How Can Women With Phospholipid Syndrome Have a Baby Usmle

Medical status

Antiphospholipid syndrome
Other names	Hughes syndrome[1]
Micrograph showing an advanced thrombotic microangiopathy, as may exist seen in APLA syndrome. Kidney biopsy. PAS stain.
Specialty	Immunology, Hematology, Rheumatology

Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable land caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such equally miscarriage, stillbirth, preterm delivery, and severe preeclampsia. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease.^[2] The diagnostic criteria require one clinical event (i.eastward. thrombosis or pregnancy complication) and 2 positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, or anti-cardiolipin antibodies.^[iii]

Antiphospholipid syndrome tin can exist primary or secondary. Chief antiphospholipid syndrome occurs in the absence of any other related disease. Secondary antiphospholipid syndrome occurs with other autoimmune diseases, such as systemic lupus erythematosus (SLE). In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "catastrophic antiphospholipid syndrome" (CAPS or Asherson syndrome) and is associated with a high chance of expiry.

Antiphospholipid syndrome ofttimes requires treatment with anticoagulant medication such as heparin to reduce the run a risk of farther episodes of thrombosis and improve the prognosis of pregnancy. Warfarin (make name Coumadin) is not used during pregnancy because it tin cross the placenta, unlike heparin, and is teratogenic.

Signs and symptoms [edit]

The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not betoken APS (see below for the diagnosis of APS). Antiphospholipid syndrome tin cause arterial or venous blood clots, in any organ system, or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most mutual arterial issue is stroke. In significant women afflicted by APS, at that place is an increased risk of recurrent miscarriage, intrauterine growth restriction, and preterm nativity.^[4] A frequent cause of such complications is placental infarctions. 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 nearly of the miscarriages in subsequently trimesters seen in concomitant systemic lupus erythematosus and pregnancy.^[5]

Other common findings, although non part of the APS classification criteria, are low platelet count, heart valve disease, and livedo reticularis. In that location are likewise associations between antiphospholipid antibodies and dissimilar neurologic manifestations^[6] including headache,^[7] migraine,^[8] epilepsy,^[ix] and dementia.^[10] Some studies have shown the presence of antiphospholipid antibodies in the blood and spinal fluid of patients with psychological symptoms.^[11] Cancer is also observed to comorbid in patients with APS.^[12]

Risk factors [edit]

Risk factors for developing antiphospholipid syndrome include:

• Genetic Markers: HLA-DR4, HLA-DR7, and HLA-DRw53^[13]
• Race: Blacks, Hispanics, Asians, and Native Americans^{[ citation needed ]}

Pathogenesis [edit]

Antiphospholipid syndrome is an autoimmune disease, in which "antiphospholipid antibodies" (anticardiolipin antibodies and lupus anticoagulant) react against proteins that bind to anionic phospholipids on plasma membranes. Like many autoimmune diseases, it is more common in women than in men. The exact crusade is not known, merely activation of the system of coagulation is axiomatic. Clinically important antiphospholipid antibodies (those that arise as a result of the autoimmune procedure) are associated with thrombosis and vascular disease.^[fourteen] The syndrome can be divided into primary (no underlying affliction state) and secondary (in association with an underlying disease state) forms.^{[ citation needed ]}

Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH. ApoH inhibits protein C, a glycoprotein with of import regulatory role of coagulation (inactivates Cistron Va and Cistron VIIIa). Lupus anticoagulant (LAC) antibodies bind to prothrombin, thus increasing its cleavage to thrombin, its active grade.^{[ citation needed ]}

In APS there are also antibodies binding to protein S, which is a co-factor of protein C. Thus, anti-protein S antibodies subtract protein C efficiency.^[xv]

Annexin A5 forms a shield around negatively charged phospholipid molecules, thus reducing their availability for coagulation. Thus, anti-annexin A5 antibodies increase phospholipid-dependent coagulation steps.^[xvi]

The lupus anticoagulant antibodies are those that prove the closest association with thrombosis; those that target β₂glycoprotein 1 have a greater association with thrombosis than those that target prothrombin. Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (over twoscore GPLU or MPLU). Patients with both lupus anticoagulant antibodies and moderate or loftier titre anticardiolipin antibodies show a greater take a chance of thrombosis than with one alone.^{[ citation needed ]}

The increased risks of recurrent miscarriage, intrauterine growth restriction and preterm birth by antiphospholipid antibodies, as supported by in vitro studies, include decreased trophoblast viability, syncytialization and invasion, deranged product of hormones and signalling molecules by trophoblasts, as well as activation of coagulation and complement pathways.^[iv]

Diagnosis [edit]

Antiphospholipid syndrome is diagnosed using either liquid-phase coagulation assays to detect lupus anticoagulant or solid phase ELISA (enzyme-linked immunosorbent assay) to notice anti-cardiolipin antibodies or anti-apolipoprotein antibodies.^{[ citation needed ]}

Genetic thrombophilia is function of the differential diagnosis of APS and can coexist in some patients with APS. Presence of genetic thrombophilia may decide the demand for anticoagulation therapy. Thus genetic thrombophilia screening can consist of:^{[ citation needed ]}

• Screening for factor 5 Leiden variant and the prothrombin G20210A and MTHFR mutations.
• Measuring serum levels of poly peptide C, free and total protein S, gene VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-one)

Antiphospholipid antibodies do non recognize isolated cardiolipin, but bind to a cardiolipin-β₂GPI (apolipoprotein H) complex.^[17] The use of testing for antibodies specific for private targets of aPL such as β₂ glycoprotein 1 and phosphatidylserine is currently under argue.^[18]

Lupus anticoagulant [edit]

This is tested for past using a minimum of 2 coagulation tests that are phospholipid-sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically take been establish to take a prolonged partial thromboplastin time (PTT) that does non correct in an 80:20 mixture with normal human plasma (50:l mixes with normal plasma are insensitive to all just the highest antibiotic levels). The PTT (plus 80:20 mix), dilute Russell's viper venom fourth dimension (DRVVT), kaolin clotting time (KCT), dilute thromboplastin time (TDT/DTT), silica clotting fourth dimension (SCT)^[nineteen] and prothrombin time (using a lupus-sensitive thromboplastin) are the main tests used for the detection of lupus anticoagulant. These tests must be carried out on a minimum of two occasions at least half-dozen 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.) beingness diagnosed every bit positive.^{[ commendation needed ]}

Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: factor VIII) is unremarkably achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation cistron antibody. The lupus anticoagulant will inhibit all the contact activation pathway factors (cistron VIII, cistron IX, factor 11 and factor XII). Lupus anticoagulant volition likewise rarely crusade a cistron analysis to requite a upshot lower than 35 iu/dl (35%) whereas a specific factor antibiotic will rarely give a result higher than 10 iu/dl (10%). Monitoring Four anticoagulant therapy past the PTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic analysis based on the inhibition of cistron Xa by antithrombin in the presence of heparin.^{[ citation needed ]}

Anticardiolipin antibodies [edit]

Anti-cardiolipin antibodies tin be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which screens for the presence of β₂glycoprotein one dependent anticardiolipin antibodies (ACA). A low platelet count and positivity for antibodies against β₂-glycoprotein 1 or phosphatidylserine may also be observed in a positive diagnosis.^{[ commendation needed ]}

Criteria [edit]

Nomenclature with APS requires testify of both one or more specific, documented clinical events (either a vascular thrombosis and/or agin obstetric consequence) 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.^[xx] Based on the most recent criteria, classification with APS requires 1 clinical and one laboratory manifestation:^{[ citation needed ]}

• Clinical:^{[ commendation needed ]}
  • A documented episode of arterial, venous, or small-scale vessel thrombosis — other than superficial venous thrombosis — in any tissue or organ by objective validated criteria with no significant show of inflammation in the vessel wall
  • one or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or straight examination of the fetus) at or beyond the 10th calendar 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
• Laboratory:^{[ commendation needed ]}
  • Anti-cardiolipin IgG and/or IgM measured by standardized, not-cofactor dependent ELISA on 2 or more occasions, non less than 12 weeks autonomously; medium or high titre (i.e., > 40 GPL or MPL,^[21] or > the 99th percentile)
  • Anti-β2 glycoprotein I IgG and/or IgM measured by standardized ELISA on 2 or more occasions, non less than 12 weeks autonomously; medium or high titre (> the 99th percentile)
  • Lupus anticoagulant detected on 2 occasions not less than 12 weeks apart according to the guidelines of the International Order of Thrombosis and Hemostasis.

In that location are iii distinct APS affliction entities: main (the absence of any comorbidity), secondary (when there is a pre-existing autoimmune condition, nigh often systemic lupus erythematosus, SLE), and catastrophic (when there is simultaneous multi-organ failure with pocket-sized vessel occlusion).^{[ citation needed ]}

Co-ordinate to a 2006 consensus argument,^[20] it is advisable to classify APS into one of the following categories for research purposes:

• I: more than one laboratory benchmark present in any combination;
• IIa: lupus anticoagulant present alone
• IIb: anti-cardiolipin IgG and/or IgM present solitary in medium or high titers
• IIc: anti-β2 glycoprotein I IgG and/or IgM nowadays alone in a titer greater than 99th percentile

The International Consensus Argument is ordinarily used for Catastrophic APS diagnosis.^[22] Based on this statement, Definite CAPS diagnosis requires:

• a) Vascular thrombosis in 3 or more than organs or tissues and
• b) Development of manifestations simultaneously or in less than a week and
• c) Evidence of small vessel thrombosis in at to the lowest degree ane organ or tissue and
• d) Laboratory confirmation of the presence of aPL.

VDRL, which detects antibodies against syphilis, may accept a simulated positive effect in aPL-positive patients (aPL bind to the lipids in the exam and go far come up out positive), although the more specific examination for syphilis, FTA-Abs, that use recombinant antigens will non take a imitation-positive result.^{[ citation needed ]}

Treatment [edit]

In people without symptoms, no treatment is required.^{[ commendation needed ]} In people with antiphospholipid antibody-associated thrombosis, anticoagulants such as warfarin are used to prevent further thrombosis. If warfarin is used, the INR is kept betwixt 2.0 and iii.0.^[23] direct-interim oral anticoagulants may exist used every bit an alternative to warfarin, simply not in people who are "triple positive" with all types of antiphospholipid antibody (lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein I antibody).^[24]

Anticoagulation appears to prevent miscarriage in pregnant women.^[25] In pregnancy, low molecular weight heparin and low-dose aspirin are used^[26] instead of warfarin because of warfarin'southward teratogenicity. Women with recurrent miscarriage are often brash to accept aspirin and to start low molecular weight heparin treatment after missing a menstrual cycle. In refractory cases plasmapheresis may exist used.^{[ commendation needed ]}

Prognosis [edit]

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 ]}

History [edit]

Antiphospholipid syndrome was described in total in the 1980s, by E. Nigel Harris and Aziz Gharavi. They published the first papers in 1983.^{[27] [28]} The syndrome was referred to as "Hughes syndrome" among colleagues later on the rheumatologist Graham R.V. Hughes (St. Thomas' Hospital, London, Uk), who brought together the team.^{[ commendation needed ]}

Research [edit]

APS ACTION (the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking), is the first-always international research network that has been created to design and conduct big-scale, multicenter clinical trials in persistently antiphospholipid antibody (aPL) positive patients.^[29] The network consists of a multidisciplinary group of physicians and investigators from around the earth who are interested in antiphospholipid syndrome (APS) enquiry. The main mission of APS ACTION is to forestall, care for, and cure antiphospholipid antibiotic (aPL) associated clinical manifestations through loftier quality, multicenter, and multidisciplinary clinical enquiry.^{[ citation needed ]}

References [edit]

1. ^ Hughes, Graham; Khamashta, Munther A. (2013-07-01). Hughes Syndrome: Highways and Byways. Springer Science & Business concern Media. ISBN9781447151616. Archived from the original on 2017-03-31.
2. ^ Islam, Md Asiful (2018). "Genetic risk factors in thrombotic chief antiphospholipid syndrome: A systematic review with bioinformatic analyses". Autoimmunity Reviews. 17 (3): 226–243. doi:10.1016/j.autrev.2017.10.014. PMID 29355608 – via Science Direct.
3. ^ "Aps | Action". Apsaction.org. Archived from the original on 2013-07-25. Retrieved 2013-11-06 .
4. ^ ^{a b} Tong, M.; Viall, C. A.; Chamley, L. W. (2014). "Antiphospholipid antibodies and the placenta: a systematic review of their in vitro effects and modulation by handling". Human being Reproduction Update. 21 (1): 97–118. doi:10.1093/humupd/dmu049. PMID 25228006.
5. ^ Lupus and Pregnancy Archived 2013-02-xviii at the Wayback Machine by Michelle Petri. The Johns Hopkins Lupus Centre. Retrieved May 2011
6. ^ Islam, Physician Asiful (2016). "'Non-criteria' Neurologic Manifestations of Antiphospholipid Syndrome: A Hidden Kingdom to be Discovered". CNS & Neurological Disorders Drug Targets. 15 (10): 1253–1265. doi:10.2174/1871527315666160920122750. PMID 27658514 – via PubMed.
7. ^ Islam, Md Asiful (2018). "Coexistence of Antiphospholipid Antibodies and Cephalalgia". Cephalalgia. 38 (3): 568–580. doi:ten.1177/0333102417694881. PMID 28952322. S2CID 3954437 – via PubMed.
8. ^ Islam, Md Asiful (2017). "Comorbid Association of Antiphospholipid Antibodies and Migraine: A Systematic Review and Meta-analysis". Autoimmunity Reviews. 16 (five): 512–522. doi:10.1016/j.autrev.2017.03.005. PMID 28279839 – via Science Directly.
9. ^ Islam, Md Asiful (2018). "Antiphospholipid Antibodies in Epilepsy: A Systematic Review and Meta-analysis". Autoimmunity Reviews. 17 (8): 755–767. doi:10.1016/j.autrev.2018.01.025. PMID 29885542. S2CID 47014367 – via Science Direct.
10. ^ Islam, Md Asiful (2017). "Presence of anticardiolipin antibodies in patients with dementia: A systematic review and meta-analysis". Frontiers in Aging Neuroscience. 12: 250. doi:ten.3389/fnagi.2017.00250. PMC5539075. PMID 28824414. S2CID 8364684.
11. ^ Sokol DK, O'Brien RS, Wagenknecht DR, Rao T, McIntyre JA (2007). "Antiphospholipid antibodies in blood and cerebrospinal fluid of patients with psychosis". Journal of Neuroimmunology. 190 (1): 151–6. doi:10.1016/j.jneuroim.2007.08.002. PMID 17868908. S2CID 11894056.
12. ^ Islam, Md Asiful (2020). "Antiphospholipid antibodies and antiphospholipid syndrome in cancer: Uninvited guests in troubled times". Seminars in Cancer Biology. 64: 108–113. doi:10.1016/j.semcancer.2019.07.019. PMID 31351197. S2CID 198952872 – via Science Direct.
13. ^ Iuliano, Annamaria; Galeazzi, Mauro; Sebastiani, Gian Domenico (September 2019). "Antiphospholipid syndrome's genetic and epigenetic aspects". Autoimmunity Reviews. eighteen (ix): 102352. doi:10.1016/j.autrev.2019.102352. PMID 31323355. S2CID 198132495.
14. ^ Islam, Md Asiful (2016). "Antiphospholipid antibiotic-mediated thrombotic mechanisms in antiphospholipid syndrome: Towards pathophysiology-based treatment". Current Pharmaceutical Design. 22 (28): 4451–4469. doi:ten.2174/1381612822666160527160029. PMID 27229722 – via PubMed.
15. ^ Triplett DA (Nov 2002). "Antiphospholipid antibodies". Athenaeum of Pathology & Laboratory Medicine. 126 (11): 1424–ix. doi:10.5858/2002-126-1424-AA. PMID 12421152.
16. ^ Rand JH (1998). "Antiphospholipid antibody syndrome: new insights on thrombogenic mechanisms". The American Periodical of the Medical Sciences. 316 (2): 142–51. doi:x.1097/00000441-199808000-00009. PMID 9704667.
17. ^ McNeil HP, Simpson RJ, Chesterman CN, Krilis SA (1990). "Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta ii-glycoprotein I (apolipoprotein H)". Proc. Natl. Acad. Sci. U.s.a.A. 87 (11): 4120–4124. Bibcode:1990PNAS...87.4120M. doi:10.1073/pnas.87.11.4120. PMC54059. PMID 2349221.
18. ^ Tebo, Anne (four October 2019). "Laboratory Evaluation of Antiphospholipid Syndrome: An Update on Autoantibody Testing". Clin Lab Med. 39 (iv): 553–565. doi:ten.1016/j.cll.2019.07.004. PMID 31668269. S2CID 204967912.
19. ^ Chantarangkul V, Tripodi A, Arbini A, Mannucci PM (1992). "Silica clotting time (SCT) as a screening and confirmatory exam for detection of the lupus anticoagulants". Thromb. Res. 67 (4): 355–65. doi:x.1016/0049-3848(92)90266-d. PMID 1329261.
20. ^ ^{a b} Miyakis South, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber Chiliad, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (February 2006). "International consensus statement on an update of the nomenclature criteria for definite antiphospholipid syndrome (APS)". J. Thromb. Haemost. 4 (2): 295–306. doi:ten.1111/j.1538-7836.2006.01753.x. hdl:11379/21509. PMID 16420554. S2CID 9752817.
21. ^ https://www.childrensmn.org/references/lab/serology/cardiolipin-(igg-igm)-antibodies.pdf
22. ^ Asherson RA, Cervera R, de Groot PG, Erkan D, Boffa MC, Piette JC, Khamashta MA, Shoenfeld Y (2003). "Catastrophic antiphospholipid syndrome: international consensus argument on classification criteria and treatment guidelines". Lupus. 12 (7): 530–4. doi:10.1191/0961203303lu394oa. PMID 12892393. S2CID 29222615.
23. ^ Horton JD, Bushwick BM (1999). "Warfarin therapy: evolving strategies in anticoagulation". American Family Physician. 59 (three): 635–46. PMID 10029789.
24. ^ "Venous thromboembolic diseases: diagnosis, management and thrombophilia testing". www.nice.org.united kingdom of great britain and northern ireland. National Institute for Wellness and Care Excellence. 2020. Retrieved 2020-08-31 .
25. ^ de Jong PG, Goddijn One thousand, Middeldorp S (2013). "Antithrombotic therapy for pregnancy loss". Man Reproduction Update. 19 (6): 656–673. doi:x.1093/humupd/dmt019. PMID 23766357.
26. ^ "The Employ of Antithrombotics in the Prevention of Recurrent Pregnancy Loss" (PDF). Archived from the original (PDF) on 2016-03-23. Retrieved 2016-03-17 .
27. ^ Ruiz-Irastorza G, Crowther Chiliad, Branch Due west, Khamashta MA (Oct 2010). "Antiphospholipid syndrome". Lancet. 376 (9751): 1498–509. doi:10.1016/S0140-6736(x)60709-X. hdl:2318/1609788. PMID 20822807. S2CID 25554663.
28. ^ Hughes GR (Oct 1983). "Thrombosis, abortion, cognitive disease, and the lupus anticoagulant". Br. Med. J. (Clin. Res. Ed.). 287 (6399): 1088–9. doi:10.1136/bmj.287.6399.1088. PMC1549319. PMID 6414579.
29. ^ Erkan D, Derksen R, Levy R, Machin S, Ortel T, Pierangeli S, Roubey R, Lockshin M (2011). "Antiphospholipid Syndrome Clinical Research Chore Strength Report". Lupus. 20 (2): 219–224. doi:10.1177/0961203310395053. PMID 21303838. S2CID 2262221.

Bibliography [edit]

• Triona Holden (2003). Positive Options for Antiphospholipid Syndrome (APS): Self-Aid and Handling. Hunter House (CA). ISBN978-0-89793-409-1.
• Kay Thackray (2003). Sticky Blood Explained. Braiswick. ISBN978-ane-898030-77-5. A personal account of dealing with the condition.
• Graham R V Hughes (2009). Understanding Hughes Syndrome: Example Studies for Patients. Springer. ISBN978-1-84800-375-0. 50 instance studies to help you lot work out whether you have it.

External links [edit]

• Antiphospholipid Syndrome Explained - Genome.gov

blacklorineve.blogspot.com

Source: https://en.wikipedia.org/wiki/Antiphospholipid_syndrome

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