Primary thrombocythemia in pregnancy: A report of two cases

B. Mercer, MD, J. Drouin, MD, E. Jolly, MD, and G. d' Anjou, MD

Ottawa, Ontario, Canada

We report two cases of primary thrombocythemia diagnosed during pregnancy. One patient developed transient visual field defects. She was treated with plateletpheresis at term and delivered of a normal child by cesarean section. The second patient was not treated. Intrauterine fetal death occurred at 36 weeks' gestation from multiple placental infarcts. In cases of primary thrombocythemia, we suggest close

monitoring of both mother and fetus throughout pregnancy. (AM J OBSTET GYNECOL 1988;159:127-8.)

Key words: Primary thrombocythemia, pregnancy, myeloproliferative disorder, plateletpheresis

Primary thrombocythemia is a rare myeloprolifera­tive disorder of unknown cause characterized by ele­vation in platelet counts and increased marrow mega­karyocytes. The disease is marked by hemorrhagic or thrombotic complications related to the abnormal platelet numbers and function. Controversy exists concerning prognosis relative to age. Some authors re­port a benign course in the younger patient, whereas others have encountered serious thrombotic problems. Tests of platelet function do not appear to correlate well with the risk of thrombotic or hemorrhagic com­plications.

Little is known about the course of this disease in pregnancy, because it usually occurs in the late repro­ductive and menopausal years. To date, only one case of primary thrombocythemia in pregnancy has been reported.'

We report two cases of this condition diagnosed dur­ing pregnancy in which both maternal and fetal com­plications occurred.

Case reports Case I. A 30-year-old woman (gravida 1, para 0)

was referred in September 1981 at 30 weeks' gesta­tion because of marked thrombocytosis. She had ex­perienced mild gum bleeding as well as transient left visual field blurring during her pregnancy. The phys­ical examination was normal. Her hemoglobin level was 11 gm/di, the white blood count was 13,000 cells/mm', and the platelet count was 1.8 x 106 cells/mm'. Me­gathrombocytes were noted in her blood film. A bone marrow aspirate showed an isolated increase in mega-

From the Departments of Medicine and Obstetrics and Gynecology, Ottawa General Hospital, University of Ottawa.

Received for publication June 22, 1987; revised October 26, 1987; accepted November 20, 1987.

Reprint requests:]. Drouin, MD, Division of Hematology, Ottawa General Hospital, 501 Smyth Road, Ottawa, Ontario KlH 8L6, Canada.

karyocyte number and volume and trace iron stores. Platelet aggregation was absent when using adenosine diphosphate, epinephrine, and collagen as agonists. The diagnosis of primary thrombocythemia was made. The patient was treated with plateletpheresis to keep her platelet count <2 x 10" cells/mm" at term. At 39 weeks' gestation a caesarean section was performed for fetal distress. A healthy male infant weighing 4020 gm was delivered, with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. The placenta showed no evidence of thrombosis or infarction. The patient suffered mul­tiple episodes of left visual field blurring and Bashes after her pregnancy. The diagnosis of right posterior cerebral artery insufficiency was made. She was sub­sequently treated with P" in 1983 and melphalan from June 1984 to the present. The patient's platelet count is <I x 10" cells/mm" and she is asymptomatic at present.

Case 2. A 26-year-old woman (gravida 2, para I) was diagnosed at 9 weeks' gestation after routine blood tests. She was asymptomatic and the physical ex­amination was normal. Her hemoglobin level was 12 .4 gm/di and the white blood count 12,400 cells/mm". Her platelet count was elevated at 1.37 x 106 cells/ mm", and her blood film showed megathrombocytes. Berne marrow aspiration showed increased megakaryocytes and numerous platelet clumps. Iron stores were nor­mal. Platelet function tests revealed decreased aggre­gation with adenosine diphosphate, epinephrine, and collagen and a normal response to ristocetin and ara­chidonic acid. The patient remained asymptomatic and her pregnancy was followed with serial clinical and ultrasonographic assessments. Platelet counts dropped spontaneously to 0.94 x 106 cells/mm' just before 36 weeks' gestation. At that time, after 3 days of decreased fetal movement, intrauterine fetal death was diagnosed. She was delivered of a macerated 2400 gm female in­fant with no identifiable anomaly in January 1986. The placenta showed numerous areas of acute and chronic infarction comprising 35% to 40% of the placental sur­face (Fig. 1). A 5 cm abruptio placentae was seen near an area of acute infarction.

127

128 Mercer et al. July 1988 Am J Obstet Gynecol

Fig. I. Placenta shows numerous chronic thrombotic infarcts (short arrows) and a 5 cm area of recent thrombosis (long arrow).

Comment Although patients with primary thrombocythemia

often have symptoms related to thrombosis or hem­orrhage, the young patient is frequently diagnosed in­cidentally at the time of assessment of an unrelated condition, as occurred in both our patients. The first patient experienced visual problems in pregnancy that were attributable to her disease. However, there were no placental infarcts and a healthy infant was delivered. The second patient lost her baby close to term because of repeated placental infarctions.

Persistent marked thrombocytosis (platelet count ;;i.1 x 106 cells/ mm') usually signifies that a myelopro­liferative disorder is present rather than reactive thrombocytosis. There is controversy as to whether the platelet count should be normalized in an attempt to minimize risks of thrombosis or hemorrhage. Platelet function studies unfortunately are of little predictive value in identifying patients at risk of these complica­tions. Primary thrombocythemia can be treated with alkylating agents, P'2 to decrease marrow prolifera­tion, plateletpheresis to decrease circulating counts, or antiaggregating agents such as acetylsalicylic acid to

minimize hyperaggregability. Myelosuppressive ther­apy is usually withheld until symptoms develop, espe­cially in young patients.

The management of primary thrombocythemia in pregnancy is problematic. Our experience supports the report of Kaibara et al. 1 that there is a risk of placental

thrombosis leading to chronic placental insufficiency, intrauterine growth retardation, and even fetal death. There are also maternal risks of hemorrhage or throm­bosis, as shown in our first patient. In pregnancy, it is preferable to avoid chemotherapeutic agents because of their potential carcinogenic and teratogenic effects. Long-term treatment with acetylsalicylic acid may help minimize the risk of thrombosis in these patients. Our experience suggests that plateletpheresis may play a useful role in decreasing the number of platelets for a short period, such as immediately before delivery.

We recommend close monitoring of mother and fe­tus in these patients, in view of the serious complications that may arise. Placental function should be monitored with fetal growth, movement, and serial nonstress test­ing. Ultrasonic Doppler flow studies may also prove to be of value. These measures, along with the use of aspirin and plateletpheresis, may decrease maternal morbidity and enhance fetal survival in this condition.

We thank Dr. Jacalyn Duffin for her helpful comments.

REFERENCE 1. Kaibara M, Kobayashi T, Matsumoto S. Idiopathic throm­

bocythemia and pregnancy: Report of a case. Obstet Gy­necol l 985;65(suppl): 18S-9S.

A complete list of references is available from the authors on request.