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

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare, acquired coagulopathy syndrome. Here, we aim to summarize the clinical features of LAHPS to improve the understanding of the disease. The clinical data of 52 patients with LAHPS retrieved through PubMed from 2019 to 2023, supplemented with a local case of a child with LAHPS, were retrospectively analyzed, and the clinical characteristics were summarized. 56.6% of LAHPS patients were female, the median age at onset was 13.0 years (range, 1.2-85 years), and the median activity of factor II was 18.0% (range, 0.1-69%). 64.2% of LAHPS patients experienced hemorrhage, with 29.4% having multisite hemorrhage and 20.6% experiencing both nonsevere and severe hemorrhage. Most of the reported cases were secondary to autoimmune diseases (60.6%), followed by infections (33.3%). Corticosteroids were administered to 79.3% of patients with hemorrhage, and 90.6% of patients with LAHPS showed improvement. In conclusion, LAHPS is most commonly observed in female patients, particularly those under 18 years of age. LAHPS is characterized by hemorrhage, occurring at various sites and with varying degrees of severity, but the majority of patients improve with appropriate treatment and management.

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.

A Chinese Boy With Lupus Anticoagulant-hypoprothrombinemia Syndrome: A Case Report and Review of the Literature.

We herein report an unusual case of lupus with bleeding diathesis in a Chinese adolescent boy. In the presence of lupus anticoagulant and hypoprothrombinemia, the diagnosis of lupus anticoagulant-hypoprothrombinemia syndrome was made. He responded promptly to immunosuppressive agents and achieved disease remission.

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 Glasgow Outcome Scale-Extended Pediatric Scores of Intracranial Bleeding Patients with Acquired Prothrombin Complex Deficiency Post Craniotomy and Duraplasty.

INTRODUCTION: Surgical evacuation of intracranial bleeding in pediatric patients due to acquired prothrombin complex deficiency (APCD) is a life-saving surgery when conservative treatment insufficient and impending brain herniation. This study aimed to evaluate the Glasgow outcome scale-extended pediatric (GOS-ePed) score of the pediatric intracranial bleeding patients with APCD after craniotomy and duraplasty. METHOD: This was a retrospective study in the last 5 years of our experience. All of the pediatric patients with intracranial bleeding due to APCD who needed surgery were investigated. The data were collected from medical records after their parents have given their written informed concern and approved by the Ethics Review Committee, Faculty of Medicine, Universitas Kristen Indonesia. The inclusion criteria were patients who operated on by craniotomy and duraplasty. The patient with a second disease was excluded. Blood tests include hemoglobin, prothrombin time, activated prothrombin time, and platelets were investigated before and after intravenous vitamin K injection, transfusion packed red cells (PRCs), and fresh frozen plasma (FFP) administration. The Glasgow coma scale (GCS) pre- and postoperatively was evaluated using a modified GCS for infants and children. The outcome was evaluated by the GOS-ePed score. All data were analyzed with the normality test and paired t test. RESULTS: There were 5 patients age between 37 and 60 days, and all patients did not get vitamin K prophylaxis after birth. The blood tests of all patients revealed anemia, prothrombin, and activated prothrombin time increased, but platelets were normal. All these values returned to normal after vitamin K injection, transfusion of PRCs, and FFP. The paired t tests were p < 0.05. The GCS of all patients before surgery was 8 or below. After surgery, the GCS of 4 patients was increased become 12 and 15. One patient did not change significantly. The GOS-ePed score showed 4 patients (80%) had upper or lower good recovery, and 1 patient (20%) was in a vegetative state. CONCLUSIONS: The GOS-ePed score of the pediatric intracranial bleeding with APCD after craniotomy and duraplasty was mostly in upper or lower good recovery.

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.

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.

Lupus anticoagulant hypoprothrombinemia syndrome associated with severe thrombocytopenia in a child.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) comprises lupus anticoagulant, acquired hypoprothrombinemia, and often mild thrombocytopenia or normal platelets. It is usually associated with autoimmunity or postviral illness. We describe a case of a 10-year-old boy with oral bleeding and severe thrombocytopenia initially suggestive of immune thrombocytopenia. Secondary to bleeding, evaluation demonstrated prolonged coagulation tests and subsequently revealed the presence of lupus anticoagulant and hypoprothrombinemia, along with marked autoimmunity, suggestive of LAHPS. He was treated with intravenous immunoglobulin and hydroxychloroquine. This case report and discussion highlight the diagnostic and therapeutic challenges associated with LAHPS and coincident severe thrombocytopenia.

Lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature.

Lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) is a rare acquired disorder caused by prothrombin antibodies. The disease is most common in the pediatric age group (<16 years), and more prevalent in women. There are well-established clinical diseases associated with LA-HPS, most notably systemic lupus erythematosus (SLE) and viral infections. The clinical manifestation of LA-HPS varies greatly in severity and it may cause severe life-threatening bleeding diathesis. LA-HPS is to be suspected when a patient presents with bleeding and a prolonged activated partial thromboplastin and prothrombin time, in combination with a lupus anticoagulant. The diagnosis is confirmed in the laboratory by identification of reduced prothrombin levels. There are no standardized recommendations for treatment of the hemorrhage associated with the syndrome; corticosteroids are used as first-line treatment. This review summarizes what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of LA-HPS, and presents two case reports.

[Lupus anticoagulant-hypoprothrombinemia syndrome revealing systemic lupus in an 11-year old girl in a context of clinical and biological emergency]. / Syndrome lupus anticoagulant-hypoprothrombinémie révélant un lupus chez une enfant de 11 ans dans un contexte d'urgence clinicobiologique.

We report a case of lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) in an 11 year old girl initially hospitalized for bleeding. The patient presented with petechia, persisting bleeding after tooth extraction performed two days before, nephritic syndrome (renal failure, proteinuria and macroscopic hematuria), severe anemia, thrombocytopenia, lymphopenia. The association of these abnormalities suggested LAHPS secondary to severe systemic lupus. Immediate treatment with fresh frozen plasma and intravenous immunoglobulins (400 mg/kg/5d) was started and followed by steroid (500 mg/d) and cyclophosphamide (800 mg/m(2)) pulse therapy leading to rapid improvement of bleeding, renal involvement and prothrombin levels within 13 days. Lupus diagnosis was confirmed by immunological investigations and renal biopsy. Two early relapses occurred despite adequate treatment. After a follow-up of two years, no further disease activity is noted while the patient is treated only by mycophenolate mofetil (1 200 mg/m(2)/d). LAHPS did not relapse during this follow-up.

[Lethal poisoning with the death-cap mushrooms].

We have analysed morphological manifestations in five cases of lethal poisoning with the Death Cap toxin and compared the relevant clinical and laboratory findings with those in 15 survived subjects. It was shown based on the results of autopsy that poisoning was associated with hepatopathy, extensive hepatic necrosis, and nephropathy. Elevated blood bilirubin levels in conjunction with lowered prothrombin and fibrin concentrations appear to be the main causative factors responsible for the unfavourable prognosis of this intoxication.

The clinical significance of the lack of arterial or venous thrombosis in patients with congenital prothrombin or FX deficiency.

Several reports have dealt with the occurrence of both arterial and venous thrombosis in patients with haemophilia A, haemophilia B, and von Willebrand disease. Similar thrombotic events have been occasionally reported also in rare congenital coagulation disorders, particularly in fibrinogen or FVII deficiencies. On the contrary no sure venous or arterial thrombotic event has ever been reported in congenital prothrombin or Factor X deficiency. The significance of this observation is discussed. This discrepancy cannot be explained on the basis of the rarity of the two conditions, since in similarly rare congenital bleeding disorders such as FV or FXIII deficiency a few patients with thrombosis have been described. It appears that only these two defects are able to allow a sure protection from thrombosis. These observations may indirectly support the rationale for the use of direct thrombin or Factor X inhibitors in the prophylaxis and/or therapy of thrombotic manifestations.

[Biochemicals markers of risk for mortality in necrotizing fasciitis]. / Marcadores bioquímicos de riesgo para mortalidad por fascitis necrotizante.

OBJECTIVE: To identify if anemia, hypoalbuminemia, hypocalcemia, elevated values of creatinephosphokinase and hypoprothrombinemia are risk for mortality in necrotizing fasciitis according to the anatomical site and affected surface. METHODS: A case and controls study was done in one prospective cohort. We documented age, associated factors, infection location, affected corporal surface, laboratory data, germs, treatment and evolution. We defined two groups of patients: deceased and survivors and we stratified in 6 subgroups according to the anatomical site. RESULTS: 394 patients were included; 252 men and 142 women, age average 52.8 years. We stratified in subgroups: extremities (n = 113), masculine genital (n = 103), trunk and abdomen (n = 64), neck and thorax (n = 44), feminine genital, perineum, groin (n = 42), sacrum and buttocks (n = 28). Hypoalbuminemia (OR = 3.8, CI = 1.5-9.5, p < 0.000), hypocalcemia (OR = 5.7, CI = 3.2-9.9, p= 0.030), elevated creatinephosphokinase (OR = 1.5, CI 1.0-2.4, p < 0.000) and anemia (OR = 4.4, CI 2.8-6.9, p < 0.000), were associated to mortality. Logistic regression analysis found that albumin (OR = 3.8, CI = 1.5-8.9), prothrombin (OR = 6.6, CI = 3.6-19.5) and evolution time (OR 5.2, IC = 1.2-8.3) showed statistically significant relationship with mortality (p < 0.05). CONCLUSIONS: Hypocalcemia, hypoprothrombinemia, anemia, elevated creatinephosphokinase and evolution time could be risk markers for mortality.

Stereoselective interaction of phenylbutazone with [12C/13C]warfarin pseudoracemates in man.

To evaluate the interaction of phenylbutazone with racemic warfarin or R,S-(+/-)-warfarin in man, S-(-)-warfarin or levowarfarin was synthesized with (13)C label in the 2-position of the coumarin nucleus and added to [(12)C]R(+)-warfarin or dextrowarfarin to form a [(12)C/(13)C]pseudoracemate of warfarin. In six normal human subjects, a single oral dose of this "cold labeled" pseudoracemate, 1.5 mg/kg body weight, was administered with and without a daily dosage of phenylbutazone, 300 mg orally, beginning 3 d before the warfarin dose and continuing throughout the hypoprothrombinemia. Plasma samples were obtained daily and analyzed for warfarin content and for one-stage prothrombin activity. Unchanged warfarin in the plasma was fractionated by normal-phase, high-pressure liquid chromatography, and the enantiomorphic ratios were determined by chemical-ionization mass spectrometry with pentadeuteriowarfarin as the internal standard. A highly significant augmentation of the hypoprothrombinemia of the pseudoracemate occurred during the phenylbutazone regimen (P < 0.001) compared with pseudoracemic warfarin administered alone. There was a highly significant increase in the plasma clearance of dextrowarfarin (P < 0.01) and a significant decrease in the plasma clearance of levowarfarin (P < 0.05) during the phenylbutazone regimen compared with administration of warfarin alone. It was concluded that phenylbutazone augmented the hypoprothrombinemia of pseudoracemic warfarin stereoselectively by inhibiting the metabolic disposition of the more hypoprothrombinemic levowarfarin, yet reduced the plasma levels of pseudoracemic warfarin by greatly augmenting the metabolic disposition of dextrowarfarin.

Monocyte procoagulant activity in glomerulonephritis associated with systemic lupus erythematosus.

Monocyte infiltration and activation of the coagulation system have been implicated in the pathophysiology of glomerulonephritis. In this study, spontaneous procoagulant activity (PCA) was measured in circulating mononuclear cells to determine whether elevated PCA correlated with the presence of proliferative glomerulonephritis in patients with systemic lupus erythematosus (SLE). No increase in PCA was found in 20 patients with end-stage renal failure, 8 patients with glomerulonephritis without SLE, and 10 patients undergoing abdominal surgical or orthopedic procedures as compared with 20 normal controls. In eight patients with SLE but with no apparent active renal disease, PCA was not elevated above normal basal levels. Seven additional patients with SLE who had only mesangial proliferation on biopsy also had no increase in PCA. In contrast, eight patients with focal or diffuse proliferative lupus nephritis, and one patient with membranous nephritis who ultimately developed a proliferative lesion, had a marked increase in PCA with greater than 100 times the base-line levels. The activity was shown to originate in the monocyte fraction of the mononuclear cells and was shown to be capable of cleaving prothrombin directly. The prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors. Monocyte plasminogen activator determinations did not correlate with renal disease activity. We conclude that monocyte procoagulant activity, a direct prothrombinase, seems to correlate with endocapillary proliferation in lupus nephritis and could be a mediator of tissue injury.