Complement inhibitor eculizumab in thrombotic microangiopathy: Single‐center case series

Our case series showed that eculizumab is efficacious and safe in treating thrombotic microangiopathy, as well as it has positive effects on quality of life. Further extensive studies are required to develop unified treatment guidelines.     

Immunoadsorption therapy for Klinefelter syndrome with antiphospholipid syndrome in a patient: A case report

BACKGROUNDKlinefelter syndrome (KS) is a genetic disease of male sex chromosome malformations that affects sperm production and reduces testosterone production. It has been reported that there is currently more than 10 cases of KS combined with antiphospholipid syndrome.CASE SUMMARYHere, we describe a 31-year-old male patient with chromosome 47, XXY type, who suffered deep vein thrombosis of the lower limbs accompanied by abnormal antiphospholipid antibody, lupus anticoagulant and factor VIII. After treatment with immunoadsorption therapy, glucocorticoids, cyclophosphamide, intravenous immunoglobulin and anticoagulant therapy, the patient showed dramatic symptomatic improvement. During the follow-up, the patient did not develop any new thrombotic events.CONCLUSIONImmunoadsorption combined with glucocorticoid and cyclophosphamide shock comprehensive treatment has achieved significant results for patients with KS combined with antiphospholipid syndrome.     

A review of antiphospholipid antibody syndrome

PURPOSE: To review the pathophysiology, clinical presentation, and management options for antiphospholipid antibody syndrome (APS), a potentially life-threatening coagulation disorder. DATA SOURCES: Selected scientific literature, consensus guidelines, and expert opinion. CONCLUSIONS: Clinical features that should alert the clinician to consider APS include recurrent fetal loss, arterial or venous thrombosis, thrombocytopenia and livedo reticularis. One should be suspicious of this diagnosis in a younger patient, one with an autoimmune disease, or family history of autoimmune disease. To confirm the diagnosis one needs both clinical and laboratory abnormalities. IMPLICATIONS FOR PRACTICE: The signs and symptoms of APS are varied and could be confused with many disorders. The primary care provider needs to be aware of this syndrome in order to include it in the differential diagnosis and appropriately recognize and refer the patient in a timely manner.     

真性红细胞增多症并肠梗阻、抗磷脂综合征一例

静脉血栓栓塞性疾病是住院患者常见的并发症之一,具有发生率高、病死率高和住院费用增加等特点。本文报道1例67岁既往有真性红细胞增多症（PV）病史的男性,进食不当后出现腹胀、腹痛。增强CT显示小肠梗阻（SBO）、肠穿孔、阑尾炎和腹膜炎。经禁食、放置肠梗阻减压管、药物抗感染等非手术治疗后,肠梗阻症状改善且病灶局限化。但患者随后出现以左侧锁骨下静脉、颈内静脉和上肢静脉为主的血栓。笔者考虑肠梗阻导致的脓毒症和PV可能是静脉血栓形成的主要因素,给予普通肝素抗凝、羟基脲治疗PV。实验室化验血清抗心磷脂抗体、抗β2糖蛋白1抗体、狼疮抗凝物阳性。经积极的抗凝、糖皮质激素、羟氯喹和抗感染治疗,患者病情改善。出院后随访半年,患者大部分血栓消失。抗磷脂综合征（APS）和骨髓增生性肿瘤（MPN）均与血栓形成风险增加有关,但二者同时存在的报道并不多见。早期针对血栓的病因诊断及治疗对改善病程、预后至关重要。     

凝血检查在抗磷脂综合征中的应用

目的了解凝血指标与抗磷脂综合征（APS）的相关性,评价其在APS诊断与监测中的价值。方法收集疑似APS患者共155例,根据2006年最新修正的APS诊断标准判别APS患者41例,非APS患者114例,检测所有患者的D-二聚体（DD）、抗凝血酶（AT）、纤溶酶原（PLG）、血小板（PLT）计数、稀释凝血酶原时间（dPT）等凝血指标,分析其与APS的相关性。结果APS患者与非APS患者间AT、PLG、PLT水平差异无统计学意义（P〉0．05）,DD水平差异有统计学意义（P〈0．05）,狼疮抗凝物（LA）阳性的APS患者与非APS患者间dPT阳性率差异有统计学意义（P〈0．05）。结论DD水平及dPT结果与APS具有相关性,有助于临床上APS血栓形成的评价。     

Therapeutic challenges after successful thrombectomy in a patient with an antiphospholipid syndrome associated M1-occlusion: A case report

Backround

Stroke is a frequent disorder in patients with an antiphospholipid syndrome (APS). Due to a high risk for further thromboembolic events, appropriate anticoagulation therapy in patients with an APS-associated stroke seems mandatory but drug eluting and duration is a matter of debate.

Case

A 48-year-old female patient presented with Broca’s aphasia and mild hemiparesis on the right side. Diagnostic work-up revealed left middle cerebral artery (MCA) occlusion yet without diffusion-weighted lesions. Due to a thrombocytopenia (67.00 g/l) systemic thrombolysis was not indicated and endovascular treatment was initiated 150 min after symptom onset. After successful clot retrieval, recurrent re-occlusions lead to the necessity of stent implantation and anticoagulation, respectively. On day 5 she developed a new severe right-sided hemiparesis. The magnetic resonance imaging (MRI) showed a subtotal restenosis of the left MCA despite the regular anticoagulation regime leading to a new left MCA ischaemic stroke. In the meantime, the unknown aetiology, the patients’ age and the thrombocytopenia let to further diagnostic workup. Elevated blood parameters such as lupus anticoagulant (LA)-1, LA-ratio, positive anti-nuclear antibody (ANA), p-anti-neutrophil cytoplasmic antibodies (ANCA), c-ANCA confirmed the diagnosis of APS.

Conclusion

This case report showed the feasibility of mechanical clot retrieval and stent implantation in patients with APS. Due to the elevated risk of in-stent thrombosis a prolonged therapy with glycoprotein (GP)IIb/IIIa receptor antagonists in the initial postoperative period and further anticoagulation with coumarin derivate might be needed.     

Increased thromboxane formation in patients with antiphospholipid syndrome

Thirty-one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine their in vivo formation of the platelet aggregating and vasoconstricting substance thromboxane A2 (TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using gas chromatography-mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2 compared with age-matched healthy controls (807 +/- 163 [SEM] vs. 230 +/- 15 pg mg-1 creatinine, P = 0.0000005). A significant increment of the formation of PGI2 was also found (189 +/- 23 (SEM) vs. 125 +/- 11 pg mg-1 creatinine, P = 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2 formation, like aspirin.     

Plasmapheresis in ABO incompatible kidney transplant

In patients with an end-stage renal disease, dialysis a or kidney transplant are required to prolong live. For survival of the transplanted kidney, besides the HLA-system, the ABO blood type of donor and patient is also of importance. When the donor organ is derived from a living donor, time can be available prior to the transplant to reduce blood type AB antibodies in case of ABO major incompatibility between organ donor and recipient by double filtration apheresis.     

Vascular complications in the adult kidney transplant recipient.

Vascular complications of renal transplantation occurred in 15% of the cases. They are thrombotic infarct, arterial stenosis, arterio-venous fistula, and chronic arterial diseases. From 900 renal transplantations performed, only 120 (made since 1989) were studied with color flow Doppler (CFD). Lack of arterial signal is indicative of main arterial thrombosis (or of renal infarct if thrombosis is limited). At the site of arterial stenosis, high velocity and turbulence are found. If the stenosis is more than 70%, the rising systolic time is longer than 0.07 sec in the post-stenotic artery. Arterio-venous fistulas are frequent after renal biopsy. They provoke vibrations transmitted to peri-vascular tissues and seen with CFD as a large area of turbulence. In the feeding artery, Fast Fourier Transformation (FFT) showed a high velocity with a low resistive index and pulsed flow in the outgoing vein. Chronic arterial diseases include cyclosporine A intoxication and chronic rejection. These two diseases cannot be diagnosed by CFD alone.     

Ultrasound assessment of the problem kidney transplant: a surgical prospective.

Ultrasound investigation contributes to the assessment of transplanted kidneys. Ureteric obstruction and peri-transplant fluid collections are shown satisfactorily, but the differentiation of graft rejection from cyclosporin A nephrotoxicity and continuing acute tubular necrosis is less straightforward. Doppler ultrasound is used to detect changes in graft blood circulation, but the results of such assessment vary between centers, and further improvements are required to improve the accuracy of diagnosis of causes of graft impairment by noninvasive methods.     

Clinical laboratory testing for the antiphospholipid syndrome

The first aCL test was developed in 1983 and subsequently standardized. Although in the last 6 to 7 years, new and more specific tests have become available, the aCL ELISA and the LA tests are still the first choice to be used in diagnosis of APS. While there is now doubt that the anticardiolipin test is useful in the diagnosis of APS, limitations of the assay have caused uncertainty and misinterpretation of the value of the test. Utilization of validated ELISA kits with well-tested calibrators and an "in-house standard" may enable more reproducible measurements. Reporting results semiquantitatively preserves the clinical utilize of the test without the misinterpretation of a quantitative result that may lack precision. The development of newer tests such as the beta2GPI ELISA and the APhL ELISA Kit, utilizing the phospholipid mixture, give promise to a more specific and reliable diagnosis of APS, while retaining good sensitivity. Other tests such as ELISA for prothrombin antibodies and annexin V antibodies are still under development and will require standardization and extensive evaluation. The aCL test should continue to be done and included in the Sapporo criteria. The aCL test is not as specific as the anti-beta2GPI test, but it is very sensitive and together with the LA test should capture the majority of the APS patients. IgA aCL and anti-beta2GPI positivity alone is rare but occasionally found and shown to be associated with major clinical manifestations of APS. Therefore, it is now recommended to include both tests, IgA aCL and IgG, IgM and IgA anti-beta2GPI to confirm diagnosis of APS.     

系统性红斑狼疮合并抗磷脂综合征患者的临床分析

目的 研究系统性红斑狼疮合并抗磷脂综合征(SLE-APS)患者的临床特点.方法 对39例SLE-APS患者的临床和实验室资料进行回顾性分析.结果 39例患者中,有31例共发生了48次血栓栓塞事件,以深静脉血栓及脑梗死为主.26例已婚有生育史女性患者中,有12例发生病态妊娠.28例抗心磷脂抗体阳性;16例狼疮抗凝物阳性.24例患者先确诊SLE,平均9.5年后又出现APS样表现;12例先出现反复病态妊娠或血栓事件,平均4.8年后演变为SLE;3例一发病便同时符合SLE和APS的分类标准.有5例在发生血栓事件或病态妊娠时的狼疮活动指数<5分.结论 SLE-APS患者血栓事件及病态妊娠发生率增多.APS可出现于SLE之前、之后或同时.狼疮患者可以在病情稳定期出现APS的表现.详细询问病史、常规检测抗心磷脂抗体,有助于发现SLE-APS的高危因素,积极预防APS的发生.     

Plasma exchange in kidney transplantation: Still a valuable option for nephrotic syndrome recurrence

About 30% of the cases of steroid resistant nephrotic syndrome display a genetically determined disease and will not recur after kidney transplant; the other cases with fully or partially immunological pathogenesis display a high risk of post transplant recurrence.Although lots of studies were carried out in the last 50 years the pathogenetic mechanism is still obscure and the therapeutic approach mostly empirical. The cornerstones principles of the therapies are based on removal of a still undefined “permeability factor” through plasma-exchange or other apheresis techniques and inhibition of its synthesis by the immunological system through different drugs.The probability of successfully inducing persistant remission is nowadays around 30%through the different schemes experimented so far which mostly include plasmapheresis. Rituximab in the last years has significantly increased the efficacy of the treatments.Non responders are rapidly evolving to graft loss and will most probably recur also in subsequent transplant.Apart from genetics no other risk factors are predictive for recurrence.     

Apheresis in grade 4 bone marrow transplant associated thrombotic microangiopathy: A case series

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in severity from a self-limited to a fatal disorder. There has been no specific therapy for this condition. We have previously described a clinical grading system for BMT-TM, based upon lactate dehydrogenase level (LDH) and percentage fragmented cells (FC) as follows: grade 0, normal or ↑ LDH and % FC ≤ 1.2%; grade 1, normal LDH and FC ≥ 1.3%; grade 2, ↑ LDH and FC = 1.3–4.8%; grade 3, ↑ LDH and FC = 4.9–9.6%; and grade 4, ↑ LDH and FC ≥ 9.7%. Patients with grade 4 BMT-TM usually have fulminant disease and generally succumb. This study summarizes results using a variety of apheresis procedures in a series of 16 patients with grade 4 BMT-TM. The apheresis procedures consisted of plasma exchange (with replacement with fresh frozen plasma or cryo-poor plasma), and protein A immunoadsorption (PAI). The PAI exchanges were not done concurrently with plasma exchange procedures. Fifteen patients had undergone an allogeneic BMT and the 16th patient had undergone an autologous peripheral blood stem cell transplant. Half showed hematologic improvement with a downstaging of their TM to grades 1–3. All non-responders died a median of 11 days following the onset of grade 4 BMT-TM. The median survival in the responders was significantly (P = 0.001) increased to 218 days with three responders surviving more than 400 days following the onset of this severe complication. These results suggest a role for apheresis in the treatment of this lethal complication. Nevertheless grade 4 BMT-TM represents a major complication of BMT; the median survival in this group of 16 patients with grade 4 BMT-TM was only 31 days. © 1996 Wiley-Liss, Inc.     

Markers of cardiovascular risk in patients with antiphospholipid syndrome: A meta-analysis of literature studies

Abstract

Several studies reported on the association between antiphospholipid syndrome (APS) and venous thrombosis. In contrast, little is known about cardiovascular (CV) risk in APS. We performed a meta-analysis on the impact of APS on major markers of CV risk.

Studies on the relationship between APS and common carotid artery intima-media thickness (CCA-IMT), internal carotid artery IMT (ICA-IMT), carotid bifurcation IMT (BIF-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), and ankle-brachial index (ABI) were systematically searched in PubMed, Web of Science, Scopus, and EMBASE databases. Twenty case-control studies (668 cases, 678 controls) were included. Compared to controls, APS patients showed a higher CCA-IMT (mean difference [MD] 0.11 mm; 95% CI 0.07, 0.14), ICA-IMT (MD 0.08 mm; 95% CI 0.05, 0.11), BIF-IMT (MD 0.09 mm; 95% CI 0.06, 0.12) and a higher frequency of carotid plaques (OR 3.87; 95% CI 1.61, 9.31). Moreover, a lower FMD was found in APS subjects than in controls (MD –4.49%; 95% CI –6.20, –2.78), with no differences in NMD (MD –1.80%; 95% CI –4.01, 0.42). Finally, an increased prevalence of pathological ABI was found in APS patients compared to controls (OR 7.26; 95% CI 1.77, 29.71).

Despite heterogeneity among studies, APS appears significantly associated with markers of subclinical atherosclerosis and CV risk. These findings can be useful to plan adequate prevention strategies and therapeutic approaches.     

Revised classification criteria for antiphospholipid syndrome and the thrombotic risk in patients with autoimmune diseases

BACKGROUND: The classification criteria for antiphospholipid syndrome (APS) were updated in 2006. Objective: The aim of the study was to analyze associations between clinical complications and laboratory test abnormalities typical for APS in a group of patients with autoimmune diseases, based on the recently updated criteria. PATIENTS/METHODS: Three hundred and thirty-six patients were enrolled into the study, with the majority (n = 235) suffering from systemic lupus erythematosus. Laboratory determinations included: lupus anticoagulant (LA), anticardiolipin (aCL) and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies (ABs) [of both immunoglobulin G (IgG) and IgM class]. RESULTS: A significant association was found between laboratory and clinical features of APS; odds ratios (ORs) for thrombosis associated with the presence of LA, aCL, and anti-beta(2)GPI Abs were 4.04 [95% CI: 2.44-6.68], 3.71 (95% CI 2.32-5.92) and 2.57 (95% CI 1.60-4.1), respectively. Detailed analysis showed marked differences between the risk of clinical complications associated with the presence of an antibody in the IgG class (OR 4.15, 95% CI 2.42-7.12, and OR 4.77, 95% CI 2.37-9.61 for aCL and anti-beta(2)GPI, respectively) and in the IgM class (OR 2.2, 95% CI 1.31-3.70, and OR 1.9, 95% CI 1.15-3.14 for aCL and anti-beta(2)GPI, respectively). The postulated inclusion of anti-beta(2)GPI antibody positivity into the previous laboratory criteria changed only slightly the number of patients diagnosed with APS (from 112 to 117). CONCLUSIONS: The updated APS classification criteria clearly represent a step forward. However, our results argue against the use of overall positivity for aCL or anti-beta(2)GPI, and favor a clear distinction between the IgG and IgM classes of antiphospholipid ABs. Patients with both LA and anti-beta(2)GPI IgG or LA and aCL IgG positivity may represent the subgroups at the highest risk of thrombotic complications.