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|MainCategory=Immunology
|MainCategory=Immunology
|SubCategory=Hematology
|SubCategory=Hematology
|Prompt=A 67 year old presents to the emergency department for bloody stools. His past medical history is significant for mechanical aortic valve replacement on warfarin therapy, dyslipidemia, and controlled hypertension. The patient denies any known allergies. Work-up is remarkable for profound anemia and significantly elevated INR. He is diagnosed with gastrointestinal bleeding due to warfarin. The physician decides to start blood transfusion to relieve the patient's anemia. During the transfusion, the patient experiences fever, chills, and intense flushing. He denies any itching or shortness of breath. Vital signs are remarkable for temperature of 38.4 degrees C (101 degrees F), heart rate of 108 bpm, respiratory rate of 18/min, and blood pressure measuring 128/78 mmHg. What is the most likely cause of this patient's reaction to the blood transfusion?
|Prompt=A 67 year old presents to the physician's office complaining of weight loss, fever, and night sweats. Following appropriate work-up, he is diagnosed with acute myelogenous leukemia (AML) and is started on scheduled chemotherapy sessions. Several weeks later, the patient is found to have profound thrombocytopenia. The physician decides to transfuse platelets. During the transfusion, the patient experiences fever, chills, and intense flushing. He denies any itching or shortness of breath. Vital signs are remarkable for temperature of 38.4 degrees C (101 degrees F), heart rate of 108 bpm, respiratory rate of 18/min, and blood pressure measuring 128/78 mmHg. What is the most likely cause of this patient's reaction to the platelet transfusion?
|Explanation=The patient is most likely presenting with febrile nonhemolytic transfusion reaction (FNHTR). Most cases of FNHTR occur in platelet transfusions. The pathogenesis of the platelet reactions is due to cytokines that are present in the product during storage. The true mechanism of the accumulation and the pathophysiology of the condition is poorly understood. Cytokines generally mediate a reaction whereby antibodies are directed against donor leukocytes and HLA antigens. In packed red blood cells, the pathophysiology is believed to be mostly caused by recipient white blood cell activation against transfused leukocytes and subsequent release of endotoxins that cause fever. Treatment is still controversial, but includes fever reduction by antipyretics (such as acetaminophen). Stopping the transfusion is also generally done. Prevention may be accomplished by acetaminophen and diphenhydramine.
|Explanation=The patient is most likely presenting with febrile nonhemolytic transfusion reaction (FNHTR). Most cases of FNHTR occur in platelet transfusions. The pathogenesis of the platelet reactions is due to cytokines that are present in the product during storage. The true mechanism of the accumulation and the pathophysiology of the condition is poorly understood. Cytokines generally mediate a reaction whereby antibodies are directed against donor leukocytes and HLA antigens. In packed red blood cells, the pathophysiology is believed to be mostly caused by recipient white blood cell activation against transfused leukocytes and subsequent release of endotoxins that cause fever. Treatment is still controversial, but includes fever reduction by antipyretics (such as acetaminophen). Stopping the transfusion is also generally done. Prevention may be accomplished by acetaminophen and diphenhydramine.


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|AnswerA=Formation of IgG and IgA immune complexes that activate the complement pathway and release C3a and C5a
|AnswerA=Formation of IgG and IgA immune complexes that activate the complement pathway and release C3a and C5a
|AnswerAExp=Anaphylactic reaction, usually in patients with IgA deficiency, is caused by formation of immune complexes that activate anaphylaxins, such as C3a and C5a. Patients typically present with features of anaphylaxis, such as hypotension and shock.
|AnswerAExp=Anaphylactic reaction, usually in patients with IgA deficiency, is caused by formation of immune complexes that activate anaphylaxins, such as C3a and C5a. Patients typically present with features of anaphylaxis, such as hypotension and shock.
|AnswerB=Reaction by recipient white blood cell antibodies against transfused leukocytes and release of endotoxin
|AnswerB=Reaction caused primarily by the accumulation of cytokines in the platelet products during storage
|AnswerBExp=In packed red blood cell transfusions, febrile nonhemolyti transfusion reaction (FNHTR) is most likely due to activation of recipient WBCs against transfused leukocytes and subsequent release of endotoxin.
|AnswerBExp=In platelet transfusions, febrile nonhemolytic transfusion reaction (FNHTR) is most likely due to cytokine-mediated targeting of antibodies against donor leukocytes and HLA antigens. Cytokines accumulate during the storage of platelet products.
|AnswerC=Hypersensitivity reaction against foreign antigens on donor red blood cells
|AnswerC=Hypersensitivity reaction against foreign antigens on donor red blood cells
|AnswerCExp=Acute and delayed hemolytic transfusion reactions are caused by hypersensitivity reactions against foreign antigens on donor red blood cells. Features of hemolysis, such as jaundice, flank pain, and hemoglobinuria, are frequently present.
|AnswerCExp=Acute and delayed hemolytic transfusion reactions are caused by hypersensitivity reactions against foreign antigens on donor red blood cells. Features of hemolysis, such as jaundice, flank pain, and hemoglobinuria, are frequently present.

Revision as of 07:50, 20 November 2013
Author [[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Immunology
Sub Category SubCategory::Hematology
Prompt [[Prompt::A 67 year old presents to the physician's office complaining of weight loss, fever, and night sweats. Following appropriate work-up, he is diagnosed with acute myelogenous leukemia (AML) and is started on scheduled chemotherapy sessions. Several weeks later, the patient is found to have profound thrombocytopenia. The physician decides to transfuse platelets. During the transfusion, the patient experiences fever, chills, and intense flushing. He denies any itching or shortness of breath. Vital signs are remarkable for temperature of 38.4 degrees C (101 degrees F), heart rate of 108 bpm, respiratory rate of 18/min, and blood pressure measuring 128/78 mmHg. What is the most likely cause of this patient's reaction to the platelet transfusion?]]
Answer A AnswerA::Formation of IgG and IgA immune complexes that activate the complement pathway and release C3a and C5a
Answer A Explanation AnswerAExp::Anaphylactic reaction, usually in patients with IgA deficiency, is caused by formation of immune complexes that activate anaphylaxins, such as C3a and C5a. Patients typically present with features of anaphylaxis, such as hypotension and shock.
Answer B AnswerB::Reaction caused primarily by the accumulation of cytokines in the platelet products during storage
Answer B Explanation [[AnswerBExp::In platelet transfusions, febrile nonhemolytic transfusion reaction (FNHTR) is most likely due to cytokine-mediated targeting of antibodies against donor leukocytes and HLA antigens. Cytokines accumulate during the storage of platelet products.]]
Answer C AnswerC::Hypersensitivity reaction against foreign antigens on donor red blood cells
Answer C Explanation AnswerCExp::Acute and delayed hemolytic transfusion reactions are caused by hypersensitivity reactions against foreign antigens on donor red blood cells. Features of hemolysis, such as jaundice, flank pain, and hemoglobinuria, are frequently present.
Answer D AnswerD::Production of IgE by plasma cells following antigen exposure
Answer D Explanation AnswerDExp::Allergic reaction is caused by IgE production by plasma cells following antigen exposure. Urticaria, pruritis, and wheezing are usually present.
Answer E AnswerE::Non-immune circulatory overload due to rapidly incoming transfused blood
Answer E Explanation AnswerEExp::Transfusion-associated circulatory overload (TACO) is caused by rapid transfusion of blood products. It is non-immune condition that causes high blood pressure, peripheral edema, dyspnea, and orthopnea.
Right Answer RightAnswer::B
Explanation [[Explanation::The patient is most likely presenting with febrile nonhemolytic transfusion reaction (FNHTR). Most cases of FNHTR occur in platelet transfusions. The pathogenesis of the platelet reactions is due to cytokines that are present in the product during storage. The true mechanism of the accumulation and the pathophysiology of the condition is poorly understood. Cytokines generally mediate a reaction whereby antibodies are directed against donor leukocytes and HLA antigens. In packed red blood cells, the pathophysiology is believed to be mostly caused by recipient white blood cell activation against transfused leukocytes and subsequent release of endotoxins that cause fever. Treatment is still controversial, but includes fever reduction by antipyretics (such as acetaminophen). Stopping the transfusion is also generally done. Prevention may be accomplished by acetaminophen and diphenhydramine.

Educational Objective: Febrile nonhemolytic transfusion reaction (FNHTR), characterized by uncomplicated fever and flushing, is most likely due to activation of recipient WBCs against transfused leukocytes and subsequent release of endotoxins.

Reference: Tenorio GC, Gupte SC, Munker R. Transfusion medicine and immunohematology. in Modern Hematology - Biology and Clinical Management, 2nd ed. 2007. pp:401-432.

Heddle NM. Pathophysiology of febrile nonhemolytic transfusion reactions. Curr Opin Hematol. 1999; 6(6):420-6.
Educational Objective:
References: ]]

Approved Approved::No
Keyword WBRKeyword::transfusion, WBRKeyword::reaction, WBRKeyword::hemolytic, WBRKeyword::hemolysis, WBRKeyword::nonhemolytic, WBRKeyword::fever, WBRKeyword::shock, WBRKeyword::anaphylaxis, WBRKeyword::warfarin, WBRKeyword::gastrointestinal, WBRKeyword::GI, WBRKeyword::bleeding, WBRKeyword::TACO, WBRKeyword::transfusion, WBRKeyword::associated, WBRKeyword::circulatory, WBRKeyword::overload
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