Retinal migraine,chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome

Summary We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome.     

Antiphospholipid antibodies and thrombosis: do test patterns identify the patients' risk?

We retrospectively analyzed the antiphospholipid profile of 103 lupus anticoagulant-positive patients to investigate whether laboratory patterns emerged for their association with arterial and venous thrombosis in the antiphospholipid syndrome. Anticardiolipin, anti-2-glycoprotein I and antiprothrombin antibodies were combined with coagulation tests in different patterns, which included from 2 to 5 laboratory variables. Overall, 22 out of 180 available associations reached significance: 14 with any type of thrombosis and eight with venous thrombosis. In all but two cases, anticardiolipin antibodies>40 units were present in the laboratory patterns that reached significance. Anti-2-glycoprotein I antibodies were present in 11 significant patterns, and antiprothrombin antibodies in seven cases. Increasing the number of variables of the laboratory patterns did not increase the odds ratio (OR) towards thrombosis.

In conclusion, this analysis confirmed that the presence of IgG anticardiolipin antibodies at medium to high titres, either alone or in various combinations with other tests, is clinically useful to establish the patients' risk of thrombosis. The role of the other antiphospholipid antibodies is less clear.     

Atypical onset of antiphospholipid syndrome in pregnancy: a case report

BACKGROUND: We present a case of an atypical onset of antiphospholipid syndrome (APS). CASE: A woman in her 15th week gestation had a thrombosis of an unknown cerebral cavernoma, which was successfully removed. Twenty-six days after, she was admitted for a severe pain in right hypochondrium and a second class HELLP syndrome was diagnosed. Two days after, she had a fetal loss. After 1 month, laboratory tests revealed high level of antiphospholipid antibodies. At the same time, she developed a spontaneous thrombosis at her right arm. After 6 weeks, antiphospholipid antibodies, tested again, result positive. CONCLUSION: Antiphospholipid antibodies often cause pregnancy complications, but, to our knowledge, this is the first report of an association of antiphospholipid antibodies, with cerebral cavernoma thrombosis and early onset HELLP syndrome.     

Risk factors for arterial thrombosis in antiphospholipid syndrome

Introduction

Antiphospholipid syndrome (APS) is associated with the risk of both arterial and venous thrombosis. However, it is not known which factors might determine the location of thrombosis.

Materials and Methods

To retrospectively characterize factors associated with the risk of arterial thrombosis in a cohort of APS patients. Analysis included laboratory and clinical criteria of APS, together with classical cardiovascular risk factors and the possible role of platelet integrin α₂β₁ (807 C/T) and α_IIbβ₃ (PI A1/2) genetic polymorphisms. We enrolled 163 APS patients (123 women and 40 men aged 21-75; mean age 43 years); 78 suffered from arterial thrombosis.

Results

There were no significant differences in the frequency or titers of different antiphospholipid antibodies with the exception of slightly increased frequency of IgG anticardiolipin antibodies (ACL) in the arterial thrombosis group. Livedo reticularis was observed significantly more often in the arterial thrombosis group, particularly in stroke patients.In univariate analysis arterial thrombosis was associated with male gender (OR-2,201; p = 0,033), arterial hypertension (OR-2,81; p = 0,002) and hypercholesterolemia (OR-3,69; p = 0,001). On multivariate analysis arterial hypertension (OR = 1,78; p = 0,008) and hypercholesterolemia (OR = 2,001; p = 0,002) remained as independent risk factors for arterial thrombosis. Platelet glycoprotein polymorphisms studied did not show any significant associations with arterial thrombosis in APS patients.

Conclusions

Among APS patients those with ACL IgG antibodies, having livedo reticularis, and suffering from hypertension an hypercholesterolemia are at the increased risk of arterial thrombosis.     

Bithalamic infarcts: embolism of the top of basilar artery or deep cerebral venous thrombosis?

Bithalamic infarcts are usually attributed to thromboembolism of the top of the basilar artery. However, in some cases, deep cerebral venous thrombosis and thrombosis of cerebral venous sinuses was proved to be the cause. The case of a 47-year-old female with ischemic thalamic and mesencephalic lesions is reported, that was attributed to thrombosis of internal cerebral veins. In cases of bithalamic infarcts, apart from the top of the basilar artery syndrome, deep cerebral venous thrombosis should be taken into consideration. Neuroimaging findings such as generalized cerebral edema, multiple infarcts or hemorrhages, hyperdense appearance of cerebral sinuses or veins and filling defects in the cerebral venous sinuses in contrast-CCT, can lead to the proper diagnosis.     

Plasma Microparticle Tissue Factor Activity in Patients With Antiphospholipid Antibodies With and Without Clinical Complications

Antiphospholipid syndrome (APS) is defined by the association of autoantibodies to certain phospholipid-binding proteins with arterial or venous thrombosis (‘AT’ or ‘VT’, respectively), and/or pregnancy-related morbidity (PM). Antiphospholipid antibodies (aPLA) promote activation of several cell types including monocytes, resulting in procoagulant tissue factor (TF) expression that may contribute to the vascular complications. Since TF synthesis by monocytes is frequently accompanied by release of TF-bearing microparticles, we hypothesized that plasma microparticle TF activity (MP-TF) may be elevated in APS patients and contribute to thrombosis and/or PM. Platelet-poor plasma specimens were obtained from 30 patients with definite APS and 72 patients with asymptomatic aPLA from the Antiphospholipid Syndrome Collaborative Registry (APSCORE). MP-TF was measured by an in-house factor Xa generation assay. The two groups were well matched for gender, age, ethnicity, proportions with underlying SLE, and aPLA profiles. MP-TF (median and (IQR)) in asymptomatic aPLA subjects was 0.09 pg/mL (0.05-0.14) compared to 0.13 pg/mL (0.10-0.17) in APS (p < 0.001). No differences in MP-TF levels were observed between APS subjects with PM, thrombosis, or PM + thrombosis. Similarly, among subjects with either APS or asymptomatic aPLA, MP-TF did not differ in the presence or absence of underlying SLE. Prospective studies will be required to determine if plasma MP-TF activity is causally related to thrombotic or gestational complications in APS.     

Dural sinus thrombosis: a mechanism-based classification and review of 42 cases

Cranial venous outflow obstruction due to dural sinus thrombosis may result in venous hypertension, cerebral infarction, cerebral haemorrhage or impaired cerebrospinal fluid (CSF) absorption with consequent pseudotumour syndrome. We propose a mechanism based classification of dural sinus thrombosis from these four outcomes. Forty two cases of dural sinus thrombosis presenting to Royal Prince Alfred Hospital between 1986-1997 were retrospectively reviewed. These cases were classified according to mechanism of presentation and relevance of this to site of thrombosis, treatment and prognosis. This study shows that the superior sagittal sinus and transverse sinus are the commonest sites of thrombosis, and multiple sites of thrombosis (69%) are more frequent than a single site. Magnetic resonance imaging (MRI) with venous flow studies is the investigation of first choice for diagnosis but angiography remains the gold standard. A pseudotumour syndrome is the commonest presentation (43%) followed by cerebral haemorrhage (31%). The overall prognosis for sinus thrombosis is good, with 71% of cases recovering to normal function.     

Platelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies

BACKGROUND: Anti-phospholipid antibodies (APLA) are often associated with thrombosis, defining the antiphospholipid syndrome (APS) but it remains unclear why many subjects who are positive for APLA chiefly anti-cardiolipin (aCL) or anti-beta2GPI (abeta2GPI) do not develop thrombosis. A related question addressed in this study is whether the target of cellular injury in APS is predominately platelets or endothelial cells (EC). METHODS: aCL and abeta2GPI were determined by ELISA in 88 patients, 60 of whom were thrombotic and 28 non-thrombotic. Platelet activation was measured by CD62P and by concentration of platelet microparticles (PMP) and EC activation was assessed by endothelial microparticles (EMP), both by flow cytometry. Lupus anticoagulant (LAC) was measured in the hospital laboratory. RESULTS: There was no difference in frequency of aCL or abeta2GPI, neither IgG or IgM, between the thrombotic and non-thrombotic groups. Both groups showed elevated EMP compared to controls but this did not differ between thrombotic and non-thrombotic groups. In contrast, PMP were not significantly elevated in non-thrombotic but were elevated in thrombotic compared to non-thrombotic (p=0.03) and controls. CD62P, an independent marker of platelet activation, was also elevated in thrombotic vs. non-thrombotic. There was a trend for increased LAC in the thrombotic group but not significant. CONCLUSION: Although all subjects had evidence of endothelial activation, only platelet activation differed between thrombotic and non-thrombotic. This supports the hypothesis that platelet activation predisposes to thrombosis in the presence of chronic EC activation. These data also raise the possibility of distinguishing risk-prone APLA-positive individuals.     

Plasma haemostatic potential of haemodialysis patients assessed by thrombin generation assay: Hypercoagulability in patients with vascular access thrombosis

Introduction

Patients with end-stage renal disease (ESRD) on maintenance haemodialysis are predisposed to bleeding and thrombotic events. Recently thrombin generation assay (TGA) has been introduced as a laboratory assessment of global haemostatic potential. We investigated the global haemostatic potential assessed by TGA in ESRD patients on haemodialysis and patients who developed vascular access thrombosis.

Materials and Methods

A total of 69 ESRD patients who underwent haemodialysis (58 stable patients and 11 vascular access thrombosis patients) were included and 33 healthy controls were included. TGA was performed on the calibrated automated thrombogram using tissue factor with/without addition of thrombomodulin or activated protein C, producing three parameters including lag time, endogenous thrombin potential (ETP) and peak thrombin.

Results

Haemodialysis patients showed low ETP values measured by thrombin generation assay compared with the healthy controls. Interestingly, patients with vascular access thrombosis exhibited short PT and aPTT and increased resistance of coagulation inhibition to APC anticoagulant protein, reflecting hyper-coagulability. Haemodialysis patients who are taking anti-platelet agents showed decreased thrombin inhibition rate, representing antithrombotic effect of anti-platelet agents.

Conclusion

Whereas the haemodialysis patients showed hypo-coagulability, the patients with vascular access thrombosis exhibited hyper-coagulability. Further study is required to investigate how this haemostatic potential may be utilized to guide the physician to more effective management of haemostatic complication.     

From antibody to clinical phenotype,the black box of the antiphospholipid syndrome: Pathogenic mechanisms of the antiphospholipid syndrome

The antiphospholipid syndrome (APS) is diagnosed by the combination of vascular thrombosis and/or pregnancy morbidity and the detection of antiphospholipid antibodies (aPLs) in plasma. In the last few years, a great effort has been made to unravel the mechanism by which aPLs cause thrombosis and a vast amount of mechanisms have been proposed. aPLs were proposed to induce a prothrombotic state by influencing the cellular blood compartment, the plasma compartment, the vascular wall and even metabolic pathways beyond the hemostatic system. However, due to the diversity in the mechanisms and the differences in the methodology, the focus of the mechanistical studies in this field seems to be largely diffused. It is hard to imagine that aPLs can exert such a diversity of effects, resulting in either thrombosis and/or pregnancy morbidity and the relationship between aPLs and the clinical manifestations remains to be a mysterious “black box”. In an attempt to get insight in what takes place inside the black box, we have analyzed 126 mechanistical studies on aPLs and discussed differences in the type of antibodies that were used, the involvement of beta2-glycoprotein I (β₂GPI), and the criteria used to diagnose APS patients.     

颈动脉支架置入术后支架内血栓形成研究进展

颈动脉支架内血栓形成是颈动脉支架置入术后的严重并发症，可导致患者严重瘫痪甚至 死亡。然而迄今为止，针对颈动脉支架内血栓形成，仍没有统一的治疗方式。虽然有很多病例报道了 颈动脉支架内血栓形成的处理方法，但是仍缺少随机双盲试验或大型临床试验来证实其可靠性、安 全性。在临床上，与手术操作相关的颈动脉支架内血栓形成，是颈动脉支架内血栓形成的最主要原 因。除此之外，抗血小板治疗不充分或停止抗血小板治疗、高凝状态、抗血小板药物抵抗也可导致 颈动脉支架内血栓形成。目前，抗血小板及抗凝治疗、溶栓治疗、颈动脉内膜剥脱术及颈动脉支架 术、机械取栓或血栓抽吸治疗等均有报道，无论何种治疗方式，使患者快速获得血管再通是颈动脉 支架内血栓形成治疗的关键。     

血小板糖蛋白HPA-1和HPA-2基因多态性与脑血栓形成的相关性研究

目的探讨血小板糖蛋白人类血小板同种异型抗原系统-1(HPA-1)和HPA-2基因多态性与脑血栓形成的相关性。方法收集脑血栓形成患者108例及无神经系统疾病的日常查体者166例,应用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)检测HPA-1、HPA-2多态性在两组中的分布频率。结果血小板糖蛋白基因HPA-1、HPA-2多态性在脑血栓组和对照组中的基因型频率和等位基因频率分布差异无统计学意义。结论血小板糖蛋白基因HPA-1、HPA-2多态性与脑血栓形成无相关性。     

硬脑膜静脉窦血栓形成的血管内介入治疗

目的 探讨硬脑膜静脉窦血栓形成(DVST)的血管内介入治疗。方法 11例由CT、MRI、DSA确诊的硬脑膜静脉窦血栓形成患者经皮股动、静脉穿刺给予介入治疗；围手术期规范抗凝、抗血小板聚集等综合治疗。结果 2例患者临床症状戏剧性改善，10例患者临床症状消失或好转，1例无变化；术后影像学均有不同程度的改善；1例机械辅助溶栓患者介入治疗时发生导丝断裂；1例机械辅助溶栓后置人支架未成功；术中、术后无其它相关并发症发生。出院时临床痊愈5例，显效3例，好转2例，无效1例。随访9例患者3～6月无复发。结论 多种介入方法联合治疗DVST的方法是可行的且安全有效。是值得在临床推广的治疗DVST的方法，其远期效果尚需观察。     

Antithrombotic activity of a polydeoxyribonucleotidic substance extracted from mammalian organs: A possible link with prostacyclin

The antithrombotic activity of Fraction P (FP), a polydeoxyribonucleotide extracted from mammalian organs, was studied in different models of experimental thrombosis. FP displays a remarkable protec ting activity against thrombosis induced by collagen (venous thrombosis), electrical stimulation (arterial thrombosis) and iontophoretic application of ADP (venular thrombosis). The activity of FP is long lasting and evident either by oral administration or intra venous injection.The antithrombotic activity of FP is partly due to its already reported fibrinolytic effect, but also other mechanisms which involve vascular reactivity and platelet function may come into play. The ability of FP to promote generation and release in the circulation of a deaggregating substance and to increase prostacyclin-like activity from incubated aortic tissue is discussed in order to explain the mode of action of FP in preventing thrombosis formation.     

Failure of aspirin at different doses to modify experimental thrombosis in rats

Aspirin inhibits the synthesis of both platelet and vascular arachidonic acid metabolites which have opposite effects on platelet function. The rationale for its clinical use as an antithrombotic drug has therefore been questioned. Previous studies in rats indicated that platelets are more sensitive to aspirin than arterial tissues and are almost as sensitive as venous tissues. We have now assessed the effects of aspirin at various doses on an arterial and a venous model of experimentally-induced thrombosis. Aspirin at high doses (50–200 mg/kg b.w.) neither reduced nor potentiated the thrombosis tendency in either model. Lower doses (2.5–10 mg/kg b.w.) — which preferentially inhibited platelet prostaglandin formation — did not protect the animals against thrombosis. It is possible, on one hand, that the metabolic pathways of arachidonic acid which are blocked by aspirin do not play a crucial role in the models used. One the other hand, the difficulty to completely dissociate the inhibitory effects of aspirin on platelet and vascular prostaglandins could be crucial for the antithrombotic activity of this drug. The concept that, when administered in large doses, aspirin — by inhibiting vascular prostacyclin activity — potentiates experimental thrombosis, is not supported by the present study.     

Uncommon cause of sinus thrombosis following closed mild head injury in a child

Object Sinus thrombosis following a closed mild head injury is rare. A case of dural sinus thrombosis following a mild closed head injury due to an uncommon cause is reported.Methods A 7-year-old child presented with GCS 15 after a road traffic accident. CT revealed an occipital fracture. Ten days later the child developed signs of increased intracranial pressure. An MR venogram at this time revealed thrombosis of the transverse sinus with hypoplasia of the contralateral transverse and sigmoid sinuses. The patients anitiphospholipid antibody titres were elevated. The patient was treated with anticoagulants and improved.Conclusions The role of inherited and acquired procoagulant factors in the aetiology of sinus thrombosis is increasingly being recognized. When a patient presents with sinus thrombosis after a closed mild head injury, it is necessary to investigate for the presence of risk factors for thrombophilia as it has implications for the long-term management of the patient.     

低颅压综合征合并颅内静脉血栓2例并文献回顾分析

目的总结分析低颅压综合征(SIH)合并颅内静脉血栓形成(CVT)的临床表现,诊断和治疗方法。方法报道2例低颅压综合征合并颅内静脉血栓形成,并回顾文献报道15例同类病例,分析其临床特征、影像学表现、治疗和病理生理机制。结果17例患者均以亚急性起病,其中14例患者表现为体位性头痛。常见的伴随症状有恶心、呕吐、复视、耳鸣等。所有患者的影像学检查都存在SIH和CVT的表现,头部核磁共振(MRI)加静脉成像(MRV)是诊断颅内静脉血栓形成的主要手段。结论低颅压综合征是颅内静脉血栓形成的危险因素之一,了解两者内在的病理生理联系和临床特征有利于对该病的早期诊断和及时治疗。     

产褥期颅内静脉系统血栓形成临床分析

目的 探讨产褥期颅内静脉血栓形成的发病机制、临床表现及治疗对策。方法 回顾性分析2000年1月～2011年12月收治的46例产后颅内静脉血栓形成患者的临床资料,并进行归纳总结。结果 产后颅内静脉血栓形成患者以高颅内压及局灶性脑损伤为主要临床表现,经低分子肝素抗凝及对症治疗,患者症状均有改善。结论 对于存在静脉血栓形成风险的产褥期女性,应尽快完成相关检查,早诊断、早治疗,以期改善患者预后。     

Neurosurgical management for complicated catastrophic antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune condition involving arterial and venous thrombosis. An unusual APS variant, catastrophic antiphospholipid syndrome (CAPS), includes rapid multi-organ failure from widespread small vessel thrombosis. Central nervous system complications arise in one-third of CAPS patients. In rare cases, CAPS co-manifests with cerebellar hemorrhage presenting a neurosurgical emergency. We present a 65-year-old woman with CAPS-related cerebellar hematoma, co-morbid idiopathic thrombocytopenic purpura, deep vein thrombosis and altered mental status, with treatment complicated by thrombocytopenia. The patient suddenly deteriorated, secondary to a cerebellar subdural hematoma, and underwent decompression and excision of the hematoma. After recovery in the intensive care unit, she developed a new spontaneous epidural hematoma requiring additional surgery. Management of these patients is hematologically complex and often requires a multi-disciplinary team of physicians. This patient provides an important learning point for clinicians – consider CAPS when hemorrhage and thrombosis are present.     

颅内静脉系统血栓形成的临床和影像学分析

目的探讨颅内静脉系统血栓形成的临床和影像学表现以及治疗和预后,为该病的临床诊断和治疗提供依据。方法选取我院就诊的颅内静脉和静脉窦血栓形成患者71例,收集人口学资料、临床症状和体征、影像学表现、生化等实验室检查、病因,以及治疗方案和预后,并进行统计学分析。结果 71例患者中,常见的临床表现为颅高压症状(头痛、恶心、呕吐)、癫痫、视物模糊或视力下降等。D-二聚体升高67例(94.4%)。横窦血栓形成34例(47.9%),乙状窦血栓形成25例(35.2%),上矢状窦血栓形成44例(62.0%),深部脑静脉血栓形成(直窦或Galen静脉)9例(12.7%),同时累及2个或以上静脉窦者52例(73.2%)。结论 CVST的临床表现缺乏特异性,临床上对于头部CT未见明显异常的不明原因的头痛患者、产褥期或口服避孕药或合并自身免疫性疾病的女性头痛患者,需考虑CVST可能性,并积极行影像学检查,早期识别,早期诊断。