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Platelets
or thrombocytes are one of the finest friends of obstetricians
and their pregnant subjects. The protective responses to
pregnancy that are abundantly found in nearly all systems of the
mother’s body also include important changes in the platelets.
If a subject enters pregnancy with a disorder that keeps her
platelet count autoimmunologicaly low like I.T.P. there can be a
risk to her as well as her child.
Infact, the commonest platelet anomaly encountered in clinical
practice is thrombocytopenia. A thrombocytopenia could be due to
four types of conditions.
A)
Gestational Thrombocytopenia
B)
Thrombocytopenia associated with maternal disease
C)
Auto-Immune Thrombocytopenic Purpura
D)
Allo-Immune Thrombocytopenia.
Before going into details of these conditions it will be
appropriate to consider the physiology of hemostasis in
pregnancy.
HEMOSTASIS
IN NORMAL PREGNANCY: -
Never is a woman as greatly exposed to the risks of bleeding as
in pregnancy and labor. It is therefore understandable that
profound changes take place in the physiology of a pregnant
mother so as to generate a tendency of hemostasis. The changes
affect the procoagulants and anticoagulants. They affect the
pro-fibrinolytic and anti-fibrinolytic, in such a way that
ultimate effect is that of hypercoagulability. In a recent
study, it has been found that there is an increase in all
coagulation factors with the sole exception of factor XI C
(1) In this study it was found that the greatest changes
were noted in factor VIII C having increased 65% above the
baseline at term. This rise was sustained upto 3rd
day post partum. The only clotting factor that fell during
pregnancy was factor XI –C. Mean anti-thrombin activity was
slightly higher in women at term. Though Protein-C remained same
in its activity before delivery, it was found to be maximally
active in 3 days post partum.
There are major changes in the balance of fibrinolytic system
during pregnancy. The concentration of plasminogen and
plasminogen activators increase significantly during pregnancy (2). It is now well known that following placental
separation maternal plasma fibrinolytic activity increases
rapidly.
We now come to the conditions associated with low platelets in
pregnancy.
GESTATIONAL
THROMBOCYTOPENIA:
-
In an interesting study by Kaplan et-al (3) showed that platelet
count decreases with gestation by about 12% between 20 to 40
weeks. In most of these cases thrombocytopenia is mild with
platelet counts between 70,000 to 1,50,000/cu. mL (4). These
states, in absence of any autoimmune cause are described as
gestational thrombocytopenia. This condition could occur due to
hormonal depression of megakaryopoesis or placental destruction
of platelets. This condition is not associated with any untoward
feto-maternal complication (4) and therefore warrants no
treatment (5).
THROMBOCYTOPENIA
ASSOCIATED WITH MATERNAL DISEASES:-
Acquired hemolytic anemia, SLE, Septicemia, HIV infection, etc.
are associated with thrombocytopenia. One of the recent entries
to this list is Antiphospholipid Antibody syndrome (6).
Pregnancy complications like P.I.H., placental abruption, etc.
and drugs like heparin and aspirin can also produce
thrombocytopenia. Kelton et al (7) have shown that all obstetric
causes of D.I.C. together can add upto 21% of causes producing
thrombocytopenia in pregnancy. Treatment of the parent
conditions and that of the obstetric complications thereof
manages the conditions of such thrombocytopenia.
AUTOIMMUNE
THROMBOCYTOPENIA:
-
Autoimmune thrombocytopenic Purpura (AITP) is 1 to 2 per 1000
pregnancies (4). Antibodies directed against platelets
tend to produce this autoimmune condition. These antibodies are
of Ig G types They can cross the placenta and cause
thrombocytopenia in the fetus. The platelets that are so coated
by the antibodies tend to sludge in the R.E. system where they
are conveniently phogocytosed.
The course of pre-existing thrombocytopenia is not affected by
pregnancy, but may influence the pregnancy outcome including a
grave risk of PPH (8). Severe fetal thrombocytopenia can occur
in 12% of such pregnancies and in about 1% there is fetal intra
cranial hemorrhage (9). The differentiation of this condition
from maternal gestation thrombocytopenia is difficult but more
or less academic rather than of significant practical bearing.
MATERNAL
MANAGEMENT:
-
Maternal management of AITP in pregnancy rests on three pillars:
A)
Corticosteroids:
Prednisolone in a dose of 0.25 – 1 mg/kg/day given upto delivery
gives a satisfactory response in upto 90% of cases. This drug
inhibits the antibody production and the response is seen within
3 week of starting of steroids (10)(11).
B)
Intravenous Gamma Globulin (Ig G)
is effective in 80% of subjects. Its effect is seen within 5-10
days and lasts upto 3 weeks. This treatment acts by interfering
with Fc receptor mediated clearance of IgG – coated
platelets.(12)
C)
Splenectomy: This is usually reserved for those subjects who
do not respond to the above two modalities of treatment.
Other therapeutic modalities like Danazol have been tried but
with modest success.
MODE
OF DELIVERY & FETAL EFFECTS:-
Risk of severe fetal thrombocytopenia at term is negligible in
the absence of a history of AITP before pregnancy. Currently
percutaneous fetal cord blood sampling is the procedure of
choice for estimating fetal thrombocytopenia. It is recommended
if: there is history of AITP with identifiable PA Ig G
antibodies in current pregnancy. Fetuses with severe
thrombocytopenia (Count 50,000/ml.) are preferably delivered by
cesarean section.
In neonatal period an immediate cord blood platelet count must
be performed. In cases with platelet counts < 50000/ml. and
petechiae, steroids or preferably IgG should be administered.
Platelet concentrate transfusions are indicated in cases of
mucous membrane bleeding. Neonatal platelet counts falls further
in the first few days of life, hence complications are likely to
occur then evaluation of platelet count for the first week is
indicated in those neonates with thrombocytopenia at delivery.
ALLOIMMUNE
THROMBOCYTOPENIA:
-
It is quite paradoxical to note that this is a serious fetal
disorder that has no maternal significance (13). Maternal IgG
antibodies directed against fetal platelets causes it. Its
mechanism is similar to red cell isoimmunization (8). However,
the problem lies in the fact that in nearly half of these cases,
the diagnosis is made in retrospect i.e. after the birth of the
child. This is also because, it occur predominately in
primiparous women (14)(15). In subsequent pregnancies it is
estimated to recur in 75% to 90% of cases. The seventy is either
similar or worse but never ameliorates.
The first affected child is unsuspected as PL?? typing is not
done routinely. Also, in Rh isoimmunization, one uses antibody
titers to monitor the severity of the disease, similar
monitoring has not been found to be useful in this condition.
Reznikoff (16) interestingly should that high mild from of the
disease and low titters were associated with hemorrhages.
Fetal blood sampling and fetal transfusion by PL?? negative
platelets is the best way to treat the problem. In high-risk
cases when past history of such a condition exists, it is wise
to perform cord blood sampling as early as 20 weeks of
pregnancy. Goldman (17) and Sagol (18) suggested an alternative
approach. They suggested a cordocentesis in all cases at 20
weeks to determine the PL?? genotype of the father. If the
genotype is heterozygous than only 50% risk of the fetus getting
affected. If the father is found to be homozygous for PL??2 than cordocentesis and maternal treatment are necessary. If on
cordocentesis the fetal platelet count is >1,00,000/ml., it may
be repeated after 10 weeks. If the same is between
50-1,00,000/ml than maternal steroids and Ig G are administered.
If the count is 50,000/ml, platelet transfusions – preferably
PL?? negative is done.
REFRENCES: -
1)
Clark P, Bernard J., Conkie JA: Hemostasis in normal pregnancy: Throm
Hemost (Submitted) 1997
2)
Walker
I.D: Inherited coagulation disorders and thrombophilia and
pregnancy: Rec. Adv. In O. & G.: 1998: 20: 35-38.
3)
Kaplan C., Forestier F., Drcyfus M.: Maternal thrombocytopenia
during pregnancy: diagnosis and etiology: Semin. Thromb. Hemost:
1995:21: 85-89
4)
Burrows R.F., Kelton J.G.: Thrombocytopenia at delivery: Am. J Obst. Gyn.:
1990:162:731-5.>
5)
Burrows R.F., Kelton J.G. Fetal thrombocytopenia and its relation to
maternal thrombocytopenia: New Eng. J. Med.: 1993: 329:1463-4.
6)
Desai P,
Desai M., Anand R: Effect of treatment on cases testing positive
for APA: Jr. O. & G. Res.: 1997: 24(3):6-10.
7)
Kelton J.G., Powers P.J. Carter CJ: A prospective study of usefulness of
the management of platelet associated Ig G for diagnosis of
thrombocytopenia: Blood: 1982:1050-3.
8)
Stephen
G., Carrolok: Maternal & fetal thrombocytopenia: Prog. In Obst.
& Gyn.: 1998: 13:43-45.
9)
Silver
RM., Branch W, Scott Jr.: Maternal thrombocytopenia: time for a
reassessment: Am Jr. O. & G. : 1995:173: 479-83.
10) Samuel P,
Brusel J.B., Braintman L.F., Estimation of the risk of
thrombocytopenia in the offspring of pregnant women with AITP:
New Eng. J Med.: 1995: 323: 229-31
11) Biswas A,
Arulkumaran S, Ratnam S S: Disorders of platelet in pregnancy. Obst. & Gyn. Survey: 1994: 49 585-589.
12) McCrae
K.R., Samuel P., Schreiber AD: Pregnancy associated
thrombocytopenia: pathogenesis and management: Blood: 1992: 80:
2697-99
13) Murphy
MF, Pullon HW, Metcalfe P.: Thrombocytopenia bi-weekly in utero
platelet transfusion: Vox Sang: 1990: 58: 45-9.
14) Mueller
Eckhardt C., Gubert A: 348 cases of suspected fetal alloimmue
thrombocytopenia: Lancet: 1990: 1: 363-7
15) Sholman
NR: Platelet immunology in Colman RW, Hirsh J., Mander VJ:
principles and clinical practice: Philadelphia. Lippincot.1st.
Ed. 1993:414-8.
16)
Reznikoff-E Management of alloimmune and autoimmune
thrombocytopenia: Vox Sang: 1988: 55; 193-5.
17) Goldman
M, Decary F, David M: Should all pregnant women be tested for
their platelet PLA: J. Hematol: 1994: 82: 670-5.
18) Sagot
P., Banneville F, Bignon J.D. management of platelet and Rh D
maternal isoimmunization by PCR phenotypes after early
amniocentesis: Fetal Diagnosis: 1995: 10: 379-84.
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