Hepatic Infarction in Pregnancy: A Systematic Review.

OBJECTIVE: Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. The objective of this review is to identify risk factors, presenting signs and symptoms, methods of diagnosis, and best management practices based on published case reviews. DATA SOURCES: PUBMED and MEDLINE: OVID databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period since database inception until the study date of December 18, 2023. Keywords included "liver infarction" OR "hepatic infarction," AND "pregnancy" OR "obstetrics." STUDY ELIGIBILITY: Case reviews or case series published in the English language were included. Our study was registered with PROSPERO (#CRD42023488176) and was conducted in accordance with published PROSPERO and MOOSE guidelines. STUDY APPRAISAL: Included papers were evaluated for bias using a previously published tool by Murad et al (2018). RESULTS: A total of 38 citations documenting 50 pregnancies published between 1979 - 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome (APS), and 22% had a history of thrombus. Of those without a pre-existing diagnosis of APS, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%) and 32% and 16% had severe blood pressure (BP) or mild BP, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. CT scan was used to confirm diagnosis of hepatic infarction in 58% of cases, MRI in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases. CONCLUSIONS: Hepatic infarction should be considered in all cases of HELLP, but specifically in patients with a history of APS who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with CT scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.

Testing for the lupus anticoagulant: the good, the bad, and the ugly.

Lupus anticoagulant (LA) represents 1 of the laboratory criteria for classification of patients as having definite antiphospholipid syndrome (APS). The other 2 laboratory criteria are anticardiolipin antibodies and anti-beta2-glycoprotein I antibodies. At least 1 of these antiphospholipid antibody (aPL) tests need to be positive, with evidence of persistence, together with evidence of at least 1 clinical criterion for APS, before a patient can be classified as having definite APS. LA and other aPL assays are also important for diagnosis or exclusion of APS, as well as for risk stratification, with triple-positive patients carrying the greatest risk. Whereas LA is identified through "uncalibrated" clot-based assays, the other aPL assays (anticardiolipin and anti-beta2-glycoprotein I antibodies) represent immunological assays, identified using calibrated solid-phase methods. Because LA is identified using clot-based assays, it is subject to considerable preanalytical and analytical issues that challenge accurate detection or exclusion of LA. In this narrative review, we take a look at the good, the bad, and the ugly of LA testing, primarily focusing on the last 10 years. Although harmonization of LA testing as a result of International Society on Thrombosis and Haemostasis guidance documents and other international activities has led to improvements in LA detection, many challenges remain. In particular, several anticoagulants, especially direct oral anticoagulants and also vitamin K antagonists, given as therapy to treat the pathophysiological consequences of aPL, especially thrombosis, interfere with LA assays and can generate false-positive or false-negative LA findings. Overcoming these diagnostic errors will require a multifaceted approach with clinicians and laboratories working together.

Disentangling the riddle of systemic lupus erythematosus with antiphospholipid syndrome: blood transcriptome analysis reveals a less-pronounced IFN-signature and distinct molecular profiles in venous versus arterial events.

INTRODUCTION: Systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS) represents a challenging SLE endotype whose molecular basis remains unknown. METHODS: We analysed whole-blood RNA-sequencing data from 299 patients with SLE (108 SLE-antiphospholipid antibodies (aPL)-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised weighted gene coexpression network analysis and machine learning were applied to distinguish disease endotypes. RESULTS: Patients with SLE-APS demonstrated upregulated type I and II interferon (IFN) pathways compared with HC. Using a 100-gene random forests model, we achieved a cross-validated accuracy of 75.6% in distinguishing these two states. Additionally, the comparison between SLE-APS and SLE-aPL-negative revealed 227 differentially expressed genes, indicating downregulation of IFN-α and IFN-γ signatures, coupled with dysregulation of the complement cascade, B-cell activation and neutrophil degranulation. Unsupervised analysis of SLE transcriptome identified 21 gene modules, with SLE-APS strongly linked to upregulation of the 'neutrophilic/myeloid' module. Within SLE-APS, venous thromboses positively correlated with 'neutrophilic/myeloid' and 'B cell' modules, while arterial thromboses were associated with dysregulation of 'DNA damage response (DDR)' and 'metabolism' modules. Anticardiolipin and anti-ß2GPI positivity-irrespective of APS status-were associated with the 'neutrophilic/myeloid' and 'protein-binding' module, respectively. CONCLUSIONS: There is a hierarchical upregulation and-likely-dependence on IFN in SLE with the highest IFN signature observed in SLE-aPL-negative patients. Venous thrombotic events are associated with neutrophils and B cells while arterial events with DDR and impaired metabolism. This may account for their differential requirements for anticoagulation and provide rationale for the potential use of mTOR inhibitors such as sirolimus and the direct fIIa inhibitor dabigatran in SLE-APS.

Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS).

OBJECTIVES: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). METHODS: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. RESULTS: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. CONCLUSION: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.

Current status of testing intervals for antiphospholipid syndrome testing: a 13-year retrospective national data analysis in South Korea.

OBJECTIVE: To assess the appropriateness of laboratory testing intervals and antiphospholipid syndrome (APS) incidence. METHODS: Between January 2010 and August 2022, insurance claims data of patients with disease codes for other thrombophilia (D68.6) and APS (V253) were retrieved in South Korea. Patients who received antiphospholipid antibody tests more than twice were classified as having suspected APS. The interval between the first 2 antiphospholipid antibody tests was evaluated in the patients with suspected APS. Patients with suspected APS who received anticoagulants for >180 days were classified as having APS. RESULTS: Overall, 8656 patients were classified as having suspected APS. The testing interval for the first 2 tests in patients with suspected APS was <6 and <12 weeks in 11.1% and 20.6% of cases, respectively, in 2010, gradually increasing to 21.0% and 35.4%, respectively, in 2021. Subsequently, 4344 patients were classified as having APS, with 65.0% being female. Only 330 patients were diagnosed with APS in 2021, down from 436 in 2020. CONCLUSION: This study showed a gradual increase in patients receiving antiphospholipid antibody testing with an inappropriate short-term interval, underscoring the need for laboratory stewardship to ensure an appropriate interval for APS testing.

Patients with antiphospholipid syndrome and a first venous or arterial thrombotic event: clinical characteristics, antibody profiles and estimate of the risk of recurrence.

OBJECTIVES: Thrombosis in antiphospholipid syndrome (APS) involves in most cases the venous circulation. Why in some patients thrombotic APS affects the arterial circulation and in particular cerebral circulation is unknown. In previous studies, both patient characteristics and antiphospholipid antibody types and titers have been associated with arterial thrombosis. Aim of this study was to compare the clinical characteristics and laboratory findings of venous and arterial thrombotic APS from a large series of patients. METHODS: Data were retrieved from the Start 2 antiphospholipid, a multicenter prospective register of long-term collected data from Thrombosis Centers in Italy. RESULTS: Of 167 patients with thrombotic APS, 114 (68 %) had a venous and 53 (32 %) had an arterial event as first clinical manifestation. Several clinical characteristics and risk factors were different among groups in univariate analysis. Using logistic regression analysis, reduced creatinine clearance and hyperlipidemia were independent variable for the occurrence of arterial APS. Notably, no difference in antiphospholipid antibody profiles and aß2-Glycoprotein I levels were found between groups. A higher adjusted global antiphospholipid syndrome score (aGAPSS) was found in arterial group indicating a possible high recurrence rate in arterial APS. CONCLUSIONS: These data have pathophysiological and clinical implication since associated conditions might predispose patients to arterial rather than venous events and call to a close monitoring and treatment of arterial APS due to their increased tendency to recurrence.

Laboratory assessment of antiphospholipid syndrome: Laboratory data.

INTRODUCTION: Thorough assessment of the antiphospholipid syndrome (APS) includes retesting of positive antiphospholipid antibody (aPL) tests after at least 12 weeks, and a full antiphospholipid antibody profile. To what extent this work-up is done in clinical practice is unknown. METHODS: Data on 25 116 in- and out-hospital patients tested for the presence of lupus anticoagulant (LA), the aPL which most strongly correlates with thrombosis, was extracted from the laboratory information system of the only laboratory that performs LA tests in the Capital Region, Denmark. We estimated fraction of repeated tests, tests repeated within the recommended time span, and fraction with a full aPL profile. RESULTS: Out of 25 116 patients, 843 were positive for LA (3.3%), and 3948 results were inconclusive (16%). Only 51% (95% CI of the proportion: 48%-54%) (n = 431) of positive tests were repeated. The proportion of inconclusive LA test results increased from 13% (12%-15%) in 2009 to 20% (19%-22%) in 2020. Out of the positive tests repeated within the first year, only 60/353 (17%; 13%-21%) were repeated within 12-16 weeks; 177/353 (50%; 45%-55%) were re-tested within the first 12 weeks of first positive test result. The proportion of patients with a full antiphospholipid antibody profile increased from 161/1978 (8%) in 2010 to 1041/1978 (43%) in 2020. CONCLUSION: We found several issues with the laboratory workup of APS. This indicates a need for increased awareness of comprehensive laboratory assessment of possible APS as well as a closer collaboration between the laboratory and clinicians.

Results and prognosis of kidney transplantation in lupus nephritis: Experience of an Argentine center.

INTRODUCTION: Although RT has improved the survival of the population with ESRD due to all causes, renal outcomes in SLE are controversial. The objective of this study is to describe the characteristics and evolution of the patients and the kidney transplant in LN, and compare it with patients transplanted for other causes. MATERIALS AND METHODS: Retrospective, observational, analytical, single-center study in which records of patients undergoing nephrotransplantation for LN were analyzed. They were compared with a group of patients transplanted at the same center for other causes of ESRD. RESULTS: 41 patients with kidney transplant due to SLE and 89 transplanted due to other causes of ESRD were registered. Graft loss occurred in 12 (29.26%) patients with LN and 34 (38.2%) patients in the comparison group (p = .428). Only one case (4.8%) presented reactivation of the LN in the graft, without graft loss. Median graft survival was 73.1 months in the LN group and 66.3 months in the comparison group (p = .221). A total of 8 (19.5%) patients with LN and 11 (12.4%) without LN died (p = .42), with infections being the main cause in both groups. There were no statistically significant differences between groups in graft and patient survival. In a sub-analysis of 28 patients with LN with aPL study, 4 thrombotic events were observed, in 3 different patients, in the aPL-positive group. There were no statistically significant differences in terms of causes of graft loss and graft survival (positive aFL 75.7 months vs negative aFL 72.7 months, p= .96). There were also no differences in mortality between the groups (p = .61). CONCLUSION: Patients transplanted for LN did not differ from the control population in terms of graft and patient survival. Infections were the main cause of death, so prophylaxis and vaccination continue to be a fundamental pillar in the prevention of infections in immunocompromised patients.

Primary antiphospholipid syndrome in a male presents with acute digital ischemia: Dramatic response to glucocorticoid.

We present a rare case of primary antiphospholipid syndrome in a 38-year-old male who presented with painful digital ischemia. Early initiation of anticoagulation and addition of glucocorticoid led to a significant improvement in the patient.

Ischemic Stroke as an Initial Manifestation of Antiphospholipid Syndrome in an Adolescent: A Case Report.

Cerebrovascular diseases in pediatric patients are relatively rare. Ischemic stroke in adolescents is associated with a poor prognosis. The most common causes include systemic diseases, such as heart disease and hypercoagulation disorders. It is important to mention that one of the most common acquired hypercoagulation states is the antiphospholipid syndrome (APS). Patients with this disease may present stroke as the first clinical manifestation, which not only increases morbidity in these patients but presents a diagnostic challenge. This case presents one example of how APS can present as a pediatric stroke. The diagnostic approach should always be through the presence of specific antibodies accompanied by the presence of a thromboembolic episode proven by catheterization or an imaging study. In the brain, the preferred imaging study is magnetic resonance imaging. Management is based on anticoagulation therapy and continuous monitoring in the intensive care unit.

Septal atrial thrombosis as a primary presentation of antiphospholipid syndrome in a patient with ANA-negative systemic lupus erythematosus: a case report.

Introduction and importance: Systemic lupus erythematosus (SLE) predominantly affects young women and is associated with an increased risk of thrombosis. Antiphospholipid antibody syndrome (APS) may complicate the clinical picture, often leading to recurrent arteriovenous thrombosis. This case report underscores the significance of two unique aspects: the rare occurrence of an atrial thrombus and the presence of antinuclear antibody (ANA)-negative SLE. Case presentation: A 32-year-old woman presented with a history of symmetric polyarticular joint pain, oral ulcers, significant weight loss, and a history of unprovoked popliteal thrombosis and two unexplained abortions. One week prior to admission, she experienced severe headaches and elevated blood pressure. Clinical evaluation revealed several abnormalities, including a systolic murmur, livedo reticularis, and a transthoracic echocardiogram showing severe mitral regurgitation and an atrial thrombus. A transesophageal echocardiogram confirmed the presence of a pedunculated lesion in the right atria, challenging differential diagnosis. Clinical discussion: ANA-negative SLE, though rare, was observed in this patient, highlighting diagnostic complexities. APS compounded the clinical presentation, emphasizing the importance of identifying specific autoantibodies and recurrent thrombotic events. In the case of atrial thrombus, differentiation from other cardiac conditions, such as myxoma or vegetation, is a key. Conclusions: This case underscores the critical importance of recognizing and managing atrial thrombus, a rare but life-threatening complication in patients with systemic lupus erythematosus and antiphospholipid syndrome. Additionally, the diagnostic challenge of ANA-negative SLE warrants careful consideration in patients presenting with characteristic features of the disease.

T cell involvement in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis, and obstetric complications in the presence of antiphospholipid antibodies (aPL), including lupus anticoagulant, anticardiolipin and anti-ß2-glycoprotein I antibodies, manifesting as single, or often as recurrent events, and rarely as a catastrophic condition. Most studies of APS pathogenesis to date have focused on the prothrombotic role of aPL, while innate immune components such as monocyte, complement and neutrophil activation have been recently recognized as part of the thrombo-inflammatory cascade in APS. While the presence of autoreactive T cells against ß2-glycoprotein I has been long known, limited data are available on their role in APS. In this review, we summarize current knowledge on the involvement of T cells in APS pathophysiology, alterations of T cell subsets in peripheral blood, and clinical associations. We also highlight potential therapeutic opportunities by targeting T helper-B cell interactions in these patients.

Antiphospholipid syndrome in the era of COVID-19 - Two sides of a coin.

In addition to the respiratory symptoms associated with COVID-19, the disease has consistently been linked to many autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome (APS). APS in particular was of paramount significance due to its devastating clinical sequela. In fact, the hypercoagulable state seen in patients with acute COVID-19 and the critical role of anticoagulant treatment in affected individuals shed light on the possible relatedness between APS and COVID-19. Moreover, the role of autoimmunity in the assumed association is not less important especially with the accumulated data available regarding the autoimmunity-triggering effect of SARS-CoV-2 infection. This is furtherly strengthened at the time patients with COVID-19 manifested antiphospholipid antibodies of different types following infection. Additionally, the severe form of the APS spectrum, catastrophic APS (CAPS), was shown to have overlapping characteristics with severe COVID-19 such as cytokine storm and multi-organ failure. Interestingly, COVID vaccine-induced autoimmune phenomena described in the medical literature have pointed to an association with APS. Whether the antiphospholipid antibodies were present or de novo, COVID vaccine-induced vascular thrombosis in certain individuals necessitates further investigations regarding the possible mechanisms involved. In our current paper, we aimed to focus on the associations mentioned, their implications, importance, and consequences.

Low recurrent thrombosis rates in single positive antiphospholipid syndrome regardless of type of anticoagulation.

Thrombotic antiphospholipid syndrome (TAPS) is characterized by thrombosis and persistently positive tests for antiphospholipid antibodies or lupus anticoagulant (LAC). Triple-positive APS has the highest risk of recurrent thrombosis, but no studies have focused on recurrent thrombosis in patients with single-positive TAPS. We conducted a retrospective cohort study of patients with single-positive TAPS diagnosed at Lifespan Health System, Rhode Island, to determine the rates and risk factors for recurrent thrombosis. Between January 2001 and April 2022, 128 patients were assessed who had single-positive APS (LAC = 98, aCL = 21, aß2GPI = 9) and who had been followed for a total of 1453.8 patient-years (median follow-up 3.04 years). The initial antithrombotic regimen was warfarin in 44 %, a direct oral anticoagulant (DOAC) in 34 %, enoxaparin in 2 %, and no antithrombotic therapy or antiplatelet therapy only in 20 %. Recurrent thrombosis occurred in 16 (12.5 %) with a recurrent thrombosis rate of 3.08 per 100 patient-years. Systemic lupus erythematosus was the only variable significantly associated with recurrent thrombosis in a model adjusted for age, sex, body mass index, and type of positive APS test. All 16 patients with recurrent thrombosis were initially treated with warfarin, and, at the time of recurrent thrombosis, 13 patients remained on warfarin and three were off anticoagulation. In conclusion, the recurrent thrombosis rate in single-positive APS is low, and not all patients with a single-positive test may need indefinite anticoagulation with warfarin. Larger prospective studies are required to confirm this finding and establish optimal anticoagulation regimens for low-risk TAPS.

Isolated gastric varices associated with antiphospholipid syndrome and protein S deficiency: a case report and review of the literature.

The mortality rate of gastric varices bleeding can reach 20% within 6 weeks. Isolated gastric varices (IGVs) refer to gastric varices without esophageal varices and typically arise as a common complication of left portal hypertension. Although IGVs commonly form in the setting of splenic vein occlusion, the combination of antiphospholipid syndrome and protein S deficiency leading to splenic vein occlusion is rare. We herein present a case of a 28-year-old woman with intermittent epigastric pain and melena. She was diagnosed with antiphospholipid syndrome based on the triad of pregnancy morbidity, unexplained venous occlusion, and positive lupus anticoagulant. Laparoscopic splenectomy and pericardial devascularization were performed for the treatment of IGVs. During the 6-month postoperative follow-up, repeated endoscopy and contrast-enhanced computed tomography revealed disappearance of the IGVs. This is the first description of splenic vein occlusion associated with both antiphospholipid syndrome and protein S deficiency. We also provide a review of the etiology, clinical manifestations, diagnosis, and treatment methods of IGVs.

Noncriteria antiphospholipid antibodies in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant, anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aß2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several noncriteria aPL have been identified. Some noncriteria aPL are well studied, such as IgA aCL and aß2GPI, the antiphosphatidylserine-prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2-glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other noncriteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin-cardiolipin complex, anti-protein S/protein C. Measurement of some of these noncriteria aPL (aPS/PT, aDI) is useful in the laboratory work-out of APS in specific situations. We have to differentiate between patients who are positive for noncriteria aPL only, and patients who have both criteria and noncriteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on noncriteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified.

Large pericardial effusion in a woman in the second trimester of pregnancy: a case report.

Background: Pericardial effusion is common in pregnancy, with causes similar to the general population. Usually, it is found in the third trimester and disappears spontaneously after labour; however, there is a risk of progression to tamponade. Management is based on expert opinion, since few studies have been published. Case summary: A woman with enlargement of a known, chronic, presumably idiopathic pericardial effusion, in the 17th gestation week, presented with mild dyspnoea, without specific echocardiographic signs of cardiac tamponade. She received double antithrombotic treatment with aspirin 100 mg, started before conception, and a prophylactic dose of tinzaparin 4500 IU, started at the beginning of the pregnancy due to obstetrical antiphospholipid syndrome. A multidisciplinary team consisting of the treating obstetrician-gynaecologist, haematologist, cardiothoracic surgeon, and cardiologist discussed the management, taking into account the large size of the effusion and the significant increase during pregnancy, the possibility of further increase during the third trimester, the antiplatelet and antithrombotic treatment, which increased the haemorrhagic risk, and the difficulty and risk to intervene later in pregnancy. A surgical pericardial window was proposed to the patient and family and was performed uneventfully. Discussion: This case demonstrates the importance of a multidisciplinary team approach and shared decision-making in the management of these complex cardio-obstetric patients in order to achieve optimal therapeutic results.

Management of cerebrospinal fluid rhinorrhea as a rare complication of antiphospholipid syndrome.

Background: Antiphospholipid syndrome is a complex autoimmune condition associated with the formation of recurrent thrombosis in any vascular bed throughout the body. Jugular vein thrombosis is very rare with only a 0.9% occurrence and is not typically associated with cerebrospinal rhinorrhea as a result of raised intracranial pressure. Case Description: A 54-year-old patient presented with a 9-month history of cerebrospinal fluid (CSF) rhinorrhea and headache on a background of antiphospholipid syndrome. Investigations showed a superior vena cava (SVC) and right internal jugular vein (IJV) obstruction with moderately elevated intracranial venous pressures. Her magnetic resonance imaging (MRI) brain was consistent with a CSF leak. The patient underwent successful endovascular stenting of her obstructed SVC and right IJV followed by surgical repair of a herniating meningocele in the posterior left ethmoid air cells. Conclusion: CSF rhinorrhea is uncommon and never previously reported associated with SVC thrombosis induced by antiphospholipid syndrome. A combination of endovascular techniques and surgical repair is recommended for this challenging presentation.

Can complement activation be the missing link in antiphospholipid syndrome?

APS is an autoimmune disorder with life-threatening complications that, despite therapeutic advantages, remains associated with thrombotic recurrences and treatment failure. The role of complement activation in APS pathogenesis is increasingly recognised, specifically in obstetric APS. However, its exact role in thrombotic APS and on the severity of the disease is not yet fully elucidated. Further mechanistic studies are needed to delineate the role of complement activation in the various APS clinical manifestations with aim to identify novel markers of disease severity, together with clinical trials to evaluate the efficacy of complement inhibition in APS. This could ultimately improve risk stratification in APS, patient tailored targeted therapy with complement inhibition identified as an adjunctive treatment. This article reviews current findings and challenges about complement activation in APS, discusses the potential role of platelet mediated complement activation in this setting and provides an overview on clinical implications and current therapeutics.