What is the appropriate anticoagulation strategy for thrombotic antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder mediated by a heterogeneous group of autoantibodies collectively known as antiphospholipid antibodies (aPL). They include lupus anticoagulant (LA), IgG and IgM anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I (anti-β2GPI) antibodies. It has been shown that those patients with all three aPL (triple positive) are at highest risk of both a first thrombotic event and of a recurrence, despite anticoagulation. In response to publication of a meta-analysis and a randomised controlled trial assessing the safety and efficacy of rivaroxaban versus warfarin in triple-positive APS with venous and/or arterial thrombosis, the Medicines and Healthcare Products Regulatory Agency (MHRA) and European Medicines Agency (EMA) issued recommendations that direct-acting oral anticoagulant (DOACs) should not be used for secondary prevention of thrombosis in all APS patients (although they did draw specific attention to the high risk of triple-positive patients). As there is less evidence for patients with single- or dual-positive patients with APS, this may be an over-interpretation of the data. In this review, we explore the available evidence on safety and efficacy of DOACs in thrombotic APS, the problem of detecting LA while on DOAC, and provide some practical guidance for managing this problem.     

Which antiphospholipid antibodies should be measured in the antiphospholipid syndrome?

The results of an analysis of studies published over a 10-year period that addressed the association between antiphospholipid antibodies (aPLs) and thromboembolic events in patients with the antiphospholipid syndrome (APS) are reported. It would appear that lupus anticoagulants are the strongest risk factor for thromboembolic events in aPL-positive patients. Consequently, it is suggested that all patients with clinical manifestations of APS should be tested for these antibodies. On the other hand, the results do not unequivocally show that measurement of anticardiolipin antibodies is of help in defining the thrombotic risk of patients. Furthermore, they only partially support the notion that anti-beta 2-glycoprotein I and antiprothrombin antibodies may be independent risk factors for thrombosis.     

What have we learned about antiphospholipid syndrome from patients and antiphospholipid carrier cohorts?

Venous or arterial thrombosis or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL) define the antiphospholipid syndrome (APS). In terms of accepted APS criteria, aPL are detected by one coagulation test (lupus anticoagulant; LAC) and two immunoassays (anticardiolipin antibodies and anti-β2-glycoptrotein I antibodies). In patients with APS, a single positive test carries a much lower risk of thrombosis recurrence or new pregnancy loss than does multiple (or triple) positivity. The same holds true for aPL carriers, namely subjects with laboratory tests but without clinical criteria for APS. Thus, very different risk categories exist among patients with APS as well as in carriers of aPL. Triple positivity apparently identifies the pathogenic autoantibody (antidomain I-II of β2-glycoptrotein I); it is in this category of patients that trials on new therapeutic strategies should focus.     

Susac's syndrome or catastrophic antiphospholipid syndrome?

Susac's syndrome is a microangiopathic disorder of unknown pathogenesis presenting with encephalopathy, hearing loss and branch retinal artery occlusions. The term 'catastrophic' antiphospholipid syndrome (APS) is used to define a subset of the APS characterized by thrombotic microangiopathy with clinical evidence of three or more organ involvement developed in a short period of time. We describe a patient with typical features of Susac's syndrome, that appeared in less than a week, in whom aPL were detected, thus fulfilling criteria for 'probable' catastrophic APS.     

What causes hemorrhoids?

Conclusions There are two main types of hemorrhoids—vascular and mucosal. Vascular piles, occurring most commonly in young men, are caused by straining at defecation, when the anal sphincter relaxes, subjecting the anorectal tissues to a high pressure gradient. The superior hemorrhoidal plexus is filled initially by blood which is forced at very high pressure from the superior rectal venous radicles lying in the lower part of the ampulla of the rectum. Distention of the plexus is limited and is confined to the veins of the upper part of the anal canal by a tube-valve mechanism which also has a similar, but less direct, effect on the inferior rectal veins. Mucosal piles, usually found in pregnant women and the aged, are caused by deterioration of the function of the anal sphincter muscle. There is no evidence that any other etiologic factor is of significance in the causation of piles. Abridgment of thesis accepted by the University of London in partial fulfillment of the requirements for the degree of Master of Surgery.     

What causes sarcoidosis?

Limited but encouraging progress has been made over the last several years in our understanding of the etiology of sarcoidosis as a result of recent investments in epidemiologic, immunologic, and molecular biologic studies. A recent US multicenter study of sarcoidosis found few environmental or occupational exposures associated with a two-fold or higher risk of development of sarcoidosis, suggesting noninfectious exposures play a small, if any, role in causing systemic sarcoidosis. In contrast, recent studies have linked infectious agents including mycobacterial and propionibacterial organisms with sarcoidosis. The association of sarcoidosis with the use of Th1-promoting biologic response modifiers is consistent with a central role for enhanced Th1 immune responses in the pathogenesis of sarcoidosis. Given evidence for a genetic predisposition to sarcoidosis, these findings suggest that the etiology of systemic sarcoidosis is linked to genetically determined enhanced Th1 immune responses to a limited number of microbial pathogens.     

What is the dumping syndrome?

Digestive Diseases and Sciences -     

Precision medicine and the antiphospholipid syndrome: what is the future?

Clinical Rheumatology -     

What causes neuropathic pain?

Although the etiology of diabetic neuropathic pain remains enigmatic, two types of neuropathic pain are now recognized: nerve trunk pain following a discrete often vascular lesion as seen in ocular mononeuropathy and hyperalgesic pain as seen in diffuse involvement of peripheral sensory fibers. Our understanding of the causes of hyperalgesic pain has been furthered by studying structural changes in sural nerve biopsies from subjects with symptomatic neuropathy or by assessing biochemical changes that lead to positive symptoms. Recent evidence suggests that both small and large fibers are involved in painful neuropathy, and axonal atrophy may contribute to pain generation. The observation that acute painful neuropathy may follow either periods of unstable glycemic control or sudden improvement of control ("insulin neuritis") suggests that blood glucose flux may precipitate pain. Sudden changes in glycemia may contribute to the generation of impulses in nociceptive fibers or even induce relative hypoxia and axonal atrophy. Pain might arise from ectopic impulses in dorsal root ganglion cells or may even be of spinal or central origin. Thus, a combination of structural and functional changes in peripheral nerve is most likely to lead to the generation of neuropathic pain.     

Diagnosis of the antiphospholipid syndrome: How far to go?

The past decade has seen an evolution in the way that thrombophilic conditions are diagnosed and understood. This has largely evolved through the detection of single nucleotide polymorphisms in critical regulating proteins that are thought to confer significant structural-functional changes at key points in the coagulation cascade. The antiphospholipid syndrome (APS) is a complex hypercoagulable disorder that as yet defies the possibility of simple, predictive testing     

Could Frida Kahlo have had antiphospholipid syndrome?

Frida Kahlo's medical history shows sequelae of polio, a severe traumatic event that caused multiple fractures and a penetrating pelvic injury, as well as a history of countless surgeries. In her biographical accounts and her works, chronic disabling pain always appears for long periods. Besides, a chronic foot ulcer, gangrene that required amputation of the right leg, a history of abortions, and a positive Wasserman reaction suggest that the artist could have suffered from antiphospholipid antibody syndrome (APS).