|
INTRODUCTION |
¡@ |
Platelets are nonnucleated cells derived from
megakaryocytes in the bone marrow, which normally live in the peripheral
circulation for as long as 10 days. Platelets play a critical initiating role in
the hemostatic system.
Primary hemostasis begins when platelets adhere to the site of endothelial
disruption, leading to platelet clumping. This is followed by platelet
activation, which is characterized by release of granules containing von
Willebrand factor, adenosine 5'-diphosphate (ADP), and serotonin. This serves to
recruit other platelets into the growing platelet plug, which acts to stop the
bleeding. Simultaneously, the synthesis of thromboxane A2 and release
of serotonin leads to vasoconstriction to reduce blood loss at the site of
vascular injury.
The secondary hemostatic phase begins when the coagulation pathway is
activated on the surface of the activated platelets to form a fibrin meshwork,
which serves to reinforce the platelet plug.
Thrombocytopenia is encountered in 7-8% of all pregnancies. The modern
recognition of the condition predominantly is due to automated CBCs, which
routinely include platelet counts. Historically, thrombocytopenia has been a
cause for unnecessary, often invasive, additional testing, as well as cesarean
deliveries.
|
DEFINITION AND CLINICAL
MANIFESTATIONS |
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Definition and
severity
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- The reference range in nonpregnant women is 150,000-400,000/mcL.
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- Counts are slightly lower during pregnancy due to accelerated destruction
leading to younger, larger platelets.
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- The commonly used classification of thrombocytopenia severity in pregnancy
is arbitrary and not necessarily clinically relevant.
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- Mild thrombocytopenia is 100,000-150,000/mcL.
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- Moderate thrombocytopenia is 50,000-100,000/mcL.
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- Severe thrombocytopenia is less than 50,000/mcL.
Manifestations
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- Common - Petechiae, ecchymoses, nose and gum bleeding, menometrorrhagia
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- Rare - Hematuria, gastrointestinal bleeding, intracranial bleeding
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- Bleeding associated with surgery is uncommon unless the platelet counts
are lower than 50,000/mcL. Clinically significant spontaneous bleeding is rare
unless counts fall lower than 10,000/mcL.
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- Most reports of spontaneous hemorrhage occur in individuals diagnosed
with leukemia.
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- Similar to the classification of thrombocytopenia severity, the above
cutoffs for bleeding are arbitrary and controversial.
|
ETIOLOGIC CLASSIFICATION
|
¡@ |
The etiologic classification for
thrombocytopenia can be divided into 3 broad categories¡Xincreased destruction or
utilization, decreased production, and sequestration.
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- Increased destruction or utilization
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- Immunologic ?Immune thrombocytopenic purpura (ITP), systemic lupus
erythematosus (SLE)
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- Consumption ?Disseminated intravascular coagulation (DIC)
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- Microangiopathies (exposure to abnormal blood vessels)
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- Hemolysis, elevated liver enzymes, low platelets (HELLP)
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- Thrombotic thrombocytopenic purpura (TTP)
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- Hemolytic uremic syndrome (HUS)
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- Increased peripheral destruction ?Gestational thrombocytopenia (GT)
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- Increased number of megakaryocytes in bone marrow is confirmatory.
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- Most thrombocytopenias in pregnancy are due to increased destruction.
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- Decreased production
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- Leukemia, aplastic anemia, folate deficiency, medications, viral
infections
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- Decreased number of megakaryocytes in bone marrow is confirmatory.
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- Sequestration ?Observed with splenic congestion (eg, cirrhosis)
|
IMMUNE THROMBOCYTOPENIC
PURPURA |
¡@ |
ITP is also known as
idiopathic thrombocytopenic purpura or autoimmune thrombocytopenic purpura
(ATP).
Incidence
Incidence is 1 per 1000-10,000 pregnancies, and it accounts for 3% of all
thrombocytopenic gravidas.
Pathophysiology
¡@
- Immunoglobulin G (IgG) antiplatelet antibodies recognize membrane
glycoproteins and coat the platelets, which then are destroyed by the
reticuloendothelial system, predominantly in the spleen.
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- Antiplatelet antibodies may cross the placenta and cause significant fetal
thrombocytopenia (<50,000/mcL), which could result in bleeding complications
in the neonate.
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- Minor bleeding complications - Purpura, ecchymoses, melena
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- Major bleeding complications - Intracranial hemorrhage leading to
neurologic impairment or death
Diagnosis
ITP is a diagnosis of exclusion.
¡@
- Persistent thrombocytopenia (<100,000/mcL), increased number of
megakaryocytes in the bone marrow, exclusion of systemic disorders or
medications/drugs, absence of splenomegaly
¡@
- Approximately 80% of cases are associated with antiplatelet antibodies
(but antiplatelet antibodies are not required for diagnosis).
Clinical manifestations
¡@
- Easy bruising, petechiae, epistaxis, and gingival bleeding, although some
women are asymptomatic
¡@
- Significant hemorrhage is rare, even when counts fall to less than 20,000/mcL.
History
In 1977, a case of neonatal intracranial hemorrhage was reported (due to
perceived trauma) after abdominal delivery of a thrombocytopenic infant to a
mother with ITP. This led to the recommendation that women with ITP be delivered
by elective cesarean delivery. By the late 1980s, cesarean deliveries were
recommended only for fetuses with known or suspected thrombocytopenia (counts
<50,000/mcL).
Unfortunately, fetal platelet counts do not correlate with maternal platelet
counts, history of splenectomy, or presence of platelet-associated antibody. The
only certain method of determining fetal platelet count would be by direct fetal
blood sampling. By assessing platelet counts in utero, most cesarean deliveries
could be avoided because most fetuses of ITP mothers have normal platelet
counts.
¡@
- Fetal scalp sampling: This is the first direct fetal blood sampling
technique. It requires ruptured membranes and a cervix dilated at least 3 cm.
Falsely low fetal platelet counts are encountered often. Due to procoagulants
in amniotic fluid, fetal platelets start to clump immediately, resulting in
falsely low platelet counts. Additionally, the capillary tube into which the
fetal blood is drawn is lined with heparin, which can cause platelet clumping
and a spuriously low count. Clumping observed on the smear from scalp sampling
usually indicates a platelet count of at least 20,000/mcL.
¡@
- Percutaneous umbilical blood sampling (PUBS): PUBS is more accurate than
scalp sampling, but it is associated with a higher complication rate (2-3%).
Contemporary studies of ITP in pregnancy
Cook in 1991 reviewed a 10-year experience (1980-90) with treatment of ITP,
which included 25 women and 32 infants. Platelet counts were obtained in 23 of
32 newborns. Of 8 infants with low platelets at birth, 3 were mild, 3 were
moderate, and 2 were severe. A total of 6 infants had severe thrombocytopenia at
birth or during the neonatal period. Median platelet nadir occurred 4 days
following delivery. Eighteen cesarean deliveries were performed, 6 with
complications (infection, hematoma, transfusion).
A review of the literature over 20 years included 474 women with ITP (Cook,
1991). Approximately 15% of infants were found to have severe thrombocytopenia
(counts <50,000/mcL). The incidence of intracranial hemorrhage among infants
with severe thrombocytopenia was 4% after cesarean delivery, compared with 5%
after vaginal delivery
Burrows in 1993 reported on his large series of maternal platelet counts
collected on all women admitted to labor and delivery over a 6-year period at
McMaster University (15,607 samples), as well as cord blood platelet counts at
the time of delivery (15,932 samples). Of 46 women with ITP, 4 infants were born
with severe thrombocytopenia. Three of these 4 infants were delivered
abdominally, and 1 was delivered by cesarean delivery. No infant experienced an
intracranial hemorrhage.
Payne in 1997 reviewed a 10-year experience with 55 newborns born to 41 women
who had ITP. A total of 16 scalp samplings were performed (platelet count range
was 0-150,000/mcL). Three PUBS were performed. Two were associated with
complications—one case of fetal bradycardia and one case of an umbilical cord
hematoma with fetal distress resulting in an infant with anoxic encephalopathy
and cerebral palsy (that infant had a platelet count of 209,000/mcL).
Of 24 (44%) cesarean deliveries reported, half were performed solely for ITP.
Five of the cesarean deliveries were associated with postpartum hemorrhage, and
3 were associated with blood transfusions. Four (8%) infants had severe
thrombocytopenia (counts <50,000/mcL) at birth. Two of the 4 infants were
delivered abdominally, 2 were delivered by cesarean delivery, and all had normal
results on head ultrasound. Three additional neonates developed severe
thrombocytopenia during the first week of life. One experienced an intracranial
hemorrhage on the fourth day of life. Scalp platelet counts did not correlate
with neonatal platelet counts.
A literature review of 18 studies on maternal ITP involved 601 neonates
(Payne, 1997). Severe thrombocytopenia occurred in 72 of 601 neonates (12%).
Intracranial hemorrhage occurred in 6 out of 601 neonates (1%) and was unrelated
to mode of delivery. PUBS complication rate was 4.6%.
Conclusions from the above studies/reviews, including Silver’s 1995 review of
15 studies of ITP in pregnancy are as follows:
¡@
- The rate of severe neonatal thrombocytopenia is approximately 12%.
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- Intracranial hemorrhage is rare (approximately 1%) and appears to be
unrelated to the mode of delivery.
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- Abdominal delivery never has been proven to cause intracranial hemorrhage.
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- Cesarean delivery should be reserved for obstetrical indications only.
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- Scalp sampling is unreliable, and the risks of PUBS appear to outweigh the
risk of an abdominal delivery of an infant with thrombocytopenia.
¡@
- Neonatal platelet counts normally decrease, sometimes dramatically, for
several days following delivery. This result may be due in part to the passage
of IgG antiplatelet antibody in the breast milk, although breastfeeding is not
contraindicated. Neonatal thrombocytopenia may lead to delayed postnatal
intracranial hemorrhage. Notifying pediatrics of any parturient with maternal
ITP is important so that neonatal platelet counts can be monitored closely.
Maternal treatment for ITP
No treatment is necessary if platelet counts remain above 50,000/mcL and
patient is asymptomatic. However, many physicians will treat for asymptomatic
platelet counts of less than 50,000/mcL, abnormal bleeding, or prior to invasive
procedures such as cesarean delivery or regional anesthesia.
None of the listed maternal treatments has been shown to adequately prevent
fetal/neonatal thrombocytopenia.
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- Steroids (eg, prednisone)
¡@
- Response time is 3-7 days; maximum effect occurs by 2-3 weeks.
¡@
- Approximately 70% of patients will respond, and 25% will enter complete
remission.
¡@
- Risks include hyperglycemia, fluid retention, and bone calcium loss.
¡@
- Intravenous immune globulin
¡@
- Intravenous immune globulin (IVIG) works by binding to platelet
receptors, blocking the binding of antiplatelet antibodies.
¡@
- IVIG is ideal when time is inadequate for steroids to take effect (prior
to surgery or low platelet counts with bleeding).
¡@
- Response time is 6-72 hours.
¡@
- Approximately 70% of patients will return to pretreatment levels within
30 days.
¡@
- This treatment is very expensive.
¡@
- Splenectomy
¡@
- Splenectomy removes the organ responsible for removing IgG-coated
platelets.
¡@
- In nonpregnant women, splenectomy is used when patients are unresponsive
to IVIG.
¡@
- Splenectomy usually is avoided during pregnancy for technical reasons,
although it remains an option in the first and second trimesters when ITP is
severe (counts <10,000/mcL) and the patient does not respond to steroids or
IVIG
¡@
- Complete remission occurs in two thirds of cases.
¡@
- Splenectomy does not have an impact on circulating antibodies that may
still cross the placenta and cause neonatal thrombocytopenia.
¡@
- Platelet transfusion
¡@
- This is a temporary measure, which should be administered for
life-threatening hemorrhage and should be available prior to surgery for
patients with severe thrombocytopenia.
¡@
- Platelet counts normally rise by 10,000/mcL for each unit of platelets
transfused, but in ITP the rise is less pronounced due to destruction of
donor platelets.
¡@
- Six to 10 units of platelets usually are administered at one time.
|
GESTATIONAL THROMBOCYTOPENIA
|
¡@ |
GT is also known as
pregnancy-induced, essential, benign, or incidental thrombocytopenia of
pregnancy.
Incidence
¡@
- Incidence is 8% of all pregnancies.
¡@
- GT accounts for more than 70% of cases of thrombocytopenia in pregnancy.
Pathophysiology
Pathophysiology is unknown but is thought to represent accelerated
consumption of platelets.
Diagnosis
¡@
- Usually, GT is detected incidentally on CBC, usually after late second
trimester.
¡@
- Similar to ITP, GT is a diagnosis of exclusion during pregnancy.
¡@
- No diagnostic test exists to distinguish GT from ITP.
¡@
- Lescale in 1996 evaluated 8 different platelet antibodies in 250 gravidas
with thrombocytopenia (160 with presumed GT, 90 with ITP) to determine if any
antibodies could distinguish the 2 conditions. Platelet-associated IgG was
comparably elevated in the majority of women with GT (69.5%) and ITP (64.6%),
P = 0.24. A significantly higher proportion of patients with ITP had
indirect IgG compared to patients with GT (85.9% versus 60.3%, P
<0.001), but significant overlap existed, limiting its clinical value.
Antiplatelet antibody tests, either alone or in combination, cannot be used to
distinguish ITP from GT.
Clinical manifestations
¡@
- Mild, asymptomatic thrombocytopenia (counts usually >70,000/mcL) occurs in
women with no prior history of low platelets or bleeding history.
¡@
- GT may reoccur in subsequent pregnancies, although the incidence is
unknown.
¡@
- Platelet counts normalize within 2-12 weeks following delivery.
¡@
- Burrows in 1990 reported that all women with GT had normal or normalizing
platelet counts by the seventh postpartum day.
Fetal/neonatal risks
¡@
- Risk of fetal or neonatal thrombocytopenia is extremely low, with no fetal
or neonatal bleeding complications.
¡@
- Samuels (1990) evaluated 162 pregnant women and their infants with
thrombocytopenia, 74 with presumed GT. No infant with platelet counts less
than 50,000/mcL or with intracranial hemorrhage had mothers with GT.
¡@
- In Burrows' large 1993 study, 756 of 1027 women who were thrombocytopenic
(73.6%) had GT. Only one infant had a platelet count less than 50,000/mcL, and
this infant had trisomy 21 and congenital marrow dysfunction. He concluded
that GT is the most frequent type of thrombocytopenia and poses no apparent
risks for either the mother or infant at delivery.
Management considerations
¡@
- Avoid antiplatelet antibody testing or fetal platelet determination.
¡@
- Cesarean delivery should be reserved for obstetrical indications only.
¡@
- Monitor maternal platelet counts periodically, watching for levels less
than 50-70,000/mcL.
¡@
- Antepartum anesthesia consultation should be obtained to discuss
availability of regional analgesia.
¡@
- Consider obtaining cord bloods for platelet count; notify pediatrician
following delivery.
¡@
- Document return of maternal platelet count to normal levels after
delivery.
Regional anesthesia considerations
The presence of a coagulopathy is cited as a specific contraindication to the
use of regional anesthesia due to concern for an epidural hematoma, which can
result in serious neurologic complications. Only 2 cases of epidural hematoma
have been reported in gravidas receiving epidurals in labor (one patient had
pregnancy-induced hypertension [PIH], as well as the lupus anticoagulant, and
the other patient had an ependymoma). All other cases of nonpregnant epidural
hematomas occurred in women receiving anticoagulants. Previously,
recommendations were that epidurals be withheld if platelet counts were less
than 100,000/mcL.
Three series have been published of gravidas undergoing regional analgesia
(epidural or spinal) with unexplained thrombocytopenia (Rolbin, 1988; Rasmus,
1989; Beilin, 1997). Platelet counts often were unavailable at the time of
epidural placement. The combined total was 105 women with platelet counts below
150,000/mcL; of these, 51 had platelet counts less than 100,000/mcL. No
anesthesia complications were reported in these series. Nevertheless, some
authors still are reluctant to advise epidurals for platelet counts below
100,000/mcL due to the small sample sizes in these studies.
Obtaining bleeding times often is recommended by the anesthesia department
prior to placing epidurals in thrombocytopenic parturients. Bleeding time is
influenced by various factors, has large interobserver variation, and cannot
predict bleeding or transfusion requirements. This is not useful in assessing
platelet function with ITP or GT, and its use should be discouraged for
quantitative platelet disorders.
|
HEMOLYSIS, ELEVATED LIVER
ENZYMES, LOW PLATELET COUNT SYNDROME |
¡@ |
The HELLP syndrome is a variant of severe preeclampsia.
Incidence
¡@
- Hypertensive disorders occur in 7-10% of all pregnancies; HELLP
complicates the cases of 10% of all women with PIH.
¡@
- HELLP syndrome accounts for 21% of maternal thrombocytopenia in pregnancy.
Pathophysiology
¡@
- HELLP syndrome is a microangiopathic process.
¡@
- Endothelial damage leads to enhanced platelet adhesion and destruction.
Diagnosis and classification of HELLP syndrome
¡@
- Hemolysis
¡@
- Abnormal results on peripheral smear (presence of schistocytes)
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- Total bilirubin greater than 1.2 mg/dL
¡@
- Lactic dehydrogenase (LDH) greater than 600 U/L
¡@
- Elevated liver enzymes (3 standard deviations above the mean)
¡@
- Aspartase aminotransferase (AST) greater than 70 U/L
¡@
- LDH greater than 600 U/L
¡@
- Low platelet count ?Platelet count under 100,000/mcL
¡@
- Approximately 50% of patients have complete HELLP (all components
present), and 50% have incomplete HELLP (one or more components present: EL,
HEL, ELLP, LP).
¡@
- Classification: Some physicians classify HELLP based on the severity of
thrombocytopenia.
¡@
- Class 1 - Platelet count less than 50,000/mcL
¡@
- Class 2 - Platelet count 50,000-100,000/mcL
¡@
- Class 3 - Platelet count 100,000-150,000/mcL
Clinical manifestations
¡@
- Clinical manifestations often are nonspecific (nausea/vomiting, headache
in 50%, epigastric or right upper quadrant pain in 50-67%).
¡@
- Not all HELLP syndromes meet the criteria for preeclampsia. Approximately
15% have diastolic blood pressure (BP) less than 90 mm Hg; 15% have minimal or
no proteinuria. Major complications can occur despite normal blood pressure
and proteinuria.
¡@
- The maternal mortality rate with HELLP is 1%.
¡@
- Thrombocytopenia usually is moderate, with counts rarely less than 20,000/mcL.
¡@
- Major hemorrhage is uncommon, but incisional site oozing or subcutaneous
hematomas may occur.
¡@
- Maternal thrombocytopenia nadirs at 24-48 hours postpartum.
Fetal/neonatal risks
¡@
- The perinatal mortality rate is 11%. Perinatal deaths may occur from
abruption, asphyxia, and extreme prematurity.
¡@
- Fetal growth restriction is common.
¡@
- Neonates may be at increased risk for thrombocytopenia.
¡@
- In Burrows' large 1993 study of women with thrombocytopenia, 216 had PIH/HELLP.
Four gave birth to infants with severe thrombocytopenia. Among 1198 women with
PIH but no thrombocytopenia, one infant had severe thrombocytopenia. Of the 5
infants with severe thrombocytopenia, all were preterm, 3 were
small-for-gestational age, and all were delivered by cesarean delivery. Two
infants experienced intracranial hemorrhages, despite being born by cesarean
delivery.
Treatment
¡@
- Delivery is the ultimate cure. Delivery may be delayed for 24-48 hours
prior to 32 weeks?gestation to administer corticosteroids if patient is
asymptomatic and fetus has reassuring testing.
¡@
- Magnesium sulfate (MgSO4) should be administered intrapartum
and postpartum, regardless of blood pressure levels.
¡@
- HELLP syndrome with thrombocytopenia does not by itself require a cesarean
delivery, although cesarean delivery may be acceptable prior to 32
weeks?gestation with an unfavorable cervix, due to an anticipated long
induction time in a clinically deteriorating gravida.
¡@
- Maintain platelet counts greater than 20,000/mcL for abdominal delivery
and 50,000/mcL for cesarean delivery. If platelets fall below 50,000/mcL prior
to cesarean delivery, be prepared to administer platelets just prior to
surgery and/or intraoperatively. A range of 6-10 units of platelets usually is
administered at the time of skin incision, and an additional 6 units are
administered if oozing is noted during the surgery.
¡@
- If thrombocytopenia is severe, regional anesthesia and pudendal blocks may
be contraindicated. In this situation, intravenous narcotics still can be
administered for analgesia during labor.
¡@
- Depending on the platelet count and degree of oozing, consider leaving the
bladder flap open and placing an intraperitoneal and/or subcutaneous closed
suction drain through a separate stab wound in an attempt to prevent wound
hematomas.
¡@
- Pfannenstiel incision with primary closure is acceptable for cesarean
delivery. Briggs in 1996 compared Pfannenstiel to midline incisions and
primary to delayed (48-72 h) closure in 104 women with HELLP syndrome. No
significant differences occurred in wound hematoma/infection by incision type
(17.3% versus 17.2%, P = 0.78) or closure type (26% versus 24% [NS]).
Subcutaneous drain did not significantly reduce wound complications (18.1%
versus 26.4%, P = 0.64).
¡@
- Thrombocytopenia and elevated liver function tests commonly worsen
postpartum. Platelets should start normalizing by the third postpartum day.
¡@
- Steroids have been shown to improve platelet counts transiently in
undelivered women with HELLP.
¡@
- Megann in 1994 randomized 25 subjects with HELLP syndrome with mild or
moderate thrombocytopenia at 24-37 weeks?gestation to antepartum
corticosteroids versus control. The steroid group received dexamethasone 10 mg
intravenously every 12 hours until delivery. The steroid group demonstrated a
significant rise in the platelet counts, lesser elevations in the liver
function tests, and a longer interval to delivery (41 versus 15 h). However,
both groups deteriorated postpartum. No difference occurred in neonatal
outcome, although the subject numbers may have been too small to detect a
statistically significant difference.
|
OTHER LESS COMMON CAUSES FOR
THROMBOCYTOPENIA |
¡@ |
Other less
common causes of thrombocytopenia discussed in this section are as follows:
Pseudothrombocytopenia
Microangiopathies
Other immunologic
conditions
Hypersplenism
Medications
Viral illnesses
Disseminated
intravascular coagulation
Alloimmune
thrombocytopenia
Pseudothrombocytopenia is a spuriously low platelet count
due to laboratory artifact.
Incidence
Incidence is 0.1% of all CBC specimens, and it accounts for 1% of all
thrombocytopenic gravidas.
Pathophysiology
¡@
- A laboratory artifact most often is due to platelet clumping.
¡@
- It often is associated with the anticoagulant (ethylenediaminetetraacetic
acid [EDTA]) in purple or lavender top tubes.
Clinical manifestations
No clinical manifestations exist.
Diagnosis
¡@
- Look for a description of platelet clumping on the peripheral smear.
¡@
- Recheck platelet count in a citrate tube. If count falls within the
reference range in the citrate tube, pseudothrombocytopenia is diagnosed. If
clumping occurs in citrate tube as well, it may indicate type 2B von
Willebrand disease, in which abnormal von Willebrand factor spontaneously
binds to and aggregates platelets.
Treatment
No treatment of pseudothrombocytopenia exists.
Microangiopathies
TTP and HUS are characterized by thrombocytopenia, hemolytic anemia, and
multiorgan failure.
Incidence
Incidence is 1 in 25,000 births. Microangiopathies often are mistaken for
preeclampsia/HELLP, leading to delay in diagnosis and treatment. Delay in
diagnosis may result in significant maternal morbidity and mortality.
Pathophysiology
¡@
- Etiology is unknown, but endothelial damage is suspected as the initiator.
¡@
- Abnormal intravascular platelet aggregation leads to microthrombi,
resulting in thrombocytopenia, hemolytic anemia, and end organ ischemia.
¡@
- TTP is known for central nervous system involvement, while HUS
predominantly affects the kidneys.
¡@
- Significant overlap exists in the clinical manifestations of TTP and HUS.
Diagnosis
TTP or HUS
¡@
- Both are clinical diagnoses. Tissue biopsy is not required.
¡@
- Obligate findings for either TTP or HUS include hemolytic anemia (hematocrit
<30% with schistocytes on peripheral smear) and thrombocytopenia under
100,000/mcL (50% of patients will have counts <20,000/mcL).
¡@
- TTP - Severe thrombocytopenia, hemolytic anemia, neurologic
abnormalities (headache, altered consciousness, seizures, hemiparesis),
fever
¡@
- HUS - Thrombocytopenia, hemolytic anemia, acute renal failure (rising
blood urea nitrogen [BUN] and creatinine with proteinuria, hematuria, or
oliguria/anuria)
¡@
- Signs and symptoms of TTP and HUS may overlap. Renal involvement occurs in
80% of cases of TTP; neurologic involvement occurs in 50% of cases of HUS
¡@
- Differentiation between TTP, HUS, and HELLP can be difficult or even
impossible, especially when the onset is in the second or third trimester.
Delivery leads to resolution with preeclampsia, but the condition will
continue or worsen after delivery with TTP/HUS. If suspected PIH/HELLP does
not improve after 48-72 after delivery, consider TTP/HUS.
Clinical manifestations
TTP and HUS
¡@
- Presenting symptoms often are nonspecific (eg, lethargy, nausea and
vomiting, headaches, weakness, fever, shortness of breath), although 67%
present with bleeding.
¡@
- Hypertension may be observed in as many as 75% of cases.
¡@
- Hemolysis and anemia may be absent at presentation in 50% of cases.
¡@
- Fibrinogen levels are within the reference range, and DIC is rare.
¡@
- Long-term sequelae, such as hypertension and chronic renal failure, are
observed in 44% of patients with TTP or HUS.
¡@
- The maternal mortality rate is 15%.
¡@
- Recurrences are common (50%).
Fetal/neonatal risks
The perinatal mortality rate is as high as 30% because of preterm delivery,
growth restriction, and intrauterine fetal demise.
Treatment
¡@
- Plasmapheresis is the first-line therapy. Plasmapheresis removes
platelet-aggregating substances causing TTP and HUS. Treatment is 90%
successful with TTP but is less successful with HUS.
¡@
- Steroids have been used, often in conjunction with plasmapheresis.
However, steroids are less effective than plasmapheresis (25% response rate).
¡@
- Platelet transfusions should be avoided when possible because they can
cause a clinical deterioration. Use platelet transfusions only for
uncontrolled or intracranial bleeding.
¡@
- Other therapies include immunosuppressive agents (vincristine,
azathioprine, cyclosporine), splenectomy for TTP, and hemodialysis for HUS.
¡@
- Premature termination of pregnancy has been associated with relapse.
Delivery should be considered only when no response to other therapies occurs.
Other immunologic conditions
Systemic lupus erythematosus, antiphospholipid syndrome
¡@
- In Burrows' study of platelet counts in pregnancy, 8 mothers had SLE,
accounting for 0.8% of all thrombocytopenic gravidas. None of their infants
had thrombocytopenia.
¡@
- Although both SLE and APS can cause fetal/neonatal complications (eg,
heart block, second and third trimester fetal demise), thrombocytopenia plays
no significant role.
Hypersplenism
¡@
- Congestion of the spleen results in sequestration of platelets.
¡@
- Hypersplenism often is observed in association with cirrhosis of the
liver.
¡@
- The spleen usually is palpable and enlarged.
¡@
- The thrombocytopenia from hypersplenism usually is not associated with
bleeding disorders.
Medications
¡@
- Well-known agents that cause thrombocytopenia include heparin, quinine,
quinidine, zidovudine (ZDV), and sulfonamides.
¡@
- Almost all medications can result in transient thrombocytopenia.
Viral illnesses
Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) are well-known
causes, although almost all viruses can result in thrombocytopenia.
Pathophysiology
Causes transient bone marrow suppression
Fetal/neonatal risks
No significant thrombocytopenia occurs.
Treatment
The condition usually is self-limited and requires no treatment.
Disseminated intravascular coagulation
DIC usually is associated with bleeding.
¡@
- DIC is observed obstetrically with abruption and postpartum hemorrhage.
¡@
- DIC is associated with low fibrinogen, elevated fibrin split products, and
D-dimers.
Alloimmune thrombocytopenia
Although not a maternal thrombocytopenia, alloimmune thrombocytopenia
represents the most common cause for profound fetal/neonatal thrombocytopenia
and intracranial hemorrhage in the infant.
Alloimmune thrombocytopenia has no effect on maternal platelet counts.
Incidence
Incidence is 1 per 1000-2000 live births.
Pathophysiology
Equivalent of Rh disease for platelets
¡@
- Maternal sensitization to antigens on the surface of the fetal platelets
results in alloantibodies, which cross the placenta.
¡@
- Involved platelet antigens include PlA1, Zwa, Bra,
Baka, and PlA2.
¡@
- Unlike Rh disease, alloimmune thrombocytopenia can affect the first
pregnancy. Half of all cases occur in the first pregnancy and are not
preventable.
Maternal clinical manifestations
No maternal clinical manifestations occur because platelet count is within
the reference range.
Fetal/neonatal risks
¡@
- Risks include petechiae, ecchymosis, and intracranial hemorrhage (10-20%).
Intracranial hemorrhage can occur in utero, resulting in hemorrhage,
porencephalic cysts, and obstructive hydrocephalus.
¡@
- In Burrows?study, 19 pregnancies were complicated by alloimmune
thrombocytopenia. Nine infants were born with severe thrombocytopenia.
Intracranial hemorrhage was observed in 3 fetuses, one with a fetal demise; no
new cases occurred in neonates. Alloimmune thrombocytopenia accounted for all
the thrombocytopenia-related fetal morbidity and mortality in the study.
Treatment
Treatment is not well established.
¡@
- Therapies have included maternal IVIG administration, steroids, weekly
fetal platelet transfusions of irradiated PlA1–negative platelets
(often from maternal source), with IVIG emerging as the first-line therapy.
¡@
- PUBS is utilized to assess the response to medical therapy; however, a
significantly higher risk of fetal exsanguination exists with PUBS.
Prevention
The key to prevention is the recognition of a previously affected infant with
alloimmune thrombocytopenia because recurrence is close to 100% and subsequent
pregnancies can be more severely affected than the first.
|
CONCLUSION |
¡@ |
- GT is the most common cause of thrombocytopenia during pregnancy (70%),
but other underlying causes must be considered as well.
¡@
- A thorough history and physical examination will rule out most causes.
¡@
- Look at the remainder of CBC and smear to rule out pancytopenia and
platelet clumping associated with pseudothrombocytopenia.
¡@
- If no antecedent history of thrombocytopenia is present and platelet
counts are above 70,000/mcL, the condition is more likely to be GT.
¡@
- If platelet counts fall below 50,000/mcL or if a preexisting history of
thrombocytopenia is present, the condition is more likely to be ITP.
¡@
- Direct or circulating antiplatelet antibodies has no utility in the workup
of thrombocytopenia in pregnancy because they usually are nonspecific and will
not distinguish GT from ITP.
¡@
- Follow platelet counts every 1-2 months or more frequently if the patient
is symptomatic.
¡@
- Cesarean deliveries should be reserved for obstetrical indications only
because abdominal delivery itself has not been demonstrated to be a cause for
intracranial hemorrhage.
¡@
- Invasive procedures to determine fetal platelet counts (scalp sampling,
PUBS) no longer are considered necessary because an infant who is
thrombocytopenic may be delivered abdominally.
¡@
- With ITP, obtain cord blood at delivery for platelet count and notify the
pediatricians to assess neonatal platelet counts due to the risk for continued
quantitative platelet decline and postnatal hemorrhage.
¡@
- For GT, document normalization of maternal platelet counts after delivery.
|
BIBLIOGRAPHY |
¡@ |
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