Setting: ED
CC: “My urine is dark.”
VS: BP: 92/50 mm Hg; P: 125 beats/minute; T: 102°F
HPI: A 43-year-old man with a recent diarrheal episode for 5 days arrives at the ED. He says that dark urine and fatigue developed over the last day. He has been febrile. There is some blood in the stool. His skin has been yellow.
Initial Orders:
Normal saline
CHEM-7
LFTs
CBC
UA
Blood cultures
Chest x-ray
When a patient is febrile and tachycardic with a systolic blood pressure <100 mm Hg, give fluids while waiting for the initial set of laboratory test results. Nothing is more important than hydration in a hypotensive patient. Although there are no respiratory symptoms, on CCS it is acceptable to order a chest x-ray on every patient with a fever.
PE:
Abdomen: mild diffuse tenderness
Chest: clear
Neurological: normal
Fever =
• UA
• Blood cultures
• Chest x-ray
Move the clock forward to get laboratory test results:
CHEM-7: blood urea nitrogen (BUN) 34 g/dL; creatinine 1.8 mg/dL
CBC: hematocrit 32%; platelets 78,000/μL
UA: hemoglobin present; no bilirubin
Blood cultures: normal
Chest x-ray: normal
Liver: bilirubin 5 mg/dL, 80% indirect; LDH elevated
What is the most appropriate next step for this patient?
a. Check the laboratory test results for hemolysis, hydrate, and observe.
b. Start ciprofloxacin.
Answer a. Check the laboratory test results for hemolysis, hydrate, and observe.
Do not start antibiotics in this patient. With hemolysis, thrombocytopenia, and renal insufficiency, HUS is possible. Antibiotics can worsen HUS.
When antibiotics kill organisms, they release toxin, potentially worsening HUS.
Orders:
CBC
Renal and LFTs
Peripheral smear
Stool culture on sorbitol MacConkey agar
Sorbitol MacConkey agar is the specific test for Escherichia coli O157:H7.
Escherichia coli O157:H7 slowly ferments sorbitol.
Repeat laboratory test results come back in 30 minutes in the ED:
CHEM-7: BUN 44 g/dL; creatinine 2.1 mg/dL
CBC: hematocrit 30%; platelets 52,000/μL
Peripheral smear: schistocytes, fragmented cells
Do not order either antibiotics or platelets. Platelets in HUS and TTP can worsen the disorder by creating more clumping out of platelets in small blood vessels.
Escherichia coli O157:H7 elicits a Shiga toxin.
HUS and thrombotic thrombocytopenic purpura (TTP) originate from a deficiency of a disintegrin and metalloprotease with thrombospondin domain 13 (ADAMTS 13) (Figure 2-7).
Figure 2-7. Pathogenesis of thrombotic thrombocytopenic purpura (TTP). Normally, the ultra-high-molecular-weight multimers of von Willebrand factor (vWF) produced by the endothelial cells are processed into smaller multimers by a plasma metalloproteinase called ADAMTS 13. In TTP, the activity of the protease is inhibited, and the ultra-high-molecular-weight multimers of vWF initiate platelet aggregation and thrombosis. (Reproduced with permission from Longo DL, et al. Harrison’s Principles of Internal Medicine, 18th ed. 2012, www.accessmedicine.com.)
You move the clock forward 12 hours and recheck the laboratory test results because rising BUN and creatinine levels, as well as a dropping platelet count, are very distressing. You will want to give platelets as the count drops, especially if it goes below 50,000/μL, but do not do it. They clump out and precipitate in the brain and kidney.
On the second hospital day, do an “Interval History.” The patient is reported as developing confusion. You review the repeat laboratory test results:
CHEM-7: BUN 58 g/dL; creatinine 2.4 mg/dL
CBC: hematocrit 26%; platelets 44,000/μL
ADAMTS 13 dissolves von Willebrand factor (vWF). Without it, platelets stay excessively aggregated and adherent.
With worsening renal function, confusion, fever, and intravascular hemolysis, and decreasing platelet concentration, the patient is now defined as having TTP. You must not give platelets. Instead, order plasmapheresis when TTP is severe, or as in this case, worsening.
Plasmapheresis in TTP is not done to remove something from the patient’s blood; it is done to add ADAMTS 13 from normal plasma.
Orders:
Move the patient to the intensive care unit (ICU).
Repeat CBC, BUN, and creatinine tests.
Consult hematology (remember, consultants on CCS never tell you what to do).
Order plasmapheresis.
ADAMTS 13 cleaves vWF, freeing platelets from each other.
Plasmapheresis adds ADAMTS 13 back to the patient.
In the ICU after plasmapheresis, the patient’s confusion resolves. The platelet count starts to rise and the BUN and creatinine levels stop decreasing. Sorbitol MacConkey culture grows Escherichia coli O157:H7.
The case ends with the patient still in the ICU. If your case continues, transfer the patient back to the hospital floor 1 to 2 days after the BUN, creatinine, and platelet counts improve.
In TTP, 100% of patients have low platelet counts and hemolysis, but only 50% of the patients have neurologic problems (Figure 2-8).
Figure 2-8. Thrombocytopenia, Thrombotic Thrombocytopenic Purpura (TTP). Blood film. Markedly decreased platelets (absent in this field) and red blood cell shape changes characteristic of TTP. (Reproduced with permission from Lichtman MA, et al. Lichtman’s Atlas of Hematology. 2007, www.accessmedicine.com.)