Another Blood donation thread

[Stewie]

Would sleep apnea be considered an additional risk factor for thrombotic events?

Yes it can though promotion of fibrinogenic activation which provokes platelet aggregation, in which can trigger the clotting cascade.

 

[Rex Feral]

Very thought-provoking Rex. Could I get your thoughts on animal models showing very clearly that supra-physiological levels of HCT lead to endothelial dysfunction, thrombogenicity, and cardiovascular risk.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225673/

I get that the phlebotomy as a 'treatment' for excessive erythrocytosis has severe drawbacks and is overused in current practice. But there is very solid evidence from animal studies that supra-physiological levels of HCT itself is also detrimental (and I have not seen any good arguments for why we can't extrapolate to humans in this context). So in severe cases (HCT 56+), I believe that phlebotomies do have a place, though more care needs to be taken in terms of watching iron status, platelet reaction, coagulation status, etc.

Well, you're comparing mice with primary polycythemia to men with secondary erythrocytosis. You are still focused on numbers and I've already tried to explain it's not the numbers but the cause. The mice were bred to have overexpression of EPO (primary polycythemia) and their HCT reached 80-90%. When is the last time you saw a person with a HCT of 90%? How many people do you know that have been bred to overexpress EPO? What are your thoughts on that study now?

You believe phlebotomy should be performed at HCT > 56? Based upon what? How did you derive this number? Any rationale or evidence at all that you can present to support your "belief?" That's the problem with adopting beliefs out of thin air you see.

Now I get to ask you, show me the evidence that T/AAS induced secondary erythrocytosis increases risk for CV events. If you think it's necessary to treat HCT > 56 show me why. To steal a phrase from John Romano, show me the bodies. I first competed in 1987. I sold steroids professionally and was even incarcerated for it. I have been deeply entrenched in bodybuilding and if this was happening I would have seen it. I've seen many people's blood work in the past 30 years. My HCT has been 54-60 for at least 32 years and I've never been phlebotomized therapeutically. Literally for a good 25-30 years roughly of widespread steroid use, 1980-2005/2010, no one gave a shit about HCT and no one ever thought of being phlebotomized. Anywhere from 25-50% of these literally hundreds of thousands of people should have needed phlebotomy according to you. So there should be a lot of these people that dropped dead of a stroke and it should be easy to show me a few of them. When TRT became ubiquitous, quack TRT doctors started treating numbers with phlebotomy because they were scared of the number despite any evidence that the number caused any harm and despite any evidence that the intervention improved the risk of harm. Non evidence based practice. Now, people like you think that it's a good idea based upon nothing because of this. Real doctors, like urologists, have since seen the fallacy in this and the move is towards abandoning phlebotomy and in 10 years it won't be done anymore.

What Romano means by show me the bodies in medical parlance is that the epidemiological evidence does not match your claims. Honestly the only people I can think of that dropped dead of a stroke adopted the practice of phlebotomy. Not one person I can think of through the 80s, 90s, early 2000s when no one cared about their HCT dropped dead of a stroke from "thick blood." This reminds of the guy at Harvard who claims that casein is a carcinogen due to whatever opiate agonist is in there. It looks plausible on paper, but when you look at epidemiologic evidence it becomes obvious that his hypothesis is complete horse shit based upon the number of people who consume casein.

Show me the strokes that cause you to treat your HCT with phlebotomy and show me the evidence that phlebotomy decreases risk in T/AAS induced secondary erythrocytosis. If it's such a strong belief for you, then it should be easy. If you can come up with nothing, you should question your process of belief adoption.

Rex.

 

[Rex Feral]

Very thought-provoking Rex. Could I get your thoughts on animal models showing very clearly that supra-physiological levels of HCT lead to endothelial dysfunction, thrombogenicity, and cardiovascular risk.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225673/

I get that the phlebotomy as a 'treatment' for excessive erythrocytosis has severe drawbacks and is overused in current practice. But there is very solid evidence from animal studies that supra-physiological levels of HCT itself is also detrimental (and I have not seen any good arguments for why we can't extrapolate to humans in this context). So in severe cases (HCT 56+), I believe that phlebotomies do have a place, though more care needs to be taken in terms of watching iron status, platelet reaction, coagulation status, etc.

From your own little mice study that you obviously didn't read.

"Furthermore, no thromboembolic complications have been reported in these mice (Ruschitzka et al. 2000). Apparently, their cardiovascular and microvascular systems are able to adjust to the substantial increase in systemic Hct"

That is with an 80-90% HCT.

Rex.

 

[MyNameIsJeff]

Well, you're comparing mice with primary polycythemia to men with secondary erythrocytosis. You are still focused on numbers and I've already tried to explain it's not the numbers but the cause. The mice were bred to have overexpression of EPO (primary polycythemia) and their HCT reached 80-90%. When is the last time you saw a person with a HCT of 90%? How many people do you know that have been bred to overexpress EPO? What are your thoughts on that study now?

You believe phlebotomy should be performed at HCT > 56? Based upon what? How did you derive this number? Any rationale or evidence at all that you can present to support your "belief?" That's the problem with adopting beliefs out of thin air you see.

Now I get to ask you, show me the evidence that T/AAS induced secondary erythrocytosis increases risk for CV events. If you think it's necessary to treat HCT > 56 show me why. To steal a phrase from John Romano, show me the bodies. I first competed in 1987. I sold steroids professionally and was even incarcerated for it. I have been deeply entrenched in bodybuilding and if this was happening I would have seen it. I've seen many people's blood work in the past 30 years. My HCT has been 54-60 for at least 32 years and I've never been phlebotomized therapeutically. Literally for a good 25-30 years roughly of widespread steroid use, 1980-2005/2010, no one gave a shit about HCT and no one ever thought of being phlebotomized. Anywhere from 25-50% of these literally hundreds of thousands of people should have needed phlebotomy according to you. So there should be a lot of these people that dropped dead of a stroke and it should be easy to show me a few of them. When TRT became ubiquitous, quack TRT doctors started treating numbers with phlebotomy because they were scared of the number despite any evidence that the number caused any harm and despite any evidence that the intervention improved the risk of harm. Non evidence based practice. Now, people like you think that it's a good idea based upon nothing because of this. Real doctors, like urologists, have since seen the fallacy in this and the move is towards abandoning phlebotomy and in 10 years it won't be done anymore.

What Romano means by show me the bodies in medical parlance is that the epidemiological evidence does not match your claims. Honestly the only people I can think of that dropped dead of a stroke adopted the practice of phlebotomy. Not one person I can think of through the 80s, 90s, early 2000s when no one cared about their HCT dropped dead of a stroke from "thick blood." This reminds of the guy at Harvard who claims that casein is a carcinogen due to whatever opiate agonist is in there. It looks plausible on paper, but when you look at epidemiologic evidence it becomes obvious that his hypothesis is complete horse shit based upon the number of people who consume casein.

Show me the strokes that cause you to treat your HCT with phlebotomy and show me the evidence that phlebotomy decreases risk in T/AAS induced secondary erythrocytosis. If it's such a strong belief for you, then it should be easy. If you can come up with nothing, you should question your process of belief adoption.

Rex.

Thanks for the reply. I think you are a bit quick to dismiss the animal study.

I don't think the difference between AAS-induced (i.e. secondary) erythrocytosis and erythrocytosis due to EPO overexpression is relevant here, since the primary mechanism through which AAS increase HCT is increased EPO expression.

And yes, an HCT of 80 is not something we'd see in AAS users. But that's not the point. The research establishes that there is such a thing as 'too high' HCT levels. Clearly a 'safe' level would be somewhere below 80, but how much lower do you need to go? Also, the study did look at lower levels, see figure below. There seems to be a linear relationship between ESL thickness and HCT levels. But again, we don't know at which point the ESL is so thin that endothelial damage and thrombogenicity become an issue.

With that being said, your point about the (lack) epidemiological evidence is well taken. There are obviously some limitations to those studies, for example highlanders being genetically adapted to high HCT. But I will read that literature with an open mind. I may well be wrong and HCT levels around 60 are harmless (if BP is controlled etc.). On a more anecdotal note, the deaths of EPO-abusing cyclists does suggest that high HCT may be a real issue. So I would rather be overly cautious before telling the bodybuilding community that they can ignore their sky high HCT levels.

 

[Rex Feral]

I should add personal experience perhaps for another perspective. I have had many tests performed, most last year at 48 after 31 years of pretty much continuous use. A few months here and there, 3-4 months off maybe 3-4 times in 31 years and 1-2 months per year off otherwise. Which is really not long enough to do much of anything to decrease HCT especially of susceptible to increase as we know. Basically I just get busy with work and quit training for a month and I don't take any drugs, or I get injured or something and can't train hard for 1-3 months and I don't take any drugs. Otherwise, if I'm training I'm taking drugs x 32 years and have had an elevated HCT x 32 years. My first use at 17 I was given a doctor who prescribed steroids to me and would do blood work every time he'd write a prescription. So I have 32 years of blood work with an elevated HCT. My last was 18.4/58.1. I had full body ultrasound, with heart size, spleen size and carotids being most significant for erythrocytosis. Heart and spleen were normal size, people with primary polycythemia have enlarged spleens and cardiomegaly. Carotids were wide open with no measurable stenosis. Cornoary calcium score was zero. My BP Sunday morning was 102/67. I have never had HTN. I'm 5'8 210-230 10-15% depending what I'm doing.. Heaviest was 246.

Rex.

 

[Rex Feral]

Thanks for the reply. I think you are a bit quick to dismiss the animal study.

I don't think the difference between AAS-induced (i.e. secondary) erythrocytosis and erythrocytosis due to EPO overexpression is relevant here, since the primary mechanism through which AAS increase HCT is increased EPO expression.

And yes, an HCT of 80 is not something we'd see in AAS users. But that's not the point. The research establishes that there is such a thing as 'too high' HCT levels. Clearly a 'safe' level would be somewhere below 80, but how much lower do you need to go? Also, the study did look at lower levels, see figure below. There seems to be a linear relationship between ESL thickness and HCT levels. But again, we don't know at which point the ESL is so thin that endothelial damage and thrombogenicity become an issue.

With that being said, your point about the (lack) epidemiological evidence is well taken. There are obviously some limitations to those studies, for example highlanders being genetically adapted to high HCT. But I will read that literature with an open mind. I may well be wrong and HCT levels around 60 are harmless (if BP is controlled etc.). On a more anecdotal note, the deaths of EPO-abusing cyclists does suggest that high HCT may be a real issue. So I would rather be overly cautious before telling the bodybuilding community that they can ignore their sky high HCT levels.

I didn't see any support for your beliefs still? You still haven't presented one case to support any of your claims yet I'm supposed to debate you just because you believe something. Please dude. Stupid shit like this is why I quit coming around here. If you want to argue, support yourself. Simple.

Rex.

 

[Rex Feral]

You're also putting words into my mouth which is not cool. I never said ignore your sky high HCT, I said quit or get over it i.e. accept the risk. This is precisely what the guidelines say, T is to be stopped at HCT > 52 or > 54 depending in the US or Canada. It doesn't say anything about performing phlebotomy, it never did. Phlebotomy is not indicated for secondary erythrocytosis. You are attempting to change practice guidelines based on zero evidence. You are precisely what the study authors in Canada were afraid of and stated in their conclusion, the fact that some quacks performed some phlebotomy that wasn't indicated made you believe that it did some good.

Rex.

 

[Black Beard]

So I have hemocrat of 18 and Doc wants it down. I've done the double cell and regular donations but not often enough. They alow blood donations of only once every 8 weeks but i may need to do it more often. Being that we have 2 blood banks in my area I can switch between them.
Question is, how often can I SAFELY DONATE a pint?

How much testosterone are you taking?


Have you re-tested levels after the donations? Is 18 after the double reds?


Thicker blood/high hematocrit has been linked to increased levels of intra-arterial plaque in HUMANS, specifically men. This IS one of the biggest risk factors for heart attack/stroke.

https://www.ncbi.nlm.nih.gov/m/pubmed/12826926/


The plaque can break off and cause the heart attack/stroke or cut off blood supply to heart/brain causing heart attack/stroke.


You are wise to be concerned about your high hemoglobin levels/hematocrit. 18 isn't too bad though and might be okay long-term, so you are on the right track. Would you happen to have your HCT level? It's a percentage usually range somewhere from 35-52%.

 

[MyNameIsJeff]

From your own little mice study that you obviously didn't read.

"Furthermore, no thromboembolic complications have been reported in these mice (Ruschitzka et al. 2000). Apparently, their cardiovascular and microvascular systems are able to adjust to the substantial increase in systemic Hct"

That is with an 80-90% HCT.

Rex.

Yeah I read that part, but I also read this one:

The ESL thinning that we observed allows platelets and leukocytes to come in closer proximity to the vessel wall, which provides those blood components with greater access to the endothelium, and may undermine the important barrier role of the ESL, making the vascular interface a more thrombogenic and proinflammatory surface than under conditions of normal haematocrit. Based on estimates of the stiffness of the ESL derived from several modelling studies (Damiano & Stace, 2002, 2005; Weinbaum et al. 2003), it is not surprising that de novo capture of leukocytes from the free stream is rare in post-capillary venules with an intact 500 nm-thick ESL (Smith et al. 2003). However, compression of the ESL to ∼100–200 nm would increase the likelihood that selectin molecules and their receptors on the endothelium come in close proximity frequently enough to allow elevated adhesive interactions, more capture events from the free stream, and more leukocyte rolling. Thus, the ESL thinning observed in tg6 mice could lead to a more chronically inflamed state for microvascular endothelium. Such inflammation could, in turn, lead to the release of cytokines, and to increased platelet aggregation and thrombogenicity. This concept is supported by findings showing that the increased incidence of leukocyte adhesion and thrombosis in polycythaemia vera is related to vascular damage and endothelial dysfunction (Neunteufl et al. 2001).

So while no thromboembolic complications arose in Ruschitzka et al. (2000), there is solid theoretical evidence that ESL thinning is prothrombogenic. Hence, in the presence of additional risk factors (e.g hereditary hypercoagulability), HCT will likely increase the risk of thromboembolic events.

Also in the text is the following:

In this context, a reduction in ESL thickness, though beneficial from a haemodynamic perspective, may be detrimental to vascular health. It is evident from experimental observations that the vessel walls in tg6 mice are extremely thin and fragile. Microscopic investigations have revealed signs of impaired vessel integrity, progressive endothelial inflammation and multiple organ degeneration in aged tg6 mice (Heinicke et al. 2006; Ogunshola et al. 2006). This, ultimately, may contribute to the substantial reduction in mean life span of tg6 mice compared to wild-type control littermates, i.e. 7.4 versus 26.7 months (Wagner et al. 2001). Thusfar, however, no study has reported either on the possible mechanisms of the putative endothelial degeneration associated with excessive erythrocytosis or on the possible effects of Hct changes on the integrity of the blood–endothelium interface.

Clearly a massive decrease in life span, multiple organ degeneration, and endothelial inflammation are not good. Clearly these changes in tg6 mice are due to elevated HCT. Granted, at an HCT of 80. But it's not like this damage would disappear if they had an HCT of 79. there is some point between an HCT of 50 and 80 that can be considered safe. Neither you nor I know that level.

The epidemiological evidence can be helpful to figure out what that level could be. But it is far from perfect. As you know, one cannot draw causal inference from observational studies.

You gave your personal perspective, which certainly is interesting. But there's also anecdotal evidence in the other direction. Not to put words in his mouth, but I believe Dante regularly warns of the risks of uncontrolled HCT, and he has seen/supervised many AAS athletes, thereby accumulating lots of anecdotal evidence. He also likes to point out the waves of professional cyclists dying while abusing EPO.

Between 1987, shortly after athletes are believed to have begun using EPO, and 1990, 20 young Belgian and Dutch cyclists died.

One of them was Johannes Draaijer, a 27-year-old racer from the Netherlands who finished 20th in the 1989 Tour de France. In February 1990 he died in his sleep of a heart blockage a few days after completing a race in Italy. An autopsy did not specify the cause of death – he had been passed fit to ride by a doctor – but in a television interview afterwards, his widow said she hoped his fate would serve as a warning to other athletes who take the drug.

Between 1989 and 1992, seven young Swedish orienteering enthusiasts died mysteriously and there was another cluster of cyclist deaths in 2003-4, when eight aged under 35 died.

https://www.theguardian.com/sport/2...t-is-it-and-has-anyone-died-as-a-result-of-it

You're also putting words into my mouth which is not cool. I never said ignore your sky high HCT, I said quit or get over it i.e. accept the risk. This is precisely what the guidelines say, T is to be stopped at HCT > 52 or > 54 depending in the US or Canada. It doesn't say anything about performing phlebotomy, it never did. Phlebotomy is not indicated for secondary erythrocytosis. You are attempting to change practice guidelines based on zero evidence. You are precisely what the study authors in Canada were afraid of and stated in their conclusion, the fact that some quacks performed some phlebotomy that wasn't indicated made you believe that it did some good.

"accept the risk". So there is a risk of having high HCT? How, then, is it unreasonable to seek (albeit experimental) treatment (i.e. phlebotomy) in order to try to reduce that risk? Of course phlebotomization, the treatment, has its own side effects.

So we have to make a risk/reward assessment: Will the overall risk of thromboembolic events decrease or increase following phlebotomization? That answer depends on the initial HCT value and the treatment protocol (frequency etc). Will the benefits of reduced HCT in terms of improved endothelial function and reduced mortality outweigh the side effects of phlebotomization? All that depends on the initial HCT value. If the initial HCT value is high enough, then the benefits will outweigh the costs.

Absent any RCTs to establish a safe long-term HCT level, we have to rely on theoretical reasoning and extrapolation from animal studies, as well as epidemiological data. The former should outweigh the latter if the data quality is insufficient. Hence why so many physicians (and many expert hematologists, not just TRT peddlers) make the informed decision that the benefits of bloodletting outweigh the risks for TRT users.

 

[Black Beard]

Yeah I read that part, but I also read this one:



So while no thromboembolic complications arose in Ruschitzka et al. (2000), there is solid theoretical evidence that ESL thinning is prothrombogenic. Hence, in the presence of additional risk factors (e.g hereditary hypercoagulability), HCT will likely increase the risk of thromboembolic events.

Also in the text is the following:


Clearly a massive decrease in life span, multiple organ degeneration, and endothelial inflammation are not good. Clearly these changes in tg6 mice are due to elevated HCT. Granted, at an HCT of 80. But it's not like this damage would disappear if they had an HCT of 79. there is some point between an HCT of 50 and 80 that can be considered safe. Neither you nor I know that level.

The epidemiological evidence can be helpful to figure out what that level could be. But it is far from perfect. As you know, one cannot draw causal inference from observational studies.

You gave your personal perspective, which certainly is interesting. But there's also anecdotal evidence in the other direction. Not to put words in his mouth, but I believe Dante regularly warns of the risks of uncontrolled HCT, and he has seen/supervised many AAS athletes, thereby accumulating lots of anecdotal evidence. He also likes to point out the waves of professional cyclists dying while abusing EPO.


https://www.theguardian.com/sport/2...t-is-it-and-has-anyone-died-as-a-result-of-it


"accept the risk". So there is a risk of having high HCT? How, then, is it unreasonable to seek (albeit experimental) treatment (i.e. phlebotomy) in order to try to reduce that risk? Of course phlebotomization, the treatment, has its own side effects.

So we have to make a risk/reward assessment: Will the overall risk of thromboembolic events decrease or increase following phlebotomization? That answer depends on the initial HCT value and the treatment protocol (frequency etc). Will the benefits of reduced HCT in terms of improved endothelial function and reduced mortality outweigh the side effects of phlebotomization? All that depends on the initial HCT value. If the initial HCT value is high enough, then the benefits will outweigh the costs.

Absent any RCTs to establish a safe long-term HCT level, we have to rely on theoretical reasoning and extrapolation from animal studies, as well as epidemiological data. The former should outweigh the latter if the data quality is insufficient. Hence why so many physicians (and many expert hematologists, not just TRT peddlers) make the informed decision that the benefits of bloodletting outweigh the risks for TRT users.

This is my reasoning as well.


A mix of "better safe than sorry" with some extrapolation from animal AND human studies, with some anecdotes sprinkled on top.

 

[nothuman]

I'm confused about something.

Is the rise in hematocrit from the cyclists that used EPO the same as people like us who just use T/AAS, but just a higher increase from the EPO using cyclists? Or are they raising H/H from different pathways?

I've asked Stewie and Dante this question (they gave opposite answers) and from reading this thread, I feel like I am getting different answers from everyone.

 

[Black Beard]

I'm confused about something.

Is the rise in hematocrit from the cyclists that used EPO the same as people like us who just use T/AAS, but just a higher increase from the EPO using cyclists? Or are they raising H/H from different pathways?

I've asked Stewie and Dante this question (they gave opposite answers) and from reading this thread, I feel like I am getting different answers from everyone.

"The mechanisms by which testosterone stimulates erythropoiesis are poorly understood. It has been postulated that testosterone induces erythrocytosis by stimulating erythropoietin production (13,14). The effects of testosterone on erythropoietin levels have been inconsistent in previous studies (15,16). Testosterone also acts directly on the bone marrow, increasing the number of erythropoietin-responsive cells (5,17). The soluble transferrin receptor (sTfR), involved in the intracellular transport of iron, correlates directly with the degree of erythropoietic activity in the bone marrow (18), and sTfR levels have been used as a marker of erythropoietic activity (18,19). We determined whether the increases in hematocrit during testosterone therapy are associated with dose-related increases in erythropoietin and sTfR levels. We also assessed whether differences in hemoglobin and hematocrit responses in older and younger men receiving graded doses of testosterone enanthate could be explained by age-related differences in the changes in erythropoietin and sTfR."


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266950/

 

[MyNameIsJeff]

I'm confused about something.

Is the rise in hematocrit from the cyclists that used EPO the same as people like us who just use T/AAS, but just a higher increase from the EPO using cyclists? Or are they raising H/H from different pathways?

I've asked Stewie and Dante this question (they gave opposite answers) and from reading this thread, I feel like I am getting different answers from everyone.

Testosterone-induced increase in hemoglobin and hematocrit is associated with stimulation of EPO and reduced ferritin and hepcidin concentrations. We propose that testosterone stimulates erythropoiesis by stimulating EPO and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022090/

 

[nothuman]

"The mechanisms by which testosterone stimulates erythropoiesis are poorly understood. It has been postulated that testosterone induces erythrocytosis by stimulating erythropoietin production (13,14). The effects of testosterone on erythropoietin levels have been inconsistent in previous studies (15,16). Testosterone also acts directly on the bone marrow, increasing the number of erythropoietin-responsive cells (5,17). The soluble transferrin receptor (sTfR), involved in the intracellular transport of iron, correlates directly with the degree of erythropoietic activity in the bone marrow (18), and sTfR levels have been used as a marker of erythropoietic activity (18,19). We determined whether the increases in hematocrit during testosterone therapy are associated with dose-related increases in erythropoietin and sTfR levels. We also assessed whether differences in hemoglobin and hematocrit responses in older and younger men receiving graded doses of testosterone enanthate could be explained by age-related differences in the changes in erythropoietin and sTfR."


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266950/

Well this talks about how testosterone may boost EPO production but I'm not sure it really explains direct EPO injections that the cyclists who died were doing (unless I'm missing something)

 

[nothuman]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022090/

So in other words from what I am reading here, it seems like direct testosterone injections increase H/H the same way direct EPO injections would?

 

[MyNameIsJeff]

Well this talks about how testosterone may boost EPO production but I'm not sure it really explains direct EPO injections that the cyclists who died were doing (unless I'm missing something)

In cyclists, they inject EPO, which then increases HCT and Hb.

In bodybuilders, we inject AAS, which then increase EPO, which then increases HCT and Hb.

So in other words from what I am reading here, it seems like direct testosterone injections increase H/H the same way direct EPO injections would?

Yes, I believe so.

 

[Black Beard]

Well this talks about how testosterone may boost EPO production but I'm not sure it really explains direct EPO injections that the cyclists who died were doing (unless I'm missing something)

You asked how it differs. It's in there.

 

[nothuman]

Thanks I understand now

 

[MyNameIsJeff]

"Furthermore, we trust that the urge to correct any abnormal laboratory data by a therapeutic intervention should be tempered by consideration of the risk-benefit ratio of any such intervention. The routine practice of phlebotomy for elevated hematocrit, with its inevitable iron deficiency (which leads to inhibition of PHD2, increased HIF, and increased erythropoietin) and potential detrimental thrombotic effects, should be re-evaluated."

Victor R. Gordeuk, Nigel S. Key, Josef T. Prchal
Haematologica April 2019 104: 653-658; Doi:10.3324/haematol.2018.210732

Rex.

From your own little study that you obviously didn't read:

Although absence of hydroxyurea therapy77 and high leukocyte counts78 are independent correlates of thrombotic risk in PV, the rate of thrombosis was greater in the higher hematocrit group whether or not the patient was treated with chemotherapy and whether or not the white blood cell count was elevated.74 Thus, we cannot rule out the possibility that hematocrit may contribute to increased risk of thrombosis in PV along with other PV-associated prothrombotic factors.

The authors are really trying hard to interpret the data in line with their story...

Therefore, optimum oxygen transport with increased blood volume occurs at a higher hematocrit value than with normal blood volume,18,19 and a moderate increase in hematocrit may be beneficial despite the increased viscosity. This may not hold true when there is a more pronounced increase in hematocrit, a circumstance in which high viscosity causes reduced blood flow19,20 that may be responsible for cerebral and cardiovascular impairment in some high-altitude dwellers21 or in patients with severely elevated hematocrit.22,23

Hmm, I thought high hematocrit was harmless? It's almost like thrombosis risk isn't the only concern...

Also interesting:

The European Collaboration on Low-Dose Aspirin in the Polycythemia Vera study (ECLAP), which included 1,638 patients from 12 countries and 94 centers, found no difference in thrombotic complications for patients with hematocrits within the range of 40–55%; however, there were not enough subjects with hematocrits >55% for evaluation.

So there is absolutely no evidence for your claim that HCT>55 is safe or that phlebotomy would be counterproductive in those patients.

If you read a bit about the nature of PV and CE, then you will see that the reservations about phlebotomy in those conditions don't necessarily translate to AAS-induced secondary erythrocytosis. In PV, it has only been shown that phlebotomy is inferior to chemotherapy (not to control), but that can be easily explained by the latter also lowering leukocyte count, which in itself is associated with thrombosis. But that's not an issue in the case of AAS use.

The you have the epidemiological evidence from CE patients. Even the authors of that study caution against interpreting their data as evidence that phlebotomies increase thrombosis risk, due to massive omitted variable bias. Yet, Gordeuk et al (2019) rely on it very heavily in explaining their edgy little story.

So overall, the evidence that phlebotomy increases thrombosis risk in AAS-induced secondary erythrocytosis is very very weak. The evidence that elevations of HCT above 55 has a number of negative health effects is strong. Any reasonable physician will conclude that the risk-reward ratio of phlebotomization in AAS users is favorable when HCT exceeds the reference range of 54.

 

[maldorf]

Here is a study

"In a category-based analysis, a hematocrit in the upper 20th percentile was found to be associated with a 1.5-fold increased risk of venous thrombosis. However, the important question that is not answered by this study is whether the relation is causal, or whether it can be explained by the presence of other diseases that cause both a high hematocrit and venous thrombosis."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817018/


"In conclusion, Brækkan and colleagues have performed an interesting, large-scale study into the relation between high levels of hematocrit and the risk of venous thrombosis. They convincingly demonstrated a dose-response relation between level of hematocrit and risk of venous thrombosis. However, questions remain on the causal interpretation and the clinical consequences of their results."

So there seems to be a link between the two, but we do not know yet if the relationship is causal or not. It certainly is a risk factor though, and chances are there are other factors involved too.

My hematologist keeps my hemoglobin down to about 15, but I almost died from a clot and we found I have factor 2. https://www.stoptheclot.org/learn_more/prothrombin-g20210a-factor-ii-mutation/

Even on coumadin, he wants to keep mine down. My doc is a very well respected oncologist/hematologist. My circumstances however aren't the usual. "A change in the prothrombin gene is present in 2-4% (or 1 in 50 to 1 in 25) of Caucasians, and is more common in individuals of European ancestry. " There are other clotting factors too like factor 5.