Hypoprothrombinemia in Febrile, Neutropenic Patients with Cancer: Association with Antimicrobial Suppression of Intestinal Microflora

Abstract

Serial, twice-weekly prothrombin times were determined in 108 febrile, granulocytopenic patients with cancer who were prospectively randomized to receive empiric antimicrobial therapy with moxalactam plus ticarcillin (M/T) or tobramycin plus ticarcillin (T/T). Thirty of 54 patients given M/T and 13 of 54 patients given T/T developed prothrombin times that were ⩾2 sec beyond control values (P < .001) after a mean of 6.5 days of antimicrobial therapy. Serious bleeding episodes were more frequent in the group given M/T than in that given T/T (10 and two patients, respectively; P ⩽ .05). Serial quantitative stool cultures revealed that both Escherichia coli and Bacteroides species were suppressed by ⩾5 log₁₀, in eight of nine patients given M/T and in three of nine given T/T (P < .05, Fisher's exact test). A significant reduction of the population of E. coli and Bacteroides fragilis, organisms that are major producers of bacterially synthesized menaquinones, was associated with a high incidence of hypoprothrombinemia. These observations support the hypothesis that menaquinones may play an important physiological role in the maintenance of blood coagulation during episodic dietary deficiency of phylloquinone.