Name:
A 44-Year-Old with Altered Mental Status and Fever
Description:
A 44-Year-Old with Altered Mental Status and Fever
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T00H06M22S
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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.
CATHY: Welcome to Episode 20: A 44 Year Old with Altered Mental Status and Fever.
CHARLIE: Here's the opening. A 44-year-old obese woman undergoes elective cholecystectomy for cholelithiasis. She takes an antidepressant but is otherwise healthy.
CATHY: So far that doesn't sound too abnormal. Women get gallstones more commonly than men, and obesity is one of the risk factors for the development of gallstones.
CHARLIE: Okay, then let's move on. Post-operatively she does well and is discharged to home after three days. However, two days after discharge, she develops altered mental status and fever and is brought to the emergency department by her family. In the emergency department, her temperature is 103 degrees Fahrenheit. Pulse is 127 per minute. Blood pressure's 110 over 78, and she has a normal respiratory rate and oxygen saturation. Physical examination is notable for confusion and a well-healed surgical incision.
CHARLIE: Routine chemistries are drawn and show normal electrolytes with the exception of a BUN of 80 milligrams per deciliter and a creatinine of 2.5. Her CBC shows her white cell count is 17,300, her hematocrit is 30%, and her platelet count is 25,000. Of note, at discharge her CBC was normal.
CATHY: So, she has the acute onset of fever and neurologic symptoms after her elective surgery. To summarize the labs, we heard that she has acute renal failure, leukocytosis, anemia and thrombocytopenia. Did she have any coagulation studies or a peripheral smear because one consideration is that she could have sepsis with DIC, but it's reassuring that the surgical sight looks good. Although, she could also have an infection in an intra-abdominal source.
CHARLIE: So, her coagulation studies in the ED are normal. A peripheral blood smear shows schistocytes and confirms low platelets without clumping.
CATHY: So, the normal coagulation studies make DIC due to sepsis less likely, but the presence of schistocytes on the peripheral smear suggests that she has a microangiopathic hemolytic anemia.
CHARLIE: So, how does that change your thinking?
CATHY: A microangiopathic hemolytic anemia with thrombocytopenia, fever and neurologic findings are consistent, if not classic for the diagnosis of TTP, or thrombotic thrombocytopenic purpura. So, that's the classic pentad and includes fever, neurologic findings, renal failure, hemolytic anemia and thrombocytopenia. It's rarely seen these days happening all together. So, in the absence of the pentad, you shouldn't be discouraged about thinking about TTP, and it really should be on the differential for any patient who has a microangiopathic hemolytic anemia and thrombocytopenia.
CHARLIE: What is the mechanism of TTP, and who gets it?
CATHY: So, typically high molecular weight multimers of von Willebrand factor are produced by the endothelial cells and are processed into smaller multimers by a plasma metalloprotease called ADAMTS13. In TTP, the activity of ADAMTS13 the protease is inhibited, and the ultra high molecular weight multimers of von Willebrand factor initiate platelet aggregation, and they form clots and shear erythrocytes. So, this causes the hemolytic anemia and the microthrombi that cause the rest of the clinical findings that were mentioned above.
CHARLIE: What typically precipitates TTP?
CATHY: Most cases are acquired and usually there is some trigger. In this case, it's probably surgery. It's obviously not a common complication of elective cholecystectomies, but definitely can trigger TTP. Infection, pancreatitis, pregnancy have also been associated, and some drugs can cause TTP, too. The drugs I typically think of as being associated tend to be the immunosuppressive agents, some chemotherapies or antiplatelet drugs, but she isn't taking any of those.
CHARLIE: Okay, so let's get to the question. The question asks: "Which of the following statements regarding her condition is true?" Option A says, a low activity of metalloprotease ADAMTS13 is likely present in her peripheral blood. Option B is, plasma exchange is unlikely to be helpful. Option C says, her condition was likely caused by an occult E. coli O157:H7 infection. Option D says, her condition is more common in men than women.
CHARLIE: Option E says, untreated mortality from this condition is low.
CATHY: As I alluded to before, the answer is A. So, you can send an ADAMTS13 activity level which can take a while to come back. So, it's not something you can generally use to make the diagnosis overnight, but that activity level will be low in patients who have TTP.
CHARLIE: What do you think about the other answers though? Why are they wrong?
CATHY: Well, it's more common in women compared to men, so that excludes D. And B and E are also the opposite of what is true. E. coli infection is associated with the development of HUS, or hemolytic uremic syndrome, and it's seen predominantly in children.
CHARLIE: What's the role of plasma exchange in TTP?
CATHY: The mortality of TTP untreated is very high, close to 90%, and that's primarily from microvascular thrombosis, and multi-organ failure. Plasma exchange is the mainstay of treatment, and it's done as soon as you make the diagnosis. Again, this is often before even the ADAMTS13 result is back. And it's repeated until the platelet count is normalized, and the signs of hemolysis are resolved.
CHARLIE: Okay, so therefore, Option B, which says plasma exchange is unlikely to be helpful is actually, again, the opposite of what is true. Right?
CATHY: That's right.
CHARLIE: Okay, so the teaching point here is that the classic pentad of TTP, that being fever, neurologic symptoms, renal failure, hemolytic anemia, and thrombocytopenia is classic for TTP, although is seldom seen in any real patient. TTP can be precipitated by surgery, or other drugs, or other precipitating events. And the diagnostic test is measurement of a low ADAMTS13 activity in the serum. Plasmapheresis is the treatment of choice and should be initiated as soon as you suspect the diagnosis.
CATHY: And you can read more about TTP in Harrison's chapter on Disorders of the Kidney and Urinary Tract, or in the section on Hematopoietic Disorders in Oncology and Hematology. ♪ (music) ♪