Catastrophic antiphospholipid antibody syndrome following initiation of hemodialysis

Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis, pregnancy morbidity, and thrombocytopenia. Some APS patients develop rapid and disseminated microthrombosis and are known as having catastrophic APS or CAPS. We document here a case of CAPS in a patient who presented with various clinical symptoms and serious abnormalities of blood coagulation following initiation of hemodialysis after bilateral nephrectomy due to renal cancer. The patient developed multiple organ symptoms, including melena, visual disturbances, skin eruptions, lymph node swelling, urinary tract bleeding, backache, arteriovenous fistula occlusion, and chest pain. Based on the clinical course and serological and histological examinations, a diagnosis of CAPS was established. The patient recovered by following intensive anticoagulation and steroid therapy. Although CAPS is rare, once symptoms develop the condition deteriorates rapidly. Because of the associated high mortality, early diagnosis and prompt treatment are necessary.     

Anesthetic implications of the catastrophic antiphospholipid syndrome

The antiphospholipid antibody syndrome (or the anticardiolipin antibody syndrome) is characterized by the presence of autoantibodies. Its major association is with systemic lupus erythematosus. 'Catastrophic' antiphospholipid syndrome (CAPS) is defined as an accelerated form of APS usually resulting in multiorgan failure and can be precipitated by surgery. We present the case of a 12-year-old male child who presented for enucleation of his left eye for fungal endopthalmitis. This patient had a history of CAPS 2 months before surgery with myocardial, gastrointestinal, renal and laryngeal involvement that improved on aggressive treatment and was subsequently managed on an outpatient basis for 2 months before presenting for enucleation. To the best of our knowledge, this is the first case of CAPS in a child reported in the anesthetic literature. Further aspects of this puzzling condition and its anesthesia implications are discussed.     

抗磷脂综合征的肾损害

目的分析抗磷脂综合征(APS)致肾损害的临床特点,旨在提高对该类疾病的认识。方法回顾性分析北京协和医院1983年至2004年期间91例APS中肾损害的临床特点及其中8例的肾组织学表现。结果原发性APS(PAPS)13例(14.3%);继发性APS(SAPS)78例(85.7%),其中系统性红斑狼疮(SLE)55例(占SAPS的70.5%)。APS伴肾损害共82例(90.1%),男性20例、女性62例;PAPS肾损害发生率为76.9%,SAPS为92.3%;发生肾损害时年龄为(38±14)岁,肾损害前病程为(4.9±6.8)年。肾损害临床表现主要为蛋白尿(92.7%)、肉眼血尿(2.4%)、镜下血尿(76.8%)、高血压(33.0%)、肾功能不全(18.3%),其中12.2%为肾病综合征。14例(15.4%)出现急性肾功能不全,病因包括血栓性微血管病、肾动脉栓塞、肾静脉血栓形成等。肾组织学检查8例,均为SLE所致PAPS,APS肾病占62.5%,表现为肾小血管、肾小球毛细血管血栓形成以及肾小叶间动脉内膜增生、洋葱皮样改变。结论APS肾损害比较常见,临床上以蛋白尿最为多见,可伴血尿、高血压,可引起血栓性微血管病、肾动脉栓塞或肾静脉血栓形成,致肾功能急剧恶化。     

系统性红斑狼疮并发继发性抗磷脂综合征肾损害11例临床病理分析

目的 分析系统性红斑狼疮（SLE）并发继发性抗磷脂综合征（APS）肾损害的临床病理表现,旨在提高对该类疾病的认识。 方法 回顾性分析北京协和医院2000年至2010年期间确诊SLE并发继发性APS（SLE伴APS）并行肾组织学检查的11例患者的资料,分析其临床病理特点,并比较其和SLE不伴APS患者在肾损害的临床病理及预后上的差异。 结果 11例SLE伴APS患者均有肾脏受累,突出表现为高血压（54.5%）、大量蛋白尿（≥3.5 g/d）（72.7%）和肾功能异常（45.5%）。SLE伴APS患者的舒张压、平均动脉压以及肾小球滤过率（eGFR）均明显高于SLE不伴APS患者（均P < 0.05）。8例（72.7%）SLE伴APS患者存在肾内血管的“血管闭塞性表现”,即符合抗磷脂综合征肾病（APSN）的病理表现,包括肾小血管、肾小球毛细血管血栓形成以及肾小动脉内膜增生、局灶性肾皮质萎缩、肾小管甲状腺样化,其中慢性APSN表现5例（45.5%）,急性APSN表现4例（36.4%）（其中1例同时有急性和慢性表现）;其APSN的发生率以及急性APSN的发生率明显高于SLE不伴APS患者（P < 0.05）。 结论 SLE并发APS肾损害患者除狼疮肾炎外,多并发APSN,临床上高血压和肾功能异常更为突出。     

Comparison of surgical methods in catastrophic antiphospholipid syndrome (CAPS)

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by vascular thromboses and/or pregnancy morbidity in the presence of antiphospholipid antibodies. The variant "catastrophic" (CAPS) is defined as a potential life-threatening disease, characterized by multiple small vessel thromboses that can lead to multiple organ failure. Surgery is between precipitating factors in CAPS International Registry, but it's still unclear the relationship between surgery and syndrome. The present study reports two surgical procedures, performed on two patients with APS admitted with diagnosis of loss of substance of the lower limb needing of reconstructive treatment. We compared and analyzed aggressive and minimally invasive surgery.     

End-stage renal disease from glomerulonephritis associated with anti-phospholipid syndrome

Primary anti-phospholipid syndrome (APS) is perceived to be an uncommon disorder, infrequently recognized as a cause of renal disease in childhood. While renal involvement in APS classically manifests as thrombotic events, other renal diseases associated with APS have been reported in adults, including membranous nephropathy and minimal change disease. We report our experience of caring for a child who presented with acute anuric renal failure due to anti-neutrophilic cytoplasmic antibody-negative rapidly progressive glomerulonephritis (RPGN), with concomitant thrombotic microangiopathy (TMA). Recognition of the APS as a cause of the patients TMA facilitated institution of anticoagulation. Our patients renal failure did not improve and the patient remained dependent on dialysis until he was successfully transplanted. The purpose of our report is to make health-care professionals aware of the previously unreported association of pauci-immune RPGN and APS in children; early recognition of APS will allow initiation of anticoagulation to prevent recurrent thromboses and enable successful transplantation.     

Case of primary antiphospholipid antibody syndrome with repeated renal biopsies

Antiphospholipid antibody syndrome (APS) is characterized by the presence of repeated arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia. Recently, renal involvement associated with APS is being increasingly recognized and discussed. In most cases, there has been a vascular nephropathy characterized by small vessel vaso-occulusive lesions associated with fibrous intimal hyperplasia of the interlobular arteries, thrombosis and focal cortical atrophy. We report a case of a 38-year-old patient with primary APS. Renal biopsies were performed three times in 26 years. Various glomerular and vascular lesions associated with APS were observed and discussed.     

Primary antiphospholipid antibody syndrome and mesangial IgA glomerulonephritis

The antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis, fetal loss, multiorgan involvement, and the presence of lupus anticoagulant and/or anticardiolipin antibody. When not associated with systemic lupus erythematosus, other collagen diseases, or ingestion of medications, the condition is called primary APS. The kidney may be involved in the APS syndrome with acute nephritis and renal failure. The cases with renal biopsy studies have shown variable glomerular morphology, ranging from mild mesangial changes to a diffuse endocapillary proliferative glomerulonephritis. The most frequent lesion is thrombotic microangiopathy or features seen in the hemolytic uremic syndrome. Apart from fibrin thrombus deposition, only a few cases have shown focal and segmental deposits of IgG and/or IgM and/or C3. We describe a patient with primary APS who had thrombosis with lower limb amputation and acute renal failure. The renal biopsy specimen showed a focal proliferative glomerulonephritis with endothelial proliferation and damage, with diffuse heavy mesangial deposits of IgA and fibrinogen. This case with diabetes mellitus, but without diabetic nephropathy, represents the occurrence of primary APS and mesangial IgA nephropathy which potentiated the renal injury, leading to acute renal failure. The relationship to the Henoch-Sch?nlein syndrome is discussed.     

Predictable removal of anticardiolipin antibody by therapeutic plasma exchange (TPE) in catastrophic antiphospholipid antibody syndrome (CAPS)

Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare life-threatening variant of antiphospholipid antibody syndrome (APS), with an associated mortality rate of > 50%. Treatment recommendations are aggressive and consist of intravenous heparin, steroids, immunoglobulins and/or therapeutic plasma exchange (TPE). At present, insufficient data exist to make precise recommendations regarding the most effective therapy for CAPS. Accumulating evidence over recent years is encouraging and may lead to future guidelines. We report predictive and effective removal of pathological anticardiolipin antibody (aCL AB) in a patient with CAPS. The case report and discussion provide valuable insight into aCL AB production and its removal by first- order kinetics using TPE.     

The antiphospholipid syndrome

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the clinical association of antiphospholipid autoantibodies (aPL) with a syndrome of hypercoagulability that can affect any blood vessel, irrespective of type or size. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or embolism, whereas involvement of smaller vessels, including capillaries, arterioles, and venules, manifests as thrombotic microangiopathy. Virtually any organ in the body, including the kidney, can be affected. Here, we review the basic principles and recent advances in our understanding of APS, and discuss the broad spectrum of renal diseases that have been observed in association with this syndrome. We also discuss the impact that APS may have on pre-existing renal disease as well as current recommendations for treatment of APS.     

"Black swan in the kidney": renal involvement in the antiphospholipid antibody syndrome

The antiphosphospholipid antibody syndrome (APS) describes a clinical entity with recurrent thrombosis, fetal loss, thrombocytopenia in the presence of lupus anticoagulant and/or antibodies to cardiolipin. These antibodies may be associated with connective tissue diseases such as systemic lupus erythematosus (secondary APS) or be found in isolation (primary APS). Renal syndromes increasingly being reported in association with these antibodies include thrombotic microangiopathy, renal vein thrombosis, renal infarction, renal artery stenosis and/or malignant hypertension, increased allograft vascular thrombosis, and reduced survival of renal allografts. Although much has been understood concerning the biology of these antibodies and the pathogenesis of thrombosis, the optimal therapy remains to be elucidated. This article presents a historical review of the renal involvement in the antiphospholipid syndrome and discusses therapeutic options. Further research is needed.     

Catastrophic antiphospholipid syndromes in systemic lupus erythematosus

The objective of this study was to look for the occurrence of catastrophic antiphospholipid syndromes (APS) and to try to detect discriminating factors for predicting a worse prognosis, related to Lupus anticoagulant (LA) and antiphospholipid antibodies (aPL), in systemic lupus erythematosus (SLE) with main renal involvement. Regression, recursive partition and logistic regression analyses were applied to our 80 SLE patients prospectively followed up since 1980. Immunologic and other laboratory parameters including beta 2-glycoprotein 1 dependence, resistance to activated protein C caused by a substitution on the coagulation factor V gene, induction of monocyte procoagulant activity. Regression studies demonstrated an overall worse prognosis in term of both thrombosis and death for the group of LA/aPL positive patients (33/80). However, recursive partition analysis was able to isolate a small high risk-subgroup (8/33) characterized by persistent LA/aPL antibodies positive result, widespread signs of noninflammatory vasculopathy (skin, brain, kidney) and renal pathology mimicking that of thrombotic microangiopathy or arteriolosclerosis, also in the absence of classic SLE-nephritis. Only in this subset, three catastrophic APS were recorded, while, in traditional SLE nephritis, even persistent LA/aPL positive results (sometimes after one previous thrombosis) did not seem to imply a particularly severe prognosis. All serologic criteria employed are unable to identify high-risk patients. We conclude that catastrophic APS is a rare event in renal SLE. Before more predictive serologic markers become available, a simple algorithm, dealing with clinical data and renal histologic patterns, may help physicians to identify putatively high risk-LA/aPL antibodies in SLE patients with main renal involvement. This ominous subset does not belong to the group of classic SLE-nephritis.     

Catastrophic antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis with the presence of circulating antiphospholipid antibodies. A diagnosis of APS requires the presence of at least one clinical and one laboratory criteria (detection of aCL IgG or IgM antibodies or the presence of lupus anticoagulant on two or more consecutive occasions 6 weeks apart). A severe, rapidly progressive form characterized by clinical involvement of at least three different organ systems with histopathological evidence of small and large vessel occlusion is termed catastrophic antiphospholipid syndrome. Early recognition of APS is crucial since aggressive management can result in a favorable outcome. We present the case of a 12-year-old boy who presented with a devastating illness with multiple thrombotic episodes and rapidly progressive renal failure.     

The intrarenal vascular lesions associated with primary antiphospholipid syndrome

Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal involvement in the course of APS is still relatively unrecognized, and is probably underestimated. The association of anticardiolipin antibodies and/or lupus anticoagulant with the development of a vaso-occlusive process involving numerous organs is now confirmed. In a multicenter study, 16 cases of "primary" APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In all 16 cases of PAPS, there was a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries (12 patients), recanalizing thrombi in arteries and arterioles (six patients), and focal cortical atrophy (10 patients). In combination, these led to progressive destruction of the kidney, accelerated by acute glomerular and arteriolar microangiopathy in five patients. Focal cortical atrophy is a distinctive lesion, present in 10 biopsies, and likely represents the histologic and functional renal analogue to the multiple cerebral infarcts detected on imaging studies. The clinical hallmark of this vascular nephropathy in PAPS is systemic hypertension, only variably associated with renal insufficiency, proteinuria, or hematuria. The ensemble of histologic renal lesions defined in this study should aid in the separation of the lesions found in cases of secondary APS, especially systemic lupus erythematosus, into those lesions related to APS and those related to the underlying disease.     

Enhanced wound‐healing performance of a phyto‐polysaccharide‐enriched dressing – a preclinical small and large animal study

Alginate is a natural rich anionic polysaccharide (APS), commonly available as calcium alginate (CAPS). It can maintain a physiologically moist microenvironment, which minimises bacterial infection and facilitates wound healing at a wound site. Patients with burn injuries suffer from pain and an inflammatory response. In this study, we evaluated the CAPS dressing and traditional dressing containing carboxymethyl cellulose (CMC) for wound healing and scar tissue formation in a burn model of rat and swine. In our pilot study of a burn rat model to evaluate inflammatory response and wound healing, we found that the monocyte chemoattractant protein (MCP)‐1 and transforming growth factor (TGF)‐β were up‐regulated in the CAPS treatment group. Next, the burn swine models tested positive for MCP‐1 in a Gram‐positive bacterial infection, and there was overproduction of TGF‐β during the burn wound healing process. Rats were monitored daily for 1 week for cytokine assay and sacrificed on day 28 post‐burn injury. The swine were monitored over 6 weeks. We further examined the pain and related factors and inflammatory cytokine expression in a rodent burns model monitored everyday for 7 days post‐burn. Our results revealed that the efficacy of the dressing containing CAPS for wound repair post‐burn was better than the CMC dressing with respect to natural wound healing and scar formation. The polysaccharide‐enriched dressing exerted an antimicrobial effect on burn wounds, regulated the inflammatory response and stimulated anti‐inflammatory cytokine release. However, one pain assessment method showed no significant difference in the reduction in levels of adenosine triphosphate in serum of rats after wound dressing in either the CAPS or CMC group. In conclusion, a polysaccharide‐enriched dressing outperformed a traditional dressing in reducing wound size, minimising hypertrophic scar formation, regulating cytokines and maximising antimicrobial effects.     

Antiphospholipid syndrome nephropathy in systemic lupus erythematosus.

In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.     

Infarction of the right hemisphere in a patient with antiphospholipid antibody syndrome

Summary Hemicraniectomy as a surgical treatment for intracranial pressure following large ischemic lesions is widely practiced in selected patients. The antiphospholipid antibody syndrome (APS), a disorder characterized by recurrent arterial and venous thrombosis, is a very rare cause of space occupying ischemic lesions. We present a case of a 35 year old female diagnosed with APS who initially presented with small ischemic lesions and within days developed a massive near-total infarction of the right hemisphere. Because of central nervous system, skin and systemic manifestations Sneddon’s syndrome and catastrophic antiphospholipid antibody syndrome (CAPS) remained a possible diagnoses. Sneddon’s syndrome is a non-inflammatory occlusive arteriopathy of small and medium size arteries predominantly of the skin and brain, whereas the catastrophic antiphospholipid antibody syndrome is characterized by acute multi-organ system thrombosis of small and large vessels. In addition to the diagnostic criteria for APS a heterozygous factor V Leiden mutation was found in this patient, which may be a contributing risk factor for cerebral ischemia. When considering invasive decompressive procedures the neurosurgeon has to be aware of the poor prognosis of some forms of APS with systemic manifestations.These authors contributed equally to this work.     

Computer-based anesthesiology paging system

For more than a century, Mayo Clinic has used various communication strategies to optimize the efficiency of physicians. Anesthesiology has used colored wooden tabs, colored lights, and, most recently, a distributed video paging system (VPS) that was near the end of its useful life. A computer-based anesthesiology paging system (CAPS) was developed to replace the VPS. The CAPS uses a hands-off paradigm with ubiquitous displays to inform the practice where personnel are needed. The system consists of a dedicated Ethernet network connecting redundant central servers, terminal servers, programmable keypads, and light-emitting diode displays. Commercially available hardware and software tools minimized development and maintenance costs. The CAPS was installed in >200 anesthetizing and support locations. Downtime for the CAPS averaged 0.144 min/day, as compared with 24.2 min/day for the VPS. During installation, neither system was available and the department used beepers for communications. With a beeper, the median response time of an anesthesiologist to a page from a beeper was 2.78 min, and with the CAPS 1.57 min; this difference was statistically significant (P = 0.021, t(67) = 2.36).We conclude that the CAPS is a reliable and efficient paging system that may contribute to the efficiency of the practice. IMPLICATIONS: Mayo Clinic installed a computer-based anesthesiology paging system (CAPS) to inform operating suite personnel when assistance is needed in procedure and recovery areas. The CAPS is more reliable than the system it replaced. Anesthesiologists arrive at a patient's bedside faster when they are paged with the CAPS than with a beeper.     

Severe Vascular Lesions and Poor Functional Outcome in Kidney Transplant Recipients with Lupus Anticoagulant Antibodies

The impact of antiphospholipid antibodies (APA) on clinical outcome and graft histology following renal transplantation remains poorly known and controversial. We retrospectively explored the functional and histological significance of APA, primarily lupus anticoagulant (LA), in kidney transplant recipients using a systematic evaluation of 3‐ and 12‐month posttransplant screening biopsies and glomerular filtration rate measurements (mGFR). During the study period, 37 patients had APA (2.7%), primarily LA, and 12 fulfiled antiphospholipid syndrome (APS) diagnostic criteria (0.8%) at the time of transplantation. Early after transplantion, 4 of the 12 APS patients died. Early thrombosis of graft vessels and deep venous thrombosis occurred more frequently in APA+ patients than in controls (27% vs. 7%, p < 0.05 and 35% vs. 14%, p < 0.05, respectively). The survival rate was significantly lower in patients with APS. Strikingly, the hallmark lesions of APS‐associated nephropathy (APSN) were found in most of screening graft biopsies in APA+ patients but not in the controls. Accordingly, APA+ patients had a dramatic increase in chronic vascular scores and a faster decline in mGFR at 1 year. In conclusion, renal transplantation may be life‐threatening in APS patients, and the presence of LA at the time of transplantation is associated with a high rate of allograft APSN and poor transplantation outcomes.     

Catastrophic antiphospholipid syndrome: report of 4 cases

Catastrophic antiphospholipid syndrome (CAPS), described by Asherson in 1992, is a rare form of antiphospholipid syndrome resulting in multiorgan failure with a mortality rate of about 50%. The syndrome occurs in patients with either systemic lupus erythematosus and other rheumatic diseases (systemic sclerosis, rheumatoid arthritis, primary Sjogren syndrome) or alone. Whereas in "classic" antiphospholipid syndrome (APS), medium-large vessels are involved, a diffuse small vessel ischemia and thrombosis (microangiopathic disease) leading to a severe multiorgan dysfunction is predominant in CAPS. "Trigger" factors have been demonstrated in 45% of patients, but in the majority, they remain unknown. Not infrequently, CAPS arises in patients without any previous thrombotic history. The kidney is the organ most commonly affected, followed by the lung, the central nervous system, the heart and the skin. Disseminated intravascular coagulation occurs in approximately 13% of patients. The present study reports the clinical and serological features of 4 patients affected by this rare form of antiphospholipid syndrome. Nephrologists should be aware of the possibility of this syndrome as a cause of multiorgan failure since prompt recognition is essential for effective treatment.