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### Show Notes

Show Notes

• Transfusing 1 unit of packed red blood cells (pRBC) should increase the hemoglobin by approximately 1g/dL in a typical 70kg male. How?
• 1 unit of pRBC contains approximately 55g of viable hemoglobin if the donor had 13g/dL of Hgb.
• How do we know the grams of hemoglobin (Hgb) donated?
• A standard blood donation in the United States is 500 milliliters(mL), or 5 deciliters (dL).
• If a typical donor has a hemoglobin of 13 g/dL:
• 13g/dL of Hgb x 5 dL of blood donation = 65g of Hgb per donation
• As a result of processing and storage only about 85% of red cells remain viable, leading to only 55g of hemoglobin staying in the bloodstream (65g x 85% = 55g).
• Where did the rest of the Hgb go?

• Splenic and hepatic macrophages eat them soon after they hit the circulation so they don’t meaningfully contribute to the hgb of the patient. This loss of viable RBCs is called the “storage lesion” in the blood bank world.

• A 70kg male has about 5.25L of intravascular volume.
• How do we know the patient’s intravascular volume?
• 2/3 of the body weight is water
• 1/3 of THAT water is extracellular
• 1/3 of THAT extracellular space is intravascular volume.
• So, intravascular volume is 2/3 x 1/3 x 1/3 = 2/27
• Thus, intravascular volume represents 2/27, or approximately 7% of total body weight.
• More specifically, it is about 6.5% for women and 7.5% for men. Thus, a 70kg male would have 5.25L of blood.
• 70 Kg x 7.5% intravascular volume = 5.25L of blood
• A 70kg male would have 5.6L of blood post-transfusion from 1 unit of pRBC.
• After being processed, a donation of 500mL of whole blood is reduced to 350mL of red cells. However, the amount of hemoglobin (55g) remains the same.
• Thus, 55g of hemoglobin in 1 unit of pRBC will increase the hemoglobin by about 1g/dL in a 70 kg male
• To make calculations easier, let’s approximate 5.6L of total post-transfusion volume to 5.5L.
• An additional 55g of hemoglobin in a total volume of 5.5L of blood equals to increase in hemoglobin by 10g/L, or 1g/dL.
• In other words, 55g of Hgb ÷ 5.5 L = 10 g/L, or 1g/dL
• A 2019 study showed that both donor and patient characteristics affect the hemoglobin response to 1 unit of pRBC
• Donor factors include
• Sex
• Men have a higher hemoglobin on average
• Rh status (small effect)
• Rh+ result in a higher hemoglobin bump
• Recipient factors include
• Body size (accounts for the most variation of any factor)
• Bigger patients tend to experience a lower increase in hemoglobin.
• Remember from above
• Intravascular volume is about 7% of a patient’s weight
• The grams of donated hemoglobin will “be diluted”/equilibrate in the intravascular space
• Larger intravascular spaces will be LESS of an increase in g/dl
• Irradiation of the pRBC also slightly decreases the amount of viable red cells, thus decreasing the increase in hemoglobin.
• In clinical practice, 1 unit of pRBC can increase the hemoglobin anywhere between 0.6 to 1.6 g/dL

### Transcript

S: Welcome to Mind the Gap where we break down some common dogmas and dive deeper into things we may have taken for granted. This is Dr. Shreya Trivedi, an hospitalist at Beth Israel Deaconess Medical Center.

J: And I’m Dr. Jason Freed, a hematologist at BIDMC.

S: Jason, I got a question today on rounds by one of my senior residents. And I actually didn’t even know where to even look up this answer. So naturally I came to you – ot’s not technically a hematology question but figured its up your alley…

F: Shreya, you know I love questions that are hard to google. They’re so FEW of them these days. I’m intrigued. What was the question?

S: We had this patient who required a transfusion, and his hgb didn’t BUMP up by one the next day. We got into this whole discussion on how we are often taught the hemoglobin should go up by 1g/dl (or if you are in Canada 10g/L). But i dont even know where that comes from and if that’s always true?

F:  Right, this idea that hemoglobin should always bump up by 1g/dl from 1 unit of red cells seems like such a convenient thing, almost too convenient, like suspiciously convenient.

S: Right even more reason for us to unpack the question that seems to get dropped on the daily- did the patient bump up “appropriately.”

J: Alright Shreya, so first,  we have to go on journey and actually break down where the 1 g/dl appropriate bump comes from. Heads up, there is gonna be math but I promise you will leave with a more nuanced understanding that you can apply to the patients in front of you.

S: And again if the math that Jason leads us to goes over ur head, no worries, I will make sure we pause and summarize throughout.

J: And then we will end with actually applying those concepts to different types of patients.

S: I’m so excited! I trust you! Let’s do it. Lets go on a journey!

F: Well in order to understand the answer, we have to think about where units of blood come from. So let me ask you this Shreya, have YOU ever donated blood?

S: Yeah, a bunch of time.

F: Do you remember how much blood they took?

S:  You know I wasn’t paying attention, I was a little busy snagging the free cookies – not looking at the blood.

F: Fair enough. So the standard blood donation in the United States is 525ml. 500 is for the donation and 25ml is for testing your blood to make sure it’s safe.

S: OK, so I’m donating 500mls of my blood, how do I figure out whether that’s going to raise someone’s hemoglobin by 1g/dl?

F: Well we need to know your hemoglobin, so what’s your hemoglobin?

S: I think the last time I actually went to see a PCP gosh was so long ago, maybe it was 13 g/dl – somewhere around there.

F: OK 13/gl, and it’s gonna be good to use that g/dl and keep that in mind as we walk through the calculations. Because Deciliter is such a weird volume, I mean I can picture what a liter is

S: Right right… I haven’t thought about deciliter in a while but if i think about it,  a deciliter is really a 10th of a liter.

F: Yes, and I promise you it’s worth diving into the units because once I started paying attention to the units, it was kind of like at the end of Matrix when Neo sees the world as those green letters. Appreciating units just makes the connections between things much more apparent.

S: Ok Neo, I will respect the units. So maybe I’ll take a tab then at how many grams of Hg I’m donating if my hg is 13g/dl?

F: Go for it!

S: bear with me for a while i do the math -I am donating 500 milliliters of my blood, which if move my decimals is 5 deciliters of blood. And then i take the 13 grams per deciliter I have so multiply by the 5 deciliters I am donating, that’s 65 total grams of hemoglobin that I am donating.

F: Yes 65 grams of hemoglobin.

S: Great so does the patient actually get the full 65g of hemoglobin from my donation?

F: Well, processing, storage and refrigeration all take a toll and only about 85% of the red cells are viable after transfusion.

S: So then I need to multiply that 65g of Hg by 85%, so then I’m down to 55g of functional hgb that i am actually giving

F: Yep, so functionally that takes it down to 55g of hemoglobin actually staying in the patient’s bloodstream.

S: OK so how do we get from that 55g of “functional” hemoglobin. How then do we figure out how much of the Hgb is then going to bump up in this patient?

F: Well you have to know the patient’s intravascular volume.

S: Wait, doesn’t the intravascular volume depend on how big the patient is then?

F: EXACTLY

S: So 1 to 1l “appropriate” bump up can’t possibly be right for everyone.

F: Nope!!

F: I’m the same way, I probably gave a thousand transfusions before I had even considered this.

S: So how do we figure out a patient’s intravascular volume?

F: We have to go back to physiology class and think about body fluid compartments… so 2/3rd of the body weight is water and 1/3rd of that water is extracellular and 1/3rd of that extracellular space is intravascular volume… so you may just have to trust me on the math here but to get the intravascular volume, we would multiply all of that. So to do the math it’s 2/3 times 1/3 times 1/3 we get 2 over 27 which is about 7%.

S: So about 7% of someone’s body weight is blood.

F: Yes, it’s a good rule of thumb to remember — that blood volume is about 7% of body weight. Technically, its about 6.5% for women and 7.5% for men which averages to 7%.

S: So if we had a 70kg male patient, and 7.5% of his weight is blood then he has 5.25 liters of blood.

F: Technically you also need to account for the volume of the blood that you just transfused, which is now also in that intravascular volume.

S: Wouldn’t that be the INITIAL 500mls of blood that I donated?

F: Well Even though 500ml of whole blood was donated, only about 350ml remain in a unit of packed red cells because you removed a lot of platelets and plasma. So really the math is 5.25 liters plus about 350ml so that gets us to 5.6 liters.

S: Ok so to recap, I know i am donating 55g of viable hemoglobin and this patient has 5.6 liters of blood after the transfusion. So then, what is the “appropriate” bump in g/dl that I’m expecting?

F: now it’s just a matter of concentration,  you divide the grams of hemoglobin you are donating  by the blood volume of the patient.  And the math works out great. The 55 grams of hemoglobin donation divided by 5.6 liters (well let’s make that 5.5 liters to make the math easy). [S: Thank you] So 55 divided 5.5 is 10. So with the units that is 10 grams hemoglobin per liter AKA 1 gram per deciliter.

S: Ah so that is where we get that hemoglobin bump of 1g/dl comes from! Its so satisfying Jason when the rule of thumb pans out like that.

J: Yeah it is really nice. Lets just recap how we got here: you donated 500ml of whole blood and we multiplied that times your hemoglobin to figure out how many grams of hemoglobin you donated and then we multiplied it by .85 because that’s the fraction that will remain viable. Then, we divided it by the patient’s intravascular volume. And if you have donor whose hemoglobin is 13g/dl, like Shreya, and a patient who is that prototypical 70kg male, that gives us 1g/dl bump per unit of RBCs.

S: Nice! But what if me as the donor did’t have a Hgb of 13, what if it was 11! That same patient’s hemoglobin wouldn’t get a bump of 1, it’d only bump up up  by a fraction of that.

F: You’re right, the donor matters. And, that why there is screening of the donors. The FDA standard is 12.5 g/dL for women and 13.0 g/dL for men. But of course some people are higher than that.

S: But wait, how do I find out the hemoglobin of the donor blood that my patients get?

F: You can’t.

S: What??

F: You can’t… I mean theoretically blood donations could come labeled with the hemoglobin of the donor, but they don’t.

S: This is crazy, now I just feel like I’m giving a drug of unknown dose after breaking all that down.

F: Haha yeah it really is a drug of unknown dose.

S: Ok this is great Jason, I love that in theory all this math pans out – has anyone actually studied whether all of this theoretical stuff shakes out in real life?

F: Amazingly, it took a really long time for anyone to look at this in a robust way! But there was an incredible paper published in blood in September 2019 on this topic by Roubinian et al. … And I’ve been talking about it ever since it was published to anyone who would listen.

S: Ok, ok, do tell

F: The authors connected the Kaiser Permanente clinical database with their blood bank database so they could see how both the donor characteristics AND patient characteristics affected how much the hemoglobin would go up after transfusion. They were basically trying to put the 1g/dl per 1 unit of red cells rule to the test in a large database of 38,000 different transfusions.

S: So did the 1 to 1 rule pan out?

F: Yes and No

S: Explain that a bit more?

F: Well on average there was a bump of 1.04 g/dl, so it really is a good rule of thumb

S: Nice! What/s the catch?

F: But for the reasons we just talked about the characteristics of the donor and the patient matter a great deal. They were even able to derive a formula from their data to predict how much the Hg will go up with 1 unit of blood.

S: Great, another formula to remember.

F: Well you don’t need to remember it, because what they saw in real life, basically validated the calculations we just did.

S: Nice, what did they find?

F: In terms of the donor factors that mattered, one of the largest was the sex of the donor which is not suprising because we know that men tend to have higher higher hemoglobins on average due the effect of testosterone. But then there was stuff that they did not expect at all like Rh pos donors resulted in slightly higher hemoglobin bumps for reasons the authors couldn’t really explain.

S: Weird who would have thought the Rh status matters. What  about the patient? What characteristics of the patient mattered?

J: The body size of the patient. The bigger the patient, the less the Hgb went up.

S: That makes a ton of sense now, especially now if think about the teaching point that everyone’s intravascular volume is different based on their weight. Anything else?

J: There is also how the donated blood is processed, like irradiation, which sort of makes sense to me because radiation could cause less viable red cells.

S: I didn’t think of that before but now that makes a ton of sense – every time I click on irradiated blood, I probably shouldn’t expect that Hgb to go up by 1!

J: Exactly

S: So the MedEd nerd in me loves cementing things a bit more. I think it would be good to apply some of this with some donor and patient characteristics and go through some cases.

F: Happily. Table 7 of this paper is really impressive, they basically use their formula to say on average how much the hemoglobin should go up in 2 different situations.

So the first one. They have an Rh-negative Female donating irradiated red cells to a 60 year old man who has a BMI of 30. So in that scenario, the hemoglobin would only go up by 0.59 g/dl on average.

S: 0.59 g/dl is a lot less than 1, and a BMI of 30 isn’t even that high!

F: And they give a second example for contrast… if you had a Rh-positive Male donating non-irradiated blood to an 85 year old woman with a BMI of 18, her hemoglobin would go up by 1.65 g/dl!!!!

S: Dang, so on one hand you have a 0.59 g/dl bump for a mildly obese man on the oncology floor receiving irradiated blood from woman. And then on the other hand you have a whopping 1.65 g/dl for a thin older woman on medicine wards receiving non-irradiated blood. I feel like this is my neo moment coming on.

F: Haha. Welcome to the matrix Shreya. So let me ask you, did they bump appropriately?

S: I guess that next time someone asks that age-old question, I guess it really depends!

S: So if I could just summarize…

The 1g/dl rule is correct on average for adults, but for a given patient and unit of blood, it could be anywhere from 0.6 to 1.6 bump after transfusion.

There are a bunch of factors that go into that. So there is the amount of Hgb the donor is giving. The patient characteristics, which I think for me is the biggest thing i’ll pay attention next time on floors & giving a transfusion is thinking about the size of the patient. So, the bigger the patient is, technically they have more intravascular volume, and so the less I will expect hemoglobin concentration to go up in that intravascular space.

F: Shreya, you are ready for rounds tomorrow. That’s gonna do it for this weeks episode. Stay tuned after the credits if you want some additional details on the content we discussed today

S: Alright for you nerds in the audience that cant get enough of all things of RBCs, we’ve got a few more points. If you have feedback or questions, please email us at hello@coreimpodcast.com.  Thank you to our peer reviewer, Dr. Bentley Rodrigue.  Thank you to Solon Kellehar  for the outstanding audio editing and Preeyal Patel for the accompanying infographic, which is so helpful especially with the math. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.

Alright, so for those of you that stuck around and can’t get enough of all things pRBCs, here’s a few points of clarification.

F: Number 1:  The rule of 7% of body weight being intravascular volume holds fairly well for patients with a normal BMI. But the question is does that scale up linearly? In other words, does a 300lb patient have twice as much blood volume as 150lbs patient. And the answer to that is no.

S: And the reason for that is if that extra weight on that 300lb patient is majority adipose tissue then what we should know that adipose tissue is less vascular than other tissues so we can expect patient’s with more adipose tissue to have less intravascular volume.

F: Yes, so the 300lb patient actually probably has only 1.5 times as much blood volume, not twice as much as a 150lb patient. And, if you are trying to get a good estimate, there are more sophisticated prediction tools available online.

S: Number 2: So we did a lot of math around donations and a lot of that was done by whole blood, which is the most common source of packed red cells in the United states. But, about 20% are collected by apheresis and in that case you need a refresher of what that is, that is basically donating pure red blood cells. This matters because If you’re in a place that uses a lot of apheresis, you can expect the donation from aphaeresis collection to results in slightly lower hemoglobin bump than whole blood.

J: Number 3: Shreya donated 500ml of whole blood but the bag of packed red blood cells you see hanging up for a patient is only 350ml. Why is that? What happens is we take off most of the plasma and platelets and often it goes through leukoreduction to get rid of WBCs. So the 350ml bag is about 200ml of red cells, 50 ml of residual plasma and then about 100ml of preservative solution.

Shreya: Remind me what’s in the preservative solution?

J: So there’s citrate (so it doesn’t clot), adenine and Phosphate so the cells can make ATP and dextrose  so that the cells don’t starve.

S: Nice that is good to know! And last but not least: one of things we did as an early step was going through the donation. yes, I donated 65g of Hg, but that went down to a functional 55 g, If you really wanted to know where the rest of the Hg went, that is actually what the blood bank world calls “storage lesions.” Unfortunately, a subset of the RBC actually degenerate into nonviable tiny RBCs, called storage microerytherocytes. And then as soon as they hit the circulation, the splenic and hepatic macrophages gobble them as soon as they hit the circulation so they don’t meaningfully contribute to hg of the patient.

J: And now that’s really a wrap for this episode for real this time! Thanks so much for listening!

S: Take care.

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