Catastrophic Antiphospholipid Syndrome Research Articles

Management of Cardiovascular Complications in Antiphospholipid Syndrome: A Narrative Review with a Focus on Older Adults

Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-β2-glycoprotein I (β2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS.

Management of Anticoagulation and Antifibrinolytics in Catastrophic Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder that presents with hypercoagulability and results in a lab artifact of prolonged PTT. The most severe form is catastrophic antiphospholipid antibody syndrome (CAPS), which manifests as rapidly progressing thromboses in multiple organ systems leading to multi-organ ischemia. The mainstay management CAPS is anticoagulation and systemic corticosteroids. Antifibrinolytic agents have previously been thought to be relatively contraindicated in CAPS due to the pro-thrombotic nature of the disease; the complex coagulation profile of CAPS can make it difficult to assess the risks and benefits of antifibrinolytic therapy. Also, should a patient with CAPS require cardiopulmonary bypass (CPB) for surgery, it poses a unique challenge in providing appropriate anticoagulation in the setting of prolonged ACT. We present a case of a 32-year-old postpartum female with CAPS requiring heart transplant who safely received intraoperative antifibrinolytic therapy and was successfully anticoagulated during CPB after perioperative plasmapheresis.

Extensive Thrombosis in Catastrophic Antiphospholipid Syndrome in a Newly Diagnosed Systemic Lupus Erythematosus: A Case Report

Extensive Thrombosis in Catastrophic Antiphospholipid Syndrome in a Newly Diagnosed Systemic Lupus Erythematosus: A Case Report

E030 Osteonecrosis of the spine in antiphospholipid antibody syndrome

Abstract Background/Aims Osteonecrosis (ON) is a well-known complication of several rheumatic diseases, affecting the hip, knee, shoulder, or ankle. The involvement of spine and other sites with ON has been reported with catastrophic APS, although the nature of this association is not completely clear. In antiphospholipid syndrome, thrombosis of blood vessels is considered a possible mechanism, along with other risk factors, such as active disease, thrombocytopenia, glucocorticoid use and associated autoimmune diseases, making the pathophysiology multifactorial. We report a case of a 66-year-old male with APS who developed bone infarcts/osteonecrosis after withdrawal of anticoagulation for APS, which was necessitated by a bleeding complication and introduction of steroids for immune thrombocytopenia. Methods A 66-year-old male came to us with history of unprovoked deep vein thrombosis (DVT) for which he was on antiplatelet and anticoagulation for over 20 years. He was diagnosed to have high titre anti cardiolipin antibody (ACA)(186 U/ml) without other autoimmune conditions. He had an episode of bladder hematoma in August 2022, needing his anticoagulation to be suspended temporarily. He was also found to have profound thrombocytopenia with raised inflammatory markers. Considering it to be immune mediated he was started on high dose oral corticosteroids and was later maintained with azathioprine while the oral prednisolone dose was gradually brought down to 10 mg daily in about 3 months’ time. His thrombocytopenia improved progressively however he developed an unprovoked DVT in October 2022 and was restarted on anticoagulation. He continued to have low dose steroids for about 6 months. Meanwhile, he started having a new onset of low back pain in December 2022. An MRI of the whole spine showed multilevel osteonecrosis with haemorrhagic cavities in a few vertebral bodies. Results This case highlights three interesting points. The first is the atypical presentation of the osteonecrosis involving vertebral bodies. Osteonecrotic lesions in the spine of a patient with catastrophic primary antiphospholipid syndrome has been reported. Our case signifies that although vertebral bodies are an uncommon site for avascular necrosis in patients with APS, it is not rare. Secondly, the pathogenesis of ON is complex. Whether ACA are directly responsible for this condition or whether they are the bystanders remains controversial. ACA have shown to be an independent risk factor for developing ON in many studies. Thirdly, steroids are known to be an important risk factor in patients presenting with osteonecrosis. The vascular compromise could be attributed to a steroid induced hypercoagulative state, abnormal lipid metabolism, or fat embolism. Conclusion ON in APS is unusual and its underlying pathophysiology remains multifactorial. However, when complicated by the high ACA levels, active disease, difficult anticoagulation (bleeding tendencies), thrombocytopenia or prolonged use of steroids, it can lead to hypercoagulable state causing micro thrombosis and avascularisation. Disclosure M. Shah: None. K. Putchakayala: None.

Antiphospholipid Patients Admitted in the Intensive Care Unit: What Must The Rheumatologist Know?

Antiphospholipid syndrome (APS) is a rare systemic autoimmune disorder that can escalate into a 'thrombotic storm' called the catastrophic antiphospholipid syndrome (CAPS), frequently requiring ICU admission for multiple organ failure. This review aims to offer insight and recent evidence on critically-ill APS patients. The CAPS classification criteria define this condition as the involvement of at least three organs/systems/tissues within less than a week, caused by small vessel thrombosis, in patients with elevated antiphospholipid antibodies levels. These criteria do not encompass the full spectrum of critically-ill thrombotic APS patients and they need to be cautiously used for the bedside diagnosis of CAPS. Thrombocytopenia is the laboratory hallmark of CAPS, sometimes dropping below 20G/L, but a complete thrombotic microangiopathy pattern is infrequent. Anticoagulation is the pivotal treatment for APS and CAPS, associated with improved outcome. Triple therapy - the combination of anticoagulation, high-dose corticosteroids, and either plasma exchange or intravenous immunoglobulins - remains the standard treatment for CAPS patients. Eculizumab, an anti-C5 monoclonal antibody, may be useful in refractory patients. Despite significant progress, CAPS mortality rate remains high. Its diagnosis and management are complex, requiring a close multidisciplinary cross talk between APS specialists and intensivists.

Eculizumab administration for myasthenia gravis also stabilizes thrombogenicity of catastrophic antiphospholipid syndrome

AbstractBackgroundThe co‐occurrence of myasthenia gravis and primary antiphospholipid syndrome (APS) is rare. Notably, both the diseases share common complement‐mediated mechanisms.Case PresentationA 36‐year‐old woman, who was previously diagnosed with myasthenia gravis and APS, developed multiple embolisms, involving the brain, kidney and spleen, with severe anemia and platelet reduction. She was diagnosed as catastrophic APS, and intensive immunotherapies, including plasma exchange, high‐dose corticosteroid and rituximab, were introduced. After these therapies, symptoms of both APS and myasthenia gravis worsened, consistent with elevation of immunoglobulin G anti‐beta‐2‐glycoprotein‐I antibody and anti‐acetylcholine receptor antibody. We started eculizumab, which resulted in stabilizing the disease activity of both diseases without notable adverse events.ConclusionsEculizumab can be effective for controlling multiple complement‐mediated pathophysiology.

Therapeutic plasma exchange in catastrophic antiphospholipid syndrome: a rare case with concomitant systemic lupus erythematosus and infection.

Therapeutic plasma exchange in catastrophic antiphospholipid syndrome: a rare case with concomitant systemic lupus erythematosus and infection.

WCN24-1287 Features of obstetric catastrophic antiphospholipid syndrome

WCN24-1287 Features of obstetric catastrophic antiphospholipid syndrome

Cardiac involvement in the catastrophic antiphospholipid syndrome (CAPS): Lessons from the “CAPS registry”

ObjectiveTo analyze the demographic, clinical, and laboratory characteristics of catastrophic antiphospholipid syndrome (CAPS) patients with cardiac involvement, and to identify the factors associated with this cardiac involvement. Material and methodsBased on the analysis of the “CAPS Registry”, the demographic, clinical, and serological characteristics of patients with cardiac involvement were analyzed. Cardiac involvement was defined as heart failure, valvular disease, acute myocardial infarction, pericardial effusion, pulmonary arterial hypertension, systolic dysfunction, intracardiac thrombosis, and microvascular disease. Univariate and multivariate analysis was used for multiple comparisons. Results749 patients (293 [39 %] women and mean age 38.1 ± 16.2 years) accounting for 778 CAPS events were included, of them 404 (52 %) had cardiac involvement. The main cardiac manifestations were heart failure in 185/377 (55 %), valve disease in 116/377 (31 %), and acute myocardial infarction in 104/378 (28 %). Of 58 patients with autopsy/biopsy, 48 (83 %) had cardiac thrombotic microangiopathy, Stroke (29% vs. 21 %, p = 0.012), transient cerebral vascular accident (2% vs. 1 %, p = 0.005), pulmonary infarction (26% vs. 3 %, p = 0.017), renal infarction (46% vs. 35 %, p = 0.006), acute kidney injury (70% vs. 53 %, p < 0.001), and livedo reticularis (24% vs. 17 %, p = 0.016) were significantly more frequent during CAPS events with versus without heart involvement. Multivariate analysis identified acute kidney injury (OR 1.068, IC 95 % 1.8–4.8, p < 0.001) as the only clinical characteristics that were, independently, associated with cardiac involvement in CAPS events. Cardiac involvement was not related to higher mortality. ConclusionsCardiac involvement is frequent in CAPS, with association with kidney involvement, and it is not related to higher mortality. The presence of cardiac microthrombosis was demonstrated in most biopsies/autopsies performed.

Diagnosis and Management of Catastrophic Antiphospholipid Syndrome and the Potential Impact of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening condition characterized by the persistence of antiphospholipid antibodies and occurrence of multiple vascular occlusive events. CAPS currently remains a diagnostic challenge and requires urgent treatment. The diagnosis of CAPS is made difficult by classification criteria used as diagnostic criteria in clinical practice, knowledge derived from retrospective data and case reports, confounding clinical and biological features, and its rapid onset and mortality. The absence of prospective studies of CAPS limits the strength of evidence for guideline treatment protocols. This comprehensive review summarizes the current understanding of the disease, and discusses how the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria impact the definition and therapeutic management of CAPS, which is considered the most severe form of APS. The correct integration of 2023 ACR/EULAR APS classification criteria is poised to facilitate CAPS diagnosis, particularly in critical situations, offering a promising avenue for improved outcomes.

History of antiphospholipid syndrome

Here, we discuss hallmark historical events occurred while investigating antiphospholipid syndrome (APS) particularly describing how lupus anticoagulant was discovered and how scientists around the world came to define APS. The prospects for exploring APS at the present time by applying current APS criteria are considered. The contribution of Russian scientists to APS study and catastrophic APS is outlined.

Fulminant Recurrent Thrombosis in a Patient with Catastrophic Antiphospholipid Syndrome and Its Thirty-Day Outcome

Fulminant Recurrent Thrombosis in a Patient with Catastrophic Antiphospholipid Syndrome and Its Thirty-Day Outcome

Antiphospholipid syndrome pathogenesis in 2023: an update of new mechanisms or just a reconsideration of the old ones?

Antibodies against phospholipid (aPL)-binding proteins, in particular, beta 2 glycoprotein I (β2GPI), are diagnostic/classification and pathogenic antibodies in antiphospholipid syndrome (APS). β2GPI-aPL recognize their target on endothelium and trigger a pro-thrombotic phenotype which is amplified by circulating monocytes, platelets and neutrophils. Complement activation is required as supported by the lack of aPL-mediated effects in animal models when the complement cascade is blocked. The final result is a localized clot. A strong generalized inflammatory response is associated with catastrophic APS, the clinical variant characterized by systemic thrombotic microangiopathy. A two-hit hypothesis was suggested to explain why persistent aPL are associated with acute events only when a second hit allows antibody/complement binding by modulating β2GPI tissue presentation. β2GPI/β2GPI-aPL are also responsible for obstetric APS, being the molecule physiologically present in placental/decidual tissues. Additional mechanisms mediated by aPL with different characteristics have been reported, but their diagnostic/prognostic value is still a matter of research.

Case report: eltrombopag induced catastrophic anti-phospholipid syndrome in a patient with immune thrombocytopenic purpura

Case report: eltrombopag induced catastrophic anti-phospholipid syndrome in a patient with immune thrombocytopenic purpura

Connective tissue disease as a challenge in heart failure: Three case reports.

Connective tissue disease (CTD) is a heterogeneous group of chronic inflammatory autoimmune disorders derived from a systemically auto-immunological deregulation. CTD may affect cardiac structures through multiple pathophysiological mechanisms, and subclinical cardiac injury is common. Heart failure (HF) is one of the common complications in these patients. Patients with CTD suffer an increased risk of cardiovascular disease and may have chest pain and shortness of breath. HF is characterized by dyspnea or exertional limitation due to impaired ventricular filling and/or blood ejection. HF can be caused by other systemic diseases, not only by cardiovascular disorders but CTD. CTD may cause HF due to diffuse myocardial damage, heart valve damage, coronary ischemia, and so on. The patient with catastrophic antiphospholipid syndrome take prednisone and warfarin. The patient with anti-synthetase syndrome was treated with immunoglobulin, followed by long-term oral medicines of prednisone, methotrexate, and folic acid. The symptoms of chest pain and shortness of breath for patients with CTD improved. HF is one of the common complications in these patients with CTD, which has poor prognosis and severe aggravation. Once such patients experience chest pain, chest tightness, shortness of breath, etc, we should consider the possibility of HF. Early identification and correct treatment can delay the progression of HF, improve the prognosis, and enhance the quality of life for patients. Therefore, we should pay more attention to patients with CTD combined with HF.

A Case Report on the Successful Management of Catastrophic Antiphospholipid Syndrome: Multidisciplinary Approach

ABSTRACT Catastrophic antiphospholipid syndrome (CAPS) is a multi-organ systemic thrombotic condition precipitated due to various secondary conditions such as infection, surgery, and estrogen use. The subsequent formation of various autoantibodies and various organ involvement such as the brain, heart, and kidneys cause rapid progression of the disease. The acute features of thrombosis and the predominant involvement of kidneys and the brain make the differentiation of this condition with other thrombotic microangiopathies difficult. However, early suspicion of CAPS with prompt management is key to favorable prognosis in such patients. Multidisciplinary approach to diagnosis and medical management plays an important role in the successful outcome of CAPS patients. The three pillars of management are therapeutic plasma exchange (TPE), steroids, and anticoagulants. TPE plays a major role in eliminating incriminating antibodies, cytokines, tumor necrosis factor, and complement. We present a case of 34-year-old female with definite CAPS, managed successfully with the triple regimen comprising a total of seven TPE sessions, pulse therapy with steroids, and anticoagulants.

Kidney disease in antiphospholipid antibody syndrome

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication. APS nephropathy has heterogeneous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension and multi-organ failure caused by catastrophic antiphospholipid antibody syndrome. Anticoagulation and thromboprophylaxis are key to management. Immunosuppression has been used with some success but lacks randomized controlled trial validation for their use.

Systemic Embolism Following Mechanical Thrombectomy for Acute Ischemic Stroke: A Case of Suspected Catastrophic Antiphospholipid Syndrome

Systemic Embolism Following Mechanical Thrombectomy for Acute Ischemic Stroke: A Case of Suspected Catastrophic Antiphospholipid Syndrome

Myocardial infarction as debut of catastrophic antiphospholipid syndrome in an adolescent

Myocardial infarction as debut of catastrophic antiphospholipid syndrome in an adolescent

Surviving Multiple Cardiac Arrests Secondary to Catastrophic Sero-Negative Antiphospholipid Syndrome: A Case Report

Antiphospholipid syndrome (APS) is an autoimmune disorder which predisposes to venous and arterial thrombosis due to the autoantibodies targeting phospholipids in cell membranes contributing to a pro-thrombotic state. The appropriately named catastrophic anti-phospholipid syndrome (CAPS) is distinguished from classical APS by the rapid involvement of 3+ organs, evidence of areas of small vessel occlusions, and significantly elevated anti-phospholipid titers (Cervera, 2018). To further complicate the matter, there is a growing body of evidence of the existence of sero-negative APS (SNAPS) that are negative for the classical lupus anticoagulant, anticardiolipin antibody (aCL), and anti-beta2 glycoprotein-I but may be positive for non-criteria APS antibodies. Presented below is a patient with SNAPS who responded to the therapy for CAPS despite negative classical autoantibodies. A 34 year old man with a past medical history of chronic alcohol use presented to the ED with a two day history of worsening shortness of breath. The patient was found to have an spO2 of 45-50% on room air and was quickly transitioned to a non-rebreather and subsequently BIPAP. Initial CBC was significant for WBC 22.1, Hg 19.3, Hct 58.5, MCV 100.8, and platelets of 166 consistent with neutrophilic leukocytosis and macrocytic polycythemia. D-dimer &amp;gt;20 was suggestive recent/on-going coagulation and/or fibrinolysis. Due to worsening respiratory failure, he was intubated and admitted to the ICU. While on 3 vasopressors he became bradycardic and a code blue was called for pulseless electrical activity (PEA). After 3 rounds of CPR he achieved return of spontaneous circulation (ROSC) and was taken for urgent CT imaging. After arriving in the radiology department he went into cardiac arrest for two rounds of CPR before achieving ROSC and being scanned and returning to the ICU. Polycythemia tests were drawn which revealed elevated erythropoietin of 52.1 (2.6-18.5) and ultimately negative JAK2. Chest CTA was significant for a PE with a heavy clot burden involving the entire right lung and the left upper and lower lobes. CT C/A/P showed findings of bilateral lower lobe pneumonia, severe gastritis, pancolitis, proctitis, pancreatitis with a 4.6cm pseudocyst, and fatty liver with congestive enhancement. Tissue-type plasminogen activator (tPA) bolus and infusion was initiated based on the imaging findings with the third cardiac arrest occurring 7 minutes later early in the morning. Repeat CBC revealed an Hgb/Hct of 22.2 g/dL and 71.5%, respectively, with a significant drop in platelets down to 103 with occasional large platelets consistent with peripheral destruction of platelets was noted on peripheral blood smear (PBS). Therapeutic phlebotomy of 300mL was subsequently performed with two additional cardiac arrests within 2 hours of each other before vascular surgery was able to perform thrombectomies of the involved pulmonary arteries and initiate catheter-directed thrombolysis. Platelet count dropped while on heparin to 25,000 so a HIT panel was ordered and he was transitioned to argatroban. At this point hematology was consulted who was concerned for CAPS and ordered aPL (anti-phospholipid) tests along with an appropriate panel of labs to rule out alternative causes. Peripheral blood smear did not reveal fragmentation of RBC to suspect TTP. Tests for ACL IgG/IgM and anti-beta2GPI IgG/IgM antibodies, COVID, HIV, ADAMTS deficiency, hereditary thrombophilia, and ANA were negative. High-dose steroids and daily plasma exchanges via vascath was initiated and within 12 hours there was significant improvement. He was extubated and off pressors in 24 hours with improved platelets. Lupus anticoagulant test results were reported after discharge with dVVT mix and PTT LA mix both being prolonged, however, repeat lupus anticoagulant 3 months later was negative. Given the potentially catastrophic effects of a missed CAPS diagnosis, a high level of clinical suspicion is needed as plasma exchange can quickly alleviate an otherwise disastrous condition. Further research into non-criteria APS autoantibodies (IgA)may be able to help guide future SNAPS diagnoses.