vitamin-k-semiquinone-radical and Diverticulitis

BACKGROUND Cefmetazole (CMZ), containing an N-methyl-tetrazole-thiol (NMTT) side chain, is a therapeutic option for diverticulitis in Japan. Cephems containing an NMTT, a methyl-thiadiazol, and a thiadiazolethiol side chain are known to induce coagulation disorders. CASE REPORT A 76-year-old woman developed hypoprothrombinemia after receiving oral levofloxacin (LVFX) 250 mg q24h for 2 days followed by intravenous CMZ 2 g q8h for sigmoid diverticulitis. On day 5 of CMZ administration (after 12 doses in total), black stool was observed. On the following day (after 14 doses), prothrombin time (PT) prolongation was noted; PT and international normalized ratio (INR) were 37.1 s and 2.47, respectively. We diagnosed the patient with hypoprothrombinemia because of vitamin K deficiency caused by markedly elevated protein levels induced by vitamin K absence or antagonist-II on day 6 of CMZ administration. Intravenous vitamin K administration and CMZ cessation rapidly restored PT and led to the disappearance of black stool. CONCLUSIONS The causes of vitamin K deficiency were considered to be an impaired vitamin K cycle due to CMZ and decreased vitamin K intake because of malnutrition. These findings are consistent with CMZ's reported adverse effects. Decreased vitamin K production due to alterations in the gut bacterial flora by LVFX and CMZ was also postulated as a cause. If a bleeding tendency is noted during diverticulitis treatment with NMTT-containing cephems, switching to intravenous quinolones or carbapenems is recommended. It remains unclear how this reaction can be avoided; however, prudent monitoring of bleeding signs and PT-INR is recommended.

Topics: Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Cefmetazole; Diverticulitis; Female; Humans; Hypoprothrombinemias; Vitamin K; Vitamin K Deficiency

A man was admitted with abdominal pain. Treatment for acute diverticulitis was instituted with intravenous antibiotics and oral limitation. Imaging demonstrated a complex inflammatory mass. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen were within normal limits. However, repeat preoperative clotting studies demonstrated a severe unexpected coagulopathy to have developed since admission that could have caused fatal intraoperative exsanguination. Direct assays showed severe, isolated deficiency of vitamin K dependent clotting factors, and mixing studies normalised both the PT and APTT, ruling out a coagulation inhibitor. The coagulopathy responded to intravenous vitamin K administration. Dietary insufficiency underlies vitamin K deficiency in the presence of normal biliary and enteral function. A significant coagulopathy can result with additional eradication of intestinal microflora. Hypoprothombinaemia is recognised as a consequence of protracted treatment with broad spectrum antibiotics, and vigilance is required for those at risk. The development of such a rapid and unexpected coagulopathy posed a complex preoperative management issue delaying operative intervention; although avoided by fortuitous preoperative screening, it could have caused significant intraoperative bleeding. The remarkably specific lack of vitamin K dependent clotting factors strongly suggested a vitamin K deficiency and administration of coumarins was ruled out.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Antifibrinolytic Agents; Diverticulitis; Humans; Hypoprothrombinemias; Male; Vitamin K; Vitamin K Deficiency