Thrombosis in Pregnant Women with Hematological Malignancies: A Case-Based Review

 

 Buy Article Permissions and Reprints

Abstract

Cancer and pregnancy induce a procoagulant environment which may lead to maternal and fetal complications, such as venous thromboembolism, fetal growth restriction, and fetal loss. The incidence of hematological malignancies diagnosed during pregnancy is rising, and thrombotic events in such malignancies are not rare. Management of thrombosis during pregnancy poses a therapeutic challenge, that is further exacerbated by the impact of cancer. The available data on managing pregnant women with hematological malignancies are limited to those with myeloproliferative neoplasms, mainly essential thrombocythemia, and, to a lesser extent, polycythemia vera. Low-dose aspirin is recommended throughout pregnancy, and considering treatment with low-molecular-weight heparin and interferon formulations is advised for high-risk patients. Currently, guidelines for handling thrombotic events in pregnant women with lymphoma or leukemia are lacking, and their management is based on data extrapolated from retrospective studies, and guidelines for prevention and treatment of cancer-associated thrombosis. The present case-based review will focus on the complex issue of thrombotic risk in pregnant women with hematological malignancies, specifically myeloproliferative neoplasms, lymphomas, and leukemias.

Publication History

Article published online:
19 December 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

• References

• 1 Maggen C, Wolters VERA, Cardonick E. et al; International Network on Cancer, Infertility and Pregnancy (INCIP). Pregnancy and cancer: the INCIP project. Curr Oncol Rep 2020; 22 (02) 17
  CrossrefPubMedSearch in Google Scholar
• 2 Brenner B, Avivi I, Lishner M. Haematological cancers in pregnancy. Lancet 2012; 379 (9815): 580-587
  CrossrefPubMedSearch in Google Scholar
• 3 Hurley TJ, McKinnell JV, Irani MS. Hematologic malignancies in pregnancy. Obstet Gynecol Clin North Am 2005; 32 (04) 595-614
  CrossrefPubMedSearch in Google Scholar
• 4 Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (08) 464-474
  CrossrefPubMedSearch in Google Scholar
• 5 Devis P, Knuttinen MG. Deep venous thrombosis in pregnancy: incidence, pathogenesis and endovascular management. Cardiovasc Diagn Ther 2017; 7 (Suppl. 03) S309-S319
  CrossrefPubMedSearch in Google Scholar
• 6 Bleau N, Patenaude V, Abenhaim HA. Risk of venous thrombo-embolic events in pregnant patients with cancer. J Matern Fetal Neonatal Med 2016; 29 (03) 380-384
  PubMedSearch in Google Scholar
• 7 Hague WM, Dekker GA. Risk factors for thrombosis in pregnancy. Best Pract Res Clin Haematol 2003; 16 (02) 197-210
  CrossrefPubMedSearch in Google Scholar
• 8 Aharon A, Brenner B. Microparticles, thrombosis and cancer. Best Pract Res Clin Haematol 2009; 22 (01) 61-69
  CrossrefPubMedSearch in Google Scholar
• 9 Aharon A, Brenner B. Microvesicles in thrombosis and inflammation. Isr Med Assoc J 2016; 18 (09) 530-533
  PubMedSearch in Google Scholar
• 10 Nadir Y, Brenner B. Heparanase multiple effects in cancer. Thromb Res 2014; 133 (Suppl. 02) S90-S94
  CrossrefPubMedSearch in Google Scholar
• 11 Nadir Y, Brenner B, Zetser A. et al. Heparanase induces tissue factor expression in vascular endothelial and cancer cells. J Thromb Haemost 2006; 4 (11) 2443-2451
  CrossrefPubMedSearch in Google Scholar
• 12 Dameshek W. Dameshek W. Some speculations on the myeloproliferative syndromes [editorial]. Blood. 1951;6(4):372–375. Blood 2016; 127 (06) 663
  CrossrefPubMedSearch in Google Scholar
• 13 Spivak JL. The chronic myeloproliferative disorders: clonality and clinical heterogeneity. Semin Hematol 2004; 41 (2, Suppl 3): 1-5
  CrossrefPubMedSearch in Google Scholar
• 14 Finazzi G, Barbui T. Risk-adapted therapy in essential thrombocythemia and polycythemia vera. Blood Rev 2005; 19 (05) 243-252
  CrossrefPubMedSearch in Google Scholar
• 15 Alvarez-Larrán A, Cervantes F, Bellosillo B. et al. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia 2007; 21 (06) 1218-1223
  CrossrefPubMedSearch in Google Scholar
• 16 Ewins K, Ní Ainle F. VTE risk assessment in pregnancy. Res Pract Thromb Haemost 2019; 4 (02) 183-192
  CrossrefPubMedSearch in Google Scholar
• 17 Gangat N, Tefferi A. Myeloproliferative neoplasms and pregnancy: overview and practice recommendations. Am J Hematol 2021; 96 (03) 354-366
  CrossrefPubMedSearch in Google Scholar
• 18 Griesshammer M, Struve S, Barbui T. Management of Philadelphia negative chronic myeloproliferative disorders in pregnancy. Blood Rev 2008; 22 (05) 235-245
  CrossrefPubMedSearch in Google Scholar
• 19 Maze D, Kazi S, Gupta V. et al. Association of treatments for myeloproliferative neoplasms during pregnancy with birth rates and maternal outcomes: a systematic review and meta-analysis. JAMA Netw Open 2019; 2 (10) e1912666
  CrossrefPubMedSearch in Google Scholar
• 20 Griesshammer M, Sadjadian P, Wille K. Contemporary management of patients with BCR-ABL1-negative myeloproliferative neoplasms during pregnancy. Expert Rev Hematol 2018; 11 (09) 697-706
  CrossrefPubMedSearch in Google Scholar
• 21 Melillo L, Tieghi A, Candoni A. et al. Outcome of 122 pregnancies in essential thrombocythemia patients: a report from the Italian registry. Am J Hematol 2009; 84 (10) 636-640
  CrossrefPubMedSearch in Google Scholar
• 22 Rumi E, Bertozzi I, Casetti IC. et al; Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators. Impact of mutational status on pregnancy outcome in patients with essential thrombocytemia. Haematologica 2015; 100 (11) e443-e445
  CrossrefPubMedSearch in Google Scholar
• 23 Sokolowska B, Sobas M, Jawniak D. et al. Pregnancy outcomes in patients with Philadelphia negative myeloproliferative neoplasms – PALG (Polish Adult Leukemia Group): a recent, extended retrospective analysis. EHA Library; 2020. Accessed September 2022, at: https://library.ehaweb.org/eha/2020/eha25th/293610/bozena.sokolowska.pregnancy.outcomes.in.patients.with.philadelphia.negative.html
  PubMed
• 24 How J, Leiva O, Bogue T. et al. Pregnancy outcomes, risk factors, and cell count trends in pregnant women with essential thrombocythemia. Leuk Res 2020; 98: 106459
  CrossrefPubMedSearch in Google Scholar
• 25 Griesshammer M, Andreoli A, Schauer S. et al. Outcomes of 121 pregnancies in patients with polycythemia vera (PV). EHA Library. 2016. Accessed September 2022, at: https://library.ehaweb.org/eha/2016/21st/135143/martin.griesshammer.outcomes.of.121.pregnancies.in.patients.with.polycythemia.html?f=m1
  PubMed
• 26 Bertozzi I, Rumi E, Cavalloni C, Cazzola M, Fabris F, Randi ML. Pregnancy outcome and management of 25 pregnancies in women with polycythemia vera. Am J Hematol 2018; 93 (09) E234-E235
  CrossrefPubMedSearch in Google Scholar
• 27 Barbui T, Tefferi A, Vannucchi AM. et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 2018; 32 (05) 1057-1069
  CrossrefPubMedSearch in Google Scholar
• 28 Lavi N, Brenner B, Avivi I. Management of pregnant women with myeloproliferative neoplasms. Thromb Res 2013; 131 (Suppl. 01) S11-S13
  CrossrefPubMedSearch in Google Scholar
• 29 Caruso V, Iacoviello L, Di Castelnuovo A, Storti S, Donati MB. Venous thrombotic complications in adults undergoing induction treatment for acute lymphoblastic leukemia: results from a meta-analysis. J Thromb Haemost 2007; 5 (03) 621-623
  CrossrefPubMedSearch in Google Scholar
• 30 Hohaus S, Bartolomei F, Cuccaro A. et al. Venous thromboembolism in lymphoma: risk stratification and antithrombotic prophylaxis. Cancers (Basel) 2020; 12 (05) 1291
  CrossrefPubMedSearch in Google Scholar
• 31 Borg IH, Bendtsen MD, Bøgsted M, Madsen J, Severinsen MT. Incidence of venous thromboembolism in patients with diffuse large B-cell lymphoma. Leuk Lymphoma 2016; 57 (12) 2771-2776
  CrossrefPubMedSearch in Google Scholar
• 32 Byun JM, Hong J, Yoon SS. et al; Korean Thrombosis and Hemostasis Working Party of Korean Society of Hematology. Incidence and characteristics of venous thromboembolism in Asian patients with primary central nervous system lymphoma undergoing chemotherapy. Thromb Res 2019; 183: 131-135
  CrossrefPubMedSearch in Google Scholar
• 33 Mahajan A, Wun T, Chew H, White RH. Lymphoma and venous thromboembolism: influence on mortality. Thromb Res 2014; 133 (Suppl. 02) S23-S28
  CrossrefPubMedSearch in Google Scholar
• 34 Rupa-Matysek J, Gil L, Barańska M, Dytfeld D, Komarnicki M. Mean platelet volume as a predictive marker for venous thromboembolism in patients treated for Hodgkin lymphoma. Oncotarget 2018; 9 (30) 21190-21200
  CrossrefPubMedSearch in Google Scholar
• 35 Rupa-Matysek J, Gil L, Kroll-Balcerzak R, Barańska M, Komarnicki M. Mean platelet volume as a predictive marker for venous thromboembolism and mortality in patients treated for diffuse large B-cell lymphoma. Hematol Oncol 2017; 35 (04) 456-464
  CrossrefPubMedSearch in Google Scholar
• 36 Antic D, Milic N, Nikolovski S. et al. Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients. Am J Hematol 2016; 91 (10) 1014-1019
  CrossrefPubMedSearch in Google Scholar
• 37 Müller AM, Ihorst G, Mertelsmann R, Engelhardt M. Epidemiology of non-Hodgkin's lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol 2005; 84 (01) 1-12
  CrossrefPubMedSearch in Google Scholar
• 38 Pereg D, Koren G, Lishner M. The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy. Haematologica 2007; 92 (09) 1230-1237
  CrossrefPubMedSearch in Google Scholar
• 39 Groves FD, Linet MS, Travis LB, Devesa SS. 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 (15) 1240-1251
  CrossrefPubMedSearch in Google Scholar
• 40 Hansen AT, Veres K, Horváth-Puhó E, Ehrenstein V, Prandoni P, Sørensen HT. Pregnancy-related venous thromboembolism and risk of occult cancer. Blood Adv 2017; 1 (23) 2059-2062
  CrossrefPubMedSearch in Google Scholar
• 41 Somigliana E, Peccatori FA, Filippi F, Martinelli F, Raspagliesi F, Martinelli I. Risk of thrombosis in women with malignancies undergoing ovarian stimulation for fertility preservation. Hum Reprod Update 2014; 20 (06) 944-951
  CrossrefPubMedSearch in Google Scholar
• 42 Samuelson Bannow BT, Lee A, Khorana AA. et al. Management of cancer-associated thrombosis in patients with thrombocytopenia: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16 (06) 1246-1249
  CrossrefPubMedSearch in Google Scholar
• 43 Held N, Jung B, Baumann Kreuziger L. Management of cancer-associated thrombosis with thrombocytopenia: impact of the ISTH guidance statement. Res Pract Thromb Haemost 2022; 6 (04) e12726
  CrossrefPubMedSearch in Google Scholar
• 44 Dunleavy K, McLintock C. How I treat lymphoma in pregnancy. Blood 2020; 136 (19) 2118-2124
  CrossrefPubMedSearch in Google Scholar
• 45 Ku GH, White RH, Chew HK, Harvey DJ, Zhou H, Wun T. Venous thromboembolism in patients with acute leukemia: incidence, risk factors, and effect on survival. Blood 2009; 113 (17) 3911-3917
  CrossrefPubMedSearch in Google Scholar
• 46 Libourel EJ, Klerk C, van Norden Y. et al. OC-10 - disseminated intravascular coagulation at diagnosis strongly predicts both arterial and venous thrombosis in acute myeloid leukemia patients. Thromb Res 2016; 140 (Suppl. 01) S172
  CrossrefPubMedSearch in Google Scholar
• 47 Horowitz NA, Lavi N, Nadir Y, Brenner B. Haematological malignancies in pregnancy: an overview with an emphasis on thrombotic risks. Thromb Haemost 2016; 116 (04) 613-617
  Thieme ConnectPubMedSearch in Google Scholar
• 48 Ganzel C, Becker J, Mintz PD, Lazarus HM, Rowe JM. Hyperleukocytosis, leukostasis and leukapheresis: practice management. Blood Rev 2012; 26 (03) 117-122
  CrossrefPubMedSearch in Google Scholar
• 49 Thomas X. Acute myeloid leukemia in the pregnant patient. Eur J Haematol 2015; 95 (02) 124-136
  CrossrefPubMedSearch in Google Scholar
• 50 Zhu D, Tang D, Chai X, Zhang G, Wang Y. Acute leukemia in pregnancy: a single institutional experience with 21 cases at 10 years and a review of the literature. Ann Med 2021; 53 (01) 567-575
  CrossrefPubMedSearch in Google Scholar
• 51 Santolaria A, Perales A, Montesinos P, Sanz MA. Acute promyelocytic leukemia during pregnancy: a systematic review of the literature. Cancers (Basel) 2020; 12 (04) 968
  CrossrefPubMedSearch in Google Scholar
• 52 Chelysheva E, Abruzzese E, Rea D. et al. Chronic myeloid leukemia diagnosed during pregnancy: therapy, outcomes and follow-up. Blood 2018; 132: 4255
  CrossrefPubMedSearch in Google Scholar
• 53 Ali S, Jones GL, Culligan DJ. et al; British Committee for Standards in Haematology. Guidelines for the diagnosis and management of acute myeloid leukaemia in pregnancy. Br J Haematol 2015; 170 (04) 487-495
  CrossrefPubMedSearch in Google Scholar
• 54 Chang A, Patel S. Treatment of acute myeloid leukemia during pregnancy. Ann Pharmacother 2015; 49 (01) 48-68
  CrossrefPubMedSearch in Google Scholar
• 55 Sanz MA, Montesinos P, Casale MF. et al. Maternal and fetal outcomes in pregnant women with acute promyelocytic leukemia. Ann Hematol 2015; 94 (08) 1357-1361
  CrossrefPubMedSearch in Google Scholar
• 56 Yang D, Hladnik L. Treatment of acute promyelocytic leukemia during pregnancy. Pharmacotherapy 2009; 29 (06) 709-724
  CrossrefPubMedSearch in Google Scholar