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Differential response of acute phase markers in lymphoid leukaemias – a probable diagnostic tool
Abstracts / Thrombosis Research 129, Supplement 1 (2012) S155–S194
S173
Abstract PO-29 – Table 1. Lymph node status and peri-operative d-dimer
All patients LN positive LN negative WLE & SNB LN positive LN negative
n
Pre-op d-dimer (ng/ml), mean* (CI)
Post-op day 1 d-dimer (ng/ml), mean* (CI)
Post-op day 14 d-dimer (ng/ml), mean* (CI)
Post-op day 42 d-dimer (ng/ml), mean* (CI)
p value
36 83
580 (428–785) 437 (386–494)
610 (460–810) 547 (475–630)
875 (704–1087) 794 (690–913)
958 (709–1295) 602 (497–729)
0.02**
19 67
546 (389–766) 419 (368–477)
585 (380–898) 496 (426–577)
789 (583–1068) 708 (620–808)
840 (614–1149) 519 (434–621)
0.05**
*Marginal mean. **General estimating equations for differences of means over time. WLE = wide local excision, SNB = sentinel lymph node biopsy.
In patients undergoing WLE and sentinel node biopsy (preoperatively assessed as node-ve); d-dimer was significantly increased following surgery in patients subsequently found to be LN positive (p=0.05, Table 1). Conclusion: D-dimer is increased in LN positive EBC and may have a role in pre-operative identification of patients with nodal metastases. Surgery induces an increased early procoagulant storm in ER-ve or PR-ve (poor prognosis phenotype) early breast cancers. There is an increased procoagulant response to surgery in node positive EBC. This may reflect a procoagulant storm from a procoagulant primary tumour or may reflect subclinical metastatic disease, and warrants further investigation.
PO-30 Platelets dysfunction in multiple myeloma I. Djunic 1 , I. Elezovic 1,2 , V. Ilic 2,3 , D. Tomin 1,2 , J. Bila 1,2 , N. Suvajdzic-Vukovic 1,2 , D. Antic 1,2 , A. Vidovic 1,2 , N. Milosevic-Jovcic 2,3 1 Clinic for Hematology, Clinical Center of Serbia; 2 Faculty of Medicine, University of Belgrade; 3 Institute for Medical Research, Belgrade, Serbia Introduction: Acquired von Willebrand syndrome (AvWS) is an uncommon complication of multiple myeloma (MM). The arising mechanism is not completely explained, but it is most frequently believed to be in connection with paraprotein. Aim: We estimated at patients with MM the role of paraprotein on disturbances of platelet function, as well as the influences of serum values of beta2-microglobulin (β2-MG) and C-reactive protein (CRP) on it. Patients and methods: At 40 patients with MM, initially were done: platelets adhesion on glass pearls, platelets aggregation induced with ADP, collagen (COL), ristocetin (RIS) and epinephrine (EPI), and serum values of β2-MG and CRP. Paraprotein has been separated from serum of 9 patients who had decreased platelet aggregation. Aggregation were done before and after addition of paraprotein in platelet rich plasma (PRP) of healthy donors, in vitro. Tests were repeated with addition of human immunoglobulins for intravenous used. We measured latent time in seconds and platelet aggregation in percent. Results: After addition of paraprotein in PRP of healthy donors, aggregation has been significantly decreased (p<0.01), while latent time was significantly prolonged (p<0.05). Addition of human immunoglobulins in PRP of healthy donors, didn’t significant change platelet function. Significant negative correlation was proved between decreased platelet aggregation and serum level of the β2-MG and CRP (p<0.05). Conclusion: This investigation has proved that paraprotein leads to platelets dysfunction in MM. Added paraprotein significantly decreased platelets aggregation of healthy donors, while addition of human immunoglobulins didn’t change platelets function. This research also proved significant correlation between serum levels of β2-MG and CRP with platelet dysfunction, but leaves opened question is paraprotein play only role in platelets dysfunction in MM.
PO-31 Differential response of acute phase markers in lymphoid leukaemias – a probable diagnostic tool O.I. Ajayi 1 , G. Nwaeke 1 , Y.A. Ojuade 2 1 University Of Benin, Benin City and 2 National Hospital, Abuja Background: Leukaemia has been severally associated with increased paraproteinaemia. The association of Leukaemias with acute phase reactants has not been fully established in our environment.
Objectives: We therefore aimed at identifying the response of acute phase proteins as a possible means of supporting the differential diagnosis and/or prognosis of different types of Leukaemia. Methods: Blood samples were taken from 22 leukaemic patients together with 20 apparently healthy individuals (age- and sex-matched) as controls. Acute phase reactant proteins such as Plasma Fibrinogen concentration (PFC) and C-Reactive Proteins (CRP) were measured with standard laboratory methods. Results: We observed a differential statistically significant raised levels of both parameters in all cases (P<0.05, respectively) and in the following order ALLCLLCMLAMLcontrols for PFC while CRP exhibited the order CLLALLCMLAMLcontrols. Conclusions: We therefore, conclude that raised levels of acute phase proteins are associated phenomena with all types of Leukaemias though at varying degrees but with a remarkable increase in Lymphoid Leukaemias. It is suggested therefore for possible inclusion in differential diagnosis of Leukaemias especially during remission phase.
PO-32 Soluble endothelial protein C receptor (sEPCR) and coagulation parameters as prognostic factors in advanced non small cell lung cancer (NSCLC) G. Sarig 1,2 , A. Meir 3 , M. Wollner 3 , I. Shafat 4 , B. Brenner 2 , N. Haim 3 1 Hematology Laboratory, Haifa; 2 Thrombosis and Hemostasis Unit, Hematology Institution and Bone Marrow Transplantation, Haifa; 3 Oncology Institution, Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa; 4 Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Introduction: Cancer is a hypercoagulation state with a high rate of thrombotic events. The activation of the coagulation system may contribute to the mechanism responsible for metastasis formation, which could lead to increased cancer aggressiveness and shortened patient survival. Aim: To study the possible value of hypercoagulation parameters as potential prognostic factors for survival in advanced non small cell lung carcinoma (NSCLC). Patients and methods: 102 newly diagnosed NSCLC patients were enrolled. Blood samples were drawn before the onset of therapy. The association between hypercoagulation, hematological and clinical parameters and survival was analyzed using Kaplan-Meier curves and Cox regression model. Results: Seven patients (6.8%) developed venous thromboembolism within six months of inclusion in the study and had a significantly shorter survival time compared to other patients (198±78 vs 466±46 days, respectively, P=0.03). Patients with high levels of soluble EPCR (sEPCR >110 mg/ml) were found to have a longer survival time compared to patients with sEPCR levels <110 mg/ml (520±130 vs 287±40 days, respectively, P=0.001). Levels of sEPCR in NSCLC patients were not significantly different from those in matched controls (146.6±94.6 mg/ml vs 135.3±86.5 mg/ml, respectively, P=0.43); however, elevated levels of sEPCR were associated with polymorphisms EPCR 6936 AG and GG. Theses congenital polymorphisms, known to be correspond to high levels of sEPCR, have potential prolonging effects on the survival time of NSCLC patients. High levels of plasma heparanase, fibrinogen and platelet count were significantly related to shorter survival time, while levels of tissue factor (TF), Prothrombin fragment 1+2 and acquired protein C resistance were not found to be connected with survival time in the current NSCLC patient group. Multivariate Cox regression revealed five significant and independent predictors of survival: weight loss
S173
Abstract PO-29 – Table 1. Lymph node status and peri-operative d-dimer
All patients LN positive LN negative WLE & SNB LN positive LN negative
n
Pre-op d-dimer (ng/ml), mean* (CI)
Post-op day 1 d-dimer (ng/ml), mean* (CI)
Post-op day 14 d-dimer (ng/ml), mean* (CI)
Post-op day 42 d-dimer (ng/ml), mean* (CI)
p value
36 83
580 (428–785) 437 (386–494)
610 (460–810) 547 (475–630)
875 (704–1087) 794 (690–913)
958 (709–1295) 602 (497–729)
0.02**
19 67
546 (389–766) 419 (368–477)
585 (380–898) 496 (426–577)
789 (583–1068) 708 (620–808)
840 (614–1149) 519 (434–621)
0.05**
*Marginal mean. **General estimating equations for differences of means over time. WLE = wide local excision, SNB = sentinel lymph node biopsy.
In patients undergoing WLE and sentinel node biopsy (preoperatively assessed as node-ve); d-dimer was significantly increased following surgery in patients subsequently found to be LN positive (p=0.05, Table 1). Conclusion: D-dimer is increased in LN positive EBC and may have a role in pre-operative identification of patients with nodal metastases. Surgery induces an increased early procoagulant storm in ER-ve or PR-ve (poor prognosis phenotype) early breast cancers. There is an increased procoagulant response to surgery in node positive EBC. This may reflect a procoagulant storm from a procoagulant primary tumour or may reflect subclinical metastatic disease, and warrants further investigation.
PO-30 Platelets dysfunction in multiple myeloma I. Djunic 1 , I. Elezovic 1,2 , V. Ilic 2,3 , D. Tomin 1,2 , J. Bila 1,2 , N. Suvajdzic-Vukovic 1,2 , D. Antic 1,2 , A. Vidovic 1,2 , N. Milosevic-Jovcic 2,3 1 Clinic for Hematology, Clinical Center of Serbia; 2 Faculty of Medicine, University of Belgrade; 3 Institute for Medical Research, Belgrade, Serbia Introduction: Acquired von Willebrand syndrome (AvWS) is an uncommon complication of multiple myeloma (MM). The arising mechanism is not completely explained, but it is most frequently believed to be in connection with paraprotein. Aim: We estimated at patients with MM the role of paraprotein on disturbances of platelet function, as well as the influences of serum values of beta2-microglobulin (β2-MG) and C-reactive protein (CRP) on it. Patients and methods: At 40 patients with MM, initially were done: platelets adhesion on glass pearls, platelets aggregation induced with ADP, collagen (COL), ristocetin (RIS) and epinephrine (EPI), and serum values of β2-MG and CRP. Paraprotein has been separated from serum of 9 patients who had decreased platelet aggregation. Aggregation were done before and after addition of paraprotein in platelet rich plasma (PRP) of healthy donors, in vitro. Tests were repeated with addition of human immunoglobulins for intravenous used. We measured latent time in seconds and platelet aggregation in percent. Results: After addition of paraprotein in PRP of healthy donors, aggregation has been significantly decreased (p<0.01), while latent time was significantly prolonged (p<0.05). Addition of human immunoglobulins in PRP of healthy donors, didn’t significant change platelet function. Significant negative correlation was proved between decreased platelet aggregation and serum level of the β2-MG and CRP (p<0.05). Conclusion: This investigation has proved that paraprotein leads to platelets dysfunction in MM. Added paraprotein significantly decreased platelets aggregation of healthy donors, while addition of human immunoglobulins didn’t change platelets function. This research also proved significant correlation between serum levels of β2-MG and CRP with platelet dysfunction, but leaves opened question is paraprotein play only role in platelets dysfunction in MM.
PO-31 Differential response of acute phase markers in lymphoid leukaemias – a probable diagnostic tool O.I. Ajayi 1 , G. Nwaeke 1 , Y.A. Ojuade 2 1 University Of Benin, Benin City and 2 National Hospital, Abuja Background: Leukaemia has been severally associated with increased paraproteinaemia. The association of Leukaemias with acute phase reactants has not been fully established in our environment.
Objectives: We therefore aimed at identifying the response of acute phase proteins as a possible means of supporting the differential diagnosis and/or prognosis of different types of Leukaemia. Methods: Blood samples were taken from 22 leukaemic patients together with 20 apparently healthy individuals (age- and sex-matched) as controls. Acute phase reactant proteins such as Plasma Fibrinogen concentration (PFC) and C-Reactive Proteins (CRP) were measured with standard laboratory methods. Results: We observed a differential statistically significant raised levels of both parameters in all cases (P<0.05, respectively) and in the following order ALLCLLCMLAMLcontrols for PFC while CRP exhibited the order CLLALLCMLAMLcontrols. Conclusions: We therefore, conclude that raised levels of acute phase proteins are associated phenomena with all types of Leukaemias though at varying degrees but with a remarkable increase in Lymphoid Leukaemias. It is suggested therefore for possible inclusion in differential diagnosis of Leukaemias especially during remission phase.
PO-32 Soluble endothelial protein C receptor (sEPCR) and coagulation parameters as prognostic factors in advanced non small cell lung cancer (NSCLC) G. Sarig 1,2 , A. Meir 3 , M. Wollner 3 , I. Shafat 4 , B. Brenner 2 , N. Haim 3 1 Hematology Laboratory, Haifa; 2 Thrombosis and Hemostasis Unit, Hematology Institution and Bone Marrow Transplantation, Haifa; 3 Oncology Institution, Rambam Health Care Campus and the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa; 4 Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Introduction: Cancer is a hypercoagulation state with a high rate of thrombotic events. The activation of the coagulation system may contribute to the mechanism responsible for metastasis formation, which could lead to increased cancer aggressiveness and shortened patient survival. Aim: To study the possible value of hypercoagulation parameters as potential prognostic factors for survival in advanced non small cell lung carcinoma (NSCLC). Patients and methods: 102 newly diagnosed NSCLC patients were enrolled. Blood samples were drawn before the onset of therapy. The association between hypercoagulation, hematological and clinical parameters and survival was analyzed using Kaplan-Meier curves and Cox regression model. Results: Seven patients (6.8%) developed venous thromboembolism within six months of inclusion in the study and had a significantly shorter survival time compared to other patients (198±78 vs 466±46 days, respectively, P=0.03). Patients with high levels of soluble EPCR (sEPCR >110 mg/ml) were found to have a longer survival time compared to patients with sEPCR levels <110 mg/ml (520±130 vs 287±40 days, respectively, P=0.001). Levels of sEPCR in NSCLC patients were not significantly different from those in matched controls (146.6±94.6 mg/ml vs 135.3±86.5 mg/ml, respectively, P=0.43); however, elevated levels of sEPCR were associated with polymorphisms EPCR 6936 AG and GG. Theses congenital polymorphisms, known to be correspond to high levels of sEPCR, have potential prolonging effects on the survival time of NSCLC patients. High levels of plasma heparanase, fibrinogen and platelet count were significantly related to shorter survival time, while levels of tissue factor (TF), Prothrombin fragment 1+2 and acquired protein C resistance were not found to be connected with survival time in the current NSCLC patient group. Multivariate Cox regression revealed five significant and independent predictors of survival: weight loss