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![Pathophysiology of pulmonary arterial hypertension (from: Armando J. Huaringa, [18]). Pathophysiology of pulmonary arterial hypertension and coagulation abnormalities in myeloid metaplasia with myelofibrosis (MMM) associated with antiphospholipid syndrome (APS). SMC = Smooth Muscle Cell.](profile/Ljudmila-Stojanovich/publication/7000482/figure/fig1/AS:696065997168645@1542966474588/Pathophysiology-of-pulmonary-arterial-hypertension-from-Armando-J-Huaringa-18.png)
Pathophysiology of pulmonary arterial hypertension (from: Armando J. Huaringa, [18]). Pathophysiology of pulmonary arterial hypertension and coagulation abnormalities in myeloid metaplasia with myelofibrosis (MMM) associated with antiphospholipid syndrome (APS). SMC = Smooth Muscle Cell.
Source publication
Pulmonary manifestations in antiphospholipid syndrome (APS) are relatively rare compared to other clinical signs of this disease. However, pulmonary microthrombosis is among the most frequent arterial complications of APS. Timely diagnosis of pulmonary manifestations is required due both to their severity and to the high mortality rate. The spectru...
Citations
... Background Antiphospholipid syndrome (APS) is a systemic autoimmune disorder with a wide spectrum of clinical manifestations. Although the main clinical manifestations are related to vascular thrombosis and pregnancy morbidity [1], APS can have neurological [2], cardiovascular [3], dermatological [4], orthopedic [5], and pulmonary manifestations [6]. Considering the wide range of symptoms and organ systems affected, other clinical manifestations are anticipated to be included in the new clinical criteria used to diagnose APS for research purposes [7]. ...
As part of the non-criteria clinical manifestations, postural orthostatic tachycardia syndrome (POTS), a multisystem autonomic dysfunction, can co-exist with antiphospholipid syndrome (APS). Several pieces of evidence hint on the autoimmune basis of POTS, and its possible association with several autoimmune diseases, including APS. Indeed, the evidence exists in the etiologies, symptomatology, and treatment options. Although infections, viral ones in particular, stress, and pregnancy are etiologies to both POTS and APS, the exact pathophysiological connection is still to be studied taking into consideration the activity of cytokines in both diseases. Nevertheless, certain immunomodulatory treatments used for the catastrophic or obstetrical forms of APS, such as intravenous immunoglobulins (IVIG) and steroids, have been also used for the treatment of POTS resistant to classical treatments. Therefore, our review aims to highlight the association between POTS and APS, shedding light on the common etiologies explaining the pathophysiology of the two disorders, the diagnostic approach to POTS as a possible clinical criterion of APS, and the treatment of APS in the context of treating POTS.
... [2][3][4] APS is seen in up to 10% to 20% of patients with chronic thromboembolic pulmonary hypertension presenting for pulmonary thromboendarterectomy (PTE). 5 Patients with APS are at particularly high risk during cardiac surgery, with early mortality of up to 20% and morbidity of nearly 50%. 3,4 Perioperative management of antithrombotic therapy in patients with APS is complicated by the fact that in vitro tests of coagulation, such as the activated partial thromboplastin time and the activated clotting time (ACT), are falsely elevated at baseline as a result of antibody inhibition of phospholipiddependent coagulation during in vitro testing. ...
... ese manifestations are due to the disruption of the vessels surface. Alveolar hemorrhage is the rarest complication of CAPS, and it is caused by the disruption in the alveolar capillaries, leading to bleeding in the alveolar space [5,6]. Alveolar hemorrhage's mortality rate increases from 35% in the absence of CAPS to approximately 50% in association with CAPS even in patients under treatement [7]. ...
... Alveolar hemorrhage in APS can be explained due to anti-phospholipid antibodies binding to the alveolar surface [6]. Such antibodies can be found in both asymptomatic patients and patients with nonthrombotic manifestations. ...
... e initial management of alveolar hemorrhage is ventilatory support and anticoagulation, followed by the treatment of CAPS. Anticoagulation is key in the treatment since it inhibits clot formation and promotes fibrinolysis and could also have an effect on preventing anti-phospholipid antibodies from binding to the endothelial surface [6]. Heparin use is recommended at doses that do not increase the risk of bleeding; however, there is insufficient evidence to support a dose that avoids this risk. ...
Alveolar hemorrhage is the rarest pulmonary complication of catastrophic antiphospholipid syndrome and is associated with high mortality risk. This life-threatening complication results from autoimmune damage to the alveolar blood vessels. Given the limited literature addressing the association of these two pathologies, we report a series of three cases with this complication and then compare our findings with 6 cases reported in the literature.
... Pulmonary manifestations of antiphospholipid syndrome (APS) have long been observed. The most common of these manifestations include pulmonary hypertension and thromboembolic disease [1,2]. A less common initial manifestation of APS includes DAH which has been described in the literature as a non-criteria manifestation of APS [1,3,4]. ...
... A retrospective study demonstrated that DAH constituted 3.7% of systemic lupus erythematosus (SLE) admissions within a single institution [4]. As such, evaluation of DAH should include diagnostic testing not only for secondary APS but also primary APS as this may be a less common initial manifestation of these disease processes [1][2][3][5][6][7][8][9]. Primary and secondary APS differ in that secondary APS has a concomitant diagnosis of another disease process, often SLE [8]. ...
... Both capillaritis and microthrombotic disease contribute to the development of alveolar hemorrhage in APS patients [2,8]. Thrombotic events remain a hallmark of APS; among those presenting with DAH, multiple causes exist due to the presence of both inflammatory and noninflammatory states [9]. ...
A 26 year old female presented for recurrent blood tinged sputum during the previous year with development of frank hemoptysis three days prior to admission. Diffuse alveolar hemorrhage (DAH) was confirmed with serial lavages. The patient had no history of autoimmune disease, vascular thrombosis or pregnancy morbidity including miscarriages or pre-eclampsia. High dose steroids were initiated along with noninvasive ventilatory support. Transthoracic echocardiogram showed severe mitral regurgitation and a vegetation on the mitral valve; transesophageal echocardiogram determined the lesion highly suggestive of Libman-Sachs endocarditis. Blood cultures were negative. Immunological evaluation established the patient was negative for: anti-nuclear antibody, anti-double-stranded DNA antibody, rheumatoid factor, anti-smith antibody, anti-cyclic citrullinated peptide, anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane antibodies. Further evaluation revealed elevated levels of anticardiolipin immunoglobulin G and anti-beta 2 glycoprotein immunoglobulin G which continued to increase for months after hospitalization. She was diagnosed with DAH secondary to acute mitral regurgitation caused by Libman-Sachs endocarditis in the presence of primary antiphospholipid antibody syndrome.
DAH is an important disease to understand given its high mortality rate. Few case reports relating the presence of Libman-Sachs endocarditis induced by antiphospholipid antibody syndrome leading to DAH have been published. Unique here is the absence of rheumatologic markers thus supporting a diagnosis of primary antiphospholipid antibody syndrome (APS). This patient had no findings associated with rheumatological disorders potentially making this diagnosis easily overlooked. This case further illustrates the importance of evaluating patients with APS presenting with DAH as there are multiple etiologies that lead to this pathology thus different treatment avenues are to be considered during management.
... Antiphospholipid syndrome (APS) or Hughes Syndrome represents a systemic autoimmune disorder characterised by arterial and/or venous thrombosis, multiple and recurrent fetal losses, often accompanied by a thrombocytopenia and elevated levels of antiphospholipid antibodies (aPL), such as lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-β 2 GPI antibodies (1)(2)(3). This syndrome is considered primary (PAPS) if unassociated with any other connective tissue disease, or secondary (SAPS) if it appears in association with other autoimmune disorders, mainly systemic lupus erythematosus (SLE) (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Antiphospholipid antibodies (aPL) are heterogenous and distinct group of antibodies that appears in variety of autoimmune diseases, particularly in systemic lupus erythematosus (SLE) (1). ...
Objectives:
The aim of this study was to investigate association between pulmonary and skin manifestations in a large group of patients with primary antiphospholipid syndrome (PAPS) as well as their connection with antiphospholipid antibodies.
Methods:
Our prospective study comprises of 390 patients with primary APS. Antiphospholipid antibody (aPL) analysis included detection of aCL (IgG/IgM), ß2GPI (IgG/IgM) and LA. Distinct pulmonary and skin associations were determined, as well as their associations with aPL.
Results:
In PAPS patients the presence of LA was more common in PTE (p=0.005) and in pulmonary microthrombosis (p=0.003). We revealed statistical significance considering the presence of aCL IgM and pulmonary microthrombosis (p=0.05). Skin ulcerations correlated with positive titres aCL IgM and ß2 GPI IgM (p=0.03 and 0.04, respectively), while pseudovasculitis correlated with positive titres ß2 GPI IgM (p=0.02). PAPS patients were more more likely to develop pulmonary thromboembolisam if they had livedo reticularis (p=0.005), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.01), superficial cutaneous necrosis (p=0.005), and digital gangrene (p=0.02). Patients were also more prone to pulmonary microthrombosis if they already had livedo reticularis (p=0.03), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.05), superficial cutaneous necrosis (p=0.006), and digital gangrene (p=0.02).
Conclusions:
There is strong link between some pulmonary and skin manifestations in PAPS patients, suggesting complexity and evolutionary nature of APS. The presence of skin manifestations may be a high risk factor for several types of serious pulmonary manifestations in PAPS. Certain aPL types are associated with distinct pulmonary and skin manifestation, suggesting their predictive role.
... a mis en évidence l'apparition d'atteinte cutanée, cardiaque ou neurologique non associée à un phénomène thrombotique (Tableau 8). Les atteintes pulmonaires (hypertension, hémorragie intra alvéolaire) sont principalement des complications d'embolie pulmonaire(50). Il existe une forme particulière de SAPL : le syndrome de Sneddon. Il associe un livedo étendu avec un AVC. ...
Le syndrome des antiphospholipides (SAPL) est un syndrome clinico-biologique caractérisé par une thrombophilie clinique ou une atteinte obstétricale, associée à la présence d’Ac antiphospholipides (APL) 2 fois à 12 semaines d’intervalle.
L’objectif est d’évaluer l’intérêt du test de génération de thrombine (TGT) dans un modèle murin de SAPL traité par hydroxychloroquine (HCQ) et chez des patients SAPL.
Matériel et méthodes :
Une mise au point du TGT a été effectuée. L’impact de la protéine C activée (PCa) a été évalué. L’étude des patients SAPL est rétrospective et a inclus tous types de SAPL.
Résultats :
En présence de PCa, nous avons observé une différence significative avec une génération de thrombine plus importante chez les souris SAPL (ETP : 237,4±53,2 nM.min ; Pic : 45,2±12,7 nM) que les souris SAPL traitées par HCQ (ETP : 145,7±21,6 nM.min; Pic:23.9±8,0 nM) et les témoins (ETP: 116,3±29,6 nM.min; Pic: 21,9±3,1 nM). Chez les patients, le TGT était très augmenté dans le groupe SAPL obstétrical (ETP : 1804,47±521,04 nM.min ; Pic : 259,72±89,67 nM) et le groupe SAPL thrombotique (ETP : 1308,11±608,86 nM.min; Pic : 162,91±79,85 nM) comparé aux témoins (ETP : 784,91±149,69 nM.min; Pic : 82,84±17,86 nM). Chez 6 patients SAPL thrombotique sur 21, les paramètres du thrombinogramme étaient très faibles et associés à une négativation des APL dans les 2 ans.
Conclusion :
La génération de thrombine était plus basse chez les souris traitées par HCQ, ce qui confirme son intérêt vasculoprotecteur. Des taux plus faibles des paramètres du thrombinogramme sont corrélés à une négativation des APL. Une étude prospective est nécessaire pour valider l’intérêt du TGT dans le suivi de l’activité du SAPL.
... The pulmonary involvement described in SLE and APS may be similar, and include pulmonary hypertension, pulmonary embo-lism and diffuse alveolar hemorrhage [45][46][47]. In our results, the association with pulmonary involvement was driven by the presence of pulmonary hypertension. ...
Objectives
To examine the prevalence and associated factors related to the coexistence of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) in a cohort of Colombian patients with SLE, and to discuss the coexistence of APS with other autoimmune diseases (ADs).
Method
A total of 376 patients with SLE were assessed for the presence of the following: 1) confirmed APS; 2) positivity for antiphospholipid (aPL) antibodies without a prior thromboembolic nor obstetric event; and 3) SLE patients without APS nor positivity for aPL antibodies. Comparisons between groups 1 and 3 were evaluated by bivariate and multivariate analysis.
Results
Although the prevalence of aPL antibodies was 54%, APS was present in just 9.3% of SLE patients. In our series, besides cardiovascular disease (AOR 3.38, 95% CI 1.11–10.96, p = 0.035), pulmonary involvement (AOR 5.06, 95% CI 1.56–16.74, p = 0.007) and positivity for rheumatoid factor (AOR 4.68, 95%IC 1.63–14.98, p = 0.006) were factors significantly associated with APS-SLE. APS also may coexist with rheumatoid arthritis, Sjögren's syndrome, autoimmune thyroid diseases, systemic sclerosis, systemic vasculitis, dermatopolymyositis, primary biliary cirrhosis and autoimmune hepatitis.
Conclusions
APS is a systemic AD that may coexist with other ADs, the most common being SLE. Awareness of this polyautoimmunity should be addressed promptly to establish strategies for controlling modifiable risk factors in those patients.
... Concerning pulmonary hypertension, our results reaffirm the known prevalence in APS, which varies in previous studies from 1% to 15%, [28][29][30] and the fact that venous thromboembolic disease with pulmonary embolism accounts for mostly all cases. In essence, we failed to demonstrate an increased prevalence of pulmonary hypertension in our cohort of APS patients with respect to controls, probably due to an insufficient sample of patients in our cohort. ...
AIM:
Non-valvular cardiac disease in the antiphospholipid syndrome (APS) has been scanty studied. We wanted to assess the prevalence and evolution of left myocardial disease, pulmonary hypertension and intracardiac thrombi in a cohort of APS patients.
METHOD:
A total of 53 patients with APS, either primary (n = 34, 64%) or associated to lupus (n = 19, 36%) and 20 controls were included. Initial transthoracic echocardiography assessment was performed in patients at diagnosis, with echocardiography controls performed along mean follow-up of 12 years. Prevalence of myocardial disease in APS cohort was assessed taking into account primary risk factors (hemodynamically significant valvular disease, systemic hypertension, diabetes, alcoholism, myocardial infarction or myocarditis), the same as for pulmonary hypertension (severe left ventricular dysfunction or chronic lung disease).
RESULTS:
Left myocardial disease had a prevalence of 3.8% (2/53 patients), not different from controls (P = 0.12). Both patients had diastolic dysfunction grade I that maintained stability throughout echocardiographic follow-up period. Pulmonary hypertension had a prevalence of 11.3% (6/53 patients), not different from controls (P = 0.12); all cases were related to pulmonary embolism. Patients diagnosed with pulmonary hypertension in baseline maintained stable pressures throughout follow-up in the absence of new thrombosis. Intracardiac thrombi had a prevalence of 1.8% (1/53 patients), not different from controls (P = 0.4), without changes along echocardiographic follow-up.
CONCLUSION:
Pulmonary hypertension is the most prevalent non-valvular cardiac manifestation in APS, with an evolution associated with thromboembolic disease, while left myocardial disease and intracardiac thrombi would be rare manifestations in APS.
... 17 Pulmonary thromboembolism is a well-known complication of antiphospholipid syndrome. 18 In our study, 4 patients (44.4%) had PH due to thromboembolic events. Two patients with SLE with the diagnosis of CTEPH improved dramatically after pulmonary endarterectomy. ...
Pulmonary hypertension (PH) is a life-threatening complication of systemic lupus erythematosus (SLE). Pulmonary hypertension in SLE has a variety of causes. Diagnosing early and defining the cause of PH accurately can provide better clinical outcome in SLE. We investigated the causes and characteristics of PH in patients with SLE.
One hundred twenty-one patients with SLE who had a visit in a 6-month period were assessed retrospectively. Patients who ever had a systolic pulmonary arterial pressure of 40 mm Hg or greater by Doppler echocardiography were considered to have PH.
Among 122 patients, 65 had echocardiography for some reason, and 10 (8.2%) were diagnosed as having PH by echocardiographic examination. This number reduced to 9 (7.4%) when we excluded the patient with normal pulmonary artery pressure at right heart catheterization. Causes of PH were as follows: thromboembolic events in 4 patients (44.4%) (2 of them had chronic thromboembolic PH), left-sided heart disease in 2 patients (22.2%), pulmonary arterial hypertension in 1 patient (11.1%), high cardiac output state in 1 patient (11.1%), and transient elevation of systolic pulmonary artery pressure in 1 patient (11.1%) who had a history of venous thromboembolism. Venous thromboembolic disease was significantly higher in patients with SLE with PH in comparison to patients with SLE without PH (7 patients [6.3%] vs 5 patients [50.0%]; P = 0.001). All patients improved clinically during their short-term follow-up.
Patients with SLE are at increased risk for PH. This study highlights the complexity of the differential diagnosis of PH in patients with SLE once again and emphasizes the importance of pulmonary thromboembolism as a cause of PH. One should investigate patients with SLE with unexplained symptoms and/or signs related to PH for possible treatable causes.
... Podstawową cechą zespołu antyfosfolipidowego jest zakrzepica, dotycząca zarówno naczyń żylnych, jak i tętniczych wszystkich kalibrów oraz często występująca wieloogniskowo. Najczęstszą postacią zajęcia płuc u tych chorych jest zator [8][9][10][11]. Manifestację objawów klinicznych mogących występować w przebiegu APS przedstawiono w tabeli 1 [9, 3], natomiast aktualnie obowiązujące kryteria diagnostyczne APS -w tabeli 2 [12,13]. ...
... W każdym przypadku obowiązuje więc przeprowadzenie skrupulatnej diagnostyki różnicowej, w której szczególnie należy uwzględnić zapalenie naczyń z obecnością przeciwciał ANCA, gdzie DAH nierzadko bywa pierwszym objawem choroby. Z drugiej strony należy też pamiętać, że przeciwciała aPL mogą być wykrywane w surowicy chorych na zapalenie naczyń, co nie stanowi oczywiście podstaw do rozpoznania APS, ale może przyczyniać się do nasilenia objawów klinicznych [8,10]. Dlatego wykonanie chirurgicznej biopsji płuca z badaniem histologicznym jest najczęściej niezbędnym elementem diagnostyki przyczyn DAH, pozwalającym ustalić ostateczne rozpoznanie. ...
The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies and the association of protean clinical manifestations as a result of both venous and arterial thrombosis. While pulmonary embolism (secondary to deep vein thrombosis) is common and well-known disturbance in antiphospholipid syndrome, recently there are growing number of case reports describing nonthrombotic lung pathologies in APS. We present here a young male with antiphospholipid syndrome, whose the only manifestation was diffuse alveolar hemorrhage.
