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。     

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.     

HELLP syndrome. Apropos of a series of 9 cases without disseminated intravascular coagulation

The Hellp syndrome defined as the association of micro-angiopathic haemolytic anemia, hepatic cytolysis and thrombocytopenia, correspond to a severe form of gravidic toxemia, combined to manifestations of classic-pre-eclampsia. This retrospective study, conducted over 6 years, concerns 9 cases of Hellp syndrome, including 2 occurring during the immediate post-partum. Only cases where this biological triad was obvious and not associated with manifestations of disseminated intravascular coagulation, were considered in this study. In addition to the usual criteria of gravidic toxemia, the early clinical manifestation occur, in this study, between 28 and 38 weeks of amenorrhea and gastrointestinal manifestations are predominant. The physiopathogenic hypotheses of this syndrome remain variable and management varies depending on the authors. Treatment is that of pre-eclampsia. Medical treatments (steroids, heparin, immunosuppressants,...) are discussed, but severe feto-maternal complications require, most of the time, a surgical approach, depending on the number of pregnancies, the obstetrical conditions, the stage of the pregnancy and the severity of the syndrome.     

Plasma exchange in a case of HELLP syndrome associated with disseminated intravascular coagulation

The Authors describe a case of HELLP syndrome associated with disseminated intravascular coagulation occurred after delivery in a patient with late hypertension without any sign or symptom of preeclampsia during pregnancy. The use of plasma exchange has contributed to the recovery from the pathology.     

The effect of heparinized blood exchange transfusion on endotoxin induced disseminated intravascular coagulation (DIC).

Sepsis of the newborn induced by gram negative bacteria, especially E. coli is often accompanied by a severe coagulation disorder. It can be treated by blood exchange transfusion (ET) with heparinized blood. In this study the hematological effect obtained by the exchange transfusion was investigated in rabbits after induction of a generalized Shwartzman reaction by two spaced injections of endotoxin (75 microgram/kg) 24 hrs. apart. Three groups of 6 animals each were investigated: group I: without endotoxin but with ET (controls); group II: endotoxin without ET; group III: endotoxin with ET. Fibrinogen, soluble fibrin monomer complexes (SFMC), fibrin(ogen) degradation products (FDP), platelet- and leukocyte counts and urine volume (ml/hr) were estimated. In group II a decline in the fibrinogen level, and in platelet and leukocyte count, as well as an increase in SFMC and FDP could be observed from 6 hrs. on after the second endotoxin injection. In group III 6 hrs. after the second endotoxin injection, exchange transfusion with heparinized blood was performed. Variance analysis showed significant differences in all parameters, except in the urine volumes after exchange transfusion between group III and group II. By exchange transfusion an approach of the values towards the values of the controls could be recognized. The findings indicate, that by blood exchange transfusion the hematological consequences of the endotoxin induced DIC can be corrected, while the dysfunction of the kidneys can be improved only slightly.     

Using recombinant activated coagulation factor VII (NovoSeven) in obstetrics

The authors share their experience about the application of the NovoSeven in four cases with different types of hemostasiologic disturbances. The possibilities for its use in obstetrics and gynecology are discussed.     

Treatment of obstetrical disseminated intravascular coagulation--sequential changes of coagulation and fibrinolytic system in DIC rabbits

A model was experimentally made with 2 hours serial infusion of thromboplastin (Tp) into rabbits to examine the drug's effect on a hemorrhagic tendency and to elucidate the coagulation and fibrinolytic system in acute DIC encountered in obstetrics, and the system was periodically observed. Groups given the drug, given it during pregnancy, those which bled massively, and those with accelerated fibrinolysis were prepared. The results are as follows. 1) Fibrinogen, PT, APTT, TEG, ELT, AT-III, antiplasmin activity, and platelet count varied markedly from the initiation of Tp injection, and returned to normal following termination. 2) Blood from the heparin dose group showed non-coagulation but decreases in the platelet count and fibrinogen were inhibited. 3) In the aprotinin dose group, serial 2 hour administration induced inhibition of fibrinolysis despite the relatively delayed appearance of anti-fibrinolytic activity. 4) No fibrinolytic effects were seen in anti-plasmin activity or ELT in the tranexamic acid dose group. 5) Lowering of parameters examined was marked in the Tp dose group during pregnancy. 6) The mortality rate up to 6 hours after Tp infusion was 54.5% with solely given, and 10% with group given drug. 7) Death within one hour of Tp infusion in the mass bleeding group, being rated for 50%, was improved to 16.7% by the pre-administration of urokinase.     

Efficacy of gabexate mesilate on disseminated intravascular coagulation as a complication of infection developing after abdominal surgery.

BACKGROUND AND PURPOSE: Gabexate mesilate (GM) is a promising anticoagulation treatment for disseminated intravascular coagulation (DIC). This study was designed to examine the effect of GM on DIC associated with the development of infection after abdominal surgery in the intensive care unit (ICU). METHODS: From January 1999 to March 2002, 50 consecutive ICU patients suffering DIC associated with the development of infection after abdominal surgery were enrolled in this study. Twenty five of the patients were randomized to receive treatment with GM by central intravenous infusion at 1 mg/kg/hour for 5 days or longer, while the remaining 25 were not treated. Blood clotting tests were performed and cytokine levels including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were examined on days 1, 3, and 7 after admission. General blood tests and D-dimer tests were conducted before and after GM administration. The gender, age, mortality, Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores and severity of DIC were compared between the 2 groups. RESULTS: No significant difference was found between the 2 groups in TNF-alpha and IL-6 concentration on days 1, 3, and 7. The mortality rate was similar between the 2 groups. However, DIC and APACHE-II scores were significantly lower in the GM-treated patients than in controls. CONCLUSION: In this study, GM (1 mg/kg/hour) did not reduce the concentration of TNF-alpha and IL-6, or alter the mortality rate in patients with DIC resulting from infectious complications after surgery. Nevertheless, APACHE-II scores indicated that GM reduced the DIC severity and improved the clinical condition of patients.     

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.     

The development of disseminated intravascular coagulation in hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP) at very early gestational age

Hemolysis, elevated liver enzymes, and low platelet count syndrome(HELLP) is a severe pregnancy complication since it is life-threatening for both mother and fetus. When HELLP syndrome associates with disseminated intravascular coagulation (DIC) or with other complications it is necessary to terminate the pregnancy; however, due to fetal prematurity, it may be advisable to wait for the effectiveness of the corticosteroid prophylaxis of neonatal respiratory distress syndrome when such complications are not present. This article reports an initially mild HELLP syndrome case, with onset at week 26 and two days of pregnancy, where it was necessary to wait for the effectiveness of respiratory distress prophylaxis and, consequently, to carry out a close monitoring of the onset and worsening of DIC. Tests for blood cell distribution width, D-dimer, plasmatic electrolytes and urinary sediment, which undergo precocious and rapid variations in DIC, are quickly processed, and useful for the conservative management of HELLP.