Test Catalog

Test Id : MCLIP

Phospholipid (Cardiolipin) Antibodies, IgM, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

The following clinical situations, when used in conjunction with other criterial antiphospholipid antibody tests:

-Unexplained arterial or venous thrombosis

-A history of pregnancy morbidity defined as 1 or more unexplained deaths of a morphologically normal fetus beyond the 10th week of gestation, 1 or more premature births before 34 weeks of gestation caused by severe preeclampsia or placental insufficiency, or 3 or more unexplained, consecutive spontaneous abortions before the 10th week of gestation with no identifiable maternal hormonal or anatomic, or maternal or paternal chromosomal causes

-Presence of a systemic autoimmune rheumatic disease, especially systemic lupus erythematosus

-Unexplained thrombocytopenia

-Presence of an unexplained cutaneous manifestations varying from livedo reticularis to cutaneous necrosis, such as leg ulcers

-Possible nonbacterial, thrombotic endocarditis

 

Method Name
A short description of the method used to perform the test

Enzyme-Linked Immunosorbent Assay (ELISA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Phospholipid Ab IgM, S

Aliases
Lists additional common names for a test, as an aid in searching

Anticardiolipin Antibodies

Antiphospholipid Antibodies

Cardiolip

Cardiolipin Antibodies, IgM, Serum

Phospholip

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.4 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 21 days
Frozen 21 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

The following clinical situations, when used in conjunction with other criterial antiphospholipid antibody tests:

-Unexplained arterial or venous thrombosis

-A history of pregnancy morbidity defined as 1 or more unexplained deaths of a morphologically normal fetus beyond the 10th week of gestation, 1 or more premature births before 34 weeks of gestation caused by severe preeclampsia or placental insufficiency, or 3 or more unexplained, consecutive spontaneous abortions before the 10th week of gestation with no identifiable maternal hormonal or anatomic, or maternal or paternal chromosomal causes

-Presence of a systemic autoimmune rheumatic disease, especially systemic lupus erythematosus

-Unexplained thrombocytopenia

-Presence of an unexplained cutaneous manifestations varying from livedo reticularis to cutaneous necrosis, such as leg ulcers

-Possible nonbacterial, thrombotic endocarditis

 

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or specific pregnancy-related death. Based on the 2006 revised Sapporo consensus classification criteria, the laboratory requirements for diagnosing APS include the presence of at least one of the following: lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-beta2 glycoprotein 1 (anti-B2GP1) IgG or IgM antibodies.(1) To avoid overdiagnosis, and to exclude patients with transient antiphospholipid (aPL) levels, the APS guidance also recommends confirmation of any positive result at least twelve weeks after the initial evaluation. Of note, aPL antibodies also occur in patients with autoimmune diseases with significant prevalence in systemic lupus erythematosus (SLE) as well as other clinical manifestations (eg, heart valve disease, livedo reticularis, thrombocytopenia, nephropathy and neurological) often associated with APS.(1-3) Thus, in addition to the 2006 APS guidance, the 2012 derivation and validation of the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE recommends testing for the criteria aPL antibody tests as well as aCL IgA and anti-B2GP1 IgA.(2)

 

Unlike LAC, which is evaluated using functional assays, aCL and anti-B2GP1 IgG and IgM antibodies are measured with diverse solid-phase immunoassays (SPA).(4) For aCL IgG and IgM determinations, the APS classification guidance recommends antibody cut-off values greater than 40 IgG phospholipid (GPL) or IgM phospholipid (MPL) units (units traceable to the Harris standards for aCL antibody assays) or more than the 99th percentile for the testing laboratory’s population for positivity. It also advocates for the use of values greater than the 99th percentile for the laboratory’s population in the establishment of reference intervals for anti-B2GPI IgG and IgM antibody tests. The use of cutoff values greater than 40 GPL or MPL units to define positivity is not be applicable to all aCL antibody immunoassays, as the threshold used to distinguish moderate-to-high positive from low positive results are test dependent.(4-6) In addition, the cutoff used at the 99th percentile of a laboratory’s testing population may not be consistent with kits from the same manufacturer or 40 GPL units, in the case of aCL antibodies.(4-7)

 

Early observations that aCL antibody determinations made in the presence of B2GPI were more specific for APS led to the recommendation of B2GPI-dependent cardiolipin enzyme-linked immunosorbent assay (ELISA) for APS evaluation.(1,8) Cardiolipin is a negatively charged phospholipid (PL) capable of binding diverse proteins, of which B2GP1 is one of the best characterized in APS. B2GP1 is a 326-amino acid protein that contains five repetitive structures or "sushi domains," termed domain 1 through to 5, for a combined molecular weight of 54?kDa for the protein.(6). Anti-B2GP1 antibodies associated with thromboembolic events target domain 1 of the molecule and are responsible for LAC (functional, phospholipid-dependent prolongation of the clotting time) and aCL antibody positivity.(7) Compared to LAC and anti-B2GPI IgG antibodies, aCL IgG antibodies are less specific but sensitive for the diagnosis of APS. Of the aCL IgG and IgM, the IgG and not IgM confers higher diagnostic relevance and risk for definite APS.(1,6,7)

 

Thrombosis and obstetric complications are common clinical events in the general population and are not unique to APS; therefore, the presence of aPL antibodies is an absolute requirement for the diagnosis of definite APS.(1,6,7) Furthermore, aPL antibodies are heterogeneous with overlapping tendencies; the lack of aPL test harmonization or standardization requires the use of all three tests for optimal APS diagnosis.(1,4) The aPL antibodies were traditionally determined using classic ELISA, with more diverse methods recently developed and adapted for clinical testing. Recognizing the analytical and diagnostic challenges associated with aPL antibody testing, initiatives to support assay harmonization and utilization, including the development of calibrators, test development, and validation efforts as well as pre-analytical, analytical, and post-analytical measures have been published. (4-8) Based on these and other published studies, the interpretation and relevance of aPL antibody tests are dependent on factors such as the type of aPL (LAC, aCL or anti-B2GPI), the source of cardiolipin and/or B2GPI, aPL antibody class (IgG, IgM, or IgA) and level as well as whether antibody positivity is single, double, or triple.(1,4-8)

 

In conclusion, although the APS classification criteria were not established for routine clinical use, in the absence of formal diagnostic guidelines, these have widely been adopted to diagnose or assess risk for APS and the need for treatment or prophylaxis. Therefore, in clinical practice, if suspicion for disease is high but criteria aPL antibody tests are inconclusive or negative, deviation from the APS diagnostic criteria may be justified. This may include testing for non-criteria aPL antibody tests such the aCL IgA and anti-B2GPI IgA recommended in 2012 SLICC guidance for SLE and/or evaluation of anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM autoantibodies amongst others.(2,6,9,10)

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

MPL refers to IgM phospholipid units. One MPL unit is 1 microgram of IgM antibody.

 

Negative: <15.0 MPL)

Weakly positive: 15.0-39.9 MPL

Positive: 40.0-79.9 MPL

Strongly positive:> or =80.0 MPL

 

Reference values apply to all ages.

Interpretation
Provides information to assist in interpretation of the test results

Moderate-to-strong positive results for anticardiolipin (aCL) IgM antibodies (> or =40 IgM phospholipid [MPL] units) are a diagnostic criterion for antiphospholipid syndrome (APS). Compared to aCL IgG, isolated and low levels aCL IgM antibodies have a very low risk for antiphospholipid syndrome (APS) and should be interpreted with a high degree of suspicion.

 

Documentation of persistent aCL IgM antibodies is a requirement for the diagnosis of definite APS. Antibodies must be detected on 2 or more occasions at least 12 weeks apart to fulfill the laboratory diagnostic criteria for APS.

 

Detection of anticardiolipin antibodies using the enzyme-linked immunosorbent assay or other solid-phase immunoassays is not affected by anticoagulant treatment.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Immunoassays for the detection of antiphospholipid (aPL) antibodies including anticardiolipin (aCL) may not completely distinguish between autoantibodies specific for antiphospholipid syndrome (APS) and those antibodies produced in response to infectious agents with or without thrombosis. Since these antibodies may be transiently produced, documentation of persistence ,as outlined for aPL IgG and IgM antibodies in the 2006 revised Sapporo guidance for definite APS, is required (see Clinical Information).

 

Comparative studies and interlaboratory proficiency surveys indicate that results of phospholipid antibody tests can be highly variable, and results obtained with different commercial immunoassays may yield different results.(4-7)

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. 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 Feb;4(2): 295-306

2. Petri M, Orbai AM, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86

3. Sciascia S, Amigo MC, Roccatello D, Khamashta M: Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol. 2017 Sep;13(9):548-560

4.  Devreese KMJ. Solid phase assays for antiphospholipid antibodies. Semin Thromb Hemost. 2022 Sep;48(6):661-671.  doi: 10.1055/s-0042-1744364

5. Ruffatti A, Olivieri S, Tonello M, et al: Influence of different IgG anticardiolipin antibody cut-off values on antiphospholipid syndrome classification. J Thromb Haemost. 2008;6(10):1693-1696

6. Lakos G, Favaloro EJ, Harris EN, et al: International consensus guidelines on anticardiolipin and anti-beta2-glycoprotein I testing: report from the 13th International Congress on Antiphospholipid Antibodies. Arthritis Rheum. 2012 Jan;64(1):1-10

7. Pengo V, Bison E, Denas G, Jose SP, Zoppellaro G, Banzato A: Laboratory diagnostics of antiphospholipid syndrome. Semin Thromb Hemost. 2018 Jul;44(5):439-444.

8. Matsuura E, Igarashi Y, Fujimoto M, et al. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol. 1992 Jun 15;148(12):3885-91

9. Abisror N, Nguyen Y, Marozio L, et al. Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study. RMD Open. 2020 Aug;6(2):0. doi: 10.1136/rmdopen-2020-001340

10. Nakamura H, Oku K, Amengual O, et al: First-line, non-criterial antiphospholipid antibody testing for the diagnosis of antiphospholipid syndrome in clinical practice: A combination of anti-beta2 -glycoprotein I domain I and anti-phosphatidylserine/prothrombin complex antibodies tests. Arthritis Care Res (Hoboken). 2018 Apr;70(4):627-634

Method Description
Describes how the test is performed and provides a method-specific reference

Purified cardiolipin antigen is bound to the wells of a polystyrene microwell plate under conditions that will preserve the antigen in its native state. Prediluted controls and diluted patient sera are added to separate wells, allowing any cardiolipin antibodies present to bind to the immobilized antigen. Unbound sample is washed away, and an enzyme-labeled antihuman IgM conjugate is added to each well. A second incubation allows the enzyme-labeled antihuman IgM to bind to any patient antibodies that have become attached to the microwells. After washing away any unbound enzyme-labeled antihuman IgM, the remaining enzyme activity is measured by adding a chromogenic substrate and measuring the intensity of the color that develops. After stopping the enzymatic production of colored product, the presence or absence of cardiolipin antibody is determined by comparing the sample optical density with that of a 5-point calibration curve. Results are reported out semiquantitatively in standard IgM anticardiolipin units (MPL).(Package inserts: QUANTA Lite ACA IgM III. Inova Diagnostics; Version 23, 08/2020)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Saturday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 3 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

86147

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
MCLIP Phospholipid Ab IgM, S 3182-3
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
MCLIP Phospholipid Ab IgM, S 3182-3

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports