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A 53-Year-Old with an Elevated Hematocrit
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A 53-Year-Old with an Elevated Hematocrit
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Upload Date:
2022-02-28T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
♪ (music) ♪
CATHY: Hi, welcome to Harrison's Podclass where we discuss important concepts in internal medicine. I'm Cathy Handy.
CHARLIE: And I'm Charlie Wiener and we're coming to you from the Johns Hopkins School of Medicine. ♪ (music) ♪ This is Episode 17, A 53-year-old with an Elevated Hematocrit. The question reads: A 53-year-old man is sent to you for evaluation of an eleveated hematocrit found incidentally on lab testing. He was removing drywall in a house and cut his upper arm. A CBC before his arm was stitched revealed a hematocrit of 59% and a hemoglobin of 20 g/dl.
CHARLIE: What do you think so far, Cathy?
CATHY: Well, that's a high hematocrit and hemoglobin which has many causes. Generally, I think about if this is relative erythrocytosis, like from diuretic use or dehydration, or if this is an absolute erythrocytosis which can be from a primary cause, like a myeloproliferative disease, or from a secondary cause like hypoxia which is seen in people who have bad lung disease, or in people who have renal disease or some tumors, or even some drugs can cause it. But why don't you tell me more about the case?
CHARLIE: Okay. So, his physical examination reveals that he has a normal BMI, and a normal room air oxygen saturation of 95%. His blood pressure is 145 over 85, his heart rate is 70, and the only real notable finding on his physical examination is that he has an easily palpable spleen. We also find out that he has no past medical history, is a non-smoker, drinks rarely on social occasions, and is taking no medication. The patient reports that his last contact with a physician was 2-3 years ago and he recalls no abnormalities reported on blood testing then.
CHARLIE: What do you think based on that additional information?
CATHY: Well, do we have the rest of his CBC, like his white blood cell count and platelet count?
CHARLIE: Yeah, so we have a white blood cell count of 15,400 with a normal differential, and a platelet count of 445,000.
CATHY: So, the combination of erythrocytosis with the elevation of the white blood cell count and the elevation of platelets, and you also mentioned that he has a palpable spleen. All of that points to polycythemia vera as the cause of his elevated hemoglobin. The rest of his history doesn't point to any of the other causes that we mentioned before.
CHARLIE: Okay, so the question then asks: Which of the following is the next diagnostic step? a) arterial blood gas; b) erythropoietin or epo level; c) red blood cell mass; d) pulmonary function tests; or e) renal ultrasound.
CATHY: Well, the next step in his evaluation would be for measurement of the RBC mass because this will tell you if he has an absolute erythrocytosis or if it's just a relative erythrocytosis. Again, the clinical history suggests that it's absolute, but that's the first diagnostic measure that we would do.
CHARLIE: So, the answer to this question is c) red blood cell mass, but are the other tests of any use in a patient like this?
CATHY: Yeah, so usually if we find an elevated RBC mass, then we'll measure the erythropoietin or epo levels, and that helps us distinguish between polycythemia vera and other causes of polycythemia such as kidney cancer or lung disease. You could also consider an arterial blood gas to look for hypoxemia, and sometimes you see that in people who have bad lung disease. Obviously, pulmonary function test would also be helpful in that case. And ultrasounds and PFTs, though, would be later tests in the evaluation.
CHARLIE: Okay. So, we suspect this patient has polycythemia vera. Tell us more about that.
CATHY: Well, it's a clonal disorder that involves multipotent hematopoietic progenitor cells in which phenotypically normal red cells, granulocytes, and platelets accumulate in the absence of any recognizable physiologic stimulus. The etiology isn't really known but most people have a mutation in the auto-inhibitory pseudokinase domain of the tyrosine kinase, JAK2, and that replaces a valine with a phenylalanine. So, typically the way this gets reported is a V617F mutation in the JAK2 gene, and that causes constituitive kinase activation.
CATHY: It seems to have a central role in the pathogenisis of polycythemia vera so, we typcially send for a JAK2 mutational analysis in anybody who we suspect has PV. Because almost 95% of patients will express this mutation.
CHARLIE: Do other patients with other myeloproliferative disorders have JAK2 mutations also?
CATHY: Yes. It's also seen in primary myelofibrosis and then also essential thrombocytosis but not necessarily to the same degree.
CHARLIE: And that becomes important because new drugs are being developed to target these specific mutations. Okay, back to our patient. How do patients with P. vera typically present?
CATHY: So, the symptoms are generally related to the high hemoglobin, so people can come in with pruritis or gout because of hyperuricemia. Sometimes they'll have splenomegaly or fatigue, and then also sometimes symptoms related to splenomegaly, like abdominal fullness and early satiety. In general, it's a pretty indolent disease and most people will still live pretty long lives, but one of the major complications is thrombosis, which is strongly correlated with the degree of erythrocytosis.
CHARLIE: How do the thromboses or the hyperviscosity present?
CATHY: So, that can present like clots. So, sometimes people will get neurologic symptoms such as vertigo or tinnitus. Sometimes people can have visual disturbances or even TIA-like symptoms.
CHARLIE: Do strokes happen?
CATHY: Yes, that can also happen, too.
CHARLIE: Alright, so actually there's a follow-up question here. And this question says: The patient had a red blood cell mass that was markedly elevated and was also found to have a low erythropoitin level confirming the diagnosis of P. vera. Which of the following is recommended therapy? a) aspirin; b) hydroxyurea; c) imatinib; d) phlebotomy to maintain a hemoglobin less than 14 g/dl; or e) warfarin.
CATHY: Treatment of polycythemia vera is generally risk adapted. Low-risk patients would be those who are less than 60 years old, who have no history of any thrombotic events, and those who are older or who have any history of clots are considered high-risk. And our patient being 53 years old, with no history that we've heard of of any thrombotic events, he would be considered to have low-risk disease. So, for that patient, the cornerstone of treatment is the correction of the abnormal blood viscosity that's associated with the high red cell volumes.
CATHY: That can really be done with just simple phlebotomy because that serves to initially reduce the hyperviscosity by bringing the red cell mass into the normal range and also allows for the expansion of the plasma volume.
CHARLIE: So, the answer to this question is d) phlebotomy to maintain hemoglobin less than 14 g/dl, is that correct?
CATHY: Yup, that's right. And just to go over the other options-- Aspirin therapy is a reasonable choice for this patient and a lot of consensus guidelines like the NCCN guidelines or in the Blood Journal the How I Treat articles will recommend using low-dose aspirin. Anticoagulation, though, like warfarin, is not used prophylactically. Imatinib is a tyrosine kinase but that's used to treat CML which this patient doesn't have. Other two therapies that are used in patients who have polycythemia vera but wouldn't be used in this case are hydroxyurea and ruxolitinib.
CATHY: Hydroxyurea is cytoreductive and occasionally used in very high-risk patients, but it's not a long-term medication and definitely not first-line. Ruxolitinib is a kinase inhibitor that inhibits JAK1 and JAK2 signalling and is also an approved therapy, but it's really only used for those with higher risk disease that have been refractory for other therapies. So again, I wouldn't use it as an initial therapy in our patient.
CHARLIE: Great. So, the teaching points in these two questions relate to the evaluation of an elevated hematocrit or hemoglobin, the diagnosis of polycythemia vera, and treatment strategies for risk-adapted strategy.
CATHY: And if you want to read more about this you can check out Harrison's chapter on Oncology and Hematology. ♪ (music) ♪