Severe Coagulation Dysfunction caused by Vitamin K Deficiency in an Elderly Patient.

BACKGROUND: Vitamin K deficiency can lead to severe coagulation dysfunction, which may be dangerous and fatal, especially in patients undergoing surgery. METHODS: We report an 84-year-old male patient with gallstones and cholecystitis who had a severe coagulation disorder without bleeding symptoms after endoscopic papillary balloon dilation for removal of bile duct stones. After vitamin K supplementation, the coagulation dysfunction was corrected the next day. RESULTS: In this case, long-term antibiotic treatment, inadequate diet, and abnormal liver function led to coagulation dysfunction. After vitamin K supplementation, the blood coagulation disorder was corrected and serious consequences were prevented. Significantly elevated coagulation function was considered to be caused by vitamin K deficiency. CONCLUSIONS: This case indicates that coagulation dysfunction caused by vitamin K deficiency may occur within a few days. Laboratory personnel should fully understand the risks of vitamin K deficiency in elderly patients undergoing surgery with severely restricted diet, impaired absorption, and long-term use of cephalosporin anti-inflammatory therapy, and promptly remind clinical doctors.

The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism-A Review.

Vitamin K (VK), a fat-soluble vitamin, is essential for the clotting of blood because of its role in the production of clotting factors in the liver. Moreover, researchers continue to explore the role of VK as an emerging novel bioactive molecule with the potential function of improving bone health. This review focuses on the effects of VK on bone health and related mechanisms, covering VK research history, homologous analogs, dietary sources, bioavailability, recommended intake, and deficiency. The information summarized here could contribute to the basic and clinical research on VK as a natural dietary additive and drug candidate for bone health. Future research is needed to extend the dietary VK database and explore the pharmacological safety of VK and factors affecting VK bioavailability to provide more support for the bone health benefits of VK through more clinical trials.

The Effect of Vitamin K2 Supplementation on PIVKA-II Levels in Patients with Severe Motor and Intellectual Disabilities Undergoing Long-Term Tube Feeding.

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

Right femoral vein and right dorsal artery thrombosis in childhood acute myeloid leukemia: A case report.

BACKGROUND: It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis. METHODS: We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency. RESULTS: After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered. CONCLUSION: For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.

Antenatal steroid as an independent risk factor for vitamin K2 deficiency in newborns: A Chinese single-center, retrospective study.

OBJECTIVES: To identified vitamin K2 deficiency rate and risk factors among newborns in China and assess the importance of high-risk maternal intakes of vitamin K2. METHODS: This retrospective study was performed at the Neonatology Department, the Affiliated Hospital of Guangdong Medical University, China. Routinely collected mother-neonate hospitalization data from July 2020 to January 2021 were analyzed. In total, data from 200 neonates who had completed vitamin K2 tests were utilized to assess the prevalence of vitamin K2 deficiency and identify the potential risk factors. According to the vitamin K2 level, the neonates were divided into 2 groups: cases (vitamin K2 deficiency) and controls (no vitamin K2 deficiency). The potential risk factors for vitamin K2 deficiency were evaluated by univariate and multivariate logistic regression. RESULTS: The vitamin K2 level in 24 of the 200 neonates was undetectable (<0.05 ng/mL). The prevalence of low serum vitamin K2 (<0.1 ng/ml) was 33%. Study subjects with antenatal corticosteroids use had an approximately 5-fold greater risk of developing vitamin K2 deficiency. In the univariate analyses, small-for-gestational-age (SGA), caesarean section, maternal gestational diabetes and premature rupture of the membranes were risk factors for vitamin K2 deficiency. In the multivariate logistic regression analysis, high antenatal corticosteroids use, cesarean section, and SGA were independently associated with vitamin K2 deficiency. CONCLUSION: The present study demonstrated that antenatal corticosteroids use is independently associated with vitamin K2 deficiency. This finding highlights the importance of routine vitamin K2 supplementation in late-stage pregnant women and neonates in China.

Vitamin K and the Visual System-A Narrative Review.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system.

Reference Range of Vitamin K Evaluating Indicators in Chinese Childbearing Women.

BACKGROUND: Vitamin K is an essential fat-soluble vitamin for the human body and its functions, such as promoting blood coagulation, bone health and preventing atherosclerosis, have attracted increasing attention. However, there is no recognized indicator and corresponding reference range for evaluating vitamin K status of different populations at present. The aim of this study is to establish a reference range for vitamin K evaluating indicators in healthy women of childbearing age in China. METHODS: The population sample in this study was from the Chinese Adult Chronic Disease and Nutrition Surveillance (CACDNS) 2015-2017. A total of 631 healthy women of childbearing age (18-49 years) were included using a series of strict inclusion and exclusion criteria. The concentrations of VK1, MK-4 and MK-7 in serum were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The other commonly-reported indicators evaluating vitamin K nutritional status, including undercarboxylated osteocalcin (ucOC), osteocalcin (OC), matrix Gla protein (MGP), desphosphorylated undercaboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), were measured by enzyme-linked immunosorbent assay (ELISA). The reference range was obtained by calculating the 2.5% to 97.5% interval of the vitamin K evaluating indicators in the reference population. RESULTS: The reference ranges of VK1, MK-4 and MK-7 in serum were 0.21-3.07 ng/mL, 0.02-0.24 ng/mL and 0.12-3.54 ng/mL, respectively. The reference ranges of ucOC, %ucOC, dp-ucMGP and PIVKA-II were 1.09-2.51 ng/mL, 5.80-22.78%, 2.69-5.88 ng/mL and 3.98-8.40 ng/mL, respectively. The cut-off values that can be used to evaluate subclinical vitamin K deficiency were as follows: VK1 < 0.21 ng/mL, MK-7 < 0.12 ng/mL, ucOC > 2.51 ng/mL, %ucOC > 22.78%, dp-ucMGP > 5.88 ng/mL and PIVKA-II > 8.40 ng/mL. CONCLUSION: The reference range of VK1, MK-4, MK-7 and vitamin K-related indicators for healthy women of childbearing age established in this study could be used to assess the nutritional and health status of this population.

Take the Shot: A Review of Vitamin K Deficiency.

Vitamin K is essential for the process of coagulation. In its absence, severe and sometimes fatal bleeding events can occur, especially in newborns. Vitamin K prophylaxis at birth has been shown to prevent morbidity and mortality associated with vitamin K deficiency bleeding (VKDB) and is recommended by multiple organizations including the American Academy of Pediatrics and the World Health Organization. Pediatricians should feel comfortable explaining the risks and benefits of vitamin K prophylaxis to families and should be equipped to recognize signs of VKDB, especially given increasing rates of parental refusal. This article aims to improve understanding of VKDB, including prevention, early recognition, and treatment. [Pediatr Ann. 2023;52(2):e42-e45.].

Low vitamin K status in adults with cystic fibrosis is associated with reduced body mass index, insulin secretion, and increased pseudomonal colonization.

Patients with cystic fibrosis (CF) are at high risk of fat-soluble vitamin deficiencies, even with supplementation. The contribution of a suboptimal vitamin K status to respiratory and endocrine pathophysiology in CF has been inadequately characterized. This is a cross-sectional study in adult CF patients (≥18 years old) from the Montreal Cystic Fibrosis Cohort. Vitamin K1 (VK1) was measured with high-performance liquid chromatography, using fasted serum samples collected during an oral glucose tolerance test (OGTT: 2 h with plasma glucose and insulin every 30 min) (n = 168). Patients were categorized according to VK1 status (suboptimal defined as <0.30 nmol/L). Suboptimal VK1 levels were observed in 66% of patients. Patients with a suboptimal VK1 status have a higher risk of colonization with Pseudomonas aeruginosa (p = 0.001), have lower body mass index (BMI) (p = 0.003), and were more likely to have exocrine pancreatic insufficiency (p = 0.002). Using an established threshold for VK1, we did show significantly reduced OGTT-derived measures of insulin secretion in patients with a VK1 status below 0.30 nmol/L (first- and second-phase area under the curve (AUC)INS/GLU (p = 0.002 and p = 0.006), AUCINS (p = 0.012) and AUCINS/GLU (p = 0.004)). Subclinical vitamin K deficiency is more common than other fat-soluble vitamin deficiencies in patients with CF. We demonstrate an association between a suboptimal VK1 status and measures of insulin secretion. We highlight the potential associations of mild vitamin K deficiency with pseudomonal colonization and lower BMI, although these need to be validated in prospective studies.

Vitamin K Deficiency in the Setting of Blenderized Tube Feeding Regimen in a Teenager: A Case Report.

Vitamin K acts a cofactor for the gamma-carboxylation of several proteins in the coagulation cascade. The clinical spectrum of vitamin K deficiency (VKD) can be asymptomatic to a significant bleeding. VKD is classically seen in newborns. However, this can manifest later in patients with risks such as sub-optimal nutrition, fat malabsorption, medications including antibiotics. A 17-year-old male with spinal muscular atrophy (SMA) Type 1, tracheostomy with ventilator dependent, gastrostomy tube feeding was seen by the gastroenterologist following treatment for small intestinal bacterial overgrowth (SIBO). Investigations showed coagulopathy following which he was transferred to the Pediatric ICU. Labs revealed prothrombin time (PT) 114 s [Normal 9.4-12.5 s], INR (International normalized ratio) 12.6 [Normal < 1.1] and partial thromboplastin time (PTT) 90 s [Normal 25.1-36.5 s]. Mixing studies and coagulation assays were consistent with VKD (low Factor VII and Factor IX with normal Factor V). His home blenderized feeding regimen met the caloric requirement but not the adequate intake (AI) values for vitamin K and other minerals. He received intravenous vitamin K (phytonadione) for five consecutive days with resolution of the coagulopathy (PT 13.2 s, PTT 37.1 s, INR 1.2). The patient was discharged on enteral vitamin K and additional supplements following dietary review by a nutritionist. Clinicians should be cognizant of VKD in patients on blenderized tube feeds which may not meet the adequate intake (AI) goals. In patients who are not receiving nutritionally complete formulas or receiving inadequate volumes, it is important to monitor macro and micronutrients.

Spontaneous haemopericardium due to vitamin K deficiency in an adult patient with cardiofaciocutaneous syndrome.

We present the case of an adult man with cardiofaciocutaneous syndrome, who initially presented to the emergency department with severe abdominal pain and distension, but was diagnosed with cardiac tamponade on CT after distended neck veins and tachycardia were identified on examination. He had emergency pericardial drainage to relieve the haemopericardium and was treated with colchicine. He was further found to be deficient in factors II, VII and X despite not being on warfarin, and was therefore supplemented with vitamin K. This confirms a diagnosis of vitamin K deficiency, likely multifactorial from malabsorption due to chronic intestinal pseudo-obstruction, small bowel obstruction and possibly exacerbated by subsequent ciprofloxacin use for small intestine bacterial overgrowth. This is the first report of spontaneous haemopericardium secondary to vitamin K deficiency in an adult patient not on anticoagulation, and is an important learning point due to the life-threatening progression of the haemopericardium and cardiac tamponade.

Vitamin K1 and K2 in the Diet of Patients in the Long Term after Kidney Transplantation.

Vitamin K, especially its K2 form, is considered to be a protective factor against developing vascular changes and bone lesions that are common complications in kidney transplant (KTx) recipients. There is a growing number of studies showing that KTx patients are at risk of vitamin K deficiency. The aim of this study was to evaluate the intake of vitamin K1 and K2 in the diet of patients in the late period after KTx. During a routine visit at one outpatient transplantation clinic in Central Europe, a diet survey questionnaire was filled in by 151 clinically stable KTx recipients and compared with medical history, anthropometric measurements and laboratory tests. Mean vitamin K1 intake was 120.9 ± 49 µg/day and vitamin K2 (MK, menaquinone) intake 28.69 ± 11.36 µg/day, including: MK-4: 25.9 ± 9.9 µg/day; MK-5: 0.1 ± 0.2 µg/day; MK-6: 0.2 ± 0.4 µg/day; MK-7: 0.2 ± 0.23 µg/day; MK-8: 1 ± 1.9 µg/day; MK-9: 0.9 ± 2.3 µg/day; and MK-10: 0.2 ± 0.5 µg/day. Our study showed that KTx recipients' diets contained adequate amounts of vitamin K1, whereas the intake of vitamin K2 seemed insufficient.

Enhanced vitamin K expenditure as a major contributor to vitamin K deficiency in COVID-19.

OBJECTIVES: Vitamin K deficiency consistently associates with worse clinical outcome in COVID-19 patients. However, whether this is due to increased expenditure during inflammation or poor vitamin K status prior to infection remained unknown. METHODS: Dp-ucMGP levels of 128 individuals were measured for the post-MONICA study and were compared to SARS-CoV-2 PCR testing results. RESULTS: Dp-ucMGP levels prior to COVID-19 infection were not significantly different comparing PCR-negative, PCR-positive and not hospitalized, and PCR-positive and hospitalized patients. CONCLUSION: In this study, we demonstrate normal vitamin K status prior to infection in SARS-CoV-2 positive patients, supporting the theory of increased utilisation during disease.

Inferring bona fide Differentially Expressed Genes and Their Variants Associated with Vitamin K Deficiency Using a Systems Genetics Approach.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes, viz., myocardial infarction, renal failure and prostate cancer. We sought to ask whether or not any DEGs harbor pathogenic variants common in these conditions, attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Vitamin K-Dependent Carboxylation of Osteocalcin in Bone-Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease?

Chronic kidney disease (CKD) commonly occurs with vitamin K (VK) deficiency and impaired bone mineralization. However, there are no data explaining the metabolism of endogenous VK and its role in bone mineralization in CKD. In this study, we measured serum levels of phylloquinone (VK1), menaquinone 4 and 7 (MK4, MK7), and VK-dependent proteins: osteocalcin, undercarboxylated osteocalcin (Glu-OC), and undercarboxylated matrix Gla protein (ucMGP). The carboxylated osteocalcin (Gla-OC), Glu-OC, and the expression of genes involved in VK cycle were determined in bone. The obtained results were juxtaposed with the bone mineral status of rats with CKD. The obtained results suggest that the reduced VK1 level observed in CKD rats may be caused by the accelerated conversion of VK1 to the form of menaquinones. The bone tissue possesses all enzymes, enabling the conversion of VK1 to menaquinones and VK recycling. However, in the course of CKD with hyperparathyroidism, the intensified osteoblastogenesis causes the generation of immature osteoblasts with impaired mineralization. The particular clinical significance seems to have a finding that serum osteocalcin and Glu-OC, commonly used biomarkers of VK deficiency, could be inappropriate in CKD conditions, whereas Gla-OC synthesized in bone appears to have an adverse impact on bone mineral status in this model.

Dysbiosis in Patients with Chronic Kidney Disease: Let Us Talk About Vitamin K.

PURPOSE OF REVIEW: This narrative review aimed to summarize the current evidence on the connection between dysbiosis and vitamin K deficiency in patients with chronic kidney disease (CKD). The presence of dysbiosis (perturbations in the composition of the microbiota) has been described in several non-communicable diseases, including chronic kidney disease, and it has been hypothesized that dysbiosis may cause vitamin K deficiency. Patients with CKD present both vitamin K deficiency and gut dysbiosis; however, the relationship between gut dysbiosis and vitamin K deficiency remains to be addressed. RECENT FINDINGS: Recently, few studies in animals have demonstrated that a dysbiotic environment is associated with low production of vitamin K by the gut microbiota. Vitamin K plays a vital role in blood coagulation as well as in the cardiovascular and bone systems. It serves as a cofactor for γ-glutamyl carboxylases and thus is essential for the post-translational modification and activation of vitamin K-dependent calcification regulators, such as osteocalcin, matrix Gla protein, Gla-rich protein, and proteins C and S. Additionally, vitamin K executes essential antioxidant and anti-inflammatory functions. Dietary intake is the main source of vitamin K; however, it also can be produced by gut microbiota. This review discusses the effects of uremia on the imbalance in gut microbiota, vitamin K-producing bacteria, and vitamin K deficiency in CKD patients, leading to a better understanding and raising hypothesis for future clinical studies.

Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth.

BACKGROUND: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1 ) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. OBJECTIVES: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla proteins, factor II (PIVKA-II), and osteocalcin (GluOC), synthesized by liver and bone, respectively. PATIENTS/METHODS: Prospective, multicenter, observational study in preterm infants born <33 weeks' gestation. Blood samples and dietary history were collected before hospital discharge, and after discharge at 2-3 months' corrected age. Outcome measures were serum VK1 , PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants after discharge. RESULTS: After discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 µg/L), higher PIVKA-II (0.10 vs. 0.02 AU/ml) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only one (2%) of 45 breastmilk-fed infants was VK insufficient. After discharge, eight (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only one (4%) of 25 formula/mixed-fed babies. CONCLUSIONS: Preterm infants who remain exclusively or predominantly human breastmilk-fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.

Neglected vitamin K deficiency causing coagulation dysfunction in an older patient with pneumonia: a case report.

BACKGROUND: The development of coagulation disorders can be dangerous and fatal in the older people, especially those with multiple medical conditions. Vitamin K-dependent coagulation disorders are easily overlooked when anticoagulant drugs are not used and the patient shows no signs of bleeding. CASE PRESENTATION: We report a case of a 71-year-old male suffering from pulmonary infection with severe coagulation disorder without bleeding symptoms. He also had a history of Parkinson's disease, Alzheimer's disease and cardiac insufficiency. Coagulation tests were normal at the time of admission, prothrombin time (PT) is 13.9 (normal, 9.5-13.1) seconds and the activated partial thromboplastin time (APTT) is 30.2 (normal, 25.1-36.5) seconds. But it turned severely abnormal after 20 days (PT: 136.1 s, APTT: 54.8 s). However, no anticoagulants such as warfarin was used and no bleeding symptoms were observed. Subsequent mixing studies with normal plasma showed a decrease in prothrombin times. Vitamin K deficiency was thought to be the cause of coagulation disorders considering long-term antibiotic therapy, especially cephalosporins, inadequate diet and abnormal liver function. After supplementation with 20 mg of vitamin K, coagulation dysfunction was rescued the next day and serious consequences were effectively prevented. CONCLUSIONS: Overall, timely vitamin K supplementation with antimicrobials that affect vitamin K metabolism requires clinician attention, especially in older patients who are multimorbid, frail or nutritionally compromised, and are admitted to hospital because of an infection that needs antimicrobial therapy are at risk of clotting disorders due to abnormal vitamin K metabolism secondary to altered gut flora, which can exacerbate existing nutritional deficiencies.

Hypoprothrombinemia During Cefmetazole Treatment: A Case Report.

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.