10.4081/btvb.2022.28
Venous thromboembolism (VTE) is one of the leading cardiovascular etiologies of maternal morbidity and mortality. Indeed, pulmonary embolism (PE) accounts for approximately 9% of pregnancy-related deaths. In addition, pregnancy-related deep-vein thrombosis (DVT) can lead to (severe) post-thrombotic syndrome [...]
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en
and the  RIETE Investigators
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Bleeding, Thrombosis and Vascular Biology
Anticoagulation
Treatment of venous thromboembolism in pregnancy: findings from the RIETE Registry
Text.Serial.Journal
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Letters
2022-05-23
2022-03-21
2022-05-23
2022-05-23
Bleed Thromb Vascul Biol
and the  RIETE Investigators
2022/05/23
10.4081/btvb.2022.28
Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona
2785-5309
2
Anticoagulation
en
Bikdeli B, Jiménez D, Hawkins M, et al. Rationale, design and methodology of the Computerized Registry of Patients with Venous Thromboembolism (RIETE). Thromb Haemost 2018;118:214-24.
Treatment of venous thromboembolism in pregnancy: findings from the RIETE Registry
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1
                                                                                                    LETTER TO THE EDITOR

Treatment of venous thromboembolism in pregnancy:
findings from the RIETE Registry
Paolo Prandoni,1 Franca Bilora,2 Raffaele Pesavento,3 Giorgina Salgueiro,4 Angeles Blanco-Molina,5 Raquel López-Reyes,5
Manuel Monreal,6 and the RIETE Investigators*
*A full list of RIETE investigators is given in the appendix
1
  Arianna Foundation on Anticoagulation, Bologna, Italy; 2Department of Medicine, University Hospital of Padua, Italy; 3Division of
Medicine, Civic Hospital of Montebelluna, Italy; 4Department of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain;
5
  Department of Internal Medicine, Hospital Universitario Reina Sofía, Córdoba, Spain; 6Department of Internal Medicine, Hospital
Germans Trias i Pujol, Badalona, Barcelona, Spain




Dear Editor,                                                                   proximately 9% of pregnancy-related deaths.2 In addition,
                                                                               pregnancy-related deep-vein thrombosis (DVT) can lead
     Venous thromboembolism (VTE) is one of the leading                        to (severe) post-thrombotic syndrome.3




                                                                                                ly
cardiovascular etiologies of maternal morbidity and mor-                           The optimal management of pregnancy-related VTE




                                                                                        on
tality.1 Indeed, pulmonary embolism (PE) accounts for ap-                      has never been addressed by proper investigations. Virtu-
                                                                               ally all major international guidelines suggest the use of
                                                                               full-dose low-molecular-weight heparin (LMWH) for as



                                                                                   e
    Correspondence: Paolo Prandoni, Arianna Foundation on Antico-              long as the pregnancy lasts and at least the first six weeks
                                                                              us
    agulation, Via P. Fabbri 1/3, 40038 Bologna (BO), Italy.                   after delivery.4-6 This indication, however, is not supported
    Tel.: +39.340.2808202.
    E-mail: prandonip@gmail.com
                                                                               by scientific evidence. Besides, it contrasts with the
                                                                               modalities of LMWH treatment that are adopted in clini-
                                                                              al

    Key words: Venous thromboembolism, Pregnancy, Low-molecu-                  cal conditions other than pregnancy. For example, based
                                                           ci

    lar-weight heparin, Anticoagulation.                                       on the findings of clinical trials conducted in patients with
                                                                               active cancer, which is by far the condition at the highest
                                                         er



    Acknowledgements: The Authors express their gratitude to Sanofi
    Spain, LEO PHARMA and ROVI for supporting this Registry with               risk of recurrent VTE while on anticoagulation,7 the initial
                                                        m




    an unrestricted educational grant. We also thank the RIETE Reg-            intensive LMWH dose is generally reduced by approxi-
    istry Coordinating Centre, S&H Medical Science Service, for their          mately one fourth after the first 3 to 4 weeks.8-10 And in
                                            om




    quality control data, logistic and administrative support and Prof.
    Salvador Ortiz, Universidad Autónoma Madrid and Silvia Galindo,            patients without cancer, whenever LMWH is used as a
    both Statistical Advisors in S&H Medical Science Service for the           standalone therapy in place of vitamin K antagonists for
    statistical analysis of the data presented in this paper.                  the initial and long-term treatment of VTE, the shift from
                                      -c




    Contributions: The Authors contributed equally.
                                                                               therapeutic to subtherapeutic doses is generally made after
                             on




                                                                               one or two weeks.11-13
    Conflict of interest: The Authors declare no potential conflict of             While the risk of VTE is expected to increase at the
    interest.                                                                  end of pregnancy and in the first six weeks after delivery,1
                       N




    Funding: None.                                                             the reasons why pregnant women with VTE should afford
                                                                               the potential risks and the inconveniences of uninterrupted
    Received for publication: 21 March 2022.                                   full-dose LMWH for as long as the pregnancy lasts are
    Accepted for publication: 6 May 2022.                                      unclear. Not surprisingly, in clinical practice several cli-
    Publisher’s note: All claims expressed in this article are solely those    nicians do not comply with these indications and give
    of the authors and do not necessarily represent those of their affili-     their patients lower doses of LMWH after an initial vari-
    ated organizations, or those of the publisher, the editors and the re-     able period of intensive treatment.14 While it would be in-
    viewers. Any product that may be evaluated in this article or claim
    that may be made by its manufacturer is not guaranteed or endorsed
                                                                               teresting to know if this approach is reasonably effective
    by the publisher.                                                          and safe, this information is lacking. As in the framework
                                                                               of the international RIETE registry, aimed at collecting
     Copyright: the Author(s), 2022                                            information on the initial and long-term follow-up of un-
    ©

    Licensee PAGEPress, Italy
    Bleeding, Thrombosis and Vascular Biology 2022; 1:28                       selected patients with VTE, several women with preg-
    doi:10.4081/btvb.2022.28                                                   nancy-related VTE had their therapy managed with lower
                                                                               than conventional doses of LMWH, we report here the
    This work is licensed under a Creative Commons Attribution-                main findings achieved in these women.
    NonCommercial 4.0 International License (CC BY-NC 4.0).
                                                                                   The Computerized Registry of Patients with Venous

                                                Bleeding, Thrombosis and Vascular Biology 2022; 1:28
24                                                             P. Prandoni et al.




Thromboembolism (RIETE, NCT: 02832245) is a large                               During the follow-up period, objectively confirmed
prospective registry that since 2001 has been enrolling                     recurrent VTE developed in two of the 201 women
consecutive patients, including pregnant women, with ob-                    (1.0%): in none during 69.13 patient-years before deliv-
jectively confirmed VTE.15 The main objective of RIETE                      ery, and in two during 25.13 patient-years after delivery
is to provide information to help physicians to improve                     (a nonfatal PE and a left proximal DVT occurring after
their knowledge on the natural history of thromboembolic                    three and 10 days, respectively). Accordingly, the annual
disease, including epidemiologic, diagnostic, prophylactic                  rate of VTE complications was 0.00% (95% CI: 0.00 to
and therapeutic information. Participants in the RIETE                      0.05) and 0.08% (95% CI: 0.02 to 0.25) before and after
registry are requested to provide accurate information on                   delivery, respectively. Major bleeding complications, de-
patient’s short and long-term outcome after the index                       fined according to the ISTH classification, developed in
event. All recurrent symptomatic VTE events are diag-                       one woman (0.5%) during the overall 94.26 patient-years
nosed according to objective tests and validated criteria                   of follow-up (a vaginal bleeding soon after delivery), ac-
for their interpretation. All enrollees provide written or                  counting for an annual rate of 0.01% (95% CI: 0.00 to
verbal informed consent according to the local ethics pro-                  0.06). No patient died during the follow-up period.
tocols of enrolling centers. The institutional review board                     As far as we know, this is the first report dealing with
at each enrolling center approves participation in RIETE                    the long-term follow-up of a considerable number of women
for the site investigators and allows the entry of de-iden-                 with pregnancy-related VTE who were managed with sub-




                                                                                                     ly
tified patient information into the RIETE database.                         therapeutic doses of LMWH following an initial short pe-




                                                                                             on
                                                                            riod of intensive treatment. Our findings suggest that in
     Out of 641 patients with pregnancy-related acute VTE
                                                                            patients with pregnancy-related VTE, the efficacy of sub-
who visited a RIETE center between January 2001 and
                                                                            therapeutic doses of LMWH following an initial intensive
April 2021 and were managed with LMWH, 201 (31.4%)


                                                                                        e
                                                                            treatment may not be lower than that of an uninterrupted
had the initial full dose reduced by 25 to 50% after a pe-                          us
                                                                            full-dose scheme before delivery, while it is expected to de-
riod ranging between one and two weeks, and were fol-
                                                                            cline after delivery.1 Of course, our findings should be in-
lowed up for as long as antithrombotic therapy was
                                                                            terpreted with caution, because of the uncontrolled nature
                                                                          al
needed, thus covering at least the first six weeks after de-
                                                                            of our observation and of the potential for selection bias, as
livery. Table 1 shows the main demographic and clinical
                                                              ci

                                                                            the therapeutic choices were left to discretion of attending
characteristics of these women.                                             physicians. Accordingly, our findings should be intended as
                                                            er



                                                                            hypothesis generating. A randomized clinical trial address-
                                                                            ing the comparison between uninterrupted full-dose LMWH
                                                           m




Table 1. Main characteristics of the study patients                         and a more prudent anti-partum strategy in the management
                                               om




Features                                   Patients (N=201)                 of VTE-related pregnancy is desirable.
                                                N. (%)
Age, years (mean ± SD)                           33±6
                                         -c




Body weight ≥90 Kg                             27 (13.4)
                                                                            REFERENCES
                                 on




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*Antithombin, protein C or S deficiency, factor V Leiden, prothrombin
G20210A mutation, antiphospholipid antibody syndrome. SD=standard               for Vascular Surgery (ESVS) 2021 Clinical Practice Guide-
deviation; VTE=venous thromboembolism; DVT=deep-vein thrombosis;                lines on the management of venous thrombosis. Eur J Vasc
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                                          Bleeding, Thrombosis and Vascular Biology 2022; 1:28
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                                                                                     ly
    parin versus warfarin in the prevention of recurrences after        2018;118:214-24.




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