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Operator
Good afternoon. My name is Chris, and I'll be your conference operator today. At this time, I'd like to welcome everyone to Penumbra's Fourth Quarter and Year-end 2021 Conference Call. (Operator Instructions)
I would like to introduce Ms. Jee Hamlyn-Harris, Investor Relations for Penumbra. Ms. Hamlyn-Harris, you may begin your conference.
Jee Hamlyn-Harris - IR Officer
Thank you, operator, and thank you all for joining us on today's call to discuss Penumbra's earnings release for the fourth quarter and year-end 2021. A copy of the press release and financial tables, which includes the GAAP to non-GAAP reconciliation can be viewed under the Investors tab on our company website at www.penumbrainc.com.
During the course of this conference call, the company will make forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements regarding our financial performance, commercialization, clinical trials, regulatory status, quality, compliance and business trends. Actual results could differ materially from those stated or implied by our forward-looking statements due to certain risks and uncertainties, including those referenced in our 10-K for the year ended December 31, 2021, which is scheduled to be filed with the SEC on February 22, 2022.
As a result, we caution you against placing undue reliance on these forward-looking statements, and we encourage you to review our periodic filings with the SEC, including the 10-K previously mentioned, for a more complete discussion of these factors and other risks that may affect our future results or the market price of our stock, including the not limited to the impact of the COVID-19 on our business, results of operations and financial conditions.
Penumbra disclaims any duty to update or revise our forward-looking statements as a result of new information, future events, developments or otherwise. On this call, certain financial measures are presented on a non-GAAP basis. A reconciliation of GAAP to non-GAAP financial measures is provided in our posted press release. We anticipate the prepared comments on today's call will run approximately 20 minutes. Adam Elsesser, Penumbra's Chairman and CEO, will provide a business update. Maggie Yuen, our Chief Financial Officer, will then discuss our financial results for the fourth quarter and full year. And Jason Mills, our Executive Vice President of Strategy, will discuss our 2022 guidance.
With that, I would like to turn over the call to Adam Elsesser.
Adam Elsesser - Co-Founder, Chairman, President & CEO
Thank you, Jee. Good afternoon, everybody. Thank you for joining Penumbra's Fourth Quarter and Year-end 2021 Conference Call. Our total revenues for the fourth quarter were $204 million, a year-over-year increase of 22.2% as reported and 23% in constant currency, and a 7.3% sequential increase from the third quarter.
For the full year 2021, our total annual revenues were $747.6 million, which represented growth of 33.4% over full year 2020. In the fourth quarter, we achieved record revenue in both our Neuro and Vascular businesses. Also, we started making progress toward our goal of building a safe and secure health care platform using immersive computing to help a significant number of patients.
In the early part of this first quarter of 2022, we navigated the same macro challenges that every company in our field is seeing, including severe staffing issues, particularly in hospitals, supply constraints, rising inflation and other COVID-related challenges. That said, our team is stronger than ever and able to take on important work necessary to help the millions of patients that reside within the 6 large under penetrated markets we're serving.
During the last 2 years of the pandemic, the Penumbra team delivered several new paradigm-changing products to our physician customers, and we continue to invest significantly in new innovation within each of these markets as well as in production to ensure as steady a supply chain as possible. These investments matter to the long-term growth and profitability for our business. And we are also excited about several new important products we expect to bring to our customers within Neuro, Vascular and Immersive Healthcare later this year.
Now I'd like to spend a few minutes discussing our team's execution during the fourth quarter. Let's start with Vascular. We reported global Vascular growth of 30.4% year-over-year to $113.6 million in the fourth quarter as we saw strong performances from both our thrombectomy and embolization franchises. Our vascular team has an enormous amount of work to do over the next several years as the opportunities for growth in both of these franchises are significant.
This quarter, the demand for our vascular embolization products accelerated following the prior COVID wave, growing 13% sequentially, which took a lot of our team's attention. We also increased our revenue both sequentially and year-over-year in all 4 vascular thrombectomy segments, ALI, DVT, coronary and PE, and are in a great position in each going forward. In just the past few years, we have launched paradigm-changing technology into all 4 of these under penetrated markets. within which there are over 1 million patients we can help each year. Nearly 90% of whom are not yet treated in single-session therapy.
On the venous side. In DVT and PE, we saw an accelerating number of patients treated with our Lightning 12 technology through the second half of 2021. Notably, the highest number of new physician customers adopted Lightning 12 in the fourth quarter. Not only do we see a long runway of continued growth ahead with this technology, we also have new innovation expected late this year for venous patients.
Similarly, we continue to expand our leadership position in ALI with Lightning 7, the adoption of which has been robust since its launch in the second quarter. Lightning 7 changed the paradigm in the treatment of ALI, and we also have plans to augment this paradigm late this year as well with additional products that build on our proprietary computer-aided innovation.
On the coronary thrombectomy side, we presented positive clinical data from the CHEETAH study in November at the TCT conference, and these data drove increasing awareness of the utility of CAT RX for patients with coronary lesions with high thrombus burden.
We saw accelerating revenue from our coronary business in the fourth quarter, and we believe we are in the early stages of growth in this market. The positive trends that underlie our strong growth in both vascular thrombectomy and embolization are a testament to our unique products, strong commercial team and clinical focus. Our best-in-class vascular team added more new thrombectomy customers in the past 4 quarters than any similar stretch in our history, including a record number of new customers added in Q4.
Further, going forward, the team is working with more physicians within our existing accounts to bring our technology to them. This is important given that they serve all 3 specialties in this field: interventional cardiologists, interventional radiologists, and vascular surgeons, many of whom do procedures in more than 1 area.
We are well positioned as we have invested significantly over the past few years to prepare our commercial team to meet the needs of physicians in all 3 specialties with continued innovation and clinical focus, including new and relevant clinical studies in DVT, ALI and PE.
Let me now turn to our Neuro business. In the fourth quarter, we recorded the fastest sequential growth in nearly 3 years, excluding initial COVID quarter as our Neuro business expanded 6.8% and over the third quarter of 2021 and accelerated to 13.3% growth year-over-year to $90.4 million, led by our stroke franchise.
Coming off last quarter's 17% sequential increase in our U.S. stroke business, the momentum with the RED catheters continued driving 11% sequential growth in the fourth quarter. The RED catheter unit volume has already eclipsed the peak for our previous-generation product set in 2019 before the pandemic and recall. RED 72 has become our best-selling product for large vessel strokes, while RED 62 has exceeded all expectations.
Not only does RED 62 utilization and distal aspiration been robust, the product is being adopted at a much higher rate than anticipated in large vessel occlusions as a primary treatment as well in large part because it is the best tracking catheter on the market. We believe catheter tractability will become an even more important trait as we move into the new paradigm in this market in the future.
As we look into 2022 and beyond, the RED portfolio is very important for 2 reasons: first, we think RED will continue to drive strong growth and share gain for our stroke business, not just in the U.S. but also in Europe, Japan and other geographies into which we are -- we'll be launching these products; second, RED sets the stage for Thunderbolt, which is our most significant innovation in stroke to date. We are even more confident in our decision to conduct a trial in the U.S. for Thunderbolt. We expect this trial will demonstrate the profound benefit of Thunderbolt, which could change the paradigm in stroke intervention by significantly enhancing the speed and completeness of clot removal.
We are also well positioned in neuro access and embolization. More than a year after our U.S. launch, we are still seeing increasing adoption of BMX96, an access with additional innovations slated for later this year.
Likewise, we are seeing a renewed interest in our larger neuro coil family, which represents a unique and important product line for some of the most challenging embolization cases.
Turning now to our Immersive Healthcare business. We have made significant progress in the work necessary to build the first platform for virtual reality in health care. To build this platform, our work in 2022 is focused on 3 important areas: first, we are making significant progress innovating on the technical side of building this platform, both in terms of hardware and software; second, we have begun important conversations with some of the leading companies across more than a dozen health care channels, within which there are more than 50 million patients who can benefit; and lastly, we are exploring dozens of partnerships with third-party companies who could eventually become a very large source of applicable content for patients on our platform.
Moving finally to our international business. We made significant progress in the fourth quarter, growing revenue 19% on a year-over-year basis. With the upcoming launches in several international markets of our RED catheters and Lightning technology, coupled with continued expansion of our business in China and Japan, we are well positioned for strong growth in our international business going forward.
I would now like to turn the call over to Maggie to go over our financial results for the quarter.
Maggie S. Yuen - CFO
Thank you, Adam. Good afternoon, everyone. Today, I will discuss our financial results for the fourth quarter and full year of 2021. Financial results on this call for revenue and gross margin are on a GAAP basis. While operating expenses, including research and development and SG&A and operating income are on a non-GAAP basis, which excludes nonrecurring and onetime expenses. A reconciliation of GAAP to non-GAAP financial measures is provided in our posted press release.
For the fourth quarter ended December 31, 2021, our total revenues were $204 million, an increase of 22.2% reported and 23% in constant currency compared to the fourth quarter of 2020 and sequential growth of 7.3% over the third quarter of 2021.
Our geographic mix of sales in the quarter were 70.8% U.S. and 29.2% international. U.S. and international reported growth of 23.7% and 18.8%, respectively, compared to the same period in 2020.
Moving to revenue by franchise. Revenue from our Vascular business grew to $113.6 million in the fourth quarter of 2021, an increase of 30.4% reported and 31.1% in constant currency compared to the same period last year.
Compared to prior quarter, revenue from our Vascular business grew by 7.7%, driven by growth across U.S. and all international regions in both peripheral embolization and thrombectomy products. Revenue from our Neuro business was $90.4 million in the fourth quarter of 2021, an increase of 13.3% reported and 14.1% in constant currency compared to the same period a year ago, with strong growth in U.S. neuro thrombectomy and international neuro access volume.
Gross margin in the fourth quarter of 2021 was 61.5% compared to 56.5% in the fourth quarter of 2020 and 63.1% compared to last quarter. The fourth quarter of 2020 included negative 900 basis point impact associated with product returns. Fourth quarter 2021 gross margin was lower than last quarter due to inflation, including labor rate adjustment and higher logistic costs as well as some product and regional mix impact.
Our accelerated investment in fixed costs, labor capacity and manufacturing capabilities in 2021 have allowed us to navigate labor shortages and supply chain disruptions. Looking forward, while these investments and inflation impacts will continue to be a headwind to gross margin, we could see a margin expansion opportunities in the second half of the year.
Now on to our operating expenses. In the quarter, we had nonrecurring research and development milestones and onetime expenses associated with Sixense acquisition and amortization of acquired intangible assets of $42.6 million, which was within the range of $35 million to $45 million that I previously shared on the last call. As such, the following fourth quarter financial metrics will represent non-GAAP financial results which exclude the impact from these nonrecurring and onetime expenses.
In the fourth quarter of 2021, our total operating expenses were $123 million or 16.3% of revenue compared to $96.1 million or 57.6% of revenue for the same quarter a year ago. Our research and development expenses for Q4 2021 were $19.4 million compared to $19.5 million in Q4 2020.
SG&A expenses for Q4 2021 were $103.5 million compared to $76.6 million for Q4 2020. The increase in operating expenses reflected the increase in head count, higher travel and in-person activities and investment in growth opportunities. We had operating income in the quarter of $2.5 million compared to operating loss of $1.7 million for the same quarter a year ago.
I will now summarize our full year performance. For the full year of 2021, our total revenue for the year was $747.6 million, which represents an increase of 33.4% reported and 32.6% in constant currency compared to full year 2020. Our geographic mix of sales in the year were 70.6% U.S. and 29.4% international. U.S. and International reported growth of 31.9% and 37.3%, respectively, compared to a year ago.
Revenue from our Vascular business for the full year of 2021 was $408.9 million, an increase of 52.7% reported and 52.3% in constant currency.
Revenue from our Neuro business for the full year of 2021 was $338.7 million, an increase of 15.7% reported and 14.6% in constant currency. Our gross margin for the year was 63.6% of revenue compared to 60.3% of revenue for the full year 2020. Excluding the 2021 impact from the nonrecurring research and development milestones, onetime expenses associated with Sixense acquisitions and amortization of acquired intangibles assets of $42.6 million that I previously discussed, and the 2020 nonrecurring expense associated with the development and product launch of Lightning 12 of $20.7 million that we discussed last year, we had nonoperating -- non-GAAP operating income for the full year of $35 million compared to a non-GAAP operating loss of $18.3 million for 2020.
Turning to cash flow and balance sheet. Accounts receivable increased by $13.9 million and net inventories increased by $5.2 million compared to third quarter 2021. Working capital level was consistent with volume trends. We ended the fourth quarter of 2021 with $254.9 million in cash and cash equivalents and marketable securities and no debt.
And now I'd like to turn the call over to Jason to discuss our 2022 guidance.
Jason Richard Mills - EVP of Strategy
Thank you, Maggie, and good afternoon, everybody. We are introducing revenue guidance for full year 2022 in the range of $860 million to $875 million, representing 15% to 17% growth over full year 2021 revenue of $747.6 million. The short-term macro challenges to which Adam referred in his remarks, were a factor in the first several weeks of this quarter as seen by other companies in our field.
Looking forward, we expect to launch new important products that will contribute to our Neuro and Vascular businesses toward the latter part of this year. In sum, we expect strong sequential revenue growth and also expect our quarterly revenue growth versus year ago periods to accelerate as we move through 2022, starting within the guidance growth range at the lower end and exiting toward the higher end.
Overall, consistent with our approach to studying guidance in the past, our 2022 revenue guidance represents our current use of our markets, timing of new product launches and other relevant inputs. I will now turn the call back to Adam for closing remarks.
Adam Elsesser - Co-Founder, Chairman, President & CEO
Thank you, Jason, Maggie and Jee. I would like to conclude our prepared remarks today with 2 key points. First, Penumbra is in one of the strongest positions it has ever been in. We have 6 large under penetrated markets, world-class technology and more innovation on the way. We acknowledge from past experience that the work ahead is hard and will take time, but the benefit to patients of opening up these new large markets is incredibly strong and our team is committed to these challenges.
Second, I'd like to end today by applauding our physician customers, the nurses and technicians, administrators and the entire staff in their hospitals. Obviously, the work they have done throughout the pandemic is amazing. However, we understand that the past 1.5 months with the severe staffing shortages in hospitals has tested even the strongest. All of our fatigue with the pandemic has not made it easier. I want you all to know that we admire your dedication, compassion and of course, just plain hard work. Thank you for what you've done, and I hope the months ahead bring a return to a more normalized schedule. Thank you.
Now thank you for your attention on the call today, and we'd like to open the call to questions. Operator, please go ahead.
Operator
(Operator Instructions) Our first question is from Robbie Marcus with JPMorgan.
Robert Justin Marcus - Analyst
Congrats on a good quarter. Adam, you mentioned new product launches in 2022. I lost track how many times you said it, but a lot in both stroke and vascular -- or Neuro and Vascular. I was hoping you could give us a little bit of color around the impact, the magnitude of these launches and a little finer point on when in the year we might start to see them?
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes, it's a great question. Let me -- without giving away things that it's premature to give away for obvious reasons, let me sort of calibrate. What we've talked about in a neuro -- we've obviously talked about Thunderbolt, we're going to do a trial. We said we have other things coming in the rest of that portfolio. So I want that to be understood. We're excited about constantly innovating in the other parts of our business as well as in stroke.
On the vascular side. It really comes down to the way we've always thought about our businesses, which is we continue to think about the spaces that we're in and how to make the products better and better and better. And we are very excited about some of the innovations that's coming. We think it will make the procedures, particularly in thrombectomy, easier, faster, more complete. And that's the goal, to move this field to the point where physicians can look at these patients that have clot, whether it's on their arterial side, DVT, PE, and even in the coronary, and just say, "Let's just take it out." And not have to think about it as some bigger question around trade-offs. So that's been our quest for many years. and these innovations fit within that very, very well.
Robert Justin Marcus - Analyst
Great. And just a quick follow-up. Adam, you had the CHEETAH study late last year in coronary. You're growing really well in vascular. How should we think about the impact of coronary? And any size of what it was in the quarter and how to think about it going into 2022 would be helpful.
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. So we haven't quantified the dollar per se other than to say the first and most obvious starting point is for the physicians that are still using manual aspiration in light of the CHEETAH data, that seems like the first obvious starting point, given how good that data was, and really in comparison. So that's folks who are already believing that aspiration is necessary in those patients. And then after that, of course, we'll move to the next group who may want to use aspiration but have been reluctant, but have looked at the CHEETAH data and believe that it is as compelling as we believe and other customers believe.
To answer the other part of your question. Obviously, we really had a part of a quarter with the CHEETAH data out there. It wasn't a full quarter. But there's no question that it has an impact. We did -- if you just were to look at the change from the beginning to the end, there was a change. But we expect that to continue throughout the year.
Operator
Our next question is from Larry Biegelsen with Wells Fargo.
Lawrence H. Biegelsen - Senior Medical Device Equity Research Analyst
Two for me, one on Thunderbolt one on REAL. Adam, we've done a bunch of checks on Thunderbolt and doctors seem pretty excited about the concept. So my questions are, what changed to lead you to do a study before approval? Any color on the trial design? How long do you think it will take to do the trial and file? It wasn't clear from your comments earlier, too, if you were including that in the 2022 launches. And I had one follow-up.
Adam Elsesser - Co-Founder, Chairman, President & CEO
Okay. Well, there's like 6 questions. So let me try to answer them all, and hopefully, I'll get the gist of it. So we've been working with the FDA. Obviously, I'm not yet prepared to lay out the exact trial design and the specific timing. But as I've said in the past, and I want to very clearly reiterate, this is -- we are really in a good position right now in stroke. The RED series is doing really well, and it's obviously a foundational part of using Thunderbolt. And so the ability to continue to bring that technology throughout this year to our customers, I think, is an important part of the strategy.
And then when the trial is over, and again, I'll -- as soon as I can, give you a more direct estimate on the timing. We'll bring that to the table as well. But even without that, and again, I'm incredibly excited about the work our team has done with that product. We have a lot of really strong runway with the RED series, and the reaction continues to be pretty extraordinary.
So I think we're -- as I think, pretty clearly alluded to, in a really, really strong position with our stroke franchise. When you add the Thunderbolt on top of that, which is not really included in this year's expectations, it just makes it even better. And you said you had a follow-up.
Lawrence H. Biegelsen - Senior Medical Device Equity Research Analyst
Yes. So just to be clear, so Thunderbolt is not included in the 2022 launches? Is that what you just said?
Adam Elsesser - Co-Founder, Chairman, President & CEO
That's right.
Lawrence H. Biegelsen - Senior Medical Device Equity Research Analyst
Okay. And then on REAL, Adam, any metrics you can share with us on the progress? I mean to date, you haven't shared anything on placements or anything like that. And what's the guidance assumed for REAL in 2022?
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. So we are not focusing on REAL as a big source of revenue in 2022. So that's just not part of the way we're thinking about that business. In the next year or so, our focus is on building the platform itself and then working to have the conversations with folks in the channel who would be using the REAL system for their patients as well as the third-party developers we want to host on the platform.
So what we're going to try to do as best we can. And really, we'll look to do this in the second half of the year, start to give some updates when we can about how those conversations are going, both with the users of the product and the third-party developers. And that really is the best way to measure whether what we're doing this the way we had anticipated or not. So again, not focusing on the short-term revenue as much as using this year, as I think we've said a couple of times, as a building block to build this, really, first ever platform in immersive healthcare.
Operator
Our next question is from Bill Plovanic with Canaccord.
William John Plovanic - Analyst
Two questions. The first is just on guidance. As we think about the first quarter and the level of impact that Omicron is having on a lot of folks, just how should we think about it? Is this something where it's significant impact to January, and so we're looking at a flattish quarter up or down? I mean how should we really think about Q1, is my first question.
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. Let me -- I'll give you sort of a quick -- sort of larger thought and Jason can you give more specifics to the second part of the question.
We called it out. As you know, we've done, I think, a really pretty good job in our company navigating COVID over the last couple of years. And there's no question that this round in January, particularly in the first part of January, the staffing issues, particularly, were very different. And we've said that before, and that was true.
There just weren't people able to be working at the same levels that is necessary. That being said, we -- that's that field is resolved, business is very strong. But I'll let Jason address the specifics to this quarter as best we can.
Jason Richard Mills - EVP of Strategy
Yes, Bill. Thanks for the question. And so we had an extraordinarily strong fourth quarter -- record quarter. If not for that record, I would expect that the first quarter would also -- would have been a record quarter. So we expect that sequentially, from the first to the fourth quarter, we will see sequential growth and accelerating year-over-year growth in the first quarter. Given what Adam talked about with respect to those first several weeks, we would expect the quarter and the first quarter to being down sequentially and then accelerating thereafter.
William John Plovanic - Analyst
Great. And then just a bigger picture thought. I mean Vascular has done very well for you. We've seen a lot of other players starting to eye up this vertical, whether it be through acquisitions or new product launches.
Just philosophically, how do you think about this as we move forward? Because it's almost like we're going from a 2-, 3-player market to all of a sudden, this is going to get pretty crowded over the next 12 to 24 months.
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. So first of all, I'll start with the most obvious, but important to say, I am really actually quite happy to see more and more people believing in this space, cares about it and wanting to help, really, a huge number of patients that need better technology and better treatment than they've been getting. So the validation that comes from other companies getting into this space, I think, is really important. And I think it will help speed up the adoption of single-session therapy. So that's important.
As it relates to our ability to stay ahead and keep innovating and "compete", we've done this for a while. As you know, we've done it in stroke for many, many years. And given where we are, we're starting at a totally different spot with Lightning than we did before in stroke. And we think we can even go further than that, as I alluded to, both in my prepared remarks and in the question.
So I think we're in a really good spot. We know the technologies that are out there. We feel good about where we are. And I think we, as a company, will stay in a really good place. That being said, again, it's great to see the attention being given to these patients. And I think that only helps us.
Operator
Our next question comes from Margaret Kaczor with William Blair.
Brandon Vazquez - Associate
This is Brandon on for Margaret. I wanted to focus first on -- just on the guidance. Last year, you had -- or in 2021, you had really outperformed the original guidance you gave. I can appreciate that COVID maybe limited the visibility you have. But it seems like last year, you had a little bit of a conservative guide and outperformed. And then, Adam, you had used the word accelerate a lot in the prepared remarks.
So as we're moving into the next year, I'm just curious how you're thinking about how you framed up the '22 revenue guidance maybe compared to how you did it in '21, and what that could mean for a potential upside as we move through the year.
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. Well, let me start with sort of reiterating how we think about guidance. We try to do -- provide guidance in the most accurate form possible. So we take everything we know almost a year out from the end of it, and do, I think, a pretty good job of planning and figuring out how things are going to go, including new products and so on. And that's how we did the guidance at the beginning of 2021, and that's how we're doing it now.
Obviously, we were fortunate in 2021, and we did outperform that. It would be premature to have looked back here from where we are today and discuss that. But I think it's the same exact metrics that we've used in the past. And Jason, do you want to add anything?
Jason Richard Mills - EVP of Strategy
Yes. I mean Brandon, thanks for the question. Maybe just a little bit of context. Obviously, 2020 the revenue was impacted for everybody by COVID, right? And 2021, a little less so, and the increase in revenue just out a dollar amount term in 2021 was well over $100 million. Notwithstanding a great 2021, we are expecting to -- at even the low point of guidance, over $100 million of incremental dollar revenue. And as we talked about, we have innovation about which we are excited for both the Neuro and Vascular businesses as well as what we expect in Immersive Healthcare that we have not included, to some extent, in this guidance, including Thunderbolt, as Adam mentioned to an earlier question.
So we feel really good about where the business is and where the guidance is. But as Adam mentioned, it factors in the contribution that we expect from those products that we anticipate having throughout the year.
Brandon Vazquez - Associate
Okay. And then we talked a little bit about international product launches coming up. Can you maybe rightsize us on which of your latest products, like the RED and Lightning catheters, are launched international already? And if not, which countries might be coming throughout the year? When we can expect those? And just remind us where I think you're international -- direct internationally, and where those products might be most impactful in the next, call it, 12 months?
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. Let's start with the RED series, and then maybe focus on Lightning. So RED is, at this point, with a few small countries really coming from the U.S. Obviously, the 2 large non-U.S. markets are Europe and Japan.
I did make those comments that, that is there for future international growth and potentially toward the back half of this year. And then Lightning is, again, with the exception of some smaller countries, primarily the U.S. today. It will be available sooner in Europe than the RED series. And we are excited about that.
There is some navigation around reimbursement in some of those countries. And it is not yet in Japan. But again, excited to eventually bring it there as well.
Operator
Our next question is from Joanne Wuensch from Citigroup.
Unidentified Analyst
This is Anthony on for Joanne. Just a quick one. The milestone related to Thunderbolt, can you just give us some more detail around what that was related to? Or what those milestones were?
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. So it's -- there was an understanding with the person who helped invent and work on that product that once we got through a certain milestone with working with the FDA, we would make this payment. That's the last payment -- or the only payment there is. Again, very similar to what happened with Lightning a couple of years ago. I think if you go back and you can look at it, I forget the exact quarter, but we did something very similar. So it's like that.
Operator
(Operator Instructions) Our next question is from David Rescott with Truist Security.
David Kenneth Rescott - Associate
Congrats on the strong end to the year. I want to start on, I guess, guidance for full year 2022. I guess how are you thinking about some of the growth in each of these different segments?
I know that neuro thrombectomy had a recall in the early part of 2021. And so the comps there are a little bit easier for neuro thrombectomy, had some structural tailwinds within that segment to likely pull forward into 2022. So I guess when you think about each of those segments, how are each of those playing into that overall growth guidance you gave for 2023?
And should we be thinking about whether or not there's any strength or acceleration specifically within each of those segments?
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes, it's a great question. So the way we look at our business is -- and the way we're talking about it, I think, shows that we have 6 large under penetrated markets, 5 in the interventional space that are going to drive our growth. This year, obviously, Immersive Healthcare is more an investment for future growth. And hopefully, in a few years, we'll be talking a lot about that driving growth.
But in the short term, we're looking at the 5 areas in interventional that are under penetrated. And then the sixth being the embolization business in peripheral that is continuing to grow, it's just not really under penetrated. We just continue to do well and take share.
All of them matter to our company's success. And I hope that we made that pretty clear. We're investing in all of them. We all have, in each one of them, sort of world-class technology right now, whether it's in stroke or in coronary with cataracts and the CHEETAH data, obviously, and PE and DVT and on the arterial side.
So it really isn't -- we're not looking at any particular one. They might slightly vary quarter by quarter based on the way certain conversations go with sales reps and hospitals, but it really is all of those that are going to drive our growth this year and into the future and then hopefully add the other large market in Immersive Healthcare on top of it. So again, not to belabor it, all of it is part of our success. And Jason, if you want to add to that?
Jason Richard Mills - EVP of Strategy
Yes. The only thing I'd add, David, is we're on really strong footing in both Neuro and Vascular businesses. So those 5 interventional markets that Adam referred to, 4 of them, as you know, are on the Vascular side. And then stroke on the Neuro side.
They're all going to contribute to our growth in 2022 and even beyond 2022 in a significant way. But obviously, the numbers are -- just 4 of them in Vascular and one of them on the Neuro side for 2022 is something to consider.
David Kenneth Rescott - Associate
Okay. That's helpful. Adam, you mentioned that RED series catheters have eclipsed the peak sales in 2019 from the prior catheter line. I guess what do you think has been the biggest driver of that?
And then when you think about that, kind of in the context of market share versus or sorry, market growth versus overall share recapture. I guess how should we think about those in the context of just the overall strength of the RED series catheter since that launch?
Adam Elsesser - Co-Founder, Chairman, President & CEO
Yes. It's a great question. So I think for us in 2021, a lot of that growth came from market share. There was some growth in the market, we think. But again, as I've talked about in the past, so much of that work is yet to really reengage. Everyone's ready, everyone wants to -- and the wave after wave last year, sort of kept people from doing some of the work necessary.
So with a little luck, we'll see that change in 2022. And I know I'm talking to customers, there's a lot of interest. They want to see it grow. They want to see more people treated. But a lot of our gains happened through share in 2021. And I think that will be true going forward as well. I think there's more share to keep gaining. Why -- the first part of the question is why or what caused that. These are just really extraordinary tools. The RED series is some of the best work we've ever done.
I'm incredibly proud of our R&D team and the innovation that they brought to it, especially given the circumstances following 2020. Couldn't be prouder and that is an incredibly important product. Again, it's not only important today by itself, but it is foundational for the future, given that it is part of what would be used with Thunderbolt after that, during the study and after the study.
Operator
There are no further questions at this time. Ms. Haymln-Harris?
Jee Hamlyn-Harris - IR Officer
Thank you, operator. On behalf of our management team, thank you all again for joining us today and for your interest in Penumbra. We look forward to updating you on our first quarter call.
Operator
This concludes today's conference call. You may now disconnect.