The child suddenly lost blood sharply, and a look at the blood film solved the mystery

【Preface】

Normal red blood cell life is 120 days, about 1% of senescent red blood cells are cleared in the spleen every day, and a considerable amount of new red blood cells are released from the bone marrow into the blood circulation, when the speed of red blood cell destruction is too fast, greater than the compensatory capacity of the bone marrow, that is, hemolytic anemia
occurs.
In the laboratory, we can suggest the direction of the disease from the abnormal red blood cell morphology of the blood smear, hereditary spherocytosis, erythrocyte glucose-6-phosphate dehydrogenase deficiency, thalassemia, etc
.

【Case History】

On April 12, colleagues at the window informed a child that his blood routine was abnormal, as shown in Figure 1, WBC 12.
11×109/L, RBC 1.
63×1012/L, HGB 54 g/L, MCV 103.
7 fL, PLT 398×109/L
.
The ratio of total red blood cells to hemoglobin is roughly normal, combined with MCV indicators, iron deficiency anemia and thalassemia can be preliminarily excluded.

Figure 1

Staining of the push sheet, there is no abnormal white blood cell morphology, platelets scattered distribution, but some abnormal morphology can be seen in the red blood cell morphology, as shown in Figure 2, some red blood cells seem to have been bitten, one side is missing hemoglobin, but you can still see the shadow remaining on the edge of the red blood cell membrane
.

Figure 2

Figure 3

Isn't this exactly the blister cell, the first reaction is that the child eats broad beans, which was later confirmed
by questioning.
After admission, further medical history was inquired and learned that the child had soy sauce-colored urine after eating broad beans yesterday, and the biochemical results of the child were shown in Figure 4, TBIL 66.
0umol/L, LDH1154 U/L, and mild increase in urea nitrogen, all of which were consistent with the changes
caused by red blood cell destruction.

Figure 4

The G6PD result was 188 U/L, which further supported the deficiency of glucose-6-phosphate dehydrogenase, as shown in Figure 5
.

Figure 5

Looking at the biochemical tube and EDTA tube specimen traits, it can be seen that the serum/plasma is strong brown or soy sauce color, as shown in Figure 6
.

Figure 6

Combined with the history of eating broad beans, soy sauce-colored urine, blood smear red blood cell morphology visible blister cells, and decreased G6PD, the final diagnosis was: G6PD deficiency
.
Urine was alkalized to prevent hemoglobin deposition in the renal tubules and other related symptomatic treatment support, and after five days his condition improved and he was discharged from the hospital, and the results of follow-up urine dry chemistry and sediment centrifugal microscopy were normal
.

【Case Study】

(1) Blister red blood cells are hemoglobin in red blood cells that retract to half of the cell to form a dense cytoplasm, and the rest of the cell is only an empty cell membrane
.
Usually we also call blister red blood cells slitter red blood cells, it should be noted that according to literature reports [1], it is still different from bite red blood cells
.

Bit-scar red blood cells are caused by the removal of hydantosomes from the spleen, a type of red blood cell with single or multiple peripheral arc-shaped deletions (bitten off) that is a feature of
hemolysis by oxidants.
Microangiopathic hemolytic anemia and mechanically damaged RBCs may produce morphologically identical cells (horned cells) due to fusion of red blood cell membranes after peripheral pseudovacuole rupture [2], the morphological picture of which is shown in Figure 7
.

Figure 7

Consult the literature [3], although the significance of vesicular erythrocytosis (should refer to blister erythrocyte) and bite scar erythrocytosis are considered G6PD deficiency, the two are still distinguished in the abnormal form of red blood cells, as shown in Figure 8, so we should pay attention to word descriptions
in our work.

Figure 8

The ingenious method of memory of blister red blood cells (or cracked red blood cells) can be referred to Mr.
Huang's description: such red blood cells resemble broken eggs, the yolk and egg white have been lost, and only the broken side of the egg shell remains
.

(2) Red blood cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is an X-linked incomplete dominant erythrocyte enzyme deficiency disease, which is caused by gene mutations in G-6-PD, G-6-PD gene is located in the X chromosome long arm 2 region 8 band (Xq28), the total length is about 18.
5kb, containing 13 exons, encoding 515 amino acids
.
[4]

The mechanism of hemolysis in this disease is not well understood, and it is currently believed that the mechanism of hemolysis induced by taking oxidizing drugs (such as primaquine): G-6-PD is an essential enzyme
in the reaction of glucose 6-phosphate (G-6-P) to 6-phosphogluconic acid (G-6-PG) in the pentose phosphate bypass 。 When G-6-PD is deficient, the reduced pyridine triphosphate (NADPH) decreases, and the reduced glutathione (GSH) that cannot maintain the physiological concentration cannot be maintained, so that methemoglobin (MHb) cannot be converted into oxygenated hemoglobin, MHb increases the formation of insoluble denatured globin bodies (Heinzbody) in red blood cells, and the red blood cell membrane hardens and is destroyed when passing through the spleen, resulting in hemolysis
.

In this case, the child had soy sauce-colored urine after eating broad beans, with symptoms of dizziness and fatigue, and the outpatient blood routine showed that hemoglobin was only 54g/L (the lower limit of our ventricular hemoglobin critical value was 50g/L), which shows that the degree of hemolysis in the body is relatively rapid, and after active treatment, hemoglobin has been increased to 95g/L
at the time of discharge.
The mechanism of fava bean-induced hemolysis is unknown, but the fava bean infusion contains dopa, dopamine, broad coume pyrimidine, isourea and other similar oxidants, which may be related to
the pathogenesis of fava bean disease.

It should be reminded that in addition to the common broad beans, I have heard the teacher explain during the training that certain drugs with oxidizing properties can also induce hemolysis similar to fava bean disease, and there are other foods that can also be induced (such as loquat rock sugar).

I have to sigh, the world is really strange
.

(3) Recalling that I had found several cases of children with low glucose-6-phosphate dehydrogenase, but they could not find blister red blood cells (split red blood cells) in their blood smears, they were puzzled, and after the guidance of the training teacher, it turned out that the newborn red blood cell G-6-PD activity was high, and there was a strong "resistance" to oxidizing drugs, when the senescent red blood cell enzyme activity was too low and destroyed, the new red blood cells were compensatory, so hemolysis no longer occurred, showing "self-limiting", As a result, I was unable to find typical blister red blood cells
before.

Therefore, if the pediatrician complains that the child is obviously G6PD deficiency (commonly known as broad bean disease), why the G6PD result in the biochemical results is not low, or the blood smear microscopy does not show abnormal red blood cell morphology, our examiners should inform the relevant bone marrow neogenesis red blood cell compensation mechanism principle
.

【Summary】

A simple blood smear can indicate the direction of a variety of clinical diseases, but it is not overnight to do a good job in the morphology of sperm cells, but requires years of accumulation and continuous learning to update novel knowledge
.
At present, the mainstream disease diagnosis methods have advanced technology, such as flow cytometry, metagenomic sequencing (mNGS), chromosomal gene and karyotype analysis, etc.
, but we can never lose the most classic and oldest morphological microscopy
.

【Acknowledgements】

The author of this article studied cell morphology in Zhongshan Boai Hospital affiliated to Southern Medical University, and through the teachings of teachers Huang Daolian and Deng Kunyi, he gained a lot from the cognition of cells and the principles of disease-related mechanisms, and I would like to thank you!

【References】

[1] YE Xiangjun, LU Xingguo.
2015 Introduction to the recommendation for naming and grading standardization of morphological characteristics of peripheral blood cells in ICSH[J] Journal of Clinical Laboratory Laboratory,2016,34(4):296-299

[2] Lu Xingguo.
Recommendations on the naming and grading standardization of morphological characteristics of peripheral blood cells in ICSH, WeChat public account for integrated diagnosis of hematological diseases, 2016-10-30

[3] Hematology and Humorology Group, Laboratory Medicine Branch, Chinese Medical Association.
Guidelines for normalization of blood cell analysis reports[J] Chinese Journal of Laboratory Medicine,2020,43(6):619-627

[4] WANG Weiping,SUN Kun,CHANG Liwen.
Pediatrics 9th Edition[M].
Beijing:People's Medical Publishing House,2018:333-335