You Make the Call
Each month in “ You Make the Call ,” we ’ ll pick a challenging clinical question submitted through ASH ’ s Consult a Colleague program and post the expert ’ s response , but we also want to know what you would do . Send in your responses to next month ’ s clinical dilemma and see how your answer matches up to the experts ’ in the next print issue .
This month , Neil A . Zakai , MD , discusses how to treat a patient with aplastic anemia who has religious objections to allogeneic blood product .
TRAINING and EDUCATION
Clinical Dilemma :
A 30-year-old man with aplastic anemia ( AA ) presented with rapidly progressive exercise intolerance over a two-week period . His white blood cell count is 2.2x10 9 / L with an absolute neutrophil count of 450 / μL . Hemoglobin is 5.5 g / dL , and his platelet count is 3,000 / μL . Lactate dehydrogenase is 180 / μL and erythrocyte sedimentation rate is 89 mm / hr . Kidney and liver function is normal . A bone marrow ( BM ) biopsy shows scant lymphocytes and BM stromal cells . Hematopoietic elements are virtually absent . No signs of paroxysmal nocturnal hemoglobinuria by flow cytometry . The patient refuses packed red blood cells or platelet transfusions for religious reasons . We have started immunosuppressive treatment with anti-thymocyte globulin ( ATG ), steroids , and cyclosporine . Since the patient does not wish to receive transfusions , BM transplant is probably out of the question . Do you think it is reasonable to add erythropoietin , eltrombopag , or granulocyte colony-stimulating factor upfront ? Is there anything else I am not thinking about ?
Expert Opinion
Neil A . Zakai , MD Associate Professor of Medicine , Hematology / Oncology Division , Department of Medicine Associate Professor of Pathology & Laboratory Medicine Larner College of Medicine , University of Vermont Burlington , Vermont
Managing patients with bone marrow failure syndromes and religious objections to allogeneic blood product support is exceedingly challenging , especially in a younger individual with effective treatment options for the underlying disorder . I would divide management into immediate / near-term issues , and then the longer term issues .
Focusing first on the immediate consequences of his bone marrow failure , ATG and cyclosporine are the mainstays of immunosuppressive treatment for individuals with AA who are not candidates for transplant . Responses , however , can take weeks to months . This individual ’ s most pressing concern is thrombocytopenia and his risk for bleeding . Antifibrinolytic agents such as tranexamic acid and aminocaproic acid have been studied for decades , reduce bleeding in individuals with thrombocytopenia , and appear safe in this population , but with mixed results concerning efficacy . 1 Thrombopoietinreceptor agonists are effective in refractory AA , and have recently shown promise in the frontline setting . 2 However , responses often take months . To help with anemia and granulocytopenia , erythropoietin agonists and filgrastim are unlikely to be effective , as his endogenous levels of these hormones are likely already high . 3
The second issue is how to deal with longer-term prognosis in a young man with AA . Some individuals with religious objections to blood products accept stem cell transplants and are able to tolerate stem cell transplants without transfusions . 4
To optimally care for this patient , my recommendations are :
• Check his B12 , folate , and iron and correct any deficiencies .
• Check his erythropoietin level and supplement if inappropriately low .
• Discuss with him the options for hematopoietic cell transplant .
• Consider adding an antifibrinolytic agent while his platelet count is critically low .
• Consider adding eltrombopag to his initial immunosuppression to maximize his chances of responding to therapy .
REFERENCES
1 . Estcourt LJ , Desborough M , Brunskill SJ , et al . Antifibrinolytics ( lysine analogues ) for the prevention of bleeding in people with haematological disorders . Cochrane Database Syst Rev . 2016 ; 3 : CD009733 .
2 . Townsley DM , Scheinberg P , Winkler T , et al . Eltrombopag added to standard immunosuppression for aplastic anemia . N Engl J Med . 2017 ; 376:1540-50 .
3 . Bessho M , Hirashima K , Asano S , et al . Treatment of the anemia of aplastic anemia patients with recombinant human erythropoietin in combination with granulocyte colony-stimulating factor : a multicenter randomized controlled study . Multicenter Study Group . Eur J Haematol . 1997 ; 58:265-72 .
4 . Mazza P , Prudenzano A , Amurri B , et al . Myeloablative therapy and bone marrow transplantation in Jehovah ’ s Witnesses with malignancies : single center experience . Bone Marrow Transplant . 2003 ; 32:433-36 .
Next Month ’ s Clinical Dilemma :
A healthy 42-year-old woman not on estrogen flew 2.5 hours to North Carolina – plus time spent sitting in the terminal . She flew home two days later . The next morning she drove 2.5 hours to her sister ’ s home and returned home the following morning . Three days later she was diagnosed with a lower extremity deep vein thrombosis ( DVT ). Would you consider her DVT provoked or unprovoked ? Would three months of anticoagulation be okay , or does she need D-dimers to help decide ? If you consider her DVT to be unprovoked , how long should she be anticoagulated ?
How would you respond ? Email us at ashclinicalnews @ hematology . org ●
Consult a Colleague Through ASH
Consult a Colleague is a service for ASH members that helps facilitate the exchange of information between hematologists and their peers . ASH members can seek consultation on clinical cases from qualified experts in 11 categories :
• Anemias
• Hematopoietic cell transplantation
• Hemoglobinopathies
• Hemostasis / thrombosis
• Lymphomas
• Lymphoproliferative disorders
• Leukemias
• Multiple myeloma & Waldenström macroglobulinemia
• Myeloproliferative disorders
• Myelodysplastic syndromes
• Thrombocytopenias
Assigned volunteers (“ colleagues ”) will respond to inquiries within two business days ( either by email or phone ).
Have a puzzling clinical dilemma ? Submit a question , and read more about Consult a Colleague volunteers at hematology . org / Clinicians / Consult . aspx or scan the QR code .
* If you have a request related to a hematologic disorder not listed here , please email your recommendation to ashconsult @ hematology . org so it can be considered for addition in the future .
DISCLAIMER : ASH does not recommend or endorse any specific tests , physicians , products , procedures , or opinions , and disclaims any representation , warranty , or guaranty as to the same . Reliance on any information provided in this article is solely at your own risk .
34 ASH Clinical News August 2017