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1.
BACKGROUND: Disseminated intravascular coagulation (DIC) is common among patients with sepsis. Leptospirosis is an important cause of sepsis in tropical areas, and pulmonary hemorrhage associated with thrombocytopenia is the major cause of death, but the coagulopathy in severe leptospirosis has not been further characterized. The aim of this study was to evaluate coagulation factors and the presence of DIC in patients with leptospirosis in northeast Thailand. METHODS: We measured plasma concentrations of fibrinogen, D-dimer, thrombin-antithrombin III complexes, and prothrombin fragment 1,2 and evaluated the DIC score in 79 patients with culture-confirmed and/or serologically confirmed leptospirosis and in 33 healthy Thai control subjects. RESULTS: The median concentrations of fibrinogen, D-dimer, thrombin-antithrombin III complexes, and prothrombin fragment 1,2 were significantly elevated in a cohort of 79 patients with leptospirosis, compared with healthy control subjects (P相似文献   

2.
Pulmonary hemorrhage is a rare but well-known complication in preterm infants. We present a case of massive pulmonary hemorrhage in a 9-day-old male infant, successfully treated with intravenous recombinant activated factor VII (rFVIIa) (NovoSeven; Novo Nordisk). The infant was diagnosed with sepsis-related disseminated intravascular coagulation and required ventilator support for respiratory distress syndrome and blood transfusions due to active bleeding from endotracheal tube. After administration of the second dose of rFVIIa (120 microg/kg per dose, every 2 h), the active bleeding subsided dramatically and a significant improvement in the oxygenation index was seen 8 h after the third dose of rFVIIa treatment. There were also significant improvements in the prothrombin time, International Normalized Ratio, activated partial thromboplastin time and plasma fibrinogen levels after the third dose of rFVIIa treatment. The infant was discharged on day 82 of life and there was no finding of thrombosis during the hospitalization period. At month 18 of follow-up, there was no morbidity related to the pulmonary and central nervous systems. This case suggests that rFVIIa is effective as an alternative therapy in controlling massive pulmonary hemorrhage of preterm infants.  相似文献   

3.
We report the ex vivo effect of recombinant activated factor VII (rFVIIa) on prothrombin activation after whole blood clotting. Two patients with severe thrombocytopenia and life-threatening haemorrhage were successfully managed using a single dose of rFVIIa (90 microg/kg). Western blotting using antiprothrombin antibody showed that rFVIIa did not induce thrombin generation in citrated platelet-poor plasma. Patient sera showed significantly impaired prothrombin activation before and after rFVIIa administration. rFVIIa administration shortened the prothrombin time, activated partial thromboplastin time and Ivy bleeding time, and normalized the clot retraction. These data indicate that rFVIIa accelerated thrombin generation without significant increase of generated thrombin.  相似文献   

4.
A 50-year-old woman was admitted to the emergency room. An appendectomy was done. On the sixth day the patient's general state deteriorated and she became somnolent with jaundice due to distal obstructive choledocholithiasis. The results of laboratory tests were platelets 12 x 10(9)/L, prothrombin time 13 seconds, international normalized ratio 1.19, activated partial thromboplastin time 31.8 seconds, and fibrinogen 8.78 g/L. There was no evidence of disseminated intravascular coagulation. In view of the patient's clinical condition, surgery was considered to be indicated. Because it was a life-threatening situation and at the time there was no platelet concentrate available for immediate transfusion, she was treated with a single dose of recombinant factor VIIa (rFVIIa) (60 microg/kg). The dose of 60 microg/kg was selected on the basis of experience with rFVIIa in the treatment of hemophilic patients. In this case, use of rFVIIa was a valid alternative to control the bleeding in a patient with thrombocytopenia. However, despite the efficacy of the treatment, it should not be forgotten that it was used because of the unavailability of platelets and that we were dealing with a life-threatening situation. Clinical trials should be carried out to verify the safety, effectiveness, and efficiency of rFVIIa in these cases.  相似文献   

5.
BACKGROUND: Cancer is one of the most common acquired causes of venous thromboembolism. AIM: To evaluate haemostasis disorders in patients with non-metastatic gastric cancer. PATIENTS AND METHODS: We studied 11 patients with non-metastatic gastric cancer (9 males and 2 females, median age 54 years) and 20 healthy subjects (15 males and 5 females, median age 48 years) control. We measured prothrombin time, activated partial thromboplastin time, coagulation time, clot lysis time, fibrinogen, clotting factors (II, VII, VIII, IX, X), C protein, S protein, AT III, activated protein C resistance, prothrombin 1+2 fragment, tissue plasminogen activator and D-Dimer in all subjects. RESULTS: Fibrinogen plasma levels were significantly higher in patients with non-metastatic gastric cancer than in control group (505+/-24 mg/dl vs 336+/-30 mg/dl, p<0.001). We also found a significant increase in prothrombin 1+2 fragment plasma concentration compared with controls (3.8+/-0.6 nM vs 0.83+/-0.09 nM, p<0.001). Plasma D-dimer levels were 20-fold higher in patients with non-metastatic gastric cancer compared with controls (9.57+/-0.4 ng/dl vs 0.4+/-0.05 ng/dl, p<0.001). Also tissue plasminogen activator was significantly higher in gastric cancer patients than in controls (20.8+/-2.32 ng/ml vs 9.1+/-1.37 ng/ml, p<0.01). Finally clot lysis time was significantly accelerated in gastric cancer patients compared with control subjects (81+/-37 min vs 233+/-74 min, p<0.01). CONCLUSIONS: Patients with non-metastatic gastric cancer are at risk for thrombotic events due to the combined increase in fibrinogen plasma levels and thrombin formation.  相似文献   

6.
BACKGROUND: Patients with cirrhosis have low levels of coagulation factors, the most pronounced deficiency being that of FVII. This may compromise haemostasis during bleeding from ruptured oesophageal varices. The objective of this trial was to evaluate the effect of rFVIIa on prothrombin time in cirrhosis patients with ongoing variceal bleeding. Safety, including signs of DIC, was monitored. METHODS: The study is a single centre, open-label trial. Ten consecutive patients with known alcoholic cirrhosis and oesophageal variceal bleeding were included. The patients received routine treatment, including Terlipressin. Each patient received one i.v. injection of rFVIIa (80 microg/kg bw). The study observation time was 12 h per patient. RESULTS: The mean age of the patients was 48 years (8 men and 2 women). The cirrhosis was classified as Child B in 5 patients and Child C in 5. At baseline, all patients had prothrombin time levels above the normal range, and all but one had FVII coagulation activity (FVII:C) levels below the normal range. rFVIIa normalized the prothrombin time in all patients within 30 min. The effect lasted for more than 4 h in 7 patients, and for about 2 h in the remaining 3 patients. Immediate bleeding control was obtained in all patients, and no patient died within the study time. There was no sign of DIC. CONCLUSIONS: rFVIIa is effective in transiently reversing the prolonged prothrombin time in cirrhosis patients with haematemesis from varices. This indicates a potential of improving haemostasis and survival in patients with compromised coagulation due to liver disease.  相似文献   

7.
Recombinant activated factor VII (rFVIIa) is indicated mainly for the treatment of patients with haemophilia and inhibitors. However, little information is available on the use of rFVIIa in the treatment of the severe bleeding associated with disseminated intravascular coagulation (DIC). We report a pregnant woman with DIC, who developed severe intra-abdominal bleeding after caesarean section. Despite treatment with fresh-frozen plasma, fibrinogen, platelet transfusions and surgery, the abdominal bleeding persisted and intravenous treatment with rFVIIa was initiated. The response to treatment was rapid, with control of the bleeding and resolution of the coagulopathy. No side-effects related to rFVIIa were noted. This case suggests a potential role for rFVIIa in the treatment of severe and refractory bleeding associated with DIC.  相似文献   

8.
Acute biphenotypic leukemia is a very rare malignancy of childhood. Hemorrhage is a frequent complication of these patients. An 18-year-old-male with acute biphenotypic leukemia developed massive gastrointestinal bleeding that was thought to be due to thrombocytopenia during chemotherapy-induced pancytopenia and did not respond to conventional therapy. Although the prothrombin time and the partial thromboplastin time were within normal limits, inspired by the success in thrombocytopenia and platelet function disorders we decided to use recombinant activated factor VII (rFVIIa) as a last resort. After using a single dose (65 microg/kg) of rFVIIa on the fifth day of bleeding, the bleeding ceased immediately. rFVIIa may be a novel therapeutic alternative in leukemia or chemotherapy-associated massive bleeding.  相似文献   

9.
Haemophilia patients with inhibitors can develop bleeding episodes, which are refractory to monotherapy with either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (APCC). Management of such bleeds is often difficult. We previously reported the safety of using a combination of rFVIIa and APCC given in sequential fashion. In this report, we update our experience with sequential therapy. A retrospective review of medical records was conducted including all reports of sequential therapy defined as receiving both rFVIIa and APCC within 6 h. Data extracted included demographic data, treatment prior to and following hospital admission, clinical data including type and location of bleed, response to therapy, physical examination and laboratory data. In addition, for some patients, thromboelastography was performed to document the effect of sequential therapy on clot formation characteristics. Four patients comprising 35 admissions, 209 hospital days and 115 days of sequential therapy were included in the updated dataset. No patient developed thrombosis or overt disseminated intravascular coagulation (DIC) although elevations in the D-dimer above 5 microg mL(-1) were noted in 42% of the courses that lasted >3 days. Efficacy is suggested by the fact that patients had resolution of their bleeds after a median of 3 days of sequential therapy after failing to respond to a median of 3 days of monotherapy. Thromboelastography demonstrated an additive effect. Sequential therapy is a safe, potentially efficacious approach in the management of refractory bleeding episodes in patients with haemophilia and inhibitors.  相似文献   

10.
Disturbances of blood coagulation were studied in 32 consecutive patients with typhoid fever on their admission to hospital. Estimations of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products (FDPs), factors VII, VIII and XII, alpha I antitrypsin, plasminogen, CI esterase inhibitor, and platelet counts were performed as well as liver function tests and blood counts. Five patients had laboratory evidence of disseminated intravascular coagulation (DIC) and two had a generalised bleeding disorder which in the other three was inapparent. The platelet count in the group as a whole was low (P less than 0.05) and the FDPs in most cases were mildly elevated. The pre-kallikrein values were depressed in three of the five with DIC, whereas factor XII was not reduced. These results indicate that bleeding disorders in typhoid fever are uncommon. The depression of pre-kallikrein indicates that the DIC is probably triggered by activation of the intrinsic coagulation pathway. Most patients had lymphopenia and monocytopenia but only two had neutropenia.  相似文献   

11.
This study aimed at investigating the impact of hemolysis on different coagulation parameters.A total of 216 venous blood samples without visible hemolysis were collected from adult patients at a tertiary referral center over six months. The plasma obtained was quantified for six coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin III, and protein C. The rest of the plasma from each blood sample was aliquoted into three tubes, each containing 1 mL of plasma with three different volumes of cell-free hemoglobin (i.e., 2, 4, 8 μL) from lysed RBCs to create simulated hemolyzed blood samples with hemoglobin concentration of approximately 0.1, 0.2, and 0.4 g/dL to mimic mild (1+), moderate (2+), and severe (3+) hemolysis, respectively, before repeating the coagulation tests to determine possible correlation between the simulated degree of hemolysis and the changes in test results of the coagulation parameters.Spearman correlation analysis showed significant decreases in the values of activated partial thromboplastin time, fibrinogen, D-dimer, and protein C values with an increasing degree of simulated hemolysis (all P < .01). Comparison of the percentage bias of biological variance showed significant positive associations of cell-free hemoglobin concentrations with the percentage bias of D-dimer and protein C. However, only the former was still within the range of biological variance under condition of simulated hemolysis. Besides, the presence of cell-free hemoglobin regardless of concentration had a notable impact on the percentage bias of activated partial thromboplastin time, whereas the influence was non-significant for prothrombin time, fibrinogen, and antithrombin III.The results showed different impacts of simulated hemolysis on six coagulation parameters, highlighting the dependence of clinical reliability on the coagulation parameter to be investigated in hemolytic blood samples.  相似文献   

12.
A multicenter and open-labeled clinical trial of human recombinant factor VIIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study 1, the pharmacokinetics, pharmacodynamics, and safety of a single dose of 120 microg/kg of rFVIIa were investigated in 8 patients. In the subsequent study 2, the hemostatic effect and safety of rFVIIa were evaluated during a 24-week period in 10 patients. In study 1, the mean maximum FVII-coagulant activity (FVII:C) was found to occur after 10 minutes; activity then decreased rapidly and returned to the baseline within 24 hours after a single intravenous infusion of rFVIIa. The mean half-life of FVII:C was 3.5 hours. The activated partial thromboplastin time and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing. In study 2, 86 microg/kg to 120 microg/kg of rFVIIa (mean, 97 microg/kg) was administered 1 to 85 times to 10 patients. A total of 58.0% (91/157) of bleeding episodes were treated excellently or effectively, with 5 (3.2%) ineffective episodes. There was no apparent trend in the relationship of the hemostatic effect with bleeding sites, mean dose, or number of injections. The efficacy rate, however, was significantly higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatment-related adverse events were observed, and there was no evidence of antibody formation to rFVIIa. In conclusion. rFVIIa is an effective and well-tolerated option for treatment of bleeding episodes in hemophilia patients with inhibitors.  相似文献   

13.
Short-term venous stasis influences routine coagulation testing.   总被引:2,自引:0,他引:2  
Preanalytical variability is a common source of errors in coagulation testing, as clotting assays are particularly susceptible to poor standardization of the whole analytical process. To investigate the effect of a short-term venous stasis on routine coagulation testing, we measured activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimer in plasma specimens collected either without venous stasis or following the application of a 60 mmHg constant, standardized external pressure by a sphygmomanometer, for 1 (1-min stasis) and 3 min (3-min stasis). When compared with blood specimens collected without stasis, the Pearson's correlation coefficients and the corresponding slopes of the Passing and Bablok regression line of samples collected following 1 and 3-min stasis were acceptable. However, statistically significant differences by paired Student's t-test could be observed for all parameters tests following 3-min stasis, and for all but the activated partial thromboplastin time after 1-min stasis. Significant difference between specimens collected after 1- and 3-min stasis was also achieved for prothrombin time (P < 0.01), fibrinogen (P < 0.01) and D-dimer (P < 0.05). The agreement between measurements was yet acceptable after 1-min stasis, but achieved clinical significance for prothrombin time, fibrinogen and D-dimer after 3-min stasis. Taken together, results of the present investigation confirm that the effects of venous stasis during venipuncture are clinically meaningful. As hematocrit values and activities of clotting factors VII, VIII and XII significantly increased, whereas that of activated factor VII remained unchanged, we hypothesize that a short-term venous stasis, as induced by up to 3-min tourniquet placing, might not be sufficient to produce additional procoagulant responses besides hemoconcentration.  相似文献   

14.
PURPOSE: The prothrombotic state that occurs in uremic patients may increase their cardiovascular risk. We studied hypertensive patients with mild-to-moderate impairment of renal function to determine if they had evidence of abnormalities in the coagulation system. SUBJECTS AND METHODS: Renal function was assessed in 382 patients with essential hypertension, in whom 24-hour creatinine clearance, urinary protein excretion, and microalbuminuria were measured. We evaluated the function of the coagulation system by measurement of platelet counts, prothrombin time, partial thromboplastin time, and plasma antithrombin III, fibrinogen, D-dimer, and prothrombin fragment 1 + 2 levels. RESULTS: Impaired renal function, defined as a creatinine clearance of 30 to 89 mL per minute per 1.73 m(2) of body surface area, was found in 168 (44%) of the patients. Age, blood pressure, duration of hypertension, and plasma levels of fibrinogen, D-dimer, prothrombin fragment 1 + 2, and lipoprotein(a) were significantly greater in these patients than in those with normal renal function; these differences persisted after adjustment for potential confounders. Creatinine clearance was significantly and inversely correlated with levels of plasma fibrinogen (Spearman's rho = -0.26, P <0.001), D-dimer (rho = -0.33, P <0.001), and prothrombin fragment 1 + 2 (rho = -0.20, P <0.001). Levels of plasma fibrinogen (P = 0.009) and D-dimer (P = 0.003) were correlated with renal function independent of age, blood pressure, duration of hypertension, triglyceride level, urinary protein excretion, and erythrocyte sedimentation rate. Lipoprotein(a) levels were correlated with fibrinogen (rho = 0.16, P = 0.003) and D-dimer (rho = 0.26, P <0.001) levels. CONCLUSIONS: Increased plasma levels of fibrinogen, D-dimer, and prothrombin fragment 1 + 2 are present in hypertensive patients with mildly decreased creatinine clearance, suggesting that the coagulation system is activated in these patients.  相似文献   

15.
Background: Patients with cirrhosis have low levels of coagulation factors, the most pronounced deficiency being that of FVII. This may compromise haemostasis during bleeding from ruptured oesophageal varices. The objective of this trial was to evaluate the effect of rFVIIa on prothrombin time in cirrhosis patients with ongoing variceal bleeding. Safety, including signs of DIC, was monitored. Methods: The study is a single centre, open-label trial. Ten consecutive patients with known alcoholic cirrhosis and oesophageal variceal bleeding were included. The patients received routine treatment, including Terlipressin. Each patient received one i.v. injection of rFVIIa (80 µg/kg bw). The study observation time was 12 h per patient. Results: The mean age of the patients was 48 years (8 men and 2 women). The cirrhosis was classified as Child B in 5 patients and Child C in 5. At baseline, all patients had prothrombin time levels above the normal range, and all but one had FVII coagulation activity (FVII:C) levels below the normal range. rFVIIa normalized the prothrombin time in all patients within 30 min. The effect lasted for more than 4 h in 7 patients, and for about 2 h in the remaining 3 patients. Immediate bleeding control was obtained in all patients, and no patient died within the study time. There was no sign of DIC. Conclusions: rFVIIa is effective in transiently reversing the prolonged prothrombin time in cirrhosis patients with haematemesis from varices. This indicates a potential of improving haemostasis and survival in patients with compromised coagulation due to liver disease.  相似文献   

16.
Collaborative studies on hemostasis in dengue hemorrhagic fever (DHF) patients by Indonesian and Japanese teams revealed that all DHF patients had manifestations of the acute type of disseminated intravascular coagulation (DIC). Prolongations of activated partial thromboplastin time and prothrombin time and decreases of platelet counts, fibrinogen, prothrombin, factor VIII, plasminogen and antithrombin III activities were observed transiently during the acute stage of DHF. It was also found that alpha 2 antiplasmin was decreased in the acute stage to 32% of the normal level on the average. This may characterize the hemorrhagic diathesis of the DHF patients.  相似文献   

17.
S ummary . In an investigation of 34 patients with laboratory evidence of disseminated intravascular coagulation (DIC), 17 were found to have a prolonged prothrombin time, 11 a prolonged partial thromboplastin time, and only 10 a prolonged thrombin time. Coagulation factor assays in these patients revealed deficiency patterns compatible with vitamin K deficiency and/or liver disease. In addition, a prolonged prothrombin time rapidly returned to normal in five of seven patients given vitamin K1. It is suggested that vitamin K deficiency and liver dysfunction occurred as a complication of the primary condition that led to DIC. The practical implications of these findings are that a prolonged prothrombin time and partial thromboplastin time may occur in patients with laboratory evidence of DIC in the presence of a normal thrombin time. Under these circumstances bleeding in patients with laboratory evidence of DIC is likely to be caused by vitamin K deficiency or liver dysfunction and therefore may be more appropriately treated with vitamin K than with heparin.  相似文献   

18.
《Amyloid》2013,20(3):129-132
Objective: Familial amyloid polyneuropathy (FAP) is an autosomal dominant form of hereditary amyloidosis. Several studies reported coagulation factor X deficiency and excessive fibrinolysis in immunoglobulin light chain amyloidosis. However, few have investigated coagulation and fibrinolysis in FAP. The objective of this study was to determine abnormalities in plasma biomarkers of coagulation and fibrinolysis in FAP. Methods: We prospectively recruited eight FAP patients with transthyretin mutations and ten age-matched control patients with other neuropathies in our university. We examined plasma biomarkers of coagulation and fibrinolysis including prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin/fibrinogen degradation products, D-dimer, α2-antiplasmin, antithrombin, plasminogen, thrombin-antithrombin complex, plasmin-α2-antiplasmin complex, prothrombin fragment 1+2, and coagulation factor X. The Mann–Whitney U test was performed for statistical comparisons between FAP and control groups. Results: FAP patients exhibited significantly decreased levels of coagulation factor X, plasminogen and α2-antiplasmin, and significantly increased levels of prothrombin fragment 1+2 compared to control patients. Conclusion: Our results indicate abnormalities of coagulation and fibrinolysis in FAP patients.  相似文献   

19.
OBJECTIVE: This autopsy study was carried out to investigate the relationship between the number of pulmonary microthromboemboli and coagulation tests in patients with coagulation abnormalities. METHODOLOGY: Fifty-one patients in whom coagulation studies were performed within 2 days prior to death were studied. The coagulation tests included platelet counts, prothrombin times expressed as International Normalized Ratios (INR), activated partial thromboplastin times, fibrinogen concentrations, plasma fibrinogen/fibrin fragment E antigen levels, and plasma D-dimer levels. For microscopic analysis, five tissue blocks of the lung were taken from each subject and the number of pulmonary microthromboemboli per 20 cm2 of tissue sections was calculated. RESULTS: Thirty-six of the 51 patients had pulmonary microthromboembolism. International Normalized Ratios were higher than 1.7 in 12 of 36 embolic and in two of 15 non-embolic patients (33.3% of sensitivity and 86.7% of specificity). There was no significant difference in D-dimer levels between the two groups. Multiple regression analysis identified that INR was significantly related to the number of microthromboemboli (P = 0.042). CONCLUSIONS: D-dimer levels appear to be inappropriate as a single screening test for disseminated intravascular coagulation (DIC) in critically ill patients because the levels in these subjects are elevated irrespective of the presence of microthromboemboli. Because of the high specificity, INR could be a specific marker for microthromboemboli. The significant association between the number of microthromboemboli and INR might indicate the importance of the extrinsic pathway in the initiation of DIC.  相似文献   

20.
目的:探讨分析老年人慢性阻塞性肺疾病急性加重期(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)并发呼吸衰竭(respiratory failure,RF)和多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)凝血功能的变化及其临床意义。方法选择2014年3月至2015年6月老年人单纯 AECOPD 患者30例(AECOPD 组),AECOPD 并发 RF 患者26例(RF 组),AECOPD 并发 MODS 患者19例(MODS 组),同时选取同期我院体检的健康老年人30名(对照组),比较各组的血小板、D-二聚体、纤维蛋白原、活化的部分凝血活酶时间、血浆凝血酶原时间、氧分压、二氧化碳分压等肺功能指标差异。结果对照组、AECOPD 组、RF 组、MODS组患者的 D-二聚体、纤维蛋白指标依次上升,差异有统计学意义(P <0.05);对照组、AECOPD组、RF 组、MODS 组患者的氧分压、二氧化碳分压等肺功能指标组间差异有统计学意义(P <0.05);而血小板、活化的部分凝血活酶时间、血浆凝血酶原时间指标在对照组、AECOPD 组、RF组、MODS 组患者中呈上升趋势,但差异无统计学意义(P >0.05)。结论老年人 AECOPD 患者处于高凝状态,当合并 RF 和 MODS 时血凝状态加重,值得临床及早重视并采取相关措施以防止病情加剧、恶化。  相似文献   

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