Analyzing and modeling massive transfusion strategies and the role of fibrinogen-How much is the patient actually receiving?

BACKGROUND: Hemorrhage is a leading cause of preventable death in trauma, cardiac surgery, liver transplant, and childbirth. While emphasis on protocolization and ratio of blood product transfusion improves ability to treat hemorrhage rapidly, tools to facilitate understanding of the overall content of a specific transfusion strategy are lacking. Medical modeling can provide insights into where deficits in treatment could arise and key areas for clinical study. By using a transfusion model to gain insight into the aggregate content of massive transfusion protocols (MTPs), clinicians can optimize protocols and create opportunities for future studies of precision transfusion medicine in hemorrhage treatment. METHODS: The transfusion model describes the individual round and aggregate content provided by four rounds of MTP, illustrating that the total content of blood elements and coagulation factor changes over time, independent of the patient's condition. The configurable model calculates the aggregate hematocrit, platelet concentration, percent volume plasma, total grams and concentration of citrate, percent volume anticoagulant and additive solution, and concentration of clotting factors: fibrinogen, factor XIII, factor VIII, and von Willebrand factor, provided by the MTP strategy. RESULTS: Transfusion strategies based on a 1:1:1 or whole blood foundation provide between 13.7 and 17.2 L of blood products over four rounds. Content of strategies varies widely across all measurements based on base strategy and addition of concentrated sources of fibrinogen and other key clotting factors. DISCUSSION: Differences observed between modeled transfusion strategies provide key insights into potential opportunities to provide patients with precision transfusion strategy.

Massive Hemorrhage Protocol: A Practical Approach to the Bleeding Trauma Patient.

Damage-control resuscitation is the standard of care for the hemorrhaging trauma patient. This approach combines rapid hemostasis and early-ratio-based blood product administration. These patients often require initiation of a massive hemorrhage protocol to support the systematic and coordinated delivery of care during this critical phase of resuscitation. Emerging evidence supports that this includes more than blood product administration alone but rather a comprehensive suite of treatments. In this article, we review the existing evidence and provide a pragmatic framework, the 7 Ts of massive hemorrhage protocol, to guide the care of patients with life-threatening traumatic hemorrhage.

The role of cryoprecipitate in human and canine transfusion medicine.

OBJECTIVE: To evaluate the current role of cryoprecipitate in human and canine transfusion medicine. DATA SOURCES: Human and veterinary scientific reviews and original studies found using PubMed and CAB Abstract search engines were reviewed. HUMAN DATA SYNTHESIS: In the human critical care setting, cryoprecipitate is predominantly used for fibrinogen replenishment in bleeding patients with acute traumatic coagulopathy. Other coagulopathic patient cohorts for whom cryoprecipitate is recommended include those undergoing cardiovascular or obstetric procedures or patients bleeding from advanced liver disease. Preferential selection of cryoprecipitate versus fibrinogen concentrate (when available) is currently being investigated. Also a matter of ongoing debate is whether to administer this product as part of a fixed-dose massive hemorrhage protocol or to incorporate it into a goal-directed transfusion algorithm applied to the individual bleeding patient. VETERINARY DATA SYNTHESIS: Although there are sporadic reports of the use of cryoprecipitate in dogs with heritable coagulopathies, there are few to no data pertaining to its use in acquired hypofibrinogenemic states. Low fibrinogen in dogs (as in people) has been documented with acute traumatic coagulopathy, advanced liver disease, and disseminated intravascular coagulation. Bleeding secondary to these hypocoagulable states may be amenable to cryoprecipitate therapy. Indications for preferential selection of cryoprecipitate (versus fresh frozen plasma) remain to be determined. CONCLUSIONS: In the United States, cryoprecipitate remains the standard of care for fibrinogen replenishment in the bleeding human trauma patient. Its preferential selection for this purpose is the subject of several ongoing human clinical trials. Timely incorporation of cryoprecipitate into the transfusion protocol of the individual bleeding patient with hypofibrinogenemia may conserve blood products, mitigate adverse transfusion-related events, and improve patient outcomes. Cryoprecipitate is readily available, effective, and safe for use in dogs. The role of this blood product in clinical canine patients with acquired coagulopathy remains unknown.

Massive hemorrhage protocol survey: Marked variability and absent in one-third of hospitals in Ontario, Canada.

BACKGROUND: Massive hemorrhage protocols (MHP) are critical to standardized delivery of timely, safe, and resource-effective coordinated care for patients with life-threatening bleeding. METHODS: A standardized MHP survey was sent to all hospitals (n = 150) in Ontario with a transfusion service. This study aim was to determine the proportion of hospitals with an MHP and assess for variability. RESULTS: The overall survey completion rate was 133 of 150 hospitals (89%) (remaining 17 providing negative affirmation that they did not have an MHP). An MHP was in place at 97 of 150 (65%) hospitals (60% of small (<5000 red cell units/year) vs. 91% of medium/large). A total of 10 different names of protocols were reported, with "Massive Transfusion Protocol" (68%) predominating. Activation criteria were present in 82 of 97 (85%); commonly activated based on volume of blood loss (70%). Blood work was drawn at the discretion of the physician (37%) or at predefined intervals (31%; majority every 60 min). Common routine laboratory tests performed were CBC (87%) and INR (84%). Fibrinogen testing was available at 88 (66%) of 133 reporting hospitals and part of the standard testing at 73 of 97 (75%) hospitals with an MHP. Median targets of hemostatic resuscitations, stated in the protocol at 49% of hospitals with an MHP, were: platelets >50 × 109/L, INR < 1.8, fibrinogen >1.5 g/L, and hemoglobin >70 g/L. Protocol required patient temperature monitoring in 65% and specified a reversal plan for patients on anticoagulants in 59%. At 36% of sites all patients are initially managed with O RhD negative blood. Overall, 61% of sites issue blood in predefined packs (vs. on demand). Hemostatic agents in protocols included: tranexamic acid (70%), prothombin complex concentrate (14%), fibrinogen concentrate (13%), and recombinant FVIIa (4%). Quality metrics were tracked in 32% of hospitals. CONCLUSIONS: A third of hospitals lack formal MHPs, with the majority lacking in smaller hospitals. The survey results indicate that there is marked variability in all key aspects of the reported MHPs. This may be due to differences in hospital resources and personnel, lack of supporting evidence to dictate requirements, and differences in knowledge base of the individuals involved in protocol setting.

Massive hemorrhage protocol activation in obstetrics: a 5-year quality performance review.

BACKGROUND: A structured approach to hemorrhagic emergencies in obstetrics has gained popularity with the implementation of massive hemorrhage protocols. The trauma literature suggests that routine quality reviews should be in place to improve patient outcomes. The aim of this study was to develop quality indicators and assess compliance by the clinical team. METHODS: A multidisciplinary team set the institutional quality indicators for the massive hemorrhage protocol review. A retrospective review of all obstetrical massive hemorrhage protocol activation events from September 2010 to January 2015 was performed. All protocol events occurred before the creation of the quality indicators. Data were retrieved from patient records. RESULTS: There were 17 (0.09%) protocol activations for 19 790 deliveries during the study period. All 17 (100%) patients received at least one unit of red blood cells. Overactivation, defined as the transfusion of <2 units of red blood cells, occurred in two cases (12%). Common causes of non-compliance were: 24% (4/17) temperature monitoring, 18% (3/17) lactate measurement, 41% (7/17) arterial blood gas sampling, and 18% (3/17) hemoglobin maintenance within the target range of 55-95 g/L. Admission to intensive care and peripartum hysterectomy occurred in 12 and 5 cases (71% and 29%), respectively. CONCLUSIONS: Suboptimal compliance was found in multiple areas, which may be attributable to the low frequency of activation of our massive haemorrhage protocol in obstetrics. The quality targets identified in this report can act as a basis for other institutions developing quality indicators to evaluate performance.