Bleeding, Hypofibrinogenemia
Conditions
Keywords
Cryoprecipitate, Pathogen Reduced Cryoprecipitate
Brief summary
The goal of this quality improvement study is to compare pathogen-reduced cryoprecipitate with traditional cryoprecipitate in liver transplant and cardiovascular patients. The investigators hypothesize that by having immediate access to a readily available thawed blood product that replaces fibrinogen (the main substrate of a blood clot), early bleeding can be treated before it escalates into uncontrolled hemorrhage, and therefore additional blood products, like platelets, plasma and red blood cells can be avoided. Participants will be given one of the two FDA-approved blood products.
Detailed description
Immediately replacing fibrinogen in perioperative bleeding patients with acquired fibrinogen deficiency improves outcomes. The product that is primarily used for fibrinogen replacement in the US, cryoprecipitate (cryo), must be stored frozen and expires six hours after thawing, resulting in a delay in transfusion of approximately 50 minutes from the time it is ordered, as well as unnecessary transfusion of more readily available but not indicated blood components that are transfused while the patients waits for cryo . A modified version of the product, pathogen reduced (PR) cryo, is now FDA approved and can be thawed and stored for 5 days, allowing the product to be available immediately when needed. In this quality improvement study, the investigators will compare the effect that readily available, pre-thawed PR cryo has on transfusion practice in cardiovascular and liver transplant patients who receive PR cryo versus those who receive traditional cryo by randomizing cryo transfusions in the blood bank by month to all cryo or all PR cryo. All clinical decisions, including the need for cryo, and laboratory testing will occur per standard of care.
Interventions
BIOLOGICALTraditional Cryoprecipitate
This is the cryoprecipitate already currently being given to patients with a cryo order.
BIOLOGICALPathogen-Reduced Cryoprecipitate
This is the pathogen-reduced cryoprecipitate that is intended to be compared to the standard cryoprecipitate.
Sponsors
Cerus Corporation
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The intervention and randomization are not made at the level of the individual patient, but rather on clusters of patients by month. The clusters will include all patients at NYP/WC for whom pooled cryo is ordered during a single month.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Adult patients undergoing cardiovascular surgery or liver transplant who receive cryo during surgery during the two year study period. 2. Cardiovascular surgery includes the following procedures: 1. coronary artery bypass grafting 2. valve repair or replacement 3. open thoracic aortic and thoracoabdominal aortic surgery 4. atrial or ventricular septal defects 5. ventricular assist device implantation or revision 6. or any combination of the above.
Exclusion criteria
1. Patients who do not receive any cryo product in the OR 2. Patients who are not cardiovascular surgery or liver transplant patients 3. Cardiac transplantation surgery 4. Patients who receive a product in error within either the cryo time period or the PR cryo time period. For example, PR cryo during a cryo month or cryo during a PR cryo time month. 5. Patients who receive less than 1 pool (5 units) of cryo 6. Pediatric patients (less than 18 years of age). 7. Patients who received both PR cryo and traditional cryo 8. Pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of RBCs Used Over Admission | Within the first 30 days after surgery. | RBCs used over admission |
| Total Number of Platelets Used Over Admission | Within the first 30 days after surgery. | Plts used over admission |
| Total Number of Plasma Used Over Admission | Within the first 30 days after surgery. | All units over admission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Platelets Used Perioperatively | 3 days post procedure | Number of platelet units transfused during perioperative period |
| Time From Operating Room (OR) Start Time to Start of Cryo Transfusion | procedure (Time from OR start time to start of cryo transfusion) | — |
| Time From Cryo Order to Start of Transfusion | procedure (Time from cryo order to start of transfusion) | Time to cryo order time to start of cryo transfusion |
| Number of Cryo Units Wasted by Blood Bank | Daily, up to approximately 24 months | This captures the Cryoprecipitate units discarded. |
| Pre Transfusion FIBTEM Amplitude 10 Min After Start of Clot Formation | Variable, but it is generally available within 15 minutes of the start of ROTEM testing. | FIBTEM before transfusion, if anesthesiologist orders it. FIBTEM is a point of care laboratory test measuring fibrinogen contribution to a clot. It is part of ROTEM testing and helps providers determine if patients need fibrinogen supplementation during surgical bleeding. |
| Post Transfusion FIBTEM Amplitude at 10 Min After Start of Clot Formation | Variable, but it is generally available within 15 minutes of the start of ROTEM testing. | FIBTEM after transfusion, if anesthesiologist orders it. FIBTEM is a point of care laboratory test measuring fibrinogen contribution to a clot. It is part of ROTEM testing and helps providers determine if patients need fibrinogen supplementation during surgical bleeding. |
| Maximum Clot Firmness (MCF) | Variable, but it is generally available within 1 hour of the start of ROTEM testing. | The maximum strength of a clot as determined by ROTEM testing. |
| Pre-transfusion Fibrinogen Level | During surgery, within 3 hours of specimen receipt by laboratory. | The fibrinogen measurement before cryoprecipitate is transfused. |
| Highest Fibrinogen Level Within 24 Hours | Within 24 hours after surgery | — |
| Lowest Fibrinogen Level Within 24 Hours | Within 24 hours after surgery | — |
| Cumulative Volume in Drains After Surgery (e.g., Chest Tube for CV Surgery) at the Time of Removal | Up to approximately 3 days | The cumulative volume in drains after surgery (e.g., chest tube for CV surgery) at the time of drain removal |
| Number of Cryo Units Used Perioperatively | 3 days post procedure | All products within 3 days |
| Time From End of Bypass Pump for CV Surgery | Until end of surgery | — |
| Length of Stay in OR | Duration of time in operating room | Operating room length of stay |
| Length of Stay in ICU | During hospitalization, approximately 5 days to 30 days | Participant length of stay in ICU setting |
| Length of Stay in Hospital | During hospitalization, approximately 5 days to 30 days | Overall length of stay in hospital |
| Need for Ventilator | During hospitalization, approximately 5 days to 30 days | — |
| Time on Ventilator | During hospitalization, approximately 5 days to 30 days | If participant was on ventilator, amount of time spent on ventilator |
| Overall Cost of Cryo vs PR Cryo, When Factoring Wastage | Daily, approximately 24 months | Cost of traditional cryoprecipitate compared to PR Cryoprecipitate. |
| Number of Participants That Experienced an Adverse Event of Fever | Within 5 days of surgery start time | All participants that experience fevers that occur during the time frame |
| Number of Participants That Experienced an Adverse Event of Infection | Within 5 days of surgery start time | All participants that experience infections that occur during the time frame |
| Number of Participants That Experienced an Adverse Event of Transfusion Reaction. | Within 5 days of surgery start time | All participants that experience transfusion reactions that occur during the time frame |
| Fibrinogen Level | Most proximal to end of procedure | Fibrinogen level most proximal to the end of surgery |
| Volume in Drains (Chest Tube for CV Surgery) | At 24 hours after surgery | — |
| Number of RBCs Used Perioperatively | 3 days post procedure | Number of RBC units transfused during perioperative period |
| Number of Plasma Used Perioperatively | 3 days post procedure | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Given Traditional Cryo These are the liver transplant and cardiothoracic (LT and CT) patients that will be given traditional cryo based on the randomization protocol. The blood bank will alternate use of PR cryo and regular cryo each month for all patients with a cryo order. All patients will receive either traditional cryo or PR cryo in a given month.
Traditional Cryoprecipitate: This is the cryoprecipitate already currently being given to patients with a cryo order. | 105 |
| Patients Given PR Cryo These are the liver transplant and cardiothoracic (LT and CT) patients that will be given PR cryo based on the randomization protocol. The blood bank will alternate use of PR cryo and regular cryo each month for all patients with a cryo order. All patients will receive either traditional cryo or PR cryo in a given month.
Pathogen-Reduced Cryoprecipitate: This is the pathogen-reduced cryoprecipitate that is intended to be compared to the standard cryoprecipitate. | 103 |
| Total | 208 |
Baseline characteristics
| Characteristic | Patients Given Traditional Cryo | Patients Given PR Cryo | Total |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 14 | 61 years STANDARD_DEVIATION 14 | 61 years STANDARD_DEVIATION 14 |
| ASA Score | 3.8 Score on a scale STANDARD_DEVIATION 0.51 | 3.8 Score on a scale STANDARD_DEVIATION 0.43 | 3.8 Score on a scale STANDARD_DEVIATION 0.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 1 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 91 Participants | 102 Participants | 193 Participants |
| Region of Enrollment United States | 105 participants | 103 participants | 208 participants |
| Sex: Female, Male Female | 39 Participants | 41 Participants | 80 Participants |
| Sex: Female, Male Male | 66 Participants | 62 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 105 | 2 / 103 |
| other Total, other adverse events | 18 / 105 | 17 / 103 |
| serious Total, serious adverse events | 0 / 105 | 0 / 103 |
Outcome results
Primary
Total Number of Plasma Used Over Admission
All units over admission
Time frame: Within the first 30 days after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Total Number of Plasma Used Over Admission | 2.7 plasma units | Standard Deviation 4.6 |
| Patients Given PR Cryo | Total Number of Plasma Used Over Admission | 3.4 plasma units | Standard Deviation 6 |
Primary
Total Number of Platelets Used Over Admission
Plts used over admission
Time frame: Within the first 30 days after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Total Number of Platelets Used Over Admission | 2.1 platelet units | Standard Deviation 3.1 |
| Patients Given PR Cryo | Total Number of Platelets Used Over Admission | 2.1 platelet units | Standard Deviation 2 |
Primary
Total Number of RBCs Used Over Admission
RBCs used over admission
Time frame: Within the first 30 days after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Total Number of RBCs Used Over Admission | 5.8 RBC Units | Standard Deviation 6.5 |
| Patients Given PR Cryo | Total Number of RBCs Used Over Admission | 6.7 RBC Units | Standard Deviation 7.2 |
Secondary
Cumulative Volume in Drains After Surgery (e.g., Chest Tube for CV Surgery) at the Time of Removal
The cumulative volume in drains after surgery (e.g., chest tube for CV surgery) at the time of drain removal
Time frame: Up to approximately 3 days
Population: This data were not available for collection in the electronic health record as intended by the investigators, as the data were not clinically documented. Therefore, the cumulative volume in drains after surgery could not be reported as intended in the study protocol.
Secondary
Fibrinogen Level
Fibrinogen level most proximal to the end of surgery
Time frame: Most proximal to end of procedure
Population: Fibrinogen was not ordered by provider for every participant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Fibrinogen Level | 197 mg/dL | Standard Deviation 52 |
| Patients Given PR Cryo | Fibrinogen Level | 201 mg/dL | Standard Deviation 38 |
Secondary
Highest Fibrinogen Level Within 24 Hours
Time frame: Within 24 hours after surgery
Population: Some data were not collected for this measure because anesthesiologists did not always order this test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Highest Fibrinogen Level Within 24 Hours | 210 mg/dL | Standard Deviation 53 |
| Patients Given PR Cryo | Highest Fibrinogen Level Within 24 Hours | 212 mg/dL | Standard Deviation 46 |
Secondary
Length of Stay in Hospital
Overall length of stay in hospital
Time frame: During hospitalization, approximately 5 days to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Length of Stay in Hospital | 12.0 days | Standard Deviation 9.4 |
| Patients Given PR Cryo | Length of Stay in Hospital | 10.9 days | Standard Deviation 10.1 |
Secondary
Length of Stay in ICU
Participant length of stay in ICU setting
Time frame: During hospitalization, approximately 5 days to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Length of Stay in ICU | 8.1 days | Standard Deviation 11.8 |
| Patients Given PR Cryo | Length of Stay in ICU | 6.9 days | Standard Deviation 8.6 |
Secondary
Length of Stay in OR
Operating room length of stay
Time frame: Duration of time in operating room
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Length of Stay in OR | 522 minutes | Standard Deviation 124 |
| Patients Given PR Cryo | Length of Stay in OR | 534 minutes | Standard Deviation 118 |
Secondary
Lowest Fibrinogen Level Within 24 Hours
Time frame: Within 24 hours after surgery
Population: Some data were not collected for this measure because anesthesiologists did not always order this test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Lowest Fibrinogen Level Within 24 Hours | 194.5 mg/dL | Standard Deviation 51 |
| Patients Given PR Cryo | Lowest Fibrinogen Level Within 24 Hours | 199.89 mg/dL | Standard Deviation 44.3 |
Secondary
Maximum Clot Firmness (MCF)
The maximum strength of a clot as determined by ROTEM testing.
Time frame: Variable, but it is generally available within 1 hour of the start of ROTEM testing.
Population: Data for MCF were not collected since clinical decisions are not made based on this value as the measure assumed. As such, there are no data to report. Clinical decisions were made based on A10 (the clot amplitude measured 10 minutes after clot formation start), not the maximum clot firmness (MCF). As A10 was not a pre-specified measure for this protocol, there are no data to report. Data will never be collected for this Outcome Measure.
Secondary
Need for Ventilator
Time frame: During hospitalization, approximately 5 days to 30 days
Population: Not all values available in the electronic health record.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Given Traditional Cryo | Need for Ventilator | 99 Participants |
| Patients Given PR Cryo | Need for Ventilator | 96 Participants |
Secondary
Number of Cryo Units Used Perioperatively
All products within 3 days
Time frame: 3 days post procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Number of Cryo Units Used Perioperatively | 2.3 cryo units | Standard Deviation 1.7 |
| Patients Given PR Cryo | Number of Cryo Units Used Perioperatively | 2.3 cryo units | Standard Deviation 1.6 |
Secondary
Number of Cryo Units Wasted by Blood Bank
This captures the Cryoprecipitate units discarded.
Time frame: Daily, up to approximately 24 months
Population: The blood bank, which is required to follow its standard operating procedures, was not able to document wastage in a way which allowed the investigators to accurately attribute wastage to a specific arm of the study. Therefore, wastage could not be accurately calculated as intended in the study protocol.
Secondary
Number of Participants That Experienced an Adverse Event of Fever
All participants that experience fevers that occur during the time frame
Time frame: Within 5 days of surgery start time
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Given Traditional Cryo | Number of Participants That Experienced an Adverse Event of Fever | 16 Participants |
| Patients Given PR Cryo | Number of Participants That Experienced an Adverse Event of Fever | 14 Participants |
Secondary
Number of Participants That Experienced an Adverse Event of Infection
All participants that experience infections that occur during the time frame
Time frame: Within 5 days of surgery start time
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Given Traditional Cryo | Number of Participants That Experienced an Adverse Event of Infection | 6 Participants |
| Patients Given PR Cryo | Number of Participants That Experienced an Adverse Event of Infection | 4 Participants |
Secondary
Number of Participants That Experienced an Adverse Event of Transfusion Reaction.
All participants that experience transfusion reactions that occur during the time frame
Time frame: Within 5 days of surgery start time
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Given Traditional Cryo | Number of Participants That Experienced an Adverse Event of Transfusion Reaction. | 0 Participants |
| Patients Given PR Cryo | Number of Participants That Experienced an Adverse Event of Transfusion Reaction. | 0 Participants |
Secondary
Number of Plasma Used Perioperatively
Time frame: 3 days post procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Number of Plasma Used Perioperatively | 2.6 plasma units | Standard Deviation 4.6 |
| Patients Given PR Cryo | Number of Plasma Used Perioperatively | 3.4 plasma units | Standard Deviation 6.01 |
Secondary
Number of Platelets Used Perioperatively
Number of platelet units transfused during perioperative period
Time frame: 3 days post procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Number of Platelets Used Perioperatively | 1.8 platelet units | Standard Deviation 1.7 |
| Patients Given PR Cryo | Number of Platelets Used Perioperatively | 2.0 platelet units | Standard Deviation 1.8 |
Secondary
Number of RBCs Used Perioperatively
Number of RBC units transfused during perioperative period
Time frame: 3 days post procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Number of RBCs Used Perioperatively | 4.6 RBC units | Standard Deviation 5.6 |
| Patients Given PR Cryo | Number of RBCs Used Perioperatively | 5.9 RBC units | Standard Deviation 6.6 |
Secondary
Overall Cost of Cryo vs PR Cryo, When Factoring Wastage
Cost of traditional cryoprecipitate compared to PR Cryoprecipitate.
Time frame: Daily, approximately 24 months
Population: Not available due to unavailable confidential contractual information that would be needed to calculate cost. The contract between the blood suppliers and hospital is confidential, and therefore the investigators were not able to report on cost-related factors as intended in the study protocol. Data will never be collected for this Outcome Measure.
Secondary
Post Transfusion FIBTEM Amplitude at 10 Min After Start of Clot Formation
FIBTEM after transfusion, if anesthesiologist orders it. FIBTEM is a point of care laboratory test measuring fibrinogen contribution to a clot. It is part of ROTEM testing and helps providers determine if patients need fibrinogen supplementation during surgical bleeding.
Time frame: Variable, but it is generally available within 15 minutes of the start of ROTEM testing.
Population: Data were not available nor collected for this measure because anesthesiologists do not routinely order this for the investigators to have been able to collect it.
Secondary
Pre-transfusion Fibrinogen Level
The fibrinogen measurement before cryoprecipitate is transfused.
Time frame: During surgery, within 3 hours of specimen receipt by laboratory.
Population: Some data were not collected for this measure because anesthesiologists did not routinely order this test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Pre-transfusion Fibrinogen Level | 145 mg/dL | Standard Deviation 68 |
| Patients Given PR Cryo | Pre-transfusion Fibrinogen Level | 191 mg/dL | Standard Deviation 33 |
Secondary
Pre Transfusion FIBTEM Amplitude 10 Min After Start of Clot Formation
FIBTEM before transfusion, if anesthesiologist orders it. FIBTEM is a point of care laboratory test measuring fibrinogen contribution to a clot. It is part of ROTEM testing and helps providers determine if patients need fibrinogen supplementation during surgical bleeding.
Time frame: Variable, but it is generally available within 15 minutes of the start of ROTEM testing.
Population: Data for all participants was not available because pre-transfusion FIBTEMs were not clinically ordered for all participants by the treating anesthesiologists. Only participants with pre-transfusion FIBTEMs available were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Pre Transfusion FIBTEM Amplitude 10 Min After Start of Clot Formation | 9.6 mm | Standard Deviation 6.8 |
| Patients Given PR Cryo | Pre Transfusion FIBTEM Amplitude 10 Min After Start of Clot Formation | 8.3 mm | Standard Deviation 4.2 |
Secondary
Time From Cryo Order to Start of Transfusion
Time to cryo order time to start of cryo transfusion
Time frame: procedure (Time from cryo order to start of transfusion)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Time From Cryo Order to Start of Transfusion | 128.3 minutes | Standard Deviation 200.7 |
| Patients Given PR Cryo | Time From Cryo Order to Start of Transfusion | 88.5 minutes | Standard Deviation 99.8 |
Secondary
Time From End of Bypass Pump for CV Surgery
Time frame: Until end of surgery
Population: Only for cardiac surgery patients. Liver transplant patients are not on bypass.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients Given Traditional Cryo | Time From End of Bypass Pump for CV Surgery | 2.75 hours |
| Patients Given PR Cryo | Time From End of Bypass Pump for CV Surgery | 2.73 hours |
Secondary
Time From Operating Room (OR) Start Time to Start of Cryo Transfusion
Time frame: procedure (Time from OR start time to start of cryo transfusion)
Population: Only the cardiac population was included for this analysis. The data was not available for liver transplant patients, so liver transplant patients were excluded from the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients Given Traditional Cryo | Time From Operating Room (OR) Start Time to Start of Cryo Transfusion | 366 minutes |
| Patients Given PR Cryo | Time From Operating Room (OR) Start Time to Start of Cryo Transfusion | 367 minutes |
Secondary
Time on Ventilator
If participant was on ventilator, amount of time spent on ventilator
Time frame: During hospitalization, approximately 5 days to 30 days
Population: Not all values available in the electronic health record.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Time on Ventilator | 2.4 days | Standard Deviation 4.9 |
| Patients Given PR Cryo | Time on Ventilator | 2.6 days | Standard Deviation 6.3 |
Secondary
Volume in Drains (Chest Tube for CV Surgery)
Time frame: At 24 hours after surgery
Population: Only the cardiac population was included for this analysis. The clinical parameter is not applicable to liver transplant patients, so liver transplant patients were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Given Traditional Cryo | Volume in Drains (Chest Tube for CV Surgery) | 897 mLs | Standard Deviation 810 |
| Patients Given PR Cryo | Volume in Drains (Chest Tube for CV Surgery) | 749 mLs | Standard Deviation 496 |