History Of Antiphospholipid Syndrome Research Articles

Enfermedad microvascular coronaria en gestante con antecedente de síndrome antifosfolípidos

Objective: to report the case of a pregnant woman with antiphospholipid syndrome history, in whom coronary microvascular disease was documented. Antenatal medical treatment improved prognosis and maternal and perinatal outcomes. Case: multigravida woman, 29.6 weeks pregnant, diagnosed with acute coronary syndrome, referred from a first level hospital. Diagnostic workup revealed microvascular disease. After receiving adequate management, she was discharged from hospital and included in the high-risk pregnancy program. Results: the diagnosis was made based on echocardiography, electrocardiography, troponin levels and cardiac catheterization. Anti-ischemic therapy was indicated considering the risk-benefit trade-off; management with aspirin was continued and the baby was born healthy. Conclusions: coronary microvascular disease should be considered, as a differential diagnosis in a pregnant woman with chest pain and history of antiphospholipid syndrome. Patients benefit from receiving antiplatelet and anticoagulant therapy soon after the diagnosis is made. Studies are required to evaluate the safest and most effective management of this condition.

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.

A phase 1 study of fianlimab (anti-LAG-3) in combination with cemiplimab (anti-PD-1) in patients with advanced ccRCC.

434 Background: Concurrent blockade of lymphocyte-activation gene 3 (LAG-3) may enhance efficacy of anti–programmed cell death protein 1 (PD-1) therapies. We present safety and clinical activity data from a Phase 1 study in patients with clear cell renal cell carcinoma (ccRCC) treated with anti–LAG-3 (fianlimab) + anti–PD-1 (cemiplimab). Methods: Patients with advanced or metastatic ccRCC who had received no more than 2 previous regimens of anti-angiogenic therapy who were anti–PD-1/PD-L1-naïve (cohort 3) or anti–PD-1/L1-experienced with most recent dose within 3 months prior to screening (cohort 4) were eligible. All patients were to receive fianlimab 1600 mg + cemiplimab 350 mg intravenously every 3 weeks for up to 24 months. Tumor measurements were performed by RECIST 1.1 every 6 weeks for 24 weeks, then every 9 weeks. Results: 15 patients (median age: 64 years) each in cohort 3 and 4 (total N=30) were enrolled and treated with fianlimab + cemiplimab as of 01 Nov 2022 data cutoff.For cohorts 3 and 4 respectively, 80% and 87% of patients were male, and 40% and 87% were White. All patients had prior cancer-related systemic therapy. 60% (9/15) and 93% (14/15) of patients in cohorts 3 and 4 had ≥2 lines of prior therapies, respectively. For cohorts 3 and 4, median treatment duration was 27 weeks and 18 weeks, and median follow-up was 13 months and 24 months, respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 53% and 33% of patients in cohorts 3 and 4, respectively. Serious TEAEs occurred in 33% and 13% of patients in cohorts 3 and 4, respectively. Treatment-related TEAEs (TRAEs) were reported in 80% of patients in cohorts 3 and 60% of patients in cohort 4. The most common TRAEs (any grade) were rash (27%) and infusion related reaction (grade 1 and 2) (27%) in cohort 3 and fatigue (20%) in cohort 4. Grade ≥3 TRAEs occurred in 27% of patients in cohorts 3. Treatment was discontinued due to any TEAE in 3 patients in cohort 3 and 1 patient in cohort 4. In cohort 3, there was one death. The patient was a 79-year-old woman with a history of antiphospholipid syndrome who died from complications of biopsy-proven ischemic colitis attributed to study treatment. RECIST 1.1-based investigator-assessed objective response rate (ORR) was 20% (3 partial responses [PRs]) in cohort 3 and 7% (1 PR) in cohort 4. The disease control rate (DCR) was 60% and 73% in cohorts 3 and 4, respectively. Kaplan–Meier estimation of median progression-free survival was 4 months (95% confidence interval [CI], 1–10) in cohort 3 and 4 months (95% CI, 1–7) in cohort 4 patients. Duration of responses were 4, 7, and 26 months in 3 responders in cohort 3; and 6 months in one responder in cohort 4. Conclusions: Fianlimab + cemiplimab demonstrated promising signs of clinical activity with durable responses among patients with anti–PD-1/PD-L1-naïve (cohort 3) and anti–PD-1/L1-experienced (cohort 4), with an acceptable safety profile. Clinical trial information: NCT03005782 .

The history of antiphospholipid syndrome.

Antiphospholipid Syndrome (APS) is an autoimmune disease which was defined in the early 1980s. The principal features include thromboembolic events and/or pregnancy losses in association with antiphospholipid antibodies (aPL). As an historical note, the full-blown picture of the syndrome resembles the illness suffered by Anne Stuart, Queen of England in the XVIII century, whose repeated miscarriages caused the end of the royal Stuart line and the Hanoverian succession. The identification of aPL started in the early XX century and was linked to the introduction of the serological test for the diagnosis of syphilis. This involves a reaction between an antibody (reagin) and a phospholipid antigen derived from bovine heart (cardiolipin). Later on, it was observed that not all subjects with a positive test had syphilis, and that the so called "false positive reaction" was often reported in patients with systemic lupus erythematosus. Different tests for the identification of aPL were subsequently developed: first lupus anticoagulant (1971) and then immunoassays for anticardiolipin (1983) and anti-beta2 glycoprotein I (1990) antibodies. In the same period the association between the presence of circulating aPL and thrombotic and obstetric events was established, both in patients with autoimmune diseases and in otherwise healthy subjects, leading to the identification of APS as a distinct autoimmune disease. This has allowed better diagnosis and more targeted treatment for many patients.

Double inferior vena cava with bilateral mild hydronephrosis: a rare case report

A 47-year-old female with a history of antiphospholipid syndrome and ischemic stroke was presented to the emergency department due to abdominal pain and bloody vomiting. Ultrasonography showed double inferior vena cava and bilateral mild hydronephrosis. Furthermore, the abdominal computed tomography (CT) scan did not show any evidence of urolithiasis. The ultrasound images of distinctive developmental variations of inferior vena cava and other veins are important to be known. Vascular anomalies, although rare, should be taken into account in the differential diagnosis of focal lesions within the abdominal cavity. Double IVC might have been the cause of hydronephrosis in our patient.

Bilateral central retinal artery occlusion: Endovenous and intra-arterial thrombolysis in a patient with a subsequent diagnosis of antiphospholipid antibody syndrome

Bilateral central retinal artery occlusion: Endovenous and intra-arterial thrombolysis in a patient with a subsequent diagnosis of antiphospholipid antibody syndrome

White Matter Hyperintensities as a Risk Factor for Ischemic Stroke in Patients With Systemic Lupus Erythematosus.

Objective: The occurrence of ischemic stroke in patients with systemic lupus erythematosus (SLE) can cause extended periods of reduced daily activities. However, the risk factors for ischemic stroke in SLE patients are not fully elucidated. Herein, we examined the effect of white matter hyperintensities (WMH) on the occurrence of ischemic stroke in SLE patients.Methods: We analyzed the relationship between WMH burden and ischemic stroke using follow-up brain magnetic resonance imaging (MRI) data of 79 patients with SLE. Of these patients, 16 developed stroke during the observation period. WMH on MRI were classified into periventricular hyperintensities and deep white matter hyperintensities (DWMH), while the lesion extent was graded using the Fazekas scale.Results: Kaplan–Meier curves showed that ischemic stroke events were significantly associated with age at initial brain MRI of ≥40 years (p = 0.015) and history of anti-phospholipid syndrome (p = 0.030). Additionally, ischemic stroke events were significantly associated with a one grade deterioration of periventricular hyperintensities (p = 0.003) and a one grade deterioration of DWMH (p = 0.002). Multivariate analysis using the logistic regression model showed that a one grade deterioration of DWMH was an independent risk factor for ischemic stroke (hazard ratio, 6.0; 95% confidence interval, 1.3–27.4).Conclusions: Although several factors affect the occurrence of ischemic stroke, SLE patients show increased risk of ischemic stroke via development of DWMH. An observation of DWMH deterioration on follow-up brain MRI may be useful for assessing the risk of ischemic stroke in SLE patients.

Regional Hypertonic Citrate Anticoagulation in Membrane Therapeutic Plasma Exchange: A Case Series.

Rationale:Protocols for regional citrate anticoagulation with the hypertonic 4% trisodium citrate solution have been recently described as an anticoagulation strategy during membrane therapeutic plasma exchange (mTPE). The effect of citrate in the patient’s systemic hemostasis is negligible, thus regional citrate anticoagulation application is advantageous in circumstances in which heparin-based protocols are deemed unsafe for patients with a high risk of bleeding. The downsides of using hypertonic citrate solutions are mainly hypocalcemia and hypernatremia that ultimately can cause adverse clinical events.Presenting concerns of the patient:(1) A 57-year-old Caucasian female with a history of active vaginal bleeding secondary to endometrial hyperplasia. She had a history of antiphospholipid syndrome, and systemic lupus erythematosus with marked refractory autoimmune thrombocytopenia. Her platelet count was persistently below 4,000/mm3 even after different immunosuppressive regimens and daily platelet transfusions. (1) A 70-year-old Caucasian female was hospitalized presenting acute kidney injury stage 3 due to rapidly progressive antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, however without the need for renal replacement therapy. At admission, serum creatinine (sCr) was 3.56 mg/dL (normal range: 0.53-1.00 mg/dL). Her baseline sCr was 0.8 mg/dL obtained 6 months earlier. Chest tomography revealed bilateral masses compatible with granulomatous lesions and no signs of alveolar bleeding. Since severe cases of ANCA vasculitis involving the lungs may evolve with alveolar hemorrhage, heparin was avoided.Diagnoses:(1) Systemic lupus erythematosus-associated autoimmune thrombocytopenia and (2) ANCA-associated vasculitis with kidney and lung involvement.Interventions:Herein, we describe a case series of 12 consecutive mTPE treatments in 2 different patients using regional 4% trisodium citrate anticoagulation.Outcomes:All the sessions were uneventful, presented only minor electrolyte imbalances, and were effectively completed without early interruptions due to clotting of the plasmafilter.Teaching points:In our 2 cases, extracorporeal regional citrate anticoagulation was successful in optimizing plasmafilter patency without bleeding events in 2 high-risk patients using established protocols for the citrate and calcium infusions.

Monitoring and Dosing of Argatroban in a Patient With Antiphospholipid Syndrome.

Background: This case reports outlines argatroban dosing and necessary dose adjustments in a 56 year-old male with a past medical history of antiphospholipid syndrome and heparin-induced thrombocytopenia. Method: Argatroban was initiated as a fixed dose of 0.5 µg/kg/min with all initial aPTTs above goal. Argatroban was held for a procedure and re-initiated at 0.25 µg/kg/min. The dose was increased or decreased by 25% from the current rate based on supratherapeutic and subtherapeutic aPTTs, respectively. Results: The patient remained on argatroban for 6 total days, while achieving goal aPTT levels with no VTE or bleeding events. Conclusion: Our patient represents the first reported case of monitoring argatroban with aPTTs in an individual with APS.

SUN-192 Spontaneous Adrenal Hemorrhage in a Patient with Antiphospholipid Syndrome on Rivaroxaban: A Potentially Fatal Complication

Introduction: Primary Adrenal insufficiency is an uncommon complication of antiphospholipid syndrome, with an incidence of 0.4% [2]. It is often secondary to bilateral adrenal hemorrhage. We present a case of bilateral adrenal hemorrhage in a patient with APLS on anticoagulation with rivaroxaban. Case: 46-year-old m with a history of antiphospholipid syndrome, recently transitioned from warfarin to rivaroxaban for anticoagulation, who presented to the ED after a syncopal episode following a prior episode of abdominal pain with an unremarkable work-up. He subsequently developed severe fatigue, dizziness, headaches, nausea and 15 lbs weight loss. On presentation, the patient was hypotensive(72/45 mmHg) and tachycardic. Intravenous hydration was started with minimal response. Initial laboratory testing showed serum sodium of 121mmol/L, potassium of 5.5mmol/L and random cortisol of 0.8mcg/dL. The patient was admitted to the intensive care unit where he was started on vasopressors and hydrocortisone 50 mg IV every 8 hours. A non-contrast CT of the abdomen and pelvis showed thickening of the adrenal glands with decreased attenuation. MRI of the abdomen showed hyper-intensity of the adrenal glands bilaterally (T1 images), without post-contrast enhancement suggestive of bilateral adrenal hemorrhage. His electrolytes normalized, and he was successfully discharged home on hydrocortisone and fludrocortisone replacement with outpatient follow-up. Discussion: Atraumatic bilateral adrenal hemorrhage is rare, but remains one of the most common endocrine-related complications of antiphospholipid syndrome (APLS). The venous anatomical configuration of the adrenal gland increases risk of thrombotic hemorrhagic infarction[1]. Patients with APLS are commonly anticoagulated to prevent thrombosis. The ideal anticoagulation regimen remains controversial. Only three other cases of spontaneous bilateral adrenal hemorrhage on patients with APLS using new oral anticoagulants (NOACs) were reported. The use of NOACs seem to increase the already-elevated risk of adrenal hemorrhage seen in patients with APLS.

A Multi-Center Quality Improvement Intervention to Reduce the Inappropriate Use of Aspirin Among Patients Anticoagulated with Warfarin for Atrial Fibrillation or Venous Thromboembolism

Introduction: For warfarin-treated patients with atrial fibrillation (AF) or venous thromboembolism (VTE), concomitant use of aspirin and warfarin increases the risk of major bleeding 1.5-1.8 fold without an apparent reduction in thrombotic events when there is no clear indication for combination therapy. As a result, each of six anticoagulation clinics in the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) consortium implemented a common intervention between late 2017 and mid 2018 aiming to reduce inappropriate aspirin use. The intervention consisted of a screening process to identify possible inappropriate aspirin use and then contacting the patient's provider to discuss the need for ongoing aspirin therapy. Site-level implementation variation included the personnel carrying out the intervention, the use of technology, and the means of provider communication. Treatment decisions were deferred to the treating provider but facilitated by the anticoagulation clinic staff. We sought to assess the impact of this intervention on the rate of inappropriate aspirin use over time and compare patient characteristics based on aspirin use post intervention. Methods: First, we compared the overall rate of inappropriate aspirin use among the six center MAQI2 anticoagulation clinic cohort immediately before and after the intervention. All patients in MAQI2 were treated with warfarin. Then, we identified a sub-cohort of warfarin-treated patients with AF and/or VTE enrolled between January 2010 to June 2019. Within that sub-cohort, we assessed aspirin use pre and post the site-specific date of implementation of the intervention. Patients with a potential indication for aspirin use were excluded (e.g., any history of coronary artery disease, myocardial infarction, percutaneous coronary intervention, mechanical heart valve replacement, left ventricular assist device placement, peripheral arterial disease, or coronary artery bypass grafting). Each site was able to further restrict who was targeted for intervention (for example, excluding patients with a history of antiphospholipid syndrome or stroke). Using site specific definitions for inappropriate aspirin use we identified four groups at the end of the study period: 1) patients not on aspirin, 2) aspirin-using patients without an apparent indication who stopped aspirin following implementation, 3) aspirin-using patients without an apparent indication who remained on aspirin following implementation, and 4) aspirin-using patients who developed an indication for aspirin during the study period. To assess inappropriate aspirin use in our cohort, the characteristics of the first three groups were compared. Results: Between August 2017 and May 2019, a total of 3,766 warfarin-treated patients enrolled in MAQI2. Following implementation, inappropriate aspirin use was reduced by 34% (from 27.9% [401/1437] to 18.5% [251/1356]). A sub-cohort of 1,007 patients who met the inclusion criteria had clinical follow-up pre and post intervention and were followed for an average of 40.1 months from enrollment to their first follow-up post-intervention. Of this sub-cohort, 226 (22.4%) were inappropriately on aspirin, with 50 (22.1%) stopping aspirin. A small number of patients 37 (3.7%) developed an indication for aspirin (e.g., myocardial infarction) during the study period and were removed from this analysis. As compared to patients not taking aspirin, patients on inappropriate aspirin were more often taking warfarin for AF, had congestive heart failure, chronic kidney disease, diabetes mellitus, hypertension, and had a higher Charlson Comorbidity index; they were less likely to have VTE or a history of VTE. As compared to patients continuing on aspirin following implementation, patients stopping inappropriate aspirin were more likely to have chronic kidney disease (p=0.02) or a history of falls (p=0.03). Conclusion: Among warfarin-treated patients with AF or VTE, inappropriate aspirin usage can be identified and significantly reduced using a simple intervention in the anticoagulation clinic. Patients at higher risk of bleeding may be more likely to have their aspirin discontinued. Further studies are needed to see if reducing inappropriate aspirin usage translates to improved clinical outcomes and to determine the reasons for patient persistence on inappropriate aspirin. Disclosures Kaatz: Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria; Portola: Honoraria. Kline-Rogers:AC Forum: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; QUANTUM-AF: Membership on an entity's Board of Directors or advisory committees. Sood:Bayer: Research Funding. Froehlich:Blue Cross Blue Shield of Michigan: Research Funding; Novartis: Honoraria; Boehringer-Ingelheim: Honoraria; Fibromuscular Dysplasia Society: Research Funding; Merck: Honoraria; Pfizer: Honoraria; Janssen: Honoraria. Barnes:Portola: Honoraria; Pfizer/Bristol Myers Squib: Research Funding; Pfizer: Honoraria; AMAG Pharmaceuticals: Honoraria; Bristol Myers Squib: Honoraria; Blue Cross Blue Shield of Michigan: Research Funding; Janssen: Honoraria.

P043: First trimester screening (FTS): is the requested information of the medical history of antiphospholipid syndrome (APS) reported properly? A preliminary report

P043: First trimester screening (FTS): is the requested information of the medical history of antiphospholipid syndrome (APS) reported properly? A preliminary report

Catastrophic antiphospholipid syndrome during pregnancy: a case report and literature review

Objective To summarize the diagnosis, management and prognosis of catastrophic antiphospholipid syndrome (CAPS) in pregnant and postpartum women through a case report and literature review. Methods The reported case was a gravida who had a history of antiphospholipid syndrome and was admitted to the Peking University First Hospital in July 2017 due to CAPS in the second trimester. She was fully recovered and discharged after effective management. Clinical data was collected and analyzed. Relevant literatures regarding the diagnosis, treatment and prognosis of pregnancy-related CAPS were reviewed. Results (1) Case report: The patient had taken warfarin after the diagnosis of antiphospholipid syndrome but stopped the medication six months before conception. She was admitted at 22 weeks of gestation due to severe upper abdominal pain accompanied by nausea and vomiting and diagnosed with CAPS based on severe low platelet count and remarkably elevated liver enzymes. After a series of treatment, including anticoagulation, glucocorticoid, plasma exchange and cesarean section, the patient became stable and was fully recovered. (2) Literature review: After searching all published literatures, 13 relevant literatures which including 35 patients were finally reviewed. It is found that CAPS was a rare and life-threatening condition with rapid progression and the mortality rate was 6/14 during gestation and 9% (2/21) after delivery. Anticoagulation, glucocorticoid, plasma exchange and immunoglobulin were the first-line treatment. Termination of pregnancy was required once CAPS was diagnosed. Conclusions CAPS is a rare but life-threatening disease. Early diagnosis and timely termination of pregnancy are crucial for gravidas with CAPS. Key words: Pregnancy complications; Antiphospholipid syndrome; Abortion, induced

Use of Intravenous Immunoglobulin Therapy at Unconventional Doses in Refractory Fulminant Systemic Lupus Erythematosus.

The use of human intravenous immunoglobulins (IVIg) in systemic lupus erythematosus (SLE) currently relies on evidence from small case series and is mainly regarded as an off-label strategy in cases that are refractory to conventional therapies or poorly controlled with high doses of corticosteroids. Standard dosage regimens typically entail the administration of a total amount of 2 g/kg of IVIg divided into five consecutive days in order to minimize the risk of severe adverse events. We herein describe the case of a 28-year-old woman with a known history of antiphospholipid syndrome (APS) who was admitted to our hospital following fulminant onset of SLE in spite of ongoing immunosuppressive therapy. Acute renal insufficiency with nephrotic-range proteinuria, central nervous system involvement, severe thrombocytopenia, malar rash, pancreatic injury and moderate-severe aortic valve steno-insufficiency were the most prominent clinical manifestations, along with high titres of anti-dsDNA antibodies. Pulses of methyl-prednisolone followed by high-dose corticosteroids proved ineffective. Strikingly, IVIg therapy delivered at unconventional doses (1.2 g/kg) due to the presence of multiple risk factors for adverse events resulted in a significant, comprehensive clinical improvement. Although large-scale randomized double-blind studies are needed, the use of IVIg might constitute a valuable therapeutic modality as a last-resort strategy in cases of fulminant SLE. The total dose of immunoglobulins should be dictated by the clinical response as well as the presence of pre-existing risk factors for adverse events.LEARNING POINTSThe use of immunoglobulins in the treatment of systemic lupus erythematosus is mainly based on small prospective studies and case series.Their use as a rescue strategy in cases of systemic lupus erythematosus that are refractory to conventional immunosuppressive therapy may be a valid therapeutic alternative in selected patients.The short-term clinical response and the presence of risk factors for adverse effects should dictate the overall dose of immunoglobulins administered to the patient.

Management of Catastrophic Antiphosphopholipid Syndrome with Eculizumab

Catastrophic antiphospholipid syndrome (CAPS) is a rare, often fatal phenomenon. Patients present with a wide range of symptomatology including thrombotic microangiopathy, cytopenias and end organ damage. The mortality rate of CAPS is as high as 33% in spite of the use of combination therapies including steroids, anticoagulation, plasma exchange (PEX) and intravenous immunoglobulin (Cervera CA 2009; Espinosa G 2011; Bucciarelli S 2006). CAPS is believed to be a disorder of complement-mediated inflammation which results in tissue injury. The proposed mechanism of the thrombotic microangiopathyisthe interaction of the coagulation cascade and complement (Mehdi AA 2010). Multiple murine-based studies demonstrate the contribution of C5a to antiphospholipid antibody-mediated intravascular thrombosis (Fischetti F 2005; Pierangeli SS 2005; Giannakopoulos B 2013). Eculizumab is a humanized monoclonal antibody that binds to C5 and inhibits its cleavage to C5a and C5b. It is FDA approved for the treatment of the complement mediated disorders paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.We present 3 cases of CAPS treated with eculizumab at our institution. Their individual diagnostic criteria and background characteristics are outlined in Table 1.Case 1: 41-year-old male with history of antiphospholipid syndrome on chronic anticoagulation presented with fevers and ventilatory-dependent respiratory failure. Upon transfer to our institution, he developed thrombocytopenia and left hand mottling; doppler revealed a radial artery thrombus. Biopsy of the involved area of skin indicated thrombotic microangiopathy. Pulse dose steroids and unfractionated heparin were initiated. He was extubated within 24 hours and fever resolved. He remained dyspneic and mildly thrombocytopenic and therefore rituximab was initiated. Oxygen requirements, liver dysfunction, and thrombocytopenia resolved. As the prednisone dose was tapered, new microangiopathic lesions were noted. The decision was made to start eculizumab which is ongoing as a maintenance dose every two weeks with no clinical recurrence of CAPS.Case 2: 68-year-old male presented with priapism. On day 2 of hospitalization, he was found to have left lower extremity (LLE) DVTs and received unfractionated heparin. On day 4, he developed fever and thrombocytopenia and was noted to have a cold LLE. Angiography demonstrated occlusion of the posterior tibial artery and heparin was discontinued in favor of an alteplase drip. The patient was subsequently transferred to our institution. Doppler demonstrated multiple DVTs in both lower extremities. Evaluation for HIT was negative. Lupus anticoagulant (LA) was strongly positive raising concern for CAPS. Steroids and PEX were initiated. However, emergency fasciotomy of the RLE was needed to relieve compartment syndrome. Skin biopsy demonstrated microangiopathy. Due to lack of clinical improvement, PEX was discontinued and eculizumab was initiated. On day 3 post-eculizumab initiation, there was evidence of regression of skin mottling. Eculizumab was redosed on day 5. Steroids were tapered and he received 2 additional doses of eculizumab. No additional thrombotic complications occurred. He eventually died during this hospitalization due to septic shock.Case 3: 37-year-old female presented with fever, hypoxia, and painful feet. She was hypotensive and labs demonstrated leukopenia, thrombocytopenia, elevated liver enzymes, and acute kidney injury. Vasopressors and antibiotics were initiated. Over the next 24 hours she developed mottling of her feet, face and breasts. The diagnosis of CAPS was made based on clinical criteria and a positive LA. Unfractionated heparin, steroids and eculizumab were initiated. Dialysis was started due to renal failure. Skin biopsy showed microangiopathy. Marked improvement of skin mottling was noted after 3 doses of eculizumab and renal function normalized after 7 doses. She was discharged with a slow steroid taper, therapeutic enoxaparin, and maintenance eculizumab.Complement blockade with eculizumab is safe and effective in patients with CAPS. These cases suggest that utilizing therapy to inhibit the complement pathway may be an integral component in treating CAPS more effectively. Future directions should include a randomized clinical trial to evaluate eculizumab as part of combination therapy for CAPS. [Display omitted] DisclosuresBroome:True North Therapeutics: Honoraria; Alexion Pharmaceuricals: Honoraria.

Prognosis Evaluation of Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension (PH) curable by pulmonary endarterectomy (PEA) necessarily made in the reference centers. We report the case of a 30-year-old woman with a history of antiphospholipid syndrome diagnosed after a thromboembolic event responsible of her first pregnancy abortion. Two years after this event, she presented a massive and bilateral pulmonary embolism after the delivery of his second pregnancy. She was hospitalized in the intensive care unit and she received thrombolytic treatment relayed by vitamin K antagonists. One year later, she developed progressive dyspnoea (class III NYHA) and hemoptysis. Ultrasonic cardiography showed severe pulmonary hypertension (Systolic arterial pulmonary pressure at 120 mmHg) and at the right cardiac catheterization (mean arterial pulmonary pressure at 90 mmHg). Computed tomography pulmonary angiogram and ventilation-perfusion lung scan concluded on CTEPH. Blood gases showed a moderate hypoxemia (58 mmHg); conventional treatment was prescribed (oxygen, vitamine K antagonists and diuretics). The patient was referred to the reference surgical center in Paris and a pulmonary endarterectomy was done. After the surgery, the patient reports an improvement of the class of dsypnea and of the sub-maximal aerobic capacity. The systolic pulmonary pressure decreased at 50 mmHg in the ultrasonic cardiography. The patient actually has a better quality of life and rapidly resumed work.

A case of catastrophic antiphospholipid syndrome: first report with advanced cardiac imaging using MRI

This present case pertains to a 48-year-old woman with a history of antiphospholipid syndrome, who presented with progressive fatigue, generalized weakness, and orthopnea acutely. She had a prior diagnosis of antiphospholipid syndrome with recurrent deep vein thromboses (DVTs) and repeated demonstration of lupus anticoagulants. She presented in cardiogenic shock with markedly elevated troponin and global myocardial dysfunction on echocardiography, and cardiac catheterization revealed minimal disease. Cardiac magnetic resonance imaging was performed, which revealed findings of perfusion defects and microvascular obstruction, consistent with the pathophysiology of catastrophic antiphospholipid syndrome (CAPS). Diagnosis was made based on supportive imaging, including head magnetic resonance imaging (MRI) revealing multifocal, acute strokes; microvascular thrombosis in the dermis; and subacute renal infarctions. The patient was anticoagulated with intravenous unfractionated heparin and received high-dose methylprednisolone, plasmapheresis, intravenous immunoglobulin, and one dose each of rituximab and cyclophosphamide. She convalesced with eventual myocardial recovery after a complicated course. The diagnosis of CAPS relies on the presence of (1) antiphospholipid antibodies and (2) involvement of multiple organs in a microangiopathic thrombotic process with a close temporal association. The myocardium is frequently affected, and heart failure, either as the presenting symptom or cause of death, is common. Despite echocardiographic evidence of myocardial dysfunction in such patients, MRIs of CAPS have not previously been reported. This case highlights the utility in assessing the involvement of the myocardium by the microangiopathic process with MRI. Because the diagnosis of CAPS requires involvement in multiple organ systems, cardiac MRI is likely an underused tool that not only reaffirms the pathophysiology of CAPS, but could also clue clinicians in to the possibility of a diffuse thrombotic process.

The Value and the Variability of Magnetic Resonance Imaging in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Objectives: The objectives of this article are twofold: To review the value and the variability of MR imaging (MRI) findings in patients with systemic lupus erythematosus (SLE) and to reveal the frequency of central nervous system (CNS) involvement. SLE is a complex multisystem autoimmune connective tissue disorder with a broad spectrum of clinical presentations. Materials and methods: We present three cases, two with neurological symptoms and one case with musculoskeletal symptoms. Patients were imaged in the MRI department of the University Hospital of Patras. All patients had a previous history of antiphospholipid syndrome and known SLE. Results: None of the pts had a normal brain MRI. Abnormal lesions were typically high on FLAIR and T2-weighted images. One patient showed myositis of the tibial muscles bilateral and although she did not reveal any neurological symptoms, because of the presence of APS, she underwent brain MRI to detect any cerebrovascular involvement. The brain MRI was abnormal and showed extensive lesions and porencephalia. In all cases the differential diagnosis of the brain MRI included vasculitis, focal ischemia, multiple sclerosis or other entities. Parenchymal volume loss-cerebral atrophy, incompatible with their age, was obvious in all patients. Conclusion: Magnetic resonance imaging is the gold standard for the investigation of central nervous system in patients suffering from lupus. Lupus patients who also develop antiphospholipid syndrome must be submitted to brain MRI because central nervous involvement is very common and serious, although symptoms may be silent as in our case.

Intricacies Of Treating Heparin Induced Thrombocytopenia With Preexisting Antiphospholipid Syndrome and Renal Insufficiency

Treatment of heparin induced thrombocytopenia (HIT) requires the use of alternatives anticoagulants, such as a direct thrombin inhibitor – argatroban. Use of argatroban relies on frequent laboratory monitoring of the activated partial thromboplastin time (aPTT) to maintain an adequate level of anticoagulation. This requirement poses a challenge in patients with prolonged baseline aPTT, such as in antiphospholipid syndrome. While other assays are being explored they require an extended turn around time because of their limited availability. We present a case of a 63 year old male with a history of antiphospholipid syndrome, end stage renal disease on hemodialysis, hepatitis C, and on long term anticoagulation with warfarin for cerebral vein thrombosis. His hospital course required transition to unfractionated heparin and subsequently developed thrombocytopenia. A heparin-platelet factor 4 ELISA antibody assay was performed for an intermediate clinical likelihood of HIT and returned positive. Although not confirmed with the gold standard serotonin release assay (SRA), clinical suspicion for HIT obligated treatment with an alternative anticoagulant. Conventional dosing and administration of argatroban however could not be performed because of the patient’s prolonged baseline aPTT. Other agents such as fondaparinux were also not possible in the setting of renal insufficiency. Short of other treatment techniques accepted in this unique set of circumstances we practiced a fixed dose argatroban (0.5 mcg/kg/min for Child’s class B cirrhosis). The patient tolerated the empiric dosing well until discontinued because of a negative SRA. This case demonstrates the limitations of current treatment recommendations of HIT and need for further investigation in similar patients. Disclosures: No relevant conflicts of interest to declare.

ADAMTS-13 metalloprotease abnormalities in systemic lupus erythematosus: is there a correlation with disease status?

To clarify the role of ADAMTS-13 in the pathogenesis of thrombotic microangiopathy in systemic lupus erythematosus (SLE) we evaluated ADAMTS-13 profile (metalloprotease antigen levels, anti-ADAMTS-13 autoantibody levels, activity) in distinct patient groups according to disease activity, extent of cumulative tissue damage and history of antiphospholipid syndrome or end-organ damage. Forty-one lupus patients were analysed. ADAMTS-13 metalloprotease antigen levels and anti-ADAMTS-13 autoantibodies were evaluated by ELISA. ADAMTS-13 activity was measured by Fluorescence resonance energy transfer (FRET) technique. ADAMTS-13 metalloprotease antigen levels were significantly decreased in patients with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) >1 (p<0.05). ADAMTS-13 metalloprotease antigen levels also exhibited a significant inverse correlation with anti-dsDNA levels (r= -0.60, p<0.05). Anti-ADAMTS-13 autoantibodies were marginally higher in patients with positive anti-dsDNA (p=0.08). Additionally, patients with positive anti-ADAMTS-13 autoantibodies exhibited the lowest activity levels (p<0.05). To our knowledge ADAMTS-13 profile in SLE has not been studied in regard to composite structured indices. The results of this study suggest that in patients with active SLE or considerable cumulative tissue damage, ADAMTS-13 levels may be decreased and anti-ADAMTS-13 autoantibodies may partially mediate this reduction. Further evaluation of ADAMTS-13 profile may explain its role in the pathogenesis of thrombotic microangiopathy in lupus patients and reveal a potential prognostic marker of microthrombotic manifestations in SLE.