January 14, 1998

James N. George, MD

Professor of Medicine

Chief, Hematology-Oncology Section

The diagnosis and management of thrombocytopenia during pregancy presents difficult diagnostic and management

problems. The diagnostic distinction among the potential etiologies for thrombocytopenia is often impossible, yet the

diagnosis has major importance for management. Furthermore, management involves not only the care of the mother, but

the anticipation of risk for thrombocytopenia in the infant. The following are the major etiologies for thrombocytopenia

during pregnancy:

Gestational Thrombocytopenia. In many women, mild thrombocytopenia occurs toward the end of pregnancy, and the

platelet count returns to normal within days after delivery. The etiology for this phenomenon is unknown. This is the most

common cause of thrombocytopenia during pregnancy, occurring in approximately 5% of women at term. Gestational

thrombocytopenia is characterized by: (1) asymptomatic, mild thrombocytopenia, (2) with no past history of

thrombocytopenia (except possibly during previous pregnancy, (3) that occurs during late gestation, (4) that is not

associated with fetal thrombocytopenia, and (5) that resolves spontaneously after delivery. Platelet counts are typically

over 70,000, with about two-thirds being between 130,000 and 150,000 (just below the lower limit of normal). Idiopathic

thrombocytopenic purpura (ITP), cannot be distinguished from gestational thrombocytopenia with certainty because the

diagnosis of both conditions is based upon the observation of thrombocytopenia with no other apparent cause. Although

ITP may compose a higher percentage of cases when the platelet count is less than 70,000, or when thrombocytopenia is

discovered earlier in pregnancy, gestational thrombocytopenia may still be the appropriate diagnosis if the

thrombocytopenia resolves spontaneously after delivery. However, severe, refractory thrombocytopenia, presumably due

to ITP, may also remit after delivery.

The differential diagnosis between ITP and gestational thrombocytopenia is generally of little clinical importance with

regard to the mother, because cases in which the diagnosis is unclear involve mild thrombocytopenia that does not threaten

maternal health. The differential diagnosis is clinically important with regard to the fetus, because ITP with even mild

thrombocytopenia may cause thrombocytopenia in the fetus, whereas gestational thrombocytopenia does not. Current

tests for identifying anti-platelet antibodies do not help in the differential diagnosis.

Idiopathic Thrombocytopenic Purpura (ITP). As described above, thrombocytopenia first discovered during

pregnancy may be either ITP or gestational thrombocytopenia. The most important diagnostic step is to search the

patient's record for evidence of thrombocytopenia when she was not pregnant. If no prior platelet counts are available,

then the distinction rests upon the severity of thrombocytopenia and the time of its occurrence during pregnancy. More

severe thrombocytopenia occurring earlier during pregnancy is more likely to be ITP. Management of the mother with ITP

during pregnancy is essentially the same as in a non-pregnant patient, only the management is more conservative.

Splenectomy hopefully is deferred until after delivery, and cytotoxic agents are avoided.

The major focus of concern is on the risk for neonatal thrombocytopenia. In contrast to fetal alloimmune

thrombocytopenia, which may be severe and cause intrauterine fetal hemorrhage, intrauterine fetal hemorrhage has not

been reported in ITP. The main concern is for trauma at birth and its risk of provoking cerebral hemorrhage in the

newborn infant. This serious complication is rare. Among infants born to women with ITP, 10% have platelet counts less

than 50,000. Only 4% have counts less than 20,000 and are therefore at risk for hemorrhage at birth. Although it seems

reasonable that cesarean section delivery is safer for the infant than vaginal delivery, there are no data to support this

hypothesis. Current obstetrical recommendations are to proceed with routine vaginal delivery, reserving cesarean section

for obstetrical indications. It is important to recognize that intracerebral hemorrhage may occur following birth, as the

platelet count may fall further during the first week.

Preeclamsia. About 5 to 10% of all pregnant women have preeclampsia, defined as hypertension and proteinuria

beginning during the second half of gestation. From a hematologic standpoint, preeclampsia is the second most common

cause of thrombocytopenia during pregnancy, since about 15% of patients with preeclampsia develop thrombocytopenia.

It is managed by obstetrical care, with delivery resulting in predictable resolution. The difficulty is to distinguish

preeclampsia from thrombotic thrombocytopenic purpura / hemolytic-uremic syndrome (TTP-HUS).

Thrombotic Thrombocytopenic Purpura / Hemolytic Uremic Syndrome (TTP-HUS). Because current treatment

with plasma exchange has changed TTP-HUS in adults from a typically fatal disease to one with predictable recovery,

urgent diagnosis is essential. Because of the urgency for diagnosis, the only diagnostic criteria currently required are

thrombocytopenia and microangiopathic hemolytic anemia without another apparent cause. Preeclampsia is another cause

of both of these criteria. Even the additional diagnostic criteria of TTP-HUS, acute renal failure and neurologic signs, can

be part of the preeclampsia-eclampsia syndrome. Therefore these two syndromes may not be distinguishable. This inability

to distinguish TTP-HUS from preeclampsia clinically is consistent with the inability to distinguish these two syndromes

pathologically. The appearance of renal biopsies in both syndromes is identical. The clinical distinction requires careful,

sometimes hourly, follow-up after delivery. Although the signs of preeclampsia spontaneously resolve, they may initially

become worse in the first several days following delivery. By definition, if the symptoms resolve following delivery,

TTP-HUS is ruled out. However, progressive and fatal TTP-HUS can occur during pregnancy, and 10% (15/155) of

patients with TTP-HUS in Oklahoma between 1989 and 1997 were associated with pregnancy.

References:

1.Burrows RF and Kelton JG: Fetal thrombocytopenia and its relation to maternal thrombocytopenia. New Eng J

Med 1993;329:1463.

2.Letsky EA and Greaves M: Guidelines on the investigation and management of thrombocytopenia in pregnancy and

neonatal alloimmune thrombocytopenia. Brit J Haematol 1996;95:21.

3.Ballem PJ: Diagnosis and management of thrombocytopenia in obstetric syndromes. In Obstetric Transfusion

Practice, Sacher RA, Brecher ME (eds), Amer Assoc of Blood Banks, Bethesda, MD, 1993, pp. 49-76.