Thrombocytopenia in Pregnancy

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 ¡@

Definition and severity

¡@

Manifestations

¡@

ETIOLOGIC CLASSIFICATION ¡@

The etiologic classification for thrombocytopenia can be divided into 3 broad categories¡Xincreased destruction or utilization, decreased production, and sequestration.

¡@

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

¡@

Diagnosis

ITP is a diagnosis of exclusion.

¡@

Clinical manifestations

¡@

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.

¡@

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:

¡@

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.

¡@

GESTATIONAL THROMBOCYTOPENIA ¡@

GT is also known as pregnancy-induced, essential, benign, or incidental thrombocytopenia of pregnancy.

Incidence

¡@

Pathophysiology

Pathophysiology is unknown but is thought to represent accelerated consumption of platelets.

Diagnosis

¡@

Clinical manifestations

¡@

Fetal/neonatal risks

¡@

Management considerations

¡@

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

¡@

Pathophysiology

¡@

Diagnosis and classification of HELLP syndrome

¡@

Clinical manifestations

¡@

Fetal/neonatal risks

¡@

Treatment

¡@

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

¡@

Clinical manifestations

No clinical manifestations exist.

Diagnosis

¡@

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

¡@

Diagnosis

TTP or HUS

¡@

Clinical manifestations

TTP and HUS

¡@

Fetal/neonatal risks

The perinatal mortality rate is as high as 30% because of preterm delivery, growth restriction, and intrauterine fetal demise.

Treatment

¡@

Other immunologic conditions

Systemic lupus erythematosus, antiphospholipid syndrome

¡@

Hypersplenism

¡@

Medications

¡@

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.

¡@

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 clinical manifestations

No maternal clinical manifestations occur because platelet count is within the reference range.

Fetal/neonatal risks

¡@

Treatment

Treatment is not well established.

¡@

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 ¡@

BIBLIOGRAPHY ¡@