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Thromb Haemost 2016; 116(04): 613-617
DOI: 10.1160/TH16-02-0099
Theme Issue Article
Schattauer GmbH

Haematological malignancies in pregnancy: An overview with an emphasis on thrombotic risks

Netanel A. Horowitz
1   Department of Hematology & Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
2   Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
,
Noa Lavi
1   Department of Hematology & Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
,
Yona Nadir
1   Department of Hematology & Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
2   Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
,
Benjamin Brenner
1   Department of Hematology & Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
2   Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
› Author Affiliations
Further Information

Publication History

Received: 07 February 2016

Accepted after major revision: 29 June 2016

Publication Date:
02 December 2017 (online)

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Summary

With increase of maternal age, the incidence of haematological malignancies during pregnancy is rising and posing diagnostic and treatment challenges. Lymphoma is the fourth most common malignancy diagnosed in pregnancy; Hodgkin lymphoma is more frequent in pregnant women than non-Hodgkin lymphoma (NHL). The proportion of highly aggressive lymphomas in pregnant women is significantly higher than in non-pregnant women of reproductive age. Reproductive organ involvement is observed in almost half of pregnant women with NHL. The association of acute leukaemia and pregnancy is infrequent and it is assumed that pregnancy does not accelerate the disease course. Both cancer and pregnancy induce a procoagulant state which can lead to maternal venous thromboembolism (VTE) and placental occlusion. Pregnancy in woman with myeloproliferative neoplasms (MPN) promotes thrombotic environment, associating with an augmented risk of placental thrombosis, intrauterine growth retardation or loss and maternal thrombotic events.Haematological malignancies during pregnancy often require urgent diagnosis and management and are associated with potential adverse fetal outcomes. Most chemotherapeutic agents are teratogenic and should be avoided during the first trimester. Their use during the second and third trimesters may cause intrauterine growth restriction, premature birth and intrauterine fetal death. All chemotherapeutic drugs should be administered only after a detailed discussion with the patient and with close fetal monitoring. Chemotherapy and biological agents might also augment thrombotic risk. Guidelines for VTE prophylaxis in pregnant women with hematologic malignancies, apart from MPN, are currently unavailable, and therefore, clinical judgment should be made in each case.

Keywords

Haematological malignancy - pregnancy - hypercoagulability - venous thromboembolism - chemotherapy
 

  • References

  • 1 Hurley TJ, McKinnell JV, Irani MS.. Haematologic malignancies in pregnancy. Obstet Gynecol Clin North Am 2005; 32: 595-614.
    CrossrefPubMedGoogle Scholar
  • 2 Abadi U, Koren G, Lishner M.. Leukaemia and lymphoma in pregnancy. Haematol Oncol Clin North Am 2011; 25: 277-291. vii
    CrossrefPubMedGoogle Scholar
  • 3 Heit JA.. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12: 464-474.
    CrossrefPubMedGoogle Scholar
  • 4 Bleau N, Patenaude V, Abenhaim HA.. Risk of venous thrombo-embolic events in pregnant patients with cancer. J Matern Fetal Neonatal Med 2016; 29: 380-384.
    PubMedGoogle Scholar
  • 5 Lishner M, Avivi I, Apperley JF. et al. Haematologic Malignancies in Pregnancy: Management Guidelines From an International Consensus Meeting. J Clin Oncol. 2015 Epub ahead of print
    PubMedGoogle Scholar
  • 6 Piccin A, Murphy WG, Smith OP.. Circulating microparticles: pathophysiology and clinical implications. Blood Rev 2007; 21: 157-171.
    CrossrefPubMedGoogle Scholar
  • 7 Aharon A, Brenner B.. Microparticles, thrombosis and cancer. Best Pract Res Clin Haematol 2009; 22: 61-69.
    CrossrefPubMedGoogle Scholar
  • 8 Tzoran I, Rebibo-Sabbah A, Brenner B. et al. Disease dynamics in patients with acute myeloid leukaemia: New biomarkers. Exp Haematol 2015; 43: 936-943.
    CrossrefPubMedGoogle Scholar
  • 9 Nadir Y, Brenner B.. Heparanase coagulation and cancer progression. Best Pract Res Clin Haematol 2009; 22: 85-92.
    CrossrefPubMedGoogle Scholar
  • 10 Nadir Y, Kenig Y, Drugan A. et al. Involvement of heparanase in vaginal and cesarean section deliveries. Thromb Res 2010; 126: e444-450.
    CrossrefPubMedGoogle Scholar
  • 11 Muller AM, Ihorst G, Mertelsmann R. et al. Epidemiology of non-Hodgkin's lymphoma (NHL): trends, geographic distribution, and etiology. Ann Haematol 2005; 84: 1-12.
    PubMedGoogle Scholar
  • 12 Pereg D, Koren G, Lishner M.. The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy. Haematologica 2007; 92: 1230-1237.
    CrossrefPubMedGoogle Scholar
  • 13 Stewart Jr. HL, Monto RW.. Hodgkin's disease and pregnancy. Am J Obstet Gynecol 1952; 63: 570-578.
    CrossrefPubMedGoogle Scholar
  • 14 Woo SY, Fuller LM, Cundiff JH. et al. Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease. Int J Radiat Oncol Biol Phys 1992; 23: 407-412.
    CrossrefPubMedGoogle Scholar
  • 15 Horowitz NA, Benyamini N, Wohlfart K. et al. Reproductive organ involvement in non-Hodgkin lymphoma during pregnancy: a systematic review. Lancet Oncol 2013; 14: e275-282.
    CrossrefPubMedGoogle Scholar
  • 16 Groves FD, Linet MS, Travis LB. et al. Cancer surveillance series: non-Hodgkin's lymphoma incidence by histologic subtype in the United States from 1978 through 1995. J Natl Cancer Inst 2000; 92: 1240-1251.
    CrossrefPubMedGoogle Scholar
  • 17 Morton LM, Wang SS, Devesa SS. et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107: 265-276.
    CrossrefPubMedGoogle Scholar
  • 18 Molyneux EM, Rochford R, Griffin B. et al. Burkitt's lymphoma. Lancet 2012; 379: 1234-1244.
    CrossrefPubMedGoogle Scholar
  • 19 Ziepert M, Hasenclever D, Kuhnt E. et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28: 2373-2380.
    CrossrefPubMedGoogle Scholar
  • 20 Nadir Y, Brenner B, Gingis-Velitski S. et al. Heparanase induces tissue factor pathway inhibitor expression and extracellular accumulation in endothelial and tumour cells. Thromb Haemost 2008; 99: 133-141.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Nadir Y, Brenner B.. Heparanase procoagulant activity. Thromb Res 2012; 129 (01) S76-79.
    CrossrefPubMedGoogle Scholar
  • 22 Nadir Y, Brenner B.. Heparanase-A Link between Coagulation, Angiogenesis, and Cancer. Rambam Maimonides Med J 2012; 03: e0002.
    PubMedGoogle Scholar
  • 23 Bartlett RM, Nickles RJ, Barnhart TE. et al. Fetal dose estimates for (18)F-fluoro-L-thymidine using a pregnant monkey model. J Nucl Med 2010; 51: 288-292.
    CrossrefPubMedGoogle Scholar
  • 24 Oto A, Ernst R, Jesse MK. et al. Magnetic resonance imaging of the chest, abdomen, and pelvis in the evaluation of pregnant patients with neoplasms. Am J Perinatol 2007; 24: 243-250.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Shellock FG, Kanal E.. Policies, guidelines, and recommendations for MR imaging safety and patient management. SMRI Safety Committee. J Magn Reson Imaging 1991; 01: 97-101.
    CrossrefPubMedGoogle Scholar
  • 26 Muhler MR, Clement O, Salomon LJ. et al. Maternofetal pharmacokinetics of a gadolinium chelate contrast agent in mice. Radiology 2011; 258: 455-460.
    CrossrefPubMedGoogle Scholar
  • 27 Thomas X.. Acute myeloid leukaemia in the pregnant patient. Eur J Haematol 2015; 95: 124-136.
    CrossrefPubMedGoogle Scholar
  • 28 Sadural E, Smith Jr LG. Haematologic malignancies during pregnancy. Clin Obstet Gynecol 1995; 38: 535-546.
    CrossrefPubMedGoogle Scholar
  • 29 Feliu J, Juarez S, Ordonez A. et al. Acute leukaemia and pregnancy. Cancer 1988; 61: 580-584.
    CrossrefPubMedGoogle Scholar
  • 30 Peleg D, Ben-Ami M.. Lymphoma and leukaemia complicating pregnancy. Obstet Gynecol Clin North Am 1998; 25: 365-383.
    CrossrefPubMedGoogle Scholar
  • 31 Shapira T, Pereg D, Lishner M.. How I treat acute and chronic leukaemia in pregnancy. Blood Rev 2008; 22: 247-259.
    CrossrefPubMedGoogle Scholar
  • 32 Chelghoum Y, Vey N, Raffoux E. et al. Acute leukaemia during pregnancy: a report on 37 patients and a review of the literature. Cancer 2005; 104: 110-117.
    CrossrefPubMedGoogle Scholar
  • 33 Davis SM, Branch DW.. Thromboprophylaxis in pregnancy: who and how?. Obstet Gynecol Clin North Am 2010; 37: 333-343.
    CrossrefPubMedGoogle Scholar
  • 34 Ku GH, White RH, Chew HK. et al. Venous thromboembolism in patients with acute leukaemia: incidence, risk factors, and effect on survival. Blood 2009; 113: 3911-3917.
    CrossrefPubMedGoogle Scholar
  • 35 Tallman MS, Brenner B, Serna Jde L. et al. Meeting report. Acute promyelocytic leukaemia-associated coagulopathy, 21 January 2004, London, United Kingdom. Leuk Res 2005; 29: 347-351.
    CrossrefPubMedGoogle Scholar
  • 36 Dally N, Hoffman R, Haddad N. et al. Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukaemia-a single center experience in 34 patients. Thromb Res 2005; 116: 109-114.
    CrossrefPubMedGoogle Scholar
  • 37 Iseminger KA, Lewis MA.. Ethical challenges in treating mother and fetus when cancer complicates pregnancy. Obstet Gynecol Clin North Am 1998; 25: 273-285.
    CrossrefPubMedGoogle Scholar
  • 38 Dameshek W.. Some speculations on the myeloproliferative syndromes. Blood 1951; 06: 372-375.
    PubMedGoogle Scholar
  • 39 Spivak JL.. The chronic myeloproliferative disorders: clonality and clinical heterogeneity. Semin Haematol 2004; 41 (2 Suppl 3) 1-5.
    PubMedGoogle Scholar
  • 40 Vannucchi AM.. JAK2 mutation and thrombosis in the myeloproliferative neoplasms. Curr Haematol Malig Rep 2010; 05: 22-28.
    PubMedGoogle Scholar
  • 41 Kubota Y, Tanaka T, Ohnishi H. et al. Constitutively activated phosphatidylinositol 3-kinase primes platelets from patients with chronic myelogenous leukaemia for thrombopoietin-induced aggregation. Leukaemia 2004; 18: 1127-1137.
    CrossrefPubMedGoogle Scholar
  • 42 Falanga A, Marchetti M, Vignoli A. et al. V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules. Exp Haematol 2007; 35: 702-711.
    CrossrefPubMedGoogle Scholar
  • 43 Chong AY, Blann AD, Patel J. et al. Endothelial dysfunction and damage in congestive heart failure: relation of flow-mediated dilation to circulating endothelial cells, plasma indexes of endothelial damage, and brain natriuretic peptide. Circulation 2004; 110: 1794-1798.
    CrossrefPubMedGoogle Scholar
  • 44 Lussana F, Caberlon S, Pagani C. et al. Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idio-pathic myelofibrosis: a systematic review. Thromb Res 2009; 124: 409-417.
    CrossrefPubMedGoogle Scholar
  • 45 Vannucchi AM, Antonioli E, Guglielmelli P. et al. Prospective identification of high-risk polycythemia vera patients based on JAK2 (V617F) allele burden. Leukaemia 2007; 21: 1952-1959.
    CrossrefPubMedGoogle Scholar
  • 46 Passamonti F, Randi ML, Rumi E. et al. Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation. Blood 2007; 110: 485-489.
    CrossrefPubMedGoogle Scholar
  • 47 Nadir Y, Brenner B, Fux L. et al. Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.. Haematologica 2010; 95: 1927-1934.
    CrossrefPubMedGoogle Scholar
  • 48 Kogan I, Chap D, Hoffman R. et al. JAK-2 V617F mutation increases heparanase procoagulant activity. Thromb Haemost 2015; 115: 73-80.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Barbui T, Finazzi G.. Special issues in myeloproliferative neoplasms. Curr Haematol Malig Rep 2011; 06: 28-35.
    PubMedGoogle Scholar
  • 50 Harrison C.. Pregnancy and its management in the Philadelphia negative myeloproliferative diseases. Br J Haematol 2005; 129: 293-306.
    CrossrefPubMedGoogle Scholar
  • 51 Griesshammer M, Struve S, Harrison CM.. Essential thrombocythemia/poly-cythemia vera and pregnancy: the need for an observational study in Europe. Semin Thromb Hemost 2006; 32: 422-429.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 52 Barbui T, Barosi G, Grossi A. et al. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Haematology, the Italian Society of Experimental Haematology and the Italian Group for Bone Marrow Transplantation. Haematologica 2004; 89: 215-232.
    PubMedGoogle Scholar
  • 53 Gangat N, Wolanskyj AP, Schwager S. et al. Predictors of pregnancy outcome in essential thrombocythemia: a single institution study of 63 pregnancies. Eur J Haematol 2009; 82: 350-353.
    CrossrefPubMedGoogle Scholar
  • 54 Elliott MA, Tefferi A.. Thrombocythaemia and pregnancy. Best Pract Res Clin Haematol 2003; 16: 227-242.
    CrossrefPubMedGoogle Scholar
  • 55 Matalon ST, Ornoy A, Fishman A. et al. The effect of 6-mercaptopurine on early human placental explants. Hum Reprod 2005; 20: 1390-1397.
    CrossrefPubMedGoogle Scholar
  • 56 Pacifici GM, Nottoli R.. Placental transfer of drugs administered to the mother. Clin Pharmacokinet 1995; 28: 235-269.
    CrossrefPubMedGoogle Scholar
  • 57 Weisz B, Meirow D, Schiff E. et al. Impact and treatment of cancer during pregnancy. Expert Rev Anticancer Ther 2004; 04: 889-902.
    CrossrefPubMedGoogle Scholar
  • 58 Greer IA, Nelson-Piercy C.. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005; 106: 401-407.
    CrossrefPubMedGoogle Scholar
  • 59 Barbui T, Barosi G, Birgegard G. et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukaemiaNet. J Clin Oncol 2011; 29: 761-770.
    CrossrefPubMedGoogle Scholar