scholarly journals Do Current Antiphospholipid Antibody Syndrome Guidelines Effectively Target at-Risk Obstetric Patients?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1208-1208
Author(s):  
Kanika Thapar ◽  
Nimesh Patel ◽  
Bolanle Gbadamosi ◽  
Daniel E Ezekwudo ◽  
Ishmael Jaiyesimi ◽  
...  
Keyword(s):  
At Risk ◽  
Venous Thromboembolism ◽  
Gestational Age ◽  
Fetal Loss ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Recurrent Fetal Loss ◽  
Clinical Criteria ◽  
Significant Difference ◽  
Positive Results

Abstract Introduction: The incidence of spontaneous miscarriages is 1%, and up to 50% of recurrent fetal losses (RFL) have unclear etiology. Antiphospholipid syndrome (APS) has been reported in 5-15% of women with RFL. Current clinical criteria for APS include venous thromboembolism (VTE) and /or fetal loss. In addition to the clinical criteria, laboratory confirmation must be obtained using tests for lupus anticoagulant (LA), anticardiolipin (ACL) and beta-2 glycoprotein I antibodies (β2GPI). These tests are often provided by many laboratories as panels; moreover, given the relatively large number of tests, judicious ordering of these panels is warranted to contain costs and to avoid mislabeling patients who have clinically insignificant positive results. Some existing literature suggests that patients with recurrent fetal loss and ACL antibodies are over-tested and/or over-diagnosed. We aim to determine the frequency and likelihood of positive antiphospholipid antibody (APA) among patients with fetal loss. Materials and Methods: A retrospective search was conducted for APA panels using data from our laboratory information system from Jan 2014 to Jan 2015. Recorded variables included age, ordering physician subspecialty and indication for testing. For patients with fetal loss, the number of losses and gestational age at the time of loss were recorded. Specimens were classified as positive, indeterminate or negative. For positive and indeterminate tests, the results of LA, ACL, and β2GPI antibody tests and titers were noted. Results: Our search identified 430 panels ordered for APA. The median age was 42 (range: 1-92). The three highest ordering physician subspecialties were Ob/Gyn (20.2%), Internal Medicine (17.7%) and Heme/Onc (17.2%). The three most common indications for ordering the APA panel were venous thromboembolism (26.5%), fetal loss (18.4%), and autoimmune disease (15.4%). The largest percentage of positive results came from panels ordered by Heme/Onc 45% (20/44) and for the indication of VTE 40.9% (18/44). Fetal loss (n=74) accounted for 4.5% (2/44) of positive results. Further investigation of the fetal loss cases showed that 82.4 % (61/74) met criteria for appropriate APA testing. There was no statistically significant difference for gestational age < 10 weeks (1 positive, 4 indeterminate, and 30 negative specimens) or > 10 weeks (1 positive, 1 indeterminate, and 37 negatives; p=0.334); ordering physician subspecialty and the APA testing result. Both fetal loss patients that tested positive for APS had increased titers of ACL IgM and β2GPI IgM. Conclusions: Despite being the second most common indication for APA testing, fetal loss only accounted for 4.5% of positive results. Compared to historical data that report an incidence of 5-15% APS in patients with recurrent fetal loss, we found an incidence of only 2.7%. The reason for this discrepancy is not clear. Confounding factors such as inappropriate work-ups or incomplete testing are unlikely as 82.7% of patients meet standard testing criteria and our APA panels included multiple tests for LA, ACL and β2GPI. Larger studies are needed to confirm our findings, as this may call for redefinition of APA testing guidelines to better target at risk obstetric patients. Disclosures No relevant conflicts of interest to declare.

Is It Time To Reconfigure Lupus Anticoagulant Panels?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2648-2648
Author(s):  
Zella Rose Zeigler ◽  
Andrea L. Cortese Hassett
Keyword(s):  
Risk Assessment ◽  
Venous Thromboembolism ◽  
Lupus Anticoagulant ◽  
Fetal Loss ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Clinical Events ◽  
Beta 2 ◽  
Record Review ◽  
Positive Results

Abstract Traditional lupus anticoagulant (LAC) panels are designed to test the presence/absence of antiphospholipid antibodies (APA). These usually include testing for a LAC with clot based assays (dRVV, Hex PL, aPTT) or with the tissue thromboplastin inhibition assay (TTI) and ELISA assays for anticardiolipin antibodies (ACA). It is now recognized that antibodies to a phospholipid binding protein, beta-2-GPI are important in the autoimmune form of the antiphospholipid syndrome (aPls). Moreover, some patients (pts.) may only be positive in this latter testing and have what is termed sero-negative aPls. The present study is a retrospective medical record review methodology to analyze the results of APA tests in 258 consecutive pts. referred to the PI at the Hemostasis & Thrombosis Clinic at the Institute For Transfusion Medicine. Inclusion criteria were any pt. who had a lupus panel and anti-beta-2-GPI (IgG, IgM and IgA) testing performed. Exclusion criteria were any pts. who did not have this testing or pts. with positive results which were not repeated > 2 months later. The cohort consisted of 258 pts (69M:189F) with a median age of 48 (range=13–85). Of these pts., 35 (13%) were referred for risk assessment, 133 (52%) for arterial or venous thrombosis, 62 (24%) for neurologic reasons, and 27 (11%) for other reasons. Patients on no anticoagulation (OAC) were considered to be LAC+, if any of the clot based assays was repeatedly positive, did not correct on a mix, and shortened with the additon of phospholipid. OAC pts. with positive ELISA assays were considered to have a LAC if the dRVV was positive on a mixing study and/or if the Hex PL test was positive. OAC pts. with only evidence for a LAC, were taken off OAC and then studied. ELISA assays were considered to be positive if low titer positive or higher, e.g. ≥ 3 STD above the mean. Positive results were found in 59/258 (22.8%) of these pts. The antibody results are listed in the table below in the pts. referred for risk assessment and in the pts. referred with events. The results are listed in categories of APA positivity. Antiphospholipid Antibody Results In Pts With Risk Assessment and Pts With Clinical Events Pt. Group LAC+beta-2-GPI LAC Only Beta-2-GPI Only ACA Only Total NOTE: 36% of the positive pts. would be missed by the traditional LAC panel. Risk Assessment 0/35 (0%) 0/35 (0%) 1/35 (3%) 0/35 (0%) 1/35 (3%) Pts. With Events 26/233 (11%) 12/233 (5%) 20/233 (9%) 0/35 (0%) 58/233 (25%) Total Positive Results 26/59 (44%) 12/59 (20%) 21/59 (36%) 0 59 These results indicate that one-third of the pts. with phospholipid antibodies were sero-negative, e.g. negative in the presently constructed panels but positive for anti-beta-2-GPI antibodies. Skeptism exists about the meaning of isolated anti-beta-2GPI positivity. Of the pts. with only + beta-2-GPI antibodies, one male was asymptomatic (5%). The remaining pts. in this group were females. Ten/twenty-one (48%) of the pts. with isolated beta-2-GPI positivity were referred for neurologic reasons. These consisted of TIA’s in 6, complex migraines with TIA’s and acral cyanosis (1), recurrent fetal loss and TIA’s in 3. Eight pts. (38%) had recurrent venous thromboembolism and 2 (9%) had both arterial and venous thromboembolism. We suggest that it may be time to consider constructing LAC screening panels containing tests for both LAC and anti-beta-2-GPI antibodies (all three isotypes) as sero-negative APls appear to be fairly common in females referred for thrombophilic testing.

Safety and Efficacy of Direct Oral Anticoagulant Therapy in Patients With Cancer

2019 ◽  
pp. 089719001989650
Author(s):  
Lindsey M. Fovel ◽  
Robert W. Seabury ◽  
Christopher D. Miller ◽  
William Darko ◽  
Luke A. Probst ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Minor Bleeding ◽  
Safety And Efficacy ◽  
Patients With Cancer ◽  
Significant Difference

Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with malignancy. The currently available guidelines have shown greater support for utilization of low-molecular-weight heparin (LMWH) over direct oral anticoagulants (DOACs) in cancer-associated VTE. Current data on the safety and efficacy of DOAC therapy in patients with cancer are lacking. Objective: To evaluate the safety and efficacy of the use of DOACs compared to LMWH in patients with cancer. Methods: A retrospective review of outpatient records was completed to identify patients with documented cancer diagnosis and either a DOAC or LMWH as a listed medication. Patients were excluded if they had atrial fibrillation, valvular disease, antiphospholipid antibody syndrome, current pregnancy, body mass index (BMI) >40 kg/m2 or weight >120 kg, severe renal or hepatic impairment, or were on concomitant therapy with a significant interacting medication. The primary outcome was frequency of VTE recurrence, and secondary outcomes included the frequency of major and minor bleeding and other thrombotic events. Results: One hundred fifty-six patients were included in the study population, 78 in both the DOAC and LMWH groups. Venous thromboembolism recurrence occurred in 5 (6.4%) patients in the DOAC group and 8 (10.3%) patients in the LMWH group ( P = .39). There was no significant difference in major or minor bleeding or other thrombotic events between the 2 groups. Conclusion: The frequency of VTE recurrence was similar between DOACs and LMWH in patients with cancer. DOACs may be an alternative agent to LMWH for the prevention of recurrent VTE in patients with cancer.

IgA Anticardiolipin Antibodies – Relation with other Antiphospholipid Antibodies and Clinical Significance

1998 ◽  
Vol 79 (02) ◽  
pp. 282-285 ◽  
Author(s):  
Josep Ordi-Ros ◽  
Francesc Monegal-Ferran ◽  
Nuria Martinez ◽  
Fina Cortes-Hernandez ◽  
Miquel Vilardell-Tarres ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Cross Sectional Study ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Serum Samples ◽  
Cross Sectional ◽  
Vein Thrombosis

SummaryObjective: To evaluate the usefulness of IgA antiphospholipid antibodies as markers of thrombosis and/or antiphospholipid antibody syndrome. Patients and Methods: A cross-sectional study design in a tertiary, university-based, autoimmune reference hospital. Seven-hundred ninety-five patients classified into five different groups – autoimmune diseases (255), deep vein thrombosis (153), transitory ischemic attacks (108), obstetric complications (196), infectious diseases (83) and controls (81) – were tested for IgA, IgG and IgM aPL, and lupus anticoagulant. Plasma and serum samples were drawn for detection of aPL using an internationally standardized ELISA method and LA was carried out using coagulometric assays. Results: True IgA aPL were found only in two patients with systemic lupus erythematosus; these patients were also positive to IgG aPL. Conclusion: The incidence of true positivity to IgA anticardiolipin antibodies is extremely low. Their determination was not helpful in diagnosing the antiphospholipid syndrome or in explaining thrombotic events or aPL related manifestations – fetal loss – in the groups studied.

scholarly journals Antiphospholipid Antibody Syndrome and Infertility

2019 ◽  
Vol 41 (10) ◽  
pp. 621-627
Author(s):  
Vivian de Oliveira Rodrigues ◽  
Adriana de Góes e Silva Soligo ◽  
Gabriel Duque Pannain
Keyword(s):  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Female Infertility ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Therapeutic Approaches ◽  
Negative Effects ◽  
The Past ◽  
New Therapeutic Approaches ◽  
Abortion Complications

AbstractAntiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies (aPLs), thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. The objective of the present study was to review the pathophysiology of APS and its association with female infertility. A bibliographic review of articles of the past 20 years was performed at the PubMed, Scielo, and Bireme databases. Antiphospholipid antibody syndrome may be associated with primary infertility, interfering with endometrial decidualization and with decreased ovarian reserve. Antiphospholipid antibodies also have direct negative effects on placentation, when they bind to the trophoblast, reducing their capacity for invasion, and proinflammatory effects, such as complement activation and neutrophil recruitment, contributing to placental insufficiency, restricted intrauterine growth, and fetal loss. In relation to thrombosis, APS results in a diffuse thrombotic diathesis, with global and diffuse dysregulation of the homeostatic balance. Knowing the pathophysiology of APS, which is closely linked to female infertility, is essential for new therapeutic approaches, specialized in immunomodulation and inflammatory signaling pathways, to provide important advances in its treatment.

Neurological manifestations of antiphospholipid antibody syndrome

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 67-74 ◽  
Author(s):  
R.L. Brey ◽  
A Escalante
Keyword(s):  
Cerebral Ischemia ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Transverse Myelitis ◽  
Symptomatic Treatment ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Neurological Manifestations ◽  
Immunosuppressant Therapy ◽  
Plausible Mechanism

Thrombosis, thrombocytopenia, recurrent fetal loss and a variety of non-thrombotic neurological disorders have all been associated with antiphospholipid antibodies (aPL). Cerebral ischemia associated with aPL is the most common arterial thrombotic manifestation. Depression, cognitive dysfunction, depression and psychosis have all been associated with aPL. The presumed pathophysiologic mechanism underlying these manifestations is thought to be a result of cerebral ischemia in some, but not all cases. Seizures, chorea and transverse myelitis all appear to be associated with aPL. An interaction between aPL and central nervous system cellular elements rather than aPL-associated thrombosis seems to be a more plausible mechanism for these clinical manifestations. Migraine on the other hand, does not appear to be associated with aPL in either lupus or non-lupus populations. Neuroimaging studies show an increased frequency of brain abnormalities in patients with aPL, but none appear to be specific. The best treatment strategy for preventing neurological manifestations of aPL is not fully defined. For thrombotic manifestations, both antiplatelet and anticoagulant therapies have been suggested. In some patients, immunosuppressant therapy has been used. For non-thrombotic manifestations, some combination of immunosuppressant therapy and symptomatic treatment may be warranted.

The Experiences and Challenges of Pregnant Women Coping with Thrombophilia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5496-5496
Author(s):  
Jessica D. Emed ◽  
Tanya Z. Martens ◽  
Susan R. Kahn
Keyword(s):  
Decision Making ◽  
Pregnant Women ◽  
Coping Strategies ◽  
Fetal Loss ◽  
Vascular Complications ◽  
Factor V Leiden ◽  
Medical Decision ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Venous Thromboembolic Events

Abstract Background and Objectives: Pregnancy may be adversely affected by thrombophilia via venous thromboembolism-induced morbidity and mortality or via gestational vascular complications such as fetal loss or preeclampsia. Women with thrombophilia are often prescribed heparin for daily self-injection during pregnancy. The purpose of this study was to explore the unique experiences, challenges, and coping strategies of pregnant women with thrombophilia who are on daily heparin injections. Study Methods: A qualitative, descriptive approach with semi-structured, individual interviews was used. Women with thrombophilia followed at the Thrombosis Clinic of a large university affiliated hospital in Quebec, Canada who were prescribed heparin during pregnancy and who were pregnant at the time of the study or within the last 12 months were eligible. Interviews lasting 45 minutes performed by a trained graduate nursing student were conducted with each participant. Thematic analysis was used throughout the processes of interviewing, transcribing verbatim, and categorizing the data. Results: Nine women (age range 30–36) participated in the study. Four participants had antiphospholipid antibody syndrome, three had the lupus anticoagulant, one had Factor V Leiden and one had Protein S deficiency. For all participants, the diagnosis of thrombophilia was made via blood testing after referral to Clinic for evaluation of multiple early pregnancy losses, late pregnancy losses, or other serious pregnancy complications. None had previous venous thromboembolic events. Four main themes were identified based on analysis of the interview transcripts: the emotional impact of diagnosis and treatment of thrombophilia, which was influenced by past pregnancy experiences as well as the experiences of others; the need for professional support, particularly concerning medical decision-making regarding whether to choose treatment in certain cases, but also with regards to information, injection technique, and emotional needs; uncertainty vis-à-vis treatment outcomes; and successful coping strategies such as taking control and maintaining perspective. Conclusions: This qualitative research shows that, during pregnancy, coping with thrombophilia and daily heparin injections can be a stressful experience. However, the ensuing challenges are perceived as manageable discomforts in light of the outcome of a healthy baby. Implications for health professionals include providing written information to complement explanations given during appointments, standardization of self-injection teaching, establishing peer networks among women who have had similar experiences, and follow-up with a nurse, who can provide ongoing support around coping with uncertainty and the stress of self-injection, revisit the information given, and provide emotional support and referral, if needed. Greater standardization of physician decision making regarding the need for thrombophilia screening and anticoagulation may also be beneficial, since differences in physicians’ approaches across institutions was reported by participants as a source of stress. Nurses, in collaboration with physicians, are in a key position to enhance the quality of care to this population. Further research should evaluate a standardized program based on interventions suggested by this study.

scholarly journals Increased Plasma Concentrations of Antiprothrombin Antibodies in Women with Recurrent Spontaneous Abortions

2007 ◽  
Vol 53 (2) ◽  
pp. 228-232 ◽  
Author(s):  
Laura Sabatini ◽  
Michela Torricelli ◽  
Valentina Scaccia ◽  
Daniela Fineschi ◽  
Monica Pescaglini ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Fetal Loss ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Recurrent Abortion ◽  
Retrospective Case ◽  
Relevant Role ◽  
Antiprothrombin Antibodies ◽  
High Concentrations ◽  
Relationship Of

Abstract Background: Antiphospholipid antibodies are associated with recurrent fetal loss, but the clinical relevance of antiprothrombin (aPT) antibodies remains controversial. This study was designed to evaluate the relationship of plasma concentrations of aPT antibodies (IgG, IgM, and IgA isotypes) and recurrent spontaneous abortion (RSA) not associated with antiphospholipid-antibody syndrome. Methods: In this retrospective case–control study, we measured plasma aPT antibodies in 100 pregnant women at 8–12 weeks of gestation who had histories of recurrent abortion not associated with antiphospholipid-antibody syndrome. The controls were 200 healthy gestational-age–matched women with uncomplicated gestations. Results: The mean (SD) plasma aPT concentrations were significantly (P &lt;0.001) higher in women with histories of recurrent abortion than in healthy controls [7.97 (0.79) and 2.08 (0.07) kU/L]. Similarly, the concentrations of IgM aPT were significantly (P &lt;0.001) higher in patients than in controls [5.73 (0.85) and 1.83 (0.05) kU/L]. No differences were found for IgA aPT (P = 0.358). Conclusions: High concentrations of aPT antibodies (IgG and IgM isotypes) are associated with pregnancy loss in women with RSA. We suggest that the antibodies may have a relevant role in the etiology and pathogenesis of the condition.

scholarly journals Venous Thromboembolism: A Survey of Oral Anticoagulant Preferences in the Treatment of Challenging Patient Populations

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 209S-216S ◽  
Author(s):  
Genevieve Claire Moyer ◽  
Bethany Samuelson Bannow ◽  
Courtney Thornburg ◽  
Rachel Rosovsky ◽  
Tzu-Fei Wang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Options ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Oral Anticoagulant Treatment ◽  
Increased Risk ◽  
Altered Metabolism

Venous thromboembolism (VTE) is a highly morbid condition with several available oral anticoagulant treatment options. Numerous studies have been published comparing warfarin to direct oral anticoagulants; however, several populations remain underrepresented in these reports. We surveyed members of The Venous ThromboEmbolism Network U.S. working group regarding their oral anticoagulant preferences for the treatment of VTE in different and challenging populations. In individuals with VTE and no other medical comorbidities, respondents preferred either rivaroxaban (48.7%) or apixaban (48.7%). Apixaban (53.3%) was preferred in elderly individuals with an increased risk of bleeding. Warfarin was preferred in individuals with liver or kidney dysfunction (42% and 47%), altered metabolism (>55%), and antiphospholipid antibody syndrome (84.2%). Low-molecular-weight heparin was preferred in individuals with malignancy (56.6%), followed by edoxaban (23.7%). These findings may help guide clinicians when choosing an anticoagulant in these challenging situations and demonstrate the urgent need for additional study in these groups.

scholarly journals Antiphospholipid syndrome: a clinical and laboratorial challenge

2014 ◽  
Vol 60 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Luci Maria Santana Dusse ◽  
Fernanda Dias e Silva ◽  
Letícia Gonçalves Freitas ◽  
Danyelle Romana Alves Rios ◽  
Sandra Cristina Armond ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Fetal Loss ◽  
Anticardiolipin Antibodies ◽  
Major Protein ◽  
Protein Targets ◽  
Clinical Criteria ◽  
Glycoprotein I ◽  
Increased Sensitivity ◽  
Commercial Kits ◽  
Positive Results

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by the presence of a heterogeneous family of antibodies that bind to plasma proteins with affinity for phospholipid surfaces. The two major protein targets of antiphospholipid antibodies are prothrombin and β2-glycoprotein I (β2GPI). APS leads to aprothrombotic state, and it is characterized by the occurrence of arterial, venous or microvascular thrombosis or recurrent fetal loss. The diagnosis of APS is based on a set of clinical criteria and the detection of lupus anticoagulant (LA), anticardiolipin antibodies (ACA) or anti-β2GPI in plasma. Although laboratory tests are essential for APS diagnosis, these tests have limitations associated with the robustness, reproducibility and standardization. The standardization of diagnostic tests for detection of APLAs has been a challenge and a variety of results have been obtained using different commercial kits and in-house techniques. An increased sensitivity of the ELISA kits for detection of ACA effectively has contributed to APS diagnosis. However, the lack of specificity associated with a high number of false-positive results is a clinical and laboratorial challenge, since such results may lead to mistaken clinical decisions, such as prescription of oral anticoagulant, leading to the risk of hemorrhaging. Furthermore, clinicians are often unfamiliar with these tests and have difficulty interpreting them, requiring interaction between clinical and laboratory professionals in order to ensure their correct interpretation.

Sign in / Sign up

Export Citation Format

Share Document