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.

Lupus anticoagulant-hypoprothrombinemia syndrome and similar diseases: experiences at a single center in Japan.

Patients with lupus anticoagulant (LA), a thrombotic risk factor, along with decreased prothrombin (FII) activity are classified as lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) and occasionally show bleeding symptoms, although this is not essential for diagnosis. We treated 20 cases of LAHPS over a 3-year period. Median FII activity was 20.9% and the anti-prothrombin antibody (anti-II Ab), shown by ELISA findings, was detected in 55%. Bleeding symptoms were observed in 20%, although that finding was not correlated with FII activity or anti-FII Ab quantity. We also observed 21 LA cases with decreased activity of coagulation factors other than FII, which we have designated LAHPS-like syndrome (LLS). Among LLS patients, anti-FII Ab and bleeding symptoms were seen in 47.6% and 14.3%, respectively. Our findings suggest that bleeding in LAHPS and LLS cannot be explained only by FII activity decreased by anti-FII Ab. Low FVIII activity and the anti-FVIII antibody (anti-FVIII Ab) were detected in some LAHPS and LLS patients, making it difficult to distinguish those from acquired hemophilia A cases. Detection of anti-FVIII Ab quantity by ELISA may be useful for accurate determination, as that was not performed in our LAHPS or LLS patients.

Effects of intravenous fluid overload on caloric and protein deficit in critically ill patients.

INTRODUCTION: intravenous fluid overload may lead to dysmotility that may impair early enteral nutrition delivery in critically ill patients. OBJECTIVES: this study aimed to compare the volume of intravenous fluids (IF) with the occurrence of caloric and protein deficits in Intensive Care Unit (ICU) patients. METHODS: this cohort study included critically ill patients with mechanical ventilation and receiving early enteral nutrition (target: 25-30 kcal/kg/day and 1.25-2.0 g of protein/kg/day). Over the first five days the volume of IF infused and caloric/protein deficits were calculated. RESULTS: eighty-six critically ill patients (SAPS III score: 62 ± 10) with a mean age of 68 (18-91) years were enrolled. Patients received a median of 2,969 (920-5,960) ml/day of IF, which corresponded to a median of 41.6 (17.0-88.2) ml/kg/day and 10.7 (3.31-21.45) g of sodium/day. All patients had a caloric deficit (mean: 1,812 ± 850 kcal over five days) and in 23 (27%) this deficit exceeded 480 kcal/day. The mean protein deficit was 94.6 ± 5.9 g over five days, and 34 patients (40%) had more than 20 g of deficit/day. Patients with caloric deficit greater than 480 kcal/day received approximately 1.5 l of IF and 10 g of NaCl more than the other patients. Similarly, patients with protein deficit greater than 20 g/day received approximately 3 l of IF and 25 g of NaCl more than the other patients. Mortality was greater in patients with critical protein deficit (69% vs 41.1%; p = 0.01). CONCLUSION: in critically ill patients receiving enteral nutrition, the volume of intravenous fluids infused affected nutrition delivery and increased caloric and protein deficits.

Effects of intravenous fluid overload on caloric and protein deficit in critically ill patients / Efectos de la sobrecarga de líquidos por vía intravenosa en el défi cit calórico y proteico en pacientes críticamente enfermos

Introduction: intravenous fluid overload may lead to dysmotility that may impair early enteral nutrition delivery in critically ill patients. Objectives: this study aimed to compare the volume of intravenous fluids (IF) with the occurrence of caloric and protein deficits in Intensive Care Unit (ICU) patients. Methods: this cohort study included critically ill patients with mechanical ventilation and receiving early enteral nutrition (target: 25-30 kcal/kg/day and 1.25-2.0 g of protein/kg/day). Over the first five days the volume of IF infused and caloric/protein deficits were calculated. Results: eighty-six critically ill patients (SAPS III score: 62 ± 10) with a mean age of 68 (18-91) years were enrolled. Patients received a median of 2,969 (920-5,960) ml/day of IF, which corresponded to a median of 41.6 (17.0-88.2) ml/kg/day and 10.7 (3.31-21.45) g of sodium/day. All patients had a caloric deficit (mean: 1,812 ± 850 kcal over five days) and in 23 (27%) this deficit exceeded 480 kcal/day. The mean protein deficit was 94.6 ± 5.9 g over five days, and 34 patients (40%) had more than 20 g of deficit/day. Patients with caloric deficit greater than 480 kcal/day received approximately 1.5 l of IF and 10 g of NaCl more than the other patients. Similarly, patients with protein deficit greater than 20 g/day received approximately 3 l of IF and 25 g of NaCl more than the other patients. Mortality was greater in patients with critical protein deficit (69% vs 41.1%; p = 0.01).Conclusion: in critically ill patients receiving enteral nutrition, the volume of intravenous fluids infused affected nutrition delivery and increased caloric and protein déficits

Introducción: la sobrecarga de líquidos por vía intravenosa puede provocar dismotilidad que puede afectar el suministro de nutrición enteral temprana en pacientes críticos. Objetivos: este estudio tuvo como objetivo comparar el volumen de líquidos por vía intravenosa (IF) con la aparición de défi cit calórico y proteico en pacientes de la Unidad de Cuidados Intensivos (UCI). Métodos: este estudio de cohorte incluyó a pacientes críticamente enfermos con ventilación mecánica que recibían nutrición enteral temprana (target: 25-30 kcal/kg/día y 1,25-2,0 g de proteína/kg/día. Durante los primeros cinco días calculamos el volumen de IF y el déficit calórico/ proteico. Resultados: ochenta y seis pacientes críticamente enfermos (SAPS III: 62 ± 10) con una edad media de 68 (18-91) años fueron estudiados. Los pacientes recibieron una mediana de 2.969 (920-5.960) ml/día de IF, que correspondió a una mediana de 41,6 (17,0-88,2) ml/kg/día y a 10,7 (3,31-21,45) g de sodio/día. Todos los pacientes tenían déficit calórico (media: 1.812 ± 850 kcal en cinco días) y en 23 (27%) este défi cit excedía las 480 kcal/día. El défi cit medio de proteínas fue de 94,6 ± 5,9 g en cinco días y 34 pacientes (40%) tuvieron más de 20 g de déficit/ día. Los pacientes con un déficit calórico superior a 480 kcal/día recibieron aproximadamente 1,5 l de IF y 10 g de NaCl más que los otros pacientes. De forma similar, los pacientes con un déficit de proteínas mayor de 20 g/día recibieron aproximadamente 3 l de IF y 25 g de NaCl más que los otros pacientes. La mortalidad fue mayor en pacientes con défi cit proteico crítico (69% vs. 41,1%; p = 0,01). Conclusión: en pacientes críticamente enfermos que reciben nutrición enteral, el volumen de líquidos intravenosos infundidos afecta el suministro de nutrición y aumenta el déficit de calorías y proteínas

[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 (LAC-HPS) in Children With Systemic Lupus Erythematosus: Report of 3 Cases.

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.

Lupus anticoagulant-hypoprothrombinemia syndrome presenting with co-existing cerebral venous thrombosis and subdural hemorrhage.

The lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) - the association of acquired factor II deficiency and lupus anticoagulant - is a rare disease that may cause a predisposition not only to thrombosis but also to severe bleeding. We are reporting on a 36-year-old female patient presenting with co-existing cerebral venous thrombosis and subdural hemorrhage. The coagulation screening showed a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and a normal fibrinogen level and platelet count. Evaluation of the clotting factors revealed decreased levels of factors II (37%). Factors V, VIII, IX and XI were normal. Lupus anticoagulant (LA) was demonstrated by the Dilute Russell's Viper Venom Test (DRVVT). Immunological work-up was positive for IgG type anticardiolipines antibodies (aCL). Successful management consisted first of oral prednisone (60mg/d). Thus, anticoagulation was introduced once factor II had stabilized.

The challenge of bleeding in antiphospholipid antibody-positive patients.

Antiphospholipid antibody-positive patients can develop bleeding due to capillaritis, microthrombosis, antiprothrombin antibodies, thrombocytopenia, and/or excessive antithrombotic therapy. Clinical characteristics of patients, e.g., renal impairment, elderly, or concomitant medications, are closely related to the risk of bleeding. The management of bleeding in antiphospholipid antibody (aPL)-positive patients is challenging due to the baseline increased risk of thrombosis. If anticoagulation is stopped, it should be restarted as soon as possible once the acute bleeding is controlled; the continuation of anticoagulation despite active bleeding may be required in selected cases. High-dose corticosteroid is the mainstay treatment for diffuse alveolar hemorrhage, lupus anticoagulant-hypoprothrombinemia syndrome, and severe thrombocytopenia; immunosuppressive drugs are also required to improve the long-term outcomes. Hydrocortisone is critical in adrenal hemorrhage patients due to concomitant adrenal insufficiency; despite bleeding, anticoagulation should be maintained as much as possible. Plasma exchange should be considered in catastrophic antiphospholipid syndrome patients with concurrent bleeding. This article will review the causes of bleeding in aPL-positive patients as well as the management strategies.

[A case of lupus anticoagulant hypoprothrombinemia syndrome following adenovirus gastroenteritis and mycoplasma pneumonia].

We describe a previously healthy 9-year-old girl who had multiple purpura several days after acute adenovirus gastroenteritis and mycoplasma pneumonia. Initial laboratory evaluation revealed a prolonged prothrombin time (PT) and APTT, low complement levels (C4, CH50), and positive immune complex (C1q) in her serum. Platelet count, fibrinogen, and other routine blood chemistry tests were normal. The prolonged APTT was not corrected by mixture of the patient's plus normal plasma. Clotting activities of factors II, V, VIII, IX, X, XI, and XII reduced. Further examinations revealed the presence of lupus anticoagulant (LA), phosphatidylserine-dependent anti-prothrombin antibodies (aPS/PT), and anticardiolipin antibodies. Mycoplasma pneumonia was treated by minocycline and the patient's skin lesions disappeared spontaneously within a week. During follow-up, she showed no other bleeding symptoms, and no signs of SLE or other autoimmune diseases. Four weeks after admission to our hospital, blood coagulation tests and serum complements normalized. Clotting activities of factors and antiphospholipid antibodies were not detected, half year later. The bleeding in this case was associated with acquired hypoprothrombinemia caused by antiphospholipid antibodies following acute adenovirus gastroenteritis and mycoplasma pneumonia.

"Cowboy's belt with revolver" scleroderma caused by vitamin K1 injections.

Vitamin K1 (phytomenadione or phytonadione) is a fat soluble vitamin used to treat certain coagulation disorders. Intra muscular injection of vitamin K1 can occasionally be complicated by different types of skin reactions: erythematous plaques, urticarial rashes or scleroderma-like lesions at the injection site. We report the case of a 52-year-old man presenting with 2 symmetrical erythematous-infiltrated scleroderma-like plaques localized on the right and left lower trunk. To correct the coagulation deficiency with hypoprothrombinemia developed as a consequence of HCV+ hepatitis, the patient was on vitamin K1 therapy, administered by i.m. injection (10 mg Vitamin K1/1 ml) once a day for 2 weeks. Three months after treatment interruption, ivory indurated morphoeiform plaques developed at the injection sites, assuming the typical appearance of a "cowboy's belt with revolver". The scleroderma-like lesions persisted 2 years after vitamin K1 withdrawal. We report this case to highlight the possibility that vitamin K1 injections can occasionally be complicated by different types of skin reactions such as sclerodermatous plaques. Due to the delay in the onset, to the variable clinical picture, to the persistence after therapy interruption, this kind of lesions can represent a tricky diagnostic challenge and in spite of different treatments can endure for years.

[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.

Anticuerpos antiprotrombina positivos en una paciente con síndrome antifosfolípido secundario y clínica hemorrágica / Antiprothrombin antibodies in a patient with secondary antiphospholipid syndrome and bleeding

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[Hypoprothrombinemia--lupus anticoagulant syndrome]. / Síndrome de hipoprotrombinémia--anticoagulante lúpico.

Diagnosis criteria, pathogenic mechanisms, incidence and prevalence of the Antiphospholipid Syndrome are focused in a brief review. Hypoprothrombinemia (HPT) may be hereditary or acquired; the first is rare and with recessive autossomic transmission. We report the case of a 66-year-old white woman with Systemic Lupus Erythematosus (SLE), autoimmune haemolytic anaemia, periostitis, haematomas, bleeding leg ulcer and rectal haemorrhages; she had decreased levels of the prothrombin. Haemorrhagic episodes were related with the anti-prothrombin specificity of Lupus Anticoagulant (LA) detected. The SLE/LA/HPT association is less frequent than the correlated to SLE/LA/anti- ß2Glycoprotein I antibodies and was first reported in 1960 by Rapaport et al, in an 11-year- -old girl with severe haemorrhagic manifestations.

Letter: Localized cutaneous reaction to intramuscular vitamin K in a patient with acute fatty liver of pregnancy.

Vitamin K1 is frequently used in the treatment and prevention of hypoprothrombinemia and hemorrhagic disease of the newborn. It also serves as an antidote to anticoagulants. Erythematous, indurated, pruritic plaques uncommonly occur in adults after intramuscular injection with vitamin K1. We present a case of a localized cutaneous reaction to intramuscular vitamin K1 in a peripartum patient with acute fatty liver of pregnancy. The history and clinical presentation of our case is presented with a discussion of the pathogenesis pathogenesis of vitamin K1 and available treatment for this condition.

Steady improvement of prothrombin levels after cyclophosphamide therapy in pediatric lupus anticoagulant hypoprothrombinemia syndrome (LAHPS).

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare acquired disorder associated with several different conditions but mostly with systemic lupus erythematosus (SLE). LAHPS probably results from the presence of anti-Factor II antibodies, which usually counterbalance the prothrombotic effect of the lupus anticoagulant (LAC). In fact, Factor II deficiency in SLE is invariably associated with the presence of LAC. No consensus exists for the treatment of LAHPS. Corticosteroids, with or without the addition of vitamin K or blood products, have been a successful first-line treatment. Immunoglobulin (IVIG) treatment has been shown to be effective in the setting of acute bleeding. However, in some patients, conservative treatment is not enough to control bleeding, and the addition of immunosuppressive therapy, usually azathioprine, is needed. In our patients, Factor II deficiency reappeared after tapering steroids. Both children achieved normal Factor II levels with cyclophosphamide. This effect was long-lasting, a phenomenon that has not been documented in children prior to this report.

Thromboembolism complicating the treatment of lupus anticoagulant hypoprothrombinemia syndrome.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare disorder characterized by a bleeding tendency due to factor II deficiency associated with the presence of lupus anticoagulant (LAC) autoantibodies. We describe a patient with systemic lupus erythematosus and LAHPS in whom successful treatment of central nervous system bleeding due to severe factor II deficiency was followed by a major thromboembolic complication. Literature review revealed 2 other patients with LAHPS who developed thrombosis resulting from the treatment of factor II deficiency. We suggest that factor II deficiency counterbalances the prothrombotic effect of LAC in LAHPS, and correcting this deficiency may promote thromboembolism.

Four factor deficiency.

Four factor deficiency is variably associated with mild to fatal bleeding. We describe a 3-month-old boy, born of consanguineous parents, who presented with a right subdural haematoma and a clotting screen showing a prothrombin time (PT) > 100 s, an activated partial thromboplastin time (aPTT) > 150 s, a fibrinogen of 0.4 g/l, and fibrinogen degradation products < 1 microg/ml. He was given 300 U of factor IX concentrate (containing factors II and X) and 1 mg of vitamin K intravenously. Forty-five minutes later, clotting tests showed a PT of 24 s, an aPTT of 31 s and a fibrinogen of 2.6 g/l. The patient was found to be deficient in all the vitamin K-dependent factors: factors II, VII, IX and X, protein C and protein S. A 14-base deletion was found in intron 1 (bases 1056-1069) of the gamma-carboxylase gene. The patient and his elder sister were homozygous for this deletion, whereas both parents were heterozygous. The deletion destroys a reverse palindromic sequence (TTGAGGCAA) of the type often associated with cis-acting elements. Our results suggest that this element may be involved in the regulation of gamma-carboxylase expression. Expression studies are being completed so that this region can be definitively ascribed as a cis-acting element involved in gene regulation.