Episodes Of Catastrophic Antiphospholipid Syndrome Research Articles

Pulmonary involvement in catastrophic antiphospholipid syndrome: A descriptive analysis from the “CAPS Registry”

ObjectivesTo describe the pulmonary involvement in patients with catastrophic antiphospholipid syndrome (CAPS), focusing on its relationship with extrapulmonary involvement, laboratory, radiological, and pathological findings. MethodsThis retrospective cross-sectional study includes all patients grouped in the “CAPS Registry”. All cases were reviewed, and those with pulmonary thromboembolism (PE) and/or diffuse alveolar hemorrhage (DAH) were selected. Data on pulmonary and extrapulmonary clinical presentation, radiologic patterns, laboratory findings, associated autoimmune diseases, treatments, and outcomes were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test, while T-test for independent variables was used to compare groups regarding continuous variables. IBM-SPSS v.22 was used for data analysis. ResultsPE was reported in 129 (48.6 %) episodes, DAH in 75 (28.3 %) episodes, and overlap (DAH plus PE) in 7 (2.6 %) episodes. Bronchoalveolar lavage (BAL) was performed in 35 (4.9 %) CAPS episodes, and lung pathology samples were obtained in 84 (10.5 %) episodes (including autopsies). A significant relationship was observed between DAH and laboratory features of thrombotic microangiopathy (TMA). A meaningful relationship was also found between triple antiphospholipid antibody positivity and pathological TMA (26.5 %) as well as hypocomplementemia and DAH (24 %). ConclusionsPulmonary involvement may include both TMA and non-thrombotic inflammation, which can be differentiated into three patterns: PE, DAH with systemic TMA with hypocomplementemia or DAH without systemic TMA with/without hypocomplementemia.

Precipitating factors of catastrophic antiphospholipid syndrome: the role of anticoagulant treatment in a series of 112 patients

BackgroundThe prevention of catastrophic antiphospholipid syndrome (CAPS), a rare complication of antiphospholipid syndrome (APS), is a major goal. ObjectivesWe analyzed its precipitating factors, focusing on anticoagulation immediately before CAPS episodes. MethodsWe retrospectively analyzed patients in the French multicenter APS/systemic lupus erythematosus database with at least 1 CAPS episode. Then we compared each patient with known APS before CAPS with 2 patients with non-CAPS APS matched for age, sex, center, and APS phenotype. ResultsWe included 112 patients with CAPS (70% women; mean age, 43 ± 15 years). At least 1 standard precipitating factor of CAPS was observed for 67 patients (64%), which were mainly infections (n = 28, 27%), pregnancy (n = 23, 22%), and surgery (n = 16, 15%). Before the CAPS episode, 67 (60%) patients already had a diagnosis of APS. Of the 61 treated with anticoagulants, 32 (48%) received vitamin K antagonists (VKAs), 23 (34%) heparin, and 2 (3%) a direct oral anticoagulant. They were less likely than their matched patients with APS without CAPS to receive VKA (48% vs 66%, p = .001). Among those treated with VKA, 72% had a subtherapeutic international normalized ratio (ie, <2) versus 28% in patients with APS without CAPS (p < .001). Finally, excluding pregnant patients (n = 14) for whom we could not differentiate the effect of treatment from that of pregnancy, we were left with 47 cases, 32 (68%) of whom had recently begun a direct oral anticoagulant, planned bridging therapy, or had VKA treatment with international normalized ratio <2. ConclusionThese results strongly suggest that suboptimal anticoagulation management can trigger CAPS in patients with thrombotic APS.

The clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome: A descriptive analysis of 73 patients from the "Catastrophic antiphospholipid syndrome registry".

To explore the prevalence and clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome (CAPS). We reviewed data from the "CAPS Registry" on C3 and/or C4 complement plasma protein levels during acute CAPS episodes. Patients were classified into those with low and normal complement levels. Data on clinical presentation, with special focus on thrombotic microangiopathy (TMA) features, diagnosis of systemic lupus erythematosus (SLE), and antiphospholipid antibody (aPL) profile were reviewed. The chi-square exact test was performed to evaluate differences between categorical data. The "CAPS Registry" includes 566 patients with a total of 578 episodes of CAPS. Data on complement plasma protein levels was available in 73 episodes from the same number of patients. Low levels of C3 and/or C4 complement plasma proteins were detected in 42 (58%) CAPS episodes. Low complement levels were more common in SLE patients (55% SLE vs. 19% No SLE; p<0.001). The frequencies of clinical TMA (72% vs. 80%; p=0.4) or TMA syndrome (86% vs. 84%, p=0.9), frequency of triple aPL triple positivity (67% vs 33%; p=0.3), or the mortality (35% vs. 31%; p=0.7) were similar between low and normal complement groups. In our study, low levels of C3 and C4 plasma proteins are detected in 58% episodes of CAPS, which were not associated with clinical presentation including TMA features, aPL triple positivity, or mortality.

Catastrophic antiphospholipid syndrome: a narrative review

The catastrophic antiphospholipid syndrome (CAPS) is a lifethreatening disorder characterized by the rapid development of multiple organs/systems thrombosis, in patients with persistently detectable antiphospholipid antibodies. The vascular occlusions predominantly affect small vessels, leading to a disseminated thrombotic microangiopathic syndrome. Most CAPS episodes are related to the presence of a precipitating factor, such as infections and malignant diseases, usually ending up in multiple organ failure. Clinical manifestations may vary according to the extent of the thrombosis, predominantly affecting kidneys, lungs, brain, heart, and skin. Treatment is based on the administration of anticoagulants, corticosteroids, plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is recommended in CAPS associated with systemic lupus erythematosus. Additionally, rituximab and eculizumab have been used in refractory cases. Overall mortality is still 36.9%, despite recent progress in the therapeutic approach.

Catastrophic antiphospholipid syndrome: Lessons from 14 cases successfully treated in a single center. A narrative report

The study aimed to evaluate the clinical significance of laboratory findings in patients with catastrophic antiphospholipid syndrome (CAPS) and to report the effects of a well-defined treatment protocol in 14 consecutive cases.Thirteen patients (12 presenting one and one presenting two episodes of CAPS) were consecutively treated and monitored between 1986 and 2017. Antiphospholipid antibody (aPL) characteristics of the patients were compared with those of 64 matched controls (45 antiphospholipid syndrome patients and 19 aPL carriers) who did not develop CAPS during the same mean follow-up period (12 years ± 9.9 SD).Triple aPL positivity (IgG/IgM anticardiolipin + IgG/IgM anti-β2Glycoprotein I + lupus anticoagulants) significantly prevailed in the CAPS patients with respect to the controls (p = 0.003). IgG anticardiolipin and IgG anti-β2Glycoprotein I mean antibody titers of the CAPS patients were significantly higher than those of the controls (p = 0.0018 and p = 0.003, respectively). Triple therapy (anticoagulation + plasma exchange + steroids) was administered to all the CAPS cases except for one. Beginning in 2009, intravenous immunoglobulin infusion has also been included in the triple therapy protocol (six patients). All the patients recovered from CAPS; five showed renal failure and one a I-II class New York Heart Association (NYHA) dilated cardiomyopathy. Long-term outcomes of CAPS included a gradual worsening of renal failure in one patient who required hemodialysis 30 years after the acute episode. Renal function improved in the other four patients. The patient affected with dilated cardiomyopathy worsened to a II class NYHA over a five year period. Currently all the patients are alive.A specific antiphospholipid antibody profile could be considered a risk factor associated to CAPS. Early use of a defined treatment protocol based on triple therapy either or not associated with IVIG was associated with recovery in all CAPS patients.

Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry

To analyze the clinical and immunologic manifestations of patients with catastrophic antiphospholipid syndrome (CAPS) from the "CAPS Registry". The demographic, clinical and serological features of 500 patients included in the website-based "CAPS Registry" were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test while T-test for independent variables was used to compare groups regarding continuous variables. 500 patients (female: 343 [69%]; mean age 38±17) accounting for 522 episodes of CAPS were included in the analysis. Forty percent of patients had an associated autoimmune disease, mainly systemic lupus erythematosus (SLE) (75%). The majority of CAPS episodes were triggered by a precipitating factor (65%), mostly infections (49%). Clinically, CAPS was characterized by several organ involvement affecting kidneys (73%), lungs (60%), brain (56%), heart (50%), and skin (47%). Lupus anticoagulant, IgG anticardiolipin and IgG anti-β2-glycprotein antibodies were the most often implicated antiphospholipid antibodies (83%, 81% and 78% respectively). Mortality accounted for 37% of episodes of CAPS. Several clinical differences could be observed based on the age of presentation and its association to SLE. Those cases triggered by a malignancy tended to occur in older patients, while CAPS episodes in young patients were associated with an infectious trigger and peripheral vessels involvement. Additionally, CAPS associated with SLE were more likely to have severe cardiac and brain involvement leading to a higher mortality (48%). Although the presentation of CAPS is characterized by multiorgan thrombosis and failure, clinical differences among patients exist based on age and underlying chronic diseases, e.g. malignancy and SLE.

Rituximab and its therapeutic potential in catastrophic antiphospolipid syndrome.

The catastrophic antiphospholipid syndrome (CAPS) is characterized by thrombosis in more than three organs or systems developing over a short period of time. Despite conventional treatment with a combination of anticoagulation plus corticosteroids plus plasma exchange, and/or intravenous immunoglobulin, mortality remains high and some patients suffer from recurrent CAPS episodes. In selected patients, new therapies such as rituximab may be a treatment option. In this review, the rationale for using rituximab in CAPS is discussed.

Recurrent thrombosis prevention with intravenous immunoglobulin and hydroxychloroquine during pregnancy in a patient with history of catastrophic antiphospholipid syndrome and pregnancy loss

We report a case of a 36-year old patient with prior history of thrombosis in a setting of antiphospholipid antibody syndrome (APS) as well as pregnancy-associated catastrophic antiphospholipid syndrome (CAPS), resulting in multi-organ infarction and pregnancy loss. The episode of CAPS occurred while she was receiving antepartum low-dose aspirin and therapeutic-dose enoxaparin. This patient presented again at 6weeks gestation and ultrasounds were consistent with fetal growth restriction, concerning for placental insufficiency and thrombosis. This time, hydroxychloroquine and monthly intravenous immunoglobulin (IVIG) infusions were added to her prophylaxis regimen, resulting in a successful delivery. Platelet count and antiphospholipid antibody titers were routinely monitored throughout pregnancy as markers of disease activity for APS. Current thromboprophylaxis guidelines do not address therapeutic options to prevent further pregnancy morbidity in women who develop recurrent episodes of thrombosis or CAPS despite receiving adequate anti-thrombotic treatment. Use of hydroxychloroquine and IVIG has been associated with good outcomes in this subset of patients.

Recurrent Thrombotic Events after Catastrophic Antiphopholipid Syndrome

To the Editor, A 40-year-old man was transferred to our hospital in March 1994 for gross hematuria and decreased urine output. The patient exhibited chest pain and shortness of breath 2 weeks prior to the initial visit. These symptoms were relieved without particular management. Fever and chills developed thereafter followed by abdominal pain. The patient visited a local clinic and was managed for acute pancreatitis and gastritis for 1 week. However, his symptoms did not subside and urine output decreased progressively. On admission, he complained of severe headache, nausea, and both flank and back pain. Initial hemoglobin levels and platelet counts were 16.9 g/dL and 478 × 109/L, respectively. In the course of 3 days, anemia and thrombocytopenia rapidly developed, with a hemoglobin level of 12.0 g/dL and a platelet count of 29 × 109/L. Peripheral blood smear showed schistocytes suggesting hemolytic anemia. Initial blood urea nitrogen and creatinine levels were 69 and 6.0 mg/dL, respectively. Magnetic resonance imaging of the kidney revealed acute cortical necrosis. He also had blood tinged sputum, and the lung perfusion scan revealed perfusion defects in the right lower lobe, suggesting pulmonary embolism. Despite fluid therapy and the administration of diuretics, azotemia progressed rapidly over a 3-day period and he consequently underwent hemodialysis. Azotemia improved with increased urine output only after hemodialysis (Fig. 1). Figure 1 Azotemia progressed rapidly with fluid and diuretics therapy. Urine output increased only after hemodialysis. HD, hemodialysis; Cr, creatinine. The serologic results showed the presence of lupus anticoagulant and IgM anticardiolipin antibody, and the patient was diagnosed with antiphospholipid syndrome (APS) with multiorgan failure. Retrospectively, his clinical presentation fits into the category of probable catastrophic APS (CAPS). However, neither intravenous heparin nor warfarin was used due to hemoptysis. Thereafter, he was admitted several times for coronary events and pulmonary infarction. Two months after the first attack, he was readmitted due to chest pain. The echocardiogram showed inferior and septal myocardial infarction and he was discharged with aspirin and clopidogrel. Three months later, he was readmitted due to chest pain, and a coronary angiogram showed right coronary artery focal stenosis (Fig. 2). He was lost to follow-up for 3 years and was readmitted to the hospital in 1997 for pleuritic chest pain. Chest computed tomography scans revealed both lower lobe pulmonary infarctions. He was lost again to follow-up without antithrombotic agents. Figure 2 Coronary angiogram showed right coronary artery 50% focal stenosis, suggesting embolic infarct rather than atherosclerosis. Recently, he was admitted for facial cellulitis associated with a burn, and the involved skin showed multiple ulcerations and necrosis (Fig. 3). His facial lesions improved with antibiotics. We started antithrombotic treatment for long-term prevention of recurrent thrombotic events. Figure 3 The patient developed facial cellulitis with multiple necrotic ulcerations after burn, suggesting possible microangiopathic thrombosis. CAPS is a life-threatening medical situation with a high mortality rate, although it represents in less than 1% of patients with APS [1]. Therefore, clinical suspicion and early diagnosis are important for improving survival from CAPS. Asherson et al. [1] and Erkan [2] noted that the recurrence of CAPS was not common, although patients had been on continuous anticoagulation therapy. Among 73 CAPS survivors, 14 patients (19%) had further APS-related manifestations but no patient developed recurrent CAPS episodes during a follow-up of median 67.2 months [3]. Our case presents recurrent APS-related events after an initial CAPS episode. No standardized treatment guideline for CAPS has been established due to the rarity of the disease and the lack of controlled studies [2]. Current treatment recommendations are based on case series. Previous studies emphasized the importance of early anticoagulation, steroid, and plasma exchange during CAPS episodes [1,4,5]. Bucciarelli et al. [4] demonstrated that the mortality rate decreased from 53% to 33% with a combination therapy of anticoagulation, steroids, and plasma exchange and/or intravenous immunoglobulins in 250 patients in the CAPS registry. The reported patient could not maintain anticoagulation therapy because he had a bleeding episode at the initial admission and did not regularly visit clinics. The recurrent thrombotic events may have been due to the lack of anticoagulation therapy. This case suggests that continuous anticoagulation is important for the prevention of recurrent thrombotic events after CAPS.

Mortality in the catastrophic antiphospholipid syndrome: Causes of death and prognostic factors in a series of 250 patients

To assess the main causes of death and the prognostic factors that influence mortality in patients with the catastrophic antiphospholipid syndrome (CAPS). We analyzed the case reports of 250 patients included in the CAPS Registry up to February 2005. To identify prognostic factors for CAPS, we compared the main clinical and immunologic features and the types of treatment in the patients who died with those features in the patients who survived. Recovery occurred in 56% of the episodes of CAPS and death occurred in 44%. Cerebral involvement, consisting mainly of stroke, cerebral hemorrhage, and encephalopathy, was considered the main cause of death, being present in 27.2% of patients, followed by cardiac involvement (19.8%) and infection (19.8%). The only factor we identified that was prognostic of a higher mortality rate was the presence of systemic lupus erythematosus (SLE). A higher recovery rate was associated with combined treatment with anticoagulants (ACs) plus corticosteroids (CS) plus plasma exchange (PE) (77.8%), followed by ACs plus CS plus PE and/or intravenous immunoglobulins (69%). In contrast, concomitant treatment with cyclophosphamide did not demonstrate additional benefit. Cerebral involvement (mainly consisting of stroke), cardiac involvement, and infections were considered the main causes of death in patients with CAPS. The presence of SLE was related to a higher mortality rate. According to the results of the present study, ACs plus CS plus PE should be the first line of therapy in patients with CAPS.