胰岛素抵抗对急性心肌梗死患者经皮冠状动脉介入治疗前后血管内皮功能、凝血功能及心肌组织灌注的影响

目的:探讨胰岛素抵抗对急性心肌梗死患者经皮冠状动脉介入治疗(PCI)术后血浆内皮素,血管性血友病因子、血小板膜糖蛋白Ⅱ b/Ⅲa受体水平及心肌组织灌注的影响.方法:根据稳态模式评估法的胰岛素指数(HOMA-IR)将128例急性心肌梗死患者分为两组,HOMA-IR≥5为胰岛素抵抗组72例,HOMA-IR＜5为非胰岛素抵抗组56例.所有入选病例均于发病后24 h内行PCI,并于术中行心肌灌注分级评价心肌微循环灌注情况,分别于PCI术前、术后即刻、30 min、4 h、12 h、24 h、48 h,72 h、7 d取外周静脉血,编码血浆标本,在-80℃条件下保存,分批检测血浆内皮素、血管性血友病因子及血小板膜糖蛋白Ⅱb/Ⅲa受体.并连续观察PCI术前、后血浆内皮素、血管性血友病因子、血小板膜糖蛋白Ⅱb/Ⅲa受体变化.结果:两组患者血浆血管性血友病因子水平、血小板膜糖蛋白Ⅱb/Ⅲa受体水平、内皮素水平变化:胰岛素抵抗组各时间点较非胰岛素抵抗组均明显升高,差异均有统计学意义(P均＜0.05).心肌梗死溶栓治疗临床试验(TIMI)3级的比率变化:128例患者均行PCI治疗开通梗死相关动脉,依据TIMI分级标准,造影显示术后两组患者TIMI 3级的比率差异无统计学意义(P＞0.05).TIMI心肌灌注分级(TMPG)分析显示:非胰岛素抵抗组56例患者中有53例(94.6%)心肌组织灌注良好,可达TMPG 2～3级,胰岛素抵抗组72例患者中有53例(73.6%)心肌组织灌注良好,可达TMPG 2～3级.两组比较差异有统计学意义(P＜0.05).结论:胰岛素抵抗会影响急性心肌梗死患者PCI术后血管内皮功能、凝血功能及心肌组织灌注.     

妊娠期高血压综合征血栓前状态、凝血功能变化及其临床意义

目的探讨妊娠期高血压综合征血栓前状态、凝血功能变化及其临床意义。方法选取湖北省洪湖市人民医院产科2016年10月—2017年10月收治的妊娠期高血压患者100例(PIH组),另选择同期体检正常妊娠妇女100例作为对照组,分别抽取两组患者静脉血,用免疫比浊法检测两组患者血浆凝血功能指标:凝血指标凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)含量,以及采用免疫吸附试验检测血栓前状态指标:血管性假性血友病因子(VWF)、血小板P选择素(GMP-140)、凝血酶-抗凝血酶复合物(TAT)、D-二聚体(D-D)含量。结果 PIH组PT、APTT、TT均显著低于对照组,Fib、VWF、GMP-140、TAT及D-D显著高于对照组(P0.05)。结论妊娠期高血压综合征患者存在高凝状态及血栓前状态,血栓形成风险较高。     

切割球囊血管成形术对不稳定性心绞痛患者血管性假血友病因子、白细胞介素-6和C-反应蛋白的影响

目的 :比较切割球囊血管成形术与普通球囊血管成形术对不稳定性心绞痛患者血浆血管性假血友病因子 (vWF)和血清白细胞介素 6(IL 6)、C 反应蛋白 (CRP)浓度的影响。方法 :选择 65例拟行冠状动脉 (冠脉 )介入治疗的不稳定性心绞痛患者 ,随机分为两组 ,分别接受切割球囊血管成形术 (切割球囊组 )或普通球囊血管成形术 (普通球囊组 ) ,球囊扩张后均放置支架。分别于术前、术后即刻、术后 2h和 6h抽取冠状静脉窦血样测定血浆血管性假血友病因子和血清IL 6的浓度 ;另于术前、术后 6h、术后 2 4h和 48h抽取肘静脉血样 ,测定血清CRP的浓度。以上指标均以酶联免疫吸附法进行测量。结果 :普通球囊组血浆血管性假血友病因子浓度术后即刻和术后 2h ;血清IL 6浓度术后即刻 ,术后 2h和 6h以及血清CRP浓度术后 6h、2 4h和 48h都明显高于切割球囊组 ,有显著性差异 (P均 <0 0 5～ 0 0 1)。结论 :单纯切割球囊血管成形术对不稳定性心绞痛患者血浆血管性假血友病因子、血清IL 6和CRP浓度的影响均小于单纯普通球囊血管成形术 ,联合支架置入术后有相似结果 ,这可能是前者通过减轻对炎症反应的影响 ,减少再狭窄及心血管事件发生的机制之一。     

尼可地尔对择期行PCI术冠心病患者心肌和血管内皮的保护作用

目的探讨尼可地尔对择期行PCI术的冠心病患者心肌的保护作用及机制。方法选取心内科行择期PCI术的冠心病患者57例随机分为治疗组和对照组,治疗组术前24~72 h给予5~10 mg/次,3次/d的尼可地尔口服,观察两组患者术前、术后12 h、24 h和48 h的超敏C反应蛋白(hs-CRP)、超敏肌钙蛋白T(hs-Tn T)和血管性血友病因子(v WF)表达水平,检测患者术后24 h外周血的CD4凋亡和CD4+Foxp3+的水平,同时对PCI术后24 h患者hs-CRP、hs-Tn T和v WF水平进行相关性分析。结果对照组和治疗组患者PCI术后的hs-CRP和hs-Tn T水平明显高于术前(P0.05),且治疗组的hs-CRP和hs-Tn T水平较对照组有明显的下降(P0.01),PCI术后24 h的v WF水平明显高于术前,且尼可地尔能够减显著降低v WF水平(P0.05);PCI术后24 h hs-Tn T与hs-CRP呈正相关;对照组的CD4+Foxp3+比例明显低于治疗组,而CD4凋亡比例明显高于治疗组(P0.05)。结论择期行PCI术患者术前短期口服尼可地尔能够诱导机体产生具有抑炎作用的CD4+Foxp3+,从而减少PCI术引起的心肌损伤。     

冠心病介入术后氧自由基的生成及其对脂质过氧化和纤溶的影响

目的:探讨冠心病介入治疗术后氧自由基的生成及其对患者体内脂质过氧化和纤溶状况的影响。方法:48例接受经皮冠脉介入治疗(PCI)术的冠心病患者分别于术前,术后即刻、30 min、1 h、24 h和一周采用ELISA法测定血浆中丙二醛、D-二聚体、血管假性血友病因子相关抗原(vWF Ag)浓度。结果:PCI术后短时间内(0～24 h)血浆中丙二醛、D-二聚体,vWFAg水平均明显升高(P<0．05)。结论:PCI术后短时间内即有大量的氧自由基生成,凝血系统的激活和继发性纤溶功能亢进。     

急性冠脉综合征冠状动脉内血栓形成与相关标志物研究进展

冠状动脉内血栓形成是急性冠脉综合征(ACS)的主要特征,并贯穿冠心病及ACS发病过程中,与冠状动脉狭窄程度无直接相关性。冠状动脉血栓标志物主要包括前纤维蛋白、死亡诱导终结因子1、P-选择素、可溶性CD40配体、凝血酶-抗凝血酶复合物。该文主要介绍ACS冠状动脉内血栓形成与相关标志物研究进展。     

肺血栓栓塞患者溶栓治疗前后血管内皮及凝血分子标志物的变化

血管内皮或凝血激活的分子标志物变化对早期诊断和观察血栓形成具有更敏感更特异的意义。临床上常见的肺血栓栓塞（PTE）主要的治疗方法是溶栓治疗。我们对PTE患者在不同溶栓治疗方法过程中血栓调节蛋白（TM）、血管性血友病因子（vWF）、凝血酶．抗凝血酶复合物（TAT）、组织因子（TF）的含量进行定量检测，探讨这些分子标志物在PTE溶栓治疗过程中的变化及意义。     

急性心肌梗死患者直接介入治疗后无再流与血浆组织因子及其途径抑制物的关系

目的 通过测定急性心肌梗死(AMI)患者直接经皮冠状动脉介入治疗(PCI)前后血浆组织因子(TF)、组织因子途径抑制物(TFPI)水平的变化,探讨TF、TFPI与无再流的关系.方法 选择2006年5月至2007年5月于我院急诊行PCI的AMI患者53例,用ELISA法检测患者PCI术前、术后即刻、术后24 h外周静脉血 TF、TFPI水平.比较其中无再流者与再灌流者不同时点TF、TFPI水平的变化.结果 PCI术前、术后即刻、术后24 h无再流组血浆TF、TFPI水平均明显高于再灌流组[TF(275.3±46.2)ng/L比(236.8±44.3)ng/L、(332.7±41.3) ng/L 比(282.3±38.7) ng/L、(315.5±47.8) ng/L 比(248.1±46.9) ng/L;TFPI(165.2±38.4) μg/L 比(128.5±18.7) μg/L、(176.3±36.8)μg/L 比(135.6±20.3) μg/L、(149.8±31.7) μg/L 比(118.7±19.2) μg/L;均P＜0.01];PCI术后即刻,丽组TF水平均较术前明显升高(P＜0.01);PCI术后24 h,无再流组TF水平仍高于术前水平(P＜0.05),再灌流组与术前比较无差异(P＞0.05);PCI前后两组TFPI水平均无明显变化(P＞0.05).结论 AMI患者直接PCI后无再流的发生与血浆,TF水平呈正相关,TF可激活外源性凝血途径,形成微血栓而导致无再流,而TFPI可阻止血栓形成而防治无再流的发生.     

超敏C-反应蛋白与冠心病患者PCI术后支架内血栓形成的相关性

目的研究冠心病患者接受PCI术后出现支架内血栓形成及血清超敏C-反应蛋白水平变化。方法回顾分析实施PCI术后再次入院行冠脉造影复查支架情况的57例患者的临床资料。所有拟行复查的患者均详细询问病史,进行详细的体格检查,并于手术前空腹抽取静脉血,测定超敏C-反应蛋白(hs-CRP)。应用冠状动脉造影的方法测量支架内血栓形成的发生率。结果 57例冠心病支架植入患者6~24个月后复查造影,11例(19.3%)出现支架内血栓形成;46例无支架内血栓形成。术后血栓形成组与无血栓形成组相比,术前PCI患者hs-CRP水平差别无统计学差异(P>0.05),但术后2~7 d、3个月、6个月,血栓形成组hs-CRP水平显著高于无血栓形成组(P<0.001),△hs-CRP(术前及术后6个月hs-CRP的差值)血栓形成组显著低于无血栓形成组(P<0.001)。结论 PCI术后血清hs-CRP增高并可能参与支架术后血栓形成的病理过程,监测患者术前及术后血清hs-CRP水平的变化,可能更好地预测PCI术后的支架内血栓形成的发生。     

老年原发性高血压患者血压变异性与血栓前状态关系的研究

目的探讨老年原发性高血压患者血压变异性与血栓前状态的关系及其临床意义。方法随机选择年龄≥60岁的老年高血压患者110例(高血压组)和老年健康体检者105例(对照组),以动态血压监测仪监测2组24 h血压变化,检测血浆血管性假血友病因子、纤维蛋白原和D-二聚体等血栓前状态指标的水平,并进行分析。结果高血压组昼间、夜间和24 h收缩压变异程度显著高于对照组(P<0.01),血浆血管性假血友病因子、纤维蛋白原和D-二聚体水平均明显高于对照组(P<0.01)。高血压组和对照组24 h收缩压变异程度与血管性假血友病因子均呈显著正相关(r=0.685,0.603,P<0.05)。结论老年原发性高血压患者血压变异性增高,并伴有明显的血管性假血友病因子、纤维蛋白原和D-二聚体水平升高,提示其存在内皮功能损害的可能,血压波动增大可能是内皮功能损害的危险因素。     

凝血功能指标、血栓前状态与子痫前期发病的关系

目的探究凝血功能指标、血栓前状态与子痫前期发病的关系。方法收集2016年3月至2018年8月黄石市中心医院收治的87例子痫前期患者为研究对象,其中轻度子痫前期组41例,重度子痫前期组46例。另同期选择于我院进行体检的40例正常妊娠晚期孕妇设为正常组。所有研究对象均于入院后抽取清晨空腹静脉血,检测活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、凝血酶时间(thrombin time,TT)、凝血酶原时间(prothrombin time,PT)及纤维蛋白原(fibrinogen,FIB)等凝血功能指标,以及D-二聚体(D-dimer,D-D)、凝血酶-抗凝血酶复合物(thrombin-antithrombin complex,TAT)、血小板颗粒膜蛋白-140(granule membrane protein-140,GMP-140)和血管性假性血友病因子(von Willebrand factor,VWF)等血栓前状态指标的浓度。结果随着子痫前期病情的进展,APTT、TT、PT均呈逐渐降低的趋势,正常组>轻度子痫前期组>重度子痫前期组,差异有统计学意义(P<0.05);D-D、TAT、GMP-140和VWF浓度均呈逐渐升高的趋势,正常组<轻度子痫前期组<重度子痫前期组,差异有统计学意义(P<0.05);而3组间的FIB浓度比较,差异无统计学意义(P>0.05)。结论子痫前期患者呈高凝、血栓前状态,并且随着病情严重程度的增加,凝血功能及血栓前状态相关指标的变化也更加明显。     

Effect of bivalirudin on coagulation function and prognosis in patients with coronary artery disease and renal insufficiency undergoing PCI

Background Renal insufficiency is associated with an excess risk of vascular complications and bleeding events in patients who undergo PCI. Heparin is still used commonly for PCI, but the bleeding complications is high. However, Bivalirudin is similar to heparin in ischemic complications and superior to the bleeding complications. Methods A total of 181 patients with coronary artery disease and renal insufficiency were randomly assigned two treatment groups: Bivalirudin(n = 90), unfractionated heparin(n = 91). Activated clotting time(ACT)was determined in patients at 5 min after undergoing PCI at the end of operation immediately(stopping drug immediately), and 30 min,1 h, 2 h after stopping drug. Activated partial thromboplastin time(APTT), thrombin time(TT), proth rombin time(PT), fibrinogen(FIB) index were measured before treatment, 6 h, 24 h and 72 h after the treatment through an automated coagulation analyzer. Platelet count was monitored before treatment and24 h after treatment. The end points were the proportion of net adverse clinical events(NACE)and stent thrombosis at 30 days. Results The use of bivalirudin was associated with a statistically significant higher at 5 min after treatment, end of operation immediately(P 0.05),with statistically significant lower at 1h after stopping drug, 2h after stopping drug(P 0.05). There were no differences between patients at blood coagulation and platelet after operation(P 0.05), no differences in the 30-day rates of stent thrombosis(0% vs. 0%, P = 1). Eleven patients(12.22%) treated with bivalirudin vs. 24(26.38%) treated with heparin experienced an adverse clinical events at 30 days(relative risk[RR], 0.46; 95%CI, 0.36-0.56; P 0.025). There were no differences in the major adverse cardiac or cerebral event at the 30-day end point(1.11% vs. 2.20%, P 0.05). The bleeding at 30 days was abated by using bivalirudin compared with unfractionated heparin(11.11% vs. 24.18%, P 0.05). Conclusions Compared with the unfractionated heparin, bivalirudin is more quickly in taking effect and recovering and more efficient for PCI in patients with coronary artery disease and renal insufficiency.     

Surgical revascularisation in patients with severe limb ischaemia induces a pro-thrombotic state

Platelet and coagulation activation are implicated in the increased incidence of ischaemic events seen in patients with peripheral arterial disease. This study aimed to assess the effect of surgical revascularisation on platelet aggregation and coagulation in patients with severe limb ischaemia (SLI). Twenty-two patients had blood samples taken: prior to surgery, on reperfusion, 2, 24 and 48 h post-surgery. Platelet aggregation through COX-mediated and thrombin receptor activator peptide (TRAP)-stimulated GPIIb/IIIa pathways was measured by the Ultegra point of care system. Thrombin-antithrombin III Complex (TAT) and D-dimer were measured by ELISA. COX-mediated aggregation increased significantly at reperfusion and remained elevated at 24 h [median increase from baseline of 9% (range -16 to 33%) P = 0.011]. TRAP-stimulated aggregation increased significantly at reperfusion and remained elevated at 2 h post-surgery [median increase 18% (range -71 to 45%); P = 0.007]. TAT levels were significantly elevated from reperfusion and remained so at 48 h (P < 0.003), whereas D-dimer only increased at 24 h (P = 0.014). For the first time, we have demonstrated that in patients with SLI, platelet aggregation is increased following surgery and there is a mismatch in the balance between the coagulation and fibrinolytic pathways despite the use of aspirin and heparin. Thus in the early post-operative these patients exhibit a pro-thrombotic state.     

Significance of hemostatic molecular markers during disseminated intravascular coagulation in patients with liver cirrhosis treated by endoscopic embolization for esophageal varices.

We studied the quantitative changes of hemostatic molecular markers with time during the course of disseminated intravascular coagulation (DIC) induced by endoscopic embolization using thrombin for esophageal varices in nine patients with liver cirrhosis. The plasma levels of D-dimer, a product of plasmin degradation of cross-linked fibrin, and thrombin-antithrombin-III complex (TAT) were significantly higher in patients before treatment when compared with 60 healthy individuals. The plasma levels of TAT, D-dimer, and plasmin alpha 2-plasmin inhibitor complex (PIC) increased significantly 5-15 min after thrombin injection into the varices, earlier than the changes of conventional coagulofibrinolytic factors, reached a maximum level after 180 min, and started to decline after 1 day. Although the plasma PIC level returned to normal after 7 days, both TAT and D-dimer were still above the pretreatment level. Although there was no change in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) increased significantly after 5 min. The plasma level of plasminogen activator inhibitor type 1 (PAI-1) showed only a slight elevation after treatment. We propose that the hemostatic molecular markers TAT, D-dimer, and PIC are suitable for the early diagnosis of DIC after endoscopic embolization using thrombin in patients with liver cirrhosis and that the increase of PAI-1 is too small for the regulation of fibrinolysis due to t-PA in DIC occurring in liver cirrhosis.     

Short-term isocapnic hypoxia and coagulation activation in patients with sleep apnea

Hemostatic changes might contribute to the increased risk of cardiovascular and cerebrovascular events in patients with obstructive sleep apnea (OSA). We investigated the effect of a short-term isocapnic hypoxic challenge on coagulation activation markers thrombin/antithrombin III complexes (TAT) and D-dimer in OSA. Thirty-two OSA patients (mean age 48 +/- 11 years) inhaled a gas mixture containing 10% O(2) and 90% N(2) and further adjusted to yield pulse oximetry saturation of 80-85% for 5 minutes. Plasma levels of TAT and D-dimer were measured immediately before and immediately after the hypoxic challenge. The hypoxic challenge provoked a significant increase in TAT (p < 0.001) and in D-dimer (p = 0.037). Mean nocturnal oxygen saturation from the sleep recordings correlated with D-dimer increase (r = -0.37, p = 0.041). Also, OSA patients with a history of hypertensive parents had greater D-dimer increase in response to hypoxia than patients having normotensive parents (p = 0.035). Parental hypertension independently explained 15% of the variance in D-dimer increase after hypoxia (p = 0.035). Oxygen desaturation during sleep may predispose OSA patients, in particular those with a parental history of hypertension, to a hypercoagulable state providing one explanation for the increased risk of atherothrombotic events in this population.     

比伐芦定对女性PCI患者凝血功能及安全性的影响

目的 探讨比伐芦定对女性拟行经皮冠状动脉介入(PCI)治疗的冠心病患者的凝血功能及安全性的影响。方法 将71例女性拟行PCI的冠心病患者随机分为普通肝素组（n=39）和比伐芦定组（n=32）。分别于PCI术前、用药后5 min、术后即刻、停药后0.5、1和2 h测定激活凝血时间（ACT）。用药前、用药结束后6、24和72 h分别测定凝血酶时间（TT）、活化部分凝血酶时间（APTT）、凝血酶原时间（PT）、纤维蛋白原（Fib）。分别在用药前、用药后24 h测定血小板计数(PLT)。30 d内主要不良心脑血管事件（MACCE）、术后出血并发症以及支架血栓事件。结果 比伐芦定用药后5 min、术后即刻ACT值显著大于肝素组（P<0.01）;停药后30 min和术前,两组患者ACT差异无统计学意义;停药后1 h、2 h ACT比伐芦定组小于普通肝素组（P<0.01）。两组术后凝血4项及PLT,比较均无统计学意义。两组患者随访30 d,MACCE及支架内血栓发生率差异无统计学意义,术后30 d出血总发生率及美国出血学术研究联合会(BARC) Ⅱ-Ⅴ型出血发生率差异有统计学意义（P<0.05）。结论 与普通肝素相比,比伐芦定对女性行PCI的冠心病患者抗凝治疗中起效更快,半衰期短,更安全有效。     

Hemostatic effects of antithrombin III supplementation during cardiac surgery: results of a prospective randomized investigation.

Failure to suppress thrombin generation during cardiac surgery promotes fibrin generation, fibrinolysis, and a consumptive coagulopathy. Acquired deficiencies of antithrombin III may play a contributory role. We hypothesized that antithrombin III supplementation to normal physiologic concentrations would decrease thrombin generation and potentially reduce peri-operative bleeding. Twenty patients undergoing coronary artery bypass graft surgery were randomized for this prospective, double-blind, placebo-controlled study. Ten patients received antithrombin III supplementation (50 U/kg) by intravenous infusion prior to incision, and 10 patients received a placebo. Blood samples were obtained pre-operatively, at 1 and 2 h following initiation of cardiopulmonary bypass (CPB), and at 1, 3, and 24 h after completion of CPB. Samples were analyzed for antithrombin III, thrombin-antithrombin III (TAT) complex, and D-dimer concentrations. Cumulative blood loss was recorded at 6 and 12 h after CPB. No statistically significant differences in patient demographics or total heparin dose administered were observed between groups. As expected, plasma antithrombin III concentrations were maintained near pre-operative values in the treatment group, but not in the placebo group. Despite this difference, no statistically significant alterations in generation of TAT complex, D-dimer, or blood loss occurred between groups. Antithrombin III supplementation to maintain normal physiologic concentrations during CPB did not alter significantly thrombin generation, fibrinolytic activity, or blood loss in adults undergoing elective cardiac surgery.     

Effects of unfractionated and low molecular weight heparins on plasma levels of hemostatic factors in patients with acute coronary syndromes.

BACKGROUND AND OBJECTIVES: Unfractionated heparin (UFH) and enoxaparin (low molecular weight heparin) constitute fundamental therapies in the treatment of patients with acute coronary syndrome (ACS). Since enoxaparin appears to offer clinical advantages over UFH in managing ACS, markers of thrombin generation, endothelial function and acute phase response could manifest different responses to UFH or enoxaparin. The purpose of the present study was to investigate the effect that treatment with either UFH or enoxaparin has on plasma hemostatic markers in 24 patients with ACS. DESIGN AND METHODS: The patients were randomized to receive 5,000 IU intravenous bolus and continuous infusion of 18 IU/Kg/h UFH (n=11) or 1 mg/kg/12h subcutaneous enoxaparin (n=13). The plasma levels of fibrinogen (Fg), prothrombin fragment 1+2 (F1+2), thrombin antithrombin complex (TAT), von Willebrand factor (vWF), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were assayed at admission and 6, 12, 24 and 48 hours after heparin treatment. RESULTS: Upon admission, UFH and enoxaparin patients showed a significant increase in all the hemostatic parameters measured with respect to the levels in the control subjects. In comparison with the baseline levels of the UFH- and enoxaparin-treated patients, Fg showed a significant increase at 48 h and TFPI at 6, 12 and 24 hours. However, at 48 hours TFPI levels were not significantly higher than the basal values. There were no significant changes in F1+2, TAT, vWF or TF. INTERPRETATION AND CONCLUSIONS: Markers of thrombin generation, endothelial function and acute-phase reactants manifest a similar response to UFH and enoxaparin. An increase in thrombin generation may be a result of persistently activated inflammatory and endothelial processes, despite UFH and enoxaparin treatment.     

Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal and heparin-treated antiphospholipid syndrome pregnancies

Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent miscarriage. We assessed levels of coagulation activation markers and aPL during normal pregnancy and in women with the antiphospholipid syndrome (aPS). Fluctuations in aPL levels were observed in all patients with aPS. No particular pattern of antibody positivity, or fluctuation in aPL level, was associated with poor pregnancy outcome. A significant increase was observed in levels of factor Xlla (FXIIa; P < 0.001), factor VIIa (FVIIa, P < 0.001), thrombin antithrombin complexes (TAT; P < 0.001), prothrombin fragment F1.2 (F1.2; P < 0.001) and D-dimer (DD; P < 0.05) during normal pregnancy. Factor VIIa, TAT, F1.2 and DD increased significantly before 20 weeks gestation, while a statistically significant increase in FXIIa levels was first detected between weeks 20 and 30 of gestation. In pregnant women with aPS, increases in FXIIa were similar to those in normal pregnancy, but increased FVIIa levels were not observed until after 30 weeks gestation. Similar to normal pregnancy, increased levels of TAT and F1.2 were detected in aPS pregnancies before 20 weeks gestation, but increased DD were not observed until after week 20. Surprisingly, women with aPS receiving low molecular weight heparin prophylaxis had significantly higher (P = 0.02) levels of TAT (median 8.6; interquartile range (IQR) 6.5-20.8) between weeks 20 and 30 of gestation compared to the normal pregnant population (median 5.9; IQR 4.7-7.9), thus indicating increased thrombin generation in women with aPS in mid-pregnancy.