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International Open Access Journal of Prevention and Research in Medicine
Director Prof. Francesco Tomei
Gestational thrombocytopenia (GT) is commonly observed in pregnancies with otherwise limited obstetric and hematologic complications.
However, few data are available on the natural history of the disease and on the recurrence of thrombocytopenia in subsequent pregnancies.
37 consecutive patients with GT were enrolled in a prospective study, with a total of 36 pregnancies observed. Vaginal delivery was carried out in 33/41 (80%); two patients were transfused with packed red cells for obstetric hemorrhage (post-partum uterine atony).
Mothers and their related foetuses- newborns were evaluated retrospectively for symptoms and/or signs of external and internal haemorrhage throughout pregnancy and early puerperium, even in relationship with mode of delivery (caesarean section versus spontaneous vaginal delivery). This study confirms, in accordance to literature, that all observed cases of GT have an uncomplicated course with no related perinatal and maternal morbidity even in patients with initial platelet count < 75.000/ml regardless of the route of delivery.
The Authors conducted a retrospective study concerning maternal platelet count fluctuation during pregnancy and puerperium and its correlation with the newborn’s platelet level in a group of 36 patients treated at the haematology-clinic of the Santo Bambino Hospital, c/o Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele, Catania.
These patients, with gestational thrombocytopenia (GT), were rolled over a 4-year period, from January 2006 to December 2009.
Gestational thrombocytopenia (GT) is commonly observed in pregnancies with otherwise limited obstetric and hematologic complications.
Thrombocytopenia is defined as a platelet count below 150 x 109/l, caused by accelerated platelet destruction or decreased production. It is classified as mild with a platelet count of 100–150 x 109/l, moderate at 50–100x109/l and severe with less than 50x109/l (1).
Thrombocytopenia is second only to anaemia as the most common hematologic abnormality during pregnancy (2).
Indeed, a platelet count <150x109/l can be observed in 6 to 15% of pregnant women at the end of pregnancy. Thrombocytopenia is usually moderate (<100 x109/l in only 1% of women) and often incidentally detected on routine blood count (3).
Gestational thrombocytopenia (GT) is considered the most prevalent cause of thrombocytopenia during pregnancy accounting for about 75% of cases (1).
The etiology is unknown, but it is considered to be due to the relative hemodilution of pregnancy, amplified by the capture or destruction of platelets in the placenta (4, 5, 6).
GT is considered a minor form of thrombocytopenia, with no substantial risk of hemorrhage for both the mother and the infant.
Gestational thrombocytopenia is characterized by:
· asymptomatic, mild thrombocytopenia (platelet count >70x109/l);
· no past history of thrombocytopenia (except during a previous pregnancy);
· occurrence during the 3rd trimester;
· no fetal / neonatal thrombocytopenia;
· spontaneous postpartum resolution.
Thrombocytopenia can also be associated with several diseases, either pregnancy-related or not, such as preeclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count), which represents about 18% of cases, and idiopathic thrombocytopenic purpura (ITP), which is found in about 5% of cases (7). Some rare conditions, such as thrombotic thrombocytopenic purpura, haemolytic uremic syndrome, disseminated intravascular coagulation and others account for about 2% of the total (8, 9) (table1).
Table 1 -Causes of thrombocytopenia in decreasing order of frequency during pregnancy
The Authors present here the results of a retrospective study concerning maternal platelet count fluctuation during pregnancy and puerperium and its correlation with the newborn’s platelet levels in a group of 36 patients referred to the haematology-clinic for gestational thrombocytopenia and who delivered in the same Hospital during a period of four years.
Between January 2006 and December 2009, 36 patients with GT (mean gestational age at diagnosis 5 months ± 3 months), who delivered at the Santo Bambino Hospital - c/o Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele, Catania, Italy - , were enrolled in this study, after carefully excluding other possible causes of this condition, and evaluated retrospectively. GT was defined as an asymptomatic thrombocytopenia occurring during gestation, in patients with a normal platelet count at the beginning and or immediately before pregnancy and without antiplatelet- antibodies. The presence of EDTA-dependent pseudothrombocytopenia was ruled out by performing platelet count also in samples anticoagulated with sodium heparin and trisodium citrate and by examination of a May-Grunwald stained peripheral smear.
A maternal platelet count was determined at least three times during pregnancy and once after delivery in each enrolled patient and at least once in every relative newborn at birth (first time on cord blood). All patients underwent specific tests for the presence of antiplatelet- autoantibodies.
Maternal thrombocytopenia was pharmacologically treated only for platelet count ≤ 90.000/ml with the following drugs: vitamin C (1-2,5 g/die) and tranexanic acid (tranex) 2-2.5 g/die, until 3-4 hours before delivery and for two days after birth.
When maternal platelet count was between 50.000 and 60.000/ml, prednisone (deltacortene) 0,5-1 mg/kg/ die was administered antenatally for about 30 days.
Mothers and their related foetuses-newborns were evaluated retrospectively for symptoms and/or signs of external and internal haemorrhage throughout pregnancy and early puerperium, even in relationship with mode of delivery (caesarean section versus spontaneous vaginal delivery).
A total of 36 patients were retrospectively followed, (22 primigravida).
The mean age was 30 ± 2 years.
Only 6 women had developed thrombocytopenia in a previous pregnancy (table 2).
Table 2
Characteristics of patients n %
Primigravide
22
7.92
Multiparous
14
5.04
Previous gestational thrombocytopenia
6
2.16
Spontaneous delivery
21
7.56
Caesarean section
15
5.4
About 45% of the enrolled patients had a caesarean delivery (however only in 1 case , patient 14, table. 4, the clinical indication was merely the significant maternal thrombocytopenia and the suspect of a concomitant severe fetal thrombocytopenia by the attending obstetrician, although no maternal antiplatelet -autoantibodies had been identified in this case).
The mean gestational age at the time of diagnosis was 12 ±3 weeks for the 6 women with a previous history of gestational thrombocytopenia and 28±3 weeks in all the other patients (table 3).
Table 3 - Gestational age at diagnosis
First onset GT
History of previous GT
28 ±3 weeks
12±3 weeks
Initially, when GT was diagnosed in the 36 studied patients, the average platelet count was at the lowest level, 101(± 26.3) x109/l, it increased to 108 (±18.8) x109/l subsequently during pregnancy and it went further up, 129 (± 27.3.) x109/l, at the time of delivery, reaching the highest level in puerperium: 154 (± 27.9) x 109/l (fig. 1 and table 4).
Table 4 - Maternal and neonatal platelet count: absolute values
CASE
PLATELED COUNT AT TIME OF DIAGNOSIS
PLATELED COUNT DURING PREGNANCY
PLATELED COUNT AT TERM
PLATELED COUNT PUERPERAL
PLATELED COUNT NEWBORN
1
91
85
90
143
150
2
100
130
150
165
165
3
90
80
90
90
140
4
147
100
103
138
135
*5
72
100
90
85
150
6
129
100
121
128
165
7
81
87
93
139
150
8
140
113
145
160
180
9
103
115
137
146
150
10
100
110
103
120
110
11
106
100
95
130
142
12
95
98
100
100
130
13
110
100
98
145
154
*14
41
33
70
90
72
15
104
96
90
110
176
16
140
147
135
167
170
17
91
90
103
90
158
18
128
130
107
159
191
*19
70
90
92
110
154
20
148
90
107
178
143
21
110
89
93
123
178
22
100
116
92
125
123
*23
92
75
110
112
154
*24
81
54
108
125
193
25
95
91
114
110
149
26
80
110
100
98
198
27
83
86
108
110
174
28
76
90
100
125
157
*29
70
85
95
100
187
30
115
110
130
135
145
31
140
147
144
156
164
32
130
160
120
188
149
33
100
108
110
138
152
34
140
144
130
182
190
35
101
120
133
132
178
*36
53
54
97
126
80
* pt with at least one platelet count ≤75 x109/l
The search for antiplatelet antibodies was negative in all women.
Table 5 -Treatment of thrombocytopenia and type of delivery
CASE
TROMBOCITOPENIA PRIOR TO PREGNANCY
TREATMENT DURING PREGNANCY
DELIVERY TYPE
AUTOANTIBODY
1
N
N
SVD
N
2
N
N
SVD
N
3
N
Y
CS
N
4
N
N
SVD
N
*5
N
Y
SVD
N
6
Y
N
SVD
N
7
N
Y
SVD
N
8
N
N
CS
N
9
N
N
CS
N
10
Y
N
SVD
N
11
N
N
CS
N
12
N
N
SVD
N
13
N
N
CS
N
*14
N
Y
CS
N
15
Y
N
SVD
N
16
N
N
SVD
N
17
N
Y
CS
N
18
N
N
SVD
N
*19
N
Y
SVD
N
20
N
N
SVD
N
21
N
Y
CS
N
22
N
N
SVD
N
*23
Y
Y
CS
N
*24
Y
Y
SVD
N
25
N
N
SVD
N
26
N
N
SVD
N
27
N
Y
CS
N
28
Y
Y
SVD
N
*29
N
Y
CS
N
30
N
N
CS
N
31
N
N
SVD
N
32
N
N
CS
N
33
N
N
SVD
N
34
N
N
CS
N
35
N
N
CS
N
*36
N
Y
SVD
N
*: pt with at least one platelet count ≤ 75 x109/l ; ο: therapy during pregnancy; N: no complications
Women during pregnancy didn’t show any sign of hemorrhage and were given a vitamin supplementation (vitamin C), and tranexanic acid only in the presence of platelet count ≤ 90 x109/l, and deltacortene (0.5-1 mg/kg/ die) for platelet count between 50.000 and 60.000/ml.
Fetal-neonatal bleeding symptoms were not observed, and only two cases of mild transitory thrombocytopenia were recorded, as reported in table 6.
Table 6 - Maternal thrombocytopenia and neonatal complications
CASE
NEONATAL COMPLICATIONS
1
N
2
N
3
N
4
N
ο *5
N
6
N
ο 7
N
8
N
9
N
10
N
11
N
12
N
13
N
ο *14
MILD ASYMPTOMATIC TROMBOCITOPENIA
15
N
16
N
ο 17
N
18
N
ο *19
N
20
N
21
N
22
N
ο *23
N
ο *24
N
25
N
26
N
ο 27
N
ο 28
N
ο *29
N
30
N
31
N
32
N
33
N
34
N
35
N
ο *36
MILD ASYMPTOMATIC TROMBOCITOPENIA
*: pt with at least one platelet count ≤ 75 x109/l ; ο: therapy during pregnancy; N: no complications
Thrombocytopenia has been more commonly diagnosed in pregnant women in the last 20 years. It may result in bleeding into mucous membranes presenting as petechiae, ecchymosed, epistaxis, gingival bleeding etc. Moreover, bruising, hematuria, gastrointestinal bleeding and rarely intracranial hemorrhage can occur (10).
The diagnosis of ITP is very difficult during pregnancy because its presentation may closely resemble gestational thrombocytopenia (11, 12).
The diagnosis of ITP should be suspected in case of:
·thrombocytopenia discovered before the 3rd trimester or present before pregnancy;
·platelet count <75 x109/l during pregnancy (in our series 7 cases)
·presence of autoantibodies (no cases reported in our series)
·persistence of thrombocytopenia postpartum (sometimes even thrombocytopenia due to ITP may promptly normalize after delivery).
The Authors found that, despite the defining criteria, GT may include cases with moderate (n=6) and severe (n=1) maternal thrombocytopenia and, despite the absence of antiplatelet-autoantibodies, it may be incidentally associated with mild neonatal thrombocytopenia: 2 cases in this series.
The present study confirms that all observed cases of GT have an uncomplicated course with no related perinatal and maternal morbidity even in patient with initial platelet count < 75.000/ml, independently from the mode of delivery.
In case of gestational thrombocytopenia, a complete normalization of maternal platelet count should be expected during the postpartum period, even if a diagnosis of a concomitant incidental neonatal thrombocytopenia cannot be excluded.
No intervention, such as a foetal platelet count or caesarean section, is necessary. Periodic platelet counts, either once a trimester or every month, are recommended depending on the level of thrombocytopenia.
In cases of thrombocytopenia ≤ 90.000/ml patients should be given drugs such as: vitamin C (1-1.5 g/die) and tranexanic acid (tranex) 2-2.5g/die to improve platelet count.
In the past, it was common practice to perform caesarean section on mothers with severe thrombocytopenia and presence of circulating antiplatelet autoantibodies to lessen the risk of neonatal intracranial haemorrhage due to the trauma of vaginal delivery, especially with foetal platelet counts < 50 x109/l.
In the above clinical scenario , however, caesarean delivery has not been proved to decrease the incidence of either maternal and or neonatal haemorrhage and of course this is particularly true in case of GT as the present study demonstrates.
Acknowledgments
Valentina Pafumi has carried out English language editing for this article.
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Carlo Pafumi
Institute of Obstetric and Gynaecological Pathology, Santo Bambino Hospital, c/o University Hospital Policlinico-Vittorio Emanuele, Catania, Italy
e-mail: info@preventionandresearch.com