Letters to the Editor 115
Management of challenging cases of patients with cancerassociated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a rebuttal T. H. OO The University of Texas MD Anderson Cancer Center, Houston, TX, USA
To cite this article: Oo TH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a rebuttal. J Thromb Haemost 2014; 12: 115–6. See also Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AYY, on behalf of the Subcommittee on Haemostasis and Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a reply to a rebuttal. This issue, pp 116–7
I read with interest the recent article by Carrier et al. [1]. Although I congratulate Dr Carrier and his colleagues for this article, I would like to make some comments on ‘Management of cancer-associated thrombosis in patients with thrombocytopenia’. The authors stated that ‘In the initial month (acute period) following the diagnosis of VTE, the risk of recurrent thrombosis is highest. Consequently, giving maximal or therapeutic anticoagulant therapy is important. In patients with acute CAT and platelet count ≥ 50 9 109 L 1, full therapeutic anticoagulation without platelet transfusion is appropriate. But, in patients with a platelet count < 50 9 109 L 1, platelet transfusion support to maintain a platelet count ≥ 50 9 109 L 1 to allow full, therapeutic anticoagulation should be considered’. Although I support the first recommendation, i.e. ‘In patients with acute CAT and platelet count ≥ 50 9 109 L 1, full therapeutic anticoagulation without platelet transfusion is appropriate’, I have reservations about the second recommendation for platelet transfusion support to maintain a platelet count of ≥ 50 9 109 L 1 to allow full, therapeutic anticoagulation, for the following reasons. 1 There is chronic national shortage of blood and platelet donors [2]. Because of this, blood bank directors do not issue donor platelets to patients for this indication (personal communication from blood bank directors). Correspondence: Thein H. Oo, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1464, Houston, TX 77030, USA. Tel.: +1 713 563 4260; fax: +1 713 563 4443. E-mail: [email protected] DOI: 10.1111/jth.12434 Received 30 August 2013 Manuscript handled by: F. R. Rosendaal Final decision: F. R. Rosendaal, 19 October 2013 © 2013 International Society on Thrombosis and Haemostasis
2 Donor platelets have a life span of 5 days. Despite platelet transfusions, platelet counts drop in patients who are thrombocytopenic for a long time (e.g. receiving myelosuppressive or high-dose chemotherapy). Platelet transfusion support will be required very frequently to keep the platelet count at ≥ 50 9 109 L 1. Platelet transfusion can also be complicated by infections, transfusion-related acute lung injury, alloimmunization, allergic reactions, and febrile non-hemolytic reactions [3]. Should patients be subjected to these potential complications during the first month? 3 In our retrospective study of 53 patients with cancerassociated thrombosis and thrombocytopenia < 50 9 109 L 1, the impact of anticoagulation dose reduction on the risk of recurrent cancer-associated thrombosis appeared to be minor. Twenty-three patients received anticoagulation for < 3 months, including 11 patients who received it for < 14 days. Fifteen patients had ≥ 25% dose reductions of anticoagulants. At 6month follow-up, the recurrent thrombosis rate was 1.8% [4]. We and our colleagues at the Memorial Sloan Kettering Cancer Center have adopted the following dynamic dosing strategy for anticoagulants, irrespective of the initial 1-month period. For a platelet count of ≥ 50 9 109 L 1, full therapeutic anticoagulation; for a platelet count of 25–50 9 109 L 1, reduced-dose enoxaparin 30–40 mg twice daily; and for a platelet count of < 25 9 109 L 1, no anticoagulation [5]. In summary, platelet transfusion support to maintain a platelet count of ≥ 50 9 109 L 1 just to allow full, therapeutic anticoagulation may not be practical. The superiority of full anticoagulation in thrombocytopenic (< 50 9 109 L 1) cancer patients with platelet transfusion support over other strategies, such as a dynamic dosing strategy for anticoagulants or the placement of retrievable inferior vena cava filters, has not been proven. Platelet transfusion itself carries many potential risks, and donor platelets are becoming harder to obtain. I would like the authors to reconsider their recommendations regarding this challenging clinical situation.
116 Letters to the Editor
Disclosure of Conflict of Interests The author states that he has no conflict of interest. References 1 Carrier M, Khorana A, Zwicker J, Noble S, Lee A, The subcommittee on Haemostasis Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost 2013; 1: 1–9.
2 Red Cross Issues Emergency Call for Blood and Platelet Donors. http://www.redcross.org/news/article/Red-Cross-Issues-EmergencyCall-for-Blood-and-Platelet-Donors. Accessed 26 August 2013. 3 Yuan S, Goldfinger D. Clinical and laboratory aspects of platelet transfusion therapy. www.uptodate.com. Accessed 26 August 2013. 4 Pemmaraju N, Kroll MH, Afshar-Kharghan V, Oo TH. Bleeding risk in thrombocytopenic cancer patients with venous thromboembolism (VTE) receiving anticoagulation. https://ash.confex.com/ ash/2012/webprogram/Paper47208.html. Accessed 26 August 2013. 5 Soff GA. Pathophysiology and management of thrombosis in cancer: 150 years of progress. J Thromb Thrombolysis 2013; 35: 346– 351.
Management of challenging cases of patients with cancerassociated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a reply to a rebuttal M . C A R R I E R , * A . A . K H O R A N A , † J . I . Z W I C K E R , ‡ S . N O B L E , § A . Y . Y . L E E ¶ and O N B E H A L F O F T H E SUBCOMMITTEE ON HAEMOSTASIS AND MALIGNANCY FOR THE SSC OF THE ISTH *Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada; †Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA; ‡Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; §Royal Gwent Hospital, Newport, UK; and ¶Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
To cite this article: Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AYY, on behalf of the Subcommittee on Haemostasis and Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a reply to a rebuttal. J Thromb Haemost 2014; 12: 116–7. See also Carrier M, Khorana A, Zwicker J, Noble S, Lee A; the subcommittee on Haemostasis Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost 2013; 11: 1760–5 and Oo TH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a rebuttal. This issue, pp 115–6.
. e thank Dr Oo for his interesting comments on the W management of patients with acute cancer-associated thrombosis (CAT) and thrombocytopenia (< 50 9 109 L–1). As discussed in our article, the guidance statement specifically addresses challenging clinical situations without high-quality evidence, with the aim of providing expert opinions and pragmatic approaches regarding the management of anticoagulation in individual cancer patients with these therapeutic challenges [1]. It is beyond the Correspondence: Agnes Y. Y. Lee, Division of Hematology, University of British Columbia, 2775 Laurel Street 10th floor, Vancouver, BC, V5Z 1M9, Canada. Tel.: +1 604 875 4952; fax: +1 604 875 4696. E-mail: [email protected]
scope of this article to anticipate and address specific national variations in practice (e.g. regional shortage of blood and platelet donors) or hospital-specific restrictions on the use of blood products. Therefore, clinicians need to interpret the Guidance Statement within their local context. As shown in many previous studies, the risk of recurrent venous thromboembolism and its associated casefatality rates are highest during the first month following the index event, and the risks associated with inadequate anticoagulation are therefore substantial [2–6]. Therefore, we recommend full therapeutic doses of anticoagulation with platelet transfusion for the management of acute CAT (i.e. ≤ 1 month) and thrombocytopenia (< 50 9 109 L–1) [1]. However, we agree with Dr Oo that platelet transfusion might not always be possible or successful in achieving a platelet count of ≥ 50 9 109 L–1, and might
DOI: 10.1111/jth.12444 © 2013 International Society on Thrombosis and Haemostasis
Management of challenging cases of patients with cancerassociated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a rebuttal T. H. OO The University of Texas MD Anderson Cancer Center, Houston, TX, USA
To cite this article: Oo TH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a rebuttal. J Thromb Haemost 2014; 12: 115–6. See also Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AYY, on behalf of the Subcommittee on Haemostasis and Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a reply to a rebuttal. This issue, pp 116–7
I read with interest the recent article by Carrier et al. [1]. Although I congratulate Dr Carrier and his colleagues for this article, I would like to make some comments on ‘Management of cancer-associated thrombosis in patients with thrombocytopenia’. The authors stated that ‘In the initial month (acute period) following the diagnosis of VTE, the risk of recurrent thrombosis is highest. Consequently, giving maximal or therapeutic anticoagulant therapy is important. In patients with acute CAT and platelet count ≥ 50 9 109 L 1, full therapeutic anticoagulation without platelet transfusion is appropriate. But, in patients with a platelet count < 50 9 109 L 1, platelet transfusion support to maintain a platelet count ≥ 50 9 109 L 1 to allow full, therapeutic anticoagulation should be considered’. Although I support the first recommendation, i.e. ‘In patients with acute CAT and platelet count ≥ 50 9 109 L 1, full therapeutic anticoagulation without platelet transfusion is appropriate’, I have reservations about the second recommendation for platelet transfusion support to maintain a platelet count of ≥ 50 9 109 L 1 to allow full, therapeutic anticoagulation, for the following reasons. 1 There is chronic national shortage of blood and platelet donors [2]. Because of this, blood bank directors do not issue donor platelets to patients for this indication (personal communication from blood bank directors). Correspondence: Thein H. Oo, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1464, Houston, TX 77030, USA. Tel.: +1 713 563 4260; fax: +1 713 563 4443. E-mail: [email protected] DOI: 10.1111/jth.12434 Received 30 August 2013 Manuscript handled by: F. R. Rosendaal Final decision: F. R. Rosendaal, 19 October 2013 © 2013 International Society on Thrombosis and Haemostasis
2 Donor platelets have a life span of 5 days. Despite platelet transfusions, platelet counts drop in patients who are thrombocytopenic for a long time (e.g. receiving myelosuppressive or high-dose chemotherapy). Platelet transfusion support will be required very frequently to keep the platelet count at ≥ 50 9 109 L 1. Platelet transfusion can also be complicated by infections, transfusion-related acute lung injury, alloimmunization, allergic reactions, and febrile non-hemolytic reactions [3]. Should patients be subjected to these potential complications during the first month? 3 In our retrospective study of 53 patients with cancerassociated thrombosis and thrombocytopenia < 50 9 109 L 1, the impact of anticoagulation dose reduction on the risk of recurrent cancer-associated thrombosis appeared to be minor. Twenty-three patients received anticoagulation for < 3 months, including 11 patients who received it for < 14 days. Fifteen patients had ≥ 25% dose reductions of anticoagulants. At 6month follow-up, the recurrent thrombosis rate was 1.8% [4]. We and our colleagues at the Memorial Sloan Kettering Cancer Center have adopted the following dynamic dosing strategy for anticoagulants, irrespective of the initial 1-month period. For a platelet count of ≥ 50 9 109 L 1, full therapeutic anticoagulation; for a platelet count of 25–50 9 109 L 1, reduced-dose enoxaparin 30–40 mg twice daily; and for a platelet count of < 25 9 109 L 1, no anticoagulation [5]. In summary, platelet transfusion support to maintain a platelet count of ≥ 50 9 109 L 1 just to allow full, therapeutic anticoagulation may not be practical. The superiority of full anticoagulation in thrombocytopenic (< 50 9 109 L 1) cancer patients with platelet transfusion support over other strategies, such as a dynamic dosing strategy for anticoagulants or the placement of retrievable inferior vena cava filters, has not been proven. Platelet transfusion itself carries many potential risks, and donor platelets are becoming harder to obtain. I would like the authors to reconsider their recommendations regarding this challenging clinical situation.
116 Letters to the Editor
Disclosure of Conflict of Interests The author states that he has no conflict of interest. References 1 Carrier M, Khorana A, Zwicker J, Noble S, Lee A, The subcommittee on Haemostasis Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost 2013; 1: 1–9.
2 Red Cross Issues Emergency Call for Blood and Platelet Donors. http://www.redcross.org/news/article/Red-Cross-Issues-EmergencyCall-for-Blood-and-Platelet-Donors. Accessed 26 August 2013. 3 Yuan S, Goldfinger D. Clinical and laboratory aspects of platelet transfusion therapy. www.uptodate.com. Accessed 26 August 2013. 4 Pemmaraju N, Kroll MH, Afshar-Kharghan V, Oo TH. Bleeding risk in thrombocytopenic cancer patients with venous thromboembolism (VTE) receiving anticoagulation. https://ash.confex.com/ ash/2012/webprogram/Paper47208.html. Accessed 26 August 2013. 5 Soff GA. Pathophysiology and management of thrombosis in cancer: 150 years of progress. J Thromb Thrombolysis 2013; 35: 346– 351.
Management of challenging cases of patients with cancerassociated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a reply to a rebuttal M . C A R R I E R , * A . A . K H O R A N A , † J . I . Z W I C K E R , ‡ S . N O B L E , § A . Y . Y . L E E ¶ and O N B E H A L F O F T H E SUBCOMMITTEE ON HAEMOSTASIS AND MALIGNANCY FOR THE SSC OF THE ISTH *Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada; †Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA; ‡Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; §Royal Gwent Hospital, Newport, UK; and ¶Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
To cite this article: Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AYY, on behalf of the Subcommittee on Haemostasis and Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a reply to a rebuttal. J Thromb Haemost 2014; 12: 116–7. See also Carrier M, Khorana A, Zwicker J, Noble S, Lee A; the subcommittee on Haemostasis Malignancy for the SSC of the ISTH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost 2013; 11: 1760–5 and Oo TH. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH: a rebuttal. This issue, pp 115–6.
. e thank Dr Oo for his interesting comments on the W management of patients with acute cancer-associated thrombosis (CAT) and thrombocytopenia (< 50 9 109 L–1). As discussed in our article, the guidance statement specifically addresses challenging clinical situations without high-quality evidence, with the aim of providing expert opinions and pragmatic approaches regarding the management of anticoagulation in individual cancer patients with these therapeutic challenges [1]. It is beyond the Correspondence: Agnes Y. Y. Lee, Division of Hematology, University of British Columbia, 2775 Laurel Street 10th floor, Vancouver, BC, V5Z 1M9, Canada. Tel.: +1 604 875 4952; fax: +1 604 875 4696. E-mail: [email protected]
scope of this article to anticipate and address specific national variations in practice (e.g. regional shortage of blood and platelet donors) or hospital-specific restrictions on the use of blood products. Therefore, clinicians need to interpret the Guidance Statement within their local context. As shown in many previous studies, the risk of recurrent venous thromboembolism and its associated casefatality rates are highest during the first month following the index event, and the risks associated with inadequate anticoagulation are therefore substantial [2–6]. Therefore, we recommend full therapeutic doses of anticoagulation with platelet transfusion for the management of acute CAT (i.e. ≤ 1 month) and thrombocytopenia (< 50 9 109 L–1) [1]. However, we agree with Dr Oo that platelet transfusion might not always be possible or successful in achieving a platelet count of ≥ 50 9 109 L–1, and might
DOI: 10.1111/jth.12444 © 2013 International Society on Thrombosis and Haemostasis
