Antiphospholipid antibodies (aPL) are a family of autoantibodies targeting phospholipid-binding proteins and are associated with several clinical settings, and most notably define the antiphospholipid syndrome (APS). These antibodies can be identified using a variety of laboratory tests, which include both solid-phase immunological assays and functional clotting assays that detect lupus anticoagulants (LA). aPLs are linked to a range of adverse medical conditions, such as thrombosis and complications affecting the placenta and fetus, potentially leading to morbidity and mortality. The specific aPL identified, along with the pattern of reactivity, correlates with the severity of these conditions. Therefore, laboratory testing for aPL is crucial for evaluating the risk of complications and for fulfilling certain classification criteria for APS, which are also applied as diagnostic markers in medical practice. This review provides an overview of the available laboratory tests currently for measuring aPL and discusses their clinical implications.

Bilateral adrenal hemorrhage (AH) is linked to various causes, including bacterial and viral infections, coagulopathies, and postoperative states. Symptoms can range from mild adrenal insufficiency to shock from Waterhouse-Friedrichsen syndrome. We present a case of a 47-year-old male with antiphospholipid antibody syndrome (APS) on warfarin who presented to the emergency department (ED) with bilateral flank pain and was found to have bilateral AH. On exam, he was hypertensive, mildly tachycardic, and in severe pain. The abdomen was tender over the bilateral flank and costovertebral regions. Labs showed thrombocytopenia but normal international normalized ratio (INR) and fibrinogen. The CT and MRI confirmed bilateral AH. Further investigations revealed low ante meridiem (AM) cortisol and elevated adrenocorticotropic hormone (ACTH). The antinuclear antibody (ANA) test was negative, but the antiphospholipid antibody panel was positive. In addition, the patient had a positive Epstein-Barr virus (EBV) nuclear antigen with a significant IgM titer. He was treated with low-dose steroids and was placed on a prophylactic dose of enoxaparin with the resolution of symptoms. At discharge, he was advised to follow up with a hematologist in six weeks to restart full-dose anticoagulation, allowing time for the bleeding to resolve. This case highlights EBV infection as a possible trigger of adrenal insufficiency from adrenal bleeding in a patient with preexisting coagulopathy, necessitating prompt recognition and treatment.

The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-β-2-glycoprotein I-IgG (aβ2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aβ2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aβ2GP1-IgG, aβ2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.

Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays have only detected IgG and IgM isotypes of this antibody. However, newer assays also detect the IgA isotype. The problem lies in the largely unknown significance of this IgA isotype. This paper describes a middle-aged male who presented with hypertensive emergency and was later found to have IgA anti-beta-2 glycoprotein I antibodies. He was treated with multiple anti-hypertensives, aspirin, and statin therapy. In addition to the case, we discuss the implications of this IgA isotype and how it may relate to antiphospholipid syndrome, despite not currently being included in the laboratory diagnostic criteria for the disease.

UNASSIGNED: The objective of this study was to compare the levels of vitamin D in non-pregnant women with a history of recurrent pregnancy loss (RPL) who were seropositive or seronegative for autoantibodies (autoAbs).
UNASSIGNED: The study examined 58 RPL patients with autoAbs (ANA, anti-TPO, or APAs), 34 RPL patients without autoAbs, and 58 healthy women with prior successful pregnancies and without autoantibodies. The levels of 25 (OH) D were measured using the sandwich ELISA technique.
UNASSIGNED: Our results showed insufficient serum 25(OH) D levels in study groups, with significantly lower levels observed in RPL patients with or without autoAbs compared to healthy women (P=0.0006). In addition, RPL patients with autoAbs had significantly lower 25(OH) D levels compared to RPL patients without autoAbs. We also found that serum levels of 25(OH) D in RPL patients with autoAbs were significantly lower than in RPL patients without autoAbs (20.51 ± 1.15 ng/ml Vs. 23.69 ± 0.74 ng/ml, P=0.0356). Further analysis indicated that RPL patients who were positive for ANA, and APAs, except anti-TPO, had significantly lower than 25(OH)D serum levels than RPL patients without autoAbs.
UNASSIGNED: These findings suggest that RPL patients, especially those with APAs or ANA, have lower vitamin D levels compared to healthy women. This may indicate a link between maternal immune dysregulation due to vitamin D deficiency and the presence of autoantibodies in RPL.

OBJECTIVE: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria.
METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria.
RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system\'s rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as \"probable APS\". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aβ2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included.
CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

UNASSIGNED: This study aimed to evaluate the impact of twin pregnancies with antiphospholipid antibody (aPL) positivity, a rare and complex clinical condition that remains a huge challenge for management.
UNASSIGNED: This study enrolled twin-pregnant women at our hospital between January 2018 and August 2023. Women with and without aPL positivity were selected using propensity score matching (PSM). Clinical features and pregnancy outcomes were compared between the two groups in the PSM cohort. To analyze the effect of aPL positivity on pregnancy outcomes, multivariate logistic models were used to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI).
UNASSIGNED: Among the 773 women with twin pregnancies, aPL positivity was found in 26 women (3.36%). In the PSM cohort, there were 24 twin-pregnant women with positive aPL, and 48 women without aPL were selected as controls. Twin-pregnant women with aPL positivity had a higher proportion of abortion (8.33% vs 0, P = 0.043), preterm birth < 34 weeks (33.33% vs 8.33%, P = 0.007) and very low birthweight (<1500 g) (20.83% vs 4.17%, P = 0.016) than the control group. In addition, stillbirth of one fetus was observed in one twin-pregnant woman with positive aPL. Multivariate logistic regression analysis revealed that twin pregnancy with aPL positivity was associated with preterm birth < 34 weeks (aOR = 2.76, 95% CI: 0.83-4.70, P = 0.005), very low birthweight (<1500 g) (OR = 2.40, 95% CI: 0.18-4.67, P = 0.034) and small for gestational age (SGA) (aOR = 1.66, 95% CI: 0.22-3.10, P =0.024).
UNASSIGNED: Twin pregnancies with aPL positivity were correlated with obstetric complications, including abortion, preterm birth < 34 weeks and very low birthweight (<1500 g). The detection of aPL may be of clinical significance for women with twin pregnancies and should be considered in future studies.

BACKGROUND: Isolated prolongation of activated partial thromboplastin time (APTT) has various causes including inheritable bleeding disorders, and has medical significance as it can lead to the cancelation of surgery. However, even an emergency surgery can be conducted in a patient presenting with severe APTT prolongation, provided careful evaluation and appropriate measures are taken. Hence, the identification of the underlying etiology of the prolonged APTT is crucial. To date, little evidence exists regarding the prevalence of isolated APTT prolongation in Japanese patients undergoing surgery. Herein, we aimed to clarify the prevalence of isolated prolongation of APTT in the preoperative setting and to identify the reasons underlying isolated, severely prolonged APTT.
METHODS: Preoperative coagulation data of all elective and emergent patients who presented to the anesthetic department between January 1, 2020, and June 30, 2023, were retrospectively collected. Isolated prolongation of APTT was defined as an APTT ≥ 37 s with an international normalized ratio of prothrombin time < 1.2. The underlying etiology of the patient with isolated, severely prolonged APTT (≥ 46 s) was investigated, and canceled surgical procedures in relation to the isolated APTT prolongation were searched.
RESULTS: Overall, 10,684 measurements from 9413 patients were included, of which 725 (6.8%) were identified as having isolated APTT prolongation. The reasons for the severely prolonged APTT (n = 60) were miscellaneous, with the most frequently detected etiology being antiphospholipid antibody positivity. Preoperative isolated APTT prolongation contributed to the cancellation of surgery in elective five cases.
CONCLUSIONS: We clarified the prevalence of preoperative isolated prolongation of APTT. The presence of antiphospholipid antibody was the most frequently detected etiology of the patient with isolated, severely prolonged APTT. The present study provides an important dataset regarding the isolated prolongation of APTT in East Asian patients undergoing surgery.

Antiphospholipid syndrome (APS) is characterized by the occurrence of thrombotic events and/or obstetric complications in the presence of antiphospholipid antibodies. It is considered one of the most common acquired thrombophilias. The presentation of stroke in patients with APS has been described in some studies; however, it is not frequent enough and there is not much information available regarding the indications for pharmacological thrombolysis and the safety of thrombolytic treatment. Likewise, current evidence does not describe contraindications to thrombolytic therapy in cases of this diagnosis, which makes management with fibrinolysis safe in these cases. A clinical case of stroke is presented in which pharmacological thrombolysis is performed with a successful outcome, without complications of angioedema or bleeding. Likewise, concerning the case, the main neurological manifestations associated with APS, especially in its association with stroke, are described.

We describe a 64-year-old Caucasian female with a history of Raynaud\'s disease, hand arthritis, photosensitivity, Sjogren\'s syndrome and leukocytoclastic vasculitis who presented with progressively worsening fingertip necrosis that began three days after receiving a first dose of Pfizer-BioNTech COVID-19 RNA vaccine. Our workup revealed cryoglobulinemia, hypocomplementemia, elevated antinuclear antibodies (ANA) and IgM antiphospholipid autoantibodies (aPL) directed against phosphatidylserine (aPL-PS), suggesting a diagnosis of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The patient failed to develop anti-spike IgG antibodies up to two months following vaccination. Disease progression was halted by plasmapheresis, anticoagulation, and immune suppression. We conclude that the vaccine RNA moiety may induce SLE manifesting in APS, cryoglobulinemia, hypocomplementemia, and digital necrosis.