Antiphospholipid syndrome laboratory findings: Difference between revisions

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Latest revision as of 20:27, 24 April 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Overview

Antiphospholipid syndrome (APS) is tested for in the laboratory by both liquid phase coagulation assays (lupus anticoagulant) and solid phase ELISA assays (anti-cardiolipin antibodies). Antibodies found in the plasma os patients with APS are lupus anticoagulant, anticariolipin (aCL), beta-2 glycoprotein I, anti-phosphatidylserine antibodies, anti-prothrombin antibodies. The criteria for testing antiphospholipid antibodies in the plasma is postivity on 2 or more occasion at least 12 weeks apart.

Laboratory Findings

The following antibodies are found in the plasma of patients with APS:^[1]^[2]^[3]^[4]

Laboratory Findings (Antibodies)
Lupus anticoagulant IgA anticariolipin (aCL) IgA beta-2 glycoprotein I Anti-phosphatidylethanolamine antibodies Anti-prothrombin antibodies Anti-phosphatidylserine antibodies

Criteria for testing Antiphospholipid antibodies:

Presence of lupus anticoagulant (LA) in plasma on two or more occasions minimum 12 weeks apart.
Presence of moderate to high levels of anticardiolipin (aCL) (IgG or IgM) in serum or plasma on two or more occasions minimum 12 weeks apart.
Presence of moderate to high levels of anti–beta-2 glycoprotein I antibodies (IgG or IgM) in plasma or serum on two or more occasions minimum 12 weeks apart.

Common Laboratory findings
Thrombocytopenia Hemolytic anemia Prolonged activated partial thromboplastin time (aPTT) Diluted Russell viper venom

References

↑ Giannakopoulos B, Passam F, Ioannou Y, Krilis SA (2009). "How we diagnose the antiphospholipid syndrome". Blood. 113 (5): 985–94. doi:10.1182/blood-2007-12-129627. PMID 18755986.
↑ Galli M (2008). "Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome". Semin Thromb Hemost. 34 (4): 329–34. doi:10.1055/s-0028-1085474. PMID 18814065.
↑ Li R, Daguzan M, Vandermijnsbrugge F, Gyling M, Cantinieaux B (2014). "Both IgG and IgM anti-beta2 glycoprotein I antibodies assays are clinically useful to the antiphospholipid syndrome diagnosis". Acta Clin Belg. 69 (6): 433–8. doi:10.1179/2295333714Y.0000000060. PMID 25103595.
↑ Musial J, Swadzba J, Motyl A, Iwaniec T (2003). "Clinical significance of antiphospholipid protein antibodies. Receiver operating characteristics plot analysis". J Rheumatol. 30 (4): 723–30. PMID 12672190.

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[pmid18755986-1] Giannakopoulos B, Passam F, Ioannou Y, Krilis SA (2009). "How we diagnose the antiphospholipid syndrome". Blood. 113 (5): 985–94. doi:10.1182/blood-2007-12-129627. PMID 18755986.

[pmid18814065-2] Galli M (2008). "Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome". Semin Thromb Hemost. 34 (4): 329–34. doi:10.1055/s-0028-1085474. PMID 18814065.

[pmid25103595-3] Li R, Daguzan M, Vandermijnsbrugge F, Gyling M, Cantinieaux B (2014). "Both IgG and IgM anti-beta2 glycoprotein I antibodies assays are clinically useful to the antiphospholipid syndrome diagnosis". Acta Clin Belg. 69 (6): 433–8. doi:10.1179/2295333714Y.0000000060. PMID 25103595.

[pmid12672190-4] Musial J, Swadzba J, Motyl A, Iwaniec T (2003). "Clinical significance of antiphospholipid protein antibodies. Receiver operating characteristics plot analysis". J Rheumatol. 30 (4): 723–30. PMID 12672190.

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[2]

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@@ Line 4: / Line 4: @@
 ==Overview==
-Antiphospholipid syndrome (APS) is tested for in the [[laboratory]] by both liquid phase coagulation assays ([[lupus anticoagulant]]) and solid phase [[ELISA]] assays ([[anti-cardiolipin antibodies]])
+Antiphospholipid syndrome (APS) is tested for in the [[laboratory]] by both liquid phase coagulation assays ([[lupus anticoagulant]]) and solid phase [[ELISA]] assays ([[anti-cardiolipin antibodies]]). Antibodies found in the plasma os patients with APS are lupus anticoagulant, anticariolipin (aCL), beta-2 glycoprotein I, anti-phosphatidylserine antibodies, anti-prothrombin antibodies. The criteria for testing antiphospholipid antibodies in the plasma is postivity on 2 or more occasion at least 12 weeks apart.
 ==Laboratory Findings==
-The following antibodies are found in the plasma of patients with APS:
+The following antibodies are found in the plasma of patients with APS:<ref name="pmid18755986">{{cite journal| author=Giannakopoulos B, Passam F, Ioannou Y, Krilis SA| title=How we diagnose the antiphospholipid syndrome. | journal=Blood | year= 2009 | volume= 113 | issue= 5 | pages= 985-94 | pmid=18755986 | doi=10.1182/blood-2007-12-129627 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18755986  }} </ref><ref name="pmid18814065">{{cite journal| author=Galli M| title=Clinical utility of laboratory tests used to identify antiphospholipid antibodies and to diagnose the antiphospholipid syndrome. | journal=Semin Thromb Hemost | year= 2008 | volume= 34 | issue= 4 | pages= 329-34 | pmid=18814065 | doi=10.1055/s-0028-1085474 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18814065  }} </ref><ref name="pmid25103595">{{cite journal| author=Li R, Daguzan M, Vandermijnsbrugge F, Gyling M, Cantinieaux B| title=Both IgG and IgM anti-beta2 glycoprotein I antibodies assays are clinically useful to the antiphospholipid syndrome diagnosis. | journal=Acta Clin Belg | year= 2014 | volume= 69 | issue= 6 | pages= 433-8 | pmid=25103595 | doi=10.1179/2295333714Y.0000000060 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25103595  }} </ref><ref name="pmid12672190">{{cite journal| author=Musial J, Swadzba J, Motyl A, Iwaniec T| title=Clinical significance of antiphospholipid protein antibodies. Receiver operating characteristics plot analysis. | journal=J Rheumatol | year= 2003 | volume= 30 | issue= 4 | pages= 723-30 | pmid=12672190 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12672190  }} </ref>
-* Anticardiolipin antibodies (aCL); IgG and IgM by enzyme-linked immunosorbent assay (ELISA)
+{| class="wikitable"
+!Laboratory Findings (Antibodies)
+|-
+|
+* Lupus [[anticoagulant]]
+* IgA anticariolipin (aCL)
+* IgA beta-2 glycoprotein I
-* Anti-beta2-GP I antibodies; IgG and IgM by ELISA.
+* Anti-[[phosphatidylethanolamine]] antibodies
-Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Thus genetic thrombophilia screening can consist of the following laboratory tests:
+* Anti-[[prothrombin]] antibodies
-* Further studies for [[Factor V Leiden]] variant and the [[thrombin|prothrombin mutation]], [[Factor VIII]] levels, [[MTHFR]] mutation.
+* Anti-[[phosphatidylserine]] antibodies
-* Levels of [[protein C]], free and total [[protein S]], [[Factor VIII]], [[antithrombin]], [[plasminogen]], [[tissue plasminogen activator]] (TPA) and [[plasminogen activator inhibitor-1]] (PAI-1)
+|}
-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.
+=== Criteria for testing Antiphospholipid antibodies: ===
+* Presence of lupus [[anticoagulant]] (LA) in plasma on two or more occasions minimum 12 weeks apart.
-===Lupus anticoagulant===
+*Presence of moderate to high levels of anticardiolipin (aCL) (IgG or IgM) in serum or plasma on two or more occasions minimum 12 weeks apart.
-This is tested for by using a minimum of two coagulation tests that are phospholipid sensitive this is 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.
+*Presence of moderate to high levels of [[Anti-β2 glycoprotein I antibody|anti–beta-2 glycoprotein I antibodies]] (IgG or IgM) in plasma or serum on two or more occasions minimum 12 weeks apart.
+{| class="wikitable"
-Distinguishing a lupus antibody from a specific coagulation factor inhibitor (eg: [[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.
+!Common Laboratory findings
-The lupus anticoagulant will inhibit all the contact activation pathway antibodies ([[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 iudl (35%) where as a specific factor antibody will rarely give a result higher than 10iudl (10%).
+|-
-Monitoring IV anticoagulant therapy by the APTR 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]].
+|
+* [[Thrombocytopenia]]
-===Anticardiolipin antibodies===
+* Hemolytic [[anemia]]
-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).
+* Prolonged activated partial thromboplastin time ([[Partial thromboplastin time|aPTT]])
+* Diluted Russell viper venom
-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.
+|}
 ==References==