Author: Liu Hongfang
Guidance: Feng Hui
Unit: Hengzhou Maternal and Child Health Hospital
On duty today, A 38-year-old pregnant woman was found, 36 weeks pregnant, and the blood routine results were: HGB 117g/L, RBC 2.84 x1012/L, HCT 32.6%, MCV 114.8fl, MCH 42.1pg, MCHC 351g/l.
The results are inconsistent with the usual empirical judgment of the increase in simultaneity and the decrease in simultaneity. Figure 1 shows that the peak of the red blood cell histogram shifts significantly to the right, which is in line with the characteristics of large red blood cells.
Figure 1
Figure 2 shows that the volume and size of erythrocytes are slightly smaller than those of neutrophils, and the characteristics of large red blood cells are still more obvious.
Figure 2
Based on this case, there are two points of doubt: first, the results of red blood cells and hemoglobin in pregnant women do not decline simultaneously; second, such a large volume of red blood cells appears, but the routine diagnosis of blood does not seem to be consistent with megaloblastic anemia.
In view of this doubt, we will pick up the diagnostic materials again and consult the relevant literature for further study.
1. Is it anemia during pregnancy?
According to continental hematologists, in continental sea level areas, adult females (non-pregnant) hemoglobin 12/L or hematocrit
The red blood cells of the pregnant woman are 2.84x1012/L, which is already anemia during pregnancy, the red blood cell histogram shows the peak to the right, the MCV, MCH, and MCHC are increased, some of the red blood cells under the microscope are large, and the central indifference area is not enlarged. What kind of anemia does this belong to?
Second, the type of anemia
Anemia is classified according to the morphology of red blood cells and can be divided into normal cellular anemia, macrocytic anemia, small cell hypochromic anemia and simple small cell anemia.
Morphological classification of anemia
According to the morphological classification of anemia, mcV, MCH, and MCHC in pregnant women are elevated, which is consistent with macrocytic anemia, which is often more common in megaloblastic anemia.
Third, what is megaloblastic anemia
Megaloblastic anemia (MgA) is anemia caused by vitamin B12 or /and folic acid deficiency, which impairs cellular DNA synthesis, leading to nucleus development disorders, while RNA synthesis continues, resulting in imbalanced development of the nucleoplasm of bone marrow trilogies and ineffective hematopoiesis, also known as deoxynucleotide synthesis disorder anemia.
Vitamin B12 and folic acid are important coenzymes in the synthesis of nuclear DNA.
When folic acid is deficient, the biochemical reaction from deoxyuracil nucleotide (dUMP) to deoxythymidine nucleotide (dTMP) is blocked, resulting in a lack of dna synthesis of the essential substance deoxy-thymic nucleoside triphosphate (dTTP). dTTP, which participates in normal DNA synthesis, is replaced by dUTP, and DNA synthesis is blocked, eventually leading to nucleus growth arrest. However, cytoplasmic synthesis RNA and hemoglobin are not affected, and their development is normal, resulting in unbalanced development of the nucleoplasm of "nuclear plasma old", forming megaloblasts with larger cell size.
When vitamin B12 is deficient, it affects the production of tetrahydrofolate, so that dUMP cannot be converted to dTMP, dTTP synthesis is impaired, dna synthesis is also blocked, nucleus is delayed, and megaloblastic anemia occurs. Most megaloblasts are destroyed by maldemetic development and maturation in the bone marrow, resulting in ineffective production of red blood cells and shortening the lifespan of red blood cells in the peripheral blood, resulting in anemia.
4. Laboratory examination of megaloblastic anemia
1. Blood routine
Hemoglobin and erythrocytes are reduced, and erythrocytopenia is more prominent than the decline in hemoglobin, showing hyperchromic anemia of large cells, significantly increased MCV and MCH content, and normal or mild increase in reticulocyte count.
2. Blood smear
Erythrocyte morphology and size are uneven, dominated by large cells, with dark cell staining and a narrowing of the central shallow stained area of red blood cells. Abnormal structures such as dot color red blood cells, kapo rings and Haoqiao small bodies can be seen. The number of white blood cells decreased, and great changes and nuclear multilobettering phenomena were seen, with 5-leaf nucleophils accounting for more than 5%, and nucleophils with more than 6 lobes could be seen. Platelets are reduced, and macroplatelets are visible.
3. Determination of serum vitamin B12 and determination of folic acid
Serum vitamin B12
4. Other inspections
Patients often have increased bilirubin, mainly indirect bilirubin, and lactate dehydrogenase is significantly increased, indicating increased cell destruction. At the same time, the liver and kidney function status can be understood, and anemia caused by chronic liver and kidney disease can be excluded.
Contact the doctor by phone to ask whether the pregnant woman has supplemented with folic acid, and the doctor feedback that the pregnant woman will supplement folic acid according to the standard three months before the pregnancy and the first three months of pregnancy. The results of folic acid and vitamin B12 are as follows:
Neither folic acid nor vitamin B12 is deficient, which is strange!
According to the laboratory examination and diagnosis of megaloblasts, the experimental results of normal hemoglobin, red blood cell reduction, thrombocytopenia, red blood cell histogram peak shifting right, MCV, MCH, MCHC are increased, and folic acid and vitamin B12 are not reduced, etc., do not support megaloblastic anemia caused by folic acid or vitamin B12 deficiency. So, what exactly causes anemia in pregnant women?
Contact the doctor again, who informs the pregnant woman that she is hive-bearing, has been confirmed for many years, and has been taking antiviral drugs. So, is it possible that the effects of HIV antiviral drugs will cause a decrease in erythrocyte production and a larger volume? What kind of drugs are they?
Consulting the relevant literature, the literature points out that zidovudine (AZT) is one of the preferred drugs for the treatment of AIDS in many developing countries, the adverse reactions of zidovudine are first of all bone marrow suppression, zidovudine nucleoside reverse transcriptase inhibitors, when the use of the regimen has Zidov timing, patients have anemia, especially the appearance of macrocytic anemia, the first thought of zidovudine adverse reactions [1-2].
Anemia occurs by the inhibitory effect of antiretroviral therapy on the bone marrow, (inhibition of erythrocyte line growth) and low immune function, zidov is able to induce megaloblastic cells, and even in patients who are not accompanied by anemia; the anemia that occurs is mostly macrocytic anemia, which is easily misdiagnosed as anemia due to folic acid or vitamin B12 deficiency [3].
After calling the doctor again, the doctor confirmed that the pregnant woman had been taking zidovudine antiviral drugs. The truth is finally out!
Literature statistics also found that after the use of zidovudine, the occurrence of anemia is relatively hidden, and most patients are found after clinical symptoms, which is more consistent with this case. The primary factor found in this case is that the MCV is severely high and is not detected as anemia, so the physician responsible for antiviral therapy should strictly monitor the patient's Hb according to the treatment requirements, detect it early, and take appropriate measures.
Summary and experience
In our grass-roots hospitals, the special cases and cases encountered are indeed relatively small, but if we can polish our eyes, observe with our hearts, learn more, think more about the relationship between test numbers and diseases, the relationship between test values and drugs, etc., boldly ask clinicians for advice and say their own guesses; starting from one abnormal result after another every day, thinking from one small problem after another, gaining knowledge and accumulating experience in the process of verification. Become a "scout" for disease diagnosis every day in the future, help doctors make more accurate disease judgments, and truly exert the value of the knowledge of testing to the fullest.
【Reference】
[1] Kang Laiyi, Pan Xiaozhang, Lu Hongzhou, etc. AIDS Prevention and Treatment[M].Shanghai: Fudan University Press,2008:151-154.]
Wang Chun,Hu Jun. Study on efficacy test indicators of HIV antiretroviral therapy and its application analysis[J]. Sino-Foreign Medical Sciences,2018,37( 28 ):178-180.DOI:10.16662 /j.cnki.1674-0742.2018.28.178.
[3] Yang Chengbin, Thunder, Fire Patch Mo Muzuo. Clinical analysis of zidovudine in the treatment of anemia caused by AIDS[J]. Rational Use of Clinical Drugs2019:21-22.
Edited by: Yeah Reviewer: Xiao Ran