Effect of hormone substitution therapy on AT III in women in the climacteric]

Anti-thrombin III is the major inhibitor of intravasal coagulation. Patients with AT III activity less than 80% are at risk for thromboembolic complications. We have examined 224 women with climacteric symptoms (flush, urogenital complaints, osteoporosis) who received estrogen replacement therapy for one year. 105 women (group I) received conjugated estrogens at 0.626 mg. 52 women (group II) were given conjugated estrogens at 1.25 mg. 67 women (group III) were treated with transdermal estrogen replacement (TTS 50 mcg). AT III activity was measured before and one year after replacement therapy. No significant alterations of AT III activity were noted between the different modalities of application. This supports epidemiologic findings suggesting that no increase in the incidence of thromboembolic complications was seen in women who received estrogen replacement therapy over several years.     

Preeclampsia as chronic disseminated intravascular coagulation. Study of two parameters: thrombin-antithrombin III complex and D-dimers

Determinations of coagulation/fibrinolysis parameters thrombin-antithrombin III complex (TAT) and D-dimers (cross-linked fibrin degradation product) were carried out in order to prove that preeclampsia is a chronic disseminated intravascular coagulation (DIC) state. Besides the parameters TAT and D-dimers, antithrombin III (ATIII), fibrin degradation products and platelets were measured as well. Even in normal pregnancy there is an activation of coagulation, reflected in a hypercoagulative state that is proceeding down to the formation of thrombin. This thrombin is, however, nearly completely inactivated by ATIII, so that no fibrin is formed. This inactivation is solely reflected by the increase of TAT in the blood. In preeclampsia, however, where no such rapid changes as in acute DIC occur, the increase of TAT is accompanied by a decrease of ATIII and platelet counts and an increase of D-dimers; this demonstrates much more clearly the chronic DIC nature of preeclampsia than the results from studies carried out so far.     

Disseminated intravascular coagulation

Disseminated intravascular coagulation in obstetrics is commonly seen associated with massive hemorrhage due to different etiological factors. It may also be seen with intrauterine demise, infections, and hepatic conditions. It is associated with very high maternal and perinatal morbidity and mortality. A battery of laboratory tests (prothrombin time, partial thromboplastin time, thrombin time, and plasma fibrinogen) can be used in the diagnosis, but no single test in isolation is sensitive and specific enough for diagnosis. Cornerstone of management is to identify the underlying pathology for disseminated intravascular coagulation. This chapter looks into molecular basis of obstetric DIC and identifies important laboratory tests, along with management. It also identifies topics of future research in the field of obstetric DIC.     

Obstetric hemorrhage and coagulation: an update. Thromboelastography, thromboelastometry, and conventional coagulation tests in the diagnosis and prediction of postpartum hemorrhage

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality. In the current treatment of severe PPH, first-line therapy includes transfusion of packed cells and fresh-frozen plasma in addition to uterotonic medical management and surgical interventions. In persistent PPH, tranexamic acid, fibrinogen, and coagulation factors are often administered. Secondary coagulopathy due to PPH or its treatment is often underestimated and therefore remains untreated, potentially causing progression to even more severe PPH. In most cases, medical and transfusion therapy is not based on the actual coagulation state because conventional laboratory test results are usually not available for 45 to 60 minutes. Thromboelastography and rotational thromboelastometry are point-of-care coagulation tests. A good correlation has been shown between thromboelastometric and conventional coagulation tests, and the use of these in massive bleeding in nonobstetric patients is widely practiced and it has been proven to be cost-effective. As with conventional laboratory tests, there is an influence of fluid dilution on coagulation test results, which is more pronounced with colloid fluids. Fibrinogen seems to play a major role in the course of PPH and can be an early predictor of the severity of PPH. The FIBTEM values (in thromboelastometry, reagent specific for the fibrin polymerization process) decline even more rapidly than fibrinogen levels and can be useful for early guidance of interventions. Data on thromboelastography and thromboelastometry in pregnant women are limited, particularly during the peripartum period and in women with PPH, so more research in this field is needed.     

Menstruation-related disseminated intravascular coagulation in an adenomyosis patient: case report and review of the literature

Disseminated intravascular coagulation (DIC) is a high mortality coagulopathy that leads to simultaneous thrombotic and bleeding problems. It occurs as a complication in different disease as malignancies, obstetrical catastrophes, bacterial sepsis and traumas. We report on an extremely rare case of acute DIC in a patient with misdiagnosed adenomyosis and massive methrorragia which led to acute kidney failure. The patient was successfully treated with hysterectomy and blood product transfusions; however, a slight reduction of renal function persisted. We were able to confirm the cause-consequence link between adenomyosis and consumptive DIC since we saw the thrombi in the adenomyotic uterus from early hysterectomy specimen. Moreover, this is the first case, for the best of our knowledge, in which systemic consequences persist in an adenomyosis patient who developed a DIC. Early diagnose and treatment of acute DIC is essential for patient’s survival and to prevent severe complications: adenomyosis should be kept in mind as a possible cause of DIC when a patient shows up with massive bleeding.     

A typical case of DIC precipitated by cesarean section done for severe toxemia of pregnancy and a follow up laboratory study of the progress of DIC

A typical case of DIC presumably precipitated by cesarean section done for severe toxemia of pregnancy is reported. A laboratory study followed up the progress of DIC, especially of the drop in the consumptive platelet count and fibrinogen level as a result of excessive blood clotting. In this case the patient was a 29-year-old nulliparous gravida 1 who developed severe toxemia at 29 weeks and underwent a cesarean section for fetal distress at 33 weeks, although the baby died immediately after birth. On the following day of operation slight bleeding from the operative wound occurred and she had pertinent laboratory tests, which yielded a platelet count of 81,000/mm3, plasma fibrinogen level of 200mg/dl and FDP of 160 micrograms/ml and led to a diagnosis of DIC. While placing her on replacement and adjunctive therapies the laboratory tests were performed serially, which permitted a close follow-up observation of the subsequent progress of DIC with the detection of lowered platelet counts and fibrinogen levels as administration of Heparin resulted in an increase in the amount of bleeding, FOY, 800mg/day, was instituted and following this treatment the DIC disappeared.     

Postpartum acquired hemophilia (factor VIII inhibitors): a case report and review of the literature

Pathologic inhibitors of blood coagulation as a cause of postpartum acquired hemostatic failure are rare. Since 1937, 96 cases of postpartum factor VIII (FVIII) inhibitors, including the current case, have been reported. Suspicion for the diagnosis of this condition is often low. We report a case of postpartum FVIII inhibitor formation in a 24-year-old woman who developed intermittent postpartum bleeding that resulted from the inhibitors she formed to FVIII. A unique form of therapy was used in treatment of her disorder. She did not respond to conventional surgical or medical management of her bleeding until Autoplex T (Baxter Healthcare, Glendale, CA), an activated prothrombin complex concentrate (aPCC) was used. The literature concerning acquired hemophilia is reviewed, and new therapeutic medical advances are emphasized.     

妇产科围手术期脓毒症的临床分析

目的：分析妇产科围手术期脓毒症的病例特点，为脓毒症的防治提供依据。方法：收集首都医科大学附属北京妇产医院2011年1月—2017年12月诊断为脓毒症的病例14例，分析其病例特点，并根据病原学分为G-杆菌组及G+球菌组（真菌感染患者仅有1例，未作统计学分析），对比组间差异。结果：妇产科围手术期脓毒症的病原体多为G-杆菌，占71.4%，脓毒症患者血白细胞计数、C反应蛋白水平、降钙素原水平均较正常参考值显著升高，G-杆菌组纤维蛋白原（FIB）较G+球菌组显著减低（P=0.045），G-杆菌组国际标准化比值（INR）（P=0.043）及D-二聚体（D-D）（P=0.039）较G+球菌组显著升高，差异均有统计学意义。5例脓毒性休克患者均为G-杆菌感染。结论：妇产科围手术期脓毒症以G-杆菌感染为主，炎症反应强烈，同时伴随严重的凝血功能异常，易发生脓毒性休克，及早发现、经验性抗感染治疗及早期应用低分子肝素预防弥散性血管内凝血（DIC）对改善预后至关重要。     

Antithrombin III deficiency and pregnancy. Apropos of a case

Congenital deficiency of antithrombin III is a disease inherited as an autosomal dominant which predisposes to thromboembolism. Pregnancy and the postpartum period constitute a major additional risk factor for thromboembolism in deficient women. However, pregnancy may be envisaged without risk since there has been an improvement in knowledge concerning the physiology of the AT III molecule, its exact role in coagulation, the application of accurate laboratory tests which measure the deficiency, and especially the programming of pregnancy under cover of preventive treatment consisting of the perfusion of AT III concentrate in association with heparin. The treatment is restricting and costly but is, nevertheless, the only one to recreate conditions that are similar to physiological conditions, and its effect is therefore more certain.     

Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the placenta and myometrium

BACKGROUND: Placental abruption is mainly due to the rupture of the uterine spiral arteries, but adjacent tissues are also damaged and substances derived from disintegrated placenta and myometrium probably cause coagulation disturbances, such as hypofibrinogenemia and disseminated intravascular coagulation (DIC). AIM: To measure whether placenta and myometrium are significant sources of tissue factor (TF) and tissue factor pathway inhibitor (TFPI), the components of key role in the initiation of coagulation. MATERIALS AND METHODS: Strips of placenta and myometrium were obtained from 48 women delivered by cesarean section at term. TF and TFPI concentrations were measured by immunoenzymatic method (ELISA) in tissue homogenates. MAIN RESULTS: Concentration of TF in placenta and myometrium was 31 (25-37) and 7.4 (4.9-11.4) ng/mg of total protein, respectively. In the plasma of the same women, it was 0.004ng/mg of total protein. TFPI concentration was 13 (10-17) ng/mg of total protein in placenta, 4.5 (3.1-7.3) ng/mg in myometrium, and 0.70 (0.50-0.80) ng/mg in blood plasma protein. CONCLUSION: The levels of TF in placenta and myometrium, over TF in blood plasma may be clinically significant in obstetrics, for instance, in the etiology of DIC in placental abruption. The concentration of TFPI-natural inhibitor of TF-seems to be too low to prevent initiation of coagulation.     

羊水栓塞DIC的处理及肝素使用问题

弥散性血管内凝血（disseminated intravascular coagulation，DIC）是羊水栓塞（amniotic fluid embolism，AFE）病理改变的重要原因之一。DIC造成大量凝血因子消耗和红细胞破坏，并加重肺动脉高压，也是AFE出血的主要原因。早期发现DIC，有助于AFE的诊断。减少促凝物质进入血液循环、抗凝治疗可阻断DIC的进一步发展。肝素应在DIC高凝期或低凝期早期使用，同时需补充凝血因子，监测凝血功能的变化。     

Fundamental studies on the management of disseminated intravascular coagulation (DIC) with antithrombin III (AT-III) concentrate

The anticoagulant effect of antithrombin III (AT-III) in the management of disseminated intravascular coagulation (DIC) was investigated. When AT-III concentrate (4 mg/0.2 ml) was added to pregnant whole blood (0.8 ml), r(21.0 +/- 0.6 mm) and K(7.2 +/- 0.3 mm) (Mean +/- SE) were prolonged as compared with the saline control (C) (r: 18.6 +/- 0.6, K: 4.6 +/- 0.2 mm), and ma was decreased from 68.8 +/- 1.2 mm (C) to 60.3 +/- 1.0 mm (AT-III) on the TEG (p less than 0.01). PT and aPTT were also prolonged by the addition of AT-III concentrate (p less than 0.01). DIC models in rabbits were induced by continuous infusion of endotoxin (E). AT-III concentrate was administered two hours after starting infusion of E. Anticoagulant activity was evident on the TEG. In the data on coagulative and fibrinolytic factors, there were no significant differences between the control and the group administered AT-III concentrate. Fibrin deposits in the renal glomeruli were reduced after administration of AT-III concentrate (control: 46.5 +/- 38.7%, AT-III: 13.4 +/- 27.9%). The decreasing rate of AT-III antigen was the same in E infusion and non-infusion groups. However, the rate of decrease in activity was higher in the former than in the latter (rate of decrease: 40.0% and 24.6% 8 hours after administration of the AT-III concentrate). This indicated that inactive AT-III combined with thrombin and Xa might remain in the blood in DIC.     

产科弥散性血管内凝血的临床诊治

弥散性血管内凝血是由不同原因引起的广泛凝血系统激活,导致弥散性微血管内纤维蛋白沉积、微血栓形成,造成全身出血及微循环衰竭为特征的综合征。本文对产科弥散性血管内凝血的概念、发病因素、病理机制、临床表现、实验室检查、治疗方法及预防进行讨论。     

Acute disseminated intravascular coagulation developed during menstruation in an adenomyosis patient

We report a case of acute disseminated intravascular coagulation (DIC) developed during menstruation in an adenomyosis patient. No known predisposing factor for DIC such as infection or pregnancy was involved in this case. As anticoagulation therapy and supplementation of coagulation factors quickly improve the state, surgical removal of the uterus was not required. We speculate that hemorrhage in the adenomyosis legion and subsequent local thrombosis played crucial role in pathophysiology of this case of acute DIC. Received: 16 August 2001 / Accepted: 17 August 2001 Correspondence to Y. Nakamura     

Postpartum heparin therapy for patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) is associated with significant hemorrhagic complications.

OBJECTIVE: To compare the outcome of two groups of 16 patients with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome treated with heparin therapy or treated conservatively in the postpartum period. STUDY DESIGN: This is a retrospective cohort study comparing 16 consecutive patients with HELLP syndrome admitted to the ICU at the University of Florence (Italy) after delivery and treated with heparin, to 16 patients with the same disease admitted to the University of Virginia (UVA, USA) and treated with supportive therapy. RESULTS: Nine patients in the Florence group developed disseminated intravascular coagulation (DIC). Six of them developed postpartum hemorrhage that was medically and surgically controlled. Five hysterectomies were performed and seven other laparotomies were necessary in four patients to control further bleeding complications. In the UVA group, one patient developed DIC and another one a retroperitoneal hematoma that resolved with no need for surgical intervention. CONCLUSIONS: Heparin therapy for postpartum patients with HELLP syndrome was associated with bleeding complications. We speculate that the heparin therapy was the cause for the bleeding complications occurred in the Florence group of patients.     

Acute blood coagulation disorders in pregnancy--changing patterns in the disease picture

The syndrome of coagulation defects in obstetrics was detected as cause for obstetrical hemorrhage during the 50 years. Some of the etiologic factors like the dead fetus syndrome or the salting out syndrome have vanished. Amniotic fluid embolism is the only syndrome which is clearly associated with disseminated intravascular coagulation. This connection between premature separation is less clear. One concept assumes that the plasma fibrinogen concentration is low because it is consumed in the retroplacental hematoma. Heparin treatment can be fatal if DIC is mistaken with a "loss coagulopathy", which is at present mostly responsible for coagulation defects and obstetrical hemorrhage. This indicates a change in pattern of disease which is due to a better pathophysiologic understanding.     

Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low platelets

The presence of disseminated intravascular coagulation (DIC) in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP) is debated. We assessed the occurrence of decompensated and compensated DIC (using predefined criteria) in 15 consecutive nulliparous pregnant patients with gestational hypertension combined with the HELLP syndrome and in 12 consecutive nulliparous controls with pregnancy induced hypertension (PIH) but without the HELLP syndrome. A combination of routine coagulation assays revealed the absence of decompensated DIC in all studied patients. However, using more specific and sensitive coagulation assays, compensated DIC was observed in all HELLP patients and in three patients in the control group. The mean values of antithrombin III, thrombin-antithrombin III complexes and protein C in the HELLP and the control group were 66 vs 87% (P = 0.0004), 21 vs 8 ng/ml (P = 0.0008) and 57 vs 90% (P = 0.0018) respectively. We conclude that HELLP patients show evidence of compensated DIC which may have pathophysiological significance for the observed organ damage.     

妊娠期凝血功能障碍与产科多器官功能障碍综合征

妊娠期弥漫性血管内凝血(DIC)是病理妊娠的严重并发症,常与产科出血、重度子痫前期及子痫、羊水栓塞、妊娠期急性脂肪肝和感染等相关。出血、高血压和感染等可启动瀑布式病理生理反应,即全身炎症反应综合征(SIRS),致使孕产妇全身低灌注、低血流,最终导致多器官功能障碍综合征(MODS)、DIC的发生。只有尽早明确病因,评估母胎血流动力学的继发改变,及时正确地在治疗窗处理凝血功能障碍,纠正低容量、低血供和低灌注,维持血流动力学稳定,才能降低孕产妇的病死率。     

Antithrombin III levels in normotensive and hypertensive pregnancy

Antithrombin III (AT III) is the main physiological inhibitor of blood coagulation. In a prospective study, plasma AT III was determined in 653 women during pregnancy, using an automated amidolytic technique. A control value 8 weeks after delivery was obtained in 192 of the women. In women with pregnancy-induced or aggravated hypertension a significant decrease in AT III levels was observed compared with normotensive controls of the same period of gestation and compared with the patients' own control values 6-8 weeks after delivery. No AT III depression occurred in patients with chronic hypertension during pregnancy. Patients with pregnancy hypertension and proteinuria had lower AT III levels than those without proteinuria, whose AT III levels were also depressed. Lowest AT III levels were seen in 2 eclamptic patients and in patients with severe preeclampsia, whose pregnancies were terminated for fetal distress while the infants were still preterm. Monitoring At III levels is of value in preeclampsia.     

The Administration of Antithrombin III in the Management of Severe Preeclampsia

In severe preeclampsia/eclampsia a disseminated intravascular coagulation (DIC)-like syndrome is a prominent feature. Low levels of antithrombin III (AT-III; heparin cofactor) have been described in this syndrome. The objective of this pilot study is to determine whether the low levels of AT-III can be increased to normal by the intravenous administration of purified, concentrated, human AT-III. All patients entered into the study manifested thrombocytopenia, hemolytic anemia, coagulopathy, evidence of liver disease, and/or a bleeding diathesis. Each patient received a dose of AT-III equivalent to the amount in 3,000 ml of plasma. The levels of AT-III as measured by a functional assay were significantly increased (1.5–2x) following the initial 3,000 unit bolus of AT-III and prior to any other blood replacement therapy. The response of individual patients is proportional to the initial level of AT-III. In the control group there was no difference between the predelivery levels of AT-III and those obtained 12–24 hr postpartum. Therefore, the intravenous administration of AT-III may be useful in the treatment of patients with severe preeclampsia or eclampsia.