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[Dr. Handy] Hi, welcome to Harrison's PodClass, where we discuss important concepts in internal medicine. I'm Cathy Handy. [Dr. Wiener] And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine. [Dr. Handy] Welcome back, everyone, to Harrison's PodClass. Today's episode is a 28-year-old woman with sickle cell disease.
[Dr. Wiener] So, today's patient is a 28-year-old who presents to you for follow-up after she's had a recent hospitalization for a sickle cell pain crisis. Before we get to the question, let's start today by talking a little bit about the pathophysiology about sickle cell disease, since I think that'll help us with today's question. [Dr. Handy] Okay, the sickle cell syndromes are caused by a mutation in the beta-globin gene that changes the sixth amino acid from glutamic acid to valine.
Hemoglobin S polymerizes reversibly when deoxygenated to form a network of fibrous polymers that stiffen the red blood cell membrane, increase viscosity, and cause dehydration due to potassium leakage and calcium influx. [Dr. Wiener] So these are the changes that produce the characteristic red blood cell sickle shape, right? [Dr. Handy] Right, and sickled cells lose the pliability needed to traverse small capillaries.
They also possess altered or sticky membranes that are abnormally adherent to the endothelium of small venules. These abnormalities provoke unpredictable episodes of microvascular vaso-occlusion and premature red blood cell destruction in the liver and the spleen. They also clog small capillaries and venules, causing tissue ischemia, acute pain, and gradually end organ damage. And this veno-occlusive component usually dominates the clinical course.
[Dr. Wiener] Okay, well, let's get back to our patient for a moment. So, her clinical course has been characterized by having, on average, about one hospitalization a month for painful crises over the past year. And she's also had at least one episode of an acute chest syndrome within the last year. So, tell me more about painful crises. [Dr. Handy] So, these recurrent painful episodes are the most common clinical manifestation and their frequency and severity can vary greatly.
Pain can develop almost anywhere in the body, it may last from a few hours to a couple of weeks. Now, repeated crises requiring hospitalization can correlate with reduced survival in adult life, suggesting that these episodes are associated with accumulation of chronic end organ damage. [Dr. Wiener] So given that this woman has had 12 episodes in the past year, she is in that really worrisome prognostic category, right? [Dr. Handy] Yeah. [Dr. Wiener] What provokes the painful crises?
[Dr. Handy] Well, we don't always know, but some provocative factors include infection, fever, excessive exercise, anxiety, abrupt changes in temperature, hypoxia or hypertonic dyes. [Dr. Wiener] Okay, and what about acute chest syndrome? [Dr. Handy] So that's a distinctive manifestation characterized by chest pain, tachypnea, fever, cough and arterial oxygen desaturation.
Acute chest syndrome is thought to be due to in-situ sickling within the lung and/or the bone marrow microemboli, producing pain and temporary pulmonary dysfunction. Often, it's difficult or impossible even to distinguish among other possibilities. Pulmonary infarction and pneumonia are the most frequent underlying or concomitant conditions in patients with this syndrome. [Dr. Wiener] I could see where that would be confusing. Okay. Let's talk about her labs.
On review of her labs, you note that she has a hemoglobin of 9.8 g/dL, a hematocrit of 28%, an MCV of 88, and an MCH of 30. Are these typical? [Dr. Handy] Yes, so most patients with sickling syndrome suffer from hemolytic anemia with hematocrits from 15% to 30%, and significant reticulocytosis. It is a microcytic or normocytic normochromic anemia. Anemia was once thought to exert protective effects against vaso-occlusion by reducing blood viscosity.
However, natural history and drug therapy trials suggest that actually an increase in the hematocrit and feedback inhibition of reticulocytosis might be beneficial, even if it's at the expense of slightly increased blood viscosity. Granulocytosis is also common. [Dr. Wiener] Okay, well, we've finally gotten to the question, and the question's going to ask about her peripheral blood smear.
It asks, on review of her peripheral blood smear, in addition to seeing sickled red blood cells, what other characteristic finding would you expect to see? And the options are, A. burr cells; option B. is Howell-Jolly bodies; option C. is schistocytes; option D. is spherocytes; and option E. is target cells. [Dr. Handy] Okay, well, the key to answering this question is to know that repeated microinfarction can destroy tissues having microvascular beds prone to sickling.
So splenic function is frequently lost within the first 18 to 36 months of life, and in the absence of a functional spleen, nuclear remnants are not culled from the red cells and remain as small homogeneously staining blue inclusions on Wright's stain, called Howell-Jolly bodies. So the answer to the question is B. you would likely see Howell-Jolly bodies. [Dr. Wiener] And importantly, the presence of those Howell-Jolly bodies probably tell you that this patient is functionally hyposplenic.
[Dr. Handy] Correct, and we have a couple other episodes that talk about clinical consequences of that. [Dr. Wiener] Cool, so where do you see the other abnormalities? Let's go through them quickly. [Dr. Handy] Burr cells are typically seen in uremia and show multiple spiny projections.
Schistocytes are helmet-shaped cells that reflect microangiopathic hemolytic anemia or fragmentation on an artificial heart valve, for example, these are also commonly seen in disseminated intravascular coagulation, or DIC. Spherocytes are small dense red blood cells that lack central pallor and biconcavity, they are typically seen in hereditary spherocytosis, but can also be seen in other autoimmune hemolytic anemias.
Target cells have a bull's eye appearance and are seen in thalassemia and in liver disease. [Dr. Wiener] Okay, great. So the teaching point in this case is that sickle cell disease is characterized by recurrent veno-occlusive episodes, which, clinically, most often manifest in the form of painful crises, and repeated microinfarction can also lead to the loss of a functional spleen.
On peripheral smear, it is common to find sickled red blood cells along with Howell-Jolly bodies, which are small homogeneously staining blue inclusions that are the nuclear remnants of RBCs. [Dr. Handy] And you can learn more about this in Harrison's chapter on disorders of hemoglobin but also in the chapter on anemias and polycythemia. [upbeat outro music] [Dr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill.
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