Abnormalities in cancer patients' coagulation system.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22207-e22207
Author(s):  
Hector Alirio Gonzalez Florez ◽  
M. Rojas ◽  
J. Quiroz ◽  
Y. Mancera

e22207 Background: It is well known cancer patients may present both hemorrhagic and thrombotic abnormalities and these phenomena are difficult to diagnose and treat. Thrombotic phenomena are developed clinicly in 15% in cancer patients and it’s higher in adenocarcinomas and myeloprolipherative disorders. These complications can be the consequence of coagulations factor direct activation or chronic DIC, because of the acquired capacity of neoplastic cells for starting coagulation cascade. Methods: In this study an untreated cancer patients group were compared with another healthy controls group, older than 14 years. Patients before treatment and controls were laboratory tested. A t – test for independent samples was employed. Results: Number: patients group: 66, control group: 73. Median age: patients: 50 (17-78). Controls: 52 (18 -93). Sex: Patients: men: 35%, women: 65%. Controls: men: 52%, women: 48%. Malignancies: breast cancer 9.7%; gastric carcinoma 8.1%; cervical carcinoma 6.5%; NH lymphomas 6.5%, unknown origen metastatic carcinoma 4.8%; oral carcinoma 4.8%. Clinical stages: I: 6.3%; II: 6.3%; III: 22.9%; IV: 62.5% (metastatic) 47.9%. Thrombotic antecedents in patients group: 19.7%. There were significant differences in: Platelets count: patients: 281121, controls: 307745 (p<0.001). Protein C: 0.87 and 3.81 UI/mL, respectively (p < 0.001). Antithrombin III: 97 and 101% (p<0.001). Plasminogen: 92.9 and 101.1% (p < 0.001). Lupus anticoagulant (RVV time): 27 and 25.6” (p<0.001). There were no significant differences in PT: 18.3 and 16.9” and PTT: 31 and 34”. The same significant differences were got when the patients of every clinical stage were compared with control patients. There were no differences when the patients of every clinical stage were compared among themselves, nor between sex. Conclusions: This study shows cancer patients may have many coagulation abnormalities: anticoagulant system defects and fibrinolytic system hipoactivity, demonstrated by the significant differences found in antithrombin III, protein C and plasminogen levels between patients and controls groups. It is suggested to practice these tests to cancer patients, even without clinical coagulation disorders, to stablish prophylactic measures.

1997 ◽  
Vol 83 (6) ◽  
pp. 948-952 ◽  
Author(s):  
Domenico De Lucia ◽  
Ferdinando DeVita ◽  
Michele Orditura ◽  
Valter Renis ◽  
Antonello Belli ◽  
...  

Aims and background Thromboembolic complications are common in patients with cancer and represent the second cause of death in patients with overt malignant disease. The aim of this study was to investigate the activated protein C pathway in cancer. Methods We studied the coagulation cascade, natural clotting inhibitors, fibrinolytic proteins and resistance to activated protein C in 20 patients with advanced gastrointestinal cancer and 84 volunteers by measuring PT, APTT, fibrinogen, AT III, PC, PS, APC resistance, fibrinolytic system (PLG, ANPL, PAI-1 and t-PA) and activation peptides (D-Dimers, prothrombin 0 fragment 1+2/F1+2). Results Laboratory tests confirmed coagulation abnormalities in cancer patients. Fibrinogen, D-Dimers and F1+2 were increased, while t-PA activity was significantly lower than that of controls. APC resistance was higher in cancer patients compared to the control group (55% vs 2%; P < 0.0001). Excess thrombin generation was manifested by increased F1+2 plasma levels in APC-resistant cancer patients. Genetic analyses showed that only one patient with a poor response to APC carried a factor V R506Q mutation in exon 10. Conclusions Our findings show a high prevalence of APC resistance in cancer, compatible with an acquired defect in the APC pathway.


2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 458-471 ◽  
Author(s):  
X. Wang ◽  
S. Fu ◽  
R. S. Freedman ◽  
J. J. Kavanagh

Venous thromboembolism (VTE) could be presented as an initial clinical feature in some cancer patients or a complication followed by various cancer treatments, which all indicates a poor outcome. This review focuses on elucidating the relationship of VTE and the main gynecological cancers including ovarian, endometrial, and cervical cancers. First, the general VTE information about gynecological cancer are introduced; second, the risk factors of VTE developing in gynecological cancer were discussed; third, we do a retrospective analysis on a novel treatment targeting coagulation cascade; and last, we analyze VTE as a remarkable complication followed by recombinant human erythropoietin and anti–vascular endothelial growth factor treatment in gynecological cancer patients. In summary, the interaction between the coagulation system and cancer progression is a novel promising area to be explored in the study of VTE in patients with gynecological cancer.


2002 ◽  
Vol 10 (2) ◽  
pp. 61-66
Author(s):  
Dragana Petrovic

BACKGROUND: Influences of CMF (cyclophosphamide, methotrexate,5-fluorouracil) chemotherapy on blood coagulation were investigated in 30 patients receiving adjuvant chemotherapy and in 30 patients receiving chemotherapy for metastatic breast cancer. METHODS: In plasma samples of 60 patients (median age 49.5), we evaluated the following parameters 1)Markers of in vivo clotting activation thrombin-antithrombin complex (ELISA) and D-dimer (ELISA), 2) Natural anticoagulants (protein C [PC] and antithrombin III [AT III] by chromogenic methods). The coagulation studies were performed at the beginning and at the end of the first cycle of CMF protocol. RESULTS: Before CMF therapy, significant difference was observed between patients with early stage and patients with metastatic breast cancer in the PC (p<0.01), AT III (p<0.01) and TAT (p<0.01) levels. After CMF therapy, patients with stage II (adjuvant) disease manifested a significant decrease in the level of PC and AT III activity (p<0.01) and an increase in TAT level (p<0.01). In patients with disseminated breast cancer CMF therapy provoked an increased level of TAT and D-dimer with a decreased activity of protein C and antithrombin III. There was significant difference in value of TAT, D- dimer, protein C and antithrombin III between the patients with adjuvant and metastatic breast cancer patients after CMF chemotherapy CONCLUSION: Our results suggest that the application of cytotoxic therapy provokes hypercoagulable condition in breast cancer patients. This effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.


2020 ◽  
Vol 20 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Amany M. Abo-Elenein ◽  
Maaly M. Mabrouk ◽  
Sabry Abou-Saif ◽  
Ola M. Saeed ◽  
Samy Khodeir ◽  
...  

Background & Aims: Chronic liver disease is characterized by complex hemostatic disorders because the liver is the site where most of the coagulation factors and their inhibitors are synthesized. The aim of this study was the evaluation of protein C and antithrombin III in different stages of chronic hepatitis B and C and to determine their possible role as markers of liver cell damage in different clinical stages. Methods: The study included 60 subjects who were subdivided into 4 groups: (Group I): 15 patients diagnosed as chronic viral hepatitis B or C, (Group II): 15 patients with compensated liver cirrhosis, (Group III): 15 patients with decompensated liver cirrhosis, and (Group IV) (control group): 15 healthy individuals. History taking, clinical examination and abdominal ultrasonography were made for all subjects. Investigations were done in the form of liver function tests (ALT, AST, ALP, serum bilirubin, and serum albumin), PT, PTT, CBC. Plasma levels of Antithrombin III & protein C were estimated by automated Stago compact coagulation analyzer. Results: In all patient groups, the mean value of Protein C showed significant decrease when compared to control group, mean value of antithrombin III showed a significant decrease in compensated and decompensated subjects when compared to chronic hepatitis and control groups. Antithrombin III and protein C showed a significant negative correlation with (ALT, AST, PT, PTT, INR). However, this correlation was positive with Albumin. Conclusion: Antithrombin III and protein C are natural anticoagulants and can be considered as markers of different stages of chronic liver disease. This is supported further by the comparison between the levels of these parameters and clinical stages of liver disease. Protein C is more sensitive than ATIII as a marker of hepatocellular damage.


2018 ◽  
Vol 46 (4) ◽  
pp. 411-417 ◽  
Author(s):  
Dominik Dłuski ◽  
Radzisław Mierzyński ◽  
Elżbieta Poniedziałek-Czajkowska ◽  
Bożena Leszczyńska-Gorzelak

Abstract Aim: (1) To evaluate the prevalence of inherited thrombophilia in pregnant women with adverse pregnancy outcomes: intrauterine growth retardation (IUGR), preeclampsia (PE) and placental abruption. (2) To assess the impact of inherited thrombophilia on the nature of obstetric complications. (3) To assess levels of protein S, protein C, antithrombin III and homocysteine in pregnant women with adverse pregnancy outcomes. Subjects and methods: The study comprised 162 pregnant women. The patients were divided into three test groups and one control group. In all 162 patients the following tests were completed: activated protein C resistance (APC-R), the level of free protein S, activity of protein C, antithrombin III and the level of homocysteine. The data were statistically analyzed via χ2 of independence or homogeneity test. Results: In 32 of 162 patients participating in clinical research thrombophilia was diagnosed (10 patients with APC-R, 21 patients with protein S deficiency, one patient with hyperhomocysteinemia): seven patients belonged to the control group and 25 patients had diagnosed adverse pregnancy outcomes (P=0.04). In 32 patients with diagnosed thrombophilia, level of protein S was decreased (P=0.04). Protein S deficiency was diagnosed, when level of protein S was lower than 30% in the second trimester and lower than 24% in the third trimester. The incidence of activated protein C resistance caused by the mutation of factor V Leiden was in six patients (5.9%) with adverse pregnancy outcomes, and in four patients (6.6%) from the control group. Results were not statistically significant. No protein C deficiency was diagnosed (diagnosis: level<60%), but in 50% of patients with thrombophilia level of protein C was over the norm (P=0.02). The level of antithrombin III was often decreased in patients with preeclampsia – (32.4%), then in the other patients – (17.2%) (P=0.04), but no patient was diagnosed with antithrombin III deficiency (diagnosis: level<60%). Conclusions: Tests for thrombophilia should be carried out in women with adverse pregnancy outcomes in their history, who are planning pregnancy, to start anticoagulant prophylaxis. Our study supports the thesis that tests for thrombophilia should be carried out in women with a history of adverse pregnancy outcomes and who are planning a pregnancy to start anticoagulant prophylaxis.


2009 ◽  
Vol 107 (6) ◽  
pp. 1825-1829 ◽  
Author(s):  
Jean-Michel Pontier ◽  
Nicolas Vallée ◽  
Lionel Bourdon

Previous studies have highlighted that bubble-induced platelet aggregation is a predictor index of decompression sickness (DCS) severity in animals and bubble formation after a single air dive in humans. The present study attempted to investigate plasmatic indexes of the coagulation system and platelet activation in our rat model of DCS. Male Sprague-Dawley rats were assigned to one experimental group with a hyperbaric exposure and one control group maintained at atmospheric pressure. Rats were compressed to 1,000 kPa (90 m saltwater) for 45 min while breathing air. The onset of death time and DCS symptoms were recorded during a 30-min observed period after rats had surfaced. Plasmatic indexes were platelet factor 4 (PF4) for platelet activation, soluble glycoprotein V (sGPV) for thrombin generation, and thrombin-antithrombin complexes for the coagulation system. Blood samples for a platelet count and markers were taken 3 wk before the experimental protocol and within the 30 min after rats had surfaced. We confirmed a correlation between the percent fall in platelet count and DCS severity. Plasmatic levels of sGPV and PF4 were significantly increased after the hyperbaric exposure, with no change in the control group. The present study confirms platelet consumption as a potential index for evaluating decompression stress and DCS severity. The results point to the participation of thrombin generation in the coagulation cascade and platelet activation in bubble-induced platelet aggregation. In our animal model of DCS, the results cannot prejudge the mechanisms of platelet activation between bubble-induced vessel wall injury and bubble-blood component interactions.


2011 ◽  
Vol 165 (6) ◽  
pp. 865-871 ◽  
Author(s):  
Renata Świątkowska-Stodulska ◽  
Sonia Kaniuka-Jakubowska ◽  
Piotr Wiśniewski ◽  
Anna Skibowska-Bielińska ◽  
Krzysztof Sworczak

ObjectiveAn increased tendency towards thromboembolic events is observed in patients with Cushing's syndrome. There are much fewer publications available about thromboembolic complications in patients with subclinical Cushing's syndrome (SCS). Therefore, a question arises whether hemostatic disturbances appear in this particular disease phase.Aim of studyEstimation of protein C (PC), free protein S (FPS), antithrombin (AT) activity, thrombomodulin (TM) concentration and activated PC resistance (APCR) in patients with SCS.Materials and methodsWe studied 35 patients with SCS. The control group consisted of 33 healthy volunteers. The activity of PC, AT, FPS, APCR and the concentration of TM was estimated in all representatives.ResultsThe comparison of the examined coagulation parameters between the patients with SCS and the healthy individuals revealed significantly higher mean PC activity and mean FPS activity in the SCS group. Mean TM concentration was significantly lower in patients with SCS compared with the control group. The differences in APCR and AT activity were not significant. We did not prove any statistically significant correlations between the examined coagulation parameters and hormonal parameters. We did not find any correlation between the concentration of cortisol and basic coagulation parameters such as international normalized ratio, activated partial thromboplastin time or fibrinogen in the group with SCS either.ConclusionsThe patients with SCS present disturbances in endogenous anticoagulation system defined as PC, FPS activity and TM concentration. This finding suggests an impact of mild autonomic cortisol overproduction on coagulation system.


1996 ◽  
Vol 76 (02) ◽  
pp. 226-233 ◽  
Author(s):  
Francesco Rodeghiero ◽  
Alberto Tosetto

SummaryA proper laboratory diagnosis of inherited thrombophilia due to defects of the coagulation system may be obtained only by a stringent definition of the diagnostic reference ranges taking into account the influence exerted by major physiological variables. To this purpose, we analyzed the data for Protein C, Antithrombin III, Heparin-Cofactor II and plasminogen coming from the first 4,000 subjects enrolled in the VITA Project. This is the first study that allows the establishment of reference ranges in a non-selected, active population using stringent standardization of clinical and laboratory measurements and multivariable regression techniques for data analysis.Serum triglycerides and total cholesterol, together with plasma fibrinogen were found to influence the functional plasma level of the four considered proteins. Menopause increased AT-III concentration, while pill use increased Heparin-Cofactor II and plasminogen. PT and PTT ratio, gender, age, smoking, body-mass index, HDL cholesterol and blood group had minor effects. The effect of these variables should be taken into account for both clinical and epidemiologic purposes, using appropriate reference ranges or covariance analysis for adjustment.


2017 ◽  
Vol 33 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Zhuanbo Luo ◽  
Yun Wang ◽  
Yanru Lou ◽  
Chao Cao ◽  
Richard Hubbard ◽  
...  

Background: There is an unmet need for identification of additional prognostic markers for lung cancer. The aim of this study was to identify novel clinical and immunological predictors of prognosis in lung cancer patients. Methods: Lymphocyte subsets CD3+, CD4+, CD8+, CD4+/8+, CD25+, CD69+, CD44+ and CD54+ were quantified in peripheral blood using flow cytometry, for 203 newly diagnosed lung cancer patients and 120 healthy controls. Results: The levels of CD3+, CD4+, CD8+, CD4+/CD8+ and CD69+ lymphocytes were significantly lower in patients with lung cancer compared with the healthy control group, while CD54+ and CD44+ lymphocytes were significantly higher. In stage III/IV patients with lymph node metastasis or distant metastasis, the levels of CD44+ and CD54+ lymphocytes were significantly increased compared with patients with stage I/II disease (p<0.05). The levels of CD44+ and CD54+ lymphocytes markedly reduced after chemotherapy, and follow-up analysis indicated that patients found without increase of CD44+ and CD54+ lymphocytes after chemotherapy had survival advantages. Independent predictors of survival in lung cancer patients included clinical stage (hazard ratio [HR] = 2.791; 95% confidence interval [95% CI], 1.42-3.54, p<0.001), CD44+ lymphocytes (HR = 1.282; 95% CI, 1.02-1.49, p = 0.002) and CD54+ lymphocytes (HR = 1.475; 95% CI, 1.22-1.73, p = 0.003). Elevated levels of CD44+ and CD54+ lymphocytes correlated with poor prognosis in lung cancer patients. Conclusions: Peripheral blood lymphocyte subsets in patients with lung cancer are different from those in healthy people, and circulating CD44+ and CD54+ lymphocytes seem to be a promising criterion to predict survival in lung cancer patients undergoing chemotherapy.


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