Ep 165: A 63-Year-Old with an Elevated Hemoglobin

This episode reviews the workup and differential diagnosis of a patient with an elevated hemoglobin (polycythemia), discovered on routine labs during an evaluation for fever and diarrhea.

Read more on this topic in Harrison's chapters:

Anemia and Polycythemia

Polycythemia Vera and Other Myeloproliferative Neoplasms

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

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[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to Harrison's Podclass. Today's patient is a 63-year-old with an elevated hemoglobin. Cathy, today's patient is a 63-year-old man who was traveling in the Caribbean and presented to a local emergency room with fever and diarrhea. As part of their evaluation, they checked a CBC, which showed a normal white cell count a normal platelet count, but his hemoglobin was 17 g/dL. They treated him with antibiotics for his gastroenteritis, which improved very quickly, and they told him to see a physician in the US on his return. 

[Dr. Handy] Well, my first question is, where in the Caribbean was he? And was he living on top of a mountain? Because that hemoglobin is quite abnormal. 

[Dr. Wiener] Good point. No, he was at the beach. I know you're going to ask for more history, so here it goes. He lives in Delaware, and he works as a software engineer. His past history is notable for hypertension, hyperlipidemia, and obstructive sleep apnea. He's never had an MI or a stroke. His medications are losartan and atorvastatin. He's variably compliant with his nocturnal CPAP, but since he works remotely and on his own schedule, he does not identify that as a problem. Notably, he's a lifelong smoker and he smokes a pack of cigarettes daily, as well as three to four cigars per week. He's tried many times to quit with counseling and medications, but has not been successful to date. 

[Dr. Handy] Lots to do here. When were his last set of labs? And then, tell me about his physical exam. 

[Dr. Wiener] Well, he's overweight with a BMI of about 30 and a ruddy complexion, but his vital signs are normal, and the only abnormality on physical examination is you think you palpate a spleen tip. 

[Dr. Handy] All right, I'm patting myself on the back for that one. The ruddy complexion is consistent with the high hemoglobin. Tell me about his labs. 

[Dr. Wiener] Yeah, his last labs were about 18 months ago, and at that time his CBC was unremarkable, but you repeat it now, and his white blood cell count is 13,000, his platelets are 500,000, his hemoglobin is 19, his hematocrit is 57%, and his MCV is normal. 

[Dr. Handy] Okay, so he has polycythemia, which is defined as an increase in the hemoglobin above normal. He also has a mild elevation of his white cell count and platelets. Concern that a patient's hemoglobin level may be abnormally high is usually triggered at 17 g/dL for men and 15 g/dL for women. Hematocrit levels above 50% in men or 45% in women may be abnormal. Hematocrits over 60% in men and over 55% in women are almost invariably associated with an increased red cell mass. Given that most automated CBC machines actually measure the hemoglobin concentration and then calculate the hematocrit, hemoglobin levels may be a better index. 

[Dr. Wiener] What are the concerns about an elevated hemoglobin in terms of signs or symptoms? 

[Dr. Handy] Patients with polycythemia may be asymptomatic or experience symptoms related to the increased red cell mass or underlying disease process that leads to the increased red cell mass. The dominant symptoms from an increased red cell mass are related to hyperviscosity and thrombosis, and that can be both venous and arterial, because the blood viscosity increases logarithmically at hematocrits above 55%. Manifestations of hyperviscosity include neurologic symptoms such as vertigo, tinnitus, headache, and visual disturbances. Hypertension is often present as well. 

[Dr. Wiener] So what's next for this patient? 

[Dr. Handy] Can you get me an EPO level? 

[Dr. Wiener] I thought the next step was measuring the RBC mass, the red blood cell mass. 

[Dr. Handy] Well, classically, the first step in a patient with an elevated hemoglobin was to document the presence of an increased red cell mass using chromium-labeled autologous red blood cells. If the red cell mass was normal, the patient had spurious or relative polycythemia. If the red cell mass was increased, the next step was to measure serum EPO levels. Practically, though, RBC mass is seldom measured now. It's more efficient to just jump to obtaining an EPO level. 

[Dr. Wiener] Okay, well, your patient's EPO level is low, and that brings us to the question. The question asks, in this patient, which of the following is the most likely cause of his polycythemia? Option A. is cigarette smoking; option B. is COPD; option C. is obstructive sleep apnea; option D. is polycythemia vera; or option E. is renal cell carcinoma. 

[Dr. Handy] Okay, well, first off, all of the things you listed can cause an elevated hemoglobin, but, in this case, the low EPO is consistent only with polycythemia vera. So the answer is D. That also confirms my palpating the spleen tip and his mildly elevated white count and platelets. 

[Dr. Wiener] Remind us a little bit about P. vera. 

[Dr. Handy] It's the most common myeloproliferative disorder and manifests typically with a clonal elevation of phenotypically normal red cells, as well as white cells and platelets. Patients are typically discovered incidentally by lab studies, like our patient, but may present with hyperviscosity or thrombosis symptoms. They may also have aquagenic pruritus symptoms related to hepatosplenomegaly, such as easy bruising, epistaxis, GI bleeding, digital ischemia, Budd-Chiari syndrome, or abdominal venous thrombosis. 90-95% of patients with polycythemia vera have a mutation in JAK2. 

[Dr. Wiener] Okay, our patient's EPO level was low, which led you to the answer. What if the EPO level had been high? 

[Dr. Handy] If serum EPO levels are elevated, one needs to distinguish whether the elevation is a physiologic response to hypoxia or related to autonomous EPO production. Patients with low arterial O2 saturations, less than 92%, should be further evaluated for the presence of heart or lung disease if they're not living at high altitude. In addition to diagnoses such as COPD, obstructive sleep apnea, or interstitial lung disease, remember, any condition that gives you a right-to-left intracardiac or extracardiac shunt may lead to hypoxemia and polycythemia. 

[Dr. Wiener] What about smokers? 

[Dr. Handy] They may have polycythemia from an elevated carboxyhemoglobin level. And remember, cigars are also a culprit in smokers' polycythemia. 

[Dr. Wiener] And if they have an elevated EPO and no evidence of hypoxemia? 

[Dr. Handy] Those patients have a source of EPO production that is not responding to the normal feedback inhibition. Hepatomas, uterine leiomyomas, and renal cancer, or cysts may present this way. 

[Dr. Wiener] And do you treat the polycythemia? 

[Dr. Handy] I mentioned that hyperviscosity symptoms can occur when the hematocrit is over 60%. In those patients, while you're looking for the underlying cause, phlebotomy is effective in lowering the hemoglobin and hematocrit to forestall symptoms or thrombophilia. 

[Dr. Wiener] Okay, so today's teaching points are that an elevated hemoglobin or polycythemia can be primary, as in P. Vera, or secondary, as in hypoxemia. An EPO level can help distinguish those causes. Patients with a hematocrit greater than 60% may derive symptomatic benefit from phlebotomy. 

[Dr. Handy] And you can find this question and other questions like it in Harrison's Self-Review. And if you want to read more about this topic, you can check out the Harrison's chapter on anemia and polycythemia, as well as the Harrison's chapter on polycythemia vera and other myeloproliferative neoplasms. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. Thanks so much for listening. 

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