11
Transfusion, Hemostasis, and Coagulation

Lindsey Karavites, MD and Kazuhide Matsushima, MD

Division of Acute Care Surgery, University of Southern California, LAC+USC Medical Center, Los Angeles, CA, USA

57‐year‐old man was brought into the trauma bay after a witnessed fall from his third‐floor apartment onto the sidewalk. He is lethargic but arousable with blood pressure 80/40 mmHg and heart rate 135 beats/min. He is noted to have a scalp laceration and bilateral lower extremity deformities with significant blood loss noted at the scene. What is one advantage of selecting low titer whole blood for his resuscitation over component therapy?
1. 24‐hour survival benefit in the severely injured.
2. Decreased 24‐hour total transfusion requirement.
3. Cost effectiveness of prolonged time to product expiration.
4. Decreased transfusion reactions due to standardized safe antibody titer levels.
5. No risk of post‐transfusion hemolysis.
Increasing retrospective data from the military medical community for use of whole blood in resuscitation have led to similar efforts in civilian trauma patients. Low titer whole blood may have institution specific definitions; however, it is generally considered unseparated blood collected from a donor with low titers of Ig M and/or IgG anti‐A and anti‐B. Implementation of cold‐stored low‐titer anti‐A and anti‐B group O whole blood (LTOWB) transfusion strategies are in place in civilian trauma centers but further prospective data are necessary to examine discrete comparisons of whole blood without simultaneous use of components, verification of appropriate safety, and determination of cost–benefit analyses. To date, the only randomized controlled pilot trial comparing the use of whole blood to component therapy demonstrated that those receiving whole blood required fewer blood products at 24 hours with no difference in mortality. Another recent study comparing between LTOWB vs. component therapy showed that the use of LTOWB was significantly associated with a reduction in post‐emergency department blood transfusion and improved 30‐day survival. Additional advantages include ease of use with single bag product storage, reduced human error with administration, decreased transfusion reactions, although no standard safe antibody titer levels have been established, as well as avoidance of excessive volume, additives and anticoagulants.

Answer: B

Cotton, B.A, Podbielski, J., Camp, E., et al. (2013) Early Whole Blood Investigators: A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions. Ann Surg ,258 (4), 527–532.

Williams, J., Merutka, D., Bai, Y., et al. (2019) Safety profile and impact of low‐titer group O whole blood for emergency use in trauma. J Trauma Acute Care Surg , 88 (1), 87–93.
When massive transfusion is indicated, the American College of Surgeons Trauma Quality Improvement Program currently recommends one unit of apheresis platelets to be given following the administration of how many units of packed red blood cells (PRBCs) in the setting of balanced component 1:1–1:2 (Plasma/PRBCs) resuscitation?
1. 1
2. 2
3. 4
4. 6
5. 8
Evidence currently supports a balanced transfusion strategy that targets a plasma:PRBC ratio approaching 1:1. There is no apparent increase in respiratory complications in the 1:1 group, despite prior retrospective associations between increased plasma transfusion and acute respiratory distress syndrome (ARDS). The latest massive transfusion guidelines from American College of Surgeons Trauma Quality Improvement Program (ACS‐TQIP) recommends a 1:1–1:2 (plasma/RBCs) transfusion ratio with one unit of apheresis platelets given for every 6 units of RBCs transfused.

Answer: D

Cryer, H.G., Nathens, A.B., Bulger, E.M. (2014), American College of Surgeons Trauma Quality Improvement Program Massive Transfusion in Trauma Guidelines. facs.org/‐/media/files/quality‐programs/trauma/tqip/transfusion_guildelines.ashx.
A 75‐year‐old woman with cirrhosis arrives in the trauma bay after being hit by a car while crossing the street. Her initial work up revealed two left‐sided rib fractures and a grade 3 splenic laceration without evidence active extravasation. She is hemodynamically stable and her initial laboratory tests reveal a hemoglobin of 9.5 g/dL, hematocrit of 29%, platelet count of 125 000/mm ³, and international normalized ratio of 3.1. While being managed nonoperatively in the intensive care unit, she becomes hypotensive. 1 unit of packed red blood cells (PRBCs) and 1 unit of fresh frozen plasma (FFP) are transfused. Shortly after the transfusions are completed, she develops tachycardia and dyspnea requiring supplement oxygen. Which of the following is the most diagnostic of transfusion‐associated acute lung injury (TRALI) as the source of her new oxygen requirement?
1. Bilateral infiltrate on chest radiography
2. Heart Rate: 135
3. PaO2/FiO2: 300
4. Systolic Blood Pressure: 90
5. Temperature 37.9
The differential diagnosis of respiratory distress is broad in the setting of polytrauma, especially in those with known rib fractures and those requiring transfusions. Transfusion‐related acute lung injury (TRALI) is defined by the documentation of acute hypoxemia with PaO₂/FIO₂ ratio (P/F) of less than 300 mm Hg, bilateral infiltrates on chest radiograph (in the absence of left atrial hypertension), and the absence of acute injury before transfusion. In addition, onset of transfusion‐related acute lung injury is required to have occurred within 6 hours of the last transfusion. Transfusion‐associated circulatory overload (TACO) was defined as acute onset or worsening respiratory distress during or up to 12 hours after transfusion, plus evidence of acute or worsening pulmonary edema and volume overload. Signs/symptoms include fever, dyspnea, and hypotension. The treatment of TRALI is respiratory support, including measures to avoid worsening of lung injury. Transfusion of all types of blood products can cause TRALI. Pathogenesis is related to donor antibodies in the transfused blood and may also be related to modifications of stored blood. Measures to prevent TRALI include a restrictive transfusion policy, as well as blood bank measures such as predominant use of plasma from male donors.

Answer: A

Semple, J.W., Rebetz, J., and Kapur, R. (2019) Transfusion‐associated circulatory overload and transfusion‐ related acute lung injury. Blood , 133 (17), 1840–1853.
A 45‐year‐old man requires helicopter evacuation following a farming accident in which he was pinned under a peanut trailer experiencing crush injuries to his lower extremities. Transport time to nearest facility is approximately 35 minutes. His heart rate is 145 per minute, systolic blood pressure is 80 mmHg, and he appears confused. Prehospital providers obtained IV access and administered 1 L of crystalloid in the field. Repeat vitals en route demonstrate a heart rate of 125 and systolic blood pressure of 90. What additional resuscitation, if any, would offer the greatest survival benefit while traveling to the nearest hospital?
1. Additional 1 L of crystalloid
2. 1 unit packed red blood cell (PRBC)
3. 1 unit fresh frozen plasma (FFP)
4. 1 unit PRBC + 1 unit FFP
5. No additional resuscitation required
More than one‐third of preventable deaths due to hemorrhage occur in the field. Evidence gathered from the Prehospital Air Medical Plasma Trial and its secondary analysis, patients with signs of shock should receive prehospital blood products whenever available. Crystalloid alone appears to be inferior to blood products and has a dose–response increase in mortality in this setting. If both PRBC and plasma are available, patients should receive both, as reduction in mortality has been demonstrated. If only 1 product can be added, plasma should be favored, as there is level 1 evidence to support it. The additive benefit of PRBC and plasma also suggests that there may be a benefit to the use of whole blood in the prehospital setting. Finding a balance between organ perfusion and hemostasis is critical when resuscitating a severely injured trauma patient. Answer E would allow for permissive hypotension which would not be advisable for this patient given that his mechanism may have also resulted in a traumatic brain and/or spinal cord injury which have yet to be ruled out. Permissive hypotension is not recommended in the setting of central nervous system injury.

Answer: D

Guette, F.X., Sperry, J.L., Peitzman, A.B., et al. (2019) Prehospital blood product and crystalloid resuscitation in the severely injured patient: A secondary analysis of the prehospital air medical plasma trial. Ann Surg. doi: 10.1097/SLA.0000000000003324.
Which of the following patients would receive the most benefit from administration of tranexamic acid (TXA)?
1. 25‐year‐old male with massive transfusion protocol activated approximately 9 hours post fall from height.
2. 80‐year‐old female with a nondisplaced pelvic fracture and stable vital signs on Warfarin.
3. 35‐year‐old male with massive transfusion protocol activated for hemodynamic instability 1‐hour after sustaining gunshot wounds to the chest.
4. 8‐year‐old male receiving 1:1 component resuscitation immediately following motor vehicle collision.
5. 65‐year‐old female with a history of stroke receiving 1:1 component resuscitation after being struck by a car.
TXA is a synthetic derivative of the amino acid lysine that inhibits fibrinolysis by blocking the lysine binding site on plasminogen. In patients undergoing elective procedures, TXA has been shown to reduce the need for blood transfusion. The CRASH‐2 trial, a randomized, placebo‐controlled trial of TXA in trauma patients with significant bleeding, demonstrated a significant reduction in all‐cause mortality, as well as deaths due to hemorrhage, in the patients who received TXA within 3 hours. Trial results have been met with both enthusiasm and controversy regarding the application antifibrinolytics for patients with traumatic bleeding. As a consequence, several high‐quality randomized controlled trials are currently underway to help further elucidate the utility of TXA and other antifibrinolytics in traumatic injury, as well as other conditions with severe bleeding. Based on current evidence, TXA is most beneficial in the setting of trauma when empirically used in massive transfusion situations in those patients presenting within 3 hours of injury. Further trials are needed to refine and optimize TXA dosing regimens due to concern for seizures with higher dosing. There was no increase in vascular occlusive events in patients receiving TXA in the CRASH‐2 trial. However, history of or risk factors predisposing to thromboembolic events is considered a relative contraindication, as is the use of TXA in patients with subarachnoid hemorrhages owing to the association with increased cerebral ischemia. Although TXA has been studied extensively in the adult trauma patient, less evidence exists for children, and its use in the pediatric trauma population is not as widespread.

Answer: C

Ramirez, R.J., Spinella, P.C., and Bochicchio, G.V. (2017) Tranexamic acid update in trauma. Crit Care Clin , 33 (1), 85–99.

The CRASH‐2 Collaborators (2010) Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage (CRASH‐2): a randomized, placebo‐controlled trial. Lancet , 376 (9734), 23–32.

A 28‐year‐old man is taken emergently to the operating room for abdominal exploration after sustaining a gunshot wound to the right upper quadrant. On arrival, he was found to be in hemorrhagic shock and massive transfusion protocol was initiated. Intraoperatively, the bleeding is difficult to control, and diffuse oozing is noted as the case progresses. Rapid thrombelastography (TEG) is performed and reveals a prolonged R value, K value is slightly prolonged, α‐angle is reduced, a normal maximum amplitude. What component replacement would aid in resuscitative efforts?

Cryoprecipitate
Platelets
Tranexamic acid
Fresh frozen plasma (FFP)
Platelets and cryoprecipitate

Thrombelastography (TEG) has been used as a guide to blood product replacement for acutely bleeding patients and has been studied as an alternative to ratio‐based mass transfusion protocols. TEG offers the advantage of real‐time point of care testing of coagulation function in whole blood. A rapid TEG differs from conventional TEG because tissue factor is added to the whole blood specimen, resulting in accelerated reaction and subsequent analysis. See graphic representation and interpretation below (Figure 11.1 and Table 11.1). The R value, which is recorded as activated clotting time (ACT) in the rapid TEG specimen, reflects clotting factor activation and the time to onset of clot formation. Normal R time ranges from 5–10 minutes. A deficiency of clotting factors will result in a prolonged ACT, which can be treated by FFP transfusion. The K value is the interval from the beginning of clot formation to a fixed level of clot firmness measured at a standard 20 mm amplitude. It reflects the activity of thrombin which cleaves fibrinogen. Normal K time is 1–3 minutes. Similarly, the α angle reflects the rate of clot formation and is another measure of fibrinogen activity. Normal α angle is 53–72°. A prolonged K value and a decreased α angle represent a fibrinogen deficit which can be treated by transfusion of FFP or cryoprecipitate. The maximum amplitude (MA) measures the final clot strength, reflecting the end result of platelet–fibrin interaction. Normal MA is 50–70 mm. If the MA is decreased after transfusion of FFP, then platelet transfusion should be considered. The patient described has a prolonged ACT as well as prolonged K time and decreased α angle. This is best treated by FFP transfusion to replace both the clotting factor deficiency and fibrinogen deficiency. If the K time remains prolonged after correction of the ACT, then cryoprecipitate can be given.