Thrombocytopenia and pregnancy

14 Dicembre 2012

 
 
Genovese F, D’Agati A, Leanza V, Carbonaro A, Leanza G, Pafumi C, Zarbo G

Authors   [Indice]

Genovese F1, D’Agati A1, Leanza V1, Carbonaro A1, Leanza G1, Pafumi C1, Zarbo G1

1Institute of Obstetric and Gynaecological Pathology, Santo Bambino Hospital, c/o University Hospital Policlinico-Vittorio Emanuele, Catania, Italy 


Citation: Genovese F, D’Agati A, Leanza V, et al. Thrombocytopenia and pregnancy. Prevent Res 2012; 2 (4): 379-387. Available from: http://www.preventionandresearch.com/doi: 10.7362/2240-2594.088.2012


doi: 10.7362/2240-2594.088.2012


Key words: gestational thrombocytopenia, fetal-neonatal haemorrhage, maternal haemorrage


Abstract   [Indice]

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.

Background   [Indice]

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
 
 
−         Incidental or gestational thrombocytopenia
−         Pseudothrombocytopenia (laboratory artifact with EDTA anticoagulant)
−         Disorders with increased platelet consumption
−         Immune thrombocytopenic purpura
−         Pregnancy induced hypertension ⁄ HELLP syndrome
−         Thrombotic thrombocytopenic purpura
−         Hemolytic uremic syndrome
−         Infection-associated (HIV, malaria)
−         Drug-induced (heparin, sulphonamides, penicillin, rifampicin, quinine)
−         Systemic lupus erythematosus
−         Antiphospholipid syndrome
−         Disseminated intravascular coagulation
−         Amniotic embolism
−         Disorders with reduced platelet production
−         Congenital trombocitopenia
−         Aplastic anemia
−         Leukaemia
−         Drug-induced
−         Myelodysplasia
 
 
 

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.

Methods   [Indice]

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).

Results   [Indice]

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).

 
 
Fig 1 - Average maternal platelet count fluctuation
 
 
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
* 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

Discussion   [Indice]

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.

Conclusions   [Indice]

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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Corresponding Author   [Indice]

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  

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Galleria fotografica
Fig 1 - Average maternal platelet count fluctuatio