Connecting the Dots with Neal – Testosterone Induced erythrocytosis, elevated hematocrit and pathophysiology of clotting
Connecting the Dots with Neal – Testosterone Induced Erythrocytosis, elevated hematocrit and pathophysiology of clotting
Specialty-Specific Advanced Training
Last newsletter I alluded to the need for staying current with our recent medical literature as well as with pertinent cases, problems, and circumstances to assure only the best of care for our patients. There is no answer as to how much training one needs as there are no specialty-specific requirements for what we do, no CME requirements or board exam. As with any specialty, we can be smart but not adequately trained and thus may miss situations/diagnosis that a seasoned veteran would not. Unfortunately, there is no on the job training in our specialty, so I will attempt to provide the best standard of care from years of experience, but more so from an evidence-based medicine review. Since there is no defined amount of training we should receive, and just reading medical journal articles does not guarantee quality of care, I will review as much as possible to assist you in providing the best possible care based on recent medical literature with my own two cents of do this, don’t do that. Specialty-specific advanced training is what we are trying to provide to assure a higher quality of medicine, although much of what we do is outside the box of current medical society guidelines.
Interested in taking a deeper dive into the enthralling topic of Modern Chronic Disease Management other evidence-based solutions for Chronic Disease? Consider attending our 8th Annual Academic Summit: Root Cause Solutions to Modern Chronic Disease Management and Mitochondrial Health.
Testosterone Induced Erythrocytosis – Connecting the Dots
Last month I addressed MHT and blood clots. We constantly deal with the same blood clot issues/concerns in men, particularly when it comes to testosterone induced erythrocytosis. Years ago, a cardiologist decompensated when I stated the physiologic erythrocytosis (Hct > 54%) does not require phlebotomy despite the endocrine, hematology, and urology guidelines stating that it does. Remember that current medical society guidelines are frequently 20 years behind current science. Recent hematology literature documents that altitude induced, COPD induced, or testosterone induced erythrocytosis does not require treatment or phlebotomy. Here, read this! Then finally, this happened. Several studies have recently been published demonstrating that elevated H&H are associated with a DECREASED CVD morbidity and mortality, but only in those men treated with testosterone. My hematologist did not find these studies, or my comments, amusing. However, they just can’t grasp the difference between PCV and physiologic erythrocytosis because there has always been an assumption of an increased morbidity/mortality associated with an elevated Hct. However, this is in the general population but not in any male patient on testosterone therapy. And do you know why this is, rather, why is an elevated Hct associated with increased CVD morbidity/mortality in the general population? Well, it is not due to the increased Hct as we are always told and misled to believe as evidenced by the above erythrocytosis scenarios. The CVD risk is due to dyslipidemia, dysglycemia, HTN, and Syndrome X of diabetes that is responsible for the CVD morbidity and mortality, and not the Hct. OK, then, why is the Hct elevated? What pathology or physiology results in the increased Hct? OK, let’s connect the dots. What other major component is present with Syndrome X? Obesity. And what does that cause? Obstructive sleep apnea. And what does that cause? Hypoxia. And what does that cause? The OSA induced hypoxia triggers the erythropoiesis to counter the OSA induced hypoxia, which is necessary in order to maintain adequate serum oxygen saturation. Here, read this! The elevated Hct may be “associated” with the increased clotting risk, but association does not prove causation.
Elevated Hematocrit Does Not Cause ‘Thick Blood’
Sorry, elevated Hct does not cause thick blood, a term derived in order to explain the increased clotting risk of PCV and OSA. Conceptually, people will better understand the term “thick blood” in order to describe the increased blood clot risk due to thick, slow-moving blood. However, this concept is incorrect. Over 200 million people live above 7500 feet elevation and have excessive erythrocytosis with an H&H > 20/60. And there is no blood clot risk from “thick blood” in anyone that lives at altitude and that has excessive erythrocytosis, or thick blood. Here, read this! Don’t extrapolate the harm seen with OSA and PCV to physiologic erythrocytosis that occurs while on testosterone therapy or that is caused by living at altitude. We’ll review all the studies and data proving the safety and lack of harm of testosterone induced erythrocytosis in contrast to the harm of polycythemia from PCV or OSA. Finally, would you like to venture a guess as to the mechanism of altitude induced erythrocytosis? Hint: It’s hormonal. Answer: Testosterone! Yep, the altitude induced erythrocytosis is the result of the increased levels of testosterone seen in people that reside at altitude. The altitude induced hypoxia triggers a physiologic increase in testosterone levels which in turn stimulates red blood cell progenitor cells in the bone marrow resulting in the increased H&H seen at altitude. Altitude induced erythrocytosis, which is driven by physiologic increased levels of testosterone, does not cause any increase in blood clots nor does it require phlebotomy. Testosterone induced erythrocytosis at sea level also does not cause any increased risk in blood clots nor does it require phlebotomy. Note: The physiology of erythrocytosis both at altitude and at sea level is the same and that is via the stimulation and proliferation of red blood cell progenitor cells in the bone marrow by testosterone. This erythrocytosis has nothing to do with an increase in erythropoietin levels as erythropoietin levels are suppressed to zero in both circumstances. Here, read this!
Pathophysiology of Clotting – how and why to Reduce the Risk
Phlebotomy will reduce platelet counts and reduce clotting seen in patients with polycythemia vera. However, the hematology literature proves that the clotting issues in PCV are secondary to thrombocytosis and platelet dysfunction that persists even when H&H are lowered by phlebotomy. It is a platelet induced clotting disorder, not an RBC induced clotting disorder. Nevertheless, our peers continue to assert that PCV and physiologic erythrocytosis are the same, produce the same harm, and must be treated the same way by phlebotomy. However, the expert reviews and literature prove otherwise. The endocrine and urology literature prove no increase in blood clots (MI, CVA, DVT, PE) with testosterone induced erythrocytosis. The hematology literature and expert reviews state the same. Here, read this! We’ll review the pathophysiology of PCV to better understand the pathophysiology of clotting, and why and how to reduce the risk.
Case Study
Recently, Keith Nichols presented a case where a patient presented with erythrocytosis induced by testosterone therapy. The original baseline CBC demonstrated normal labs. After testosterone initiation, the CBC became abnormal with the typical erythrocytosis seen with testosterone use. However, Keith astutely picked up on the increased WBC and platelet counts which should not occur with testosterone therapy. Keith ordered the JAK-2 test which was positive and diagnostic for PCV. Had Keith not picked up on the abnormal lab results which were originally normal at baseline, the patient might have progressed to having a significant risk for a blood clot. The patient can still be treated with testosterone but will now be followed by hematology for cytoreductive therapy for clot prevention. We’ll review the cases and literature on PCV and contrast them with testosterone RCTs. You are aware that medical society guidelines state that a Hct > 54% is a contraindication to testosterone use. Prescribing testosterone under these circumstances could be problematic. So, how does one navigate around these guidelines to stay safe? Stay tuned.
Respectfully,
Neal
Interested in taking a deeper dive into the enthralling topic of Modern Chronic Disease Management other evidence-based solutions for Chronic Disease? Consider attending our 8th Annual Academic Summit: Root Cause Solutions to Modern Chronic Disease Management and Mitochondrial Health.
