Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/- anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.

Prevalence of Anti-Nuclear Antibodies and Anti-Phospholipid Antibodies in an Egyptian Cohort with Schizophrenia: A Case-Control Study

Background: Psychiatric disorders, including schizophrenia could herald other manifestation(s) of systemic lupus erythematosus (SLE) potentially hindering timely and optimal management. Moreover, schizophrenia is among the described ‘extra-criteria’ manifestations of anti-phospholipid syndrome (APS). Hence, screening schizophrenia patients for SLE and APS may pose diagnostic and therapeutic implications. Objectives: Examine schizophrenia patients with no overt connective tissue disease(s) manifestation(s) for clinical and/or serologic evidence of SLE and/or APS. Methods: The study included 92 schizophrenia patients [61 (66.3%) males] and 100 age- and gender-matched healthy controls. Both groups were tested for anti-nuclear antibodies (ANAs), anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies, complement 3 (C3) and C4, and criteria anti-phospholipid antibodies (aPL) [anticardiolipin Immunoglobulin (Ig) G and IgM, anti-beta-2-glycoprotein I IgG and IgM, and lupus anticoagulant (LAC)]. Results: The patients’ mean age and disease duration were 28.8 ± 8.1 and 5.7 ± 2.2 years, respectively. The prevalence of ANA positivity, height of titre, and pattern was comparable between patients and controls (p = 0.9, p = 0.8 and p = 0.1, respectively). Anti-dsDNA antibodies and hypocomplementemia were absent in both groups. A significantly higher frequency of positive LAC was observed among patients compared with controls (7.6 % vs. 1 %, p = 0.02), whereas other aPL were comparable between both groups. None of the patients or controls demonstrated clinically meaningful (medium or high) aPL titres. Conclusion: In our study, schizophrenia was solely associated with LAC. Thus, in the absence of findings suggestive of SLE or APS, routine screening for both diseases is questionable.

Anti-Phosphatidylserine/Prothrombin Antibodies at Two Points: Correlation With Lupus Anticoagulant and Thrombotic Risk

Antibodies to phospholipids (aPL) and associated proteins are a hallmark in the diagnosis of anti-phospholipid syndrome (APS). Those included in the classification criteria are the lupus anticoagulant (LA) and the IgG and IgM isotypes of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (β2GPI) antibodies. Non-classification criteria markers such as autoantibodies that recognize the phosphatidylserine/prothrombin (aPS/PT) complex have been proposed as biomarkers for APS. Studies of aPS/PT antibodies have shown a strong correlation to clinical manifestations and LA. We aimed to study the value and the persistence of aPS/PT IgG and IgM antibodies in a cohort of consecutive patients with clinical suspicion of APS and their utility as thrombotic risk markers. Our study, with 103 patients, demonstrates that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) > than 9 points (p < 0.01, for each condition). On the other hand, no association was seen with pregnancy morbidity (p = 0.56) and SLE (p = 0.07). Persistence of aPS/PT antibodies, defined according to the current laboratory classification criteria, likely improves the diagnosis and clinical assessment of patients with APS.

The Role of Antiphospholipid Antibodies in COVID-19

Purpose of the Review Elevated levels of anti-phospholipid (aPL) antibodies are the most important criterion in the diagnosis of anti-phospholipid syndrome (APS) and are usually responsible for promoting the risk of thrombotic complications. Now, in the course of the global coronavirus disease 2019 (COVID-19) pandemic, measurable aPL antibodies have also been detected in a noticeable number of patients showing a variety ranging from studies with only isolated positive tests to cohorts with very high positivity. Thus, the question arises as to whether these two different clinical pictures may be linked. Recent Findings The ambivalent results showed a frequent occurrence of the investigated aPL antibodies in COVID-19 patients to an individually varying degree. While some question a substantial correlation according to their results, a number of studies raise questions about the significance of a correlation of aPL antibodies in COVID-19 patients. Within the scope of this review, these have now been described and compared with each other. Summary Ultimately, it is necessary to conduct further studies that specifically test aPL antibodies in a larger context in order to make subsequent important statements about the role of APS in COVID-19 and to further strengthen the significance of the described comparisons.

A Rare Case of Anti Phospholipid Syndrome Associated Intermediate and Posterior Uveitis

Introduction: Autoimmune disorders are often associated with Uveitis. Anti-Phospholipid syndrome(APS) is characterized by increased hypercoagulability and divergent ocular features. Case Presentation: A 45-year-old male patient presented with complaints of headache for 2 days. The patient gives a history of fever and loss of consciousness 20 days back and was treated symptomatically. On examination Visual acuity was 6/6 in the right eye and 6/12 in the left eye. On slit-lamp examination, the anterior segment was normal, vitreous cells were 2+ suggestive of vitritis in the left eye. Dilated fundus examination showed exudates in both eyes with macular parafoveal edema in the left eye. Laboratory investigations showed Antiphospholipid Antibody Immunoglobulin M (IgM) and Beta 2 glycoprotein IgM positive and raised ESR, PTT, and triglycerides. MRI brain showed acute embolic infarcts in multiple areas. Management: Topical Steroids and cycloplegic for uveitis and systemic steroids and anticoagulants for systemic manifestations were given and the patient's vision improved to 6/6 and macular edema reduced in the left eye during the follow-up. Conclusion: APS is a life and vision-threatening multisystem disorder, needs monitoring for INR and Anti phospholipid antibodies. A rare manifestation of uveitis is noted and prompt treatment with topical, oral steroids resolves the uveitis. But to prevent recurrences and further thrombotic events long-term immunosuppression, anticoagulation treatment is required.