Hemolysis attributed to high dose vitamin C: Two case reports

Table 1 Hemoglobin changes during high-dose vitamin C and rescue treatment

Items	Case 1				Case 2				Reference ranges	Units
	Before VC	After VC	Minimum hemoglobin	Post-treatment	Before VC	After VC	Minimum hemoglobin	Post-treatment
RBC	4.81	1.75	1.06	3.54	2.69	1.26	1.16	2.69	4.3-5.8	× 1012/L
HGB	152	63	37	112	96	44	41	86	130-175	g/L
HCT	0.444	0.173	0.105	0.335	0.285	0.144	0.129	0.274	0.40-0.50	L/L
MCV	92.3	98.9	99.1	94.7	105.9	114.8	110.9	101.9	82-100	fL
MCH	31.6	36	34.9	31.6	35.7	35.4	35.2	32	27-34	pg
MCHC	342	364	352	334	2.69	1.26	1.16	2.69	316-354	g/L

VC: Vitamin C; RBC: Red blood cell; HGB: Hemoglobin; HCT: Hematocrit; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular hemoglobin concentration.

Table 2 Cases of hemolysis attributed to intravenous high-dose vitamin C treatment

Year	Nationality	Sex	G6PD deficiency	Dose, g/d	The lowest level of hemoglobin, g/L	Treatment	Complications and prognosis	Ref.
1975	United States	M	Yes	80	58	Blood transfusion + glucocorticoids (day 3) + hemodialysis (after anuria)	AKI, DIC, death	[19]
1993	United Kingdom	M	Yes	80	67	Drink plenty of water + folic acid orally	AKI	[20]
2014	Taiwan, China	M	Yes	75	54	Supportive treatment	None	[21]
2017	United States	M	Yes	60	59	Intravenous fluids + glucocorticoids	AKI, methemoglobinemia, acute oxalate nephropathy	[22]
2019	United States	M	Yes	65-200	-	-	None	[23]
2020	Hong Kong, China	F	Yes	30	63	Blood transfusion	Methemoglobinemia	[6]
2022	Taiwan, China	M	Yes	50	71	-	AKI	[24]
2023	Mainland China	M	Yes	90	37	Plasmapheresis + glucocorticoids	Methemoglobinemia	This text
2023	Mainland China	F	Yes	60	41	Hemofiltration + glucocorticoids	Methemoglobinemia	This text

All patients who developed hemolysis after HVCT had G6PD deficiency, and two patients reported here had lower hemoglobin levels than previous patients, and no serious complications occurred after early blood transfusion and hormone therapy. G6PD: Glucose 6 phosphate dehydrogenase; M: Male; F: Female; AKI: Acute kidney injury; DIC: Disseminated intravascular coagulation.

Table 3 Reticulocyte analysis during hemolysis

Items	Results		Units	Reference ranges
	Case 1	Case 2
RET1	1.8	6.9	%	0.59-2.07
RET2	32.2	207.8	´109/L	22.4-93.5
LFR	92.4	77.3	%	87.8-99.5
MFR	7.4	15.7	%	1.8-14.4
HFR	0.2	7	%	0-2.4
IRF	7.6	22.7	%	2.1-17.5

Low LFR indicates a lack of hematopoietic raw materials, inducing more severe hemolysis. Results in Case 2 with myelosupression was significantly different from Case 1 without myelosuppression in reticulocyte analysis, which shows that hematopoietic capacity is significantly reduced in patients with myelosuppression, which may be the cause of more severe hemolysis. RET¹: Reticulocyte percentage; RET²: Total reticulocytes; LFR: Low fluorescence intensity reticulocytes; MFR: Medium fluorescence intensity reticulocytes; HFR: High fluorescence intensity reticulocytes; IRF: Percentage of immature reticulocytes.