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

Abstract

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 Anticoagulant-Hypoprothrombinemia Syndrome: Literature Review and Description of Local Case in a 3-Year-Old Chinese Girl

“…Gynecological hemorrhage was associated with menorrhagia, and gastrointestinal hemorrhage presented with hematochezia or melena. Notably, 19 (35.8%) patients did not report any bleeding symptoms, 5,6,12 including our own case.…”

“…Additionally, if LA interference is not accounted for during coagulation factor detection, there is a risk of misdiagnosis. 12 Therefore, it is crucial for laboratories to closely communicate with clinical departments, enabling them to fully understand potential interference factors in laboratory testing and avoid misunderstandings when interpreting the results. For patients experiencing unexplained bleeding and testing positive for LA, it is important to be cautious of LAHPS.…”

“…Two cases without bleeding symptoms received non-immunosuppression treatment (including our patient). 12 Four patients with nonsevere bleeding were observed without specific treatment. 4,20,21 In one lymphoma patient with severe hematuria, who had liver and kidney metastasis, chemotherapy was the only viable treatment option.…”

“…The detection rates of LA, aPT, aPS/PT, aCL and aβ2GPI in LAHPS patients were 100% (53/53), 58.3% (14/24), 1,5,15,22,24 50% (12/24), 1,5,6,15,21 47.8% (22/46), 1,2,5,[9][10][11][12][13]15,19,[22][23][24]26,27 and 47.4% (18/38), 1,5,9,11,15,19,[22][23][24]26,27 respectively. There were no significant differences in the detection rates of each of these antiphospholipid antibodies before versus after the age of 18 years (p > 0.05; ►Table 3).…”

“…Underlying Etiology ►Table 3 presents 33 valid cases with information, excluding 20 cases without a description of the underlying disease. Among these cases, 20 (60.6%) were associated with autoimmune diseases, 2,4,7,9,10,12,14,18,22,24-27 11 (33.3%) were related to infections, 1,6,[11][12][13]16,17,20,21,23 and 2 (6.1%) were linked to tumors. 8,15 The most prevalent autoimmune disease was SLE (14/20, 70.0%), while viruses were the most common etiologic agent of infectious diseases (6/11, 54.5%).…”