Massive Transfusion Protocol in Traumatic Hemorrhage

 

Aurora Jin, MD (edited by Kent Li, MD)

Background

Hemorrhage is a major cause of death in patients who suffer traumatic injuries, even after they reach the hospital. Prolonged hemorrhagic shock and hypoperfusion have well-established effects on morbidity and mortality that are attributable to the lethal triad of hypothermia, coagulopathy, and acidosis. More recent literature suggests the addition of hypocalcemia as a fourth element, creating the lethal diamond. Massive transfusion protocols (MTP) exist to expedite blood replacement in patients who are identified to be suffering from or at risk of hemorrhagic shock. Early replacement of blood products (rather than crystalloid) helps both to restore intravascular volume and address the acute coagulopathy and decreased oxygen-carrying capacity resulting from traumatic blood loss. Classically, massive transfusion is defined as transfusion of at least 10 units of packed red blood cells (pRBC) within 24 hours of ED arrival or transfusion at a rate greater than 4-5 units of pRBCs per hour. MTP is highly institution-dependent, but the overall principle is that blood should be replaced at a 1:1:1 ratio of RBCs to platelets to fresh frozen plasma (FFP), as various studies have suggested improved outcomes with balanced transfusion compared to different ratios of blood products or pRBCs alone.

 

Fig. 1&2: The concepts of the lethal triad and lethal diamond

PCC can be considered in patients who present with massive hemorrhage and require emergency reversal of anticoagulation such as warfarin or direct thrombin inhibitors without a reversal agent. PCC is typically dosed by weight and INR, but a flat dose can be given in emergency scenarios. INR is checked 30 minutes after PCC administration, then periodically after (e.g. q4-6h during the first 24 hours). Subsequent dosing is typically not required, especially if vitamin K is concurrently given, but may be considered if repeat INR measurement shows inadequate correction. While PCC is not currently a part of most MTP protocols, preliminary research suggests it may have benefit when given empirically. Additional research suggests fixed dosing of PCC is likely cheaper and easier to administer compared to INR & weight-based dosing, although the efficacy of achieving hemostasis with fixed dosing is less clear.

Cryoprecipitate may be empirically given in addition to a standard MTP bundle in specific circumstances, including acquired hypofibrinogenemia (e.g. dilution from already receiving massive transfusion), DIC, and uremia if desmopressin is ineffective or alternate blood product replacements are unavailable. Additional dosing of cryoprecipitate is determined by the fibrinogen level, which can be monitored daily. Although less widely available and more expensive, fibrinogen concentrate may be a superior alternative to cryoprecipitate given decreased risk of transfusion reactions and volume overload.

Clinical Decision Making

The diagnosis of hemorrhagic shock can often be made clinically with the appropriate history, vital sign abnormalities, and physical exam findings that suggest peripheral vasoconstriction or ongoing hemorrhage. While delay in activation of MTP is associated with increased mortality, pulling the trigger to activate MTP can be tricky, and clinical decision-making guidelines exist to aid with this. 

The shock index (SI) is calculated using the ratio of the heart rate (HR) to the systolic blood pressure (SBP). It is easy to calculate and is thought to be a better predictor of severity of shock and mortality compared to HR and SBP alone. These vital signs may be normal in mild shock states or because of chronic blood pressure medication use. Some studies have suggested that in blood loss, SI increases before tachycardia or hypotension manifest, and an SI of >0.9 may predict need for MTP. Other literature suggests use of a modified shock index (MSI) over the traditional SI, which substitutes the MAP for the SBP.

The Assessment of Blood Consumption (ABC) score also uses SBP and HR but adds on a positive FAST exam and the presence of penetrating injury to predict the need for MTP activation, which is suggested by a score ≥2. The literature suggests that ABC score leads to quicker activation of MTP and has high accuracy in identifying patients who ultimately require MTP. However, some suggest that this, instead, leads to over activation of MTP. In addition, ABC score accuracy is dependent upon ultrasound proficiency.





Special Considerations

Hypocalcemia

Critically ill, hemorrhaging patients are often already hypocalcemic due to blood loss and disruption of calcium homeostasis and calcium-dependent pathways. Additionally, citrate is a component present in donor blood that acts as an anticoagulant. Thus, patients who receive MTP also receive large amounts of citrate to a degree that often surpasses its hepatic metabolism, which is already impaired in hemorrhagic shock. Buildup of citrate leads to calcium chelation and a decline in plasma free calcium, which leads to impaired clotting ability (due to calcium’s involvement in the clotting cascade) and cardiac contractility, further leading to hypoperfusion and worsening metabolic acidosis. Transfusion of at least 15 units of pRBCs is thought to increase risk of hypocalcemia. Thus, if MTP is activated, regular supplementation of calcium gluconate (3g) or calcium chloride (1g) with each MTP pack should be strongly considered with concurrent monitoring of the ionized calcium level to prevent overcorrection. 

Hypothermia

Hypothermia occurs with severe blood loss and hypoperfusion and further exacerbates clotting ability. Mortality from hypothermia in trauma patients is thought to be >40% and approaches 100% when the core body temperature is less than 32ºC. Blood is stored at 4°C, and rapid transfusion of 6 units of pRBCs straight from the cooler will lower the body temperature of a 70kg adult by 1°C. Furthermore, hypothermia can be exacerbated by evaporative heat loss both in the trauma bay and with an open body cavity in the operating room. Thus, a blood warmer should be used to warm blood products prior to transfusion when MTP is activated.

Tranexamic acid (TXA)

TXA is a reversible competitive inhibitor of plasmin, the activated form of plasminogen, and thus prevents breakdown of clots in the coagulation cascade. It is FDA-approved for use in obstetric hemorrhage, but may prove beneficial in other causes of massive hemorrhage as well. CRASH-2, a multi-center, randomized, placebo-controlled trial, suggested that in massive hemorrhage due to trauma, administration of TXA lowered all-cause mortality within 4 weeks of admission. TXA should be administered as a loading dose of 1g within 3 hours of injury, followed by a continuous infusion of 1g over the next 8 hours.

Hemophilia A & B

Life-threatening bleeding in patients with a history of hemophilia A or B must be treated immediately with targeted factor replacement. Transfusion of products containing the desired factors (e.g. FFP or PCC) will not sufficiently raise the factor level. Specific indications include CNS, deep muscular, intraabdominal, and ocular bleeding, severe mechanism of injury, bleeding affecting the airway, or bleeding not responsive to home therapy or requiring RBC transfusion. Initial dosing aims to bring the factor level, assumed to be at 0%, to 100%, followed by additional transfusion to maintain a >50% factor level.

  • Hemophilia A: initial bolus of factor VIII at 50 units/kg, followed by approximately q8-12h dosing (at half-life of specific product) of ½ the bolus dose OR a continuous infusion, typically 4 units/kg/hour.

  • Hemophilia B: initial bolus of factor IX at 100-120 units/kg, followed by approximately q18-24h dosing (at half-life of specific product) of ½ the bolus dose OR a continuous infusion, typically 6 units/kg/hour.

References

  1. Hess JR. Massive blood transfusion. UpToDate. Ed. Silvergleid AJ, Tirnauer JS. 9 Sep 2021. https://www.uptodate.com/contents/massive-blood-transfusion. Accessed 30 Sep 2021.

  2. Eggeman D et al. Massive transfusion. WikEM. Ed. Cunningham R. 10 Dec 2020. https://wikem.org/wiki/Massive_transfusion. Accessed 30 Sep 2021.

  3. Holcomb JB et al. Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 ratio and Mortality in Patients with Severe Trauma: The PROPPR Randomized Clinical Trial. JAMA. 2015 Feb 3;313(5):471-82.

  4. Bartikoski S. Whole Blood in Trauma: Ready for Primetime? emDocs. 18 Mar 2019. http://www.emdocs.net/whole-blood-in-trauma-ready-for-primetime/. Accessed 13 Nov 2021. 

  5. Colwell C. Initial management of moderate to severe hemorrhage in the adult trauma patient. UpToDate. Ed. Grayzel J. 01 Mar 2021. https://www.uptodate.com/contents/initial-management-of-moderate-to-severe-hemorrhage-in-the-adult-trauma-patient. Accessed 15 Nov 2021.

  6. Tobian A. Clinical use of cryoprecipitate. UpToDate. Ed. Tirnauer JS. 22 Jul 2021. https://www.uptodate.com/contents/clinical-use-of-cryoprecipitate. Accessed 15 Nov 2021.

  7. Abdoellakhan RA, Khorsand N, Ter Avest E, Lameijer H, Faber LM, Ypma PF, Nieuwenhuizen L, Veeger NJGM, Meijer K. Fixed Versus Variable Dosing of Prothrombin Complex Concentrate for Bleeding Complications of Vitamin K Antagonists-The PROPER3 Randomized Clinical Trial. Ann Emerg Med. 2021 Sep 14;S0196-0644(21)00516-3. 

  8. Koch E, Lovett S, Nghiem T, Riggs RA, Rech MA. Shock index in the emergency department: utility and limitations. Open Access Emerg Med. 2019 Aug 14;11:179-199.

  9. Lawrence C, Lafollette R. Massive Transfusion Triggers: Back to the ABCs (score). Taming the SRU. University of Cincinnati. 31 Dec 2018. https://www.tamingthesru.com/blog/diagnostics/massive-transfusion. Accessed 30 Sep 2021.

  10. Mohan S, Su M. Shock Index vs. ABC Score in Predicting Need for Massive Transfusion. Core EM. NYU Langone Health. 8 Feb 2018. https://coreem.net/journal-reviews/si-vs-abc-score-mtp/. Accessed 30 Sep 2021.

  11. Motameni AT, Hodge RA, McKinley WI, Georgel JM, Strollo BP, Benns MV, Miller KR, Harbrecht BG. The use of ABC score in activation of massive transfusion: The yin and the yang. J Trauma Acute Care Surg. 2018 Aug;85(2):298-302.

  12. Schroll R, Swift D, Tatum D, Couch S, Heaney JB, Llado-Farrulla M, Zucker S, Gill F, Brown G, Buffin N, Duchesne J. Accuracy of shock index versus ABC score to predict need for massive transfusion in trauma patients. Injury. 2018 Jan;49(1):15-19.

  13. Roberts I et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013 Mar;17(10):1-79.

  14. Ditzel Jr RM et al. A review of transfusion- and trauma-induced hypocalcemia: Is it time to change the lethal triad to the lethal diamond? J Trauma Acute Care Surg. 2020 Mar;88(3):434-439.

  15. Wray JP, Bridwell RE, Schauer SG, Shackelford SA, Bebarta VS, Wright FL, Bynum J, Long B. The diamond of death: Hypocalcemia in trauma and resuscitation. Am J Emerg Med. 2021 Mar;41:104-109.

  16. Vasudeva M, Mathew JK, Groombridge C, Tee JW, Johnny CS, Maini A, Fitzgerald MC. Hypocalcemia in trauma patients: A systematic review. J Trauma Acute Care Surg. 2021 Feb 1;90(2):396-402.

  17. Jurkovich JG, Greiser WB, Luterman A, Curreri PW. Hypothermia in trauma victims: an ominous predictor of survival. J Trauma. 01 Sep 1987;27(9):1019-1024.

  18. Hoots WK, Shapiro AD. Treatment of bleeding and perioperative management in hemophilia A and B. UpToDate. Ed. Tirnauer JS. 13 Oct 2021. https://www.uptodate.com/contents/treatment-of-bleeding-and-perioperative-management-in-hemophilia-a-and-b. Accessed 21 Nov 2021.

 
Booth EM