aCL Testing Research Articles

A Systematic Review of Lower Extremity Return to Sport

Category: Sports; Ankle; Other Introduction/Purpose: A uniform criterion has not been established for return to sport (RTS) testing which is complicated by the lack of a standardized definition of the term RTS. Most commonly, RTS is defined as playing in at least one game of the athletes' respective sport, or the first game played after treatment.1 However, the timeline from the injury and/or treatment date to RTS varies amongst each physician or institution. Regarding the ankle, there is an enormous paucity of functional testing research. Therefore, the purpose of this project is to review current literature for joint-specific and global lower extremity testing to determine the most valid functional test that can be utilized to prevent re-injury as athletes RTS. Methods: A systematic search of PubMed, PubMed Central, Cochrane Library, OVID, and Embase databases was conducted to identify clinical studies that included evaluation of a return to sport test or functional test (single test or test battery) for the lower extremities. Both operative and non-operative treatments included in this review. Only studies that had patients between the ages of 14 years old and 40 years old were included. Specfici rehab protocik or treatment plan, non-English publications, non- human or cadaver studies, and studies that did not evaluate return to sport test or function test were excluded. Results: Of 8,705 studies, 65 (0.7%) studies published through October of 2021 met inclusion criteria and were analyzed. 52 out of 65 (80%) articles discussed RTS for the knee. Furthermore, 50 out of the 52 (96%) specifically analzyed RTS following ACLR. With this said, we did not abandon ankle and hip RTS cases. Discussed herein, are numerous RTS tests including the most common, isokinetic dynamometry testing which is seen in 38 out of the 52 (73%) of the knee RTS cases. Unfortunately, only 4 out of 65 (6.2%) studies analyzed RTS for the hip and 1 out of the 65 (1.5%) barely touched on the ankle. The remaining studies analyzed healthy participants only. Conclusion: More research is clearly required to identify the most valid functional test batteries for joint-specific RTS lower extremity testing. Even with the enormous amount of literature that exists regarding ACL injuries and testing there is no standardized criterion for RTS clearance. As seen in this review, the research available for the hip and ankle is substantially scarcer in regards functional testing. We hope that the suggested test batteries from this review can serve as a framework for future research and validation for joint-specific RTS functional testing.

432 ACS-STEMI in a young man with triple positive antiphospholipid syndrome: clinical implications about antithrombotic therapy management

Abstract Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and arterial thromboembolic (TE) disease, and/or pregnancy morbidity, associated with persistent elevated antiphospholipid antibodies (lupus anticoagulant, LA, anticardiolipin, aCL, and anti-beta2-glycoprotein I, anti-β2GPI). A 51 year-old man, smoker, presented to our ER with chest pain. EKG showed Q waves and STE in the anterior leads, with increased troponin levels. A diagnosis of anterior STEMI was made and he was taken into our catheterization laboratory, where a high burden thrombotic plaque determining LM and ostial LAD subocclusion was treated with PPCI and a DES implantation; in addition, multiple failed PCI attempts were performed on a distal LAD occlusion, and an integrilin bolus was administered. The patient was admitted to our CICU and a DAPT with ASA and Ticagrelor was started. TTE showed LVEF 40%, apical akinesis, septal and anterior hypokinesis, and no significant valve disease. An aPTT abnormal value (100.5 s; reference range 25–38.5 s) was detected, not corrected by aPTT mixing study. Given suspected autoimmune prothrombotic state, normal Hb and PLT values and low bleeding risk, LMWH 100 IU/kg every 12 h was started, in addition to DAPT with switch from Ticagrelor to Clopidogrel. LA and aCL and anti-β2GPI IgG were positive, with negativity of others rheumatologic tests, confirming primary APS diagnosis. Repeat TTE showed EF 50%. The patient was discharged in ‘triple therapy’ (DAPT plus LMWH), and referred to the rheumatology clinic. LA, aCL, and anti-β2GPI tests 12 weeks later were positive, confirming a triple positive APS and satisfying revised Sapporo criteria. The rheumatologist switched therapy to Clopidogrel plus Warfarin. At 3 months follow-up, the patient, former smoker, was asymptomatic and TTE confirmed EF 50%, so he was recommended to continue with his medical therapy. APS is rarely associated with AMI (∼5.5%) and in only 2.8% cases AMI represents the onset of the disease. AMI pathogenesis in APS is considered to be acute thrombosis of coronary arteries, in contrast with atherosclerotic plaque rupture in typical AMI. Key discriminators to identify APS as potential underlying cause of AMI include young age, previous unprovoked thromboses, low platelets count (they are consumed in the thrombotic process), high aPTT value (LA may interfere with assembly of the prothrombinase complex on phospholipids), coronary artery thromboses in the setting of otherwise normal otherwise appearing coronary arteries. APS antibodies have also pro-inflammatory activity on vascular endothelial cells, leading to accelerated atherosclerosis. aGAPSS score (high risk ≥10) is useful for risk stratification of recurrent thrombosis and AMI in young patients with APS. The treatment of AMI in APS is therefore a clinical challenge. Strict management of additional CV risk factors is crucial. VKA (INR >3 with Warfarin, INR2–3 with Warfarin and ASA) should be provided for life, because of the very high risk of recurrent TE. DOACs are less effective and less safe than VKAs for TE prevention in APS. The role of coronary stents, considering higher rates of stent thrombosis after PCI in APS patients triple therapy concomitant risks, requires further studies. Due to lack of large, randomized, prospective studies, there is no clear experts consensus about optimal antithrombotic therapy in secondary prevention after arterial TE. APS patients with STEMI should undergo PCI, usually associated with thrombus aspiration, and in selected cases DES implantation in culprit lesion followed by triple antithrombotic therapy with short-term DAPT and long-term VKA.

Study of the Effect of Intralipid Infusion during Pregnancy as an Additive Treatment for Reducing Pregnancy Complications Caused by Antiphospholipid Antibody Syndrome

Aim: To evaluate the safety and efficacy of intralipid infusion in addition to other lines of treatment in reduction of complications caused by antiphospholipid antibody syndrome. Methods: This study was held in the period from June 1, 2016, to December 1, 2019. This study was conducted in the Department of Obstetrics and Gynecology, Tanta University on patients attending the antenatal care clinic and also on patients attending the researcher’s private clinics for antenatal care, 105 patients were enrolled after application of strict inclusion and exclusion criteria. They were randomized into 2 groups. In group A (study group 1) the patients received in addition to the conventional basic treatment of APS, intralipid 20% (Frezenius, Clayton, NC, USA) in a dose of 4 ml diluted in 250 ml 0.9% regular saline IV and to be repeated every 2 weeks. In group B (control group 2) the patients received the conventional basic treatment of APS. The outcome measures were the incidence of pregnancy complications of APS namely fetal loss, premature delivery, IUGR and preeclampsia. Results: 49 patients were enrolled in the study group, and 48 patients were enrolled in the control group, after exclusion of the skipped cases. The demographic data and the gestational age at the beginning of the study show insignificant differences. There were insignificant differences as regard the gestational age at which the pregnancy was terminated and fetal birth weight in patients with positive ACL test, positive LA test and positive B2 however the mean gestational age at which pregnancy was terminated was higher in study group. Also, there was insignificant difference as regards no of patients who complicated with abortion or who completed to full term. But had significant decrease number of case who complicated with preeclampsia (8, 21 patients in study and control group respectively). Conclusion: Intralipid infusion is a promising treatment option for control and prevention of problems caused by antiphospholipid antibody syndrome.

Comparison of Diagnostic Accuracy of Physical Examination and MRI in the Most Common Knee Injuries

Purpose: This study evaluated the diagnostic accuracy of physical examination and magnetic resonance imaging (MRI) in knee injuries. Methods: Ninety-six patients at a regional hospital were included in the study. Each participant underwent a physical examination in which menisci and ACL were evaluated. Knee joint MRI was collected from each patient. Physical examination and MRI scans were then compared with knee arthroscopy findings as a golden standard for meniscal and ligamentous lesions. The data were analyzed and specificity and sensitivity were calculated and correlated on receiver operating characteristics (ROC) curves. Results: Knee arthroscopy diagnosed 32 total ACL ruptures, 45 medial meniscus and 17 lateral meniscus lesions. Three patients were diagnosed with bilateral meniscal lesions. The highest sensitivities were the McMurray test (87.5%) for medial meniscus (MM) and the Thessaly test (70%) for lateral meniscus (LM). The most sensitive ACL test was Lachman (84.5%), whereas, the pivot shift and Lelli tests were the most specific (98.5%). MRI was highly sensitive for MM (96%) with specificity of 52%. MRI showed lower sensitivity (70%) and higher specificity (85.5%) for LM. The specificity of MRI for ACL rupture was 92%, with sensitivity only 75%. Conclusion: McMurray and Apley tests for meniscal lesions seem the most appropriate in daily practice. A combination of lever signs, pivot shifts (PSs) and Lachman tests showed the best sensitivity and specificity in detecting ACL deficiency, and was superior to MRI.

The comparison of real world and core laboratory antiphospholipid antibody ELISA results from antiphospholipid syndrome alliance for clinical trials & international networking (APS ACTION) clinical database and repository analysis

BackgroundThe APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies (aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network. ObjectiveTo assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β2-glycoprotein-I antibody (aβ2GPI) ELISA testing results. MethodsPatients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available. Results497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen's kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβ2GPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβ2GPI). ConclusionsThe results of inclusion for aCL and aβ2GPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβ2GPI results showed very good categorical agreement. This agreement increased when considering high titer (>40 units) samples. APS ACTION is a reliable and useful research resource for APS.

A brief history of antiphospholipid antibodies and antiphospholipid syndrome

AIMS: To review the historical reports on antiphospholipid antibodies (aPL) from the early years of the 20th century; to outline the cardinal features of the antiphospholipid syndrome (APS) from 1983 on, including clinical criteria, etiopathogenesis and current therapy.METHODS: Literature review using PubMed. Articles on the history of aPL and APS were selected.RESULTS: The original aPL were described in patients with syphilis yet in 1906 by Wassermann. A first definition of lupus anticoagulant was proposed in 1963,while the anticardiolipin antibody (aCL) test was depicted twenty years later. The APS, initially reported by Hughes in 1985as the “aCL syndrome”, is one of the most prevalent acquired thrombophilia. Venous and arterial thrombosis, associated or not to pregnancy morbidity, comprise the main features. It is a novel disorder firstly associated to systemic lupus erythematosus. A primary form of APS was put forward in 1989, and many APS variants are currently known. Lifelong, full-dose anticoagulation is the mainstream for treatment of thrombotic APS. In obstetric APS, the combination of acetil-salicilic acid and enoxoparin has been a mostly effective therapy.CONCLUSIONS: The sequential characterization of aPL since Wassermann in 1906, and later of the APS in the 1980-thies, is a rather interesting example of how a new entity is sketched step by step. APS is an intriguing novel cause of autoimmune thrombophilia, with a complex pathogenesis and a plethora of clinical and laboratory abnormalities. Treatment is based on life-long anticoagulation.

Solid Phase Immunoassay for the Detection of Anticardiolipin Antibodies.

The anticardiolipin (aCL) test was first developed in the 1980s and proved to be a valuable addition to the lupus anticoagulant assay for identifying patients with a disorder that came to be later known as the antiphospholipid syndrome (APS). Although the test has relatively poor specificity for APS diagnosis, particularly at low positive levels, it has continued to play a major role in the identification and management of these patients because of its high sensitivity and ability to be measured in both serum and plasma, and despite concomitant presence of anticoagulants normally given to APS patients. In this chapter we outline the procedure for producing essential assay components and for performing the aCL ELISA, which can be used to determine the presence of IgG, IgM and IgA aCL antibodies in human samples. We also provide general guidelines that will facilitate optimal performance of the aCL ELISA assay.

The Effect of Frequency and Automation of Internal Control Testing on External Auditor Reliance on the Internal Audit Function

ABSTRACTFailure of the internal audit function (IAF) to detect a significant deficiency in internal controls is a significant shortcoming in the IAF's work performance. This shortcoming in the IAF's work performance reduces external auditors' willingness to rely on the IAF's work. Using a two-stage experiment, we investigate how the implementation of three different internal control testing remediation strategies (akin to CCM, ACL, and periodic manual testing), which vary in their automation and frequency, affect external auditors' perceptions of IAF strength and planned reliance on the IAF's work. We find that automated remediation strategies fully remediate external auditors' perceptions of poor IAF work performance and low degree of reliance on the IAF, whereas manual remediation strategies result in only partial remediation. Counterintuitively, less frequent remediation strategies are more effective at improving perceptions of poor IAF work performance and low levels of reliance on the IAF, relative to continuous remediation strategies.

73: Comparison of ELISA and Chemiluminescent Immunoassay Methodologies for Detection of Autoantibodies Associated With Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is associated with increased risk of thrombosis and pregnancy loss and can be diagnosed after compatible clinical events and testing for lupus anticoagulants and antiphospholipid autoantibodies: anti-cardiolipin (aCL) and anti-β2-glycoprotein I (β2GP-I) IgG/IgM antibodies. We recently compared the clinical diagnostic performance of two instruments for performing aCL and β2GP-I antibody testing: the Inova Diagnostics DSX automated ELISA and the Inova Diagnostics BIO-FLASH automated chemiluminescent analyzer. The BIO-FLASH bead-based testing system enhances sensitivity by increasing antigen exposure; furthermore, …

A New Eu3+-Labeled Method for Anticardiolipin Antibody IgM

The anticardiolipin antibodies (aCL) test has become a laboratory standard for the clinical diagnosis of antiphospholipid syndrome (APS). To better the quantitative detection of aCL-IgM so as to classify patients correctly and timely as APS positive, we established herein a new immunoassay based on a time-resolved fluoroimmunoassay (TRFIA). The complex of cardiolipin plus bovine anti-β2 glycoprotein-I was used as antigen fixed on microtiter plates to detect serum aCL-IgM, and Eu(3+) -labeled rabbit antihuman IgM was used as conjugate. The precision, sensitivity, specificity, coefficient of recovery, and stability of the assay were evaluated, and comparison with the traditional, classical enzyme-linked immunosorbent assay (ELISA) was also made. The detection limit of the aCL-IgM TRFIA kit we established was 0.1 MPL U/ml, with a wider detectable range than commercial ELISA ones when a strong-positive specimen was diluted from 2,630.9 to 0.08 MPL U/ml. There was a good liner range within 0.16 to 2,630.9 MPL U/ml, whereas it was within 5.14 to 328.86 MPL U/ml when using three commercial ELISA ones. The average intra- and interassay variability was 3.19 and 3.70%, respectively. The mean recovery rate was 101.95%. The clinical diagnostic specificity was 98%. Additionally, the established assay kit presented good characteristics of stability and correlated well with the ELISA, and the correlation coefficient was 0.955. The aCL-IgM TRFIA provides an approach to a more sensitive and reliable diagnosis of APS. Further validation of its use is required.

Bouquet variety of antiphospholipid antibodies in recurrent pregnancy loss.

Seventy-six female patients with two or more recurrent pregnancy losses (RPL) during the 1st trimester were studied. Based on the results of the aCL and aB2GPI antibodies testing, patients were divided in two groups: 22 patients with RPL and elevated immunoglobulin (Ig) G/IgM aCL and/or aB2GPI [RPL + antiphospholipid syndrome (APS)] and 54 patients with RPL alone (without high antibodies). Immunoglobulin G aPS and IgG a-AnV in patients with RPL + APS were higher than in controls and IgG aPS were higher in RPL + APS than in RPL alone. Additionally IgG a-AnV and IgM aPE are higher in RPL alone than in controls. In 18/22 (81%) patients with RPL + APS and 29/54 (54%) patients with RPL alone, there were one or more positive antibodies: aPS, aPT, a-AnV or aPE. These results raise a question whether or not these antiphospholipid antibodies should be routinely tested in women with RPL and especially in the context of the so-called “seronegative APS”.

The association of serum antiphospholipid antibodies and dilute Russell's viper venom times

AimsWe hypothesised that there is a threshold value for the association of dilute Russell's viper venom times (dRVVT) with positive immunoglobin G antiphospholipid antibody (IgG-APLA) test results.MethodsWe tested 120 controls...

Evaluation of different immunoassays for the detection of antiphospholipid antibodies: Report of a wet workshop during the 13th International Congress on Antiphospholipid Antibodies

BackgroundThe performance and standardization of anticardiolipin (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) tests for the confirmation of diagnosis of antiphospholipid syndrome (APS) remain a matter of debate and concern. We evaluated the performance of different ELISAs and other new immunoassays for the detection of aCL and aβ2GPI in a wet workshop at the 13th International Congress on Antiphospholipid Antibodies in Galveston, TX (April 13th, 2010, APLA 2010). MethodsAliquots of 26 un-identified APS or persistently aPL positive serum samples and 21 controls (9 from healthy individuals and 5 from patients with infectious diseases and 7 with various autoimmune diseases) were distributed to all participants/groups. All serum samples were evaluated in various aCL and aβ2GPI ELISAs, a chemiluminescent immunoassay, a fluoro-enzyme immunoassay, and in a multiplexed immunoassay system. Monoclonal and polyclonal calibrators were also evaluated. ResultsAlthough not all the assays reported the titers of aCL and aβ2GPI in the same units, the correlation of positive titers among the assays was good. All aCL and aβ2GPI tests showed excellent clinical sensitivities, specificities and positive predictive values and good agreement with respect to the levels of the IgG and IgM antibodies, regardless of assay type, or whether tests were done using automated or “manual” systems. ConclusionsNew methodologies for the detection of aPL look promising and comparable to currently approved ELISA tests. This study provides evidence of progress of efforts of harmonization of tests used to detect aPL.

Diagnosis of antiphospholipid syndrome in routine clinical practice

The updated international consensus criteria for definite antiphospholipid syndrome (APS) are useful for scientific clinical studies. However, there remains a need for diagnostic criteria for routine clinical use. We audited the results of routine antiphospholipid antibodies (aPLs) in a cohort of 193 consecutive patients with aPL positivity-based testing for lupus anticoagulant (LA), IgG and IgM anticardiolipin (aCL) and anti-ß2glycoprotein-1 antibodies (aß2GPI). Medium/high-titre aCL/aβ2GPI was defined as >99th percentile. Low-titre aCL/aβ2GPI positivity (>95th < 99th percentile) was considered positive for obstetric but not for thrombotic APS. One hundred of the 145 patients fulfilled both clinical and laboratory criteria for definite APS. Twenty-six women with purely obstetric APS had persistent low-titre aCL and/or aβ2GPI. With the inclusion of these patients, 126 of the 145 patients were considered to have APS. Sixty-seven out of 126 patients were LA-negative, of whom 12 had aCL only, 37 had aβ2GPI only and 18 positive were for both. The omission of aCL or aβ2GPI testing from investigation of APS would have led to a failure to diagnose APS in 9.5% and 29.4% of patients, respectively. Our data suggest that LA, aCL and aβ2GPI testing are all required for the accurate diagnosis of APS and that low-titre antibodies should be included in the diagnosis of obstetric APS.

Pulmonary involvement in asymptomatic systemic lupus erythematosus patients with antiphospholipid syndrome multislice CT angiography and pulmonary involvement in asymptomatic SLE patients with APS

ObjectiveTo detect the pulmonary involvement in asymptomatic secondary APS patients by pulmonary function tests (PFTs) and chest multislice HRCT angiography. Comparing the pulmonary findings to those of asymptomatic SLE patients without APS was considered. Patients and methodsThirty-four SLE patients with APS and another 34 SLE patients without APS and with a negative ACL test were included as control. All patients were asymptomatic for any pulmonary manifestations. Plain chest X-ray, HRCT angiography and PFTs were performed for all patients in an attempt to assess the pulmonary vasculature and lung parenchyma. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) while assessment of organ damage was made using the Systemic Lupus International Collaborating Clinics/ACR (SLICC/ACR) index. ResultsThere were abnormal pulmonary CT findings in 11 (32.35%) of the asymptomatic secondary APS patients with an obvious association to lupus anticoagulants. However, plain X-ray showed basal atelectasis and/or elevation of the copulae in four patients. Pulmonary abnormalities included a high frequency of pulmonary artery aneurysms (20.59%) thrombosis, basal atelectasis, embolism, bronchiectasis, pleural effusion and thickening. The SLEDAI and SLICC were significantly higher in APS patients. More SLE patients without APS were receiving hydroxychloroquine which suggests a protective role on the thromboembolic events occurring in APS. ConclusionMultislice HRCT pulmonary angiography, with its multiplanar capability, vascular reconstruction and high quality, is useful in demonstrating the entire thoracic spectrum in asymptomatic APS patients. Particular concern about the medications used in APS could prevent the risk of developing noticeable thromboembolic events.

Definition and significance of high positivity aCL ELISA

We conducted a prospective study of anticardiolipin antibody (aCL) testing, performed in our university hospital. Among 6321 consecutive patients tested for both IgG and IgM aCL, 91 patients with medium or high positivity (>99th percentile) had a subsequent confirmatory test. Among them, 53 had a persistent positivity at 12 weeks. In this real world setting, patients with transient positivity had lower values than patients with persistent positivity.

Internal Quality Control and External Quality Assurance in Testing for Antiphospholipid Antibodies: Part I—Anticardiolipin and Anti-β2-Glycoprotein I Antibodies

Over 30 years since it was first described as a discrete clinical entity, the antiphospholipid antibody syndrome (APS) remains a challenge for both laboratory workers and clinicians in a wide range of specialties. In addition to the presence of appropriate clinical features, the diagnosis of APS also fundamentally requires the finding of positive antiphospholipid antibody (aPL) test result(s), which comprise clot-based assays for the identification of lupus anticoagulant (LA) and immunologic ("solid-phase") assays such as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI). This article is the first of two that review the process for, and provides recommendations to improve, internal quality control (IQC) and external quality assurance (EQA; or proficiency testing) for aPL assays. These processes are critical for ensuring the quality of laboratory test results and thence the appropriate clinical diagnosis and management of APS. This article covers aCL and aβ2GPI testing. In brief, IQC is a process that helps control the quality of laboratory test results on a test-by-test basis; IQC should include samples that provide values around the assay critical cut-off values, and there is added value in the inclusion of non-kit assay controls. EQA is a process that helps laboratories assess their performance against those of their peers. For aCL and aβ2GPI testing, we provide some updated findings from the Royal College of Pathologists of Australasia Immunology Quality Assurance Program, and covering testing for the past 3 years (2009 to 2011 inclusive). Findings show similar trends to past years, indicating limited improvement in cross-laboratory test results and interpretations. In summary: (1) EQA participants reported greatly varying numerical test data for both aCL and aβ2GPI, with interlaboratory coefficients of variation > 50% with most test challenges; (2) there was considerable overlap in the interpretation (negative, positive, low positive, moderate positive, strong positive) that different participants ascribed to identical numerical test results; and (3) there was limited consensus among participants as to whether test results for individual EQA specimens were either positive or negative for aCL and/or aβ2GPI.

Guidelines on the investigation and management of antiphospholipid syndrome

This guidance updates and replaces the previous guideline on the investigation and management of antiphospholipid syndrome (APS) published in 2000 (Greaves et al, 2000), though where there have not been changes we refer back to them when appropriate. The guidance is updated with reference to relevant publications since 2000. Publications known to the writing group were supplemented with additional papers identified by searching PubMed for publications in the last 11 years using the key words: lupus anticoagulant, anticardiolipin, antiphospholipid, b2–glycoprotein I, antiprothrombin and limits (clinical trial, randomized control trial, meta-analysis, humans, core clinical journals, English language). The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the Royal College of Obstetricians and Gynaecologists (RCOG), and the British Committee for Standards in Haematology (BCSH) Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMEN DATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with antiphospholipid syndrome though individual patient circumstances may dictate an alternative approach.

An update on international consensus guidelines for antiphospholipid antibody testing

In spite of the publication of several proposals, consensus documents and expert opinions, there still exists significant inter-assay and inter-laboratory variation in the results of both aCL and anti-b2GPI testing, which affects the consistency of the diagnosis of the antiphospholipid syndrome (APS). The USA-based but internationally-represented Clinical and Laboratory Standards Institute (CLSI) therefore convened a Document Development Committee on Antiphospholipid Antibodies in mid 2011. The overall purpose of this committee is to provide clinical laboratories, assay users and kit developers and manufacturers with recommendations and consensus guidelines that will hopefully improve the consistency, performance and reliability of aCL and anti-b2GPI immunoassays.

Symmetrical peripheral gangrene: a rare presentation of antiphospholipid syndrome

A 25-year-old woman presented with complaints of dark discolouration of the hands, feet and the tip of the nose 1 week after normal delivery of a preterm baby (28 weeks) in April 2009. The onset was subacute and the discolouration progressed to the wrists and just above the ankles in a bilaterally symmetrical fashion. There was a history of fever from the onset of symptoms. There was no prior history of diabetes or cardiovascular illness. The baby had to be kept in the neonatal intensive care unit for 2 weeks hospitalization, as he was premature, and suffering from acute respiratory distress. On examination, the vital signs were: pulse 94 beats per minute and blood pressure of 118/72 mm/Hg, respirations 18 breaths/min. She had superficial pregangrene of the tip of the nose (Fig. 1), hands and feet extending to the distal leg. Superficial ulcerations were absent (Fig. 2). The skin of pregangrenous area was dry. The patient could move her hands and feet, but there was partial loss of sensation in the area of superficial pregangrene. She had moderate pallor, but no cyanosis. Examinations of the chest and abdomen were normal. The hemoglobin was 9.5 gm%, blood urea 22 mg% and serum creatinine 1 mg%. Her platelet count, prothrombin time and activated partial thromboplastin time were normal. A blood culture was negative. The anticardiolipin antibody (aCL) test was positive however a Lupus anticoagulant (LCA) test was not done. Protein C, protein S and antithrombin III levels were normal. Antinuclear antibody test and antibodies to double stranded DNA (ds-DNA) for systemic lupus erythematosus were negative. The chest X-ray study as well as a urinalysis was normal. The ultrasonography of the pelvis showed a mildly enlarged uterus without any fluid collection in the pelvis. The aCL test was still positive after 6 weeks.