Predictors of Pregnancy Outcome in Essential Thrombocythemia: A Single Institution Study of 63 Pregnancies.
Authors: Gangat Naseema , Wolanskyj Alexandra , Schwager Susan , Tefferi Ayalew 
Published: April 2020

Background: Essential thrombocythemia (ET) frequently occurs in women of childbearing age. Recently, an increased risk of pregnancy complications was reported in patients with ET carrying the JAK2V617F mutation (Passamonti et al. Blood. 2007;110:485). In the current study, we sought to validate this observation as well as identify other predictors of pregnancy loss in ET.

Methods: Data was abstracted from the medical records of a consecutive cohort of patients with WHO-defined ET seen at the Mayo Clinic. Patient characteristics and pregnancy outcome are summarized using descriptive statistics. The analysis of risk factors associated with pregnancy complications was carried out by both univariate and multivariate analyses.

Results: i) Patient characteristics at ET diagnosis A total of 63 pregnancies were recorded in 36 women at or after their diagnosis of ET. At diagnosis of ET, median (range) values were: age 26 years (15–36), platelet count 1350 x 109/L (683–3300), hemoglobin level 13.3 g/dL (10.5–16) and leukocyte count 9.3 x109/L (5–26.9). JAK2V617F mutation analysis was performed in 20 patients; half were positive. Only 5 patients had a history of thrombosis at diagnosis. Follow-up after ET diagnosis was for a median of 82.9 months (range, 6.5–340.8 months).

ii) Outcome of first pregnancy at or after diagnosis of ET A total of 36 first pregnancies were documented at or after the diagnosis of ET. At the time, median (range) values were: time from diagnosis 25.5 months (0–155), age 28 years (20–36), platelet count 840 x 109/L (255–1998), hemoglobin 12.9 g/dl (9–16.6) and leukocyte count 8.4 x109/L (6.6–19.8). Seven of the 36 (19%) women were receiving cytoreductive therapy at time of conception: anagrelide (n=4), interferon (n=1), hydroxyurea (n=1) and radiophosphorus (n=1). Aspirin therapy was documented in 53% of the women at time of conception and in 69% during the first trimester of their pregnancy.

Among the 36 first pregnancies, 61% (n=22) resulted in live birth and 39% (n=14) in fetal loss. Twelve of the 14 pregnancy losses occurred during the first trimester (10 spontaneous miscarriages, 1 ectopic pregnancy and 1 therapeutic abortion) and the remaining two during the second trimester. Maternal complications occurred in 11% (n=4) of pregnancies and included pre-eclampsia (n=1), hematoma after Cesarean-section (n=2) and post-partum hemorrhage (n=1).

iii) Predictors of first pregnancy outcome in ET Pregnancy outcome, in terms of live birth versus miscarriage did not correlate with age (p=0.27), presence of cardiovascular risk factor (p=0.76), platelet count (p=0.49), leukocyte count (p=0.67) or hemoglobin level (p=0.31). Similarly, pregnancy loss was similar between JAK2V617F-positive (4 of 10 pregnancies) and JAK2V617F-negative (4 of 10 pregnancies) patients (p&gt;0.9). Furthermore, among 5 cases of 3 consecutive miscarriages, 4 were JAK2V617F-negative. Interestingly, the rate of pregnancy loss was only 21% among 24 patients receiving aspirin therapy during the first trimester as compared to 75% among the 12 patients in whom no such treatment was documented (p=0.002).

iv) Second and subsequent pregnancy outcome Seventeen second pregnancies were recorded; 71% (n=12) resulted in live birth that included 8 of 9 patients with successful and 4 of 8 with unsuccessful first pregnancies (p=0.07). The trend was similar among 7 third pregnancies, which resulted in only one live birth; 5 of the 6 fetal losses occurred in women with history of first pregnancy loss (p=0.09).

Conclusion: The current study does not support the recently communicated association between the presence of JAK2V617F and increased risk of pregnancy loss in ET. Instead, two parameters of potential importance for predicting pregnancy outcome in ET were identified; the occurrence of a miscarriage might be a marker for a similar event during subsequent pregnancies whereas aspirin therapy during the first trimester might be beneficial.