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[[zh:抗磷脂综合征]] |
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{{Infobox disease | |
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Name = Antiphospholipid syndrome | |
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ICD10 = {{ICD10|D|68|8|d|65}} ([[ILDS]] D68.810) | |
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ICD9 = ICD9 289.81 | |
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Image = Thrombotic microangiopathy - very high mag.jpg | |
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Caption = [[Micrograph]] showing an advanced [[thrombotic microangiopathy]], as may be seen in ALPA syndrome. [[Kidney biopsy]]. [[PAS stain]]. | |
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OMIM = 107320 | |
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MedlinePlus = | |
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eMedicineSubj = med | |
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eMedicineTopic = 2923 | |
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DiseasesDB = 775 | |
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MeshID = D016736 | |
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}} |
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'''Antiphospholipid syndrome''' or '''antiphospholipid antibody syndrome''' (APS or APLS or), often also '''Hughes syndrome''', is an [[autoimmune]], [[coagulation|hypercoagulable]] state caused by [[antibody|antibodies]] against cell-membrane [[phospholipids]] that provokes blood clots ([[thrombosis]]) in both [[artery|arteries]] and [[vein]]s as well as pregnancy-related complications such as [[miscarriage]], [[stillbirth]], [[premature birth|preterm delivery]], or severe [[preeclampsia]]. The syndrome occurs due to the [[autoimmune disorder|autoimmune]] production of [[antibody|antibodies]] against [[phospholipid]] (aPL), a [[cell membrane]] substance. In particular, the disease is characterised by antibodies against [[cardiolipin]] ([[anti-cardiolipin antibodies]]) and [[apolipoprotein H|β<sub>2</sub> glycoprotein I]]. The term "primary antiphospholipid syndrome" is used when APS occurs in the absence of any other related disease. APS however also occurs in the context of other autoimmune diseases, such as [[systemic lupus erythematosus]] (SLE), in which case the term "secondary antiphospholipid syndrome" is used. In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "[[catastrophic antiphospholipid syndrome]]" (CAPS) and is associated with a high risk of death. |
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Antiphospholipid syndrome is diagnosed with [[blood test]]s. It often requires treatment with [[anticoagulant]] medication such as [[heparin]] to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. [[Warfarin]]/[[Coumadin]] is not used during pregnancy because it can cross the placenta, unlike heparin, and is teratogenic. |
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==Signs and symptoms== |
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The presence of ''antiphospholipid antibodies'' (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS). |
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Antiphospholipid syndrome can cause ([[artery|arterial]]/[[vein|venous]]) [[blood clot]]s (in any organ system) or [[pregnancy]]-related complications. In APS patients, the most common venous event is [[deep vein thrombosis]] of the lower extremities (blood clot of the deep veins of the legs) and the most common arterial event is [[stroke]]. In pregnant women affected by APS, [[miscarriage]] can occur prior to 20 week of gestation, while [[pre-eclampsia]] is reported to occur after that time. Placental [[infarction]]s, early deliveries and [[stillbirth]] are also reported in women with APS. |
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In some cases, APS seems to be the leading cause of mental and/or development retardation in the newborn, due to an aPL-induced inhibition of [[trophoblast]] differentiation. The antiphospholipid syndrome responsible for most of the miscarriages in later trimesters seen in concomitant [[systemic lupus erythematosus and pregnancy]].<ref name=hopkins>[http://www.hopkinslupus.org/lupus-info/lifestyle-additional-information/lupus-pregnancy/ Lupus and Pregnancy] by Michelle Petri. The Johns Hopkins Lupus Center. Retrieved May 2011</ref> |
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Other common findings, although not part of the APS classification criteria, are [[thrombocytopenia]] (low [[platelet]] count), heart valve disease, and [[livedo reticularis]] (a [[skin]] condition). Some patients report [[headache]]s, [[migraine]]s, and [[oscillopsia]].<ref name="pmid9669481">{{cite journal |author=Rinne T, Bronstein AM, Rudge P, Gresty MA, Luxon LM |title=Bilateral loss of vestibular function: clinical findings in 53 patients |journal=J. Neurol. |volume=245 |issue=6–7 |pages=314–21 |year=1998 |pmid=9669481 |doi= 10.1007/s004150050225|url=}}</ref> |
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Very few patients with primary APS go on to develop [[systemic lupus erythematosus|SLE]]. |
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==Risk factors== |
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Risk factors for developing antiphospholipid syndrome include:{{citation needed|date=October 2011}} |
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*Primary APS |
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**[[genetic marker]] [[HLA-DR7]] |
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*Secondary APS |
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**[[SLE]] or other autoimmune disorders |
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**[[Genetic markers]]: [[HLA-B8]], [[HLA-DR2]], [[HLA-DR3]] |
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**[[Race (classification of humans)|Race]]: [[Blacks]], [[Hispanics]], [[Asians]], and [[Indigenous peoples of the Americas|Native Americans]] |
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==Mechanism== |
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Antiphospholipid syndrome is an [[autoimmune disease]], in which "antiphospholipid antibodies" (anticardiolipin antibodies and lupus anticoagulant) react against proteins that bind to anionic [[phospholipid]]s on [[plasma membrane]]s. Like many [[autoimmune disease]]s, it is more common in women than in men. The exact [[etiology|cause]] is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid antibodies (those that arise as a result of the autoimmune process) are associated with thrombosis and vascular disease. The syndrome can be divided into primary (no underlying disease state) and secondary (in association with an underlying disease state) forms. |
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Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH, which in turn inhibits [[Protein C]], a [[glycoprotein]] with regulatory function upon the common pathway of coagulation (by degradating activated [[factor V]]). |
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LAC antibodies bind to [[prothrombin]], thus increasing its cleavage to [[thrombin]], its active form. |
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In APS there are also antibodies binding to: |
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[[Protein S]], which is a co-factor of protein C. Thus, anti-protein S antibodies decrease protein C efficiency; |
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[[Annexin A5]], which forms a shield around negatively-charged phospholipid molecules, thus reducing their availability for coagulation. Thus, anti-annexin A5 antibodies increase phospholipid-dependent coagulation steps. |
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The Lupus anticoagulant antibodies are those that show the closest association with thrombosis, those that target β<sub>2</sub>glycoprotein 1 have a greater association with thrombosis than those that target prothrombin. |
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Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (>40 GPLU or MPLU). |
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Patients with both Lupus anticoagulant antibodies and moderate/high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone. |
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==Diagnosis== |
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Antiphospholipid syndrome is tested for in the [[laboratory]] using both liquid phase coagulation assays ([[lupus anticoagulant]]) and solid phase [[ELISA]] assays ([[anti-cardiolipin antibodies]]). |
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Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus genetic thrombophilia screening can consist of: |
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* Further studies for [[Factor V Leiden]] variant and the [[thrombin|prothrombin mutation]], [[Factor VIII]] levels, [[MTHFR]] mutation. |
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* Levels of [[protein C]], free and total [[protein S]], [[Factor VIII]], [[antithrombin]], [[plasminogen]], [[tissue plasminogen activator]] (TPA) and [[plasminogen activator inhibitor-1]] (PAI-1) |
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The testing of antibodies to the possible individual targets of aPL such as [[apolipoprotein H|β<sub>2</sub> glycoprotein 1]] and [[antiphosphatidyl serine]] is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though [[cardiolipin]] is not considered an [[in vivo]] target for antiphospholipid antibodies. |
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===Lupus anticoagulant=== |
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This is tested for by using a minimum of two coagulation tests that are phospholipid sensitive, due to the heterogeneous nature of the [[lupus anticoagulant]] antibodies. The patient on initial screening will typically have been found to have a prolonged [[APTT]] that does not correct in an 80:20 mixture with normal human [[Blood plasma|plasma]] (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The APTT (plus 80:20 mix), [[dilute Russell's viper venom time]] (DRVVT), the [[kaolin clotting time]] (KCT), [[dilute thromboplastin time]] (TDT/DTT) or [[prothrombin time]] (using a lupus sensitive [[thromboplastin]]) are the principal tests used for the detection of [[lupus anticoagulant]]. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion demonstrating persistent positivity to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc.) being diagnosed as positive. |
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Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: [[Factor VIII]]). This is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. |
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The lupus anticoagulant will inhibit all the contact activation pathway factors ([[Factor VIII]], [[Factor IX]], [[Factor XI]] and [[Factor XII]]). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) whereas a specific factor antibody will rarely give a result higher than 10 iu/dl (10%). |
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Monitoring IV anticoagulant therapy by the [[partial thromboplastin time|APTT ratio]] is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of [[Factor Xa]] by [[antithrombin]] in the presence of [[heparin]]. |
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===Anticardiolipin antibodies=== |
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These can be detected using an [[ELISA|enzyme-linked immunosorbent assay]] (ELISA) [[immunology|immunological test]], which screens for the presence of β<sub>2</sub>glycoprotein 1 dependent anticardiolipin antibodies (ACA). |
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A [[Thrombocytopenia|Low platelet count]] and positivity for antibodies against β<sub>2</sub>-glycoprotein 1 or [[phosphatidylserine]] may also be observed in a positive diagnosis. |
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==Criteria== |
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Classification with APS requires evidence of both one or more specific, documented clinical events (either a vascular thrombosis and/or adverse obstetric event) and the confirmed presence of a repeated aPL. The Sapporo APS classification criteria (1998, published in 1999) were replaced by the Sydney criteria in 2006.<ref>{{cite journal |author=Miyakis S |title=International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) |journal=J. Thromb. Haemost. |volume=4 |issue=2 |pages=295–306 |year=2006 |month=February |pmid=16420554 |doi=10.1111/j.1538-7836.2006.01753.x |url= |author-separator=, |author2=Lockshin MD |author3=Atsumi T |display-authors=3 |last4=Branch |first4=D. W. |last5=Brey |first5=R. L. |last6=Cervera |first6=R. |last7=Derksen |first7=R. H. W. M. |last8=De Groot |first8=P. G. |last9=Koike |first9=T.}}</ref> Based on the most recent criteria, classification with APS requires one clinical and one laboratory manifestation: |
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* Clinical: |
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** A documented episode of arterial, venous, or small vessel thrombosis—other than superficial venous thrombosis in any tissue or organ by objective validated criteria with no significant evidence of inflammation in the vessel wall and/or |
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** 1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or direct examination of the fetus) at or beyond the 10th week of gestation and/or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded or at least 1 premature birth of a morphologically normal neonate before the 34th week of gestation due to eclampsia or severe pre-eclampsia according to standard definitions, or recognized features of placental insufficiency ''plus'' |
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* Laboratory: |
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** Anti-cardiolipin IgG and/or IgM measured by standardized, non-cofactor dependent ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (i.e., > 40 GPL or MPL, or > the 99th percentile) and/or |
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** Anti-β2 glycoprotein I IgG and/or IgM measured by standardized ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (> the 99th percentile) and/or |
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** Lupus anticoagulant detected on 2 occasions not less than 12 weeks apart according to the guidelines of the International Society of Thrombosis and Hemostasis. |
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There are 3 distinct APS disease entities: primary (the absence of any comorbidity), secondary (when there is a pre-existing autoimmune condition, most frequently systemic lupus erythematosus, SLE), and catastrophic (when there is simultaneous multi-organ failure with small vessel occlusion). |
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According to a 2006 consensus statement,<ref name="pmid16420554">{{cite journal |author=Miyakis S, Lockshin MD, Atsumi T, ''et al.'' |title=International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) |journal=J. Thromb. Haemost. |volume=4 |issue=2 |pages=295–306 |year=2006 |month=February |pmid=16420554 |doi=10.1111/j.1538-7836.2006.01753.x |url=http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2006.01753.x/full}}</ref> it is advisable to classify APS into one of the following categories for research purposes: |
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* I: more than one laboratory criterion present in any combination; |
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* IIa: lupus anticoagulant present alone |
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* IIb: anti-cardiolipin IgG and/or IgM present alone in medium or high titers |
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* IIc: anti-β2 glycoprotein I IgG and/or IgM present alone in a titer greater than 99th percentile |
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The International Consensus Statement is commonly used for Catastrophic APS diagnosis.<ref>{{cite journal |author=Asherson RA |title=Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines |journal=Lupus |volume=12 |issue=7 |pages=530–4 |year=2003 |pmid=12892393|doi=10.1191/0961203303lu394oa |author-separator=, |author2=Cervera R |author3=de Groot PG |display-authors=3 |last4=Erkan |first4=D |last5=Boffa |first5=M-C |last6=Piette |first6=J-C |last7=Khamashta |first7=MA |last8=Shoenfeld |first8=Y |author9=Catastrophic Antiphospholipid Syndrome Registry Project Group}}</ref> Based on this statement, Definite CAPS diagnosis requires: |
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* a) Vascular thrombosis in three or more organs or tissues '''and''' |
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* b) Development of manifestations simultaneously or in less than a week '''and'' |
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* c) Evidence of small vessel thrombosis in at least one organ or tissue '''and''' |
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* d) Laboratory confirmation of the presence of aPL. |
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Some serological tests for syphilis may be positive in aPL-positive patients (aPL bind to the lipids in the test and make it come out positive) although the more specific tests for syphilis that use recombinant antigens will be negative. |
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==Treatment== |
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Often, this disease is treated by giving [[aspirin]] to inhibit platelet activation, and/or [[warfarin]] as an [[anticoagulant]]. The goal of the [[prophylaxis|prophylactic]] treatment is to maintain the patient's [[Prothrombin time|INR]] between 2.0 - 3.0.<ref>{{cite journal |author=Horton JD, Bushwick BM |title=Warfarin therapy: evolving strategies in anticoagulation |journal=American Family Physician |volume=59 |issue=3 |pages=635–46 |year=1999 |pmid=10029789 |doi=}}</ref> It is not usually done in patients who have not had any thrombotic symptoms. During [[pregnancy]], low molecular weight [[heparin]] and low-dose [[aspirin]] are used instead of warfarin because of warfarin's [[teratogen]]icity. Women with recurrent miscarriage are often advised to take aspirin and to start [[low molecular weight heparin]] treatment after missing a [[menstrual cycle]]. In refractory cases [[plasmapheresis]] may be used. {{Citation needed|date=January 2008}} |
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==Prognosis== |
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The long-term prognosis for APS is determined mainly by recurrent [[thrombosis]], which may occur in up to 29% of patients, sometimes despite antithrombotic therapy.{{citation needed|date=October 2011}} |
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==History== |
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Antiphospholipid syndrome was described in full in the 1980s, after various previous reports of specific antibodies in people with systemic lupus erythematosus and thrombosis.<ref name=Antiphospholipid>{{cite journal |author=Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA |title=Antiphospholipid syndrome |journal=Lancet |volume=376 |issue=9751 |pages=1498–509 |year=2010 |month=October |pmid=20822807 |doi=10.1016/S0140-6736(10)60709-X}}</ref><ref name=Hughes>{{cite journal |author=Hughes GR |title=Thrombosis, abortion, cerebral disease, and the lupus anticoagulant |journal=Br. Med. J. (Clin Res Ed) |volume=287 |issue=6399 |pages=1088–9 |year=1983 |month=October |pmid=6414579 |pmc=1549319 |doi=10.1136/bmj.287.6399.1088}}</ref> The syndrome is sometimes [[eponym|referred to]] as "Hughes syndrome", after the [[rheumatology|rheumatologist]] Dr. Graham R.V. Hughes ([[St. Thomas' Hospital]], [[London]], [[United Kingdom|UK]]) who worked at the Louise Coote Lupus Unit at [[St Thomas' Hospital]] in London and played a central role in the description of the condition.<ref name=Hughes/><ref>{{cite journal |author=Sanna G, D'Cruz D, Cuadrado MJ |title=Cerebral manifestations in the antiphospholipid (Hughes) syndrome |journal=Rheum. Dis. Clin. North Am. |volume=32 |issue=3 |pages=465–90 |year=2006 |month=August |pmid=16880079 |doi=10.1016/j.rdc.2006.05.010}}</ref> |
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==References== |
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{{reflist}} |
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==Bibliography== |
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*{{cite book |author=Triona Holden |title=Positive Options for Antiphospholipid Syndrome (APS): Self-Help and Treatment |publisher=Hunter House (CA) |location= |year=2003 |pages= |isbn=0-89793-409-1 |oclc= |doi= |accessdate=}} |
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*{{cite book |author=Kay Thackray |title=Sticky Blood Explained |publisher=Braiswick |location= |year=2003 |pages= |isbn=1-898030-77-4 |oclc= |doi= |accessdate=}} A personal account of dealing with the condition. |
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*{{cite book |author=Graham R V Hughes |title=Understanding Hughes Syndrome: Case Studies for Patients |publisher=Springer |year=2009 |pages= |isbn=1-84800-375-7 |oclc= |doi= |accessdate=}} 50 case studies to help you work out whether you have it. |
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==External links== |
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*[http://www.apsfa.org APS Foundation of America, Inc.] |
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*[http://www.hughes-syndrome.org Hughes Syndrome Foundation] |
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*[http://www.telegraph.co.uk/health/4400796/Hughes-Syndrome-simple-to-treat-but-all-too-often-ignored.html Interview with Hughes] [[The Daily Telegraph]] February 2, 2009. Accessed February 3, 2009. |
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House Md, 6:4 Instant karma |
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{{Autoantibodies}} |
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{{Hematology}} |
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{{DEFAULTSORT:Antiphospholipid Syndrome}} |
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[[Category:Coagulopathies]] |
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[[Category:Rheumatology]] |
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[[Category:Autoimmune diseases]] |
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[[Category:Neurological disorders]] |
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[[Category:Obstetrics]] |
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[[Category:Syndromes]] |
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Revisión del 04:25 26 mar 2012
| Síndrome antifosfolípido | ||
|---|---|---|
| Especialidad | hematología | |
| eMedicine | med/2923 | |
El síndrome antifosfolípido (o síndrome del anticuerpo antifosfolípido) es un desorden de coagulación, que produce trombosis tanto en las arterias como en las venas. También produce enfermedades relacionadas con el embarazo, como el aborto, parto prematuro, o preeclampsia severa.
En algunas ocasiones se hace referencia a este síndrome como el síndrome Hughes, en honor al reumatólogo Dr. Graham R. V. Hughes (St. Thomas' Hospital, Londres, Reino unido) que trabajó en la unidad de Lupus Louise Coote Lupus de dicho hospital.
Este síndrome comúnmente coexiste con otras enfermedades autoinmunes, como lupus. Cuando se lo encuentra en ausencia de enfermedades autoinmunes se emplea el término síndrome primario antifosfolípido, si no se lo llama síndrome secundario antifosfolípido. Además hay una variante rara y de alta tasa de mortalidad, el síndrome catastrófico antifosfolípido, en la que se produce una múltiple y rápida trombosis y disfunción de los órganos.
Síntomas
La presencia de los anticuerpos en ausencia de los coágulos de sangre o de las complicaciones de embarazo no indica la presencia del síndrome (solo un 30% de los pacientes con anticuerpos antifosfolípido presentan manifestaciones clínicas). las manifestaciones clínicas son múltiples y evidencian los acontecimientos trombóticos a nivel venoso, arterial y en pequeños vasos; destacándose manifestaciones cutáneas, cardiovasculares, neurológicas, ginecoobstétricas, respiratorias, renales y hematológicas
Diagnóstico
Se diagnostica este síndrome si se presenta un evento clínico (trombosis venosa o arterial, trombocitopenia o en caso de embarazo, pérdida fetal), y resultan positivas las pruebas de laboratorio (en dos o más ocasiones separadas por seis semanas) , es necesaria la repetición de la prueba porque el antígeno se presenta naturalmente en bajos niveles luego de infecciones. Los anticuerpos específicos y presentes son: Ac anticardiolipinas, anticoagulante lúpico y la prueba de Coombs directa. Algunas pruebas serológicas para la sífilis (específicamente la prueba de VDRL) pueden dar un falso-positivo en los pacientes debido principalmente al anticoagulante lúpico con este síndrome, aunque las pruebas más específicas (los anticuerpos recombinantes) resultarán negativas. (ver Anexo L. A.O. de Filandia Q)
Tratamiento
Las recomendaciones actuales son mantener una INR entre 2.0 y 3.0 con warfarina; en mujeres embarazadas, debido al efecto teratogénico de la warfarina, se utiliza ácido acetilsalicílico y heparina.