Elsevier

Blood Reviews

Volume 22, Issue 5, September 2008, Pages 235-245
Blood Reviews

Review
Management of Philadelphia negative chronic myeloproliferative disorders in pregnancy

https://doi.org/10.1016/j.blre.2008.03.007Get rights and content

Summary

The management of pregnancy in Philadelphia negative chronic myeloproliferative disorders (CMPDs) is an increasingly frequent problem. In the literature, most pregnancies are reported for women with essential thrombocythemia (ET) with about 400 pregnancies in about 200 women. In ET, first trimester abortion is the most frequent complication occurring in about one third of pregnancies. Interestingly, the incidence of maternal complications is relatively low with 3% for major thromboembolic and 2% for major bleeding events. The presence of the Jak2 mutation seems to be an independent predictor of pregnancy complications. Pregnancies in ET should be stratified according to underlying risk factors in low, high and highest risk pregnancies. Women with low risk pregnancies are treated with low-dose aspirin, whereas women with high and higher risk pregnancies may benefit from low-dose aspirin plus interferon alpha ± low molecular weight heparin throughout pregnancy and at least for six weeks post-partum. In polycythemia vera (PV) there is only very few information on pregnancy outcome with 36 pregnancies reported in the literature. According to these data pregnancy in PV is per se a high risk situation. Accordingly, all women with PV should be treated with low-dose aspirin. Some pregnant PV patients may benefit from a more intensive therapy including interferon alpha ± low molecular weight heparin throughout pregnancy and at least for six weeks post-partum.

Section snippets

Pregnancy in CMPDs: an increasingly frequent problem

In the last decade, two factors have largely contributed to a higher prevalence and earlier diagnosis of CMPDs. First, the advent of automatic platelet counting has revealed an increased number of asymptomatic patients. The last point is becoming more relevant, if the test for the presence of the Jak2 mutation will be more widely used in patients with an otherwise unexplained thrombocytosis or erythrocytosis.6 Second, earlier forms of CMPDs are being increasingly detected in patients presenting

Review of the literature on ET and pregnancy

Essential thrombocythemia (ET) is a disease with a female preponderance and a second peak incidence in women of childbearing age.12 Accordingly, most literature relating to pregnancy exists for ET. Since the first report of Hoagland and Silverstein 1978 on an uncomplicated course of pregnancy in two young women with ET about 400 pregnancies have been reported in various case reports in about 200 women with ET.13 It is important to note, that the available data on ET in pregnancy are both

Increased risk of pregnancy complications in patients with ET carrying the Jak2 mutation

Until recently, risk factors to predict pregnancy outcome in women with ET have not been identified. In a recent paper risk factors associated with pregnancy complications were studied in 103 pregnancies in 62 women with ET.23 The live birth rate was 64% and thus very similar compared with the above reported live birth rate of 61% in our literature review. A full-term normal delivery (FTND) was seen in 51% (53% in our literature review). Foetal complications occurred in 40% of pregnancies

Treatment options for managing ET and pregnancy

The various reported treatment options range from no therapy with close observation, antiplatelet therapy with aspirin, heparin or low molecular weight heparin (LMWH), plateletpheresis to the use of cytoreductive agents.28 Before making a decision to use a specific therapy one should analyze whether the potential beneficial effects outweigh the potential hazards.

Aspirin is the most frequently used drug in all published pregnancies in ET.2 In most papers there is the impression of a positive

Review of the literature on PV and pregnancy

In comparison with the situation in essential thrombocythemia, pregnancy in polycythemia vera (PV) is a rare event. Polycythemia vera is a disease with a male preponderance. The mean age of diagnosis is 60 years and only 15% of patients are <40 years or below at presentation. In the largest single centre series reported so far, 18 pregnancies in eight patients with PV were published.38 In a review on PV in pregnancy containing the results of the mentioned single centre experience a total of 36

Treatment options for managing PV and pregnancy

In the largest single centre series 18 pregnancies were reported in eight PV patients.38 Seven of these pregnancies were managed by standard antenatal care without any specific therapy concerning PV. The remaining 11 of 18 pregnancies were managed following a formal protocol. These patients received tailored management principally comprising tight control of the hematocrit by venesection. The target hematocrit was less than 45%. All patients received aspirin (75 mg) and prophylactic LMWH for

Planning pregnancy and preconception phase in ET or PV

Before planning pregnancy thorough discussions with the mother and father about the problems and complications should take place. If pregnancy is already established there is generally no indication for a therapeutic abortion.3 Of course, the individual risk is dependent on the patient’s history, prior complications and additional risk factors. Patients should ideally be under joint care of a consultant obstetrician experienced in the care of patients with high-risk pregnancies and a

Risk stratification of pregnancy in ET

In ET and pregnancy, we suggest defining three different categories of risks: low, high and highest risk.

If all of the following factors are present then the pregnancy should be considered at low risk:

  • 1.

    No prior ET related complications, and

  • 2.

    Absence of hereditary thrombophilic factors, and

  • 3.

    Age <35 years

  • 4.

    Platelet count <1000 × 109/l

If any of the following factors are present then the pregnancy should be considered at high risk:

  • 1.

    Previous microcirculatory disturbances, or

  • 2.

    Presence of two or more hereditary

Management of an established pregnancy in ET (see Fig. 1)

Close monitoring of the blood count is mandatory. We recommend a full blood count (FBC) every 4 weeks until the 24th week and then 2 weekly. Platelet counts should not exceed 1000–1500 × 109/l because an acquired von Willebrand’s syndrome is frequently encountered at very high platelet counts and may cause severe bleeding. However, the natural fall of the platelet count may anyway obviate or reduce the need for a therapeutic intervention. Blood pressure and urinanalysis should be performed at

Risk stratification of pregnancy in PV

Due to a higher complication rate pregnancy in PV is per se a high risk situation. We suggest two different categories of risks: high and highest risk pregnancy.

If any of the following factors are present then pregnancy in PV should be considered at high risk:

  • 1.

    Previous microcirculatory disturbances, or

  • 2.

    Presence of two or more hereditary thrombophilic factors (e.g. Factor V Leiden mutation plus a positive lupus anticoagulants etc.),or

  • 3.

    Severe complications in a previous pregnancy (⩾3 first trimester

Management of an established pregnancy in PV (see Fig. 2)

Close monitoring of the blood count is mandatory. We recommend a full blood count (FBC) every 4 weeks until the 24th week and than 2 weekly (see Fig. 2). The hematocrit should be kept in the middle of the normal range appropriate for gestation with venesection and/or cytoreductive therapy. However, the natural fall of the hematocrit during pregnancy may anyway obviate or reduce the need for a therapeutic intervention. Ion supplementation is not recommended during pregnancy because this may

Delivery in ET or PV

Epidural or spinal analgesia is not generally contraindicated in ET or PV. Some obstetric anesthetists advocate the termination of aspirin therapy one or two weeks prior to delivery. In these situations aspirin should be replaced by heparin. The last dose of heparin should be administered about 12 hours before labour is expected. During labour dehydration should be avoided and the use of thromboembolic deterrent stockings is necessary. Regional anaesthetic techniques should not be used until 12

Postpartum period and breast feeding in ET and PV

The immediate puerperium is indeed the time of greatest risk for venous thrombosis for which prophylaxis with LMWH is indicated.9 Due to this persistent thromboembolic risk during the postpartum period it is recommended to continue both low-dose aspirin and LMWH prophylaxis for at least six weeks postpartum. Severe platelet-mediated microvascular disturbances as well as venous thromboembolic complications have been reported in ET post-delivery. Rebound thrombocytosis is encountered during the

Acknowledgments

This work was supported by the German Kompetenznetz “Acute and chronic Leukemias” and the European LeukemiaNet (ELN).

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