vitamin-k-semiquinone-radical and Lupus-Erythematosus--Systemic

Autoimmune myelofibrosis is a distinct clinicopathological entity that occurs with autoimmune disorders. We report the case of a 44-year-old woman admitted with pancytopenia and clinical features of systemic lupus erythematosus, Sjogren's syndrome and antiphospholipid antibodies syndrome. Bone marrow biopsy showed decreased global cells and an increase of reticulin fibres on argentic coloration, consistent with myelofibrosis. The JAK2 V617, Myeloproliferative leukemia (MPL) and calreticulin mutations were negative. The patient's condition improved after treatment with hydroxychloroquine, vitamin K antagonists and prednisone.

Topics: Adult; Anti-Inflammatory Agents; Antiphospholipid Syndrome; Antirheumatic Agents; Autoimmune Diseases; Diagnosis, Differential; Female; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Pancytopenia; Prednisone; Primary Myelofibrosis; Sjogren's Syndrome; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Antiphospholipid Syndrome; Antirheumatic Agents; Drug Therapy, Combination; Endocarditis; Follow-Up Studies; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Multifocal avascular osteonecrosis (AON) is a serious manifestation of systemic lupus erythematosus (SLE). Prothrombotic factors, especially antiphospholipid antibodies (aPL), have been associated with the development of AON; therefore, attenuating the procoagulant state while balancing the haemorrhagic risks might have a rationale when managing this condition. We report a case of a 37-year-old patient with SLE, treated with low doses of corticosteroids and immunosuppressive therapy, who was started on vitamin K antagonist following an episode of deep vein thrombosis while having persistent positivity for aPL. After 2 years, he presented with multifocal AON, involving both femurs and shoulders. The patient underwent a bilateral hip replacement, but despite appropriate anticoagulation therapy after 2 years, he developed another episode of AON at both distal epiphyses of the femurs and proximal epiphyses of the tibias. Multifocal AON should be suspected, especially in the presence of aPL positivity. Its aetiology is still unknown and is most likely multifactorial. Its management is challenging and requires combined approaches.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Diagnosis, Differential; Humans; Lupus Erythematosus, Systemic; Male; Osteonecrosis; Rare Diseases; Treatment Outcome; Venous Thrombosis; Vitamin K

Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population.. Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples.. Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients.. The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE.

Topics: Adult; Female; Humans; Intercellular Signaling Peptides and Proteins; Lupus Erythematosus, Systemic; Male; Middle Aged; Peptide Fragments; Polymorphism, Single Nucleotide; Protein S; Real-Time Polymerase Chain Reaction; Receptor Protein-Tyrosine Kinases; Vitamin K

To describe ocular manifestations and particularly optical coherence tomography (OCT) findings in choroidopathy revealing a systemic lupus erythematosus, without systemic hypertension.. Observational case report.. The diagnosis of systemic lupus erythematosus choroidopathy was suggested by the ocular presentation. Serous retinal detachments were confirmed using fluorescein and indocyanine green angiography. OCT was useful to monitor the regression of the serous retinal detachments. The anatomical and functional evolution was good under immunosuppressive treatment.. In this case, the choroidopathy was inaugural and signed the lupus activity. The OCT follow-up facilitated the monitoring of the efficacy of systemic medications.

Topics: 4-Hydroxycoumarins; Adolescent; Adrenal Cortex Hormones; Angiography; Antibodies, Antinuclear; Aspirin; Azathioprine; Choroid Diseases; Drug Monitoring; Female; Fluorescein; Humans; Immunosuppressive Agents; Indenes; Lupus Erythematosus, Systemic; Organic Chemicals; Retinal Detachment; Tomography, Optical Coherence; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Clinical Trials as Topic; Female; Hemorrhage; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Pregnancy; Recurrence; Retrospective Studies; Risk; Vitamin K; Warfarin

Oral anticoagulant therapy, which is used for prophylaxis and management of thrombotic disorders, causes similar reductions in plasma levels of vitamin K-dependent procoagulant and anticoagulant clotting factor zymogens. When we measured levels of circulating activated protein C, a physiologically important anticoagulant and anti-inflammatory agent, in patients on oral anticoagulant therapy, the results unexpectedly showed that such therapy decreases levels of activated protein C substantially less than levels of protein C, prothrombin, and factor X, especially at lower levels of prothrombin and factor X. Thus, we suggest that oral anticoagulant therapy results in a relatively increased expression of the protein C pathway compared with procoagulant pathways not only because there is less prothrombin to inhibit activated protein C anticoagulant activity, but also because there is a disproportionately higher level of circulating activated protein C.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation Factors; Factor X; Heart Diseases; Humans; Lupus Erythematosus, Systemic; Protein C; Prothrombin; Vitamin K

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Female; Hematuria; Humans; Hypoprothrombinemias; Lupus Erythematosus, Systemic; Prednisone; Prothrombin; Prothrombin Time; Thromboplastin; Vitamin K

Topics: Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Diagnosis; Diet; Diet Therapy; Female; gamma-Globulins; Hepatitis; Hepatitis A; Hepatitis B virus; Hyperemesis Gravidarum; Liver Function Tests; Lupus Erythematosus, Systemic; Methyltestosterone; Norethindrone; Pneumonia; Prednisone; Pregnancy; Pregnancy Complications, Infectious; Pyelonephritis; Thioguanine; Toxicology; Vitamin K