Coagulopathy Associated with the use of Cephalosporin or Moxalactam Antibiotics in Acute and Chronic Renal Failure

Abstract

Nine azotemic patients who developed a coagulopathy associated with the use of either cephalosporin or moxalactam antibiotics are reported. The acute renal failure patients had neoplastic disorders and were considered to be septic at the time that multiple antibiotics were administered. Four of 5 chronic hemo- or peritoneal dialysis patients also received multiple antibiotics. Nevertheless, the coagulopathy seemed to be most closely associated with the administration of the cephalosporin. One patient received moxalactam as part of the combination therapy for diffuse pulmonary infiltration during renal transplant rejection. Bleeding occurred into the gastrointestinal tract in four patients, into the kidney-urinary tract in three patients, into vascular surgical sites in two patients, and one each into the pulmonary-bronchial and cerebral-ventricular systems. Five operations were performed in four patients: a nephrectomy for massive subcapsular hemorrhage with a prothrombin time that exceeded 100 seconds; arteriovenous graft complicated by post-operative bleeding associated with prolongation of the prothrombin time; elective femoral-popliteal bypass complicated by a prolonged prothrombin time, bleeding into the graft site, hypotension, and a subendocardial myocardial infarction; elective cholecystectomy complicated by a two unit bleed associated with a slightly prolonged prothrombin time, followed by elective femoral-popliteal bypass complicated by a fatal intercerebral bleed associated with a more than twice normal prothrombin time. Cephalosporins are most likely associated with Vitamin K deficiency. Moxalactam is more likely to be associated with platelet dysfunction. Monitoring of the prothrombin time for cephalosporins or the bleeding time for moxalactam is the most reliable way to prevent what may be rapid emergence of clinical bleeding in patients with renal failure.

Fat-Soluble Vitamins in Patients with Acute Renal Failure

“…Total osteocalcin was reduced as was carboxylated osteocalcin and thus, the percentage of carboxylation was decreased. In patients with ARF, deficiencies of vitamin K have only been reported during the use of certain cephalosporin antibiotics [28]. In patients on regular hemodialysis therapy it was shown that the vitamin K status is correlated with bone health with vitamin K deficiency present in patients with previous bone fractures [29].…”

Cefazolin Administration and 2-Methyl-1,3,4-Thiadiazole-5-Thiol in Human Tissue: Possible Relationship to Hypoprothrombinemia

“…ylation of glutamate residues in clotting factors by MTT, a sulfhydryl leaving group present in the structures of the cephalosporin antibiotics most often associated with hypoprothrombinemia (Black et al, 1983;Lipsky, 1983Lipsky, , 1984Lipsky et al, 1984). Although the structure of cefazolin also includes a potential sulfhydryl leaving group, MTD, and although MTD is also a potent in vitro inhibitor of the ␥-carboxylation of glutamate (Kerremans et al, 1985), hypoprothrombinemia is an unusual complication of cefazolin therapy (Lerner and Lubin, 1974;Clark et al, 1983;Dupuis et al, 1984). In addition, even though MTT can be easily detected in the tissues of subjects treated with cephalosporins which contain that structure (Black et al, 1983), MTD has not been reported to be present in human tissues after cefazolin exposure.…”

“…If MTD, like MTT, is a leaving group that is released in human tissues, and if MTD is, as previously reported, more potent than MTT as an inhibitor of the ␥-carboxylation of glutamate (Kerremans et al, 1985), why does hypoprothrombinemia occur so much less frequently after exposure to cefazolin than after exposure to cephalosporins that include MTT in their structures. It should be noted that cefazolin administration has been associated with hypoprothrombinemia, not only in patients (Lerner and Lubin, 1974;Clark et al, 1983;Dupuis et al, 1984) but also in vitamin K depleted rats (Lipsky FIG. 6…”

“…MTT inhibits the ␥-carboxylation of glutamic acid, a vitamin Kdependent reaction required for the formation of active clotting factors (Suttie, 1978). Hypoprothrombinemia has also been reported to occur, but much less frequently, after the administration of another cephalosporin, cefazolin (Lerner and Lubin, 1974;Clark et al, 1983;Dupuis et al, 1984). The structure of cefazolin also includes a heterocyclic sulfhydryl moiety, 2-methyl-1,3,4-thiaziazole-5-thiol (MTD) (Fig.…”