Antiphospholipid syndrome is a still incompletely understood autoimmune disorder that possesses a highly variable clinical presentation, as virtually any organ or part of the body may be affected by the vascular pathological changes that occur [1]. The symptoms stem from two events - formation of venous (or sometimes arterial) thrombosis and thrombotic microangiopathy (TMA) [1] [2] [3]. Venous thrombosis of the lower extremities is regarded as a frequent finding in patients with antiphospholipid syndrome, whereas pulmonary embolism (developing either from distal thrombi or cardiac valve vegetations) can appear in up to 50% of cases [1]. In addition to the lower extremities, thrombotic changes often affect the subclavian, retinal, and renal arteries [1]. In fact, the kidneys are the primary site where both thrombotic and TMA-related effects of antiphospholipid syndrome are exerted [1] [2]. Occlusion of both larger and smaller renal vessels leads to profound hypertension, proteinuria, and renal insufficiency that presents with anuria [1]. Apart from the kidneys, other organs that are prone to damage are the brain, the heart, the lungs, and the skin [1] [4]. The term "catastrophic antiphospholipid syndrome" is used to describe patients who suffer from life-threatening forms of this disease [1] [5]. Hypertension, hemolytic anemia, disseminated intravascular coagulation (DIC), microthrombotic events involving the heart and the brain, as well as adult respiratory distress syndrome (ARDS), are hallmarks of catastrophic antiphospholipid syndrome, which carries a mortality rate of 50% [1] [4] [5].

• Difficulty Walking

  Some individuals have reported symptoms that resemble multiple sclerosis including numbness or a sensation of pins and needles, vision abnormalities such as double vision, and difficulty walking, but it is not known if these problems are related to APS [rarediseases.org]

• Leg Pain

  On post biopsy Day 6, the patient experienced right leg pain. A contrast CT and lower extremity ultrasonography detected a massive deep vein thrombosis and partial left pulmonary artery thrombosis. [ncbi.nlm.nih.gov]

  Signs of a blood clot include leg pain or swelling and trouble breathing. You should also call your healthcare provider if you’re bleeding or bruising more than normal. [uchealth.org]

• Ulcer

  Skin ulcerations correlated with positive titres aCL IgM and ß2 GPI IgM (p=0.03 and 0.04, respectively), while pseudovasculitis correlated with positive titres ß2 GPI IgM (p=0.02). [ncbi.nlm.nih.gov]

  We report a case of APS manifesting as cutaneous ulceration and necrosis in a patient with severe RA. [mdedge.com]

  Other features include: Splinter haemorrhage (one or more red or black streaks on a nail) Leg ulcers, both arterial and venous ulcers Superficial thrombophlebitis Blue toe syndrome Vasculitis involving medium-sized and small vessels Neurological defects [dermnetnz.org]

• Headache

  KEYWORDS: antiphospholipid antibody syndrome; cerebral venous thrombosis; headache; tadalafil [ncbi.nlm.nih.gov]

  Headaches—particularly migraines—going back to childhood and often with family history can be an early feature of APS.2 Recognizing the following clinical manifestations is an important step toward an earlier diagnosis:4 Thrombocytopenia (30%) Livedo [thermofisher.com]

  Three weeks after admission, the patient complained of headache and double vision. Neurologic examination revealed new horizontal diplopia, partial right sixth nerve palsy, and bilateral ptosis. [ajnr.org]

  For those patients with less serious problems such as headaches, a daily low-dose of aspirin 75mg is usually advised. [lupusuk.org.uk]

The recognition of antiphospholipid syndrome rests on a thorough clinical and laboratory assessment and the diagnostic criteria are comprised of the following:

• Clinical criteria - Pregnancy-related events that raise suspicion toward antiphospholipid syndrome are death of previously healthy fetuses after the 10th week of gestation, premature births due to eclampsia, pre-eclampsia, or insufficiency of the placenta, or unexplained spontaneous abortions before the 10th week of gestation [2] [3] [6] [7]. For this reason, it is imperative for physicians to obtain a detailed history that will reveal these findings. Confirmation of vascular thrombosis in any organ, regardless of vessel size, is the second clinical criteria [2] [3] [6] [7].
• Laboratory criteria - Detection of either lupus anticoagulant (LA), immunoglobulin (Ig) M or IgG anticardiolipin antibodies, or IgM or IgG anti-β2-glycoprotein-1 antibodies on two separate tests that are done 12 weeks apart using standard methods is crucial for identifying antiphospholipid syndrome [2] [3] [6] [7]. Values of anticardiolipin and anti-β2-glycoprotein-1 antibodies should be greater than the 99th percentile [2] [6]. Values of LA may not be accurate in the presence of antithrombic drugs, which implies that their use should be temporarily stopped for proper testing [2].

Although nephropathy, thrombocytopenia, and valvular heart disease are notable findings in these patients, at least one clinical and one laboratory criteria are needed in order to make the diagnosis of the antiphospholipid syndrome [2] [3] [7].

Nevertheless, this tool is a late indicator to suggest any additional treatments. [ncbi.nlm.nih.gov]

In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS. [eurekaselect.com]

The aim of this review article is to update on the medical care of pregnancy in these women to ensure the best maternal and fetal prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved. [ncbi.nlm.nih.gov]

Links: aetiology epidemiology clinical features detection of lupus coagulant detection of anticardiolipin antibodies diagnostic criteria definitive diagnosis of antiphospholipid syndrome treatment prognosis antiphospholipid antibodies catastrophic antiphospholipid [gpnotebook.co.uk]

KEYWORDS: Antiphospholipid syndrome/complications; disease progression; endocarditis/etiology/pathology/surgery; heart valve prosthesis; lupus erythematosus, systemic/complications; treatment outcome; tricuspid valve insufficiency/etiology/surgery [ncbi.nlm.nih.gov]

Etiology Pathophysiology Formation of procoagulatory antiphospholipid antibodies Antibodies form complexes with anticoagulant proteins, thereby inactivating them (e.g., protein C and S, antithrombin III) Antibodies activate platelets and vascular endothelium [amboss.com]

Epidemiology of Antiphospholipid Syndrome: A Population-Based Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/epidemiology-of-antiphospholipid-syndrome-a-population-based-study/. [acrabstracts.org]

Links: aetiology epidemiology clinical features detection of lupus coagulant detection of anticardiolipin antibodies diagnostic criteria definitive diagnosis of antiphospholipid syndrome treatment prognosis antiphospholipid antibodies catastrophic antiphospholipid [gpnotebook.co.uk]

Name Handbook of Systemic Autoimmune Diseases Volume 12 ISSN (Print) 15715078 Fingerprint Antiphospholipid antibodies epidemiology thrombosis Immunology and Allergy Endocrinology, Diabetes and Metabolism Cite this APA Standard Harvard Vancouver Author [jhu.pure.elsevier.com]

This Primer provides an update on the epidemiology, pathogenesis, diagnosis and therapeutic aspects and offers an outlook on future research topics. [nature.com]

Thrombosis in the young: epidemiology and risk factors: a focus on venous thrombosis. Thromb Haemost 1997 ; 78: 1 – 6. Google Scholar | Medline | ISI 9. Roubey, RA. [doi.org]

The goal of this review is to update clinicians and scientists on mechanistic and clinically relevant studies from the past 18 months, which have especially focused on inflammatory aspects of APS pathophysiology. [ncbi.nlm.nih.gov]

Etiology Pathophysiology Formation of procoagulatory antiphospholipid antibodies Antibodies form complexes with anticoagulant proteins, thereby inactivating them (e.g., protein C and S, antithrombin III) Antibodies activate platelets and vascular endothelium [amboss.com]

The complement block, which interrupts this amplification cycle, could prevent CAPS in patients with early TMA who face precipitating events. [ncbi.nlm.nih.gov]

1. Fischer MJ, Rauch J, Levine JS. The Antiphospholipid Syndrome. Semin Nephrol. 2007;27(1):35-46.
2. Lim W. Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program. 2009:233-239.
3. Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology Am Soc Hematol Educ Program. 2015;2015:53-60.
4. Cervera R, Font J, Gómez-Puerta JA, et al. Validation of the preliminary criteria for the classification of catastrophic antiphospholipid syndrome. Ann Rheum Dis. 2005;64:1205–1209.
5. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore). 1998;77:195–207.
6. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.
7. Pengo V, Tripodi A, Reber G, et al. Update of the guidelines for lupus anticoagulant detection: Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009;7(10):1737–1740.