A 20-year-old man is brought to the emergency department due to fever, headache, and neck pain for the last day. He has no significant medical history. Temperature is 38.7 C (101.7 F), blood pressure is 120/72 mm Hg, pulse is 112/min, and respirations are 26/min. There is neck stiffness and a petechial rash on the trunk. Cerebrospinal fluid (CSF) analysis reveals the following:
| Glucose | 30 mg/dL |
| Protein | 180 mg/dL |
| Leukocytes | 1,500/mm3 |
| Neutrophils | 70% |
CSF gram stain shows gram-negative diplococci. In the emergency department, the patient's hemodynamic status deteriorates rapidly. Blood pressure drops to 80/50 mm Hg, and the venous access sites are oozing blood. Which of the following findings is most likely to be seen on this patient's peripheral blood smear?
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This patient's clinical findings (fever, headache, neck stiffness, rash) and cerebrospinal fluid analysis (elevated protein, low glucose, leukocytosis, gram-negative diplococci) are indicative of meningococcal meningitis; he subsequently developed septic shock (severe hypotension) while in the emergency department. His bleeding from venous puncture sites is highly suggestive of disseminated intravascular coagulation (DIC), a consumptive coagulopathy associated with sepsis, malignancy, trauma, and obstetric complications.
In DIC due to gram-negative sepsis, the coagulation cascade is activated by bacterial endotoxins, leading to widespread fibrin deposition and the consumption of coagulation factors and platelets, with eventual bleeding. Deposition of fibrin strands in small vessels can cause shearing of circulating erythrocytes, resulting in schistocytes (fragmented erythrocytes) on peripheral smear. Laboratory values in DIC typically show decreased platelet count and fibrinogen level and prolonged PT and PTT (indicating a consumption of coagulation factors).
(Choice A) Atypical lymphocytes are reactive lymphocytes with abundant, pale-blue cytoplasm and large nuclei. They are often seen in viral infections, particularly infectious mononucleosis.
(Choice B) Howell-Jolly bodies are round, dark, purple/red inclusions within erythrocytes. These represent nuclear fragments that are typically removed by the spleen; they can be seen in patients with splenectomy or reduced splenic function (eg, sickle cell).
(Choice C) Hypersegmented neutrophils are characterized by nuclei with ≥6 lobes. They are a feature of megaloblastic anemia (vitamin B12 or folate deficiency).
(Choice D) Reactive thrombocytosis is common in infection due to cytokine-mediated megakaryocyte proliferation and the release of platelets into the peripheral bloodstream. In contrast, patients with DIC have thrombocytopenia due to platelet consumption.
(Choice F) Severe pancytopenia is often seen in patients with aplastic anemia, which is characterized by destruction of hematopoietic stem cells and profoundly hypocellular bone marrow. Although patients with severe pancytopenia are at risk for bleeding, oozing from venipuncture sites in the setting of sepsis almost always indicates DIC.
Educational objective:
Disseminated intravascular coagulation is a common complication of gram-negative bacterial sepsis due to activation of the coagulation cascade by bacterial endotoxins, which leads to the formation of microthrombi. Peripheral smear shows fragmented erythrocytes (schistocytes) and thrombocytopenia. Laboratory tests show decreased fibrinogen levels and prolonged PT and PTT.