“Comments on management during labor for pregnancy with indopathic thrombocytopenia in the National hospital of Obstetrics and Gynecology 2012”.. “Clinical, characteristics, subclinic
Trang 1MINISTRY OF EDUCATION MINISTRY OF HEALTH AND TRAINING
HANOI MEDICAL UNIVERSITY
DAO THI THANH HUONG
INNITAL STUDY ON CLINICAL FEATURE, LABORATORY AND TREATMENT BEHAVIOR IN
PREGNANCY WOMEN WITH THROMBOCYTOPENIA
Speciality : Obstetrics and Gynaecology
Code : 62720131
PH.D THESIS SUMMARY
HANOI - 2022
Trang 2THE THESIS WAS FULFILLED AT HANOI MEDICAL UNIVERSITY
Trang 3LIST OF RESEARCH WORKS PUBLISHED RELATED
TO THE THESIS
1 Đao Thi Thanh Huong (2015) “A case report on the
thrombocytopenia in pregnancy and newborn Journal of Obstetrics and
Gynecology; volume 13(01), 05-2015, page 74-76
2 Đao Thi Thanh Huong (2015) “Comments on management during
labor for pregnancy with indopathic thrombocytopenia in the
National hospital of Obstetrics and Gynecology 2012” Journal of
Obstetrics and Gynecology; volume 13(02), 05-2015, page 86-88
3 Đao Thi Thanh Huong, Tran Danh Cuong (2016) “Clinical,
characteristics, subclinical, access management for thrombocytopenia pregnancy during labor in the National hospital of Obstetrics and
Gynecology 2015” Journal of Obstetrics and Gynecology; volume
14(01), 05-2016, page 56-60
4 Đao Thi Thanh Huong, Tran Danh Cuong (2017) “Impact of
maternal thrombocytopenia in pregnancy to neonates” Obstetrics and
Gynecology; volume 15(02), 05-2076, page 70-74
5 Đao Thi Thanh Huong, Tran Danh Cuong (2015) “Clinical,
characteristics, subclinical, access management for thrombocytopenia pregnancy during labor in the National hospital
of Obstetrics and Gynecology 2014-2015” Doctor of Philosophy
students meeting, page 160-161
6 Đao Thi Thanh Huong, Tran Danh Cuong, Le Xuan Hai (2020)
“Impact of maternal thrombocytopenia in pregnancy to neonates” Việt
Nam medical journal; volume 496, page 510-513
Trang 4thrombocytopenia during pregnancy Platelet value is usually above 80G/l and returns toal levelwithin the first three months postpartum The pathophysiology
of gestational thrombocytopenia is unknown, but it might relate to increased blood volume during pregnancy The diagnosis is sometimes made after having
a test result The treatment of thrombocytopenia in pregnancy is complicated due to maternal and fetal safety concerns and having a tough choice between the intervention or followup monitoring
Thrombocytopenia in pregnancy has been mentioned since the 1980s around the world Many researches on the management of thrombocytopenia in pregnancy during delivery and the follow up monitoring of newborns have been done The relationship between maternal conditions and the degree of fetal thrombocytopenia has been also assessed and this matter remains challenging to obstetricians In Vietnam, there have been few studies on thrombocytopenia, therefore this study is set to explore:
1 Clinical and subclinical characteristics of pregnant women with thrombocytopenia
2 The management of thrombocytopenia in pregnancy
3 Estimation of hematologic value of new-borns whose mothers diagnosed with thrombocytopenia during pregnancy
New contributions from the thesis
thrombocytopenia to the number of thrombocytes in newborns whose mothers are diagnosed with thrombocytopenia in pregnancy
pregnancy and ITP
antibodies test in pregnant women and newborns In addition, antiplates antibodies test is screened by flow cytometric
Thesis outline
The thesis consists of 145 pages, covering: introduction (2 pages), overview (35 pages), object and method of research (19 pages), results (34 pages), discussion (52 pages), conclusion (2 pages), proposal (1 page) It has 34 tables, 12 figures, 12 charts
163 Referecnce, including English and Vietnamese versions
Trang 5Chapter 1 OVERVIEW 1.1 Platelet
Figure 1.1.Diagram of platelet growth and maturation
1.2 Thrombocytopenia and the causes
1.3.2 Immune thrombocytopenic purpura
The pathophysiology of ITP is autoimmune mechanism It is demonstrated that the lifespan of intravascular platelet of ITP is shortened and primary mechanism is the platelet destruction in peripheral tissue Even nowadays, initial factors producing anti-platelet antibodies are still unknown, but it is the fact that antiplatelet antibodies from lymphocyte B is specificallyresponded to glycoprotein in platelet membrane and theyweredestroyed by macrophages or
Trang 6dendritic cells in the liver and spleen via receptor Fcy Activated cytokine like IL-2 results in lymphocyte TCD4 proliferation (Th1, Th2) Lymphocyte TCD4s stimulate lymphocyte B to produce anti-platelet glycoprotein antibodies
1.3.3 Neonatal thrombocytopenia (NT)
Neonatal thrombocytopenia is not caused by thrombocytopenia in pregnancy, but it could be by ITP with antiplatelet antibodies passing through placental barrier (IgG) It is the standard of diagnose of GT or immune thrombocytopenia Nevertheless, not all cases of ITP cause neonatal thrombocytopenia
Hemorrhage in NT are the common immune pathologies This disease is characterized by platelet in peripheral vascular destroyed in the reticuloendothelial system associated with ant- platelet antibodies
Although the correlation between the magnitude of platelet level decline and the occurrence of neonatal thrombocytopenia is unfound, some studies show that themoderate and server neonatal diseasesrelated to ITP mothers account for 10% and 4%, respectively and the hemorrhage rate approx 1% Evaluation
of prenatal fetal platelet count through fetal blood sampling or fetal scalp blood sampling is not routine due to the high rates of complications and fetal loss In clinical practice, the best predictable factor of neonatal thrombocytopenia is based on the history of GT with thrombocytopenia of preceding infants
1.4 Anti- platelet antibodies
Alloimmunity is an immune response to non-self antigens from members of the same species, commonly due to blood infusion or transplanted tissues andpregnancy The reaction is caused by the role of alloantibody HPA with HPA1a antibody approximately 80% specific HPA anti platelet antibody Alloantibodies against HPAs and HLA is related to platelet disorders via immune mediation Hemorrhage in fetal immune thrombocytopenia is due to fetal HPA that stimulates the immune system of mother and produces antibodies against fetal platelet
Trang 7 The correlation between antiplatelet antibodies and thrombocytopenia Now, anti-HPA antibody can be detectable by highly sensitive measures However, ani-HPA antibody evidence did not demonstrate that these antibodies led to decrease in platelet count In clinical practice, it is clearly important to determine whether antibody leading to thrombocytopenia present or not Few reports showed that very low antibody titer may lead to declined platelet count in animal There is strong evidence that antibody may make platelet decrease, even the antibody level
is lower than the detectable limitones by common measures
1.4.3.Antibody tests
Some measures such as available taget cell help to detect anti–HPA antibodies
immunoassay), MPHA-mixed passive haemagglutination), flwcytometry analysis, ELISA, Luminex lab test These attribute are abstracted in table Anti–HLA antibody may create problems with platelet antibody test, such as MPHA and flow cytometry but, not specific test like MAIPA MAIPA is highly sensitive and specific, therefore, it is considered to golden standard
CHAPTER 2 MATERIALS AND METHOD 2.1 Studyparticipants
This descriptive study was conducted at National Hospital of Obstetrics and Gynacology in the period from March 2014 to December 2018 The study protocol was approved by the Ethics Committee of Nation hospital for Obstetrics and Gynecology Informed written consent was provided from all participants
All participants was diagnosis with thrombocytopenia at one of the hospitals including: National Hospital of Obstetrics and Gynecology, Bach Mai Hospital, and National Institute of Haematology and Blood Tranfusion and thier newborn
2.1.1 Inclusion
Pregnant women included in the study had to fulfil all of the following criteria:
- Normal health history
- Platelet counts is below 150G/l
- Not been diagnosed with thrombocytopenia due to bone marrow failure, viral infection, cancers, or drugs,…
2.1.2 Exclusion criteria
Women were excluded if they: not end their pregnancy at National Hospital of Obstetrics and Gynecology
2.2 Setting and time
The study was conducted at all three hospitals include: National hospital of Obstetrics and Gynecology, Bach Mai Hospital, and National Institute of Haematology and Blood Tranfusion from March 2014 to December 2018
Trang 8+ Patients who met all the criteria will be chosen to our study
+ All of them will be examined thoroughly and carefully and have their blood sample taken
+ Haematological consultation to decide when we should terminate pregnancy + Pediatric consultation to decide
2.4 Variables
2.4.1 Basic characteristics of participants
+ Age: divided into aged groups: under 18 years old, 18-34 year-old group, above 35 year-old group
+ Career: officer, worker, farmer and others
+ Parity: 1, 2 or more than 2
+ A history of thrombocytopenia in previous pregnancy: yes or no
+ Timing of thrombocytopenia diagnosed: ≤ 14-week gestation, 15-28 week gestation, or ≥28 week gestation
2.4.2 Clinical, subclinical characteristics and causes of thrombocytopenia
+ Platelet count at the time of diagnosis
+ Platelet count at the time of delivery
+ Anti-platelet antibodies: negative or positive
+ The level of anemia:
+ Postpartum follow-up: yes or no
2.4.3 The evaluation of neonatal hematological status whose mothers are diagnosed with thrombocytopenia
+ Gestation
+ Weight
+ Platelet counts: <50G/l; 50-100 G/l; >100G/l
+ Anti platelet antibodies: positive or negative
2.4.4 Management of thrombocytopenia in pregnancy
+ Delivery: vaginal delivery, C – section
Trang 9in Flowcytomater
2.5.2.2 Sample
+Whole blood sample
+ 2ml in blood collection tube containing EDTA
+Send blood sample to laboratory to refine serum by using 3000 cycle centrifugal method
+ Take serum out of the blood sample (300µl)
+ Preserve serum sample at 2-8℃
+ Serum samples are transferred to National Institute of Haematology and Blood Tranfusion to do indirect anti-platelet antibodies test
2.5.2.3 Assessment Criteria
+ Platelets which are refined should not contain erythrocytes and lymphocytes + Negative sample or O sample are takes from donors who never had a platelets transfusion before
+ Assess platelets base on SS and FS
+ Blood collection tube should be sterilized
+ The number of antibodies should be adequate
+ The chemicals should not out of date
+ The timing for testing should be adequate
2.6 Data analysis
+The statistical analyses were performed by using SPSS 22 package program + Categorical data were expressed as number and percentage For qualitative data, Chi-square test was used
+ P<0.05 considered to be statistically significant
2.7 Ethical consideration
This study was of a descriptive study and approved by the Ethics Committee of Nation hospital for Obstetrics and Gynecology Informed written consent was provided from all participants
The study aimed to early diagnosis thrombocytopenia in pregnancy to benefit prophylaxis and early treatment This study was not involved in any harmful intervention or put patients in danger The assessment of hematological status
is compulsory during pregnancy
Trang 10CHAPTER 3 STUDY RESULTS 3.1 The common characteristics of the patient in the study group
From April 2014 to April 2018, we conducted a blood test using the Sysmex XT2000i and found 58 pregnant women with thrombocyto-penia with the following common characteristics:
Average age of the study group is 28.6 ± 5.5 years (19-40 years old) The most common age group is from 18-34 years old, accounting for 79.3% The majority of patients have professional staff is 25, accounting for 43% The proportion of farmers and workers is almost the same (24%; 23%) The number
of patients who had giving birth for the first time and which for the second time that was the same (50.0%)
3.2 The clinical and paraclinical characteristics of studyparticipants pantient
3.2.1 The gestational age when diagnostic of thrombocytopenia
Table 3.2 Patient distribution stratified by gestational age when diagnostic
Comment: The mainly of thrombocytopenia was occurs in the third trimester
of pregnancy (75.9%), of which 8 pregnant women detected thrombocytopenia during labor The group of women in the first trimester was the lowest (8,6%) The Averange gestational age in the study group was 30,2±7.8 (08-41 weeks) The maximum: 41 weeks and the minimum: 08 weeks
3.2.5 The reason for the thrombocytopenia was detected
Figure 3.3 Patient distribution stratified by the reason for the
thrombocytopenia was detected
Comment: The common cases are those who was detected for
thrombocytopenia mainly due to having their blood count test when they
check-up by their doctor (62.1%) The less common cases are those who detected due to accidental testing (17.2%) The least cases are those who detected due to hemorrhagic symptoms (only 6.9%: 4 patients)
Trang 113.2.7 Symptoms of hemorrhage
Table 3.7 Patient distribution stratified by symptoms of hemorrhage
Symptoms of hemorrhage Number Rate (%)
Comment: There are only 04 of 58 study patients (6.9%) had moderate
symptoms of bleeding (bleeding gums, nosebleed); no symptoms of severe bleeding
3.3.4 Comparison of platelet count in diagnosis and in labor
Table 3.8 Patient distribution stratified by platelet count in diagnosis and
that was in labor
fisher's exact test p=0.033
Comment: The platelet count in labor was lower than that in diagnosis: 65.7±33.4G/l (2-125G/l) and 79.07 ± 33.74G/l (14-158G/l) In the group of
severe thrombocytopenia (<50G/l): this rate was decrease than that in diagnosis (22.4% and 37.5%) In contrast, the rate of groups with mild and moderate thrombocytopenia in labor that was increase (21.4%→29.3% and
41.1%→46.6%) This difference was significant (p <0.05)
3.3.5 The maternal anti-platelet antibodies
Figure 3.3 Patient distribution stratified by the maternal anti-platelet
antibodies Comment: The rate of women with anti-platelet antibodies in the study group
for 31.0% The thrombocytopenia subgroup regarding immune causes accounted for 82.7% of total58 women However, the percentage of positive anti-platelet antibody tests in this subgroup was only 37.5%
Trang 123.3.6 The maternal anaemia before and after delivery
Table 3.9 Patient distribution stratified bythe maternal anaemia before
and after delivery
fisher's exact p=0.000, pair test p=0.000
Comment: The rate of maternal anaemia after delivery was 2 times more than
poir delivery (100% -79.3% = 20.7% compared with 100% -51.0% = 48.3%) This rate was increases at all grades of anemia:grade1→grade2 (respectively: 20.7%→43.1%; 0%→5.9%) There was no pregnant woman with grade 3 anemia in both before and after delivery groups.This rate was the highest increase in the grade 1 anemia subgroup This difference was insignificant (p
fisher's exact test p=0.010
Comment: In the first trimester of pregnancy, thrombocytopenia was detected
mainly due to screening and antenatal check-ups (60%) For the second trimester and third trimester it was found by anteatal care and they got the highest proportion(55.6% and 68.2%) This difference was insignificant (p <0.05)
3.2.15 Relationship between gestational age and the maternal platelet count
in diagnosis
Trang 13Table 3.12 Patient distribution stratified by gestational age and the maternal platelet count
Maternal platelet count
fisher's exact test p=0.303
Comment: The ratio of thrombocytopenia diagnosis decreased accordingly to gestational age (7.14%; 16.07%; 76.79%)
In the group of thrombocytopenia appearing from the first trimester of pregnancy, the rate of severe thrombocytopenia was the highest more than the other two groups (75%; 0%; 25%) However, in the group of the second trimester, the rate of mild, moderate and severe was similar (33.33%; 33.33%;
33.33%).This difference no was insignificant (p >0.05)
3.2.23 Relationship between level thrombocytopenia in delivery and maternal anti-platelet antibodies
Table 3.19 Patient distribution stratified by level thrombocytopenia in
delivery and maternal anti-platelet antibodies
Maternal platelet
count APA