Massive transfusion: a question of timing, detail, a golden ratio

“Our data underscore the importance of expeditious product availability and emphasize that massive transfusion is a complex process in which product ratio and time to transfusion represent only the beginning of understanding,” the study’s authors concluded (Riskin DJ, et al. J Am Coll Surg. 2009;209[2]:198–205).

Beth H. Shaz, MD, chief medical officer of the New York Blood Center, a member of the AABB’s board of directors, and former medical director of the transfusion service for Atlanta’s Grady Memorial Hospital, makes the point well.

“The massive transfusion protocol is about more than just the blood,” she says. “The logistics of it are not simple. . . . You really need to spell out each person’s role, and what’s expected for each step.”

She also voiced a note of hope that treatment of life-threatening bleeds will see a superior fix that bests early delivery of plasma.

“We’re getting a better understanding of early trauma induced coagulopathy, or acute trauma coagulopathy. We’re finally learning about what that is. Right now, we just have plasma to address it. As we learn more, maybe there’s something better, right?” Dr. Shaz says. “[The MTP] is the next rung on the ladder, but we’re not done.”

One potential improvement in the treatment of life-threatening bleeding is greater use of antifibrinolytics such as tranexamic acid. The CRASH-2 trial found that early use of the medication helped cut the mortality rate among trauma patients by nine percent, and the risk of bleeding death by 15 percent compared with placebo (CRASH-2 trial collaborators. Lancet. 2010;376[9734]:23–32). The World Maternal Antifibrinolytic Trial, WOMAN for short, has so far randomized nearly 15,000 patients as part of its study of whether tranexamic acid could help reduce deaths in severe postpartum hemorrhage. The World Health Organization already recommends the medication in treating such bleeds.

Trying to refine the MTP process at participating centers was one of the key charges for Dr. Holcomb and the team conducting the PROPPR trial. An important goal of the study was to eliminate substantial differences in blood product delivery as a factor that could skew the intended comparison between component ratios. After much work, the participating medical centers were able to reduce the median delivery time of that first round of products to eight minutes (Baraniuk S, et al. Injury. 2014;45[9]:1287–1295).

How can other hospitals achieve that kind of turnaround time when the MTP is initiated?

“What they should do is what we did for this study,” Dr. Holcomb says. “There’s no reason why not to do it for routine clinical practice. You get your ER doctors, blood bankers, and nurses all in the room and figure out how to make the delivery of blood products faster. You put the products in the ED. You put those blood products in prehospital, so you don’t have to rely on crystalloid. You hone every step of the practice. These patients need a different process than patients who get one unit on the floor who are hemodynamically stable.”

“We had 12 centers and 680 patients,” Dr. Holcomb says of the PROPPR trial. “We had literally hundreds and hundreds of providers who were able to do this. I think that speaks of the ability of any center to do this if they want to.”

To get the sites participating in PROPPR up to speed, Dr. Holcomb’s team organized clinical site visits that involved unannounced MTP simulations.

“We’d call or email or use whatever the system was in the hospital to say we have a massive transfusion case, that a guy’s rapidly bleeding, and we need six [units of plasma], six [units of RBC], and one [unit of platelets, typically a pool of six units]. And then we timed how long it took to get the blood products from that call to the bedside. We had an observer on the way who observed, independent of the actions being taken. If this guy had to stop and fill out 27 forms, well that’s a problem. That might be OK if the patient needs one unit of blood product and is hemodynamically stable, has a hemoglobin of six and you just want to go to seven.”

Improvement came from emphasizing the urgency to blood bank technologists and technicians, and “creating not a separate, but a streamlined process,” Dr. Holcomb says. “I would emphasize that each place is very, very different. So I’m not sure there was a common denominator, but each site could get better by many minutes.”

Dr. Holcomb’s previous research, the Prospective, Observational, Multicenter, Major Trauma Transfusion Study (called PROMMT for short), found room for improvement in transfusion among the 10 level-one trauma centers studied. Among the massively bleeding adult trauma patients studied, 10 percent of those who survived for three hours—“the peak time of hemorrhagic death”—had not received any plasma by that point, while 28 percent had not yet received platelets. “Once bleeding patients have been identified, constant ratios are not infused and heterogeneous transfusion practice persists,” the study concluded (Holcomb JB, et al. JAMA Surg. 2013;148[2]:127–136).

Dr. Lockhart, now associate medical director of the transfusion service at the University of New Mexico Hospital, a level-one trauma center, says that simulations are a crucial part of the iterative process of making MTPs go more smoothly. This can especially be the case at smaller hospitals where massive transfusions—defined as patients needing or predicted to need 10 units or more of packed red blood cells during the course of 24 hours—are even rarer events.

“It’s part of developing and validating the protocol, before you go live, to put it through its paces from stem to stern,” she says. “Does the team recognize when there’s excessive hemorrhage? Does the team activate the protocol appropriately? Everyone should be notified . . . there should be a communications tree in place. Are the blood samples collected that need to be collected? Are they going where they need to go? Does the runner know where they need to go—is there a clear path from point A to point B?”

In another Duke MTP simulation done in the middle of the night, a runner found an unexpectedly locked door, Dr. Lockhart says.

“The runner had to do a big loop around to reach the blood bank. You’ve got to know that sort of thing beforehand. And do [the simulation] at all times, when you’re at the most skeletal of skeletal.”

In her CAP ’14 talk, Dr. Lockhart emphasized the it-could-happen-to-you nature of massive postpartum hemorrhage and advised hospitals of any size with an obstetrics ward to be prepared. She recalled one case at Duke where more than 200 blood products were used.

She noted CDC statistics listing postpartum hemorrhage as the cause of 11 percent of pregnancy-related deaths. About three percent of deliveries involved postpartum hemorrhage, while the overall PPH rate rose by 28 percent between 1995 and 2004, Dr. Lockhart said. Massive postpartum hemorrhage with coagulopathy is only seen in between 0.15 to 0.5 percent of births, she noted, but a routine delivery can quickly become a matter of maternal life and death.

At Duke, Dr. Lockhart took on the role as the on-call coordinator and consultant for the OB hemorrhage service. She spent “about 15 bucks” at Staples to develop toolkits to put on the labor-and-delivery crash carts as “one-stop shopping for hematologic management.” Blood tubes were tied together and came with prefilled lab-routing slips. The forms were color coordinated to the tube tops. Also included are emergency release forms, transfusion algorithms, and scripts for each person’s role.

When Dr. Lockhart was at Duke, the massive hemorrhage algorithm called for four units each of red blood cells and plasma and one unit of cryoprecipitate in round one, and six and six of RBC and plasma and one unit of platelets in round two. Rounds three, four, and five—if needed—would see six and six of RBC and plasma, and alternating one unit of cryo or platelets. Dr. Lockhart said delivery and transfusion of blood products should be done in parallel with a definitive clinical intervention such as use of uterotonic agents, tamponade, arterial embolization or ligation, or hysterectomy.

Dr. Lockhart noted that it is difficult to apply the findings from trauma-specific MTP to obstetrics, because trauma data are based on mostly male subjects whose coagulation physiology differs significantly from that of women giving birth. But research has shown that OB hemorrhage protocols can improve how quickly clinicians initiate an MTP, cut blood product use by 62 percent, and slash the rate of disseminated intravascular coagulation by 64 percent (Shields LE, et al. Am J Obstet Gynecol. 2011;205[4]:368.e1–e8).

In October 2006, the American College of Obstetricians and Gynecologists issued a practice bulletin on postpartum hemorrhage recommending the posting of management protocols in delivery rooms or operating room suites. In 2010, the California Maternal Quality Care Collaborative issued an obstetric hemorrhage toolkit—available at https://cmqcc.org/ob_hemorrhage—which is now in the process of being updated. Despite the imprimatur of ACOG and quality improvement organizations such as the Joint Commission, adoption of OB-specific MTPs appears far from universal.

A survey of 220 ob-gyns conducted in 2009 found that 58 percent practiced in hospitals that had no MTP to treat severe postpartum hemorrhage. There was a range in practice by birth volume. Nearly 60 percent of hospitals with more than 10,000 deliveries annually had an OB-specific MTP, compared with 32 percent of hospitals with fewer than 2,000 deliveries a year (Triche EW, et al. Open J Obstet Gynecol. 2014;4[6]:279–293). Another survey, conducted in 2012 among 60 directors of academic obstetric anesthesia units, found that 67 percent of their units had a PPH protocol (Kacmar RM, et al. Anesth Analg. 2014;119[4]:906–910).

ACOG’s New York chapter, District II, has undertaken an initiative to address the shortage of OB hemorrhage plans. Of the state’s 127 obstetric hospitals, 115 are participating. The statewide effort, known as the Safe Motherhood Initiative, is simultaneously targeting care improvements in severe hypertension and venous thromboembolism, two additional leading causes of maternal death. Checklists, algorithms, risk-assessment tables, and other materials are available at http://j.mp/acognypph. Hospital implementation visits began in September, says Donna Montalto, executive director of ACOG District II. Baseline data have been collected, and the organization is collecting 14 months of data on outcomes post-implementation.

“All the hospitals are required to create and invoke an MTP, and we provided them with a protocol template on what should be included. That’s a new phenomenon for very small hospitals. There’s usually a hospitalwide massive transfusion protocol, but not specifically for the OB unit,” Montalto says. “Hospitals need to know how to activate the MTP, notify the appropriate staff to release blood and blood products to the OB unit, and perform all the stat labs in a timely fashion. Any provider involved in a severe obstetric hemorrhage can make the decision about escalation and whether to activate an MTP. Again, it’s new for them.”

“It’s a culture change,” she adds. “It’s about embracing that protocol, and systematically looking at a staged checklist. Is everyone on the same page? Oftentimes, they’re not.”

Kevin B. O’Reilly is CAP TODAY senior editor.