The role of TLR4 in pathophysiology of antiphospholipid syndrome‐associated thrombosis and pregnancy morbidity

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Antiphospholipid antibodies (aPL), particularly against the phospholipid binding protein beta‐2 glycoprotein I (β2GPI), play an important role in APS pathological mechanisms. aPL can activate intracellular signal transduction in a β2GPI‐dependent manner to induce inflammatory responses, and promote hypercoagulable state and recurrent spontaneous abortion when β2GPI is associated with the cell surface receptor. In vivo and in vitro studies show that Annexin A2 (ANXA2) is the high affinity receptor that connects β2GPI to the target cells. However, ANXA2 is not a transmembrane protein and lacks an intracellular signal transduction pathway. Growing evidences suggest that the transmembrane protein toll‐like receptor 4 (TLR4) might act as an ‘adaptor’ for intracellular signal transduction. This review focuses on the role of TLR4 and its signalling pathway in APS pathological mechanisms which will help us better understand the pathological processes of this syndrome.     

Infant perinatal thrombosis and antiphospholipid antibodies: a review

Perinatal thrombosis in infants born to mothers with antiphospholipid antibodies (aPL) is a rare event, but with risk of death or severe sequelae. We analysed 16 infants with such perinatal thrombosis reported in the literature in the last 20 years. Thromboses were arterial (13/16), mostly strokes (8/16). Hydrops fetalis with left renal vein thrombosis was associated to a lupus anticoagulant (LA) present only in the child. Risk factors additional to aPL: either prenatal (preeclampsia and/or intra-uterine growth retardation) or perinatal (asphyxia, sepsis, arterial or venous catheter and congenital thrombophilia) were present (one to four of them) in nine out of the 14 evaluable babies. aPL were the only risk factor found in five full term babies who suffered from stroke in four cases and from renal thrombosis in another. Eleven of these infants with aPL in their serum presented a neonatal APS with the same antibody (LA or aCL IgG) found in neonates and their mothers, while the other infants had thrombosis with aPL only in their mother's blood. aCL IgM was only found in one neonate who suffered from sepsis. Thrombosis treatments were diverse. This analysis suggests that women with aPL should be investigated for other thrombophilic risk factors and that aPL should be detected systematically at birth in the offspring of mothers with APS.     

The relation between protein Z polymorphism and the risk of thrombosis in Egyptian patients with antiphospholipid syndrome

Background

The genetic background plays an important role in thrombosis and pregnancy morbidities. Low levels of protein Z is associated with increased risk of thrombosis. The G79A polymorphism in the protein Z gene may be a genetic risk factor for thrombosis.

Anti-annexin II antibody is associated with thrombosis and/or pregnancy morbidity in antiphospholipid syndrome and systemic lupus erythematosus with thrombosis

This study investigated the prevalence of antibody against annexin II (A2) in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). It also explored the role of this antibody in thrombosis. Purified recombinant A2 was used in ELISA to measure the levels of IgG anti-A2 antibody in 101 APS patients, 41 SLE patients with thrombosis, 124 SLE patients without thrombosis, and 120 healthy controls. The positive rates of IgG anti-A2 antibody in APS patients and SLE patients with thrombosis were 21.8 and 26.8%, respectively. Both values are significantly higher than that in SLE patients without thrombosis (6.5%). IgG anti-A2 antibody is associated with thrombosis and/or pregnancy morbidity (P?相似文献   

HIV infection and antiphospholipid antibody: literature review and link to the antiphospholipid syndrome

There is a high incidence of antiphospholipid antibodies, detected by assays for anticardiolipin or lupus-like anticoagulant, in HIV disease. However, a link to the antiphospholipid syndrome, with clinical thrombosis, is tenuous. We report a case of a 25-year-old man with undetermined risk factors for HIV presenting with possible antiphospholipid syndrome manifesting as necrotic skin lesions as the initial clinical presentation for HIV. We also review the literature exploring the association between HIV and antiphospholipid syndrome.     

Choledochal cysts in pregnancy： Case management and literature review

AIM: To evaluate the diagnosis, management principles and long-term results of congenital choledochal cysts in pregnancy. METHODS: Three adult patients were diagnosed as choledochal cysts in pregnancy from 1986 to 1989 and their long-term results were evaluated. RESULTS: The first patient had a Roux-en-Y cysto-jejunostomy with T-tube external drainage and died of septic shock and multi-organ failure 25 d after operation. In the second patient, 4 wk after percutaneous trans-choledochal cyst was drained externally with a catheter under US guidance, four weeks later the patient delivered vaginally, and had a cysto-jejunostomy 3 mo after delivery, and lived well without any complications for 15 years after operation. The third patient received Roux-en-Y cysto-jejunostomy after a vertex delivery by induced labor at 28 wk gestation, and demonstrated repetitively intermittent retrograde cholangitis within 10 years, and then died of well-differentiated congenital cholangioadenocarcinoma one month after re-operation with exploratory biopsy at the age of 36. CONCLUSION: More conservative approaches such as external drainage of choledochal cyst should be considered for pregnant patients with high risk, complete excision of choledochal cyst during hepaticojejunostomy or modified hepaticojejunostomy is highly recommended at the optimal time.     

Chylothorax occurring 23 years post-irradiation: literature review and management strategies

Chylothorax is an uncommon condition rarely seen outside the clinical scenario of trauma or malignancy, and management may be difficult. We report the case of a 52-year-old man with a right chylothorax occurring 23 years after mantle irradiation for Hodgkin's disease. In addition, a Medline literature search was performed. Chylothorax occurring post-irradiation is rare and the aetiology is uncertain. Recurrent malignancy must be excluded. There are a number of management options and our patient was successfully treated with a combination of thoracocentesis, medium chain triglyceride diet and thoracoscopy with talc pleurodesis. There was no evidence of recurrent chylothorax at 2 years follow up. Prompt assessment and treatment is required. Surgical measures need to be considered early if medical treatment is unsuccessful.     

De novo neonatal antiphospholipid syndrome: A case report and review of the literature

Objectives

Neonatal antiphospholipid syndrome (APS) is rare and only few cases have been reported, most of them describing trans-placental passage of penetrable maternal antibodies. The current article aims at defining the clinical and biochemical features of the de novo occurrence of neonatal APS and considerations for long-term treatment.

Methods

We present a case and review the medical literature using PubMed.

Results

Including the current report, there are 11 reports of de novo neonatal APS. These include 8 cases of acute ischemic stroke, 2 of venous thrombosis, and 1 of mixed arterial and venous thrombosis. All cases had an additional thrombotic risk factor, either inherited or acquired. Negative maternal history together with low clinical suspicion led to late diagnosis in most cases. In all cases aPL antibodies persisted in the serum throughout the follow-up period. No recurrence of thrombotic events was reported in patients under long-term anticoagulation with either low-molecular-weight heparin (LMWH) or aspirin. There is 1 report of recurrent thrombosis where the patient did not receive anticoagulation. In this case diagnosis was made only retrospectively after recurrence.

Conclusions

We recommend that de novo APS be considered in all cases of unexplained neonatal thrombosis aiming at early diagnosis and implementation of long-term anticoagulation to prevent recurrent thrombotic events.     

Evidence-based management of thrombosis in the antiphospholipid antibody syndrome

Recommendations for the management of thrombosis in the antiphospholipid antibody syndrome have been based largely on retrospective case series. Several clinical trials have been recently published on the management of thrombosis in general. Two clinical trials have specifically addressed thrombosis in antiphospholipid antibody syndrome, and one is underway. These new clinical trials have challenged the previous dogma of a target International Normalized Ratio of 3 to 4 (“high-intensity” warfarin).     

抗磷脂抗体综合征肠系膜血管血栓形成的特点

目的 了解抗磷脂抗体综合征(APS)患者发生肠系膜血管血栓的特点.方法 在Pubmed及中国生物医学文献数据库(1983年1月至2007年7月)检索、分析、总结有关APS发生肠系膜血管血栓的病例报道.结果 共检索病例报道21例,男性13例,女性8例,年龄5个月～69岁,平均(37±17)岁.既往深静脉血栓形成病史3例(14%),自然流产史4例(19%).病程4 h～4个月.表现腹痛18例(86%)、便血或黑粪4例、呕吐3例、腹泻2例、呕血2例,其他有发热等表现.查体腹部压痛10例(48%)、腹膜刺激征5例(24%)、移动性浊音3例、肠鸣音减弱或缺如3例.10例行B超检查,其中3例(33%)检测到肠系膜血管血栓,13例行CT检查者中9例(69%)发现肠系膜血管血栓,4例行磁共振成像(MRI)检查及4例行多普勒超声均发现肠系膜血管血栓(100%),6例通过血管造影证实血栓形成.21例中抗心磷脂抗体阳性18例(86%),其中IgG型占14例(67%).16例行剖腹探查,发现肠缺血坏死者9例(56%).21例中肠系膜上静脉血栓17例(81%),肠系膜上动脉血栓4例(19%),肠系膜下动脉血栓1例(5%),其中肠系膜静脉血栓中7例同时存在门静脉血栓(33%).结论 APS肠系膜血管血栓以肠系膜上静脉为主,常同时存在门静脉血栓,男性略多,中青年略多,可有血栓或自然流产史,可急性起病或逐渐进展,常表现为肠梗阻、肠缺血坏死,IgG型抗心磷脂抗体阳性多见,多种影像学方法联合检测利于及时发现血栓,抗凝及必要时及时手术对多数患者有益.     

Adalimumab-associated antiphospholipid syndrome: a case report and review of the literature

This study aims for the presentation of the first reported case of adalimumab-associated antiphospholipid syndrome (APS) and review of the literature on adalimumab-induced vasculitis and APS. A case of APS associated with adalimumab use in a 67-year-old woman is reported. The English medical literature was reviewed for antitumor necrosis factor (TNF) agents and their association with APS and vasculitis. Adalimumab is a fully humanized monoclonal antibody targeted against TNF alpha that is widely used in the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and Crohn’s disease. Literature review reveals several cases of anti-TNF-induced vasculitis including cases associated with adalimumab. We report the first case of adalimumab-induced APS in a 67-year-old woman who developed APS and vasculitis associated with de novo positive anti-cardiolipin (aCL) antibody following the third dose of adalimumab therapy for the treatment of spondyloarthropathy. This is the first case demonstrating that a short course of adalimumab therapy may induce immunoglobulin M aCL autoantibodies leading to APS. With the growing use of anti-TNF medications in immune-mediated and inflammatory diseases, adalimumab and other anti-TNF medications should be considered as a possible explanation for APS.     

Diagnosis and management of subclavian vein thrombosis: three case reports and review of literature

Axillosubclavian vein thrombosis is seen relatively infrequently in clinical practice when compared with lower limb deep-venous thrombosis; however, it is a condition that can result in significant morbidity if managed suboptimally. A multimodal treatment approach has been increasingly adopted with thrombolysis and/or thoracic outlet decompression being favored over anticoagulation alone, although the evidence base to support this approach is limited. In all, 3 cases are reported, which highlight numerous pertinent issues relating to the diagnostic and therapeutic options available.     

Transcatheter mitral valve thrombosis: A case report and literature review

Transcatheter mitral valve replacement (TMVR) is an exciting alternative therapy for complex patients with mitral valve disease. Experience with TMVR is new and there is a lot yet to discover about their durability, long-term outcomes, and complications including mitral transcatheter heart valve (THV) thrombosis. Many factors have been speculated to increased risk of THV thrombosis. Here, we report a case of a 72-year-old woman who developed mitral THV thrombosis after undergoing TMVR for severe mitral regurgitation with mitral annular calcification. We reviewed 42 TMVR papers with 1,484 patients, including 60 with mitral THV thrombosis. We discussed the most common strategies used for mitral THV thromboprophylaxis and treatment.     

Iron deficiency and thrombosis: literature review.

Compared to primary thrombocytosis such as that caused by essential thrombocytosis, reactive thrombocytosis is generally regarded as benign. However, reactive thrombocytosis has infrequently been reported to cause severe and even fatal complications. Two fatal cases of reactive thrombocytosis and iron deficiency anemia associated with peripheral/pulmonary vascular and cerebrovascular thrombosis are described. The literature on thrombosis and reactive thrombocytosis associated with iron deficiency anemia is reviewed.     

Nonthrombotic proliferative vasculopathy associated with antiphospholipid antibodies: A case report and literature review

Abstract

A 20-year-old man presented with recurrent hemoptysis for seven months. A small subpleural nodule in his right lower lobe was found and excised surgically. Based on the presence of antiphospholipid antibodies (aPL) and vascular wall hypertrophy without vasculitis or an intraluminal thrombus, nonthrombotic proliferative vasculopathy (NTPV) affecting pulmonary arteries was diagnosed. Recently, aPL have been postulated to directly induce the proliferation of vascular cells in the intima and media, leading to NTPV. We review 5 cases of NTPV-associated aPL with critical ischemia in the lower extremities and gastrointestinal infarction. NTPV-associated aPL might be distinct from classic antiphospholipid syndrome and should be considered in aPL-positive patients who present with vascular occlusions of medium-sized vessels in the absence of atherosclerotic risk factors and systemic or local inflammation.