Serum Fibrin Degradation Products Research Articles

Predictive value of serum chlorine and interleukin-6 combined with coagulation indexes on severity of severe acute pancreatitis

To explore the predictive value of combined detection of serum interleukin-6 (IL-6), chloride (Cl-), D-dimer and fibrin degradation products (FDP) for severity of acute pancreatitis (AP). From December 2020 to March 2022, 132 AP patients who met the criteria for inclusion were screened for retrospective analysis from 292 AP patients admitted in emergency surgery at the First Affiliated Hospital of Zhengzhou University and they were divided into severe acute pancreatitis (SAP) group and non-SAP group, with 63 in SAP group and 69 in non-SAP group, according to classification criteria. The data including lab results, abdominal doppler ultrasound and chest and abdominal CT, etc. The bedside index for severity in acute pancreatitis (BISAP) score was calculated. Multivariate Logistic regression analysis was carried out to find the risk factors for the severity of AP patients. The receiver operator characteristic curve (ROC) was drawn to judge the clinical predictive value of each factor. A total of 132 AP patients were enrolled. The serum IL-6, D-dimer, FDP levels and the BISAP score in SAP group were significantly higher than those in non-SAP group [serum IL-6 (ng/L): 62.73 (21.54, 187.47) vs. 8.22 (4.13, 14.70), D-dimer (mg/L): 5.36 (2.94, 8.25) vs. 0.94 (0.42, 2.21), FDP (mg/L): 13.54 (6.76, 22.45) vs. 3.20 (2.50, 6.10), BISAP score: 2.00 (1.00, 3.00) vs. 1.00 (0, 2.00), all P < 0.05], while the serum Cl- level was significantly lower than that of non-SAP group (mmol/L: 97.90±4.86 vs. 101.73±4.32, P < 0.05). Multivariate Logistic regression analysis showed that increased levels of IL-6 [odds ratio (OR) = 1.02, 95% confidence interval (95%CI) was 1.01-1.04], D-dimer (OR = 1.21, 95%CI was 1.05-1.40) and decreased Cl- level (OR = 0.88, 95%CI was 0.79-0.98) were risk factors for SAP (all P < 0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of IL-6, Cl-, D-dimer and FDP combined to predict the severity of AP patients was larger (0.89), and the sensitivity (82.50%) and specificity (85.50%) were higher. Compared with single index, the combined detection of serum IL-6, Cl-, D-dimer and FDP is more precise in determining the condition of AP.

Elevated Admission Cardiac Troponin I Predicts Adverse Outcomes of Acute Type B Aortic Dissection after Endovascular Treatment.

BackgroundThere is a lack of evidence about the predictive role of serum cardiac troponin I (cTnI) on the long-term adverse outcomes of acute type B aortic dissection (aTBAD) patients after thoracic endovascular aortic repair (TEVAR). In this study, we identified whether cTnI was an independent risk factor of 5-year adverse outcomes for aTBAD patients after TEVAR.MethodsWe reviewed consecutive aTBAD patients without previous heart disease who were admitted for TEVAR. The total study population was divided into the cTnI(+) group (≥0.03 ng/mL) and the cTnI(−) group (<0.03 ng/mL) according to the time-dependent receiver operating characteristic curve analysis. The differences in clinical characteristics, operative details and clinical outcomes were compared between the two groups.ResultsThere was no difference in age and male prevalence between the two groups. Compared with the cTnI(−) group, the incidence of chronic kidney disease was higher in patients with cTnI ≥0.03 ng/mL. In addition, the cTnI(+) group presented with more frequent premature beats and non-myocardial-infarction ST-T segment changes. In terms of laboratory examinations, white blood cell counts, neutrophil counts, serum D-dimer and serum fibrin degradation products showed an increase in the cTnI(+) group, while lymphocyte and platelet counts showed a decrease in these patients. Patients with elevated cTnI suffered from increased risks of 5-year aortic-related adverse events (hazard ratio, HR = 1.822, 95% confidence interval, CI: 1.094–3.035; p = 0.021) and all-cause mortality (HR = 4.009, 95% CI: 2.175–7.388; p < 0.001).ConclusionAmong aTBAD patients without previous heart disease, preoperative elevated cTnI identified patients at an increased risk of long-term adverse outcomes after TEVAR.

Integrated Analysis of Microbiome and Transcriptome Data Reveals the Interplay Between Commensal Bacteria and Fibrin Degradation in Endometrial Cancer.

The gut-uterus axis plays a pivotal role in the pathogenesis of endometrial cancer (EC). However, the correlations between the endometrial microbiome and endometrial tumor transcriptome in patients with EC and the impact of the endometrial microbiota on hematological indicators have not been thoroughly clarified. In this prospective study, endometrial tissue samples collected from EC patients (n = 30) and healthy volunteers (n = 10) were subjected to 16S rRNA sequencing of the microbiome. The 30 paired tumor and adjacent nontumor endometrial tissues from the EC group were subjected to RNAseq. We found that Pelomonas and Prevotella were enriched in the EC group with a high tumor burden. By integrating the microbiome and hematological indicators, a correlation was observed between Prevotella and elevated serum D-dimer (DD) and fibrin degradation products (FDPs). Further transcriptome analysis identified 8 robust associations between Prevotella and fibrin degradation-related genes expressed within ECs. Finally, the microbial marker of Prevotella along with DD and FDPs showed a high potential to predict the onset of EC (AUC = 0.86). Our results suggest that the increasing abundance of Prevotella in endometrial tissue combined with high serum DD and FDP contents may be important factors associated with tumor burden. The microbe-associated transcripts of host tumors can partly explain how Prevotella promotes DD and FDPs.

THE IMPORTANCE OF THROMBOELASTOMETRY IN THE HEMOSTATIC DISORDERS DIAGNOSIS IN INTENCIVE CARE PATIENTS WITH TRAUMAS (CLINICAL CASE)

thromboelastometry and coagulogram in patients with polytrauma.&#x0D; Materials and methods. The results of thromboelastometry (TEM) and standard coagulogram of 12 patients aged 18 to 74 years with a diagnosis of trauma were analyzed. Analysis of thromboelastometry was performed using a ROTEM delta blood analyzer (Tem Innovations GmbH, Germany), which evaluates the physical properties of a clot. Patients' blood stabilized with sodium citrate was placed in special disposable microcuvettes with the addition of various activators of coagulation reactions. The following indicators of thromboelastometry were determined: CT, CFT, angle alpha (α), MCF, A5, A10 in the tests INTEM, EXTEM and FIBTEM. The determination of coagulogram parameters was carried out according to a standard method. The following parameters were identified: APTT, INR, fibrinogen A content, serum fibrin degradation products (SFDP) concentration.&#x0D; Results. Coagulogram and thromboelastometry data at different stages of treatment were compared. In patients with the development of traumatic shock, coagulogram indices were changed to varying degrees depending on the stage of a shock. At the first stage of shock, the analysis showed only a 2-fold increase in SFDP and a slight increase in fibrinogen in dynamics. In a patient with a third stage of traumatic shock, the coagulogram indices were within normal limits, but according to TEM (EXTEM and FIBTEM tests), hypocoagulation was observed due to platelets. Only a coagulogram was evaluated in dynamics, hypocoagulation was observed in parameters of internal and external hemostasis pathways (prolongation of APTT, decrease in IPT and increase in INR), increase in fibrinogen A and SFDP. In the group of male patients with closed craniocerebral injuries, an increase in SFMC in the coagulogram had always been combined with changes in the FIBTEM test during TEM.&#x0D; Conclusion. Thus, in most patients, there is no change in classic coagulogram tests immediately after the injury. At the same time, rotational thromboelastometry makes it possible to fill this deficiency at an earlier date, which indicates a high sensitivity of the method.

Usefulness of serum fibrin degradation products and D-dimer levels as biomarkers to predict return of spontaneous circulation in patients with cardiopulmonary arrest on arrival: comparison with acid-base balance.

We evaluated the usefulness of fibrin degradation products and D-dimer levels in blood to predict return of spontaneous circulation in patients with cardiopulmonary arrest on arrival compared with anion gap and albumin-corrected anion gap. We retrospectively reviewed the medical records of patients with cardiopulmonary arrest on arrival who had been transferred to the emergency department of our hospital in 2012. Patients were divided into two groups: patients with return of spontaneous circulation (ROSC(+) group), and those without (ROSC(-) group). The levels of anion gap, albumin-corrected anion gap, fibrin degradation products and D-dimer measured on arrival were compared between the two groups. Fifty-three patients could be analyzed. The anion gap and albumin-corrected anion gap levels were significantly better in the ROSC(+) group than in the ROSC(-) group (anion gap, 28.7 mmol/L [median] versus 39.1 mmol/L; albumin-corrected anion gap, 31.1 mmol/L versus 40.9 mmol/L). The fibrin degradation product and D-dimer levels were significantly lower in the ROSC(+) group than in the ROSC(-) group (fibrin degradation products, 32.1 μg/mL versus 157.4 μg/mL; D-dimer, 9.9 μg/mL versus 37.4 μg/mL). The area under receiver operating characteristic curves to evaluate the relationship with return of spontaneous circulation of anion gap, albumin-corrected anion gap, fibrin degradation products, and D-dimer were 0.664, 0.667, 0.714, and 0.707, respectively. Fibrin degradation products and D-dimer levels might be more useful as predictors of return of spontaneous circulation than anion gap and albumin-corrected anion gap.

Abstract 18350: A Composite Risk Score of Biomarkers of Inflammation, Thrombosis, and Cell Stress Pathways Significantly Predict Risk of Adverse Cardiovascular Outcomes

Background: An aggregate biomarker risk score of C-reactive protein (CRP), heat shock protein (HSP)-70, and fibrin degradation products (FDP) significantly predicts adverse outcomes in patients with CAD. Soluble Urokinase Plasminogen Activator Receptor (suPAR) is an inflammatory biomarker that has been associated with incident CVD. We sought to investigate the value of adding plasma suPAR level to the 3 original biomarkers in predicting risk of adverse outcomes. Methods: 3,280 patients (aged: 62± 11, 83% white, 32% diabetics, 64% with CAD ≥50%) undergoing diagnostic angiography were followed for death and/or MI over median 2.3 yrs. Plasma suPAR (ViroGates, Denmark), and serum CRP, HSP-70, and FDP (Firstmark Inc) were measured using ELISA. Severity of CAD was assessed by the Gensini score. Cox proportional survival and C-statistic analyses were performed adjusting for traditional risk factors, ejection fraction, serum creatinine, and Gensini. Results: Patients with suPAR level ≥ 3.5ng/ml (ROC cutoff) had a greater CAD burden (Gensini: 49± 68 vs. 41± 64, p=0.003). Plasma suPAR ≥ 3.5 also predicted future death/MI (HR=1.76, p&lt;0.001) after adjustment for all covariates and the 3 biomarkers, CRP, HSP-70, and FDP; the C-statistic improved (0.69 to 0.71, p=0.01). A 4 biomarker aggregate score composed of suPAR, CRP, FDP, and HSP-70 below/above cutoffs significantly predicted risk of death/MI. Thus, compared to those with 0 biomarkers, HR of death/MI for those with 1, 2, 3, or 4 positive biomarkers were: 1.5, 2.1, 4.4, and 7.3 respectively (P&lt;0.001). Addition of the 4-marker score significantly improved the C-statistic compared to a model of traditional factors (0.68 to 0.75, p=0.004). Conclusion: An aggregate risk score of CRP, HSP-70, FDP, and suPAR representing inflammatory, thrombotic, and cell stress pathways, identifies CAD patients at low and very high risk of death/MI. Thus, the score allows individualization of risk in CAD patients.

What role do coagulation disorders play in the pathogenesis of leptospirosis?

Leptospirosis is a zoonosis of worldwide distribution, spread by the urine of infected animals. It is a major public health problem, especially in developing countries, where circumstances for transmission are most favourable. The clinical picture varies from mild disease to a severe illness with haemostatic derangements and multiorgan failure eventually leading to death. Although the haemorrhagic complications of severe disease are serious, the pathophysiology is scarcely elucidated. The complex mechanisms involved in inflammation-induced coagulation activation are extensively studied in various infectious diseases, i.e. Gram-negative sepsis. Tissue factor-mediated coagulation activation, impairment of anticoagulant and fibrinolytic pathways in close concert with the cytokine network are thought to be important. But for human leptospirosis, data are limited. Because of the growing interest in this field, the impact of leptospirosis, and the availability of new therapeutic strategies, we reviewed the evidence regarding the role of coagulation in leptospirosis and provide suggestions for future research.

Meaning of the DR-70™ Immunoassay for Patients with the Malignant Tumor

The DR-70 TM immunoassay is a newly developed cancer diagnostic test which quantifies the serum fibrin degradation products (FDP), produced during fibrinolysis, by antibody reaction. The purpose of this study was to evaluate the potential of DR-70 TM Immunoassay in screening malignant tumor. Methods: Sample subjects were 4,169 adults, both male and female, who visited the health promotion center of a general hospital from March 2004 to April 2005 and underwent the DR-70 TM immunoassay test and other tests for cancer diagnosis. The patient group was defined as 42 adults out of the sample subjects who were newly diagnosed with cancer during the same time period when the DR-70 TM immunoassay test was performed. Final confirmation of a malignant tumor was made by pathological analysis. Results: The mean DR-70 TM level was 0.83±0.65μg/ml (range: 0.00 (0.0001)∼7.42μg/ml) in the control group (n=4,127) as opposed to 2.70±2.33μg/ml (range: 0.12∼9.30μg/ml) in the cancer group (n=42), and statistical significance was established (0.0001, Student t-test). When categorized by the type of malignant tumor, all cancer patients with the exception of the subgroups of colon and rectal cancer showed significantly higher mean DR-70 TM levels compared with the control group (0.0001, Kruscal-Wallis test). The receiver operating characteristic (ROC) curve analysis revealed 1.091μg/ml as the best cut-off value. Using this cut-off value, the DR-70 TM immunoassay produced a sensitivity of 71.4%, a specificity of 70.1%, a positive predictability of 69.4%, and a negative predictability of 69.2% (1). Conclusion: A significant increase in the mean DR-70 TM value was observed in the cancer group (thyroidal, gastric, breast, hepatic and ovarian) com pared with the control group. In particular, the specificity and sensitivity of the DR-70 TM immunoassay was relatively high in the subgroups of breast, gastric, and thyroidal cancer patients. There is need for further studies on a large number of malignant tumor patients to see how the DR-70 TM level might be changed according to the differentiation grade and postoperative prognosis of the malignant tumor.

Plasma fibrinolysis and postoperative deep vein thrombosis.

In 23 high risk patients the change in plasminogen activator activity in response to surgical operation was studied by euglobulin lysis time (ELT) and fibrin plate lysis before, during and for up to 6 days following a major surgical procedure. Fibrin degradation products (FDP) were also measured. The aim was to relate any changes to postoperative deep vein thrombosis (DVT) as diagnosed by the 125I fibrinogen test. Peroperative increase and postoperative inhibition of fibrinolytic activity were seen in all the patients. Changes in fibrinolytic activity as measured by the ELT and during the first 24 hours by the fibrin plate technique were similar. This suggests that during this period the response was independent of plasma fibrinogen changes. There was no significant difference in these parameters between patients who developed DVT and those who did not. The relationship between venous thrombo-embolism and elevation of serum FDP was confirmed.

The new DR‐70 immunoassay detects cancer of the gastrointestinal tract: a validation study

Malignant cells characteristically possess high levels of plasminogen activator, which induce local fibrinolysis. The DR-70 immunoassay is a newly developed test, which quantifies fibrin degradation products in serum by a proprietary antibody. To evaluate the DR-70 immunoassay as a detection assay for the presence of gastrointestinal cancers. We prospectively collected blood sera of 85 patients with histologically proven tumour and 100 healthy blood donors. Ten microlitres of the sera was used for the DR-70 immunoassay. Nineteen patients had a hepatocellular and 10 cholangiocellular carcinoma, 13 cancer of the pancreas, 30 colorectal cancer, 10 stomach cancer and three cancer of the oesophagus. Receiver-operator curve analysis revealed <0.7 microg/mL as the best cut-off value to distinguish between patients with cancer and healthy controls. Using this cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 91% and a specificity of 93%. Patients with advanced tumour spread showed significantly higher DR-70 values than those with early-stage tumours (P < 0.0003). The DR-70 immunoassay reliably differs between cancer patients and healthy controls. Therefore, it promises to become a useful test for the detection of cancer in clinical practice.

Rapid detection of fibrinogen and fibrin degradation products using a smart QCM-sensor

We have developed a rapid immunosensor for fibrinogen and fibrin degradation products (FDP) that combines a quartz crystal microbalance (QCM) with the agglutination reaction of anti-FDP antibody immunized latex beads. We measured FDP concentration successfully in human serum within 10 min with a smart QCM-sensor. The detection range of the smart QCM-sensor is covered with screening concentration of FDP in serum (less than 10 μg ml −1 of FDP).

Rapid detection of fibrinogen and fibrin degradation products using a smart QCM-sensor

We have developed a rapid immunosensor for fibrinogen and fibrin degradation products (FDP) that combines a quartz crystal microbalance (QCM) with the agglutination reaction of anti-FDP antibody immunized latex beads. We measured FDP concentration successfully in human serum within 10min with a smart QCM-sensor. The detection range of the smart QCM-sensor is covered with screening concentration of FDP in serum (less than 10μgml−1 of FDP).

Conventional detection method of fibrinogen and fibrin degradation products using latex piezoelectric immunoassay

We developed a conventional immunosensor for fibrinogen and fibrin degradation products (FDP) to combine a quartz crystal microbalance (QCM) with the agglutination reaction of immunized latex beads. FDP induced an immunoreaction due to anti-FDP antibody immobilized latex particles. We successfully measured FDP concentration of in human serum within 10 min by QCM method. The detection range of QCM immunosensor is covered with screening concentration of FDP in serum (<10 μg/ml of FDP). The time course of latex agglutination obtained from QCM immunosensor is synchronized to that of latex photometric immunoassay. SEM was used to observe the surface of QCM that applied FDP serum. The size of latex particles agglutinated on the QCM electrode increased concomitant with FDP concentration. Frequency shift on immunoreaction explains the increased adsorption amount of agglutinated latex on QCM.

Bacterial lipopolysaccharide decreases thrombomodulin expression in the sinusoidal endothelial cells of rats – a possible mechanism of intrasinusoidal microthrombus formation and liver dysfunction

Background/Aims: To elucidate the mechanism of liver dysfunction occurring in patients with sepsis, we evaluated the effect of bacterial lipopolysaccharide (LPS) on the expression of thrombomodulin (TM) in rat sinusoidal endothelial cells (SECs) and the therapeutic efficacy of exogenous recombinant TM. Methods: We induced endotoxemia in rats by bolus intraperitoneal injection of LPS. TM antigen levels within tissues were assessed by immunohistochemistry. We measured TM in cultured SECs by enzyme immunoassay, functional analysis and real-time polymerase chain reaction (PCR). Results: TM antigen and activity levels were significantly decreased in SECs isolated from LPS-treated rats after 3 and 6 h treatment, and recovered after 12 h treatment, correlating with immunohistochemical observations. In contrast, TM messenger RNA was decreased after 6 and 12 h treatment, and slightly recovered after 24 h treatment. TM expression in cultured SECs isolated from normal rats was also reduced after treatment with LPS and tumor necrosis factor (TNF)-α in vitro. The increased levels of serum fibrin degradation products (FDP), fibrin deposition within liver sinusoids, injury of SECs and liver dysfunction induced by LPS in our rat model was improved by recombinant TM treatment. Conclusions: Decreased TM expression in SECs of LPS-treated rats may result in intrasinusoidal microthrombus formation and subsequent liver dysfunction during sepsis.

Clinicopathologic evidence of disseminated intravascular coagulation in horses with acute colitis.

To detect subclinical disseminated intravascular coagulation (DIC) in horses with colitis and to determine any association between the diagnosis of subclinical DIC and outcome or occurrence of complications in horses with colitis. Prospective study. 37 horses admitted to a veterinary teaching hospital for treatment of acute colitis. Coagulation profiles were obtained on each horse 0, 24, and 48 hours after admission. Six tests were performed: platelet count, plasma fibrinogen concentration, prothrombin time, activated partial thromboplastin time, antithrombin activity, and serum fibrin degradation products concentration. A clinicopathologic diagnosis of subclinical DIC was made if 3 of the 6 tests had abnormal results at any 1 sample period. No horse had clinical signs of DIC at the time of sampling. Twelve of 37 (32%) horses met the criteria for diagnosis of subclinical DIC within a 1-year period. Outcome was defined as survival or nonsurvival. Five of 12 horses with subclinical DIC and 2 of 25 horses without subclinical DIC did not survive. Crude odds ratio analysis revealed a horse with acute colitis was 8 times as likely to die or be euthanatized if a diagnosis of subclinical DIC was made. Clinicopathologic evidence of DIC is common and is significantly associated with a poor outcome in horses with acute colitis. Treatment of subclinical DIC may influence outcome in horses with acute colitis.

Catastrophic Antiphospholipid Syndrome

Catastrophic Antiphospholipid Syndrome

Evaluation of the potential causes of epistaxis in dogs with natural visceral leishmaniasis

Haemostasis was evaluated in 19 dogs with natural Leishmania infection, six of them with a history of epistaxis, and the results were compared with the results from 24 healthy dogs....

Disseminated intravascular coagulation

Healthy pregnancy is accompanied by changes in the haemostatic system which convert it into a hypercoagulable state vulnerable to a spectrum of disorders ranging from venous thromboembolism to disseminated intravascular coagulation (DIC). This latter is always a secondary phenomenon triggered by specific disorders such as abruptio placentae and amniotic fluid embolism due to release of thromboplastin intravascularly or endothelial damage resulting from pre-eclampsia and sepsis. In modern obstetric practice the most common cause is haemorrhagic shock with delay in resuscitation leading to endothelial damage. The initial management of massive obstetric haemorrhage is the same whether associated with coagulopathy initially or not. Low-grade DIC, associated with pre-eclampsia, is monitored haematologically by serial platelet counts and serum fibrin degradation products (FDPs). Supportive measures and removal of the triggering mechanism are the key to successful management. Outcome depends primarily on our ability to deal with the trigger and not on direct attempts to correct the coagulation deficit.

Variations and clinical significance of coagulation and fibrinolysis parameters in patients with diabetes mellitus.

We observed the changes of parameters of coagulation and fibrinolytic system in order to understand the clinical implication of these variations in type II diabetic patients. Subjects consisted of 22 patients with type II diabetes mellitus and 25 healthy controls. Compared with the control, activated partial thromboplastin time, prothrombin time were shortened in the patients. The diabetic subjects also displayed higher levels of D-dimer, serum fibrin degradation products, median concentrations of fibrinogen (3.99 vs 2.96 g/L, P < 0.01) and von Willebrand factor (149% vs 87%, P < 0.01). Levels of antithrombin III activity or antigen were not different from control values. Simple linear regression analysis revealed a negative correlation between antithrombin III activity and fast blood glucose. Diabetic patients with vascular complications had significantly higher levels of fibrinogen and D-dimer than those without diabetic angiopathy. Our data demonstrated that patients with type II diabetes mellitus had a hypercoagulable state. We believed the activation of coagulation might contribute to the vascular complications in diabetics.

Blood coagulopathy in dogs with shock induced by injection of heartworm extract

Summary A crude, whole-body extract of female heartworms was administered iv to 10 dogs with and 13 dogs without heartworm (hw) infection. Shock developed in 8 of 10 infected dogs and 11 of 13 noninfected dogs, and blood coagulopathy was observed in 12 of 19 dogs with shock. Prevalence and severity of blood coagulopathy were proportionate to prevalence and severity of shock. Platelet count decreased in all dogs with shock with or without blood coagulopathy; thus, the decrease in platelet count might be related to shock. In 4 dogs, activated partial thromboplastin time (aptt) was prolonged - 192.0 seconds at 30 minutes after hw injection - and prothrombin time (pt) was increased-13.8 seconds at initial collapse. In 8 dogs, aptt was increased - 200 seconds for 2 hours after hw injection - and pt was increased - 200 seconds at 30 minutes after the injection. The aptt prolongation might have been caused mainly by decreases in activities of factors VIII, IX, XI, and XII of the intrinsic blood coagulation pathway. In dogs with severely prolonged pt plasma fibrinogen concentration and factor II activity decreased slightly. Prolonged pt was corrected in vitro by addition of normal plasma at high concentration (&gt; 80 %), but prolonged aptt could not be corrected in vitro by addition of 80 % normal plasma. Serum fibrin degradation products concentration was &lt; 10 μg/ml, and soluble fibrin monomer complex was negative in all dogs. Thrombi were not found in blood vessels of any organ at necropsy and after histologic study. Therefore, it was suggested that blood coagulopathy resulting from inhibition of coagulation factor activities might develop in shock induced by hw extract.