Tag Archives: transfusion

Jehovah’s Witnesses And Blood Transfusion Demystified

Injury can be a bloody business, and trauma professionals take replacement of blood products for granted. Some patients object to this practice on religious grounds, and their health care providers often have a hard time understanding this. So why would someone refuse blood when the trauma team is convinced that it is the only thing that may save their life?

Jehovah’s Witnesses are the most common group encountered in the US that refuse transfusion. There are more than 20 million Witnesses worldwide, with over 7 million actively preaching. It is a Christian denomination that originated in Pennsylvania during the 1870s.

Witnesses believe that the bible prohibits taking any blood products, including red cells, white cells, platelets or plasma. It also includes the use of any dialysis or pump equipment that must be primed with blood. This is based on the belief that life is a gift from God and that it should not be sustained by receiving blood products. The status of certain prepared fractions such as albumin, factor concentrates, blood substitutes derived from hemoglobin, and albumin is not clear, and the majority of Witnesses will accept these products. Cell saver techniques may be acceptable if the shed blood is not stored but is immediately reinfused.

Why are Witnesses so adamant about refusing blood products? If a transfusion is accepted, that person has abandoned the basic doctrines of the religion, and essentially separates themselves from it. They may then be shunned by other believers.

So what can trauma professionals do to provide best care while abiding by our patient’s religious belief? In trauma care it gets tricky, because time is not on our side and non-blood products are not necessarily effective or available. Here are some tips:

  • Your first duty is to your patient. Provide the best, state of the art care you can until it is absolutely confirmed that they do not wish to receive blood products. In they are comatose, you must use blood if indicated until the patient has been definitively identified by a relative who can confirm their wishes with regard to blood. Mistaken identity does occur on occasion when there are multiple casualties, and withholding blood by mistake is a catastrophe.
  • Talk with the patient or their family. Find out exactly what they believe and what they will allow. And stick to it.
  • Aggressively reduce blood loss in the ED. We are not always as fastidious as we should be because of the universal availability of blood products. Use direct pressure or direct suture ligation for external bleeding. Splint to reduce fracture bleeding.
  • Aggressively use damage control surgery. Don’t go for a definitive laparotomy which may take hours. Pack well, close and re-establish normal physiology before doing all the final repairs.
  • Always watch the temperature. Pull out all the stops in terms of warming equipment. Keep the OR hot. Cover every bit of the patient possible with warming blankets. All fluids should be hot. Even the ventilator gases can be heated.
  • Think about inorganic and recombinant products such as Factor VIIa, tranexamic acid and Vitamin K. These are generally acceptable.
  • Consider angiography if appropriate, and call them early so their are no delays between ED and angio suite or OR and angio suite.

Bottom line: Do what is right for your patient. Once you are aware of their beliefs, avoid the use of any prohibited products. Speak with them and their family to clarify exactly what you can and cannot do. This is essentially an informed consent discussion, so make sure they understand the consequences. Follow their wishes to the letter, and don’t let your own beliefs interfere with what they want.

What’s The Difference? Liquid Plasma vs FFP

Plasma is an important component of any trauma center’s massive transfusion protocol (MTP). Coagulopathy is the enemy of any seriously injured patient, and this product is used to attempt to fix that problem.

And now there are two flavors available: liquid plasma and fresh frozen plasma. But there is often confusion when discussing these products, especially when there are really three flavors! Let’s review what they are exactly, how they are similar, and how they differ.

Fresh frozen plasma (FFP)
This is plasma that is separated from donated whole blood. It is generally frozen within 8 hours, and is called FFP. However, in some cases it may not be frozen for a few more hours (not to exceed 24 hours total) and in that case, is called FP24 or FP. It is functionally identical to FFP. But note that the first “F” is missing. Since it has gone beyond the 8 hour mark, it is no longer considered “fresh.” To be useful in your MTP, it must be thawed, and this takes 20-40 minutes, depending on technique.

Thawed plasma
Take a frozen unit of FFP or FP, thaw, and keep it in the refrigerator. Readily available, right? However, the clock begins ticking until this unit expires after 5 days. Many hospital blood banks keep this product available for the massive transfusion protocol, especially if other hospital services are busy enough to use it if it is getting close to expiration. Waste is bad, and expensive!

Liquid plasma (never frozen)
This is prepared by taking the plasma that was separated from the donated blood and putting it in the refrigerator, not the freezer. It’s shelf life is that of the unit of whole blood it was taken from (21 days), plus another 5, for a total of 26 days. This product used to be a rarity, but is becoming more common because of its longer shelf life compared to thawed plasma.

Finally, a word on plasma compatibility. ABO compatibility is still a concern, but Rh is not. There are no red cells in the plasma to carry any of the antigens. However, plasma is loaded with A and/or B antibodies based on the donor’s blood type. So the compatibility chart is reversed compared to what you are accustomed to when giving red cells.

Remember, you are delivering antibodies with plasma and not antigens. So a Type A donor will have only Type B antibodies floating around in their plasma. This makes it incompatible with people with blood types B or AB.

Type O red cells are the universal donor type because the cells have no antigens on the surface. Since Type AB donors have both antigens on their red cells, they have no antibodies in their plasma. This makes AB plasma is the universal donor type. Weird, huh? Here’s a compatibility chart for plasma.

Next time, I’ll discuss the virtues of the various types of plasma when used for massive transfusion in trauma.

Are Transfusing Too Much Blood During The MTP?

The activation of the massive transfusion protocol (MTP) for hypotension is commonplace. The MTP provides rapid access to large volumes of blood products with a simple order. Trauma centers each design their own protocol, which usually includes four to six units of PRBC per MTP “pack.”

This rapid delivery system, coupled with rapid infusion systems, allows the delivery of large volumes of blood and other blood products very quickly. But could it be that this system is too slick, and we are a bit too zealous, and could even possibly transfuse too much blood?

The trauma group at Cedars-Sinai in Los Angeles retrospectively reviewed their own experience via registry data with their MTP over a 2.5 year period for evidence of overtransfusion. All patients who received blood via the MTP were included. Patients who had a continuous MTP > 24 hours long, those who died within 24 hours, and those who had a missing post-resuscitation hemoglobin (Hgb) were excluded.

The authors arbitrarily defined overtransfusion as a Hgb > 11 at 24 hours. They also compared the Hgb at the end of the MTP and upon discharge with this threshold. They chose this Hgb value because it allows for some clinical uncertainty in interpreting the various endpoints to resuscitation.

Here are the factoids:

  • 240 patients underwent MTP during the study period, but 100 were excluded using the criteria above, leaving 140 study patients
  • Average injury severity was high (24) and 38% suffered penetrating injury
  • Median admission Hgb was 12.6
  • At the conclusion of the MTP, 71% were overtransfused using the study definition, 44% met criteria 24 hours after admission, and 30% did at time of discharge
  • Overtransfused patients were more likely to have a penetrating mechanism, lower initial base excess, and lower ISS (median 19)

The authors concluded that overtransfusion is more common than we think. This may lead to overutilization of blood products, which has become much more problematic during the COVID epidemic. They recommend that trauma centers track this metric and consider it as a quality of care measurement.

Bottom line: This is a nicely crafted and well-written study. It asks a simple question and answers it with a clear design and analysis. The authors critique their own work, offering a comprehensive list of limitations and a solid rationale for their assumptions and conclusions. They also offer a good explanation for their choice of Hgb threshold in defining overtransfusion.

I agree that overtranfusion truly does occur, and I have seen it many times first-hand. The most common reason is the lack of well-defined and reliable resuscitation endpoints. How do we know when to stop? What should we use? Blood pressure? Base excess? TEG or ROTEM values? There are many other possibilities, but none seem reliable enough to use in every patient. 

Patients with penetrating injury proceeding quickly to OR more commonly experience overtransfusion. This may be due to the reflexive administration of everything in each cooler and the sheer speed with which our rapid infuser technology can deliver products. The more product in the cooler, the more that is given, which may lead to the overtranfused condition. 

The authors suggest reviewing the makeup of the individual MTP packs, and this makes sense. Are there too many in it? This could be a contributing factor to overtransfusion. It might be an interesting exercise to do a quick registry review at your own center to obtain a count of the number of MTP patients with a final Hgb > 11. If you find that your numbers are high, consider reducing the number of red cell packs in the cooler to just four. But if you already only include four, don’t reduce it any further. And in any case, critically review the clinical indicators your  surgeons use to decide to end the MTP to see if, as a group, they can settle on one to use consistently. 

Reference: Overtransfusion of packed red blood cells during massive transfusion activation: a potential quality metric for trauma resuscitation. Trauma Surg Acute Care Open 7:e000896., July 26 2022.

Best Of EAST #13: Whole Blood And Hypocalcemia

Hypocalcemia has long been known to exacerbate coagulopathy. Calcium is involved at several points in the coagulation cascade. Once serum levels drop below about 0.25 mmol/L (normal value 1.2-1.4 mmol/L) thrombin generation and clot formation cease. Although levels this low are probably rare, anything between this low and the normal level can significantly lower clot strength.

Trauma patients are more likely to have bleeding issues than most, and trauma professionals do their best to avoid coagulopathy. Unfortunately, the products we use to replace shed blood are preserved with citrate, which binds calcium. Given in even modest to large quantities, transfusion itself can lead to hypocalcemia.

Most blood transfused in the US has been broken down into separate components (packed cells (PRBC), plasma, platelets) and the effect on calcium levels is well known. The trauma group at Oregon Health Sciences University studied the impact on calcium of whole blood transfusions.

They performed a retrospective review of data collected prospectively over a 2.5 year period on patients receiving whole blood. This included the number of transfusions, ionized calcium levels, and calcium replacements administered. Patients were divided into two groups, those who received whole blood only and those who were given whole blood and component therapy. Outcomes evaluated were ionized calcium levels, hypocalcemia correction, and death.

Here are the factoids:

  • During the study period, 335 patients received whole blood, but only 67% met inclusion criteria
  • About half (103) received a median of 2 units of whole blood (only!)
  • The authors do not state how many component units the whole blood plus component therapy group received
  • There was no difference in calcium levels based on average ISS in the two groups, although ISS does not differentiate injuries that bleed very well
  • Hypocalcemia occurred in only 4% of whole blood patients vs 15% of whole blood + components, which was significant
  • Hypocalcemia within the first hour was significantly associated with death in the first 24 hours and 30 days, although the standard deviation or SEM of this value was large
  • Whole blood only patients received less calcium replacement, and failure to correct was associated with 24 hour mortality
  • Median time to death in patients that “failed to correct” was 7.5 hours after admission

The authors conclude that hypocalcemia rarely occurs in whole blood only resuscitation, and that adding components increases its incidence and overall mortality. They state that aggressive calcium supplementation should be prioritized if component therapy is used.

Bottom line: There’s a lot to “unpack” here! Packed red cells are preserved with 3g of citrate per unit, whereas whole blood units contain only half that amount (1.66g to be exact). One would expect that one unit of packed cells would have twice the anticoagulant effect as a unit of whole blood.

This study is a blended model, where every patient got some whole blood, but some got components as well. Why? Is there a blood refrigerator in the ED stocked with whole blood, and when it is exhausted there is a switch to components? This model makes it more difficult to tease out the impact of the components given. Perhaps it could be done by matching patients with a given amount of whole blood. That is, comparing patients with 3 whole blood with those who received 3 whole blood + 2 PRBC.

There was no room in the abstract to explain why one third of patients were excluded from the study. This needs to be provided to ensure that the remaining two thirds are representative and can legitimately be analyzed. 

The number of units of whole blood per patient was low, with a median of two units given. Is it surprising that these patients did better than ones who received many more? Remember, from a citrate anticoagulant perspective, hanging two units of whole blood is the same as giving just one unit of PRBC.

This abstract raises a lot of questions, and the most important ones deal with how it was designed and the exact numbers of product given. Only then can we be confident that the rest of the associations described are significant.

Here are my questions for the authors and presenter:

  • Why did you choose the whole blood vs whole blood + components for your study? Wouldn’t it have been cleaner to do whole blood only vs components only? Perhaps all of your patients get whole blood? It seems like this might make the results more difficult to tease out.
  • How is whole blood made available for your trauma patients, and did this have an impact on your study? Do you have a limited number beyond which component therapy is used?
  • What were the inclusion criteria? These were not stated in the abstract, but a third of patients were excluded from the study based on them.
  • Could excluding a third of patients have skewed your results, and how?
  • How many component units were given along with the whole blood in the combination group? This was not provided in the abstract and will have a major impact on outcomes if the median total product numbers are significantly higher.
  • What does “failed to correct” mean? Were the patients not responding to large amounts of administered calcium, or were they not receiving large amounts of it?

I am very interested in the fine details in this abstract and will be listening intently to the presentation!


Best Of EAST #2: Pay Attention To Platelet Ratios In Your MTP!

More MTP stuff! Every trauma center has a massive transfusion protocol, and current literature encourages them to try to achieve an “optimal” transfusion ratio. The literature has converged on a red cell to plasma ratio of somewhere between 1:1 and 2:1. Less has been written about platelet ratios, and trauma centers often don’t pay as much attention to this ratio when reviewing MTPs.

But is it important? The trauma group at the Massachusetts General Hospital examined the impact of platelet ratios on mortality in patients undergoing MTP. This was another TQIP data analysis, performed over a nine year period.

The authors defined massive transfusion as ten or more units of PRBC in the first 24 hours, or any number of units of red cells, plasma, or platelets given within the first four hours. They also defined “balanced” as a ratio of RBC to FFP and RBC to platelets <2. Multivariate regression analysis was performed to gauge the impact of ratios and achievement of a balanced resuscitation on 24-hour mortality.

Here are the factoids:

  • A total of 7,520 patients in the dataset underwent MTP
  • Nearly 83% achieved RBC to FFP balance, but only 6% had RBC to platelet balance (!)
  • Patients with both balanced FFP and platelets had the lowest mortality at 24 hours
  • Mortality increased by 2x with unbalanced plasma, a little more than 2x with unbalanced platelets, and 3x if both were out of balance (see figure)

The authors concluded that the platelet component of the MTP was frequently out of balance, and that it is associated with mortality to a greater degree than with unbalanced plasma.

Bottom line: This paper confirms my observations that trauma centers pay a lot more attention to the red cell to plasma ratio and don’t get as excited when the platelets are out of line. Part of this is probably due to confusion over how to count platelet packs. Typically they are delivered in packs called “pheresis” or “apheresis.” Each is the equivalent of about 6 units of platelets (check with your blood bank for more exact numbers). This means that a ratio of 6 RBC to 5 plasma to 1 platelets would be considered balanced. But a ratio of 28:28:2 would not.

According to this abstract, the use of sufficient platelets is important. This makes sense. However, the exact mechanism cannot be determined from this type of study. It could be a direct effect of not having enough platelets to form good clot. Or it could be something completely outside the clotting mechanism, just an association with something in the care processes that occurs as these patients undergo resuscitation. 

The why doesn’t matter so much, though. This abstract presents compelling data that suggests that we really need to pay attention to the platelet ratios given during the MTP. They should be analyzed just as closely as plasma ratios during PI review, and changes to the MTP process implemented to normalize this important ratio.

Here are my questions for the authors and presenter:

  • There is a statement in the methods section that is not clear. “only patients with steady RBC/PLT and RBC/FFP ratios between 4-and 24-hr were analyzed.” What is your definition of “steady?”
  • Did you see any mortality patterns in the data you analyzed that might suggest why lower platelet volumes were more deadly?

This was a nicely done abstract, and I look forward to the live presentation and the finished manuscript!