change in heart rate. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.
• Respiratory Rate [Pre-infusion and 1 hour post-infusion]: Change in respiratory rate. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.
• Body Temperature [Pre-infusion and 1 hour post-infusion]: Change in body temperature. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.
• Oxygen Saturation [Pre-infusion and 1 hour post-infusion]: Change in oxygen saturation. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1\. Patients must be aged ≥ 18 years old and require plasma transfusion for one of the following indications:

1. Management of preoperative or bleeding patients who require replacement of multiple plasma coagulation factors (e.g., liver disease, disseminated intravascular coagulation \[DIC\])
2. Patients undergoing massive transfusion who have clinically significant coagulation deficiencies
3. Patients taking warfarin who are bleeding or need to undergo an invasive procedure before vitamin K could reverse the warfarin effect or who need only transient reversal of warfarin effect

Exclusion Criteria:

1. Patients aged < 18 years old
2. Receipt of any plasma product within 72 hours prior to the expected start of the index transfusion episode
3. Known intolerance to plasma or to any excipients (including citrate) in the investigational product (IP) formulation
4. Known history of any of the following:

   1. Hypersensitivity reaction to plasma or plasma-derived products
   2. Immunoglobulin A (IgA) deficiency with documented antibodies against IgA
   3. Congenital platelet disorder
   4. Congenital or acquired thrombophilia
5. Extracorporeal membrane oxygenation (ECMO) therapy at the time of screening
6. Undergoing or may require therapeutic plasma exchange (TPE) for thrombotic thrombocytopenic purpura (TTP)
7. Prisoner
8. Adults under legal guardianship or state custody, as defined by applicable local regulations
9. Trauma patients with the following:

   1. Traumatic cardiac arrest lasting > 5 minutes
   2. Glasgow Coma Score (GCS) of ≤ 8, with an exception for drug-induced lowered GCS
   3. Injury deemed nonsurvivable by trial team using established trauma assessment criteria
   4. Injury Severity Score (ISS) of 75 (when available)
   5. Known complete cervical spinal cord transection
   6. Third-degree burns of > 20% total body surface area
10. Female patients who are pregnant
11. Current or planned participation in any phase of another investigational trial during participation in this trial
12. Patients who self-report previous enrollment in the SAFE-PLASMA trial at any participating medical center