Catastrophic Antiphospholipid Syndrome

Introduction Abbreviations used in this article: aCL, anticardiolipin antibodies, ANA, antinuclear antibodies, anti-dsDNA, anti-dsDNA antibodies, aPL, antiphospholipid antibodies, APS, antiphospholipid syndrome, ARDS, acute respiratory distress syndrome, CSF, cerebrospinal fluid, CT, computed tomography, DIC, disseminated intravascular coagulation, ECG, electrocardiogram, ENA, extractable nuclear antigen antibodies, ESR, erythrocyte sedimentation rate, HPF, high power field, INR, international normalized ratio, LA, lupus anticoagulant, PT, prothrombin time, PTT, partial thromboplastin time, SLE, systemic lupus erythematosus, TTP, thrombotic thrombocytopenic purpura, WBC, white blood count The antiphospholipid syndrome (APS), originally defined as the combination of venous or arterial thrombotic events, recurrent fetal loss, and, frequently, a moderate thrombocytopenia in association with antiphospholipid antibodies (aPL), was subsequently greatly expanded to include diverse conditions, for example, heart valve lesions, adrenal insufficiency, and pulmonary syndromes such as acute respiratory distress syndrome (ARDS), “capillaritis,” and pulmonary alveolar hemorrhage, among others (16,17). It was then realized that several “microangiopathic syndromes” also existed, as opposed to large vessel occlusive disease. Single organs, such as the kidneys, heart, skin, and brain, have been affected by this “thrombotic microangiopathy” in the context of the “classic” or “simple” APS. The temporal occurrence of thrombotic events in patients with this classic APS usually extends over months or years. In 1992, the existence of a new “subset” was described in which multiple vascular occlusive events, usually affecting small vessels supplying organs and presenting over a short period of time, were the outstanding features. This subset was termed the “catastrophic” APS. Although large vessel occlusions were also present, their prevalence did not in any way approach that in patients with the classic APS. The occlusions occurred over days to several weeks, and more than 50% of patients usually succumbed despite seemingly adequate therapy, including anticoagulation, steroids, etc. (6). In 1998, a comprehensive review article with the clinical and laboratory description of 50 such patients was published (8). In the present paper we describe the clinical and serologic features of the largest series of patients with catastrophic APS hitherto reported, including 30 new cases from interested physicians in many different countries, as well as a comprehensive literature review of 50 additional recently published case reports with this syndrome. This new series, comprising a total of 80 patients, enables us to analyze further and clarify not only the clinical importance of this syndrome, but also its pathogenesis. Methods We undertook a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of catastrophic APS published in English, Spanish, and French from 1996 (when the previous comprehensive review series of catastrophic APS was completed 8) through 2000 (keywords:lupus anticoagulant, coagulation inhibitor, lupus inhibitor, anticardiolipin, cardiolipin, anticardiolipin antibody, antiphospholipid, phospholipid, antiphospholipid antibody, antiphospholipid syndrome, catastrophic antiphospholipid syndrome). We also retrospectively analyzed several original cases categorized as having catastrophic APS that were not included in the previous series. Additionally, the bibliographies of all articles were systematically scanned for references not identified in the initial search. Patients were considered as having catastrophic APS if they presented an acutely devastating APS with multiple organ involvement, as previously defined (6). Data from these patients were summarized using a standardized data form, including sex, age, diagnosis of the underlying condition, precipitating factors, main thrombotic clinical manifestations, immunologic features, treatment, and evolution. Thirty new and previously unpublished cases (14 patients from the European Union, 8 from the United States, and 8 from other countries) were added to the literature review. The bilateral Fisher exact test was used for statistics. Case Reports The most relevant data of the 80 case reports described in clinical and and case reports described in clinical of 80 patients with catastrophic clinical of patients the of catastrophic of patients with catastrophic The was a with of and systemic lupus in presented with and included antinuclear antibodies anti-dsDNA, and antibodies and lupus were not a with and an of syndrome in which to was well of a In of and small bilateral and a The was the blood and were and the anti-dsDNA antibodies were was as for a lupus was with and was The heart was and blood was was was bilateral the were and the were but The was but not were and was blood prothrombin partial thromboplastin and were all were but were were but and were a heart and were the and a with The pulmonary was of the of small a and the of but lupus and with thrombotic was was for days by was also with of were also for the all the of the arterial the and was bilateral was and was to the with the of the that the was the In was by was the with the of a which The the and were of of the of a of the with The of the small the the the was with and the the and of were and the were and with and syndrome from bilateral to over the and and with The was to with white count to with and disseminated intravascular coagulation to and as well as succumbed to The subsequently APS in a with a previous of as a lupus but the of in this syndrome to and not to Case This with presented with and been for an respiratory did not any to in acute and was white blood count was was count was was was was and was was of and a in the of the small acute the and thrombotic was with and with and to was then and was a with or with 50% and 50% and of with of as well as to of in and was the clinical was by and but only of did not any further in The was and an of and an of The were of the small acute the and respiratory catastrophic APS in a with Case was in of and for been as having with as well as valve The erythrocyte sedimentation was was but were and were were anti-dsDNA antibodies was of with was of months this was and well the of the was a in the and valve the count and blood power as well as was for was with was as was were in the was anti-dsDNA antibodies were and antibodies were was diagnosis of was and the of and with bilateral multiple pulmonary with pulmonary and pulmonary The heart was with a was diagnosis of APS the of was and the was of and the clinical The with of only were also an and The was to the a days of and precipitating for the of catastrophic APS. Case was in 1996 with and days a of The diagnosis of been in and been with In months to a was and was that time, was the a in with thrombocytopenia was and anti-dsDNA, and antibodies were The of was to and was was months was to the of bilateral in and and thrombocytopenia were was by and was vascular in the of the of a diagnosis of APS to was was 50 and was In and the was and were and was well the of the present and in and as well as in the was was a and was with a of blood was and was and an of with a of of and count of of and and were and were and with was anti-dsDNA antibodies and were was and of pulmonary In the a of pulmonary was of the with in the of the and and The of a was The heart were and of was diagnosis of to pulmonary the of with APS was and The was and to of therapy, and and In a days of and the and in the pulmonary with a The of was was by and other were in the of the the of an with partial in the and its the of the with was and pulmonary and Although of small vessels the of catastrophic APS, large vessels Case was in with and days previously the of as well as the In a diagnosis of been been with the been many to of In of and was and anti-dsDNA antibodies were was with and the of these presented with lesions, and In the diagnosis of APS in the of was of venous in the of and antibodies was with the acute and The of from 30 to 80 was and with in and were blood was with an of and of and and were and was was and anti-dsDNA antibodies were was and were were were were The multiple in diagnosis of pulmonary was but pulmonary not 80 of and and this and The from to and in and of clinical and the was to the was and the of was the to respiratory and features of in the of catastrophic APS. Case was in of in and the been for In was of acute of was with valve and valve insufficiency, heart and bilateral in the with The laboratory of and of The was not and were and was The blood was of and were and pulmonary The in the pulmonary was 30 an of with and was for and were and was anti-dsDNA antibodies were was antibodies were high were was The of was diagnosis of APS was and was of was and bilateral the which but the the diagnosis of was of and to the with and therapy, days and and of a in the of catastrophic APS and a of Case The was a with a of and APS with insufficiency, and was to but was to the venous was of the and of the a of of count of of and of and a The was for of by heart was with and was of and venous was for venous The was also to have and of of an of and of The to and was was then to have antibodies in to aCL, and a in blood and were for of to that was not to of the and were the and was with for the to and was to have and was for of and to the that and a new was was and the was with with of the was was to and an of was for and with were a to and were was to have the a and was of the was for a a in blood to new The count and was to The were which several days The and to for the of the were to but than the an acute in and that a to and was with but to to and with a blood of was with a small It was to including but new The 80 days multiple small and vessel in different of were multiple organs Although catastrophic APS also in patients with other than or APS Case 8 This was a of but was or with an of the with arterial and venous pulmonary and of the and of the was with and with and which to The cerebrospinal of were was by of and a and acute also were present the of and were and all for and including and were was for diagnosis of catastrophic APS was and the was therapy, with and In of treatment, clinical was added the of total of was over was the and by the and of occurred by the was the to and an of of was the normalized was The clinical of the was over the for the was the with of the and of the precipitating for catastrophic APS. Case The a a of of and from and presented with acute and to have a and moderate thrombocytopenia which to was respiratory occurred and a of the the with a of were with of were blood The was and were of count was ANA, anti-dsDNA, nuclear antigen antibodies and were was The was and then and was was to of the The was with and and with the with of the was of and and been with of the valve with and of blood of patients with catastrophic APS. Case The was a with a of the of in of and the was to have blood and of the and power was thrombocytopenia The was 8 and 8 The was and the of and The was anti-dsDNA antibodies were and and were The a diagnosis of was and to the was that count to and was the of and was The blood and was with a of was with thrombotic was and of a and blood were for to the was of and was then with and was was then of the with The were was and was for the the to and of were was for was for APS and by were an and was blood the was by an in to with and the other of was of of The of that to the of was with multiple were and for syndrome and a precipitating the presenting of catastrophic APS. Case of for and was in a of by pulmonary in 1996 a and was as having APS with for and as well as was with and was to a in for a a were a of a respiratory of and blood to by was was and was present over the was a The was and were the and were and of was with 50 50 a with of with a heart The was with the the were The main were and were The and were the The was not and were The a short the of the This was to to in the of clinical of of the The of the was small of was the The and features. diagnosis of to APS was and was the of was by The was over the and The was not but were venous was the not to the and were to but were with to the The was also the main was to It with The a that they were with in the Although the not with a small venous was in the of the The was in The was not well The of the main and were with previous but were The and were were and the were in was and the a main pulmonary was the of a was and a of of and blood was The a heart a large in the pulmonary and and an of in the of the was to the and was subsequently to to acute pulmonary was with by The of was considered but of high was by acute to acute or but was to have a of the of and was of through a was days and was of the was and with days of and well the precipitating of catastrophic APS. Case presented to the in was by the and was with and The was small for and the subsequently an a days a of a in been that an vessel that did not with was also to have valve the of in a of and and a and a with a anti-dsDNA antibodies a of and a of also by a and a a was in and of a small for with large of that from to by vascular The was with and for the was and to well for with and then and was subsequently with of and with of a This and an in a This an of the was was for and then and was and was The was for a months and then from for of of this also In 1998, presented with an of as an and a a and with of was but several of to the was and was but of this a of and of and an of The was and the was this acute the the only to a a of the a with multiple and multiple in the It was that the have a and a of the of the occlusive of in the with of these of was in the of the of the with been but these reports was that The to well of and and a lupus the precipitating of catastrophic APS. of the series of patients in the 80 patients were and were ratio, with from to from defined SLE, from APS, from from systemic and and than patients from and from of 80 patients with catastrophic and of APS were present in were with pulmonary recurrent fetal and previous were and arterial thrombotic syndrome, heart valve lesions, and of the precipitating of catastrophic APS that the most in more than of the patients was from respiratory to and other conditions, such as and such as in 80 patients with catastrophic most precipitating was and from a to and other association with was in of the of or to of the cases of catastrophic APS. association was with such as or the syndrome. were with or to The clinical of catastrophic APS was usually several the most the of the were and of catastrophic APS in 80 the clinical to thrombotic events the of catastrophic APS. patients catastrophic APS. total of of catastrophic APS of catastrophic was identified in of and adrenal were in of and pulmonary but involvement, and or valve lesions, but of but or venous and venous were present in and arterial occlusive by occurred in were also and of purpura, of small and lesions, and multiple were and and The laboratory of the 80 patients of this series in count than was in patients, of in of with laboratory features of and prothrombin and in and small of was blood in and immunologic features in 80 patients with catastrophic was in of the patients in which this test was The was in of patients patients presented high of of the The were in of patients usually in The anti-dsDNA antibodies were in of the patients with defined SLE, but in of the patients with other The of was in of and the 80 patients, In most patients, to the of to acute heart and was also present in several of of catastrophic APS was considered including in the patients Data were not for 80 of catastrophic APS were analyzed occurred in of and in by was the most treatment, used in of 80 in high were used in in in and in patients, a combination of the or of a treatment, occurred in of with in were not in of with in were not in of with in were not in of with in were not and in of with in were not diverse occurred in of with in were not in of with anticoagulation, steroids, and of with anticoagulation, steroids, and and of with anticoagulation, steroids, and or for of 80 of catastrophic The “catastrophic” APS was in to describe the clinical of a subset of patients with APS (6). patients of small vessels affecting multiple organs such as the heart, brain, adrenal or in of the 80 patients presented these additional several clinical example, ARDS, adrenal and from the present series. the pulmonary of catastrophic APS and in patients with APS. It a of pulmonary that from acute to the In previous been that the with by the or by with or to a of the The of such as in that a been to in and this to catastrophic APS patients with this in the of the that in the systemic syndrome which by affecting the vascular and by and in to and also of and In of systemic syndrome, antibodies also The of adrenal in catastrophic APS to as with this in patients with APS. It also more than of the venous for example, their from the The for this and to in and the have over the case in which this in patients with APS been The adrenal with of the syndrome in patients with catastrophic the diagnosis include other of a presenting in these or more than and of importance its occurrence pulmonary the of a as a further The for of adrenal and the of more adrenal also described in patients in association with as been by and patients have a of in the many which have the of APS. The of that of adrenal venous bilateral which to of the and of the arterial in adrenal been in several patients with other coagulation for example, with and and also as a of any underlying coagulation was the of cases with as opposed to than patients from the present series this a condition, most in patients with acute or and this added catastrophic APS. in the association APS and in a this the The occurrence of this days been by This a previous of recurrent and occurrence in was by in in a with a of a and high of in this with and In the literature with APS patients reported, of from catastrophic APS. It among the well of the in catastrophic APS patients for the present catastrophic APS most as opposed to patients with thrombotic thrombocytopenic this not patients in series presented the of their The described by and a presented with pulmonary and adrenal as well as features of but a further of catastrophic APS a pulmonary therapy, and also and by was a with of catastrophic APS only to months from a pulmonary the The affected the and in the not only were but also the clinical respiratory the and patients with this “catastrophic” others present with the “classic” APS. the present comprehensive review of the clinical of 80 patients we the of this APS, a to have a to in other were in such as example, serologic for have been in a of from and to and example, and of the to of the in that their to not this not not that in a the or or other the the of the the and the of the from the of the of by with or the of the fetal and to a in and in This also the of in by with and their the the of by with with and APS in this and APS by a series of additional a they identified that with the the of the antibodies and the in and of APS in the they a high of the with different and were with a of the with the the to the relevant to was from the were and the of clinical was the with antibodies from with or with to the the of clinical which APS. The that the of by and included in with of the that many diverse and in these catastrophic APS. We as in which the and the in the the of the and The of that these to the in patients with catastrophic APS. It to more with in patients with APS and to these patients also to the of the of events in catastrophic APS with by as well as other then of the including for the of as well as of the The of the to of of aPL, the of and The then the coagulation which in the of to also a for and in this also by of which in the and of of to the to which also of The also to and an and have been to The for catastrophic APS was a in the of It also that in the and a to the catastrophic of the disease. for example, a precipitating for catastrophic APS to factors, and the of also the for the association of catastrophic APS with example, such as or for to days to by recurrent and cases of catastrophic APS have been these also to its a in patients with APS for or if of the high of with coagulation The association of with the of catastrophic APS, which to a 50% the The by in the of this in the patients as with termed “thrombotic were of catastrophic APS, and, were not in the that these were also of the that the in patients with to then by the in to as and coagulation prothrombin and and a in the such as and and also The case by patients catastrophic APS that of the affected by to the and catastrophic APS. It been that large of in of patients with TTP, and these in the of to vascular a these large It been that this in patients with and that an to the for its in patients with a more of by a acute The existence of these large of not been in patients with catastrophic APS not been in of have not been In patients catastrophic APS, several or of this patients an with a and to the and then have to a of several in a to of this have been in the present review. It not that in the cases in which APS was to SLE, the of the catastrophic was to an these with an and the existence of an of also the In cases in which a precipitating not the to a or to as that to the It well in any with APS, an underlying the example, a small or only a The that with catastrophic APS and the patients included the of this The of in to in patients with and several have been in the pathogenesis. have been to in to of patients and also been that a inhibitor, which by and a blood coagulation have been to such as have been to with of have been to with and, patients have the of in this of patients, but also other The in patients with to patients have The of catastrophic APS in the present series was to that in the from 50% to these data considered an the with the of considered as to in a acute thrombotic did not in series and of catastrophic APS did not include in of in the present series in the physicians were of its in and thrombocytopenic patients, presenting with to that the with the of from from the and the present series for a of we a of in patients with in its In additional the of a of to for the (8). we that in association with anticoagulation, as a in to the in catastrophic APS and, a which catastrophic APS in patients with also of but their not to to in catastrophic APS. Additionally, and of in case of in of the of patients in to the of catastrophic APS include and of precipitating in this and We analyzed the clinical and laboratory of 80 patients with catastrophic antiphospholipid syndrome new cases and 50 from a computer-assisted review of the literature from 1996 through from defined systemic lupus from APS, from syndrome, from systemic and and of patients in this series was The most precipitating were and and of or international normalized The of the acute was usually multiple organs or in a short The of patients occlusive vascular affecting small vessels or organs, brain, heart, and a of patients large vessel was in patients, in disseminated intravascular coagulation in and in The antibodies were anticardiolipin antibodies lupus of patients with antinuclear antibodies and was used in of the in in in and in patients, a combination of occurred in of the 80 In to the of In several of respiratory was also present, usually to acute respiratory distress syndrome and alveolar occurred in of with in were not and in of with in were not other combination was with a in The and for us their patients with catastrophic antiphospholipid syndrome.