Development and validation of a nomogram for predicting cefoperazone/sulbactam-induced hypoprothrombinaemia in Hospitalized adult patients.

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed.

Lupus anticoagulant-hypoprothrombinemia syndrome in children: Three case reports and systematic review of the literature.

OBJECTIVE: Children with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) are characterized by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT), lupus anticoagulant positivity and low prothrombin (factor II, FII) levels. Bleeding or thrombosis tendencies related to LAHPS in children can occur due to the development of anti-prothrombin antibodies that are usually linked to autoimmune or infectious diseases. METHODS: We report three pediatric cases of LAHPS and describe details on their clinical symptoms, laboratory characteristics, treatment. PubMed, Medline, and Web of Science searches were conducted on LAHPS in children between 1960 and 2023; articles in English were included. RESULTS: The coagulation profile revealed prolonged PT and APTT, with low prothrombin levels (19.4%, 21.0% and 12.9%, respectively) and positive lupus anticoagulant in 3 pediatric cases. Fifty-nine relevant articles reported 93 pediatric LAHPS cases (mean age: 9 years (0.8-17 years)); 63 females and 30 males, 87 patients presented with minor to severe bleeding diathesis, and 3 patients presented with thrombosis events. Among 48 patients ≥9 years old, 36 had SLE; among 45 patients <9 years, 29 had viral infection. When all patients were divided into two groups based on age, associated disease, and factor II level, Pearson's χ2 tests were performed, p =.00, and there was clinical significance between autoimmune and infectious disease in patients ≥9 years old and <9 years old, and in patients FII level ≤10% and >10%. LAHPS patients with autoimmune disease had a protracted course and needed prolonged treatment with immune-modulating therapy, while those patients with infectious disease resolved spontaneously or needed short-term immune-modulating therapy. CONCLUSION: LAHPS caused by autoimmune disease are common in patients ≥9 years old, especially SLE, and FII level ≤10% is often reported in patients caused by autoimmune disease, suggesting that children ≥9 years old diagnosed with LAHPS-related autoimmune disease should pay special attention to the FII level. While LAHPS caused by infectious disease is more frequently observed in patients <9 years, especially viral infection. Early diagnostic investigations are critical to differentiating LAHPS caused by autoimmune or infectious disease, as the prognosis, treatment and outcome are distinct.

Lupus anti-coagulant hypoprothrombinemia syndrome across different ages: a case report and review of the literature.

Lupus anti-coagulant hypoprothrombinemia syndrome (LAHPS) is a rare condition that can be difficult to treat. It increases the risk of thrombosis and bleeding due to the presence of lupus anti-coagulant and factor II deficiency, respectively. There are a limited number of cases described in the literature. Herein we describe a case of LAHPS with bleeding symptoms as a first clinical manifestation of systemic lupus erythematosus (SLE) in an 8-year-old female. She has had multiple recurrences of her bleeding symptoms, requiring treatment with steroids, cyclophosphamide, mycophenolate mofetil, and rituximab. Her course was later complicated by development of arthritis and lupus nephritis. Her complicated course provides a new perspective on the clinical course and treatment of LAHPS. We also present a comprehensive literature review which demonstrates the difficulty in treating patients with LAHPS with underlying SLE and the variability of the clinical course and management of LAHPS depending on the age at presentation.

Lupus anticoagulant-hypoprothrombinemia syndrome: A cerebral bleeding case report as systemic lupus erythematosus debut.

Lupus anticoagulant-hypoprothrombinaemia syndrome (LAHPS) is a rare disorder caused by the presence of lupus anticoagulant (LA) and acquired prothrombin deficiency, which may present with severe haemorrhagic manifestations. LAHPS is usually associated with systemic lupus erythematosus (SLE), or infections and it is more frequent in the paediatric population and female gender. We describe a 42-year-old man with thrombotic antiphospholipid syndrome (APS) on chronic anticoagulation treatment with acenocoumarol who presented with spontaneous intracranial bleeding, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and low factor II levels (after optimal anticoagulation reversal) as a debut of SLE.

Lupus anticoagulant-hypoprothrombinemia syndrome: A cerebral bleeding case report as systemic lupus erythematosus debut / Síndrome anticoagulante lúpico-hipoprotrombinemia: caso clínico de hemorragia cerebral como inicio de lupus eritematoso sistémico

Lupus anticoagulant-hypoprothrombinaemia syndrome (LAHPS) is a rare disorder caused by the presence of lupus anticoagulant (LA) and acquired prothrombin deficiency, which may present with severe haemorrhagic manifestations. LAHPS is usually associated with systemic lupus erythematosus (SLE), or infections and it is more frequent in the paediatric population and female gender. We describe a 42-year-old man with thrombotic antiphospholipid syndrome (APS) on chronic anticoagulation treatment with acenocoumarol who presented with spontaneous intracranial bleeding, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and low factor II levels (after optimal anticoagulation reversal) as a debut of SLE.(AU)

El síndrome de anticoagulante lúpico-hipoprotrombinemia (LAHPS, por sus siglas en inglés) es un trastorno raro, causado por la presencia de anticoagulante lúpico (AL) y deficiencia adquirida de protrombina, que puede cursar con manifestaciones hemorrágicas graves. El LAHPS suele asociarse a lupus eritematoso sistémico (LES) o infecciones, y es más frecuente en población pediátrica y en el género femenino. Describimos a un varón de 42 años con síndrome antifosfolípido (SAF) trombótico en tratamiento anticoagulante crónico con acenocumarol que presentó sangrado intracraneal espontáneo, prolongación tanto del tiempo de protrombina (TP) como del tiempo de tromboplastina parcial activada (TTPA) y factor bajo de nivel II (después de la reversión óptima de la anticoagulación) como inicio de LES.(AU)

Hypoprothrombinemia-lupus anticoagulant syndrome secondary to Sjogren's syndrome: A case report. / å¹²ç‡¥ç»¼åˆå¾ç»§å‘ä½Žå‡è¡€é ¶åŽŸè¡€ç—‡-狼疮抗凝物综合征1例.

Hypoprothrombinemia-lupus anticoagulant syndrome (HLAS) is a rare disease in which patients present with varying degrees of bleeding and positive lupus anticoagulant with reduced prothrombin on laboratory tests. This article reports a case of HLAS in a middle-aged woman with recurrent gingival bleeding and epistaxis as the first presentation. After admission, tests revealed prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and reduced coagulation factor II activity, and positive lupus anticoagulant (LA). Meanwhile, the patient had symptoms of dry mouth and dry eyes for a long time, and the examination of autoantibodies, tear secretion test and salivary gland emission computed tomography (ECT) were consistent with the diagnosis of Sjogren's syndrome. The final diagnosis was HLAS secondary to Sjogren's syndrome. After treatment with methylprednisolone and cyclophosphamide, the coagulation disorder gradually improved, and no recurrent bleeding occurred. HLAS is a rare clinical case, which reminds medical staff to be alert to the possibility of HLAS when encountering patients with unexplained prolonged APTT and PT and positive lupus anticoagulant.

Lupus anticoagulant-hypoprothrombinemia syndrome with severe bleeding diathesis after coronavirus disease 2019: a case report.

Acquired antibodies against factor II (prothrombin) are rare and most commonly associated with severe liver disease or vitamin K antagonist treatment. In very rare cases, these antibodies and associated hypoprothrombinemia are found in patients with lupus anticoagulant (LAC), an antiphospholipid antibody that inhibits phospholipid-dependent coagulation tests. This uncommon entity, called lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), may cause both severe, life-threatening bleeding and a predisposition to thrombosis. Coronavirus disease 2019 (COVID-19) is associated with a variety of coagulation abnormalities and an increased risk of thrombosis. Bleeding may occur, but it is less common than thromboembolism and has mostly been described in association with the severity of the disease and anticoagulation treatment in hospitalized patients, rarely in the post-acute phase of the disease. We report on a case of an 80-year-old man who developed LAHPS with prothrombin antibodies and severe bleeding after COVID-19.

Errate: Hypoprothrombinemia During Cefmetazole Treatment: A Case Report.

The authors contacted the journal with the following corrections to the published article: 1. Table 1. PT-INR at 6th hospital day. 2.46 is incorrect; Correct: 2.47. 2. Table 2. Line 5, at Purpose of use of CMZ. NA is incorrect; Correct: Infection secondary to Pneumothorax. 3. Table 2. Line 11, at PT-INR, 2.46 is incorrect; Correct: 2.47. 4. References No. 22 and No. 23 are reversed. The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Reference: Yuichiro Haba, Hikaru Akizuki, Naoyuki Hashiguchi, Toshio Naito. Hypoprothrombinemia During Cefmetazole Treatment: A Case Report. Am J Case Rep. 2022; 23: e936712. DOI: 10.12659/AJCR.936712.

Lupus Anticoagulant-Hypoprothrombinemia Syndrome and Pseudotumor Cerebri as an Initial Presentation of Systemic Lupus Erythematosus in a 16-Year-Old Male Patient: A Case Report and Literature Review.

BACKGROUND Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is an exceptionally rare disease caused by prothrombin antibodies, resulting in reduced factor II levels. This disease can present with significant bleeding and is usually associated with autoimmune disorders, particularly systemic lupus erythematosus (SLE). There are currently no guidelines for the treatment of LAHPS, and corticosteroids remain the criterion standard therapy. Pseudotumor cerebri is a disease that involves an idiopathic rise in intracranial pressure in association with papilledema. The coexistence of pseudotumor cerebri with SLE is rare, with an overall incidence of 0.7%. CASE REPORT A 16-year-old male initially presented to our hospital with nausea, headaches, and decreased visual acuity. He was diagnosed with pseudotumor cerebri based on the findings of papilledema and a raised opening pressure on lumbar puncture. Three months later, he presented with macroscopic hematuria and persistent epistaxis. Further investigation revealed a prolonged activated partial thromboplastin time and prothrombin time, along with positive LA and reduced Factor II levels, resulting in a diagnosis of LAHPS. The patient received a dose of 1 mg/kg/day of prednisolone along with hydroxychloroquine, and he had a complete recovery with cessation of bleeding and normalization of laboratory parameters. CONCLUSIONS We are reporting a case of pseudotumor cerebri with a further presentation of LAHPS in a patient found to have SLE. As both associations are rare in the presence of SLE, it is vital to recognize them early to initiate adequate management and intervention to avoid life-threatening complications.

[Recurrent epistaxis with coagulation disorders in a boy aged 2 years]. / 2岁男孩反复鼻衄伴凝血功能异常.

A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.

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.

Recurrent epistaxis with coagulation disorders in a boy aged 2 years / 中国当代儿科杂志

A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.

Lupus anticoagulant-hypoprothrombinaemia syndrome: subdural haematoma as an unusual and initial manifestation.

We describe the case of a 50-year-old woman with a history of SLE and APS that presented with a spontaneous subdural haematoma, prolonged aPTT, PT and INR and positive LA. The activity of the coagulation factors II, VIII, IX and XI was extremely low, and anti-prothrombin antibody IgG was positive. LAHS was established, with inhibition of the intrinsic pathway, as an acquired haemophilia. The patient received corticosteroids and cyclophosphamide as treatment. To the best of our knowledge, this is one of the few reports of spontaneous intracranial bleeding, an unusual and initial manifestation of LAHS in an adult patient.HighlightsLAHS is characterised by the presence of LA and hypoprothrombinaemia caused by anti-prothrombin antibodies.Prolonged aPTT and INR, and positive LA are important laboratory findings that help the suspicion of LAHS.Intracranial bleeding is an unusual manifestation of LAHS associated with low factor II activity.Corticosteroids are the first-line treatment of LAHS.The prognosis of LAHS is good with adequate treatment, with a reported mortality of 5%.