Role of coagulopathy in patients with head trauma

Coagulation disorders are a well known complication in patients with head injuries. A prospective study was undertaken to determine the incidence and prognostic value of haemostatic abnormalities in this group of patients. Clotting mechanisms in 105 patients with an isolated head injury were evaluated using platelet count (PC), prothrombin time (PT), activated partial thromboplastin time (APPT), thrombin clotting time (TCT), plasma fibrinogen concentration (Fib), level of fibrin-fibrinogen degradation products (FDP) and increased consumptive coagulopathy grade (ICCG) in the first 24 h after injury. The clinical severity of the head injuries was represented by the post-resuscitation Glasgow coma score (GCS) divided into four coma groups (CG). Test results were compared between two outcome groups of patients: discharged and dead. The incidence of disseminated intravascular coagulation (DIC) by laboratory criteria in the two groups was 12% and 38%, respectively. The differences between mean values of the discharged and dead patients for GCS, APTT, FDP and ICCG were statistically significant (P < 0.001). There was a very strong correlation between the GCS and values of the FDP, APTT, TCT and ICCG (P < 0.01). Stepwise logistic regression analysis demonstrated that GCS, FDP level, and ICCG predicted outcome in 84% of cases. Other tests did not provide additional predictive value. We conclude that evaluation of coagulation and fibrinolysis in patients with head injuries is not only important in identifying the occurrence of coagulopathy, but also useful in predicting head injury outcome.     

Extrinsic pathway inhibitor (EPI) released to the blood by heparin is a more powerful coagulation inhibitor than is recombinant EPI

EPI released to the blood after injection of heparin, as well as recombinant EPI (r-EPI) added to normal plasma prolonged both the dilute Tissue Thromboplastin (TIP) time and the Activated Partial Thromboplastin Time (APT-1). It is known that EPI inhibits both factor Xa and the factor VIIa-TTP complex. The prolongation of the APTT by EPI reflects only its inhibition of factor Xa. Addition of anti-EPI immunoglobulins (IgG) to normal plasma shortened the dilute TTP time 7.3 seconds (p< 0.001) and the APTT by 0.7 seconds (p<0.001). In postheparin plasma, with polybrene added to neutralize the direct effect of heparin, the TTP was about 26 seconds longer and the APTT about 9 seconds longer than baseline values. These effects were completely abolished by anti-EPI IgG, as were the effects of r-EPI. The EPI activity (chromogenic substrate-assay) of this postheparin plasma was 1.7 U/ml. The EPI activity of the plasma spiked with r-EPI to obtain comparable effects on clotting were much higher; about 22 U/ml for the TTP effect and about 5 U/ml for the APTT effect. The findings indicate that r-EPI is considerably less potent than postheparin EPI as inhibitor of plasma coagulation. This is most striking when coagulation is initiated through the extrinsic pathway. Possibly, the anticoagulant effect of r-EPI mainly depends on its Xa inhibitory effect.     

电凝热灼和激光照射猴脑浅表皮层后其形态学改变的对比研究

目的　探讨不同功率电凝热灼对正常猴运动区皮层所造成的形态学改变 ;探讨激光热灼猴运动区皮层青霉素致痫后的形态学改变。为治疗功能区癫痫寻求理论依据。方法　实验分两组 :每组为三只恒河猴。在电凝热灼组 :分别用 8、10、12三种输出功率 ,每间隔 5mm左右热灼一次正常猴的中央前回皮层 ,每次热灼时间 1～ 2秒。在激光热灼组 ,首先建立青霉素局限性致痫模型猴 3只 ,再激光热灼 2只 ,另 1只为对照。应用光源直径为 0 .1nm ,波长为 10 6 4nm的Nd -YAG激光 ,将输出功率设置为 4W ,每间隔 5mm左右垂直照射一次致痫区 ,每次照射 2～ 3秒。将上述两种方法热灼后的组织进行病理分析。结果　电凝热灼仅损伤脑浅表皮层结构 ,深部组织结构未见异常。激光照射可使浅表皮层断裂 ,深部组织结构变化不明显。两种方法在皮层的损伤宽度、深度上无显著性差异。手术后均未见猴的行为学异常和MRI异常。结论　适当的电凝热灼和激光照射猴脑的功能区皮层 ,可起到与MST一样的治疗功能区癫痫的效果 ,上述两种方法安全可靠 ,且效果较好     

颅脑损伤后的凝血功能异常

颅脑损伤能引起凝血功能异常，这种凝血功能异常可加重脑损害。影响病人预后。本就颅脑损伤后凝血功能异常改变的发生率，发生机制，对机体影响，临床意义及治疗进行综述。     

抗癫痫药物影响血浆纤维蛋白原水平分析

目的:探讨口服抗癫痫药物对患者血浆纤维蛋白原(fibrinogenemia,Fbg)水平的影响。方法:对410例服用抗癫痫患者的临床特点、凝血功能、肝功能、血小板计数等资料进行回顾性研究。结果:59例癫痫患者的Fbg水平低于正常水平。结论:对于口服抗癫痫药物患者需注意凝血功能,特别是Fbg的变化,尤其当该类患者行外科手术、严重外伤等情况,若Fbg定量检查低于正常,应该及时补充,避免因凝血功能障碍导致相应的临床症状。     

Effects of histidine-rich glycoprotein on cerebral blood vessels

Delayed cerebral vasospasm is thought to be caused by factors released from a subarachnoid blood clot. Because vasospasm occurs several days after hemorrhage, we hypothesized that clotted blood releases vasoactive factors as it ages. Targeted proteomics identified histidine-rich glycoprotein (HRG) as a potentially vasoactive factor released within the first 72 hours of clot formation. In vitro studies revealed that HRG caused moderate (∼30%) dilation of cannulated cerebral arterioles and proliferation of cerebrovascular endothelial cells. We conclude that HRG released from clotted blood, while unlikely to contribute to cerebral vasospasm, might provide important vasodilatory or angiogenic stimuli after hemorrhagic stroke.     

Activation of factor B of the complement system by kallikrein and its light chain

The cleavage of factor B, a protein of the alternative pathway of complement, by kallikrein was studied. Like factor D, kallikrein can cleave B to generate the alternative pathway C3 convertase C3bBb. When this convertase was formed on erythrocytes previously coated with C3b, lysis was observed indicating that a functionally active C3 convertase was formed. B was also cleaved by kallikrein in the presence of fluid phase C3b, and this resulted in B fragments comparable in size to those generated in the presence of D. The capacity of kallikrein to cleave B is localised in the light chain of the kallikrein molecule, which is the same chain of kallikrein that is responsible for its other enzymatic activities. Since on a molar basis D is much more active then kallikrein in cleaving B, a physiological role for B activation by kallikrein is only likely under certain conditions, and still has to be established.     

Plasma fibronectin concentration in patients with acquired consumptive coagulopathies

Plasma fibronectin was assayed in 179 hospitalized patients referred for workup of possible acquired coagulopathy. Based on laboratory results and chart review, these patients were classified as having no coagulopathy (N = 36), defibrination syndrome (N = 31), compensated defibrination syndrome (N = 100), microangiopathic thrombocytopenia (N = 7), and primary fibrinolysis (N = 5). Compared to patients with no coagulopathy, fibronectin concentration was reduced in patients with defibrination syndrome (p less than 0.005) and compensated defibrination syndrome (p less than 0.10). Fibronectin concentration was not reduced in patients with microangiopathic thrombocytopenia and primary fibrinolysis. In patients with defibrination syndrome, the reduction of fibronectin was correlated to the degree of liver impairment. This finding is consistent with the liver being the primary site of synthesis of plasma fibronectin. Fibronectin was significantly correlated to plasminogen and antithrombin III. The sensitivity of fibronectin for the diagnosis of coagulopathy is low except for patients with defibrination syndrome.     

The effect of hirudin on endotoxin induced disseminated intravascular coagulation (DIC)

The inhibitory effect of hirudin was investigated in rabbits, which developed the generalized Shwartzman reaction after two endotoxin injections spaced 24 hours apart. Hirudin was infused for a period of 6 hrs after the second endotoxin injection. In the controls glomerular microthrombosis and reduced urinary output were associated with laboratory signs of intravascular coagulation such as decrease of fibrinogen, antithrombin III, platelets, leukocytes, and an increase of high molecular weight derivatives of fibrinogen. Hirudin infusion prevented acute renal failure and glomerular microthrombosis in ten of twelve animals and consumption of coagulation factors. The decrease of platelets was also reduced while the decrease of leukocytes was unaffected. The findings indicate that the hematological and functional consequences of the GSR can be prevented by infusion of hirudin.     

Simulation: An underutilized approach to coagulation system model evaluation

Simulation and mathematical modeling have proven useful in evaluating diverse physiological and biochemical systems. However, simulation methods have had extremely limited application in the formulation and evaluation of models of the blood coagulation system. The utility of this tool is illustrated via a mathematical model of the interactions of thrombin with fibrinogen, antithrombin III, and heparin-antithrombin III complex. This model provides exemplary simulations consistent with several empirical characteristics of the anticoagulant effect of heparin. Simulation methods provide a powerful tool with which to characterize the dynamic nature of the hemostatic process and its responsiveness to endogenous perturbations or pharmacological interventions.     

Desialylation of fibrinogen with neuraminidase. Kinetic and clotting studies

The removal, with time, of sialic acid residues from human fibrinogen by neuraminidase, can be explained, as a result of a mathematical analysis, by the summation of two first order reactions with clearly different rate constants. Quantitative studies on the bound sialic acid to isolated fibrinogen chains, after reduction and alkylation of the partially desialylated fibrinogen, show that the fast reaction takes place with the sialic acid bound to the Bβ chains. This indicates that the carbohydrate located in the γ chains is somehow protected or less accesible to the enzyme. Coagulation with thrombin of desialylated fibrinogen shows that the aggregation rate increases linearly as the amount of sialic acid residues decreases, regardless of their location in the fibrinogen molecule.     

轻中度颅脑损伤后凝血功能变化与手术预测的关系

目的探讨轻中度颅脑损伤(TBI)后凝血功能变化与手术预测之间的关系。方法 2013年10月~2015年9月在我院治疗的55例轻中度TBI患者,根据住院期间是否需要开颅手术分为手术组(8例)和非手术组(47例)。比较两组患者入院时血小板计数、纤维蛋白降解产物(FDP)、国际标准化比值(INR)、部分凝血活酶时间(APTT)、纤维蛋白原和D-二聚体之间的差异。结果手术组患者凝血功能明显低于非手术组,其中APTT、FDP和D二聚体明显低于非手术组(P0.05~0.01);而两组血小板计数、INR和纤维蛋白原比较,差异无统计学意义(均P0.05)。结论轻中度TBI患者凝血功能障碍和异常纤维蛋白原溶解与手术预测相关;临床应将其用于预测TBI患者的手术需要及预后。     

病灶切除与热灼联合术治疗顽固性癫痫

目的　观察病灶切除辅以皮质痫灶横纤维热灼术治疗顽固性癫痫的临床效果。方法　病灶切除辅以皮质痫灶热灼组的病人和单纯病灶切除组病人的疗效进行分析比较。结果　病灶切除辅以皮质痫灶热灼组效果优于单纯病灶切除组 ,两者的临床效果存在极显著性差异 (P <0 .0 1) ;同时 ,病灶切除辅以皮质痫灶热灼组无永久性的术后并发症。结论　病灶切除辅以皮质痫灶热灼术是治疗顽固性癫痫安全有效的方法 ,长期疗效有待于进一步观察     

Immunoelectrophoretic studies of prekallikrein in human plasma

Using a rabbit anti-human prekallikrein antibody crossed immunoelectrophoresis (CIE) and Laurell rocket antigen determinations were done in plasmas of subjects with Fletcher (prekallikrein, PKA), Fitzgerald (high molecular weight kininogen), Hageman (XII), and PTA (XI) deficiencies as well as in patients with activation of coagulation (intravascular coagulation syndromes). Abnormal CIE patterns were seen in the Fletcher and Fitzgerald deficient plasmas and also in some of the patients with intravascular coagulation. $\text{In}$$\text{vitro}$ studies of plasma treated with thrombin, plasmin, and contact activating agents indicated that abnormal CIE patterns and increased PKA antigen levels were indicative of activation of the Hageman factor dependent pathway and not the result of plasma clotting by thrombin. $\text{In}$$\text{vivo}$ activation of the Hageman factor dependent pathway frequently results in an abnormal CIE and a low PKA antigen level.     

A fully automated method for clot based coagulation panels using an MCA Multistat Centrifugal Analyzer

Small modifications of the commercially available software of the I.L. Multistat Centrifugal Analyzer (MCA) enabled us to evaluate clot based prothrombin times (PT), activated partial thromboplastin times (APTT) and thrombin times (TT) simultaneously within one run. This imparted a great deal of flexibility to this procedure in that batches and/or panels of clot based and other types of turbidimetric tests can be performed concurrently in any combination. The PT and TT by this turbidimetric procedure correlated very well with those of the Fibrometer in normal specimens as well as in a wide variety of coagulation defects. The turbidimetric APTT procedure, however, often produced clotting times longer than those achieved with the Fibrometer. The discrepancy between the Fibrometer and turbidimetric APTT procedures was shown to be the consequence of greater sensitivity of the latter to detect low concentrations of heparin, elevated fibrinogen split products and mild factor deficiencies. The available clot based procedures are suitable for use in detecting specific factor deficiencies and the presence of coagulation inhibitors.     

急性脑梗死患者炎症因子、血凝状态的变化

目的 探讨急性脑梗死患者血小板功能、凝血与纤溶功能及炎症因子的变化情况。方法 采用血凝仪和全自动生化分析仪测定106例急性脑梗死患者APTT、FIB、D-二聚体、hs-CRP、IL-6、TNF-α、PAgT等指标水平,并与100名健康者进行对照。结果 急性脑梗死组患者凝血功能中APTT值明显缩短,FIB值和D-二聚体值明显增大,炎症因子中IL-6值、hs-CRP和TNF-α值明显升高,PAgT值增大,与对照组比较均有明显差异(P<0.01)。重度脑梗死组与中度和轻度脑梗死组比较,中度脑梗死组与轻度脑梗死组比较,各项检查值均明显改变(P<0.05)。采用多联指标分析,四项检测指标联合和五联项检测指标联合进行急性脑梗死预测与诊断,其灵敏性(100%,97%)、特异性(98%,100%)、阳性预测值(98%,100%)和阴性预测值(100%,97%)较理想。结论 检测APTT值、FIB值、D-二聚体值、IL-6值、hs-CRP、TNF-α值和PAgT值对急性脑梗死的诊断和预后判断有一定的临床意义。     

Evaluation of the soluble fibrin monomer complexes and other coagulation parameters in obstetric patients

The soluble fibrin monomer complexes (SFMC) in 154 obstetric patients with possible disseminated intravascular coagulation (DIC) were evaluated in SDS polyacrylamide gel electrophoresis (PAGE) after precipitation with β-alanine. Other coagulation tests were performed on these patients. The patients were classified into three groups: A) patients with a clinical history of DIC (6 cases); B) patients with only the analytical alterations of DIC (35 cases); and C) patients who showed pathological obstetric diagnoses but without a clinical nor analitical history of DIC (113 cases).

In the three groups, well-defined bands of less electrophoretic mobility than fibrinogen were obtained. A significant increase in the second electrophoretic band was found in group A (5.1 per cent) when compared to group C (0.5 per cent). The second electrophoretic band appeared in greater proportion in the group of patients with an unfavorable clinical evolution.