Thrombocytopenia in the Sepsis Syndrome: Role of Hemophagocytosis and Macrophage Colony-stimulating Factor

• Published in: The American journal of medicine Vol. 103; no. 2; pp. 114 - 120
• Main Authors: François, B., Trimoreau, F., Vignon, P., Fixe, P., Praloran, V., Gastinne, H.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1997; Elsevier; Elsevier Sequoia S.A
• Subjects: Adult; Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood; Blood Cells - pathology; Bone Marrow - pathology; Bone Marrow - physiopathology; Emergency and intensive care: infection, septic shock; Female; Humans; Incidence; Intensive care medicine; Macrophage Colony-Stimulating Factor - blood; Male; Medical disorders; Medical research; Medical sciences; Middle Aged; Multiple Organ Failure - complications; Odds Ratio; Phagocytosis; Prospective Studies; Risk Factors; Sepsis - blood; Sepsis - complications; Sepsis - physiopathology; Severity of Illness Index; Thrombocytopenia - blood; Thrombocytopenia - microbiology; Thrombocytopenia - physiopathology; Human; Evaluation; Pathophysiology; Cytokine; Hemopathy; Infection; Prospective; Sepsis syndrome; Thrombocythemia; Myeloproliferative syndrome; Hemophagocytic syndrome; Etiology; Macrophage colony stimulating factor; Resuscitation
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/S0002-9343(97)00136-8

BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients with the sepsis syndrome, but its mechanisms frequently remain undetermined. Hemophagocytosis has been reported as a cause of thrombocytopenia in various diseases. This prospective study was designed to assess: (1) the incidence of hemophagocytosis in patients suffering from both the sepsis syndrome and unexplained thrombocytopenia, and (2) the circulating level of the macrophage-colony-stimulating factor (M-CSF) according to the presence or absence of hemophagocytosis. METHODS: Fifty consecutive patients diagnosed with both the sepsis syndrome and thrombocytopenia of undetermined origin were studied. Hemophagocytosis was diagnosed based on microscopical examination of sternal bone marrow aspiration by two independent observers. Serum M-CSF concentrations were measured in each patient and compared with levels of a normal population (n = 59). Causes and severity of sepsis syndromes as well as serum M-CSF levels were compared beween patients with and without hemophagocytosis. RESULTS: Hemophagocytosis was diagnosed in 32 patients (64%). Mean serum M-CSF levels were increased in patients when compared with normal subjects (539 ± 141 versus 208 ± 82 IU/mL: P <0.001), and higher in patients with than without hemophagocytosis (580 ± 145 versus 457 ± 89 IU/mL: P = 0.01). Multiorgan dysfunction and infection were independent risk factors of hemophagocytosis (odds ratio = 31.3 and 6.8, 95% confidence interval (CI) = 5.4 to 177.6 and 1.0 to 47.4, P <0.0001 and P = 0.03, respectively). CONCLUSIONS: Hemophagocytosis is a frequent cause of unexplained thrombocytopenia in patients with severe sepsis syndrome. Our results suggest that M-CSF is overproduced in the sepsis syndrome, particularly when hemophagocytosis is present. The role of M-CSF in the initiation and development of hemophagocytosis remains to be determined.