Life-threatening bleeding—what’s the right call?

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‘Forgetting about the fibrinogen. The fibrinogen gets low and the patient gets very coagulopathic. That’s probably the one [serious error] we see most often.’
—Tom DeLoughery, MD

Dr. DeLoughery described the next case as “the disaster everybody always fears.” A 30-year-old woman delivers a baby and has massive blood loss estimated to be 1,700 mL upon delivery of the placenta. The clinical team triggers its hemorrhagic protocol.

The coagulation test results are not yet available. Should you start with four units of red cells and four units of plasma; or four units of red cells, four units of plasma, plus some platelets; or four units of red cells and four units of plasma and cryoprecipitate? Or something different?

“Recommendations for postpartum hemorrhage are different than what we recommend for trauma,” he said. The answer is “four units of red cells, four units of plasma, and then the next round is four more units of red cells, four plasma, 10 units of cryoprecipitate, and one pheresis unit of platelets.” (The source of this recommendation is Collins P, et al. J Thromb Haemost. 2016;14[1]:205–210.)

The reason this recommendation is different “is that you tend not to see thrombocytopenia like you do in the trauma patient until you are really into the massive resuscitation,” Dr. DeLoughery explained. “We don’t use platelets as early and as aggressively in postpartum hemorrhage because thrombocytopenia is much less common—unless there’s already been a [placental] abruption or a massive transfusion. This is a situation where getting frequent labs will help you. If you see the platelets dive or discover the fibrinogen is low, then you do more targeted therapy.”

The patient’s serum fibrinogen result is 150 mg/dL. Dr. DeLoughery asked the audience if they would recommend cryoprecipitate. “[Fibrinogen] levels rise in normal pregnancy and lower levels tend to be more of a predictor for postpartum hemorrhage.” So it’s been decided that for a postpartum hemorrhage, a goal of 200 mg/dL may be more appropriate than the usual goal of 150 mg/dL, he said.

Evelyn Lockhart, MD, medical director, University of New Mexico (UNM) Hospital Transfusion Service, who was a speaker in a separate CAP16 session on massive transfusion protocols, tells CAP TODAY that in prospective observational studies conducted in obstetric hemorrhage, the platelet count doesn’t predict severe postpartum hemorrhage. Nor does “the clotting factor activity as reflected in the prothrombin time or partial thromboplastin time. Only fibrinogen levels have been observed to predict severe postpartum hemorrhage,” she says, adding that in her personal experience, “it’s surprising how quickly the fibrinogen can drop in these women.”

The Royal College of Obstetricians and Gynaecologists’ 2015 guidelines recommend maintaining fibrinogen at 200 mg/dL or more in a bleeding obstetric patient, she says. The International Society on Thrombosis and Haemostasis suggests maintaining fibrinogen above 200. “We don’t have good randomized data to support this at this time,” Dr. Lockhart says. Data are due out soon from a group in the United Kingdom but it’s a smaller study, says Dr. Lockhart, who is also section director of clinical pathology and an associate professor of pathology and obstetrics/gynecology at UNM. She notes there are still many questions in obstetrics about how much to raise the patient’s fibrinogen level so that it exceeds what you think will reduce the risk of bleeding or help to treat bleeding.

Is it necessary to check the fibrinogen level before administering cryoprecipitate in postpartum hemorrhage? “If they are doing a C-section on a woman and she quickly loses three liters of blood, I’m giving her empiric cryoprecipitate,” Dr. Lockhart says. “As much as possible, you try to have things driven by laboratory data, but how fulminant and violent these hemorrhages can be precludes waiting the 20 or 30 minutes it takes to get the test results back. So sometimes you do have to make empiric transfusion decisions.”

‘If they are doing a C-section on a woman and she quickly loses three liters of blood, I’m giving her empiric cryoprecipitate.’
—Evelyn Lockhart, MD

In fact, she says, UNM has a special obstetric hemorrhage protocol that diverges from its trauma massive transfusion protocol in that it calls for preparing cryoprecipitate for each round of blood products. “The lab testing at UNM is very fast—we can get fibrinogen results in 10 minutes,” which she says is about the length of time it takes them to thaw one pool of cryoprecipitate. “It is a rare circumstance when we don’t have lab data to guide cryo transfusion.”

The antifibrinolytic agent tranex­amic acid, or TXA, could also help. “TXA,” Dr. Lockhart says, “is kind of related to fibrinogen in some ways in that tranexamic acid stabilizes a fibrin clot and reduces enzymatic breakdown of that clot by plasmin.” She notes that the results of the WOMAN trial, which enrolled 20,000 subjects with postpartum hemorrhage to examine the efficacy of TXA in lowering maternal mortality, were published April 26, 2017 in Lancet. The authors wrote, “Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for post-partum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.”

In his presentation, Dr. DeLoughery said there’s increasing evidence that tranexamic acid may prevent blood loss in C-sections and postpartum bleeding. “The CRASH-2 trial showed that the early use of TXA both reduced bleeding and mortality in trauma,” he said.

What about recombinant VIIa? “This used to be the rage but now we have seen decreasing use in massive transfusion of recombinant VIIa due to both negative trial data and definite increasing risk of thrombosis.” Dr. DeLoughery said there is an open label study on postpartum hemorrhage that showed giving 60–90 mg/kg decreased the need for procedures, although not blood loss or blood product use.

An audience member asked the speakers what they would recommend as a massive transfusion protocol for a rural hospital that has an obstetrics service and a busy emergency department in which trauma patients are seen. Their main purpose, Dr. Nester said, is to stabilize the OB patient and trauma patient and air-flight them to another facility. The hospital is three to four hours from an urban center and a blood center so it doesn’t stock platelets but does have packed red blood cells and fresh frozen plasma.

Dr. Nester noted there is an article in the literature about development of a massive transfusion protocol at a Veterans Affairs hospital that may or may not have platelets on hand when a bleeding emergency occurs (Gehrie EA, et al. Mil Med. 2014;179[10]:1099–1105). “That institution chose to have four red cells and four plasma units as their pack for the initial cycle, with platelets and cryoprecipitate typically issued in the second cycle. The number of patients is small, but overall the authors feel that the patient outcome supports this approach. So perhaps until you can transfer, that may be what you want to be doing. An OB hemorrhage is more complicated because about 20 percent of patients can have florid DIC.” She recommended giving the hemorrhaging OB patient a pool of cryoprecipitate before transfer.

Dr. Nester asked Dr. Lockhart, who was in the audience, if she recommended fibrinogen concentrate for rural hospitals, because of easier storage conditions and potentially faster preparation time. Dr. Lockhart said it depends on whether they can afford one vial of it. “The thing is, if they are so resource strapped that they cannot have cryoprecipitate, they probably aren’t going to have fibrinogen testing. So it would be entirely empiric. It’s a difficult thing to say.” Dr. Lockhart said tranexamic acid is an excellent product for these hospitals to have on hand.

Rural hospitals have several strategies for stocking expensive products. One is for several hospitals to group together and have one depot for the product so it is available to all in the group. Another is to obtain the products on consignment, where the drug is paid for only if it is used.

When asked by CAP TODAY what he sees as some of the most serious errors in managing massive hemorrhages, Dr. DeLoughery said “forgetting about the fibrinogen. So the fibrinogen gets low and the patient gets very coagulopathic. That’s probably the one we see most often.”

Dr. Nester noted that if there is insufficient fibrinogen in the patient’s system, the PTT and PT will be “eternally prolonged,” and the patient will be unable to clot. She has observed trauma residents make the mistake of seeing very long PT, PTT and ordering “many units of plasma, when in fact what they probably need is cryoprecipitate to boost the fibrinogen in the patient.”

Creating protocols in hospitals is critical to improving patient outcomes, she said. She advised devising protocols that “improve communication, decrease the delivery time of blood, and provide clearly defined roles, responsibilities, and resources.” For example: Are you coming to get the blood or do I have to provide a technologist to get it to you?

“That becomes such a critical question when you are trying to set up these protocols,” she said. “A technologist can prepare the blood in rec­ord time, but if it is not clear who has the role of transporting the blood, it will just sit on the counter.”
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Karen Lusky is a writer in Brentwood, Tenn. The CAP course “Your Turn: Management of the Bleeding Patient” is cosponsored by the American Association of Blood Banks.