What does the increased proportion of split red blood cells indicate after transplantation?

With the widespread application of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in hematological malignancies, more and more attention has been paid to transplantation-related complications.
Among them, hemolytic anemia (HA) is a more common and serious one
.

Transplantation-related HA is mainly divided into alloimmune hemolysis and autoimmune hemolysis (AIHA).

Case history

Case history

The patient is a 61-year-old male who has been diagnosed with myelodysplastic syndrome (MDS) for more than two years
.

Allo-HSCT pretreatment was initiated on December 21, 2020.

The white blood cells increased after the medication, and the blood test showed WBC 5.
38×109/L on +11 days after transplantation (January 8, 2021), which showed an increasing trend for 3 consecutive days.
The leukocyte-increasing drugs were not used, and the granule line has been successfully implanted
.

+14 days after transplantation (January 11) bone marrow has reached complete chimerism (donor chimerism rate: 99.

Morphology group staff re-photograph: categorized and counted 100 white blood cells, and 60 nucleated red blood cells were found, and there were pathological changes.
Split red blood cells (8.
5%) and pleochrotrophic red blood cells were easily seen.
The laboratory immediately recommended that clinicians complete hemolysis-related tests
.

Routine blood scatter diagrams and peripheral blood smears are as follows:

Hemolysis related tests: the direct anti-human globulin test (Coombs test) is positive, the plasma free hemoglobin is significantly increased (164mg/L), and the haptoglobin is decreased
.

Biochemical and other test results: total bilirubin, direct bilirubin, and indirect bilirubin are all within the normal range, LDH is significantly increased (2065U/L), urine protein is positive (1+), CMV and EB quantification are both low At the detection limit, the activity of Von Willebrand Factor Cleavage Protease 13 (ADAMTS13) was normal and the inhibitory antibody test (negative)

Coagulation test showed that fibrinogen decreased, D dimer increased, and fibrinogen degradation products increased
.

case analysis

case analysis

Hemolysis after transplantation related factors are: basic diseases, infections, HLA typing, graft versus host disease (of GVHD), transplant type, and the like of ABO blood group incompatibility
.

This case is a transplantation of the main blood type incompatibility for A and O.

The patient had no hypertension, CMV and Epstein-Barr virus negative, no acute GVHD manifestations, PLT and Hb did not decrease but increased, Coombs test was positive, and no special clinical symptoms.
Although the red blood cell split reached 8.
5%, the possibility of TA-TMA was still ruled out first
.

The implantation of granule lines on +11 days after transplantation and the complete chimerism of bone marrow donors on +14 days after transplantation indicated that the donor's stem cell implantation was smooth, and the possibility of autoimmune hemolysis of the donor's antibodies and the donor's red blood cells could be ruled out

The patient is donated by an unrelated donor from the bone marrow bank, and the blood type is incompatible (A for O), and it is in the blood group conversion period +15 days after transplantation.
There is anti-A antibody in the patient's body, and the antigen-antibody reaction with the donor A antigen leads to hemolysis, and the ratio of schistocytes reaches Peak
.

With the successful blood group conversion, the anti-A antibody titer gradually weakened to disappear, and the proportion of schistocytes decreased accordingly.

Experience

Experience

The undergraduate room automatic blood analyzer has 2 channels to detect PLT, one is the RBC/PLT channel, which is used for routine detection of RBC and PLT.
This channel is based on the principle of electrical impedance method and generates different resistance signals according to the size of RBC and PLT.
In order to get the RBC/PLT volume histogram
.

When there are cleavage red blood cells in the specimen, due to their small size, which is similar to platelets, the electrical impedance method of the instrument recognizes them as platelets, which can cause double peaks in the RBC and PLT histograms or the phenomenon of tail-lifting in the PLT histograms
.

In allo-HSCT, the donor and recipient human leukocyte antigens (HLA) match and ABO blood type non-contract accounted for 30%-40%.
ABO blood type incompatibility includes: main ABO blood group incompatibility (A for O, B for 0, AB for A , AB for B), secondary ABO blood group incompatibility (O for A, O for B, O for AB), primary and secondary incompatibility (A for B, B for A)
.

Since the surface of hematopoietic stem cells does not express ABO antigen, the combination of ABO blood type does not affect the engraftment of hematopoietic stem cells, nor does it increase the incidence and severity of GVHD.
Therefore, all0-HSCT with incompatible ABO blood types is safe
.
However, the transplantation of ABO blood type incompatibility is due to the mismatch of donor and recipient blood type antigens and antibodies.
After implantation, the expression of ABH antigen in the erythroid is gradually increased during the differentiation and development process, but the recipient may continue to have blood group antigens against the donor.
Antibodies can produce an immune hemolytic reaction, which in turn affects the reconstitution of erythroid hematopoiesis
.

Studies have shown that recipients who receive hematopoietic stem cells with blood group A antigens are more likely to undergo immune hemolysis after transplantation, because blood group A antigens are more antigenic than blood group B antigens and are more likely to stimulate the recipient's cells to produce antibodies
.

This case is A for O.
Short-term hemolytic reaction after transplantation is common, but in general, this type of hemolytic reaction does not appear to split red blood cells, and the proportion of split red blood cells in this patient is not low
.
Split red blood cells are produced by external mechanical damage of red blood cells in the blood circulation, and are usually related to blood turbulence caused by pathological changes of vascular endothelial cells
.

After the occurrence of split red blood cells in this case, the possibility of TA-TMA and AIHA was first ruled out.
The patient did not change the treatment plan or special treatment.
The split red blood cells decreased to disappearance, and the erythroid hematopoiesis gradually recovered, so it was not considered.
It may be caused solely by drugs
.

Recalling the course of the disease, the patient had a deep vein puncture on December 24, 2020.
A large area of ​​bruise occurred at the puncture site, and the bruise lasted for more than one month.
The puncture may have damaged the vein and surrounding capillaries, and blood flowed into the surrounding area.
In tissues, the coagulation mechanism in the body is activated, fibrin synthesis is increased, and microthrombi composed of platelets and fibrin are formed, and then the fibrinolytic system is activated (the coagulation test indicates hyperfibrinolysis)
.

Split red blood cells coincide with the time period of puncture and large-area bruises.
Our guess is that ABO blood type incompatibility will cause hemolysis, and the damage of pretreatment drugs to vascular endothelium cannot be ruled out.
The red blood cells in the immune response produce split red blood cells
.

Concluding remarks

Concluding remarks

The appearance of split red blood cells in peripheral blood after hematopoietic stem cell transplantation indicates that there may be a hemolytic reaction in the patient's body, and hemolysis is one of the serious complications of transplantation and may be fatal
.
Therefore, timely improvement of various laboratory examinations, careful identification and analysis of the cause of hemolysis can help the clinical diagnosis as soon as possible, and adopt corresponding treatment programs for different causes to save the lives of patients
.

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