Antiphospholipid antibodies(aPLs)are a heterogeneous group of autoantibodies that include anticardiolipin antibodies,anti-β2 glycoprotein I antibodies,and lupus anticoagulant.The presence of aPLs is the main characte...Antiphospholipid antibodies(aPLs)are a heterogeneous group of autoantibodies that include anticardiolipin antibodies,anti-β2 glycoprotein I antibodies,and lupus anticoagulant.The presence of aPLs is the main characteristic feature of antiphospholipid syndrome(APS),an autoimmune disease with multifactorial etiology.Kidney involvement is a well-recognized complication associated with both primary and secondary APS.Kidney involvement in APS presents with renal artery thrombosis,renal vein thrombosis,allograft loss due to thrombosis after kidney transplantation,and injury to the renal microvasculature,also known as APS nephropathy(APSN).APSN is the characteristic manifestation of kidney involvement in APS and occurs as a result of vaso-occlusive disease in the intrarenal vasculature.Diagnosis and risk stratification of APS are complex and still evolving.This review synthesizes and updates the available evidence in literature regarding risk factors,pathogenesis,and diagnosis of APS and APSN.展开更多
Antiphospholipid syndrome(APS)is a systemic autoimmune disorder characterized by the presence of antiphospholipid antibodies and is associated with thrombotic events and pregnancy complications.The classification and ...Antiphospholipid syndrome(APS)is a systemic autoimmune disorder characterized by the presence of antiphospholipid antibodies and is associated with thrombotic events and pregnancy complications.The classification and management of APS has evolved over time.The classification criteria for APS include laboratory,macrovascular,microvascular,obstetric,cardiac,and hematologic domains.Management focuses on prevention of thrombotic events and/or anticoagulation as the primary treatment for thrombosis.Postpartum and long-term thromboprophylaxis after delivery are recommended to reduce the risk of thrombotic events.Despite these recommendations,optimal anticoagulation agents and intensity of treatment are still topics of debate.Further research is needed to understand the pathophysiology of APS and improve its management during pregnancy.In this review,we discuss the classification and pathophysiology of APS.Current treatment options and clinical trials are also discussed.展开更多
BACKGROUND Cardiac sarcoidosis(CS)is an infiltrative disease with manifestations such as nonsustained ventricular tachycardia(NSVT)and heart failure(HF).Antiphospholipid syndrome(APS)and antiphospholipid positivity(AP...BACKGROUND Cardiac sarcoidosis(CS)is an infiltrative disease with manifestations such as nonsustained ventricular tachycardia(NSVT)and heart failure(HF).Antiphospholipid syndrome(APS)and antiphospholipid positivity(APP)are prothrombotic phenomena which elevate risk for thromboembolism.CS with active systemic sarcoid and APS/APP is a rare combination of diseases.CASE SUMMARY A 54 year old male with HF presented with several cardiopulmonary symptoms.Chest imaging showed bilateral patchy and reticulonodular infiltrates.Subsequent lung biopsy confirmed pulmonary sarcoidosis.Positron emission tomography revealed active systemic sarcoidosis(SS)and fibrotic CS.Positive antiphospholipid antibodies without thromboembolism confirmed APP.HF and APP were managed with medical therapy.Fibrotic CS and NSVT required permanent cardiac device and antiarrhythmic therapy.SS was managed with early taper of steroids and transition to biologics.CONCLUSION Fibrotic CS with active SS and APS/APP has not been previously described in literature.This case utilized a modified approach for the management of this combination of diseases.As immunosuppressants such as steroids have limited utility in fibrotic sarcoidosis and a potential for thromboembolic complications in the presence of APP,an accelerated transition to non-thrombotic immunosuppressants can be advantageous in the long term treatment of this combination of diseases.展开更多
Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a histo...Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a history of venous thromboembolism (VTE) on warfarin presented to the hospital with nausea, vomiting, and abdominal and flank pain shortly following colonoscopy preparation. Initial imaging of the abdomen and pelvis was notable for hyperdense thickening of the bilateral adrenal glands raising concerns for hemorrhages, and subsequent magnetic resonance imaging (MRI) confirmed BAH. During hospitalization, the patient was placed on prophylactic heparin, and shortly after decompensating, he became tachycardic, hypotensive, and febrile. This led to heparin reversal followed by administration of a single dose of Hydrocortisone 100 mg and Hydrocortisone 50 mg TID due to concern for adrenal insufficiency. The patient also necessitated sepsis work-up and fluid resuscitation. Repeat CT imaging showed no significant change in hemorrhage size bilaterally. Endocrinology, vascular surgery, hematology/oncology, and rheumatology were consulted for the management of adrenal insufficiency, anticoagulation in the presence of hemorrhage, thrombocytopenia, and hypercoagulable state. Towards the end of his hospital course, the patient had asymptomatic diffuse ST elevations, elevated troponin, and an ejection fraction of 10% - 15%, leading to cardiac catheterization and placement of an intra-aortic pump. During subsequent stay in the ICU, the patient developed hemodynamic shock and was transferred to a facility with a higher level of care and medical support therapies. After this transfer, the patient was stabilized from a cardiac standpoint but developed acute respiratory failure suspected to be secondary to diffuse alveolar hemorrhage and immune thrombocytopenic purpura, necessitating platelet transfusion. He was on continued monitoring from rheumatology given his myocarditis believed to be secondary to his antiphospholipid antibodies, and was treated with IVIG, rituximab, and hydroxychloroquine. A repeat echocardiogram revealed an improved ejection fraction of 52% and the patient was then discharged on an enoxaparin bridge to warfarin and a cardiac home event monitor. Discussion: BAH is a life-threatening condition that should be promptly identified and managed in patients presenting with nonspecific symptoms and a history of hypercoagulability or anticoagulation. In these cases, the risk of AH and subsequent adrenal insufficiency is drastically increased, so immediate imaging as well as initiation of steroid therapy is crucial to stabilize patients and prevent adrenal crisis. A multidisciplinary approach, involving endocrinology, hematology, and cardiology as in this case is also imperative to optimize patient outcomes and increase survival. Conclusion: BAH should be considered in patients presenting with a history of VTE and hypercoagulable state when precipitating stressors or predisposing risk factors are present. This case report highlights the importance of clinical awareness of BAH for clinicians to accurately identify and manage it to prevent fatal sequelae and ensure long-term favorable patient outcomes.展开更多
Thrombotic events,both arterial and venous,are a major health concern worldwide. Further,autoimmune diseases,such as systemic lupus erythematosus,anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis,and an...Thrombotic events,both arterial and venous,are a major health concern worldwide. Further,autoimmune diseases,such as systemic lupus erythematosus,anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis,and antiphospholipid syndrome,predispose to thrombosis,and thereby push the risk for these morbid events even higher. In recent years,neutrophils have been identified as important players in both arterial and venous thrombosis. Specifically,chromatin-based structures called neutrophil extracellular traps(NETs) play a key role in activating the coagulation cascade,recruiting platelets,and serving as scaffolding upon which the thrombus can be assembled. At the same time,neutrophils and NETs are emerging as important mediators of pathogenic inflammation in the aforementioned autoimmune diseases. Here,we first review the general role of NETs in thrombosis. We then posit that exaggerated NET release contributes to the prothrombotic diatheses of systemic lupus erythematosus,ANCA-associated vasculitis,and antiphospholipid syndrome.展开更多
Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From...Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From September to November 2020,clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang,Indonesia.Antiphospholipid antibodies were measured by finding Ig M anti-β2 glycoprotein,lupus anticoagulant,and Ig M/Ig G anticardiolipin.Clinical characteristics,thrombotic events,ICU admission,and mortality during hospitalization were recorded.Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19,Indonesia.Results:Among 50 patients,5 patients(10.0%)were positive for antiphospholipid antibodies:4 patients(80.0%)had Ig M anti-β2 glycoprotein and 1 patient had Ig G anti-cardiolipin(20.0%)and Ig M anti-cardiolipin(20.0%),none of lupus anticoagulant was detected.Antiphospholipid antibodies were associated with anosmia(OR 8.1;95%CI 1.1-57.9;P=0.018),nausea and vomiting(OR 12.4;95%CI 1.2-122.6;P=0.010),diarrhea(OR 9.8;95%CI 1.3-70.9;P=0.010),cardiovascular disease(OR 1.4;95%CI 1.0-1.9;P=0.001),chronic kidney disease(OR 12.0;95%CI 1.6-90.1;P=0.05),acute coronary syndrome(OR 29.3;95%CI 2.0-423.7;P=0.001),moderate(OR 0.11;95%CI 0.01-1.10;P=0.031)and severe(OR 18.5;95%CI 1.8-188.4;P=0.002)disease severity,and in-hospital mortality(OR 8.1;95%CI 1.1-57.9;P=0.018).However,there is no correlation between the presence of antiphospholipid antibody and ICU admission.Conclusions:In summary,the prevalence of antiphospholipid antibodies in COVID-19 patients is low,mainly against Ig M anticardiolipin,and is associated with an acute coronary syndrome,gastrointestinal manifestations,moderate and severe disease severity,and increased risk of mortality.展开更多
Warfarin is a widely used anticoagulant.Interindividual differences in drug response,a narrow therapeutic range and the risk of bleeding render warfarin difficult to use clinically.An 18-year-old woman with antiphosph...Warfarin is a widely used anticoagulant.Interindividual differences in drug response,a narrow therapeutic range and the risk of bleeding render warfarin difficult to use clinically.An 18-year-old woman with antiphospholipid syndrome received long-term warfarin therapy for a recurrent deep vein thrombosis.Six years later,she developed right flank pain.We diagnosed intrahepatic and subgaleal hemorrhages secondary to anticoagulation therapy.After stopping oral anticoagulation,a follow-up computed tomography showed improvement in the hemorrhage.After restarting warfarin because of a recurrent thrombosis,the intrahepatic hemorrhage recurred.We decided to start clopidogrel and hydroxychloroquine instead of warfarin.The patient has not developed further recurrent thrombotic or bleeding episodes.Intrahepatic hemorrhage is a very rare complication of warfarin,and our patient experienced intrahepatic and subgaleal hemorrhage although she did not have any risk factors for bleeding or instability of the international normalized ratio control.展开更多
This article reports a rare case of bilateral choroidal occlusion that occurred in a 24-year-old woman with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE). This young lady concurred...This article reports a rare case of bilateral choroidal occlusion that occurred in a 24-year-old woman with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE). This young lady concurred with aorta ventralis thrombosis and bilateral iliac artery occlusion when presented, and experienced a rapid deterioration of vision. She also has a history of recurrent miscarriage. Corticosteroid,immunosuppression and anticoagulation therapy were administered. Patients with APS associated with SLE are at risk for thrombotic phenomena, which may affect the ocular vessels of all sizes, including choroidal vessel.Our case alerts ophthalmologists and rheumatologists that bilateral choroidal occlusion may indeed be developed in patients with APS associated with SLE, and is a potential cause of visual morbidity.展开更多
Antiphospholipid syndrome(APS)or Hughes syndrome is an acquired thromboinflammatory disorder.Clinical criteria of APS diagnosis are large-and small-vessel thrombosis as well as obstetric problems;laboratory criteria a...Antiphospholipid syndrome(APS)or Hughes syndrome is an acquired thromboinflammatory disorder.Clinical criteria of APS diagnosis are large-and small-vessel thrombosis as well as obstetric problems;laboratory criteria are the presence of antiphospholipid antibodies(lupus anticoagulant,anticardiolipin antibodies and anti-β2-glycoprotein-1).The presence of at least 1 clinical and 1 laboratory criterion allows definitive diagnosis of APS.Primary APS is diagnosed in patients without features of connective tissue disease;secondary APS is diagnosed in patients with clinical signs of autoimmune disease.A high frequency of catastrophic APS as well as a high tendency to evolve from primary APS to secondary syndrome during the course of lupus and lupus-like disease is a feature of pediatric APS.The most characteristic clinical presentation of APS in the pediatric population is venous thrombosis,mainly in the lower limbs,and arterial thrombosis causing ischemic brain stroke.Currently,no diagnostic criteria for pediatric APS exist,which probably results in an underestimation of the problem.Similarly,no therapeutic procedures for APS specific for children have yet been established.In the present literature review,we discussed data concerning APS in children and its role in cerebrovascular diseases,including pediatric arterial ischemic stroke,migraine and cerebral venous thrombosis.展开更多
AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 ...AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.展开更多
BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to t...BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to thrombosis.In contrast,patients with primary hyperfibrino-lysis tend to bleed.CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with"tuberculous pleurisy"and treated with anti-tuberculosis drugs and prednisone.The coagulation-related laboratory results showed decreased fibrinogen,PC activity,PS activity,and antithrombinШactivity.The immune-related laboratory results showed positive antinuclear antibody,anti-Smith antibody,anticardiolipin antibody(ACL),anti-β2-glycoprotein I antibody(aβ2GPI)and direct Coomb’s test and decreased complement 3 and complement 4.Thoracoscopy was performed and bloody pleural fluid was drained.Pathology of the pleural biopsy showed lymphocytes,plasma cells,and a few eosinophils in adipose and fibrous connective tissue.Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases.The patient was finally diagnosed with SLE and primary hyperfibrinolysis,and was treated with prednisolone,hydroxychloroquine,and compound cyclophosphamide.CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI.SLE and primary hyperfibrinolysis can coexist in one patient,with both a risk of thrombosis and a risk of bleeding.展开更多
Antiphospholipid syndrome is a multi-system disease characterized by the formation of thromboembolic complications and/or pregnancy morbidity, and with persistently increased titers of antiphospholipid antibodies. We ...Antiphospholipid syndrome is a multi-system disease characterized by the formation of thromboembolic complications and/or pregnancy morbidity, and with persistently increased titers of antiphospholipid antibodies. We report the case of a 50-year-old, previously healthy man who presented with fever and new-onset, dull abdominal pain. A contrast-enhanced computed tomography scan showed segmental small bowel obstruction, for which an emergency laparotomy was performed. Histopathologic examination of resected tissues revealed multiple intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum antiphospholipid(anticardiolipin Ig M) and anti-β2-glycoprotein I antibodies were positive. Despite proactive implementation of anticoagulation, steroid, and antibiotic therapies, the patient's condition rapidly deteriorated, and he died 22 d after admission. This case highlights that antiphospholipid syndrome should be suspected in patients with unexplainable ischemic bowel and intestinal necrosis presenting with insidious clinical features that may be secondary to the disease, as early diagnosis is critical to implement timely treatments in order to ameliorate the disease course.展开更多
The antiphospholipid syndrome(APS)is a multi-systemic disease being characterized by the presence of antiphospholipid antibodies that involves both arterial and venous systems resulting in arterial or venous thrombosi...The antiphospholipid syndrome(APS)is a multi-systemic disease being characterized by the presence of antiphospholipid antibodies that involves both arterial and venous systems resulting in arterial or venous thrombosis,fetal loss,thrombocytopenia,leg ulcers,livedo reticularis,chorea,and migraine.We document a previously unreported case of a 37-year-old female in whom APS was first manifested by infarction and cecal perforation following cesarean section.At laparotomy the underlying cause of colonic perforation was not clear and after resection of the affected bowel an ileo-colostomy was performed.The diagnosis of APS was established during post-operative hospital stay and the patient was commenced on warfarin.Eventually,she made a full recovery and had her stoma reversed after 4 mo.Pregnancy poses an increased risk of complications in women with APS and requires a more aggressive approach to the obstetric care.This should include full anticoagulation in the puerperium and frequent doppler ultrasound monitoring of uterine and umbilical arteries to detect complications such as preeclampsia and placental insufficiency.展开更多
Gallbladder disease is no more common in patients with systemic lupus erythematosus (SLE) than in the general population. We describe a 17-year-old patient with SLE, who developed nephritis that was well controlled wi...Gallbladder disease is no more common in patients with systemic lupus erythematosus (SLE) than in the general population. We describe a 17-year-old patient with SLE, who developed nephritis that was well controlled with medications. Initial treatment consisted of azathioprine, aspirin and prednisone with stable control of her symptoms. Two years later she developed a right quadrant abdominal pain, and an abdominal ultrasound revealed microlithiasic cholecystitis. Open cholecystectomy was performed and the histopathological findings revealed vasculitis with thrombotic microangiopathy in the gallbladder. This case presentation illustrates that calculous or acalculous cholecystitis should be considered as a manifestation of active SLE and APS.展开更多
MAKING accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations.The possibility that vasculitis associated with systemic lupus erythematosus(SLE...MAKING accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations.The possibility that vasculitis associated with systemic lupus erythematosus(SLE)and antiphospholipid syndrome(APS)can be misdiagnosed as cysticercosis has not been discussed in the literatures.展开更多
The antiphospholipid syndrome(APS) is an acquired thrombophilic disorder in which autoantibodies are produced to a variety of phospholipids determinants of cell membranes or phospholipid binding proteins. There are fe...The antiphospholipid syndrome(APS) is an acquired thrombophilic disorder in which autoantibodies are produced to a variety of phospholipids determinants of cell membranes or phospholipid binding proteins. There are few reports about association between antiphospholipid antibodies and development of BuddChiari syndrome(BCS). We report the case of BCS development in young Russian male with primary APS. The patient underwent orthotopic liver transplantation on August 26, 2012. At present time his state is good, the blood flow in the liver restored and its function is not impaired. We report about the first time the successful use of dabigatran etexilate for prolonged anticoagulation therapy in APS patient with BCS. In addition patient is managed with immunosuppressive drugs.展开更多
BACKGROUND Paraneoplastic syndromes are characterized by atypical clinical manifestations.Several reports of hepatocellular carcinoma(HCC)paraneoplastic phenomena have been reported.They usually manifest as one type i...BACKGROUND Paraneoplastic syndromes are characterized by atypical clinical manifestations.Several reports of hepatocellular carcinoma(HCC)paraneoplastic phenomena have been reported.They usually manifest as one type in an individual,but it is not common for the two clinical manifestations to occur simultaneously.CASE SUMMARY A 52-year-old female patient was admitted to hospital with pale skin and numbness of the second to fifth fingers in the left hand,which rapidly developed into severe digital ischemia.Computed tomography angiography revealed uneven thickness of the left ulnar artery with severe local luminal stenosis.Blood analysis during hospitalization showed persistent mild to medium thrombocytopenia and insensitive to hormonal therapy.Antiphospholipid antibody testing showed high titer of IgG anticardiolipin antibodies(aCLs),IgA aCLs,IgG anti-β2-glycoprotein-I(anti-β2 GPI),and IgA anti-β2 GPI.The exact diagnosis was HCC when the high a-fetoprotein levels,computed tomography findings,and the history of chronic hepatitis B came together.This was a rare case of coexisting manifestations as presenting symptoms of malignancy-associated antiphospholipid syndrome.The patient underwent several operations,antithrombotic treatments and hormonal therapy.However,the patient refused chemotherapy and died 8 wk after diagnosis.CONCLUSION This report highlights the importance of atypical clinical changes that could alert the physicians to vigilance for a concomitant underlying malignancy.展开更多
Objective: To gain further understanding of the antiphospholipid syndr ome(APS). Methods: Analysing clinical and laboratory data on ten cases of APS. R esults: Thrombocytopenia appeared in all cases. Venous thrombi of...Objective: To gain further understanding of the antiphospholipid syndr ome(APS). Methods: Analysing clinical and laboratory data on ten cases of APS. R esults: Thrombocytopenia appeared in all cases. Venous thrombi of limbs appeared in five cases and neurological abnormalities in two cases. Renal impairments we re found in three cases. One case manifested left renal venous thrombi and the o ther two cases thrombotic microangiopathy. Budd-Chiari syndrome was found in on e case. One of the ten cases was catastrophic APS(CAPS) presented as acute diffus e swel ling,cyanosis,pain,ischemia and necrosis in fingers and limbs,recurrent shoc k,ascites,hepatic and respiratory dysfunction. Anticoagulants and corticosteroids could be effective for dealing with APS. It was critical to trea t catastrophic APS with anticoagulants or plasmapheresis as early as possible. C onclusions: APS shows variable manifestations for good prognosis,but catastroph ic APS has fatal risk. The main treatment for APS is the use of anticoagulants a nd immunosuppressives.展开更多
文摘Antiphospholipid antibodies(aPLs)are a heterogeneous group of autoantibodies that include anticardiolipin antibodies,anti-β2 glycoprotein I antibodies,and lupus anticoagulant.The presence of aPLs is the main characteristic feature of antiphospholipid syndrome(APS),an autoimmune disease with multifactorial etiology.Kidney involvement is a well-recognized complication associated with both primary and secondary APS.Kidney involvement in APS presents with renal artery thrombosis,renal vein thrombosis,allograft loss due to thrombosis after kidney transplantation,and injury to the renal microvasculature,also known as APS nephropathy(APSN).APSN is the characteristic manifestation of kidney involvement in APS and occurs as a result of vaso-occlusive disease in the intrarenal vasculature.Diagnosis and risk stratification of APS are complex and still evolving.This review synthesizes and updates the available evidence in literature regarding risk factors,pathogenesis,and diagnosis of APS and APSN.
文摘Antiphospholipid syndrome(APS)is a systemic autoimmune disorder characterized by the presence of antiphospholipid antibodies and is associated with thrombotic events and pregnancy complications.The classification and management of APS has evolved over time.The classification criteria for APS include laboratory,macrovascular,microvascular,obstetric,cardiac,and hematologic domains.Management focuses on prevention of thrombotic events and/or anticoagulation as the primary treatment for thrombosis.Postpartum and long-term thromboprophylaxis after delivery are recommended to reduce the risk of thrombotic events.Despite these recommendations,optimal anticoagulation agents and intensity of treatment are still topics of debate.Further research is needed to understand the pathophysiology of APS and improve its management during pregnancy.In this review,we discuss the classification and pathophysiology of APS.Current treatment options and clinical trials are also discussed.
文摘BACKGROUND Cardiac sarcoidosis(CS)is an infiltrative disease with manifestations such as nonsustained ventricular tachycardia(NSVT)and heart failure(HF).Antiphospholipid syndrome(APS)and antiphospholipid positivity(APP)are prothrombotic phenomena which elevate risk for thromboembolism.CS with active systemic sarcoid and APS/APP is a rare combination of diseases.CASE SUMMARY A 54 year old male with HF presented with several cardiopulmonary symptoms.Chest imaging showed bilateral patchy and reticulonodular infiltrates.Subsequent lung biopsy confirmed pulmonary sarcoidosis.Positron emission tomography revealed active systemic sarcoidosis(SS)and fibrotic CS.Positive antiphospholipid antibodies without thromboembolism confirmed APP.HF and APP were managed with medical therapy.Fibrotic CS and NSVT required permanent cardiac device and antiarrhythmic therapy.SS was managed with early taper of steroids and transition to biologics.CONCLUSION Fibrotic CS with active SS and APS/APP has not been previously described in literature.This case utilized a modified approach for the management of this combination of diseases.As immunosuppressants such as steroids have limited utility in fibrotic sarcoidosis and a potential for thromboembolic complications in the presence of APP,an accelerated transition to non-thrombotic immunosuppressants can be advantageous in the long term treatment of this combination of diseases.
文摘Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a history of venous thromboembolism (VTE) on warfarin presented to the hospital with nausea, vomiting, and abdominal and flank pain shortly following colonoscopy preparation. Initial imaging of the abdomen and pelvis was notable for hyperdense thickening of the bilateral adrenal glands raising concerns for hemorrhages, and subsequent magnetic resonance imaging (MRI) confirmed BAH. During hospitalization, the patient was placed on prophylactic heparin, and shortly after decompensating, he became tachycardic, hypotensive, and febrile. This led to heparin reversal followed by administration of a single dose of Hydrocortisone 100 mg and Hydrocortisone 50 mg TID due to concern for adrenal insufficiency. The patient also necessitated sepsis work-up and fluid resuscitation. Repeat CT imaging showed no significant change in hemorrhage size bilaterally. Endocrinology, vascular surgery, hematology/oncology, and rheumatology were consulted for the management of adrenal insufficiency, anticoagulation in the presence of hemorrhage, thrombocytopenia, and hypercoagulable state. Towards the end of his hospital course, the patient had asymptomatic diffuse ST elevations, elevated troponin, and an ejection fraction of 10% - 15%, leading to cardiac catheterization and placement of an intra-aortic pump. During subsequent stay in the ICU, the patient developed hemodynamic shock and was transferred to a facility with a higher level of care and medical support therapies. After this transfer, the patient was stabilized from a cardiac standpoint but developed acute respiratory failure suspected to be secondary to diffuse alveolar hemorrhage and immune thrombocytopenic purpura, necessitating platelet transfusion. He was on continued monitoring from rheumatology given his myocarditis believed to be secondary to his antiphospholipid antibodies, and was treated with IVIG, rituximab, and hydroxychloroquine. A repeat echocardiogram revealed an improved ejection fraction of 52% and the patient was then discharged on an enoxaparin bridge to warfarin and a cardiac home event monitor. Discussion: BAH is a life-threatening condition that should be promptly identified and managed in patients presenting with nonspecific symptoms and a history of hypercoagulability or anticoagulation. In these cases, the risk of AH and subsequent adrenal insufficiency is drastically increased, so immediate imaging as well as initiation of steroid therapy is crucial to stabilize patients and prevent adrenal crisis. A multidisciplinary approach, involving endocrinology, hematology, and cardiology as in this case is also imperative to optimize patient outcomes and increase survival. Conclusion: BAH should be considered in patients presenting with a history of VTE and hypercoagulable state when precipitating stressors or predisposing risk factors are present. This case report highlights the importance of clinical awareness of BAH for clinicians to accurately identify and manage it to prevent fatal sequelae and ensure long-term favorable patient outcomes.
基金Supported by NIH K08AR066569a career development award from the Burroughs Wellcome Fund(Knight JS)Kazzaz NM was supported by Security Forces Hospital Program,Ministry of Interior,Riyadh,Saudi Arabia
文摘Thrombotic events,both arterial and venous,are a major health concern worldwide. Further,autoimmune diseases,such as systemic lupus erythematosus,anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis,and antiphospholipid syndrome,predispose to thrombosis,and thereby push the risk for these morbid events even higher. In recent years,neutrophils have been identified as important players in both arterial and venous thrombosis. Specifically,chromatin-based structures called neutrophil extracellular traps(NETs) play a key role in activating the coagulation cascade,recruiting platelets,and serving as scaffolding upon which the thrombus can be assembled. At the same time,neutrophils and NETs are emerging as important mediators of pathogenic inflammation in the aforementioned autoimmune diseases. Here,we first review the general role of NETs in thrombosis. We then posit that exaggerated NET release contributes to the prothrombotic diatheses of systemic lupus erythematosus,ANCA-associated vasculitis,and antiphospholipid syndrome.
文摘Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From September to November 2020,clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang,Indonesia.Antiphospholipid antibodies were measured by finding Ig M anti-β2 glycoprotein,lupus anticoagulant,and Ig M/Ig G anticardiolipin.Clinical characteristics,thrombotic events,ICU admission,and mortality during hospitalization were recorded.Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19,Indonesia.Results:Among 50 patients,5 patients(10.0%)were positive for antiphospholipid antibodies:4 patients(80.0%)had Ig M anti-β2 glycoprotein and 1 patient had Ig G anti-cardiolipin(20.0%)and Ig M anti-cardiolipin(20.0%),none of lupus anticoagulant was detected.Antiphospholipid antibodies were associated with anosmia(OR 8.1;95%CI 1.1-57.9;P=0.018),nausea and vomiting(OR 12.4;95%CI 1.2-122.6;P=0.010),diarrhea(OR 9.8;95%CI 1.3-70.9;P=0.010),cardiovascular disease(OR 1.4;95%CI 1.0-1.9;P=0.001),chronic kidney disease(OR 12.0;95%CI 1.6-90.1;P=0.05),acute coronary syndrome(OR 29.3;95%CI 2.0-423.7;P=0.001),moderate(OR 0.11;95%CI 0.01-1.10;P=0.031)and severe(OR 18.5;95%CI 1.8-188.4;P=0.002)disease severity,and in-hospital mortality(OR 8.1;95%CI 1.1-57.9;P=0.018).However,there is no correlation between the presence of antiphospholipid antibody and ICU admission.Conclusions:In summary,the prevalence of antiphospholipid antibodies in COVID-19 patients is low,mainly against Ig M anticardiolipin,and is associated with an acute coronary syndrome,gastrointestinal manifestations,moderate and severe disease severity,and increased risk of mortality.
文摘Warfarin is a widely used anticoagulant.Interindividual differences in drug response,a narrow therapeutic range and the risk of bleeding render warfarin difficult to use clinically.An 18-year-old woman with antiphospholipid syndrome received long-term warfarin therapy for a recurrent deep vein thrombosis.Six years later,she developed right flank pain.We diagnosed intrahepatic and subgaleal hemorrhages secondary to anticoagulation therapy.After stopping oral anticoagulation,a follow-up computed tomography showed improvement in the hemorrhage.After restarting warfarin because of a recurrent thrombosis,the intrahepatic hemorrhage recurred.We decided to start clopidogrel and hydroxychloroquine instead of warfarin.The patient has not developed further recurrent thrombotic or bleeding episodes.Intrahepatic hemorrhage is a very rare complication of warfarin,and our patient experienced intrahepatic and subgaleal hemorrhage although she did not have any risk factors for bleeding or instability of the international normalized ratio control.
文摘This article reports a rare case of bilateral choroidal occlusion that occurred in a 24-year-old woman with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE). This young lady concurred with aorta ventralis thrombosis and bilateral iliac artery occlusion when presented, and experienced a rapid deterioration of vision. She also has a history of recurrent miscarriage. Corticosteroid,immunosuppression and anticoagulation therapy were administered. Patients with APS associated with SLE are at risk for thrombotic phenomena, which may affect the ocular vessels of all sizes, including choroidal vessel.Our case alerts ophthalmologists and rheumatologists that bilateral choroidal occlusion may indeed be developed in patients with APS associated with SLE, and is a potential cause of visual morbidity.
文摘Antiphospholipid syndrome(APS)or Hughes syndrome is an acquired thromboinflammatory disorder.Clinical criteria of APS diagnosis are large-and small-vessel thrombosis as well as obstetric problems;laboratory criteria are the presence of antiphospholipid antibodies(lupus anticoagulant,anticardiolipin antibodies and anti-β2-glycoprotein-1).The presence of at least 1 clinical and 1 laboratory criterion allows definitive diagnosis of APS.Primary APS is diagnosed in patients without features of connective tissue disease;secondary APS is diagnosed in patients with clinical signs of autoimmune disease.A high frequency of catastrophic APS as well as a high tendency to evolve from primary APS to secondary syndrome during the course of lupus and lupus-like disease is a feature of pediatric APS.The most characteristic clinical presentation of APS in the pediatric population is venous thrombosis,mainly in the lower limbs,and arterial thrombosis causing ischemic brain stroke.Currently,no diagnostic criteria for pediatric APS exist,which probably results in an underestimation of the problem.Similarly,no therapeutic procedures for APS specific for children have yet been established.In the present literature review,we discussed data concerning APS in children and its role in cerebrovascular diseases,including pediatric arterial ischemic stroke,migraine and cerebral venous thrombosis.
基金Supported by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,Internal Research Grant of University of Debrecen and the IOIBD Research Grant
文摘AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) patients.METHODS: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.RESULTS: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients.Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes.Changes in antibody status were more remarkable in CD than UC(ACA IgA: 49.9% vs 23.3% and ACA IgG:21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However,presence of different APLAs were not associated with the clinical phenotype or disease course.
文摘BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to thrombosis.In contrast,patients with primary hyperfibrino-lysis tend to bleed.CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with"tuberculous pleurisy"and treated with anti-tuberculosis drugs and prednisone.The coagulation-related laboratory results showed decreased fibrinogen,PC activity,PS activity,and antithrombinШactivity.The immune-related laboratory results showed positive antinuclear antibody,anti-Smith antibody,anticardiolipin antibody(ACL),anti-β2-glycoprotein I antibody(aβ2GPI)and direct Coomb’s test and decreased complement 3 and complement 4.Thoracoscopy was performed and bloody pleural fluid was drained.Pathology of the pleural biopsy showed lymphocytes,plasma cells,and a few eosinophils in adipose and fibrous connective tissue.Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases.The patient was finally diagnosed with SLE and primary hyperfibrinolysis,and was treated with prednisolone,hydroxychloroquine,and compound cyclophosphamide.CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI.SLE and primary hyperfibrinolysis can coexist in one patient,with both a risk of thrombosis and a risk of bleeding.
文摘Antiphospholipid syndrome is a multi-system disease characterized by the formation of thromboembolic complications and/or pregnancy morbidity, and with persistently increased titers of antiphospholipid antibodies. We report the case of a 50-year-old, previously healthy man who presented with fever and new-onset, dull abdominal pain. A contrast-enhanced computed tomography scan showed segmental small bowel obstruction, for which an emergency laparotomy was performed. Histopathologic examination of resected tissues revealed multiple intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum antiphospholipid(anticardiolipin Ig M) and anti-β2-glycoprotein I antibodies were positive. Despite proactive implementation of anticoagulation, steroid, and antibiotic therapies, the patient's condition rapidly deteriorated, and he died 22 d after admission. This case highlights that antiphospholipid syndrome should be suspected in patients with unexplainable ischemic bowel and intestinal necrosis presenting with insidious clinical features that may be secondary to the disease, as early diagnosis is critical to implement timely treatments in order to ameliorate the disease course.
文摘The antiphospholipid syndrome(APS)is a multi-systemic disease being characterized by the presence of antiphospholipid antibodies that involves both arterial and venous systems resulting in arterial or venous thrombosis,fetal loss,thrombocytopenia,leg ulcers,livedo reticularis,chorea,and migraine.We document a previously unreported case of a 37-year-old female in whom APS was first manifested by infarction and cecal perforation following cesarean section.At laparotomy the underlying cause of colonic perforation was not clear and after resection of the affected bowel an ileo-colostomy was performed.The diagnosis of APS was established during post-operative hospital stay and the patient was commenced on warfarin.Eventually,she made a full recovery and had her stoma reversed after 4 mo.Pregnancy poses an increased risk of complications in women with APS and requires a more aggressive approach to the obstetric care.This should include full anticoagulation in the puerperium and frequent doppler ultrasound monitoring of uterine and umbilical arteries to detect complications such as preeclampsia and placental insufficiency.
文摘Gallbladder disease is no more common in patients with systemic lupus erythematosus (SLE) than in the general population. We describe a 17-year-old patient with SLE, who developed nephritis that was well controlled with medications. Initial treatment consisted of azathioprine, aspirin and prednisone with stable control of her symptoms. Two years later she developed a right quadrant abdominal pain, and an abdominal ultrasound revealed microlithiasic cholecystitis. Open cholecystectomy was performed and the histopathological findings revealed vasculitis with thrombotic microangiopathy in the gallbladder. This case presentation illustrates that calculous or acalculous cholecystitis should be considered as a manifestation of active SLE and APS.
文摘MAKING accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations.The possibility that vasculitis associated with systemic lupus erythematosus(SLE)and antiphospholipid syndrome(APS)can be misdiagnosed as cysticercosis has not been discussed in the literatures.
基金Supported by VA Nasonova Scientific Research Institute of Rheumatology,Moscow,Russian Federation
文摘The antiphospholipid syndrome(APS) is an acquired thrombophilic disorder in which autoantibodies are produced to a variety of phospholipids determinants of cell membranes or phospholipid binding proteins. There are few reports about association between antiphospholipid antibodies and development of BuddChiari syndrome(BCS). We report the case of BCS development in young Russian male with primary APS. The patient underwent orthotopic liver transplantation on August 26, 2012. At present time his state is good, the blood flow in the liver restored and its function is not impaired. We report about the first time the successful use of dabigatran etexilate for prolonged anticoagulation therapy in APS patient with BCS. In addition patient is managed with immunosuppressive drugs.
文摘BACKGROUND Paraneoplastic syndromes are characterized by atypical clinical manifestations.Several reports of hepatocellular carcinoma(HCC)paraneoplastic phenomena have been reported.They usually manifest as one type in an individual,but it is not common for the two clinical manifestations to occur simultaneously.CASE SUMMARY A 52-year-old female patient was admitted to hospital with pale skin and numbness of the second to fifth fingers in the left hand,which rapidly developed into severe digital ischemia.Computed tomography angiography revealed uneven thickness of the left ulnar artery with severe local luminal stenosis.Blood analysis during hospitalization showed persistent mild to medium thrombocytopenia and insensitive to hormonal therapy.Antiphospholipid antibody testing showed high titer of IgG anticardiolipin antibodies(aCLs),IgA aCLs,IgG anti-β2-glycoprotein-I(anti-β2 GPI),and IgA anti-β2 GPI.The exact diagnosis was HCC when the high a-fetoprotein levels,computed tomography findings,and the history of chronic hepatitis B came together.This was a rare case of coexisting manifestations as presenting symptoms of malignancy-associated antiphospholipid syndrome.The patient underwent several operations,antithrombotic treatments and hormonal therapy.However,the patient refused chemotherapy and died 8 wk after diagnosis.CONCLUSION This report highlights the importance of atypical clinical changes that could alert the physicians to vigilance for a concomitant underlying malignancy.
文摘Objective: To gain further understanding of the antiphospholipid syndr ome(APS). Methods: Analysing clinical and laboratory data on ten cases of APS. R esults: Thrombocytopenia appeared in all cases. Venous thrombi of limbs appeared in five cases and neurological abnormalities in two cases. Renal impairments we re found in three cases. One case manifested left renal venous thrombi and the o ther two cases thrombotic microangiopathy. Budd-Chiari syndrome was found in on e case. One of the ten cases was catastrophic APS(CAPS) presented as acute diffus e swel ling,cyanosis,pain,ischemia and necrosis in fingers and limbs,recurrent shoc k,ascites,hepatic and respiratory dysfunction. Anticoagulants and corticosteroids could be effective for dealing with APS. It was critical to trea t catastrophic APS with anticoagulants or plasmapheresis as early as possible. C onclusions: APS shows variable manifestations for good prognosis,but catastroph ic APS has fatal risk. The main treatment for APS is the use of anticoagulants a nd immunosuppressives.
