Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts

Introduction: Even though our understanding of the antiphospholipid syndrome (APS) has improved tremendously over the last decades, we are still not in a position to replace symptomatic anticoagulation by pathogenesis based causal treatments.

Areas covered: Recent years have provided further insights into pathogenetically relevant mechanisms. These include a differentiation of pathogenic subtypes of antiphospholipid antibodies (aPL), novel mechanisms modulating disease activity, for example, extracellular vesicles and microRNA, and novel players in pathogenesis, for example, neutrophils and neutrophil extracellular traps (NETs).

Expert commentary: It is evident that aPL induce a proinflammatory and procoagulant state and recent data suggest that different aPL species activate different signaling pathways which sometimes converge into a common cellular response. This implies that presence of more than one aPL species may disproportionally increase the risk for the major manifestations of APS, that is, thrombosis and fetal loss. Further delineation of the pathogenic mechanisms will hopefully provide clues to causal rather than symptomatic treatments of APS.     

Effect of Antiphospholipid Antibodies on β2Glycoprotein I-Phospholipid Interaction

PROBLEM: β₂ glycoprotein I (β₂GPI) physiologically binds to negatively charged phospholipids (PLs) and is a natural regulator of the coagulation cascade. Thrombotic clinical complications and recurrent fetal loss associated with autoimmune antiphospholipid (aPL) antibodies are thought to be related to their binding to β₂GPI-PL complex and interference with the physiological function of β₂GPI. METHOD OF STUDY: To investigate the effect of aPL on β₂GPI-PL interaction, we studied the binding of biotinylated β₂GPI to cardiolipin (CL) by enzyme-linked immunosorbent assay (ELISA) in the presence and absence of purified aPL immunoglobulin G (IgG) antibodies. RESULTS: Adding five different aPL IgG antibodies with different levels of aPL activity isolated from the sera of five patients with aPL-associated recurrent fetal death greatly increased the binding of biotinylated β₂GPI to CL-coated plates. The optical densities (ODs) were 0.635, 0.890, and 1.265 in the presence of three aPL IgG antibodies, compared to 0.425 in the absence of aPL IgG. In contrast, normal human IgG had no enhancing effect. The OD was 0.480 and 0.425, respectively. The enhancement of β₂GPI binding to CL by aPL IgG correlated with the titers of aPL antibodies. The use of phosphate-buffered saline with increasing salt concentrations as a washing buffer for the ELISA resulted in more stable binding of β₂GPI to PL in the presence of aPL IgG. CONCLUSIONS: These findings suggest that the binding of autoimmune aPL antibodies to β₂GPI-PL complex results in abnormally tighter interaction between β₂GPI and PLs, which may lead to physiological dysfunction of β₂GPI as a regulator of coagulation.     

Interpretation of venous occlusion plethysmography using a nonlinear model

Venous occlusion plethysmography (VOP) is a noninvasive technique widely employed for the detection of deep-vein thrombosis. Previous reports that VOP outflow curves are closely fit by a first-order exponential suggest that venous compliance and resistance are nearly constant. Typically, however, the venous compliance function has a sigmoid shape; in addition, the resistance in a collapsing tube must increase. This paradox was resolved by the surprising finding that for realistic nonlinear compliance and resistance these nonlinearities cancel, producing a quasilinear venous outflow that approximates a simple exponential.     

人TFPI基因转染对兔移植静脉血栓形成和近期通畅率的影响

目的： 为减少冠状动脉旁路移植术后血栓形成，探讨人组织因子途径抑制因子(TFPI)基因转染对兔移植静脉血栓生成的影响。方法：构建真核表达质粒pCMV-(Kozak)TFPI。采用阳离子脂质体和腔内加压灌注法，转染移植静脉内皮细胞。RT-PCR、Western blotting和免疫组化法检测外源基因在兔移植静脉中的表达。病理标本、扫描电镜观察移植静脉血栓形成情况，血管多普勒观测其通畅率。结果：移植静脉中有人TFPI基因和蛋白表达。静脉移植术后3 d，基因转染组、空载体和空白对照组分别有1条、8条和7条移植静脉发生血栓，术后30 d，以上各组分别有0条、5条和5条移植静脉完全闭塞，前者静脉血栓发生率和闭塞率均低于后两者(P<0.05)。扫描电镜显示两对照组内皮表面有红细胞和血小板黏附、聚集，而转染组基本正常。结论：人TFPI基因干预，减少了兔移植静脉血栓形成，提高了近期通畅率。     

Three novel PROC gene lesions causing protein C deficiency

Hallam PJ, Mannucci P, Tripodi A, Bevan D, Laursen B, Tengborn L, Wacey A, Cooper DN. Three novel PROC gene lesions causing protein C deficiency. Clin Genet 1998: 54: 231–233. 0 Munksgaard, 1998
Missense mutations. three of them novel (Am210→Val, Asn248→ Ile, Ah355→Val), were found in the protein c ( PROC ) genes of 7 patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX causing hdernophilia B and the use of molecular modelling has provided explanations as to how these lesions might alter either the structure, function or secretion of the protein C molecules encoded.     

Portomesenteric vein thrombosis following sleeve gastrectomy: Case report focusing on the role of pathogenetic factors

IntroductionSleeve gastrectomy has currently become the most commonly performed bariatric. procedure worldwide according to the last IFSO survey, overtaking gastric bypass with. a share of more than 50% of all primary bariatric-metabolic surgery. Gastric leak, intraluminal bleeding, bleeding from the staple-line and strictures are the most common complications. Portomesenteric vein thrombosis (PMVT)after sleeve gastrectomy is. another complication that has been increasingly reported in case-series in recent.years, although it remains uncommon. In this case report is described an extended portomesenteric vein thrombosis after. sleeve gastrectomy interesting splenic vein too with a favorable course and an. uneventful follow-up. We try to search in this case for pathogenetic factors involved in. this complication.Case reportA 42-year old man, with a body mass index (BMI) of 45 kg/m2, with a medical history of Obstructive Sleep Apnea Sindrome (OSAS) underwent laparoscopic sleeve gastrectomy. Early postoperative course was uneventful. Six days after discharge he complained abdominal pain and was admitted at the Emergency Department. A CT scan with intravenous contrast showed an occlusion of the portal vein, of the intrahepatic major branches and an extension to the superior mesenteric vein and the splenic vein. The patient received heparin and oral anticoagulation together with intravenous hydration and proton pump inhibitors. Considering the favourable course the patient was discharged after six days with long-term oral anticoagulation therapy. Anticoagulation with acenocumarol was continued for six months after a CT scan showed resolution of the PMVT without cavernoma. He had no recurrence of symptoms.DiscussionPorto-mesenteric thrombosis after sleeve gastrectomy is a rare complication but it has been increasingly reported over the last 10 years along with the extensive use of sleeve gastrectomy. Because PMVT is closely associated with sleeve gastrectomy in comparison with other bariatric procedures, we need to investigate what pathogenetic factors are involved in sleeve gastrectomy. Thrombophylic state, prolonged duration of surgery, high levels of pneumoperitoneum, thermal injury of the gastroepiploic vessels during greater curvature dissection, high intragastric pressure, inadequate antithrombotic prophylaxis and delayed mobilization of the patient after surgery have been reported as pathogenetic factors of portmesenteric vein thrombosis. Most of the cases presented in the literature such as our clinical case resolve with medical therapy, although portal vein thrombus extends into the superior mesenteric vein and the splenic vein.ConclusionPortomesenteric venous thrombosis is a rare but serious complication of bariatric surgery, especially associated with sleeve gastrectomy. Diagnosis is based on CT examination with intravenous contrast, and initial therapy is anticoagulation. Etiologic factors reported in the literature include a long duration of surgery, a high degree of pneumoperitoneum, high intragastric pressure after sleeve gastrectomy and thermal injury to the short gastric vessels and gastroepiploic arcade. Limited operative time, controlled values of pneumoperitoneum, careful dissection with energy device of gastric greater curvature, appropriate prophylaxis with low molecular weight heparin may be useful tools to prevent and limit this complication. Nonetheless we have to search which factors may condition the evolution of an extended PMVT as that described in this case towards resolution or to a further worsening clinical state. Early diagnosis? Correct treatment? Undiscovered patientrelated factors?     

下腔静脉滤过器的临床应用(附29例分析)

目的 :评价置入下腔静脉滤过器预防静脉血栓脱落引起肺栓塞的效果和安全性。方法 :2 9例下肢深静脉血栓患者均经股静脉置入下腔静脉滤过器于下腔静脉内 ,术后立即摄腹部平片及血管造影 ,观察滤器位置、形态及血流情况 ,并积极进行局部溶栓治疗。结果 :全部滤过器均成功放置 ,在随后的溶栓、抗凝、祛聚、扩血管等治疗中 ,患肢肿胀和肺栓塞症状消失或明显减轻。随访 1个月～ 4 3个月 ,仅 1例出现滤过器移位。结论 :置入下腔静脉滤过器是预防肺栓塞安全有效的方法。     

螺旋CT动态扫描对肝癌大血管侵犯的对比研究

目的 :进一步认识肝癌大血管侵犯的螺旋CT表现特征。方法 :75例肝癌伴大血管侵犯的病例中 ,2 6例前瞻性设计了动脉期同层面扫描加全肝门静脉期扫描的程序 ,选择兼顾病变及门静脉的靶平面 ,并与 31例双期扫描和 18例单纯门静脉期扫描的病例作对照。结果 :动脉期同层面扫描在动 静脉瘘和门静脉早显方面优于双期扫描 ,动脉期对显示大血管侵犯征象有特征性 ,癌栓在动脉期总强化率为 66 67% ( 38/ 5 7例 ) ,单纯门静脉期扫描不能显示动 静脉瘘和癌栓新生血管。结论 :动脉期同层面扫描能显示肿瘤和大血管侵犯引起的血流动力学异常 ,有助于定性和发现动 静脉瘘     

脑血栓形成患者急性期和恢复期血小板α颗粒膜蛋白-140的变化

目的研究血小板α颗粒膜蛋白－１４０（ＧＭＰ－１４０）在脑血栓形成患者急性期和恢复期的变化。方法测定５０例 （其中３０例急性期患者,２０例恢复期患者）脑血栓形成患者血浆ＧＭＰ－１４０的含量,并分别与２６名健康人作比较。结果 脑血栓形成患者急性期ＧＭＰ－１４０浓度明显高于恢复期和正常对照组（Ｐ＜０．０１）,恢复期与正常对照组间比较差异无显 著性（Ｐ＞０．０５）。结论脑血栓形成患者急性期血浆ＧＭＰ－１４０含量处于较高水平。