Catastrophic antiphospholipid syndrome (CAPS) is a very severe variant of the classic APS, characterised by clinical evidence of multiple organ involvement developing over a very short period of time, histopathological evidence of multiple small vessel occlusions and laboratory confirmation of the presence of antiphospholipid antibodies (aPL), usually in high titre. Although patients with catastrophic APS represent less than 1% of all patients with APS, this is usually a life-threatening condition.
In this article, we aimed to review the state-of-the art about current knowledge in pathogenesis, clinical manifestations, diagnosis and treatment strategies in CAPS.
Introduction
Catastrophic antiphospholipid syndrome (CAPS) was first described by Asherson in 1992 . It characterised by multiple vascular occlusive events, presenting over a short period of time, in patients with antiphospholipid antibodies (aPL) positive. It is an uncommon presentation that occurs in <1% of APS patients, often after a triggering factor such as anticoagulation withdrawal, surgery, minor surgical procedures or infections. Mortality rate is around 50% and treatment includes corticosteroids, anticoagulation, intravenous immunoglobulin (IVIG) and plasma exchange .
Pathogenesis
The aetiopathogenesis of catastrophic APS remains incompletely understood. Several mechanisms have been proposed such as molecular mimicry, infections and activation of endothelium in the microvasculature and microvascular occlusions . Kitchens et al. have suggested that the vascular occlusions are themselves responsible for the ongoing thrombosis. Clots continue to generate thrombin, fibrinolysis is impaired by an increase in plasminogen activator inhibitor type-1 (PAI-1), and there is consumption of the natural anticoagulant proteins such as protein C and antithrombin. These multiple small vessel occlusions cause extensive tissue necrosis which results in a systemic inflammatory response syndrome (SIRS), with excessive cytokine release from affected and necrotic tissues . Proinflammatory cytokines, several products of the activated complement system (e.g., C3b, iC3b and C5a) and aPL themselves have each been demonstrated to activate endothelial cells, provide a stimulatory signal and up-regulate adhesion molecules and tissue factor. These molecules can also act on leukocytes and platelets to increase their adhesion to vascular endothelium and to promote microthrombosis and the local release of toxic mediators, including proteases and oxygen-derived free radicals. The interaction between all these cells in the presence of aPL leads to the diffuse microvasculopathy that characterises CAPS and leads to multi-organ failure .
Pathogenesis
The aetiopathogenesis of catastrophic APS remains incompletely understood. Several mechanisms have been proposed such as molecular mimicry, infections and activation of endothelium in the microvasculature and microvascular occlusions . Kitchens et al. have suggested that the vascular occlusions are themselves responsible for the ongoing thrombosis. Clots continue to generate thrombin, fibrinolysis is impaired by an increase in plasminogen activator inhibitor type-1 (PAI-1), and there is consumption of the natural anticoagulant proteins such as protein C and antithrombin. These multiple small vessel occlusions cause extensive tissue necrosis which results in a systemic inflammatory response syndrome (SIRS), with excessive cytokine release from affected and necrotic tissues . Proinflammatory cytokines, several products of the activated complement system (e.g., C3b, iC3b and C5a) and aPL themselves have each been demonstrated to activate endothelial cells, provide a stimulatory signal and up-regulate adhesion molecules and tissue factor. These molecules can also act on leukocytes and platelets to increase their adhesion to vascular endothelium and to promote microthrombosis and the local release of toxic mediators, including proteases and oxygen-derived free radicals. The interaction between all these cells in the presence of aPL leads to the diffuse microvasculopathy that characterises CAPS and leads to multi-organ failure .
Clinical manifestations
The most common known trigger for CAPS is infection. Other less common causes are anticoagulation withdrawal or low international normalised ratio (INR), medications (e.g., oral contraceptive), obstetric complications, neoplasia, systemic lupus erythematosus (SLE) flares, trauma and surgery. Nevertheless, in almost half of the cases, no obvious precipitating factors have been identified and CAPS can often occur in patients without any previous thrombotic history .
The clinical manifestations of CAPS depend on the organs that are affected, by the thrombotic events and the extent of the thrombosis, together with manifestations of the SIRS.
In contrast to classic APS, single venous or arterial medium to large blood vessel occlusions are uncommon in patients with catastrophic APS. Multiple organ dysfunction and failure, as a consequence of thrombotic microangiopathy, are responsible for the majority of the clinical features; however, large venous or arterial thrombosis can also occur in about one-fifth of patients. In a review of 280 patients with CAPS from the website-based international CAPS registry, Cervera et al. reported that the first clinical manifestation at the time of the catastrophic episode was a pulmonary complication in 24% of the cases, a neurologic feature in 18% and a renal feature in 18%. Although the initial presentation of CAPS may involve a single organ, in a very short period of time, typically days to weeks, patients develop clinical evidence of multiple organ thrombosis and dysfunction leading to organ failure that requires intensive care unit (ICU) admission. In the same cohort of CAPS patients during the catastrophic episode, intra-abdominal involvement was identified in the majority of patients, mainly consisting of renal (71%), hepatic (33%), gastrointestinal (25%), splenic (19%), adrenal (13%) and pancreatic (8%) manifestations. Intrathoracic involvement was also common and included pulmonary complications (64%), mainly acute respiratory distress syndrome (ARDS) and pulmonary embolism, but occasionally intra-alveolar haemorrhage, as well as cardiac manifestations (51%), mainly cardiac failure and myocardial infarction or valve lesions. Cerebrovascular complications were also frequently present (62%), mainly consisting of encephalopathy and cerebrovascular accidents, but occasionally seizures, headache or silent brain infarcts. Skin manifestations were also frequent (50%) with livedo reticularis, leg ulcers, necrotic lesions, digital gangrene, purpura, splinter haemorrhages and multiple ecchymosis. Deep venous thrombosis (23%) and peripheral arterial occlusive disease (11%) were less frequently detected. Other lesions occasionally encountered were retinal involvement (7%), mononeuritis multiplex (5%) and bone marrow necrosis (4%) .
APS-related laboratory findings
The most common APS-related laboratory findings are thrombocytopaenia, haemolytic anaemia (often accompanied of schistocytes as in thrombotic microangiopathic haemolytic anaemia) and disseminated intravascular coagulation (DIC). The presence of aPL, namely anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2GPI) and lupus anticoagulant (LA) is mandatory for the diagnosis. aPL are usually detected in high titre in CAPS patients. The role of other aPL, such as anti-phosphatidylserine/prothrombin or anti-prothrombin in solid phase has been reported , but its role is still controversial.
Diagnosis
The diagnosis of CAPS can be challenging because of the acute onset of thrombosis at multiple levels with simultaneous dysfunction of different organs. The survival of the patients very much depends on an early diagnosis and treatment.
Preliminary CAPS classification criteria ( Table 1 ) was proposed and agreed in Taormina, (Sicily) during the 10th International Congress on aPL. Although these criteria are accepted for classification purposes, they might be a guide to a more consistent approach to the diagnosis . An update of the diagnostic algorithm for CAPS was recently proposed and discussed in ‘Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations’ developed on the occasion of the 13th International Congress on Antiphospholipid, held in Galveston (Texas) in 2011 . This approach represents a step forward in diagnosis of CAPS but it needs to be validated versus other thrombotic microangiopathy.
|
|
|
|
| Definite CAPS |
|
| Probable CAPS |
|
|
|
|
Related posts:
A variety of diseases with a common trunk
IgG4-related diseases
Biological treatment in adult-onset Still’s disease
Nephrogenic systemic fibrosis: A systemic fibrosing disease resulting from gadolinium exposure
Multicentric reticulohistiocytosis and fibroblastic rheumatism
Autoinflammatory syndromes and cellular responses to stress: pathophysiology, diagnosis and new treatment perspectives
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
