Case report: Timing of eculizumab treatment in catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition of small-vessel thrombosis with acute multiple-organ involvement and visceral damage. In this report, we present a case of a patient with CAPS who is refractory to conventional therapy. For the first time in a patient with CAPS, marked C5b-9 formation was demonstrated on microvascular endothelial cells, suggesting the usefulness of therapeutic complement inhibition in this setting. Eculizumab, a C5-blocking monoclonal antibody, is remarkably effective in the treatment of different forms of thrombotic microangiopathy by controlling complement system hyperactivation. It halted the "thrombotic storm" and promptly achieved full recovery of thrombocytopenia. However, kidney function did not recover, possibly because eculizumab was administered too late. Conceivably, the timing of treatment is crucial to achieving disease remission before irreversible structural damage occurs in target organs, thereby preventing their complete functional recovery.

Persistently High Platelet Factor 4 Levels in an Adolescent with Recurrent Late Thrombotic Complications after SARS-CoV-2 mRNA Vaccination.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients with a thrombophilic predisposition. Herein, we present a 17-year-old female who had underlying antiphospholipid syndrome (APS) and developed deep vein thrombosis (DVT) 6 months after her second BNT162b2 vaccine dose. Although she had no family history of thrombosis, she had previously developed DVT at 6 years of age, with thrombus formation in the right common iliac vein and the inferior vena cava, along with concomitant left pulmonary infarction. The patient had received anticoagulant therapy for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine was hypothesized to exacerbate the patient's APS by activating coagulation. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

Therapeutic apheresis treatment in rheumatic diseases: Insights from a single-center experience.

INTRODUCTION: We aimed to evaluate the characteristics of the patients with a rheumatologic disease who underwent TPE. METHOD: A single-center, retrospective study was conducted between January 2016 and June 2023. RESULTS: Twenty patients with a median age of 51 years received a median of 6 TPE sessions. Concurrently, immunosuppressive therapy was administered to 18 (90%) of them. During the follow-up period, 9 patients (45%) died. Creatinine (p = 0.001), C-reactive protein (p = 0.001), sedimentation rate (p = 0.002), leukocyte (p = 0.003), thrombocyte (p = 0.003), and neutrophil (p = 0.003) counts was decreased after TPE. Similarly, in the ROC analysis of post TPE laboratory parameters, urea, creatinine, CRP, hemoglobin, platelets, and lymphocytes predicted mortality with areas under the curve values ranging from 0.747 to 0.869. In the Cox regression analysis for mortality, creatinine was predictive for mortality (p = 0.030), HR 1.59 (95% CI: 1.05-2.41). CONCLUSION: In rheumatologic conditions, TPE is beneficial to fill the gap until the effects of immunosuppressants become apparent.

Catastrophic Antiphospholipid Syndrome: A Life-Threatening Condition.

Antiphospholipid syndrome (APS) is characterized by thrombosis in any organ or tissue, accompanied by the presence of antiphospholipid antibodies. Although rare, APS can progress to catastrophic APS (CAPS), a life-threatening complication involving the development of multi-organ thromboses. The mortality rate is high. Treatment consists of triple therapy with anticoagulation, glucocorticoids, and therapeutic plasmapheresis or intravenous immunoglobulins. We present a case of a patient with CAPS, requiring a multidisciplinary team approach to help diagnose and treat this complex disease.

Systemic Lupus Erythematosus Causing Rapid Progression of Mitral Valve Disease.

A 33-year-old woman with systemic lupus erythematosus presented with rapid progression of mitral valve disease within a 5-year period, highlighting concerns regarding routine surveillance guidelines for mild to moderate valvular disease.

Placental Pathologic Features and Perinatal Outcomes in Pregnant Woman With Autoimmune Connective Tissue Disease.

INTRODUCTION: We aimed to investigate the association between perinatal outcomes and placental pathological features in pregnant women with ACTD, including systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS), and undifferentiated connective tissue disease (UCTD). MATERIALS AND METHODS: Placental tissue from SLE (n = 44), APS (n = 45), and UCTD (n = 45) were included, and contemporaneous deliveries of placenta were served as a control group (n = 46) between September 2015 and March 2021. The placental histopathology was evaluated using the Manual of Human Placental Pathology and classified according to the Amsterdam consensus framework. RESULTS: SLE pregnant women have a higher rate of cesarean section (61.40%), premature birth (24.56%), and SGA (26.32%) when compared to control group (p = 0.008, p = 0.005, and p = 0.000, respectively). The rate of vascular malperfusion, inflammatory-immune lesions, and other placental lesions in the SLE group was 47.73%, 56.82%, and 63.64%, which were higher than the control group (p = 0.000, p = 0.000, and p = 0.006, respectively). In the meantime, the incidence of inflammatory-immune lesions in the APS group (42.22%, p = 0.004) and vascular malperfusion in the UCTD group (37.78%, p = 0.007) were increased when compared to the control group. CONCLUSIONS: SLE appeared to confer increased risk for a wide range of adverse perinatal outcomes. We determined elevated placental histopathology risk for most women with ACTD, including vascular maldevelopment, vascular malperfusion, and inflammatory-immune lesions.

Severe Hypertrophic Cardiomyopathy Associated With Hydroxychloroquine in a Young Woman With Systemic Lupus Erythematosus: A Case Report and Review of the Literature.

The use of the antimalarial drug hydroxychloroquine is a standard treatment in patients with systemic lupus erythematosus. It helps reduce disease-associated damage, prevents disease flare, and improves overall survival. The mechanism of action of hydroxychloroquine includes interference with lysosomal degradation of cells leading to the accumulation of vacuoles. Retinopathy is a well-described adverse effect of hydroxychloroquine, thus requiring screening with an ophthalmologist after prolonged use. Although rarely reported, cardiac adverse effects of hydroxychloroquine can also occur. In this report, we present a case of a 23-year-old woman with systemic lupus erythematosus on hydroxychloroquine who presented with stroke possibly due to Libman-Sacks endocarditis and was found to have severe hypertrophic cardiomyopathy on transthoracic echocardiogram.

Clinical and Laboratory Diagnosis of Antiphospholipid Syndrome: A Review.

The antiphospholipid syndrome (APS) manifests through venous or arterial thrombosis, with or without pregnancy complication alongside the continuous presence of antiphospholipid antibodies (aPL). APS classification relies on three aPL subtypes: anticardiolipin (aCL), anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulants (LA) antibodies. Given that thrombosis and pregnancy issues are not unique to APS, the precise and reliable identification of aPL forms the basis for diagnosis. Semi-quantitative solid-phase assays identify two antibodies, aCL and anti-ß2GPI, while LA detection occurs through various phospholipid-dependent coagulation assays that are based on antibody behaviour. LA, specifically, is conclusively associated with thrombosis, prompting discussions around the serological criteria for APS. Despite advancements in LA detection, the standardisation of all aPL detection assays remains imperative. The combined presence of aCL and anti-ß2GPI with thrombosis inconsistently triggers concern. Initial presentations by APS patients commonly exhibit a heightened risk of stroke, miscarriages in the later stages of pregnancy, positive results of LA tests, and widespread thrombosis across multiple organs, often leading to adverse outcomes. Correctly diagnosing this condition is pivotal to avoid unnecessary long-term secondary thromboprophylaxis.

Beta-2 Glycoprotein I IgA Isotype: An Important Consideration in Secondary Hypertension.

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.

Multifaceted Cerebral Venous Thrombosis With Extensive Intra-cerebral Hemorrhage in a Young Man With Mitral Valve Replacement Due to Thrombosis and IgA Nephropathy: A Challenging Case Report From Saudi Arabia.

Cerebral venous thrombosis (CVT) is a cerebrovascular condition characterized by cerebral venous sinus thrombosis, resulting in venous infarction. The condition can manifest through a range of signs and symptoms such as headaches, benign intracranial hypertension, subarachnoid hemorrhage, localized neurological deficits, seizures, unexplained changes in consciousness, and meningoencephalitis. Its causes are linked to numerous different conditions and factors. We report a complicated case and course of antiphospholipid antibody syndrome in a young patient. The case began two years prior, involving a 33-year-old man who had chronic kidney disease due to IgA nephropathy, pneumonia, and a large mass on his native mitral valve. He developed deep vein thrombosis (DVT) in his upper limb, for which he was prescribed warfarin. He was transferred to our hospital with a five-day history of severe headaches followed by a decrease in consciousness and seizures requiring intubation. He was found to have a subdural hematoma with a high international normalized ratio (INR). He underwent hematoma evacuation and a right decompressive craniotomy. CT of the brain via CT venography revealed intracerebral haemorrhage along with ischemic infarction in the right frontal-parietal and temporal lobes and cerebral venous thrombosis. He was treated with heparin infusion but later developed heparin-induced thrombocytopenia (HIT) and was switched to fondaparinux. Plasma exchange and intravenous methylprednisolone were given. His hospital course was complicated by recurrent infections, a new left intraparenchymal hemorrhage with intraventricular extension, and the need for extra ventricular drainage (EVD). The diagnosis of antiphospholipid antibody syndrome was confirmed. This case report provides invaluable insights into managing a complex scenario that requires balanced decisions between anticoagulation in the context of severe ICH and the necessity of immunosuppressive therapy. The emphasis is on the significance of using a personalized and multidisciplinary strategy to address CVT situations and their issues.

Triumph Over Adversity: A Comprehensive Case Series on Successful Pregnancy Outcomes in Antiphospholipid Antibody (APLA)-Positive Patients.

The intricate relationship between antiphospholipid antibody (APLA) syndrome and pregnancy outcomes challenges the prevailing notion of inevitable reproductive complications associated with APLA. The introduction provides a comprehensive overview of APLA, its autoimmune thrombophilic nature, and its common association with adverse pregnancy outcomes, emphasizing the need for a nuanced understanding. Here we discuss five case reports to showcase diverse scenarios, each highlighting successful pregnancies in APLA-positive patients, thereby contributing valuable insights into the management of this complex condition. The cases span various clinical presentations, patient demographics, and therapeutic approaches, emphasizing the heterogeneity of APLA-positive pregnancies and the importance of personalized care. The discussion delves into the broader context of APLA's impact on pregnancy, emphasizing recurrent miscarriage and venous thromboembolism (VTE) as severe complications. It underscores the significance of pre-conceptional counseling, a multidisciplinary approach, and regular antenatal monitoring in managing APLA-positive pregnancies. The identification of commonalities among the cases provides a basis for recognizing mitigating factors that contribute to positive outcomes, offering valuable guidance for healthcare providers. The series acknowledges the existence of catastrophic antiphospholipid syndrome (CAPS) and underscores the importance of early recognition and intervention in high-risk cases. Despite the challenges posed by APLA, the cases in the series offer a ray of hope by showcasing instances of successful pregnancies, attributing positive outcomes to optimized therapeutic interventions and vigilant antenatal care. In conclusion, the case series serves as a valuable resource for healthcare professionals, researchers, and policymakers, providing a nuanced perspective on APLA-positive pregnancies. By synthesizing diverse experiences and outcomes, the series contributes to the ongoing dialogue surrounding optimal management strategies, ultimately aiming to improve the quality of care for individuals facing the unique challenges posed by APLA during their reproductive journey.

Granulocyte colony-stimulating factor-producing lung cancer complicated with antiphospholipid antibody syndrome: a case report.

No reports on granulocyte colony-stimulating factor-producing lung cancer associated with antiphospholipid antibody syndrome. A 73-year-old man was referred to our department to undergo surgery for lung cancer in the right upper lobe. His examination results suggested that his condition was caused by an elevated white blood cell count and an increased inflammatory response due to granulocyte colony-stimulating factor production. The presence of antiphospholipid antibody syndrome was suspected, and the decrease in coagulation factors was considered to be inhibited by the lupus anticoagulant. Perioperatively, the patient was treated with heparin and steroids, and a thoracoscopically assisted right upper lobectomy was performed. Postoperatively, histopathological examination revealed pleomorphic carcinoma, and the patient tested negative for anticardiolipin IgG antibodies. In lung cancer patients with elevated white blood cell counts, fever, and an inflammatory response, granulocyte colony-stimulating factor-producing lung cancer is an important differential diagnosis. Additionally, when coagulation abnormalities are observed preoperatively, a thorough examination is necessary to prepare for perioperative management.

How We Interpret Thrombosis with Thrombocytopenia Syndrome?

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.

Antiphospholipid antibody syndrome complicating infective endocarditis - case report.

A 37-year-old lady with infective endocarditis of the mitral valve presented in congestive cardiac failure. However, the clinical scenario became complicated when she was also found to have antiphospholipid antibody syndrome. Meticulous optimization and timely surgical intervention by a multidisciplinary team helped mitigate this not so common situation and lead to successful outcome.

Splenic Marginal Zone Lymphoma in a Patient With Antiphospholipid Syndrome Treated With Rituximab: A Case Report.

Splenic marginal zone lymphoma (SMZL) usually presents with splenomegaly or symptoms related to cytopenia. We report a case of a 56-year-old female with previously diagnosed antiphospholipid syndrome (APS) on warfarin therapy who initially presented with abdominal pain and was found to have massive splenomegaly and splenic infarction on CT imaging. Initial clinical presentations and imaging findings were attributed to the subtherapeutic coagulation profile. The patient was later diagnosed with SMZL following workup for pancytopenia including bone marrow biopsy, flow cytometry, and PET scan. Cytopenias, splenomegaly, and abnormal metabolic activity in the spleen on the PET scan improved after treatment with four cycles of weekly rituximab. Our report presents a case of a patient with longstanding APS presenting with splenic infarction and pancytopenia who was subsequently diagnosed with SMZL and successfully treated with rituximab.

Prolongated Activated Partial Thromboplastin Time (aPTT) in Pediatric Patients before Surgery-Crying Wolf: Lupus (Anticoagulant) Does Not Always Threaten Children.

A prolonged preoperatory aPTT in children is often the cause of a delay of scheduled surgeries and the repetition of multiple blood tests, with the consequent wasting of resources and significant discomfort for children and parents. The aim of this review is to analyze the situations in which an isolated prolongation of aPTT is found during preoperative evaluation in children, especially when it is due to the presence of antiphospholipid antibodies, providing the readers with the keys to interpret this situation and the possibility to correctly evaluate the hemorrhagic risk of a patient.

A Rare Case of Postpartum Paraplegia: A Case Report.

In this case report, a 27-year-old woman who had pre-eclampsia in the past and had a cesarean section as a result of the condition presents with an uncommon and difficult form of postpartum paraplegia. She experienced bilateral lower limb paralysis and urine incontinence soon after the surgery, which quickly led to unconsciousness and required mechanical ventilator support and intensive care treatment. Comprehensive diagnostic testing, which included magnetic resonance imaging scans of the brain and spinal cord, identified signs typical of "Posterior Reversible Encephalopathy Syndrome (PRES)" and spinal cord infarction affecting segments C3 to D2. "Antiphospholipid Antibody Syndrome (APLA)" was identified by laboratory testing, highlighting the significance of taking a thorough approach to comprehending this uncommon clinical condition. Treatment included anticoagulant therapy, high-dose steroid therapy, and antihypertensive drugs, emphasizing the crucial importance of inter-disciplinary care in handling such complex situations. Even if the patient's symptoms have partially improved, their condition is still being closely monitored in the intensive care unit. In the context of postpartum neurological problems and the complex interplay between pre-eclampsia, spinal cord infarction, and related clinical symptoms, this case emphasizes the need for increased awareness and prompt management.

A Rare Association of Epstein-Barr Virus and Budd-Chiari Syndrome.

Budd-Chiari syndrome (BCS) is a rare hepatic venous outflow obstruction typically associated with hypercoagulable states. We present a unique case of a 29-year-old male with BCS triggered by a recent Epstein-Barr virus (EBV) infection. Workup unveiled antiphospholipid antibody syndrome as an underlying prothrombotic condition. Diagnostic challenges included inconclusive ultrasound findings, necessitating magnetic resonance imaging for confirmation. This case underscores the importance of considering infectious triggers for venous thromboembolism in BCS. Understanding the potential link between EBV and thrombosis warrants further investigation.