Clinical features and treatment of 70 children with lupus anticoagulant-hypoprothrombinemia syndrome: a retrospective study from a single center in China.

Background: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder characterized by the presence of lupus anticoagulant (LA) and acquired hypoprothrombinemia. Objectives: To summarize the experience of diagnosis, clinical features, and treatment of lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS). Methods: A retrospective study of 70 children diagnosed with LAHPS from January 2019 to February 2024 at a single center was conducted. Results: A total of 70 subjects (32 boys and 38 girls), with a mean age of 5.58 years, were included in the study. Among these subjects, 15 had autoimmune diseases (AIDs), 51 had infections, and 4 had unknown causes. Fifty-six of 70 (80%) subjects experienced bleeding with the median bleeding score of 4, 1 of 70 (1.4%) presented with thrombosis, and 13 of 70 (18.6%) were asymptomatic. All patients exhibited prolonged prothrombin time, significantly prolonged activated partial thromboplastin time, decreased factor (F)II activity (FII:C), and positive lupus anticoagulant. There was a weak negative correlation between the severity of bleeding and FII:C level (rs = -0.4283; P < .001). Patients with infection-associated LAHPS were younger than those with AIDs-associated LAHPS (P < .0001). In the study, LAHPS subjects are treated with corticosteroids as the first-line therapy, or in combination with immunosuppressants. Coagulation factor replacement therapy can effectively prevent and control bleeding events. After follow-up, lupus anticoagulant of all patients had turned negative within 12 weeks. And, prothrombin time and FII:C were completely normalized of all patients without recurrence of bleeding and without thrombosis. Conclusion: Children develop LAHPS most commonly after AIDs and infection. Most patients presented with mild to moderate bleeding. The severity of bleeding symptoms was not exactly parallel to the decreased FII:C level.

ROTEM could be useful for lupus anticoagulant hypoprothrombinemia syndrome.

BACKGROUND: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disease caused by acquired factor II (FII) deficiency and lupus anticoagulant. Patients with LAHPS typically present with thrombosis and bleeding. However, little information is available on the evaluation of coagulation potential in patients with LAHPS. We examined global coagulation potentials in patients with LAHPS during the clinical course in this study. METHODS: Coagulation potentials in two pediatric patients with LAHPS were assessed by measuring clotting time (CT) and clot formation time using Ca2+-triggered rotational thromboelastometry (ROTEM), CT and maximum coagulation velocity using clot waveform analysis (CWA), and lag time and peak thrombin using the thrombin generation assay (TGA). The day of admission was defined as day 0. RESULTS: In case 1, the bleeding symptoms disappeared by day 5. However, the TGA and CWA results were markedly lower than normal, although FII activity (FII:C) returned to within the normal range by day 14. In contrast, ROTEM revealed a recovery to near-normal levels (day 14). All coagulation parameters (day 80) were within normal ranges. In case 2, coagulation potential was severely depressed until day 12, although FII:C returned to normal levels. Bleeding symptoms disappeared on day 19, and the ROTEM data revealed that the parameters were close to the normal range. The coagulation parameters in all assays were normalized on day 75. CONCLUSIONS: Recovery of coagulation potential in patients with LAHPS was slower than the recovery of FII:C. Moreover, ROTEM appeared to be clinically useful for assessing coagulation potential in patients with LAHPS.

Lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus / Síndrome de LAHS asociado a lupus eritematoso sistêmico

Abstract Introduction: thromboembolic phenomena are among the most common hematologic mani festations in patients with systemic lupus erythematosus (SLE) who have lupus anticoagulant, while hemorrhagic events are less frequent and tend to occur with Factor II deficiency. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHS) is a rare disorder and its association with SLE is uncommon, especially in adults. Case presentation: we present the case of a 19-year-old male patient diagnosed with LAHS associated with SLE, with kidney and skin involvement evidenced by lower extremity purpura and hematuria. Treatment was begun early with corticosteroid pulses, cyclophosphamide and mycophenolate mofetil, with an adequate clinical response. Conclusion: understanding the association between LAHS and SLE helps providers suspect this condition in patients with acquired coagulation disorders and recognize it as the initial manifestation of an underlying systemic disease. Early diagnosis and prompt treatment reduce mortality in these patients. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2745).

Resumen Introducción: los fenómenos tromboembólicos hacen parte de las manifestaciones hematológicas más comunes de los pacientes con lupus eritematoso sistémico (LES) que presentan anticoagulante lúpico, mientras que los eventos hemorrágicos son menos frecuentes y suelen manifestarse en pre sencia de deficiencia de factor II. El síndrome de LAHS es una afección rara y su asociación con LES es infrecuente, especialmente en etapa adulta. Presentación del caso: se presenta el caso de un paciente masculino de 19 años diagnosticado con síndrome de LAHS asociado a LES con compromiso renal y cutáneo manifestado por púrpuras en extremidades inferiores y hematuria. Se instauró tratamiento con pulsos de corticoides, ciclofosfamida y micofenolato mofetil de forma temprana observándose una adecuada respuesta clínica. Conclusión: conocer la asociación entre el síndrome de LAHS y LES permite sospechar esta entidad en pacientes con trastornos adquiridos de la coagulación y reconocerla como manifestación inicial de una enfermedad sistémica subyacente. El diagnóstico temprano y tratamiento oportuno reduce la mortalidad en estos pacientes. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2745).

Successful treatment of lupus anticoagulant hypoprothrombinemia syndrome with rituximab.

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder secondary to development of antibodies against prothrombin protein, in the presence of antiphospholipid antibodies. We describe the case of a 13-year-old girl who presented with severe menorrhagia and symptomatic anemia. Labs indicated anemia, thrombocytopenia, elevated PT and aPTT, high-titer inhibitor on mixing studies, positive ANA and anti-dsDNA antibodies, along with a triple-positive antiphospholipid antibody panel. Given additional systemic manifestations, systemic lupus erythematosus was diagnosed. High dose steroids and hydroxychloroquine subsequently started. Her clinical course was complicated by femoral deep venous thrombosis and post renal biopsy retroperitoneal hematoma. Further workup revealed low prothrombin level and the diagnosis of lupus anticoagulant hypoprothrombinemia syndrome. In view of suboptimal response to initial immunosuppressive therapy, rituximab was added to her regimen, leading to an improvement in clinical symptoms and resolution of hypoprothrombinemia. She remains recurrence free 5 years from the event.

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.

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.

Autoimmune hemolytic anemia as an initial presentation in children with systemic lupus erythematosus: two case reports.

We report the cases of two children who presented with autoimmune hemolytic anemia (AIHA) as an initial presentation of systemic lupus erythematosus (SLE). Both patients had a positive Coombs test, anemia, and an increased number of spherocytes in their blood smear. The patient in Case 1 presented with fever, urticarial erythema, facial paresis, AIHA, and leucopenia. Immunological screening revealed low complement protein levels and positive anti-nuclear antibody, anti-double-stranded DNA, and antiphospholipid antibody results. A further laboratory workup revealed a positive lupus anticoagulant (LA) result and low factor II levels. She was diagnosed with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) in addition to SLE. The patient in Case 2 presented with fever, butterfly rash, thyroid enlargement, leucopenia, and AIHA. She was diagnosed with SLE with thyroiditis. Both patients were started on combined immunosuppressive therapy, and both patients' clinical symptoms finally resolved. A literature review on childhood SLE showed that AIHA is common in patients with SLE. LAHPS is an uncommonly identified cause of bleeding in patients with SLE, and it must be considered when evaluating children with a positive LA result.

[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.

Cefazolin and rifampin: A coagulopathy-inducing combination.

PURPOSE: To identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy. SUMMARY: An 86-year-old man with a history of rheumatoid arthritis on chronic prednisone and stage 3 chronic kidney disease, notably not on warfarin, presented to the hospital with a 10-day history of right hip pain, swelling, and drainage after a recent right total-hip arthroplasty. The patient underwent a combination of surgical intervention and medication therapy with rifampin and ceftriaxone. After discharge and at postoperative day 9, ceftriaxone was changed to cefazolin due to increasing alkaline phosphatase levels. Four weeks after the initial debridement, antibiotics, and implant retention, the patient underwent a second irrigation and debridement due to persistent infection. Cefazolin and rifampin therapy was extended. Three days later, the patient presented to the emergency room with significant bleeding at the surgical site and a profoundly elevated prothrombin time and international normalized ratio (INR). No potential contributors were identified. The Naranjo adverse drug reaction probability scale identified cefazolin and rifampin as the probable cause of elevated INR. The Liverpool adverse drug reaction avoidability assessment tool classified this adverse event as "definitely avoidable." CONCLUSION: Rifampin-containing regimens are often recommended to treat staphylococcal prosthetic joint infections when the implant is retained. In methicillin-susceptible staphylococcal infections, cefazolin is routinely employed as the ß-lactam backbone of definitive antimicrobial regimens. Although rifampin- and cefazolin-induced hypoprothrombinemia seems to be rare, adverse consequences of its occurrence may be prevented with appropriate monitoring.

A case of congenital prothrombin deficiency with two concurrent mutations in the prothrombin gene.

Congenital prothrombin deficiency is an extremely rare, autosomal recessive bleeding disorder with a prevalence of 1 in 2 million individuals. Here, we report a case of congenital prothrombin deficiency with two concurrent mutations in the prothrombin gene (F2), affecting the heavy B chain. The patient presented with a history of multiple bleeding events in his youth that are mostly trauma associated, with a family history of prothrombin deficiency. Laboratory analysis showed a prolonged activated partial thromboplastin time and a prothrombin activity level of 5%. Genetic analysis of the F2 gene identified two heterozygous variants; one is a previously reported pathogenic deletion (c.1814_1815del; p.His605Argfs*13), and the other is a novel missense variant (c.1147C>T; p.Arg383Trp). In silico analysis predicted that p.Arg383Trp is likely to be disease causing, as it affects one of the anion-binding exosites-I of the B chain. This case highlights the significance of molecular findings in confirming the diagnosis of patients with congenital prothrombin deficiency.

Lupus anticoagulant hypoprothrombinemia syndrome associated with bilateral adrenal haemorrhage in a child: early diagnosis and intervention.

BACKGROUND: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is characterized by bleeding and thrombosis in patients with autoimmune diseases or infections. Paediatric LAHPS exhibits various degrees of bleeding, ranging from mild to severe; however, adrenal haemorrhage due to LAHPS and its long-term clinical course have not been sufficiently described. CASE PRESENTATION: A 9-year-old boy presented with prolonged abdominal pain and abnormal coagulation screening tests. The laboratory tests showed prolonged activated partial thromboplastin time and subsequently revealed the presence of lupus anticoagulant, anti-nuclear antibodies, and hypoprothrombinemia, leading to diagnosis of LAHPS. An enhanced computed tomogram demonstrated nodular lesions in the adrenal glands bilaterally, suggestive of adrenal haemorrhage. Laboratory and clinical manifestations exhibited life-threatening adrenal insufficiency that required hydrocortisone administration. The patient developed systemic lupus erythematosus, diagnosed 12 months later. CONCLUSIONS: This patient with LAHPS developed rare adrenal failure due to adrenal haemorrhage, a life-threatening event that should be recognized and treated early. In our case, renal dysfunction was also observed when systemic lupus erythematosus was diagnosed 1 year after LAHPS. Our case emphasizes that early recognition of adrenal failure and careful long-term observation is required in patients with autoantibodies.

Pediatric systemic lupus erythematosus with lupus anticoagulant hypoprothrombinemia syndrome-A case series with review of literature.

INTRODUCTION: Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare phenomenon that leads to concomitant thrombosis and hemorrhage in children with SLE. LAHPS in pediatric SLE (pSLE) has a protracted course requiring long-term immunosuppressive therapy. Due to the rarity of this syndrome and paucity of reported cases, there is lack of standardized management. We herewith report 5 children with pSLE with LAHPS.Methodology: We retrospectively reviewed clinical features, laboratory features, treatment and outcome for 5 children with lupus anticoagulant hypoprothrombinemia syndrome with SLE and a review of literature of similar cases published. RESULTS: Mean age of presentation was 10.2 ± 2.38 years (mean ± SD) and female to male ratio was 4:1. All children presented with mild to severe bleeding manifestations like gum bleed, epistaxis, hematuria, menorrhagia and subarachnoid bleed. Coagulation profile revealed prolonged PT and aPTT, with low prothrombin levels and positive Lupus anticoagulant in all children. Mixing studies were characteristic in these children. On comparing laboratory parameters majority had low C3, C4 levels, ANA and anti-DsDNA antibody positivity and three children had anticardiolipin positivity. One child had lupus nephritis along with LAHPS at presentation. All responded well to steroids and supportive measures. CONCLUSION: High index of suspicion is needed when child with lupus presents with bleeding manifestations for early diagnosis and treatment.

[Lupus anticoagulant-hypoprothrombinemia syndrome associated with follicular lymphoma].

A 56-year-old woman was referred to our hospital with symptoms of swelling, purpura, and pain in her limbs. Prior to referral, bleeding in her limbs had spontaneously appeared and disappeared several times. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged, and the factor II level was 17%. The plasma-mixing test indicated lupus anticoagulant (LA), which was confirmed using aPTT-LA and dilute Russell's viper venom time (dRVVT). Therefore, she was diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS). During screening for underlying disorders, chest computed tomography (CT) revealed a retrosternal mass. Biopsy was not performed because the administration of freshly frozen plasma failed to correct her coagulopathy. Prednisolone (PSL) treatment (1 mg/kg) was initiated, which normalized the coagulation tests. The retrosternal mass also disappeared. PSL was tapered without LAHPS recurrence; however, the follow-up CT revealed systemic lymphadenopathy. Follicular lymphoma was diagnosed using lymph-node biopsy. Considering the subsequent LAHPS recurrence, six cycles of bendamustine + rituximab were administered. Complete response with no LAHPS recurrence was observed at the time of drafting this report. LAHPS is rare and distinct from antiphospholipid syndrome because it can cause severe bleeding. Underlying disorders should be evaluated in cases of LAHPS.

A case report of severe bleeding due to lupus anticoagulant hypoprothrombinemia syndrome.

Association of acquired factor II deficiency and lupus anticoagulant is a rare disease that can be related to sudden, severe or fatal haemorrhage. We present a 74-years-old woman with history of myelodysplastic syndrome, admitted to the Emergency Department due to spontaneous mucocutaneous bleeding. Coagulation assays revealed prolonged prothrombin time and activated partial thromboplastin time with evidence of an immediate acting inhibitor. Antithrombotic therapy usage, drug ingestion, disseminated intravascular coagulation, liver dysfunction and sepsis were excluded. Patient was admitted for close monitoring and etiological evaluation. A comprehensive bleeding diathesis workup was performed showing factor II levels severely decreased and transient positive lupus anticoagulant. Immunosuppression with methylprednisolone lasted for 3 days, followed by prednisolone. After 20 days she was discharged and follow-up was scheduled. Early diagnosis of lupus anticoagulant hypoprothrombinemia syndrome is critical, as it may result in fatal complications if not treated appropriately. There is no consensus regarding the best treatment, most being based on immunosuppression.

The Association Between Cephalosporin and Hypoprothrombinemia: A Systematic Review and Meta-Analysis.

Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events; however, a comprehensive evaluation regarding the association is lacking. A systematic review and meta-analysis were conducted to assess the safety profile of NMTT-cephalosporins with respect to hypoprothrombinemia and bleeding. The MEDLINE, Embase, Cochrane, and RISS databases were systematically searched for clinical studies up to October 2018. The association between NMTT-cephalosporins and hypoprothrombinemia was estimated using an odds ratio (OR) with a 95% confidence interval (CI). A total of 15 studies on cefamandole, cefoperazone, cefotetan, cefmetazole, and moxalactam were identified and included in the meta-analysis. Hypoprothrombinemia (OR 1.676, 95% CI 1.275-2.203) and prothrombin time (PT) prolongation (OR 2.050, 95% CI 1.398-3.005) were significantly associated with NMTT-cephalosporins, whereas bleeding was not (OR 1.359, 95% CI 0.920-2.009). Subgroup analyses revealed that cefoperazone (OR 2.506, 95% CI 1.293-4.860), cefamandole (OR 3.247, 95% CI 1.083-9.733), and moxalactam (OR 3.367, 95% CI 1.725-6.572) were significantly associated with hypoprothrombinemia. An Antimicrobial Stewardship Program led by a multidisciplinary team could play a critical role in monitoring cephalosporin-related hypoprothrombinemia or PT prolongation in patients with underlying clinical conditions at risk for bleeding. The multidisciplinary team could also assist in communicating the potential safety concerns regarding NMTT-cephalosporin use with healthcare professionals to decrease the risk of adverse events.

Lupus anticoagulant-hypoprothrombinemia syndrome and immunoglobulin-A vasculitis: a report of Japanese sibling cases and review of the literature.

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare bleeding disorder caused by antiprothrombin antibodies. LAHPS is associated with systemic lupus erythematosus (SLE) or infections. We describe two Japanese brothers with immunoglobulin-A vasculitis (IgAV) who met the diagnostic criteria of LAHPS. They presented with palpable purpura and abdominal pain, and had a prolonged activated partial thromboplastin time (APTT) and prothrombin deficiency with the presence of lupus anticoagulant. Pediatric LAHPS was reviewed in abstracts from the Japan Medical Abstracts Society that were written in Japanese and PubMed or Web of Science-listed articles in English between 1996 and 2019. Including our cases, pediatric LAHPS has been reported in 40 Japanese and 46 non-Japanese patients. We summarized the clinical and laboratory characteristics of all 86 cases, and found only one Japanese LAHPS case with IgAV, except for our cases. Of the 86 cases, most were associated with infections followed by SLE. The presence of SLE, older age, lower prothrombin levels, severe bleeding symptoms, and positivity of immunoglobulin G anticardiolipin antibodies and anticardiolipin/ß2-glycoprotein I antibodies and/or ß2-glycoprotein I-dependent anticardiolipin antibodies had higher odds of requiring treatment. Measuring the APTT and prothrombin time (PT) might be required in patients with IgAV when they do not have a typical clinical course or distinctive symptoms. LAHPS should be considered with prolongation of the APTT and/or PT. Additionally, it is important to maintain a balance between the risk of thrombosis and hemorrhage when normalization of the PT and FII levels occurs in LAHPS cases under treatment.

[Thrombo-haemorrhagic disease-related hypoprothrombinemia-lupus anticoagulant syndrome revealing a light chains multiple myeloma]. / Un tableau thrombo-hémorragique en rapport avec un syndrome hypoprothrombinémie ­ anticoagulant lupique révélant un myélome multiple à chaînes légères.

Thrombosis and hemorrhage are two opposing manifestations of multiple myeloma. These hemostatic disorders are present in less than 12% of patients at diagnosis and involve various pathophysiological mechanisms. We report the case of a 39-year-old patient with multiple myeloma revealed by the association of a hemorrhagic syndrome and deep vein thrombosis related to a hypoprothrombinemia-anticoagulant lupus syndrome.

Lupus anticoagulant hypoprothrombinemia syndrome associated with systemic lupus erythematosus in children: report of two cases and systematic review of the literature.

We report two children with systemic lupus erythematosus (SLE) having severe bleeding manifestations and lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) along with a review of published cases of childhood SLE and LAHPS. We report clinical and laboratory profile of two children diagnosed with childhood SLE and LAHPS. We also conducted literature search to identify similar published cases and a review was performed. An 8-year-old girl had presented with fever, arthralgia, alopecia, anasarca and bleeding from multiple sites. She was diagnosed to have SLE based on laboratory investigations which showed anemia, thrombocytopenia, low complements, positive anti-nuclear antibody (ANA) and double standard DNA (dsDNA) antibodies. She was also found to have prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), positive lupus anticoagulant (LA) and low factor II levels. She was diagnosed to have SLE with LAHPS and treated with intravenous methylprednisolone, intravenous immunoglobulin and cyclophosphamide with good outcome. Patient 2 was a 7-year-old-boy who was diagnosed to have SLE when he presented with fever, anasarca, malar rash, arthritis and bleeding from skin and mucosa. Laboratory investigations revealed anemia, proteinuria, low complements, positive ANA and anti-dsDNA titre. Coagulation studies showed deranged PT and aPTT, positive LA and low factor II levels. He was diagnosed to have SLE with LAHPS and was treated with intravenous methylprednisolone and oral mycophenolate mofetil. Review of literature of cases with childhood SLE and LAHPS showed that there are 32 cases have been reported till date which have been summarized. LAHPS is an uncommonly identified cause of bleeding in patients with SLE and must be suspected while evaluating these children.

Rituximab use in pediatric lupus anticoagulant hypoprothrombinemia syndrome - report of three cases and review of the literature.

Lupus anticoagulant hypoprothrombinemia syndrome (LA-HPS) is a rare condition that may predispose both to thrombosis and bleeding due to positive lupus anticoagulant (LA) and factor II (FII) deficiency. It can be seen in association with infections or systemic lupus erythematosus (SLE) and may require glucocorticoids (GCs) and/or immunosuppressive medications. Pediatric LA-HPS cases in the literature and three cases that received only rituximab (RTX) for LA-HPS (in addition to GCs) at two institutions between January 2010 and June 2017 were analyzed descriptively. Pediatric LA-HPS cases (≤18 years) with bleeding or thrombotic events were included. Information obtained included demographics, presenting symptoms, diagnoses, treatments, pre-/post-treatment prothrombin time (PT)/partial thromboplastin time (PTT)/LA/FII levels, and outcomes. In addition to three LA-HPS cases identified at our institutions, as of June 2017, 37 articles reported 54 pediatric LA-HPS cases (mean age: 8 years (0.9-17 years); female/male: (2:1); viral illness 27 (50%), SLE 20 (37%), and other six (11%)). All cases had a positive LA and FII deficiency (range: 0%-40%). All cases presented with bleeding diathesis and were treated with various regimens, but there was no reported use of RTX. The purpose of this report is to describe the novel use of RTX as a steroid-sparing agent in three pediatric SLE cases and to systematically review the literature on pediatric cases of LA-HPS.