- Email: [email protected]
C0321: Risk Factors for Thrombosis in Acute Promyelocytic Leukemia
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POSTERS / Thrombosis Research 133S3 (2014) S35–S123
often coexisting with other intercurrent complications. The rates of venous thromboembolic recurrences and major bleeding events at 30 and 90 days were low and comparable in both groups. Conclusions: A high proportion of cancer patients with PE may be safely managed as outpatients, especially those with incidental PE. Further studies addressed to better define low risk patients in this setting should be developed.
C0299 HEMORHEOLOGIC DISTURBANCES IS VENOUS THROMBOEMBOLISM RISK FACTOR IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (PILOT STUDY)
C0272 SCREENING OF GENETIC POLYMORPHISMS IN THE FOLATE PATHWAY IN TURKISH PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS
Background: Acute lymphoblastic leukaemia is the commonest childhood malignancy with high risk of venous thromboembolism (VTE). From this point of view, the aim was to investigate blood rheology properties in children with acute lymphoblastic leukemia during first remission time and without any symptomatic organs failures. Methods: The study’s population was 48 children (age <16 y.o.). Six patients had VTE during follow-up despite standard antiVTE prevention. Whole blood viscosimetry, plasma viscosimetry, erythrocytes aggregability and deformability were investigated. Additionally B-type natriuretic peptide (BNP) level and plasma ions concentrations were assayed. Results: All patients had normal plasma viscosity and unimpaired erythrocyte deformability. However, whole blood viscosity was increased by shear rates 5–300 s−1 and mainly by shear rates 5–75 s−1 . We found erythrocytes hyperaggregability in all patients. The combination “most increased whole blood viscosity – erythrocytes hyperaggregability” was identified with high BNP-level in patients who did not have symptomatic heart failure. Elevated BNP level was found in 16 patients, and from them six VTE had been developed. Conclusions: Totally increased blood viscosity with erythrocytes aggregability are factors leading to thrombosis. The slightly decrease of blood flow rate might be assumed when BNP-level have been raised. Both signs elevate the risk of VTE. Despite antithrombotic prevention directed to hypocoagulation the revealed hemorheologic disturbances could be be as a trigger to start of VTE in children with acute lymphoblastic leukemia. The obtained results suggest that the study should be continued.
D. Fatma Akin1 , E. Karekci1 , K. Sipahi1 , N. Akar1 . 1 LOSEV the Foundation for Children with Leukemia, Ankara, Turkey Background: Folate is essential for the synthesis of purine bases, and therefore, its levels affect the DNA biosynthesis. Different gene polymorphisms have proven to play a role in the susceptibility to childhood ALL but it is unlikely that single genetic defects are responsible for the development of ALL. The objective of this study was to investigate, whether genetic polymorphisms in genes related to folate metabolic pathway influence the risk to childhood ALL. Methods: This study population consisted of patients, aged between 1 and 15 years who were admitted to our hospital with the diagnosis of childhood ALL. Blood samples were collected with EDTA-containing tubes and DNA was extracted from peripheral blood leukocytes according to MagNApure DNA isolation system. Genotyping of MTHFR 677C - T (rs1801133) and 1298A - C (rs1801131) were screened with RT-PCR using fluorescence melting curve detection analysis by means of the Light Cycler 480 II System. The 19-bp deletion of DHFR and 68-bp insertion of CBS were performed using PCR. To determine the 2R-3R TYMS using PCR. PCR products were analyzed by 3% agarose gel electrophoresis and deletion and insertion were determined based on the length of PCR products. The 3RG-3RC SNP (rs2853542) was analyzed by the RFLP method. PCR products were digested with the HaeIII enzyme. Results: We investigated the associations of 5 SNPs in 4 genes in the folate metabolic pathway with the development of childhood ALL. The prevalence of MTHFR SNPs were determined for 180 childhood ALL and 296 healthy individuals. No significant difference was found for MTHFR 677 C–T frequency between same groups (OR: 1.0, 95% CI 0.6–1.5; p: 0.8)]. No difference was observed in the distribution of MTHFR 1298 A–C frequency between same groups (OR: 1.48, 95% CI 0.7–2.8; p: 0.2). The prevalence of DHFR 19 bp deletion was determined for 63 ALL patients and 296 healthy individuals. It was similar in study groups (OR: 0.8, 95% CI 0.4–1.6); p: 0.5). 124 of the 136 patients were heterozygous for the 2R-3R TYMS. Heterozygosities of 2R-3R TYMS demonstrated a difference between same groups (OR: 0.09, 95% CI 0.04–0.2; p: 0.000). There was no significant difference between the heterozygosity frequency of CBS 844ins68 between same groups (OR: 0.9, 95% CI 0.5–1.8; p: 0.9). Three of all patients had thromboembolism (TE); sinus thrombosis, the cerebral ischemia and deep vein thrombosis were the diagnosis of these cases. A patients had TE was dead. All patients had TE had TYMS polymorphism. Patients had sinus thrombosis carried MTHFR 1298 A–C SNP. Patients had cerebral ischemia carried MTHFR 677 C–T and the 19-bp deletion of DHFR. Conclusions: We investigated the frequency of folate metabolism pathway polymorphisms in pediatric ALL and compare to healthy controls. Only 2R-3R TYMS had marked difference among the SNPs studied so far. Further study is needed in order to evaluate the effects of these SNPs on survival in pediatric ALL.
I. Kolesnikova1 , E. Roitman1 , S. Roumiantsev1 , L. Ershova1 , J. Roumiantseva1 . 1 Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia
C0321 RISK FACTORS FOR THROMBOSIS IN ACUTE PROMYELOCYTIC LEUKEMIA M. Mitrovic1 , N. Suvajdzic1 , I. Elezovic1 , A. Bogdanovic1 , V. Dordevic2 , I. Djunic1 , M. Gvozdenov1 , N. Colovic1 , M. Virijevic1 , A. Vidovic1 , D. Tomin1 . 1 Clinic of Hematology CCS, Koste Todorovica 2, Belgrade, Serbia; 2 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia Background: Acute promyelocytic leukemia (APL) carries the highest risk for thrombotic events (TE) among the hematological malignancies. However, information about the risk factors for thrombosis in adults with APL are still scarce. Methods: We retrospectively analyzed data on TE in 63 newly diagnosed APL patients (median age 41 years, range 19–69; 33/30 female/male ratio) managed in the Clinic of Hematology from 2004 to 2013 with all-trans retinoic acid and anthracyclines. The diagnosis of deep vein thrombosis (DVT) was established by Color Doppler ultrasonography, Budd-Chiari syndrome (BCS) by CT and central retinal vein occlusion (CRVO) by ophthalmoscopy and fundus angiography. Diagnosis of acute myocardial infarction (AMI) was based on cardiac enzyme modifications and diagnosis of ischemic stroke on CT/MRI findings. Aim of this study was to interrogate predictive values of clinical and laboratory parameters for TE development. Results: Thirteen patients 13/63 (20.6%) developed TE. Arterial TE (ATE) developed in 4/63 (6.3%) patients (AMI and cerebrovascular accident in 2 cases each). Patients with ATE had significantly higer early death rate in comparison with patients without TE (50% vs. 24%, P = 0.027). Neither of interrogated parameters was predictive
POSTERS / Thrombosis Research 133S3 (2014) S35–S123
for ATE development. Vein TE (VTE) developed in 9/63 (14.29%) patients: DVT in 7, CRVO in one and BCS in one case. Significant differences between groups of patient with VTE and without TE were found in: female/male ratio (P = 0.046), PT (P = 0.022), aPTT (P = 0.044), ISTH DIC score (P = 0.001), bcr3 (P = 0.02) and FLT3ITD (P = 0.028) expression. The most significant risk factor for VTE in multivariate Cox’s proportional regression was FLT3-ITD expression (P = 0.034, RR 10.036, 95% CI 1.197–84.123). FV Leiden heterozygous mutation, prothrombin 20120 and PAI-1 4G/4G was in 2.02, 2.88 and 2.33 times frequent than in healthy population. However differences were not significant (P = 0.53, P = 0.36, P = 0.21 respectively). Conclusions: Our study suggests the possible relationship between TE occurrence on one side and laboratory findings (PT, aPTT, ISTH DIC score, bcr3, FLT3-ITD) on the other. FV Leiden, FII 20210 and PAI-1 4G/4G mutations were frequented in patients with TE than in healthy population. However, whether thrombophilia is important in APL related thrombosis needs further investigation. C0331 HYPOFIBRINOLYSIS, THROMBOEMBOLIC COMPLICATIONS AND CANCER O. Petrova1 , V. Sukhanov1 . 1 Regional Oncology Dispansary. Ekaterinburg, Russia Background: The frequency of thromboembolic complications (VTE) in cancer patients (cp) is increased by 10% during chemotherapy (CT). The combination of systemic blood hypercoagulation (SHC) and hypofibrinolysis (F) are the most dangerous risks of VTE. Thromboelastography (TEG) investigation of SHC and F can help in the selection of patients for thromboprophylaxis with subsequent evaluation of its effectiveness. The aim of this study was to evaluate TEG parameters (SHC, F) for evaluation of the antithrombotic effect of low molecular weight heparin (LMWH). Methods: We studied 80 cp (M/F = 45/55, mean age 56 yrs) with a high risk of VTE (Khorana score) before CT: at baseline and 2–3 hrs after the injection of LMWH (dalteparin 2500 IU daily). Investigated TEG (TEG analyzer 5000, USA) parameters were: r (our modification, RF patent #2015515) – time of reaction (normal range = 660–970 s), fibrinolysis (our modification, RF patent #2358657) (normal range = 60–120%). To evaluate the complex of procoagulant interaction of these two parameters, we decided to introduce a scoring assessment of their combined action: r < 500 s = 1 score (normal range = 0), F <40% = 1 score (normal range = 0). Results: Thus, only 39% of patients before prescribing LMWH had moderate/pronounced SHC (mean score = 0.4) but 100% – moderate/ pronounced F (mean score = 1): overall score (OS) = 1.4. At the peak of anticoagulant (dalteparin) action the OS decreased by 64% (p < 0.01). In 10% of patients with OS = 1 we increased the dose of LMWH to 5000 IU daily. The control study of TEG parameters showed additional reduction of OS by 14% of the original. Thus, the total drug correction of hemostasis and fibrinolysis by LMWH reduced OS by 78% from the initial. Conclusions: Hypofibrinolysis is the main risk of VTE in cp. Combined (score) assessment of SHC and F allows better estimate the risk of VTE. These TEG parameters are the most suitable for evaluation of the antithrombotic effect of LMWH. C0396 THROMBOPHILIA IN THROMBOSIS AND CANCER R. Otero1 , E. Arellano2 , C. Font1 , A. Montes1 , T. Elias1 , L. Jara1 , A. Carmona-Bayonas1 . 1 Servicio de Neumolog´ıa. Hospital Virgen del Roc´ıo, Sevilla, Spain; 2 HUVR-IBIS, CIBERES, Sevilla, Spain Background: Hereditary and acquired status of hypercoagulability are known to increase the risk of venous thromboembolism (VTE) in general population. Cancer is currently the major acquired factor of
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hypercoagulability. Information on the prevalence and contribution of hereditary thrombophilic disorders in the development of cancer-related VTE is scarce. The aim of the present report was to determine the prevalence of hereditary thrombophilic factors in cancer patients. Methods: Consecutive patients with VTE confirmed by objective tests and healthy blood donors were included from a cooperative work between two Spanish university hospitals. Laboratory testing consisted of a panel of genetic, functional and antigenic assays: Factor V Leiden and Prothrombin gene (G20210A) polymorphisms, anti-phospholipid antibody (APA), lupus anticoagulant-, specific antibodies against cardiolipin by ELISA assay and antibodies against b2 glycoprotein 1, Protein S free and total, Protein C antigen level and antithrombin antigen levels. Testing was performed more than 30 days after the VTE. In patients who were receiving vitamin K antagonists therapy it was switched to low-molecular weight heparin 21 days before blood samples were taken for thrombophilic tests. A second blood sample should be taken at least 12 weeks after the first in antiphospholipid antibodies (aPL) positive. Results: 1282 subjects (age: 59±17 yrs; 50% men) were studied: 484 VTE patients without cancer (NC-VTE), 292 cancer patients without VTE (NVTE-C), 351 patients with cancer-related VTE (C-VTE) and 155 healthy blood donors (Healthy). In cancer patients the prevalence of tumours was: 24% lung, 21% digestive, 18% breast, 9% urologic, 8% gynecologic and 15% other origins. VTE patients were diagnosed 62% deep venous thrombosis, 33% pulmonary embolism, thrombosis related to central catheter 4% and cava vein thrombosis 2%. There were no differences in gender or age between thrombosis or cancer patients but healthy donors were younger. In patients with VTE (groups NC-VTE and C-VTE) antiphospholipid antibody/lupus anticoagulant were the most frequent thrombophilic disorder found (12% in group NC-VTE and 8% in group C-VTE) followed by FVL (11.4% in group NC-VTE and 5.2% in group C-VTE). Adjusted Odds ratios for VTE in patients without cancer were significantly higher for FVL [OR: 3.81 (95% CI: 1.49–9.71), p = 0.005] and Prothrombin G20210A [OR: 2.35 (95% CI: 1.04–5.33), p = 0.040]. However, in cancer patients only FVL had a significant and independent VTE risk [OR: 3.04 (95% CI: 1.11–8.31), p = 0.030]. Conclusions: Our results suggest that some genetic hypercoagulable disorders, such as FVL could have a pathogenic role in the development of thrombosis in cancer patients. Consequently it should be considered in primary prophylaxis planning. C0451 UPPER-EXTREMITY DEEP VENOUS THROMBOSIS: A REPORT OF 17 CASES T. Amira1 , N. Boussetta1 , I. Boukhris1 , Y. Ariba1 , S. Azzabi1 , L. ben Hassine1 , N. Khalfallah1 . 1 Military hospital, Tunis, Tunisia Background: Deep venous thrombosis of the upper limb appears to be more frequent today, composing about 3% of all deep venous limb thrombosis. Main causes are either increasing use of central venous catheters or malignancies. Doppler ultasonography made the diagnosis of this disease easier. Methods: In this retrospective series, in an internal medicine department, 17 male consecutive patients with upper extremity deep venous thrombosis documented by Doppler ultrasonography were included in the study. Results: Deep venous thrombosis of the upper limb composed 5.3% of all deep venous limb thrombosis in our department. Clinical manifestations were mainly pain and edema. Mean time between the onset of clinical signs and diagnosis was 6.3 days. Main thrombosis localizations were humeral, axillary, subclavian and jugular veins. All cases were documented by Doppler ultrasonography. Causative factors were malignancies (35.29%), deep venous thrombosis related to effort or thoracic outlet syndrome (11.76%), Behcet’s ¸ disease (5.88%) and thrombophilic
POSTERS / Thrombosis Research 133S3 (2014) S35–S123
often coexisting with other intercurrent complications. The rates of venous thromboembolic recurrences and major bleeding events at 30 and 90 days were low and comparable in both groups. Conclusions: A high proportion of cancer patients with PE may be safely managed as outpatients, especially those with incidental PE. Further studies addressed to better define low risk patients in this setting should be developed.
C0299 HEMORHEOLOGIC DISTURBANCES IS VENOUS THROMBOEMBOLISM RISK FACTOR IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (PILOT STUDY)
C0272 SCREENING OF GENETIC POLYMORPHISMS IN THE FOLATE PATHWAY IN TURKISH PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS
Background: Acute lymphoblastic leukaemia is the commonest childhood malignancy with high risk of venous thromboembolism (VTE). From this point of view, the aim was to investigate blood rheology properties in children with acute lymphoblastic leukemia during first remission time and without any symptomatic organs failures. Methods: The study’s population was 48 children (age <16 y.o.). Six patients had VTE during follow-up despite standard antiVTE prevention. Whole blood viscosimetry, plasma viscosimetry, erythrocytes aggregability and deformability were investigated. Additionally B-type natriuretic peptide (BNP) level and plasma ions concentrations were assayed. Results: All patients had normal plasma viscosity and unimpaired erythrocyte deformability. However, whole blood viscosity was increased by shear rates 5–300 s−1 and mainly by shear rates 5–75 s−1 . We found erythrocytes hyperaggregability in all patients. The combination “most increased whole blood viscosity – erythrocytes hyperaggregability” was identified with high BNP-level in patients who did not have symptomatic heart failure. Elevated BNP level was found in 16 patients, and from them six VTE had been developed. Conclusions: Totally increased blood viscosity with erythrocytes aggregability are factors leading to thrombosis. The slightly decrease of blood flow rate might be assumed when BNP-level have been raised. Both signs elevate the risk of VTE. Despite antithrombotic prevention directed to hypocoagulation the revealed hemorheologic disturbances could be be as a trigger to start of VTE in children with acute lymphoblastic leukemia. The obtained results suggest that the study should be continued.
D. Fatma Akin1 , E. Karekci1 , K. Sipahi1 , N. Akar1 . 1 LOSEV the Foundation for Children with Leukemia, Ankara, Turkey Background: Folate is essential for the synthesis of purine bases, and therefore, its levels affect the DNA biosynthesis. Different gene polymorphisms have proven to play a role in the susceptibility to childhood ALL but it is unlikely that single genetic defects are responsible for the development of ALL. The objective of this study was to investigate, whether genetic polymorphisms in genes related to folate metabolic pathway influence the risk to childhood ALL. Methods: This study population consisted of patients, aged between 1 and 15 years who were admitted to our hospital with the diagnosis of childhood ALL. Blood samples were collected with EDTA-containing tubes and DNA was extracted from peripheral blood leukocytes according to MagNApure DNA isolation system. Genotyping of MTHFR 677C - T (rs1801133) and 1298A - C (rs1801131) were screened with RT-PCR using fluorescence melting curve detection analysis by means of the Light Cycler 480 II System. The 19-bp deletion of DHFR and 68-bp insertion of CBS were performed using PCR. To determine the 2R-3R TYMS using PCR. PCR products were analyzed by 3% agarose gel electrophoresis and deletion and insertion were determined based on the length of PCR products. The 3RG-3RC SNP (rs2853542) was analyzed by the RFLP method. PCR products were digested with the HaeIII enzyme. Results: We investigated the associations of 5 SNPs in 4 genes in the folate metabolic pathway with the development of childhood ALL. The prevalence of MTHFR SNPs were determined for 180 childhood ALL and 296 healthy individuals. No significant difference was found for MTHFR 677 C–T frequency between same groups (OR: 1.0, 95% CI 0.6–1.5; p: 0.8)]. No difference was observed in the distribution of MTHFR 1298 A–C frequency between same groups (OR: 1.48, 95% CI 0.7–2.8; p: 0.2). The prevalence of DHFR 19 bp deletion was determined for 63 ALL patients and 296 healthy individuals. It was similar in study groups (OR: 0.8, 95% CI 0.4–1.6); p: 0.5). 124 of the 136 patients were heterozygous for the 2R-3R TYMS. Heterozygosities of 2R-3R TYMS demonstrated a difference between same groups (OR: 0.09, 95% CI 0.04–0.2; p: 0.000). There was no significant difference between the heterozygosity frequency of CBS 844ins68 between same groups (OR: 0.9, 95% CI 0.5–1.8; p: 0.9). Three of all patients had thromboembolism (TE); sinus thrombosis, the cerebral ischemia and deep vein thrombosis were the diagnosis of these cases. A patients had TE was dead. All patients had TE had TYMS polymorphism. Patients had sinus thrombosis carried MTHFR 1298 A–C SNP. Patients had cerebral ischemia carried MTHFR 677 C–T and the 19-bp deletion of DHFR. Conclusions: We investigated the frequency of folate metabolism pathway polymorphisms in pediatric ALL and compare to healthy controls. Only 2R-3R TYMS had marked difference among the SNPs studied so far. Further study is needed in order to evaluate the effects of these SNPs on survival in pediatric ALL.
I. Kolesnikova1 , E. Roitman1 , S. Roumiantsev1 , L. Ershova1 , J. Roumiantseva1 . 1 Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia
C0321 RISK FACTORS FOR THROMBOSIS IN ACUTE PROMYELOCYTIC LEUKEMIA M. Mitrovic1 , N. Suvajdzic1 , I. Elezovic1 , A. Bogdanovic1 , V. Dordevic2 , I. Djunic1 , M. Gvozdenov1 , N. Colovic1 , M. Virijevic1 , A. Vidovic1 , D. Tomin1 . 1 Clinic of Hematology CCS, Koste Todorovica 2, Belgrade, Serbia; 2 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia Background: Acute promyelocytic leukemia (APL) carries the highest risk for thrombotic events (TE) among the hematological malignancies. However, information about the risk factors for thrombosis in adults with APL are still scarce. Methods: We retrospectively analyzed data on TE in 63 newly diagnosed APL patients (median age 41 years, range 19–69; 33/30 female/male ratio) managed in the Clinic of Hematology from 2004 to 2013 with all-trans retinoic acid and anthracyclines. The diagnosis of deep vein thrombosis (DVT) was established by Color Doppler ultrasonography, Budd-Chiari syndrome (BCS) by CT and central retinal vein occlusion (CRVO) by ophthalmoscopy and fundus angiography. Diagnosis of acute myocardial infarction (AMI) was based on cardiac enzyme modifications and diagnosis of ischemic stroke on CT/MRI findings. Aim of this study was to interrogate predictive values of clinical and laboratory parameters for TE development. Results: Thirteen patients 13/63 (20.6%) developed TE. Arterial TE (ATE) developed in 4/63 (6.3%) patients (AMI and cerebrovascular accident in 2 cases each). Patients with ATE had significantly higer early death rate in comparison with patients without TE (50% vs. 24%, P = 0.027). Neither of interrogated parameters was predictive
POSTERS / Thrombosis Research 133S3 (2014) S35–S123
for ATE development. Vein TE (VTE) developed in 9/63 (14.29%) patients: DVT in 7, CRVO in one and BCS in one case. Significant differences between groups of patient with VTE and without TE were found in: female/male ratio (P = 0.046), PT (P = 0.022), aPTT (P = 0.044), ISTH DIC score (P = 0.001), bcr3 (P = 0.02) and FLT3ITD (P = 0.028) expression. The most significant risk factor for VTE in multivariate Cox’s proportional regression was FLT3-ITD expression (P = 0.034, RR 10.036, 95% CI 1.197–84.123). FV Leiden heterozygous mutation, prothrombin 20120 and PAI-1 4G/4G was in 2.02, 2.88 and 2.33 times frequent than in healthy population. However differences were not significant (P = 0.53, P = 0.36, P = 0.21 respectively). Conclusions: Our study suggests the possible relationship between TE occurrence on one side and laboratory findings (PT, aPTT, ISTH DIC score, bcr3, FLT3-ITD) on the other. FV Leiden, FII 20210 and PAI-1 4G/4G mutations were frequented in patients with TE than in healthy population. However, whether thrombophilia is important in APL related thrombosis needs further investigation. C0331 HYPOFIBRINOLYSIS, THROMBOEMBOLIC COMPLICATIONS AND CANCER O. Petrova1 , V. Sukhanov1 . 1 Regional Oncology Dispansary. Ekaterinburg, Russia Background: The frequency of thromboembolic complications (VTE) in cancer patients (cp) is increased by 10% during chemotherapy (CT). The combination of systemic blood hypercoagulation (SHC) and hypofibrinolysis (F) are the most dangerous risks of VTE. Thromboelastography (TEG) investigation of SHC and F can help in the selection of patients for thromboprophylaxis with subsequent evaluation of its effectiveness. The aim of this study was to evaluate TEG parameters (SHC, F) for evaluation of the antithrombotic effect of low molecular weight heparin (LMWH). Methods: We studied 80 cp (M/F = 45/55, mean age 56 yrs) with a high risk of VTE (Khorana score) before CT: at baseline and 2–3 hrs after the injection of LMWH (dalteparin 2500 IU daily). Investigated TEG (TEG analyzer 5000, USA) parameters were: r (our modification, RF patent #2015515) – time of reaction (normal range = 660–970 s), fibrinolysis (our modification, RF patent #2358657) (normal range = 60–120%). To evaluate the complex of procoagulant interaction of these two parameters, we decided to introduce a scoring assessment of their combined action: r < 500 s = 1 score (normal range = 0), F <40% = 1 score (normal range = 0). Results: Thus, only 39% of patients before prescribing LMWH had moderate/pronounced SHC (mean score = 0.4) but 100% – moderate/ pronounced F (mean score = 1): overall score (OS) = 1.4. At the peak of anticoagulant (dalteparin) action the OS decreased by 64% (p < 0.01). In 10% of patients with OS = 1 we increased the dose of LMWH to 5000 IU daily. The control study of TEG parameters showed additional reduction of OS by 14% of the original. Thus, the total drug correction of hemostasis and fibrinolysis by LMWH reduced OS by 78% from the initial. Conclusions: Hypofibrinolysis is the main risk of VTE in cp. Combined (score) assessment of SHC and F allows better estimate the risk of VTE. These TEG parameters are the most suitable for evaluation of the antithrombotic effect of LMWH. C0396 THROMBOPHILIA IN THROMBOSIS AND CANCER R. Otero1 , E. Arellano2 , C. Font1 , A. Montes1 , T. Elias1 , L. Jara1 , A. Carmona-Bayonas1 . 1 Servicio de Neumolog´ıa. Hospital Virgen del Roc´ıo, Sevilla, Spain; 2 HUVR-IBIS, CIBERES, Sevilla, Spain Background: Hereditary and acquired status of hypercoagulability are known to increase the risk of venous thromboembolism (VTE) in general population. Cancer is currently the major acquired factor of
S105
hypercoagulability. Information on the prevalence and contribution of hereditary thrombophilic disorders in the development of cancer-related VTE is scarce. The aim of the present report was to determine the prevalence of hereditary thrombophilic factors in cancer patients. Methods: Consecutive patients with VTE confirmed by objective tests and healthy blood donors were included from a cooperative work between two Spanish university hospitals. Laboratory testing consisted of a panel of genetic, functional and antigenic assays: Factor V Leiden and Prothrombin gene (G20210A) polymorphisms, anti-phospholipid antibody (APA), lupus anticoagulant-, specific antibodies against cardiolipin by ELISA assay and antibodies against b2 glycoprotein 1, Protein S free and total, Protein C antigen level and antithrombin antigen levels. Testing was performed more than 30 days after the VTE. In patients who were receiving vitamin K antagonists therapy it was switched to low-molecular weight heparin 21 days before blood samples were taken for thrombophilic tests. A second blood sample should be taken at least 12 weeks after the first in antiphospholipid antibodies (aPL) positive. Results: 1282 subjects (age: 59±17 yrs; 50% men) were studied: 484 VTE patients without cancer (NC-VTE), 292 cancer patients without VTE (NVTE-C), 351 patients with cancer-related VTE (C-VTE) and 155 healthy blood donors (Healthy). In cancer patients the prevalence of tumours was: 24% lung, 21% digestive, 18% breast, 9% urologic, 8% gynecologic and 15% other origins. VTE patients were diagnosed 62% deep venous thrombosis, 33% pulmonary embolism, thrombosis related to central catheter 4% and cava vein thrombosis 2%. There were no differences in gender or age between thrombosis or cancer patients but healthy donors were younger. In patients with VTE (groups NC-VTE and C-VTE) antiphospholipid antibody/lupus anticoagulant were the most frequent thrombophilic disorder found (12% in group NC-VTE and 8% in group C-VTE) followed by FVL (11.4% in group NC-VTE and 5.2% in group C-VTE). Adjusted Odds ratios for VTE in patients without cancer were significantly higher for FVL [OR: 3.81 (95% CI: 1.49–9.71), p = 0.005] and Prothrombin G20210A [OR: 2.35 (95% CI: 1.04–5.33), p = 0.040]. However, in cancer patients only FVL had a significant and independent VTE risk [OR: 3.04 (95% CI: 1.11–8.31), p = 0.030]. Conclusions: Our results suggest that some genetic hypercoagulable disorders, such as FVL could have a pathogenic role in the development of thrombosis in cancer patients. Consequently it should be considered in primary prophylaxis planning. C0451 UPPER-EXTREMITY DEEP VENOUS THROMBOSIS: A REPORT OF 17 CASES T. Amira1 , N. Boussetta1 , I. Boukhris1 , Y. Ariba1 , S. Azzabi1 , L. ben Hassine1 , N. Khalfallah1 . 1 Military hospital, Tunis, Tunisia Background: Deep venous thrombosis of the upper limb appears to be more frequent today, composing about 3% of all deep venous limb thrombosis. Main causes are either increasing use of central venous catheters or malignancies. Doppler ultasonography made the diagnosis of this disease easier. Methods: In this retrospective series, in an internal medicine department, 17 male consecutive patients with upper extremity deep venous thrombosis documented by Doppler ultrasonography were included in the study. Results: Deep venous thrombosis of the upper limb composed 5.3% of all deep venous limb thrombosis in our department. Clinical manifestations were mainly pain and edema. Mean time between the onset of clinical signs and diagnosis was 6.3 days. Main thrombosis localizations were humeral, axillary, subclavian and jugular veins. All cases were documented by Doppler ultrasonography. Causative factors were malignancies (35.29%), deep venous thrombosis related to effort or thoracic outlet syndrome (11.76%), Behcet’s ¸ disease (5.88%) and thrombophilic