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Venous thromboembolism in cancer patients
S182
Abstracts / Thrombosis Research 129, Supplement 1 (2012) S155–S194
PO-54 Variability of response of thromboprophylaxis with fixed dose of enoxaparin in patients with primary adenocarcinoma of the lung undergoing lobectomy C. Papageorgiou 1,2 , E. Marret 1 , P. Van Dreden 3 , F. Bonnet 1 , B. Woodhams 3 , A.C. Spyropoulos 4, G.T. Gerotziafas 2,5 , I. Elalamy 2,5 1 Service Anesthésie -Réanimation Hôpital Tenon APHP, Paris, France; 2 ER2UPMC, Faculté de Médecine, Université Paris 6, Hôpital Tenon, APHP, Paris, France; 3 Diagnostica Stago, Gennevilliers, France; 4 University of Rochester Medical Center, Division of Hematology/Oncology, Rochester, NY, USA; 5 Service d’Hématologie Biologique, Hôpital Tenon APHP, Paris, France Background: Patients with lung adenocarcinoma are at high risk of VTE. Lobectomy is a major risk factor for VTE. Lung-cancer patients receive LWMH prophylaxis at the same dose as that recommended in major abdominal surgery. Aim of the study: We studied the impact of post-operative prophylaxis with enoxaparin on cellular and plasma markers of hypecoagulability in patients with primary, localised lung adenocarcinoma undergoing lobectomy. Patients and methods: Selected patients suffering from primary lung adenocarcinoma without metastasis (n=15) scheduled for lobectomy were studied. None of the patients received anti-cancer or antithrombotic treatment before inclusion in the study. None of the patients was hospitalized for surgery or acute medical illness or received any transfusion during the 3 months before inclusion. The control group consisted of 15 healthy age and sex-matched individuals. All patients received post-operative thromboprophylaxis with o.d enoxaparin 40 mg. The first injection was administered 6 hours after the end of surgery. Platelet poor plasma was prepared from blood drawn at the end of surgery (T1), 24 h after the end of the surgery 18 hours after the 1st s.c. injection of enoxaparin (T2); 48 h after the end of the surgery - 18 h after the 2nd s.c. injection of enoxaparin) (T3); at the 7th postoperative day - 18h after the 5th s.c. injection of enoxaparin (T4). Platelet derived microparticles (Pd-MP) were assessed using standardized flow cytometry assay. Thrombin generation (TG) was measured with the CAT assay (PPP-reagent 5pM, Thrombinoscope, The Netherlands). The Mean Rate Index (MRI) of TG was calculated [MRI = Peak/(ttPeak – lagtime)]. Tissue factor activity (TFa) was measured with a home-made test. Procoagulant phospholipid dependent activity was assessed with ProcoagPPL clotting assay, FVIIa with Staclot FVIIa-rTF, anti-Xa activity with STA Rotachrome Heparin, TFPI with Asserachrom Free TFPI assay (Diagnostica Stago, Asnieres, France). Results: Enoxaparin inhibited TG despite a significant increase of Pd-MP and TF. The MRI was the most sensitive parameter of thrombogram to detect the effect of enoxaparin. At T4 the inhibition of MRI was maximal (45% versus T1; p<0.05). After enoxaparin administration TFPI significantly increased whereas FVIIa did not significantly change compared to T1. At T4, the MRI remained abnormally high in 20% of patients although the anti-Xa activity was within the expected range for thromboprophylaxis. Conclusion: The TG inhibition by thromboprophylaxis with enoxaparin was significant on the 7th day (T4) after lobectomy. The MRI is the most relevant parameter of the thrombogram to evaluate the antithrombotic activity of enoxaparin. Based on MRI 20% of patients showed a “biological resistance” to enoxaparin that was not predicted by the anti-Xa activity in plasma. This observation needs to be further evaluated.
PO-55 A pulmonary severity index (PESI)-based competency that underpins a modular outpatient nurse lead PE (pulmonary embolism) service for cancer patients J. Palmer 1 , G. Bozas 1 , G. Avery 2 , A. Stephens 2 , A. Maraveyas 1,3 1 Queen’s Centre for Oncology and Hematology; 2 Department of Radiology; 3 Postgraduate Medical Institute University of Hull Introduction: Outpatient treatment of PE is described in the literature but the criteria for eligible patients in these retrospective studies are broad. A typical statement being: “All hemodynamically stable patients that do not require supplemental oxygenation and have no contra-indications to LMWH or significant co-morbidities should be considered for outpatient management”. Cancer is commonly a co-morbidity that necessitates admission. This approach based on clinical acumen and interpretation is neither teachable nor measurable nor transferable. Over the last 2 years in HEY
we have developed a nurse lead, evidence based, protocol driven modular pathway to manage all cancer patients with incidental PE. Training is based on a competency programme. Aim: To describe the development of a Nurse-Training competency Programme and supporting documentation that underpinned the development of an outpatient nurse lead service in Hull and East Yorkshire Hospitals Trust (UK). Methods: The competency is mapped to the STEPS 2 programme and the practitioner is required to demonstrate knowledge and understanding through observation and assessment by an identified supervisor. The theoretical component of the competency includes the understanding of the coagulation cascade, and the effect of heparins within this; the understanding of a normal and abnormal coagulation screen and the significance of D-dimers as a test; the knowledge of the clinical signs of PE and DVT; the scoring of findings according to the Pulmonary Severity Index (PESI); understanding of Heparin-Induced thrombocytopenia that underpins the assessment of the platelet count at 5-7 days. Subsequently the practitioner is observed on the completion of assessment tools, questionnaire and prescription pathway –which includes Dalteparin patient pack, patient information booklet, instructional DVD, emergency contact number, consent for subsequent telephone follow –up and immediately faxed GP letter. The practitioner is observed and scored on the management on two separate occasions. Feedback and appraisal is on a one to one basis. Results: Four specialist chemotherapy nurses (Grade 7) underwent this training and have managed incidental PE on an outpatient basis from March 2010. All practitioners were deemed competent (STEP 2) after having assessed 3 patients. These practitioners have to date (November 2011) assessed and managed 91 patients with incidental PE. No significant inter operator variability was found between the practitioners in scoring the PESI. The least reliable measurement was that of body temperature with an agreed action to have both tympanic and mouth temperature taken for all patients and the higheset recorded in the PESI scoring sheet. Conclusion: We have developed a teachable, measurable and transferable competency that can provide nurses efficient training to allow the safe outpatient management of patients with incidental PE.
PO-56 Venous thromboembolism in cancer patients S. Sawant, A.A. Dhir, A. Daddi, P.T.V. Nair Tata Memorial Hospital, Mumbai, India Aims and Objectives: Venous thromboembolism (VTE) has been considered to be rare in Indian population and is under reported in patients with malignancy. We studied the clinical profile and outcome of patients with VTE and cancer in Indian population. Methods: Retrospective analysis of data of cancer patients diagnosed with VTE in the year 2010 at a tertiary cancer centre was done. Demographic data, details of cancer, co-morbidities, details of VTE and treatment given for VTE and their outcomes were recorded and analyzed. Results: Fifty two cancer patients were diagnosed to have VTE. Females were predominant 36/52 (69.2%). The median age in females was 51 yrs (19-74) and in males 53 yrs (19-76). In females gynecologic malignancies 20/36 (55.6%) and in males genitourinary malignancies 9/16 (56.7%) were the commonest sites. Adenocarcinoma (42.3%) was commonest histopathology. 39/46 (84.8%) patients had advanced disease. 46 (88.46%) patients had only DVT, 3 (5.8%) patients had only PE and 3 (5.8%) patients had PE was associated with DVT. Majority of the patients had lower limb DVT 41 (78.8%). The associated risk factors included immobilization 3 (5.8%) and postoperative 5 (9.6%). 49/52 (94%) were treated with low molecular weight heparin of these 16 were give long term low molecular weight heparin and others were shifted to oral anticoagulants. One patient underwent catherter directed thrombolysis and IVC filter placement. The mean survival in months after diagnosis of DVT is 17 months (range 14 -19.6 months). Conclusion: A higher incidence of DVT is noted in female patients with gynecological malignancies and in male patients with genitourinary malignancies. Most patients had advanced disease. Clinicians should have a high index of suspicion for DVT while managing cancer patients. Risk stratification for VTE should be done in all cancer patients and thromboprophylaxis should be optimally used.
Abstracts / Thrombosis Research 129, Supplement 1 (2012) S155–S194
PO-54 Variability of response of thromboprophylaxis with fixed dose of enoxaparin in patients with primary adenocarcinoma of the lung undergoing lobectomy C. Papageorgiou 1,2 , E. Marret 1 , P. Van Dreden 3 , F. Bonnet 1 , B. Woodhams 3 , A.C. Spyropoulos 4, G.T. Gerotziafas 2,5 , I. Elalamy 2,5 1 Service Anesthésie -Réanimation Hôpital Tenon APHP, Paris, France; 2 ER2UPMC, Faculté de Médecine, Université Paris 6, Hôpital Tenon, APHP, Paris, France; 3 Diagnostica Stago, Gennevilliers, France; 4 University of Rochester Medical Center, Division of Hematology/Oncology, Rochester, NY, USA; 5 Service d’Hématologie Biologique, Hôpital Tenon APHP, Paris, France Background: Patients with lung adenocarcinoma are at high risk of VTE. Lobectomy is a major risk factor for VTE. Lung-cancer patients receive LWMH prophylaxis at the same dose as that recommended in major abdominal surgery. Aim of the study: We studied the impact of post-operative prophylaxis with enoxaparin on cellular and plasma markers of hypecoagulability in patients with primary, localised lung adenocarcinoma undergoing lobectomy. Patients and methods: Selected patients suffering from primary lung adenocarcinoma without metastasis (n=15) scheduled for lobectomy were studied. None of the patients received anti-cancer or antithrombotic treatment before inclusion in the study. None of the patients was hospitalized for surgery or acute medical illness or received any transfusion during the 3 months before inclusion. The control group consisted of 15 healthy age and sex-matched individuals. All patients received post-operative thromboprophylaxis with o.d enoxaparin 40 mg. The first injection was administered 6 hours after the end of surgery. Platelet poor plasma was prepared from blood drawn at the end of surgery (T1), 24 h after the end of the surgery 18 hours after the 1st s.c. injection of enoxaparin (T2); 48 h after the end of the surgery - 18 h after the 2nd s.c. injection of enoxaparin) (T3); at the 7th postoperative day - 18h after the 5th s.c. injection of enoxaparin (T4). Platelet derived microparticles (Pd-MP) were assessed using standardized flow cytometry assay. Thrombin generation (TG) was measured with the CAT assay (PPP-reagent 5pM, Thrombinoscope, The Netherlands). The Mean Rate Index (MRI) of TG was calculated [MRI = Peak/(ttPeak – lagtime)]. Tissue factor activity (TFa) was measured with a home-made test. Procoagulant phospholipid dependent activity was assessed with ProcoagPPL clotting assay, FVIIa with Staclot FVIIa-rTF, anti-Xa activity with STA Rotachrome Heparin, TFPI with Asserachrom Free TFPI assay (Diagnostica Stago, Asnieres, France). Results: Enoxaparin inhibited TG despite a significant increase of Pd-MP and TF. The MRI was the most sensitive parameter of thrombogram to detect the effect of enoxaparin. At T4 the inhibition of MRI was maximal (45% versus T1; p<0.05). After enoxaparin administration TFPI significantly increased whereas FVIIa did not significantly change compared to T1. At T4, the MRI remained abnormally high in 20% of patients although the anti-Xa activity was within the expected range for thromboprophylaxis. Conclusion: The TG inhibition by thromboprophylaxis with enoxaparin was significant on the 7th day (T4) after lobectomy. The MRI is the most relevant parameter of the thrombogram to evaluate the antithrombotic activity of enoxaparin. Based on MRI 20% of patients showed a “biological resistance” to enoxaparin that was not predicted by the anti-Xa activity in plasma. This observation needs to be further evaluated.
PO-55 A pulmonary severity index (PESI)-based competency that underpins a modular outpatient nurse lead PE (pulmonary embolism) service for cancer patients J. Palmer 1 , G. Bozas 1 , G. Avery 2 , A. Stephens 2 , A. Maraveyas 1,3 1 Queen’s Centre for Oncology and Hematology; 2 Department of Radiology; 3 Postgraduate Medical Institute University of Hull Introduction: Outpatient treatment of PE is described in the literature but the criteria for eligible patients in these retrospective studies are broad. A typical statement being: “All hemodynamically stable patients that do not require supplemental oxygenation and have no contra-indications to LMWH or significant co-morbidities should be considered for outpatient management”. Cancer is commonly a co-morbidity that necessitates admission. This approach based on clinical acumen and interpretation is neither teachable nor measurable nor transferable. Over the last 2 years in HEY
we have developed a nurse lead, evidence based, protocol driven modular pathway to manage all cancer patients with incidental PE. Training is based on a competency programme. Aim: To describe the development of a Nurse-Training competency Programme and supporting documentation that underpinned the development of an outpatient nurse lead service in Hull and East Yorkshire Hospitals Trust (UK). Methods: The competency is mapped to the STEPS 2 programme and the practitioner is required to demonstrate knowledge and understanding through observation and assessment by an identified supervisor. The theoretical component of the competency includes the understanding of the coagulation cascade, and the effect of heparins within this; the understanding of a normal and abnormal coagulation screen and the significance of D-dimers as a test; the knowledge of the clinical signs of PE and DVT; the scoring of findings according to the Pulmonary Severity Index (PESI); understanding of Heparin-Induced thrombocytopenia that underpins the assessment of the platelet count at 5-7 days. Subsequently the practitioner is observed on the completion of assessment tools, questionnaire and prescription pathway –which includes Dalteparin patient pack, patient information booklet, instructional DVD, emergency contact number, consent for subsequent telephone follow –up and immediately faxed GP letter. The practitioner is observed and scored on the management on two separate occasions. Feedback and appraisal is on a one to one basis. Results: Four specialist chemotherapy nurses (Grade 7) underwent this training and have managed incidental PE on an outpatient basis from March 2010. All practitioners were deemed competent (STEP 2) after having assessed 3 patients. These practitioners have to date (November 2011) assessed and managed 91 patients with incidental PE. No significant inter operator variability was found between the practitioners in scoring the PESI. The least reliable measurement was that of body temperature with an agreed action to have both tympanic and mouth temperature taken for all patients and the higheset recorded in the PESI scoring sheet. Conclusion: We have developed a teachable, measurable and transferable competency that can provide nurses efficient training to allow the safe outpatient management of patients with incidental PE.
PO-56 Venous thromboembolism in cancer patients S. Sawant, A.A. Dhir, A. Daddi, P.T.V. Nair Tata Memorial Hospital, Mumbai, India Aims and Objectives: Venous thromboembolism (VTE) has been considered to be rare in Indian population and is under reported in patients with malignancy. We studied the clinical profile and outcome of patients with VTE and cancer in Indian population. Methods: Retrospective analysis of data of cancer patients diagnosed with VTE in the year 2010 at a tertiary cancer centre was done. Demographic data, details of cancer, co-morbidities, details of VTE and treatment given for VTE and their outcomes were recorded and analyzed. Results: Fifty two cancer patients were diagnosed to have VTE. Females were predominant 36/52 (69.2%). The median age in females was 51 yrs (19-74) and in males 53 yrs (19-76). In females gynecologic malignancies 20/36 (55.6%) and in males genitourinary malignancies 9/16 (56.7%) were the commonest sites. Adenocarcinoma (42.3%) was commonest histopathology. 39/46 (84.8%) patients had advanced disease. 46 (88.46%) patients had only DVT, 3 (5.8%) patients had only PE and 3 (5.8%) patients had PE was associated with DVT. Majority of the patients had lower limb DVT 41 (78.8%). The associated risk factors included immobilization 3 (5.8%) and postoperative 5 (9.6%). 49/52 (94%) were treated with low molecular weight heparin of these 16 were give long term low molecular weight heparin and others were shifted to oral anticoagulants. One patient underwent catherter directed thrombolysis and IVC filter placement. The mean survival in months after diagnosis of DVT is 17 months (range 14 -19.6 months). Conclusion: A higher incidence of DVT is noted in female patients with gynecological malignancies and in male patients with genitourinary malignancies. Most patients had advanced disease. Clinicians should have a high index of suspicion for DVT while managing cancer patients. Risk stratification for VTE should be done in all cancer patients and thromboprophylaxis should be optimally used.