Transfusion medicine

Table 1: Infusion toxicity by etiology

	DMSO	Cytokines	RBC / hemoglobin	Plasma	Volume	Citrate
Nausea / emesis	X
Fever / chills	X	X	X
Cough	X			X
Flushing	X	X
Shortness of breath, hypoxia	X	X	X	X	X
Hypotension	X			X		X
Hypertension	X		X		X
Bradycardia	X				X
Arrythmia	X	X	X			X
Neurologic	X	X			X
Gastrointestinal pain	X		X			X

A 49 year old, 82.7 kg man with a medical history of multiple myeloma is admitted for an autologous hematopoietic stem cell transplant (HSCT) with cryopreserved, plasma reduced HPC(A). He was premedicated with 650 mg of Tylenol and 50 mg of intravenous (IV) Benadryl. He was infused with a total of 200 mL HPC(A) containing 9.1 x 10⁶ CD34+ cells/kg, 6.9 x 10⁸ MNC/kg and 20 mL dimethyl sulfoxide (DMSO). Shortly after the infusion, the patient began to experience headaches, facial flushing, coughing and difficulty taking deep breaths. The nurse slowed the infusion and the patient's symptoms improved. Vital signs before, during and after infusion are shown below. What was the most likely cause of the patient's reaction?

	Before	During	After
Time	12:03	12:44	16:33
Temperature (Celsius)	36.5	36.5	37.1
Heart rate	92	97	86
Resp rate	16	20	16
Blood pressure	148/83	132/78	120/66
SpO2%	96	95	99
O2 device	None (room air)	None (room air)	None (room air)

1. Anxiety: psychological stress and anxiety surrounding the infusion
2. DMSO toxicity from cryopreservation
3. Severe allergic reaction without anaphylaxis due to plasma
4. Volume overload: due to rapidly increasing intravascular volume

B. DMSO toxicity from cryopreservation. The patient began to have difficulty with deep breaths, flushing, coughing and headaches shortly after his infusion began. This patient was experiencing a classic reaction to DMSO. DMSO can cause a wide array of reactions including headache, nausea, dizziness, halitosis, hypoxia, chest tightness, coughing and hypotension. DMSO is hyperosmolar with expansion of intravascular volume and capable of inducing histamine release with flushing, coughing, chest tightness or dyspnea. Answer A is incorrect because the question stem does not mention any signs or symptoms specifically related to anxiety. In addition, he was premedicated with 50 mg IV Benadryl, which is very sedating; however, it is paramount to keep a broad differential diagnosis when assessing patients with possible reactions to infusion of any products. Answer C is incorrect because a severe allergic reaction is unlikely since this was plasma reduced and autologous stem cells. Answer D is incorrect because a volume overload is unlikely since the infusion was only (2 units - 200 mL). One strategy to reduce reactions due to infusion includes slowing the rate (Kopko: Transfusion Reactions, 5th Edition, 2021).

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Reference: Cellular therapy reactions

A 19 year old, O+ blood type, 52.1 kg woman with acute myeloid leukemia (AML) was admitted for a matched (8/8), unrelated, allogeneic ABO incompatible HPC(M) bone marrow transplant from a group A+ donor. The original marrow volume was exceptionally large (1,694 mL) and bloody (Hct = 30%). After red cell and plasma depletion, the processed marrow was 390 mL with 164.6 mL residual donor red blood cells (RBC) and a total cell loss of 8% for a final yield of 3.1 x 10⁶ CD34 cells/kg. The patient was premedicated with Tylenol 500 mg PO, intravenous (IV) Solu-Cortef 100 mg and IV diphenhydramine 50 mg. HPC(M) was infused by gravity flow at 3 - 4 mL/minute. During infusion, the patient developed headaches that did not resolve with Tylenol. Toward the end of the transplant, her blood pressure rose from 123/74 to 152/92. Hydralazine and magnesium boluses were ordered and blood pressure began to downtrend. Hemoglobinuria was noted after the completion of the transplant. What is the reaction this patient is experiencing and what is the most likely cause?

1. Acute dimethyl sulfoxide (DMSO) toxicity: due to rate of infusion
2. Adverse medication reaction: premedication with Solu-Cortef
3. Dehydration: patient has not consumed any fluids since the procedure due to an upset stomach
4. Immune hemolysis: due to major ABO incompatibility (A donor / O recipient)

D. Immune hemolysis: due to major ABO incompatibility (A donor / O recipient). This patient is experiencing an acute hemolytic transfusion reaction due to infusion of ABO incompatible HPC(M) marrow transplant. HPC(M) are quite bloody and still contain significant red cells even after RBC depletion because of the need to balance depletion against CD34 cell losses. Her pretransplant anti-A IgG titer was 256 and anti-A IgM titer was 32. Her headache was caused by a dramatic increase in systolic blood pressure (123 → 154) because of excess volume from transplant and aggressive hydration to prevent acute kidney injury and nitric oxide scavenging with heme mediated vasoconstriction. Answer A is incorrect because she was not exposed to DMSO; the patient received an allogeneic marrow transplant, which is not cryopreserved and infused fresh. Answer B is incorrect because this patient would not have hemoglobinuria due to an adverse medication reaction to Solu-Cortef . Answer C is incorrect given hypertension, not hypotension (Kopko: Transfusion Reactions, 5th Edition, 2021).

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Reference: Cellular therapy reactions