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.

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.

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.

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.

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.

Congenital Heart Block and Its Association With Anti-Ro and Anti-La Antibodies in Pregnancy: A Case Report of a Rare Entity and a Review of the Current Evidence.

Systemic lupus erythematosus (SLE) is a heterogeneous chronic, multisystem, inflammatory autoimmune disorder with variable clinical features, with its manifestations being attributed to the presence of multiple autoantibodies and their subsequent autoimmune reactions. Multiple organs may be involved, with the kidneys, the joints, and the skin being the most common, increasing maternal and fetal morbidity and mortality. Our current article describes the case of a 32-year-old primigravida who was referred to our department after the detection of fetal bradycardia and the strong suspicion of an underlying cardiac abnormality. After a detailed fetal and maternal assessment, the diagnosis of SLE-associated fetal congenital heart block was established, and the appropriate management and treatment were provided, factors that led to the uncomplicated delivery and prompt successful management of an otherwise severely affected fetus. Our work, also, includes a detailed review of the accumulated evidence regarding the association between autoantibodies and congenital heart block, the available screening modalities of the condition, and its potential therapeutic interventions.

Catastrophic Antiphospholipid Syndrome: A Complex Diagnosis in the Setting of Lupus.

This case report aims to highlight the importance of keeping catastrophic antiphospholipid syndrome (CAPS) high on the list of differentials in patients with lupus who present with digital ischemia and to understand the workup and treatment of the disease. Catastrophic antiphospholipid syndrome is a life-threatening variant of antiphospholipid syndrome (APS), and it is distinguished on the APS spectrum by its increased intensity and extent of thrombotic outcomes. Less than 1% of patients with APS develop CAPS and the demographic of patients affected are primarily females, 37 ± 14 years old, and have underlying primary APS or systemic lupus erythematosus (SLE). This is the case of a young female with lupus and end-stage renal disease secondary to lupus nephritis who presented to the emergency department for shortness of breath and bilateral leg swelling that eventually progressed to catastrophic antiphospholipid syndrome. She developed pulmonary embolisms, axillary hematoma, and bilateral lower extremity digital gangrene. The treatment course consisted of anticoagulation, steroids, intravenous immunoglobulin (IVIG), above-knee amputation, and eventually rituximab. Diagnosis and treatment of digital ischemia can be complex, especially, in the setting of lupus where the differential diagnosis is broad. A high index of suspicion for CAPS is essential for early diagnosis and treatment.

Right Hemisyndrome Secondary to Underlying Antiphospholipid Syndrome: A Case Report.

Antiphospholipid syndrome is an autoimmune disorder characterized by antiphospholipid antibodies, which can lead to both arterial and venous thrombosis. Neurological manifestations of antiphospholipid syndrome are diverse and can include stroke, seizures, and transient ischemic attacks. We present the case of an elderly patient with right hemisyndrome secondary to underlying antiphospholipid syndrome. This report aims to highlight the importance of recognizing antiphospholipid syndrome as a potential cause of neurologic deficits, precisely right hemisyndrome, and to emphasize the need for early diagnosis and appropriate management.

A Probable Catastrophic Antiphospholipid Antibody Syndrome/Thrombotic Storm Presenting As Rapidly Evolving Multifocal Ischemic and Hemorrhagic Strokes: A Case Report.

Catastrophic antiphospholipid antibody syndrome (CAPS) is a life-threatening disorder. It is a rare and severe form of antiphospholipid antibody (APL) syndrome characterized by widespread multisystemic thrombosis. We present a 55-year-old male patient with acute cerebellar hemorrhagic stroke who developed widespread progressive microthrombosis and macrothrombosis manifesting as progressive bilateral ischemic strokes with lower extremities deep vein thrombosis (DVT) and acute renal failure within a week of presentation. The diagnosis and initiation of therapy were established after serological confirmation. This case adds to a limited number of cases of CAPS in literature and is interesting given the rarity of CAPS and thrombotic storm (TS) as well as the lack of inciting factor triggering CAPS/thrombotic syndrome. This case also helps to remind the clinicians of the importance to consider CAPS, even prior to serological confirmation, in those with rapidly progressive thrombotic events, as delayed diagnosis and therapy can yield poor clinical outcomes.

Autoimmune Diseases Affecting Hemostasis: A Narrative Review.

Hemostasis reflects a homeostatic mechanism that aims to balance out pro-coagulant and anti-coagulant forces to maintain blood flow within the circulation. Simplistically, a relative excess of procoagulant forces can lead to thrombosis, and a relative excess of anticoagulant forces can lead to bleeding. There are a wide variety of congenital disorders associated with bleeding or thrombosis. In addition, there exist a vast array of autoimmune diseases that can also lead to either bleeding or thrombosis. For example, autoantibodies generated against clotting factors can lead to bleeding, of which acquired hemophilia A is the most common. As another example, autoimmune-mediated antibodies against phospholipids can generate a prothrombotic milieu in a condition known as antiphospholipid (antibody) syndrome (APS). Moreover, there exist various autoimmunity promoting environments that can lead to a variety of antibodies that affect hemostasis. Coronavirus disease 2019 (COVID-19) represents perhaps the contemporary example of such a state, with potential development of a kaleidoscope of such antibodies that primarily drive thrombosis, but may also lead to bleeding on rarer occasions. We provide here a narrative review to discuss the interaction between various autoimmune diseases and hemostasis.

A Cryptogenic Stroke Associated With Infective Endocarditis and Antiphospholipid Antibody Syndrome: Case Report and Literature Review.

Introduction: Accurate definition of stroke etiology is crucial, as this will guide effective targets for treatment. Both antiphospholipid antibody syndrome (APS) and infective endocarditis (IE) can be independent risk factors for ischemic stroke in young adults. When an embolic stroke occurs with IE and APS simultaneously, the origin of the embolic source is difficult to identify. Case Report: A 19-year-old man was admitted to the hospital for the onset of stroke. A diagnosis of APS accompanied by IE was made after a series of examinations. We identified aortic valve vegetation as the embolic source. Although both APS and IE can induce valve vegetation, we considered IE to be the primary cause according to the infective clues. Despite treatment with ampicillin, the patient's fever persisted, and surgical aortic valve replacement was performed urgently. The patient recovered without recurrence of stroke during the 1-year follow-up. Conclusion: A considerable challenge for physicians is evaluating all the signs suggestive of embolic sources in acute stroke and identifying the primary etiology when there are multiple causes. Early diagnosis and surgical intervention for bicuspid aortic valve (BAV) vegetation complicated by acute stroke may yield favorable clinical results.

Neurological and Neuropsychiatric Manifestations of Antiphospholipid-Antibody Syndrome (APS).

Antiphospholipid antibody syndrome (APS) is an autoimmune disorder mediated by the presence of a group of autoantibodies, specifically the anticardiolipin antibody (aCL), the beta-2 glycoprotein I (ß2GPI), and the lupus anticoagulant (LA). Patients diagnosed with antiphospholipid antibody syndrome (APS) present with many symptoms, the most common being the consequence of thrombotic events that can be catastrophic and lead to mild to severe residual disabilities over a significant amount of time and can impair the quality of life. These events are often present in the younger population. Many times, these thrombotic events are heralded by a spectrum of psychiatric symptoms, which when worked up in the right direction may hint toward an oncoming thrombotic event and may potentially prevent those events by prompting primary prophylaxis treatment by the treating physician. In this review, we aim to comprehensively put forth the many neurological and neuropsychiatric manifestations of APS, their pathology, and management.

[Clinical Confusion Concerning Increased D-Dimer Value during Pregnancy].

Plasma D-dimer, a special cross-linked fibrin derivative, is produced when fibrin is degraded by plasminase. During pregnancy, D-dimer increases along with the increase of gestational age, and the reference value of plasma D-dimer (≤0.5 mg/L) traditionally used for the screening of venous thrombosis in the normal population is not applicable to the pregnant population. Due to the lack of uniform D-dimer detection methods or measurement units, there is currently no unified D-dimer reference values for pregnancy or puerperium. Each region or laboratory should establish its own pregnancy D-dimer reference value for different gestational weeks through blood coagulation function testing of large numbers of samples of different gestational periods. More and more studies have been conducted to investigate the association between D-dimer and venous thromboembolism (VTE) during pregnancy, gestational hypertensive disorders (GHD) and pregnancy outcome. We reviewed, herein, the generation and measurement of D-dimer, the reference values of D-dimer during normal pregnancy, and the association between D-dimer and some pathological pregnancies, intending to help clinicians develop a more thorough understanding of D-dimer during pregnancy.

Successful treatment of sirolimus in a Chinese patient with refractory LN and APS: a case report.

It has been reported that the mammalian target of rapamycin (mTOR) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE), and increasing evidence has shown the effect of mTOR-targeted therapies with sirolimus in SLE. The objective of this study was to report the successful treatment of sirolimus in a Chinese patient with refractory lupus nephritis (LN) and anti-phospholipid antibody syndrome (APS). A 44-year-old female with a previous diagnosis of autoimmune hemolytic anemia (AIHA) and APS secondary to SLE presented with lupus nephritis refractory to cyclophosphamide and mycophenolate. Renal biopsy met the criteria of WHO class III LN complicated by acute tubular injury and immunofluorescence confirmed the activation of the mTOR pathway. Treatment with the mTOR inhibitor sirolimus was initiated in this patient. Complete remission (CR) was achieved after 6 months, and flare-free remission was maintained for the next 3.5 years. The literature on the efficacy of sirolimus in patients with LN was reviewed. Although the available evidence is limited to retrospective studies with small sample sizes, sirolimus appeared to be efficacious in some patients with refractory LN. Well-designed clinical trials are warranted, and pathology-guided precision medicine might assist in guiding physicians' treatment decisions.

Anti-beta 2 glycoprotein 1 domain IgA positive antiphospholipid syndrome secondary to incomplete Behcet's disease: a case report.

Antiphospholipid syndrome (APS) is an autoimmune systemic disorder characterized by arterial, venous, or small vessel thrombosis, and/or recurrent early pregnancy loss, fetal loss, or pregnancy morbidity. APS is induced by persistent positive antiphospholipid antibodies (aPL), the main being lupus anticoagulant (LA), and/or anticardiolipin (aCL) antibodies, and/or anti-beta 2 glycoprotein 1 (ß2-GP1) antibodies. Some studies have shown that the incidence of APS is about 5 new cases per 100,000 persons per year, and the prevalence is around 40-50 cases per 100,000 persons. APS can be primary or secondary. Secondary APS often coexists with another autoimmune disorder, most commonly systemic lupus erythematosus (SLE). Behcet's disease (BD) is usually characterized by recurrent oral and genital aphthous ulcers and ocular involvement. It can occasionally affect the venous system. BD usually affects small vessels, but can sometimes affect large veins or even a variety of veins. Because most of APS is secondary to SLE, APS secondary to incomplete BD is quite rare. This report describes a case in which a 15-year-old male experienced bilateral leg swelling and pain. The patient had a long history of self-healing recurrent mouth ulcers. Laboratory tests revealed positive ß2-GP1 immunoglobulin A (IgA). His symptoms improved by using steroids, prednisolone, uro-kinase, and hirudin. In this rare case of secondary APS, the patient was diagnosed with anti-ß2-GP-1 IgA positive to incomplete BD. It is a rare case of secondary APS with positive anti-ß2-GP1 IgA to incomplete BD. It is suggested that patients with recurrent mouth ulcers should be closely examined to prevent thrombosis, and more laboratory markers should be used to avoid a risk of misdiagnosing patients with APS.

Brainstem infarction associated with HHV-6 infection in an infant.

INTRODUCTION: The relevant literature includes several case reports on cerebral infarction in children with HHV-6 infection; however, there is no report of brain stem infarction. CASE: An 11-month-old girl was hospitalized because of fever. She was unable to stand up and meet her mother's gaze. Magnetic resonance imaging (MRI) indicated a right pons and mid-brain lesion; a diagnosis of brainstem infarction was made. After her fever subsided, a rash developed on her trunk and limbs; blood examination results indicated a primary HHV-6 infection. She was treated with aspirin, edaravone, and mannitol to prevent further complications. At the age of 18months, the auditory brainstem response (ABR) was unremarkable and she is developing well. DISCUSSION AND CONCLUSION: A limited number of studies have reported HHV-6 infection-associated infarction, and no cases of brainstem infarction have been reported. One possible cause of cerebral infarction is antiphospholipid antibody syndrome (APS) triggered by the infection. HHV-6 may also directly infect vascular endothelial cells and cause angiopathy. However, the real mechanism of infarction remains unclear. Our patient had a favorable prognosis despite brainstem infarction.