Transfusion Reactions: A Case Study of an Ocular Adverse Event During Autologous Transplantation

Ijeoma Julie Eche-Ugwu

Myrna Nahas

Elissa Dunn

Ijeoma Julie Eche-Ugwu

Kerry L. O’Brien

adverse events, stem cell transplantation, platelet transfusion, ocular reaction
CJON 2019, 23(5), 509-513. DOI: 10.1188/19.CJON.509-513

Background: Transfusion of blood products is an integral part of hematopoietic stem cell transplantation. Because of the risk for myelotoxicity during conditioning regimens, adequate transfusion support is needed. Typical signs and symptoms of transfusion reactions include fever, chills, hives, and itching. Uncommon symptoms, such as conjunctival erythema, periorbital itching, erythema, and edema, can also occur.

Objectives: The purpose of this article is to describe atypical transfusion-related reactions in a patient undergoing stem cell transplantation.

Methods: This article presents a case study of a patient with cancer undergoing autologous stem cell transplantation who experienced an adverse ocular reaction following platelet transfusion.

Findings: Ensuring that oncology nurses are proactive in identifying and managing symptoms that can result from atypical transfusion reactions can reduce morbidity and mortality and improve overall patient care outcomes.

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    Hematopoietic stem cell transplantation (HSCT) is an aggressive therapy that is used for the treatment of hematologic malignancies, solid tumors, bone marrow failure, autoimmune diseases, and inherited metabolic and immunodeficiency disorders (American Cancer Society [ACS], 2016). Autologous and allogeneic are two of the most common types of stem cell transplantation. The patient’s own stem cells are used during autologous transplantation, whereas donor stem cells are used with recipients of allogeneic transplantations (ACS, 2016). Because conditioning regimens, such as ablative chemotherapy, can result in potentially fatal bone marrow myelosuppression, adequate support through the transfusion of blood products is an integral care component for patients undergoing HSCT. Blood product transfusions prior to stem cell engraftment can prevent HSCT-related morbidity and mortality; however, risk factors, such as allergic reactions and sepsis, and adverse events may jeopardize outcomes in patients undergoing HSCT (de Freitas, de Almeida, & Guedes, 2014).

    Autologous stem cell transplantation can be used to treat leukemia, lymphoma, multiple myeloma, testicular cancer, neuroblastoma, and autoimmune disorders. Stem cells are collected or harvested peripherally from the bloodstream or bone marrow. Tandem transplantations, which are often used to treat testicular cancer and multiple myeloma, are administered to patients using their own stem cells following two or three cycles of high-dose chemotherapy (ACS, 2016). Ensuring that oncology nurses can recognize adverse events of transfusions can help to minimize transfusion-associated morbidity and mortality among patients with cancer.

    Transfusion-Related Reactions

    Transfusion-related reactions (TRRs) are potential adverse events that occur either during or following the administration of blood transfusions or transfusion components (Webb, Norris, & Hands, 2018). TRRs can be acute (within 24 hours of administration) or delayed (at least 24 hours after administration). Acute TRRs can include acute hemolytic reactions, febrile nonhemolytic reactions, allergic reactions, transfusion-related acute lung injury, transfusion-associated circulatory overload, hypotensive transfusion reactions, and bacterial contaminations (Case et al., 2017; Fung, Grossman, Hillyer, & Westhoff, 2014). Delayed TRRs can include transfusion-associated graft-versus-host disease, post-transfusion purpura, delayed hemolytic transfusion reactions, and delayed serologic reactions. The most common types of transfusion reactions are febrile nonhemolytic and allergic (urticarial) (Delaney et al., 2016; Frazier, Higgins, Bugajski, Jones, & Brown, 2017). Additional transfusion reaction types and clinical manifestations are described in Figure 1.

    Allergic Reactions

    Allergic TRR rates are highest with platelet and fresh frozen plasma transfusions compared to transfusions using other blood products (Suddock & Crookston, 2019). Cutaneous manifestations (e.g., hives, rash, pruritis, flushing) are common allergic TRRs. Although they are rare, severe reactions, such as anaphylaxis (e.g, bronchospasm, angioedema, hypotension), can also occur (Suddock & Crookston, 2019). The mechanisms of action for less severe allergic reactions are unclear; however, severe allergic TRRs (e.g., anaphylactic shock) have been linked to immunoglobin E (IgE) (Vamvakas & Pineda, 2001). Passive transfers of human leukocyte antigen antibodies, allergens, preexisting antibodies to serum proteins, and IgE antibodies are believed to increase the propensity of less-severe TRRs (Savage et al., 2013). The management of allergic TRRs depends on the severity of the reaction. Mild allergic TRRs typically respond to antihistamines, whereas more severe reactions, such as anaphylaxis, require the use of epinephrine and corticosteroids as adjunctive therapies (Wood, Traub, & Lipinski, 2013). Wood et al. (2013) recommend that epinephrine via IV is administered only for patients who are hypotensive (unresponsive to aggressive fluid resuscitation) and patients who are in respiratory or cardiac arrest. Intramuscular epinephrine is the most effective medication for anaphylaxis management (Savage et al., 2013; Wood et al., 2013). In addition, steroids can be considered for moderate allergic TRRs (Delaney et al., 2016).

    Febrile Nonhemolytic Transfusion Reactions

    Leukocyte-reduced blood products are used in patients with cancer to reduce the incidence of febrile nonhemolytic transfusion reactions (King et al., 2004). Alloimmunization and transfusion-associated infections, such as transfusion-transmitted cytomegalovirus, are substantially decreased when leukocyte-reduced blood products are used. According to the Centers for Disease Control and Prevention ([CDC], 1998), the presence of allergens or chemicals in the blood collection filtration system has been linked to allergic TRRs. However, a study by Stroncek et al. (2014) suggests that leukocyte-reduction filters are no longer recommended; instead, leukocytes are reduced in apheresis platelets by elutriation. Elutriation is a process in which particles in fluids are separated based on their size and density using centrifugal force. In addition, elutriation allows for the separation of rich plasma platelets within the apheresis instrument (Perez et al., 2014).

    Ocular Reactions

    Reports on adverse ocular manifestations of TRRs are limited; however, they are believed to be driven by allergens (CDC, 1998). From 1997 to 1998, several case reports described 106 adverse ocular reactions observed within 24 hours of red blood cell transfusions in 74 patients from 14 U.S. states. Ocular reactions are characterized by severe conjunctival erythema, conjunctival hemorrhage, eye pain, photophobia, periorbital edema, and decreased visual acuity. Respiratory symptoms, including dyspnea, headache, arthralgias, and nausea, have also been reported. The following case presentation describes an ocular adverse reaction that occurred during a platelet transfusion for a patient who was being treated for a mixed germ cell tumor 10 days following stem cell transplantation.

    Case Study

    R.S. is a 43-year-old married, White, non-Hispanic man who presented with a right scrotal mass and elevated human chorionic gonadotropin and lactate dehydrogenase levels. Pathology derived from a right radical orchiectomy revealed a mixed germ cell tumor, comprised of seminoma (40%), choriocarcinoma (20%), embryonal carcinoma (20%), and yolk sac (20%), with extensive lymphatic vascular invasion. Evaluation of R.S.’s medical and surgical history was unremarkable. Based on these clinical findings, R.S.’s treatments began with three chemotherapy cycles of adjuvant bleomycin, etoposide, and cisplatin followed by paclitaxel and ifosfamide-carboplatin/etoposide in anticipation of autologous (tandem) stem cell transplantation. R.S. presented to the inpatient bone marrow transplantation unit for the first of three tandem autologous transplantations.

    During post-transplantation follow-up care, R.S. experienced complications that interrupted his treatment course. R.S. required supportive care for febrile neutropenia without a clear source of infection and chemotherapy-induced gastrointestinal toxicities, including nausea and vomiting, diarrhea, and decreased appetite. On the tenth day following transplantation, R.S.’s complete blood count with differential was notable for leukopenia (white blood cell count of 0.7 K/mcl), severe neutropenia (absolute neutrophil count of 200), anemia (hemoglobin of 8 g/dl and hematocrit of 23%), and severe thrombocytopenia (10 K/mcl). Liver and renal function tests were within the normal range. R.S. required several blood product transfusions following admission that did not show evidence of adverse events, including five units of platelets and two units of packed red blood cell products.

    To minimize the risk for bleeding during nadir (period when blood counts are low), R.S.’s healthcare providers ordered one leukocyte-reduced irradiated apheresis platelet unit to be administered to R.S. for one hour. About 20 minutes into the platelet transfusion, R.S. reported the acute onset of bilateral eye stinging with a filmy sensation and itching that resulted in transient blurred vision. Transfusion was stopped immediately and vital signs were assessed (temperature = 97.9ºF, heart rate = 93, oxygen saturation = 97% room air, respiratory rate = 20, blood pressure = 117/80 mmHg). On physical examination, R.S. was noted to have moderate bilateral conjunctival erythema, mild lower eyelid edema, and clear watery discharge from both of his eyes. In addition, he had some labored breathing. After the transfusion was interrupted, symptoms improved without additional intervention. The platelet transfusion was restarted with close monitoring after 15 minutes. However, four minutes prior to completion of the platelet transfusion (after receipt of 186 ml), R.S. reported the acute onset of chest tightness followed by mild dyspnea and a dry cough. R.S. was treated via IV with 100 mg of hydrocortisone, 25 mg of diphenhydramine, and 20 mg of famotidine. Following receipt of medications, he had complete resolution of his ocular and respiratory symptoms. A chest x-ray was performed, which showed no pleural effusion or acute cardiopulmonary process. After stabilization of symptoms, a transfusion reaction investigation was initiated by personnel at the blood bank.

    Clinical Recommendations

    Following the transfusion reaction investigation, the donor platelet product was found to be ABO (type A, B, or O) compatible with the recipient’s blood type (AB). R.S.’s post-transfusion plasma was clear and yellow. The results of a direct antiglobulin test, which was administered to evaluate for antibodies attached to red blood cells circulating in the patient, were negative. The blood bank personnel did not find the presence of chemicals associated with the production of the blood collection system or allergens in the blood collection filtration system. In addition, no clerical discrepancies were detected.

    Based on the findings and R.S.’s clinical presentation, the blood bank investigators did not recommend changes to the standard transfusion practice at this clinical setting. His presenting symptoms—particularly the ocular symptoms—were believed to be coincidental; however, the risk for an allergic TRR when receiving a leukocyte-reduced and irradiated apheresis platelet product should be considered during future administrations. Because allergic reactions are typically idiosyncratic, the incidence of one allergic TRR does not necessarily predict future reactions, and, therefore, it is recommended that premedication is avoided with subsequent transfusions (Savage et al., 2015). In previous randomized controlled trials, premedication with diphenhydramine was not found to reduce the incidence of allergic transfusion reactions (Kennedy, Case, Hurd, Cruz, & Pomper, 2008; Savage et al., 2015; Wang et al., 2002). Although practitioners may favor premedicating patients with a history of allergic TRRs, Savage et al. (2015) recommend avoiding premedication. In the event that another allergic TRR occurs, repeat workup should be performed (Savage et al., 2013).

    In clinical settings, platelets may be washed prior to administration to prevent the risk for TRRs in patients with a medical history of adverse events. According to Kim et al. (2012), using washed platelets during transfusions may minimize TRRs because the presence of plasma components in platelets can cause mild or even severe allergic TRRs, such as anaphylaxis. Barring concerns for platelet loss and recovery after transfusion with washed blood products, the clinical benefits of platelet washing may be considered for eligible patients to prevent allergic reactions (Bhattacharya, Marwaha, Dhawan, Roy, & Sharma, 2011). A study by Azuma et al. (2009) indicated that the TRR rate in patients who received washed platelets was significant compared to patients who did not. In the same study, however, no clinically significant bleeding episodes occurred in either group.

    Implications for Nursing

    Patients with cancer undergoing HSCT are at substantial risk for acute or delayed transfusion reactions because of their of exposure to blood products. Oncology nurses are well positioned to assess patients during and following transfusions to reduce these complication risks. Thorough risk assessments and continuous monitoring are important to prevent clinical deterioration. Ensuring that nurses are educated on and understand the symptoms associated with transfusions would allow for the early identification of atypical presentations. Ocular symptoms, such as conjunctival erythema, conjunctival hemorrhage, eye pain, photophobia, periorbital edema, and periorbital itching, may develop during transfusions. In addition to early symptom identification, following evidence-based transfusion practices can improve patient outcomes. As exemplified in this case study, the onset and clinical manifestations of TRRs can vary and continued nursing education on TRR is needed. Patient education on early symptom detection and management is also critical. Ensuring that nurses and other healthcare providers continue to report any adverse events following platelet transfusions can improve care standards and overall patient outcomes.


    For patients with cancer who receive multiple blood product transfusions throughout the course of HSCT, strict adherence to standard transfusion practices is needed to ensure the early detection and treatment of uncommon adverse events. Vigilant identification and management of atypical TRRs is critical when an ocular reaction is suspected following platelet transfusion during HSCT. Adverse events during platelet transfusions can be investigated by members of the interprofessional care team, and gaps in transfusion practices can be addressed. In addition, standardized transfusion practices can lead to overall improved patient outcomes.

    About the Author(s)

    Ijeoma Julie Eche, PhD, FNP-BC, AOCNP®, CPHON®, BMTCN®, is a nurse practitioner and postdoctoral research fellow, Myrna Nahas, MD, is an instructor of medicine in the Division of Hematology-Oncology, Elissa Dunn, RN, is a bone marrow transplantation staff nurse, Ifeoma Mary Eche, PharmD, BCPS, BCCP, CACP, is a critical care clinical pharmacy manager, and Kerry L. O’Brien, MD, is a medical director, all at the Beth Israel Deaconess Medical Center in Boston, MA. The authors take full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. The article has been reviewed by independent peer reviewers to ensure that it is objective and free from bias. Ijeoma Julie Eche can be reached at, with copy to (Submitted March 2019. Accepted May 16, 2019.)



    American Cancer Society. (2016). Stem cell transplant for cancer. Retrieved from…

    Azuma, H., Hirayama, J., Akino, M., Miura, R., Kiyama, Y., Imai, K., . . . Ikeda, H. (2009). Reduction in adverse reactions to platelets by the removal of plasma supernatant and resuspension in a new additive solution (M-sol). Transfusion, 49, 214–218.

    Bhattacharya, P., Marwaha, N., Dhawan, H.K., Roy, P., & Sharma, R.R. (2011). Transfusion-related adverse events at the tertiary care center in North India: An institutional hemovigilance effort. Asian Journal of Transfusion Science, 5, 164–170.

    Case, J.J., Khan, N., Delrahim, M., Dizdarevic, J., Nichols, D.J., Schreiber, M.A., . . . Khan, A. (2017). Association of massive transfusion for resuscitation in gastrointestinal bleeding with transfusion-related acute lung injury. Indian Journal of Critical Care Medicine, 21, 506–513.

    Centers for Disease Control and Prevention. (1998). Adverse ocular reactions following transfusions—United States, 1997–1998. Morbidity and Mortality Weekly Report, 47(3), 49–50.

    Centers for Disease Control and Prevention. (2018). National healthcare safety network biovigilance component hemovigilance module surveillance protocol. Retrieved from

    de Freitas, J.V., de Almeida, P.C., & Guedes, M.V.C. (2014). Transfusion reactions profile in oncology pediatrics patients. Journal of Nursing UFPE, 8, 3030–3038.

    Delaney, M., Wendel, S., Bercovitz, R.S., Cid, J., Cohn, C., Dunbar, N.M., . . . Ziman, A. (2016). Transfusion reactions: Prevention, diagnosis, and treatment. Lancet, 388, 2825–2836.

    Frazier, S.K., Higgins, J., Bugajski, A., Jones, A.R., & Brown, M.R. (2017). Adverse reactions to transfusion of blood products and best practices for prevention. Critical Care Nursing Clinics of North America, 29, 271–290.

    Fung, M.K. Grossman, B.J., Hillyer, C.D., & Westhoff, C.M. (2014). Technical manual (18th ed.). Bethesda, MD: American Association of Blood Banks.

    Kennedy, L.D., Case, L.D., Hurd, D.D., Cruz, J.M., & Pomper, G.J. (2008). A prospective, randomized, double-blind controlled trial of acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention of transfusion reactions. Transfusion, 48, 2285–2291.

    Kim, H., Choi, J., Park, K.U., Kim, H.S., Min, Y.H., Kim, M.J., & Kim, H.O. (2012). Anaphylactic transfusion reaction in a patient with anhaptoglobinemia: The first care in Korea. Annals of Laboratory Medicine, 32, 304–306.

    King, K.E., Shirey, R.S., Thoman, S.K., Bensen-Kennedy, D., Tanz, W.S., & Ness, P.M. (2004). Universal leukoreduction decreases the incidence of febrile nonhemolytic transfusion reactions to RBCs. Transfusion, 44, 25–29.

    Perez, A.G., Lana, J.F., Rodrigues, A.A., Luzo, A.C., Belangero, W.D., & Santana, M.H. (2014). Relevant aspects of centrifugation step in the preparation of platelet-rich plasma. ISRN Hematology, 2014, 176060.

    Savage, W.J., Tobian, A.A.R., Savage, J.H., Wood, R.A., Schroeder, J.T., & Ness, P.M. (2013). Scratching the surface of allergic transfusion reactions. Transfusion, 53, 1361–1371.

    Savage, W.J., Tobian, A.A., Savage, J.H., Hamilton, R.G., Borge, P.D., Kaufman, R.M., & Ness, P.M. (2015). Transfusion and component characteristics are not associated with allergic transfusion reactions to apheresis platelets. Transfusion, 55, 296–300.

    Stroncek, D.F., Fellowes, V., Pham, C., Khuu, H., Fowler, D.H., Wood, L.V., & Sabatino, M. (2014). Counter-flow elutriation of clinical peripheral blood mononuclear cell concentrates for the production of dendritic and T cell therapies. Journal of Translational Medicine, 12, 241.

    Suddock, J.T., & Crookston, K.P. (2019). Transfusion reactions. In StatPearls. Retrieved from

    Vamvakas, E.C., & Pineda, A.A. (2001). Allergic and anaphylactic reactions. In M.A. Popovsky (Ed.), Transfusion reactions (2nd ed., pp. 83–127). Bethesda, MD: American Association of Blood Banks.

    Wang, S.E., Lara, P.N. Jr., Lee-Ow, A., Reed, J., Wang, L.R., Palmer, P., . . . Wun, T. (2002). Acetaminophen and diphenhydramine as premedication for platelet transfusions: A prospective randomized double-blind placebo-controlled trial. American Journal of Hematology, 70, 191–194.

    Webb, C., Norris, A., & Hands, K. (2018). An acute transfusion reaction. Clinical Medicine, 18, 95–97.

    Wood, J.P., Traub, S.J., & Lipinski, C. (2013). Safety of epinephrine for anaphylaxis in the emergency setting. World Journal of Emergency Medicine, 4, 245–251.