Tag Archives: Plasma

Abstracts

EAST 2018 #8: 4-Factor PCC Plus Plasma. What?

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Many trauma centers have moved toward reversing warfarin with prothrombin complex concentrate (PCC) in place of plasma due to the speed and low volume of infusate with the former. In the US, 3-factor PCC was approved by the FDA first, but it has a lower Factor VII content. This usually required infusion of plasma anyway to make up the Factor VII, so what was the point (although there was some debate on this)?

Then 4-factor PCC was approved, and it alone could be used for warfarin reversal. But so far, PCC has not been routinely used for reversal of coagulopathy from trauma. We still rely on plasma infusion for this. The abstract I am discussing today compares reversal with 4-factor PCC alone to reversal with 4-factor PCC and plasma in coagulopathic patients.

This study retrospectively reviewed adult patients who received one of the above treatments over a 3 year period. Patient who were on oral anticoagulants were excluded. The goal INR was 1.5, and time to correction and number of PRBC transfused were measured.

Here are the factoids:

  • There were 516 patients who met criteria, but only 80 FFP patients and 40 PCC+FFP patients were analyzed
  • Patients were an average of 58 years old, had an ISS of 29, and 87% had sustained blunt injury
  • PCC+FFP resulted in faster correction of INR (373 min vs 955 min)
  • PCC+FFP received fewer units of PRBC (7 vs 9 units) and FFP (5 vs 7 units)
  • Mortality rate was lower in the PCC+FFP group (25% vs 33%)
  • There was no difference in thrombotic complications

Bottom line: Well, this is an interesting start. I think this abstract suggests that we should incorporate giving 4-factor PCC into the massive transfusion protocol to try to reduce the INR faster. However, the patient numbers are low and several of the results are only weakly significant (units transfused, mortality, p=0.04). Some additional confirmative studies will be needed before this is ready for prime time!

Here are some questions for the authors to consider before their presentation:

  • Why did your study group drop from 516 to 120? What impact might this have had on you analyses?
  • Did you look at the correction times stratified by initial INR? Severely coagulopathic patients could skew the numbers, especially if they were predominantly in only one of the study groups.
  • It did not look like the patients received much PRBC or plasma (<10 units of each). How injured / coagulopathic were they?
  • The mortality rates are rather high for an average ISS of 29. Did you analyze to see what impact ISS had on mortality? Could this have influenced your analysis?
  • Big picture question: Should we consider routinely giving PCC as part of the massive transfusion protocol in patients who are known to be coagulopathic? Based on the graph, it looks like patients will need more than a single dose. Reversal time was still very long for PCC+FFP.

Thanks for an intriguing abstract!

Reference: EAST 2018 Podium paper #12.

Abstracts

EAST 2018 #1: Plasma Over-Resuscitation And Mortality In Pediatric TBI

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The first EAST abstract I will discuss is the very first to be presented at the annual meeting. This is a prospective, observational studied that was carried out at the University of Pittsburgh. It looked at the association between repeated rapid thromboelastography (rTEG) results in pediatric patients and their death and disability after plasma administration. They specifically looked at the degree of fibrinolysis 30 minutes after maximum clot amplitude and tried to correlate this to mortality.

For those of you who need a refresher on TEG, the funny sunfish shape above shows the clot amplitude as it increases from nothing at the end of R, hits its maximum at TMA, then begins to lyse. The percent that has lysed at 30 mins (LY30%) gives an indication if the clot is dissolving too quickly (LY30% > 3%) or too slowly (LY30% < 0.8%).

The authors selected pediatric patients with TBI and performed an initial rTEG, then one every day afterward. They looked at correlations with transfusion of blood, plasma, and platelets.

Here are the factoids:

  • A total of 101 patients under age 18 were studied, with a median age of 8, median ISS of 25, and 47% with severe TBI (head AIS > 3)
  • Overall mortality was 16%, with 45% having discharge disability
  • On initial analysis, it appeared that transfusion of any product impeded fibrinolysis, but when controlling for the head injury, only plasma infusion correlated with this
  • Increasing plasma infusion was associated with increasing shutdown of fibrinolysis
  • The combination of severe TBI and plasma transfusion showed sustained fibrinolysis shutdown, and was associated with 75% mortality and 100% disability in the remaining survivors
  • The authors conclude that transfusing plasma in pediatric patients with severe TBI may lead to poor outcomes, and that TEG should be used for guidance rather than INR values.

Bottom line: There is a lot that is not explained well in this abstract. It looks like an attempt at justification for using TEG in place of chasing INR in pediatric TBI patients. This may be a legitimate thing, but I can’t really come to any conclusions based on what has been printed in this abstract so far.

Here are some questions for the authors to consider before their presentation:

  • There seem to be a lot of typos, especially with < and > signs in the methods.
  • Disability is a vague term. What was it exactly? Was it related to TBI or the other injuries as well?
  • These children also appear to have had other injuries, otherwise why would they need what looks like massive transfusion activation? Why did they need so much blood? Could that be the reason for their fibrinolysis changes and poor outcomes?
  • I can see the value of the initial rTEG, and maybe one the next day. But why daily? What did you learn from the extra days of measurements? Would a pre- and post-resuscitation pair have been sufficient?
  • Plasma is the focus of this abstract, but it does not describe how much plasma was given, or whether there was any departure from the usual acceptable ratios of PRBC to plasma administration.
  • Big picture questions: Most importantly, why would you think that poor outcomes, which are the focus of this paper, are related to plasma administration? Why haven’t we noticed this correlation before? And how does daily TEG testing help you identify and/or avoid this? What questions raised here are you going to pursue?

Reference: EAST 2018 Podium paper #1.

Laboratory

How Much Plasma Does It Take To Reverse Warfarin?

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For decades, plasma (with vitamin K) was the mainstay for reversing warfarin. Over the past several years, prothrombin complex concentrates (PCC) have made inroads in the management of this problem because of its sheer speed of action.

There are two problems with plasma. First, most hospitals still have only fresh frozen plasma (FFP), and it takes 20-30 minutes to thaw. This adds some up-front time to administration. Then, it takes time to infuse the 250cc or so of volume in each unit. This may be 1 or 2 hours, depending on policy and patient tolerance of a bolus of colloid.

If it always just took one unit of plasma to correct the INR to a desirable range (typically 1.5-1.6), then the whole PCC conversation might be moot. You could potentially have the INR corrected in 30-60 minutes depending on your patient’s cardiovascular system.

But how many does it really take? A group at Eastern Virginia Medical School in Norfolk, VA looked at this problem and tried to come up with a mathematical formula. They examined a year of warfarin reversal data at their hospital. Patients with severe clotting disturbances (advanced cirrhosis, DIC) and those who received additional products (PCC or activated Factor VII) were excluded.

Using data from nearly 1,000 patients, the following formula was derived and validated:

∆ INR = (0.57 ∙ preINR) – 0.72

So a patient with an INR of 3.0 would be expected to show a decrease of 0.99 to about 2.0 after one unit. This formula can be used iteratively to figure out how many units will drop the INR to the goal range.

I don’t know about you, but I hate doing math in the middle of a trauma resuscitation. I need something quick and dirty. A physician from NYU Langone in NYC commented on the article, and derived a nice little table to simplify the process. He calculated the number of plasma units based on some common INR ranges, assuming that the goal was to get it down under 1.5. Here is the table:

Bottom line: This is a nice little piece of information to tuck into your pocket or phone. For patients inside the usual therapeutic values, it will take 2-3 units of plasma to reverse. For your average older human with average comorbidities, expect this to take 4-6 hours, not counting ordering, thawing, and delivery. If my definitions of “life-threatening bleeding” are met (see below), your patient may have significant adverse events during this time frame. So think very seriously about using PCC instead.

Related posts:

Reference: Fresh Frozen Plasma Dosing for Warfarin Reversal: A Practical Formula. Mayo Clin Proc 88(3):244-250, 2013.

Complications

EAST 2017 #11: Use of Incompatible (Type A) Plasma For Massive Transfusion

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Type AB plasma is considered “universal donor” plasma, as it contains no antibodies to red cells with either A or B antigens on their surface. Unfortunately, only about 4% of the US population have this blood type and can provide the product. Due to this shortage, some trauma centers have decided to use Type A plasma initially for massive transfusion, and switch to type specific plasma once patient blood has been typed and screened.

This works, since only about 13% of the population have red cells with B antigens on the surface. But are there any adverse effects in those patients who receive potentially incompatible plasma? The EAST Multicenter Study group performed a retrospective study using trauma registry and blood bank data from 5 trauma centers. They looked at adult patients who received plasma as part of the massive transfusion protocol (MTP) over a 4+ year period. Incompatible type A plasma transfusion was defined to occur if a patient had either Type B or AB blood.

Here are the factoids:

  • There were a total of 1212 patients in the study; 93% were compatible and 7% were incompatible type A initial transfusions
  • The usual trauma demographics were seen (young, male) and the average ISS was 25 (they triggered an MTP, remember?)
  • By chance, the incompatible group had a slightly higher ISS (29) and penetrating injury rate (45% vs 33%)
  • The incompatible group received significantly more plasma during the first 4 hours and during the first day
  • There was no difference in mortality sepsis, ARDS, thromboembolic events, or renal failure
  • Regression analysis showed that incompatible plasma was not a predictor of mortality or morbidity
  • There was one hemolytic reaction and one occurrence of TRALI, both in the compatible group

Bottom line: This is the largest study around on the topic, and it does not show any significant problems (at least the ones that were studied) with giving incompatible plasma in acute trauma. How can this be, you ask? Remember, only the first one or two units (the first MTP pack) is potentially incompatible. Hopefully, by the time the second pack is delivered, the blood has been typed. And these patients are potentially receiving multiple units of typed plasma after the initial transfusion which dilutes the incompatible, and multiple transfusions overall which may blunt their immune response. 

This is an important paper that all centers should consider as they update their massive transfusion protocols!

Questions and comments for the authors/presenters:

  1. The abstract states that 5 centers participated, but the tables only list 4. Please explain this.
  2. It is not stated explicitly whether all centers used type A plasma initially. Is this the case?
  3. This is important work! Have any other centers converted to initial use of type A plasma?

Click here to go the the EAST 2017 page to see comments on other abstracts.

Related posts:

Reference: Use of incompatible type A plasma transfusion in patients requiring massive transfusion protocol: outcomes of an EAST multicenter study. Paper #16, EAST 2017.

General

What’s The INR Of Fresh Frozen Plasma?

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So what’s the INR of FFP? Or stated another way, what’s the lowest you can correct a patient’s INR using infusions of fresh frozen plasma?

One of the mainstays of correcting coagulopathy, either from hemorrhage or due to medication like warfarin, is transfusion of FFP. Frequently, clinicians will write orders to administer FFP until a certain INR is achieved. What is a reaonable INR?

A “normal” INR is 1.0, plus or minus about 0.2, depending on your laboratory. However, two separate studies have shown that transfusion of FFP will not reliably decrease the INR below about 1.7. 

Bottom line: The answer to the question is about 1.6. If any clinician orders FFP transfusions with a goal INR below this, it probably won’t happen. And since transfusions of any product have risks, my “juice to squeeze” ratio of risk vs benefit begins to fail at an INR of 1.6. Below that point, the patient needs a normal temperature and good perfusion to drop their INR further.

References:

  • Toward rational fresh frozen plasma transfusion: the effect of plasma transfusion on coagulation test results. Am J Clin Pathol 126(1):133-139, 2006.
  • Effect of fresh frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion 46(8):1279-1285, 2006.