Search PubMed⌕ Search

Biomedical subjects

R A Asherson

Publications and source records attributed to R A Asherson.

At least 19 recordsLinked to original sources
PubMed2006

Catastrophic antiphospholipid (Asherson's) syndrome and genetic thrombophilic disorders in obstetrics.

Catastrophic antiphospholipid syndrome (CAPS) (Asherson's Syndrome), is a life-threatening condition characterized by a rapidly progressive thromboses resulting in a multiorgan dysfunction syndrome (MODS), evidence of systemic inflammatory response syndrome (SIRS) in the presence of antiphospholipid antibodies. CAPS differs from the classic APS by predominantly affecting small vessels, involvement of unusual organs, rapid onset of MODS, and the development of acute respiratory distress syndrome (ARDS) in 25% of patients, which is a feature of SIRS. Obstetric-related multiorgan failure may be a feature of a subset of CAPS more frequently than was previously thought. Patients with obstetric complications should be tested for antiphospholipid antibodies and genetic thrombophilia in order to institute early prophylaxis. Low-molecular-weight heparin is the drug of choice for preventing obstetric complications and CAPS due to its anticoagulant and anti-inflammatory properties.

Antiphospholipid Syndrome↗
PubMed2006

The catastrophic antiphospholipid (Asherson's) syndrome and malignancies.

The catastrophic antiphospholipid syndrome is characterised by the rapid chronological development of fulminant thrombotic complications that predominantly affect small vessels. It has been reported as frequently occurring in patients with underlying malignancies. We analysed the web site-based international registry of patients with catastrophic APS. The clinical characteristics of patients with CAPS and an underlying malignancy were evaluated. Of the 262 patients included in the CAPS registry, information on associated malignancies was available in 23 (9%) cases. Haematological malignancies were present in 6 (26%) patients. Four of the patients suffered from lung carcinoma (17%), and two patients (9%) from colon carcinoma. In most of the patients (61%), malignancy was the precipitating factor for CAPS. In 4 patients (17%), however, surgical procedures related to the carcinoma were noted as precipitating factors. In one patient CAPS occurred during allogenic stem cell transplantation after diagnosis of acute lymphoblastic leukemia (ALL). Cerebral manifestations were most common and consisted mainly of cerebral infarcts and encephalopathy. Recovery occurred in 9/23 (39%) patients. Malignancy may be an important risk factor for CAPS. 9% of patients with CAPS presented with an underlying malignancy. In most of these patients, the malignancy and/or surgical procedures were the precipitating factors for CAPS.

Adolescent↗
PubMed2006

High titres of IgM-antiphospholipid antibodies are unrelated to pathogenicity in patients with non-Hodgkin's lymphoma.

Heterogeneity in the mechanisms of coagulation may contribute to an increased thrombotic risk for patients with malignancies. The coincidence of malignancies and antiphospholipid antibodies (aPL) have been described in several important epidemiological studies. The pathological significance of aPL in patients with malignancies is, however, still unclear. In this study, we investigated the clinical manifestations of four patients with elevated IgM-aPL titres lying outside the region signifying 95% of normal cases and with a history of non-Hodgkin's lymphoma. The patients had elevated IgG- and IgM-anticardiolipin antibodies (aCL) and also tested positive for lupus anticoagulants. Other aPL were measured, and we found high positive results for all tested antibodies in three patients. The production of aPL, however, occurred in the absence of thrombotic complications. No thromboembolic manifestations occurred during the follow-up period either. It could also be demonstrated that the degree to which the aCL titre was elevated resembles the elevation of the non-classical antiphospholipid antibodies, but not that of beta2-GP-1 or anti-annexin antibodies. Therefore, it can be postulated that these extremely high levels of IgM-aCL antibodies do not enhance the risk of thrombosis and may be completely different from aCL antibodies in an antiphospholipid syndrome patient population without malignancies. In particular, haematological and lymphoproliferative malignancies may indeed be associated with the generation of aPL, but do not necessarily enhance the thrombophilic risk in these patients.

Aged↗
PubMed2006

"Primary" antiphospholipid syndrome evolving into Waldenstrom's macroglobulinaemia: a case report.

A 57-year-old woman with a history of transient ischaemic attacks and six recurrent foetal losses accompanied by elevations of antiphospholipid antibodies was diagnosed as having a "primary" antiphospholipid syndrome. She was followed up for 5 years, and she developed anaemia, leucopenia and splenomegaly. A bone marrow trephine was diagnostic of Waldenstrom's macroglobulinaemia. A false positive serological test for syphilis was demonstrated and apparently had been noted in her second pregnancy more than 20 years prior to her presentation with an antiphospholipid syndrome. There had previously been no indication to perform serum electrophoretic studies. This case illustrates the importance of this investigation in any middle-aged patient presenting with an antiphospholipid syndrome and a monoclonal gammopathy This finding might presage the development of a more serious condition, even years later (as in our patient).

Antiphospholipid Syndrome↗
PubMed2005

The acute respiratory distress syndrome in catastrophic antiphospholipid syndrome: analysis of a series of 47 patients.

BACKGROUND: The acute respiratory distress syndrome (ARDS) is a non-cardiogenic form of pulmonary oedema characterised by severe hypoxaemia refractory to oxygen therapy, with diffuse pulmonary infiltrates on chest radiographs. It can be precipitated by various serious medical and surgical conditions, including systemic autoimmune diseases. The "catastrophic" variant of the antiphospholipid syndrome (APS) is an accelerated form of this systemic autoimmune condition which results in multiorgan failure because of multiple small vessel occlusions. OBJECTIVE: To analyse the clinical and laboratory characteristics of patients with catastrophic APS who develop ARDS. METHODS: Cases with ARDS were selected from the web site based international registry of patients with catastrophic APS (CAPS registry) (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) and their characteristics examined. RESULTS: Pulmonary involvement was reported in 150 of 220 patients with catastrophic APS (68%) and 47 patients (21%) were diagnosed as having ARDS. Nineteen (40%) of these patients died. Pathological studies were undertaken in 10 patients and thrombotic microangiopathy was present in seven. There were no differences in age, sex, precipitating factors, clinical manifestations, or mortality between catastrophic APS patients with and without ARDS. CONCLUSIONS: ARDS is the dominant pulmonary manifestation of catastrophic APS. Thus the existence of ARDS in the context of an APS makes it necessary to rule out the presence of the catastrophic variant of this syndrome.

Adolescent↗
PubMed2005

Validation of the preliminary criteria for the classification of catastrophic antiphospholipid syndrome.

OBJECTIVE: To describe the characteristics of patients with catastrophic antiphospholipid syndrome (APS) included in the International Registry of patients with this condition (CAPS registry) and to analyse the value of the recently proposed preliminary criteria for the classification of catastrophic APS. METHODS: A review of the first 220 patients included in the website based CAPS registry was undertaken and the preliminary criteria for their classification were tested; 175 unselected patients with systemic lupus erythematosus or APS, or both, acted as controls. RESULTS: The mean age of the patients was 38 (14) years (range 7 to 74), with a female preponderance (F/M, 153/67). The main clinical manifestations included renal involvement in 154 (70%), pulmonary in 146 (66%), cerebral in 133 (60%), cardiac in 115 (52%), and cutaneous in 104 (47%); 114 patients (52%) recovered after the catastrophic APS event (mortality 48%). Patients who received the combination of anticoagulation plus steroids plus plasma exchange or intravenous immunoglobulins had the best survival rate (63%, p = 0.09). Sufficient data could be analysed for application of the classification criteria in 176 patients. According to the preliminary criteria, 89 patients (51%) could be classified as having "definite" and 70 (40%) as having "probable" catastrophic APS, thus given a sensitivity of 90.3% with a specificity of 99.4%. Positive and negative predictive values were 99.4% and 91.1%, respectively. CONCLUSIONS: The preliminary criteria for the classification of catastrophic APS and the CAPS registry are useful tools for epidemiological studies.

Adolescent↗
PubMed2005

Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients.

BACKGROUND: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by formation of microthrombi and fibrin deposition in the microvasculature. The catastrophic antiphospholipid syndrome (APS) is characterised by multiorgan thrombosis, mainly involving small vessels. A broad spectrum of disorders may develop DIC features; however, the catastrophic APS has not previously been recognised as a cause of DIC. OBJECTIVE: To analyse the clinical and laboratory characteristics of catastrophic APS patients with DIC features. METHODS: The web site based international registry of patients with catastrophic APS (CAPS registry) (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) was analysed and the cases with DIC features selected. RESULTS: In 173 patients with catastrophic APS, 23 (13%) were found with DIC features. The clinical and immunological characteristics were similar in catastrophic APS patients with and without DIC features; a significant difference was found only in the prevalence of thrombocytopenia (100% in patients with DIC features v 59% in those without DIC features). CONCLUSIONS: DIC features are not rare in catastrophic APS, supporting the need for systematic screening of antiphospholipid antibodies in all patients with DIC features without precipitating factors. The presence of DIC features in the context of an APS makes it imperative to rule out the catastrophic variant of this syndrome.

Adolescent↗
PubMed2004

Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation.

We report on a 32-year old female patient with primary antiphospholipid syndrome (PAPS) and several thromboembolic events despite stable doses of oral anticoagulation, good patient compliance and maintained INR values of >3. Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding occurred while she was anticoagulated. The clinical features appeared to be refractory to oral anticoagulation with phenprocoumon. They were life threatening on each occasion and she developed repetitive episodes of organ damage with cardiac insufficiency (NYHA III), pulmonary hypertension and other residual defects. Even during heparinization recurrent thromboembolism supervened as well as livedo reticularis of the extremities. Lupus anticoagulants (LAC), anticardiolipin (aCL) antibodies and anti-beta(2)-glycoprotein-1 (beta(2)GPI) titers were all markedly elevated. This case report shows that recurrent episodes of thrombosis can occur despite seemingly adequate anticoagulation in patients with CAPS.

Administration, Oral↗
PubMed2004

Antiphospholipid syndrome infectious origin.

Antiphospholipid syndrome (APS) is characterized by the presence of pathogenic autoantibodies against beta 2-glycoprotein-I (beta 2GPI). The factors causing production of anti-beta 2GPI remain unidentified, but an association with infectious agents has been reported. Studies on experimental APS models proved that molecular mimicry between beta 2GPI-related synthetic peptides and structures within bacteria, viruses, tetanus toxoid, and CMV are a cause for experimental APS. Any explanation of how microbial infections might set off APS must take into account the observation that all individuals appear to harbor potentially autoreactive lymphocytes, as well as natural antiphospholipid antibodies, but that these cells or antibodies remain innocuous unless somehow activated. Herein, we discuss the association of antiphospholipid antibodies in the infectious state, molecular mimicry as a proposed cause for development of APS, and the contribution of the database to this topic.

Animals↗
PubMed2004

Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies.

OBJECTIVE: To analyse the clinical and laboratory features of patients with thrombotic microangiopathic haemolytic anaemia (TMHA) associated with antiphospholipid antibodies (aPL). METHODS: A computer assisted (PubMed) search of the literature was performed to identify all cases of TMHA associated with aPL from 1983 to December 2002. RESULTS: 46 patients (36 female) with a mean (SD) age at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%) patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical manifestation of APS in 26 (57%) patients. The clinical presentations were haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%), and HELLP (haemolysis, elevated liver enzymes, and low platelet count in association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in 86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in 89%. Steroids were the most common treatment (69% of episodes), followed by plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%), immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes treated with PE. Death occurred in 10/46 (22%) patients. CONCLUSIONS: The results emphasise the need for systematic screening for aPL in all patients with clinical and laboratory features of TMHA. The existence of TMHA in association with an APS forces one to rule out the presence of the catastrophic variant of this syndrome. PE is indicated as a first line of treatment for all patients with TMHA associated with aPL.

Adult↗
PubMed2004

Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients.

OBJECTIVE: To describe and analyse the clinical characteristics of 100 patients with antiphospholipid syndrome (APS) associated with infections. METHODS: Patients were identified by a computer assisted search (Medline) of published reports to locate all cases of APS published in English, Spanish, and French from 1983 to 2003. The bilateral Fisher exact test was used for statistics. RESULTS: 59 female and 41 male patients were identified (mean (SD) age, 32 (18) years (range 1 to 78)): 68 had primary APS, 27 had systemic lupus erythematosus, two had "lupus-like" syndrome, two had inflammatory bowel disease, and one had rheumatoid arthritis. APS presented as a catastrophic syndrome in 40% of cases. The main clinical manifestations of APS included: pulmonary involvement (39%), skin involvement (36%), and renal involvement (35%; nine with renal thrombotic microangiopathy, RTMA). The main associated infections and agents included skin infection (18%), HIV (17%), pneumonia (14%), hepatitis C (13%), and urinary tract infection (10%). Anticoagulation was used in 74%, steroids in 53%, intravenous immunoglobulins in 20%, cyclophosphamide in 12%, plasma exchange in 12%, and dialysis in 9.6%. Twenty three patients died following infections and thrombotic episodes (16 with catastrophic APS). Patients given steroids had a better prognosis (p = 0.024). The presence of RTMA and requirement for dialysis carried a worse prognosis (p = 0.001 and p = 0.035, respectively). CONCLUSIONS: Various different infections can be associated with thrombotic events in patients with APS, including the potentially lethal subset termed catastrophic APS. Aggressive treatment with anticoagulation, steroids, and appropriate antibiotic cover is necessary to improve the prognosis.

Adult↗
PubMed2003

Anticardiolipin, anti-beta(2)-glycoprotein I and antiprothrombin antibodies in black South African patients with infectious disease.

OBJECTIVES: To investigate IgG, IgM, and IgA, antiphospholipid antibodies (aPL), against cardiolipin (aCL), beta(2)-glycoprotein I (anti-beta(2)GPI), and prothrombin (anti-PT), in black South African patients with infectious disease. Unlike patients with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS), raised levels of aPL in infectious diseases are not usually associated with thrombotic complications. PATIENTS AND METHODS: Serum samples from 272 patients with a variety of infectious diseases (100 HIV positive, 112 leprosy, 25 syphilis, 25 malaria, and 10 HCV patients) were studied and compared with autoantibody levels in 100 normal controls. All three aPL were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. RESULTS: Raised levels of all three aPL were found in all patient groups studied: aCL in 7%, anti-beta(2)GPI in 6%, and aPT in 43% of 100 HIV patients, in 29%, 89%, and 21% of 112 patients with leprosy, in 8%, 8%, and 28% of 25 patients with syphilis, in 12%, 8%, and 28% of 25 patients with malaria, and in 20%, 30%, and 30% of 10 HCV patients studied, respectively. CONCLUSIONS: The prevalence of aCL and anti-beta(2)GPI in black South African HIV positive patients, or those with syphilis, malaria, or hepatitis C virus is lower than reported for mixed race or white populations. aPT were the most prevalent aPL detected in these patient groups, except in patients with leprosy, for whom anti-beta(2)GPI was the most prevalent, and where the spectrum of aPL was similar to that seen in patients with SLE and APS.

Adult↗
PubMed2003

Antiphospholipid antibodies and infections.

Many infections have been found to be associated with antiphospholipid antibodies (aPL), although a pathogenic role for these antibodies has not usually been obvious except in a few isolated cases. Two types of aPL have been referred to as "autoimmune" and "infectious" types. This distinction, however, has subsequently been found not to be absolute.

Antibodies, Antiphospholipid↗
PubMed2003

Long term outcome of catastrophic antiphospholipid syndrome survivors.

BACKGROUND: Catastrophic antiphospholipid syndrome (APS) is defined as life threatening multiple organ thromboses developing simultaneously or over a short period. The survival rate of catastrophic APS is about 50%, but the long term outcome of patients who survive is unknown. OBJECTIVE: To determine the long term outcome of patients with catastrophic APS and provide further information on patients who survived. PATIENTS AND METHODS: The clinical characteristics and outcomes of 130 patients with catastrophic APS have been reported previously. Six new cases were recently added to this series. Based on these publications, the authors who reported patients who had survived were contacted. Each author was asked (a) what treatment they gave their patients after the catastrophic APS; (b) if their patients had any further thrombosis. RESULTS: 63/136 (46%) patients died at the initial event. Of the remaining 73 patients, information was available for 58 (79%). Thirty eight (66%) patients did not develop further APS related events during an average follow up of 67.2 months. Eleven (19%) patients developed further APS related events but were still alive. No patients developed further catastrophic APS. Nine (16%) patients died: due to multiple organ failure (three patients); myelofibrosis (one); pneumonia (one); and APS related events (four). CONCLUSION: Sixty six per cent of patients who survive an initial catastrophic APS event remained symptom free with anticoagulation during an average follow up of 67.2 months. Twenty six per cent of the survivors developed further APS related events and the mortality rate of these patients was about 25%.

Adolescent↗
PubMed2003

Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines.

The term 'catastrophic' antiphospholipid syndrome (APS) is used to define an accelerated form of APS resulting in multiorgan failure. Although catastrophic APS patients represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. The careful and open discussion of several proposals by all participants in the presymposium workshop on APS consensus, held in Taormina on occasion of the 10th International Congress on aPL and chaired by Munther A Khamashta and Yehuda Shoenfeld (29 September 2002), has allowed the acceptation of a preliminary set of classification criteria. On the other hand, the optimal management of catastrophic APS must have three clear aims: to treat any precipitating factors (prompt use of antibiotics if infection is suspected, amputation for any necrotic organ, high awareness in patients with APS who undergo an operation or an invasive procedure), to prevent and to treat the ongoing thrombotic events and to suppress the excessive cytokine 'storm'. Anticoagulation (usually intravenous heparin followed by oral anticoagulants), corticosteroids, plasma exchange, intravenous gammaglobulins and, if associated with lupus flare, cyclophosphamide, are the most commonly used treatments for catastrophic APS patients.

Antiphospholipid Syndrome↗
PubMed2003

Adrenal involvement in the antiphospholipid syndrome.

Although Addison disease and hypoadrenalism are rare in patients with systemic lupus erythematosus (SLE), early reports of the association suggested the presence of antiphospholipid antibodies (aPL) in these patients. Data from literature reveal that adrenal failure was present in between 10 and 26% of patients with catastrophic APS and that one-third of patients presented with adrenal involvement during the course of catastrophic APS. Adrenal involvement may be the first clinical manifestation of this syndrome, whereas a few patients may have a history of Addison's disease in the past. The pathological mechanisms involved in the production of adrenal insufficiency in APS are still not clearly understood, but the hypercoagulable state in these patients supports the concept that adrenal haemorrhagic infarction may possibly be related to adrenal vein thrombosis. In the present article,we review the pathogenic mechanisms and main clinical, laboratory and treatment features of patients suffering adrenal involvement with aPL to support the idea that APS leads to the development of adrenal insufficiency.

Adrenal Insufficiency↗
PubMed2002

The lung in the antiphospholipid syndrome.

Patients with antiphospholipid syndrome (APS) may develop a broad spectrum of pulmonary disease. Pulmonary thromboembolism and pulmonary hypertension are the most common complications, but microvascular pulmonary thrombosis, pulmonary capillaritis, and alveolar haemorrhage have also been reported. Clinicians should seriously consider these types of vascular injury when evaluating patients with APS who present with dyspnoea, fever, and infiltrates on chest radiography.

Antiphospholipid Syndrome↗