Blood Podcast – Special Episode: Maternal Health in Hematology (December 5, 2025)

Overview

This bonus episode explores two recent studies summarized in Blood, focusing on important intersections between maternal health and hematology:

1. Beta thalassemia minor and its association with worsening anemia during pregnancy (Dr. Arielle Langer).
2. Longitudinal profile of estrogen-related thrombotic biomarkers after stopping combined hormonal contraceptives (Dr. Mark Blondin).

Host Dr. Laura Michaels interviews both lead authors, unpacking the motivation, methodology, main findings, clinical implications, and future research directions.

Segment 1: Beta Thalassemia Minor and Anemia in Pregnancy

Guest: Dr. Arielle Langer
Timestamps: 00:31–13:02

Motivation and Background

• The study was inspired by a "real-life patient encounter," where Dr. Langer saw a pregnant woman with beta thalassemia minor presenting with significant anemia, which was not explained by iron, B12 deficiency, or hemolysis, leading her to question current knowledge gaps.

  "I just stood there and I was very worried I was missing something. ... I didn't have the answers. ...It really lit a fire in me because then when I went back ... it wasn't there [in the literature]." — Dr. Langer, [01:04]

• Conventional teaching treats beta thalassemia minor as "minor or trait" and "not really a true disorder," but Dr. Langer's clinical experience suggested otherwise:

  "**I really realized that maybe it was incidence. ...It was actually happening with some regularity ... not obscurely, ... but actually happening with some regularity." — Dr. Langer, [03:44]

Study Population and Methods

• The study analyzed 347 pregnancies in 240 women with beta thalassemia minor within the Mass General Brigham network. The denominator is pregnancies, not distinct individuals.

• Measurements were regimented: one hemoglobin value in the first/second trimester, one in the third, and one at presentation to labor and delivery, to avoid bias from sicker patients being tested more.

Key Findings

• Anemia Prevalence:

  • Only 7% had hemoglobin under 9 g/dL in the first/second trimester.
  • This rose sharply to 31% by the third trimester.
  • At presentation for labor and delivery, anemia prevalence dropped again to ~7%.

  "Nearly a third of [patients] were dropping down [to hemoglobin in the eights] by the third trimester." — Dr. Langer, [04:02]

• Potential Mechanism:

  • The episodic anemia pattern did not entirely match the hypothesis of exaggerated dilutional anemia, as levels recovered at labor/delivery.

• Iron Supplementation Issues:

  • Many women received iron (including IV), but about half were not actually iron deficient (using a ferritin cutoff of 50 or transferrin saturation <20%).
  • Over-supplementation risks iron overload and worsens pregnancy side effects.

  "Almost half of the women who got IV iron actually weren't iron deficient. ...these are people who actually had it measured, shown that the driver wasn't iron deficiency, and still got iron IV." — Dr. Langer, [07:22]

• Fetal Outcomes:

  • No adverse outcomes noted:
    • No increase in low birth weight, fetal anomalies, or prematurity.
    • "Pretty reassuring" for patients and OB-GYN colleagues.

• Generalisability:

  • Study drawn from the Boston area (Massachusetts General Brigham Network).
  • Exclusions: Home births not captured; only beta thalassemia minor (not alpha).
  • Ethnic distribution noted: Beta-thal more common in Southern European/Middle Eastern backgrounds; alpha-thal in Asian/Southeast Asian ancestry.

• Maternal Outcomes:

  • Slight increase in postpartum hemorrhage in beta-thal minor pregnancies.
  • Mechanism unclear, but may relate to anemia-associated increases in hemorrhage risk.

  "There is this signal here for increased rates of postpartum hemorrhage. ... Amongst the things to keep in mind is there's a lot of data about the risks of postpartum hemorrhage being higher for women who enter delivery anemic." — Dr. Langer, [12:22]

Future Directions

• Investigate similar patterns in hereditary spherocytosis and other congenital anemias.
• Delve into basic science questions on globin regulation and pregnancy anemia mechanisms.
• Develop or test effective treatments to raise counts and reduce postpartum hemorrhage risk in these populations.

Segment 2: Thrombotic Risk after Stopping Combined Hormonal Contraceptives

Guest: Dr. Mark Blondin
Timestamps: 13:04–19:58

Motivation and Background

• Clinical quandary: "How long does the pro-thrombotic risk of estrogen-containing contraceptives last after cessation?"

• Critical for managing:

  • Women with recent deep vein thrombosis (DVT) or pulmonary embolism,
  • Patients undergoing planned surgery on contraceptives.

  "One of the key variables that we had identified is the lack of knowledge of how long the risk of thrombosis related to the Pill would actually last once a user has stopped the Pill." — Dr. Blondin, [13:56]

• Surrogate biomarkers for estrogen-related VTE were used due to the impracticality of large event-based cohort studies.

Methods

• Recruited women in Geneva planning to stop their contraceptives (mainly through social media).
• Serial blood draws pre- and post-cessation to track biomarker shifts over time.

Key Findings

• Rapid Normalization:

  • Pro-thrombotic markers largely returned to baseline within two weeks of stopping estrogen, surprising researchers.
  • About 75% reduction in pro-thrombotic risk by two weeks, near-normal at four.

  "We were expecting that this prothrombotic risk would last several weeks, perhaps six weeks after cessation of the pill. But ... already after two weeks most of these prothrombotic risk ... disappeared." — Dr. Blondin, [15:51]

Clinical Implications

• For Women on Anticoagulation:

  • Women with acute VTE on estrogen can generally remain on contraceptives.
  • Cessation should occur about 1 month before stopping anticoagulation to ensure baseline risk by anticoagulation withdrawal.

  "Just that month interval between the stop of the pill until the stop of the anticoagulation means that there won't be any effect of the pill once the lady comes out of the anticoagulation." — Dr. Blondin, [17:15]

• Perioperative Management:

  • Clarity that only 2 weeks off estrogen is needed pre-surgery (not prolonged withdrawal), minimizing risks of abnormal bleeding or unintended pregnancy.

Future Directions

• Efforts to identify the safest hormonal contraceptive preparations ("newer estrogenic preparations" in need of careful evaluation).

• Move toward more personalized predictions of VTE risk (beyond broad markers like obesity or family history).

  "I think we could get more detailed personalized prediction for individual patients." — Dr. Blondin, [19:43]

Memorable Quotes & Takeaways

• Dr. Langer (on research motivation):

  "I just had no idea that she could be this anemic. ... And so, you know, we made our best of that care ... but it really lit a fire in me." — [01:04]

• Dr. Langer (on actionable clinical findings):

  "Almost half of the women who got IV iron actually weren't iron deficient. ... these are people actually had it measured ... and still got iron iv. And so I think that's also a potential harm here." — [07:22]

• Dr. Blondin (on the main surprise):

  "We were expecting that this prothrombotic risk would last several weeks ... but actually ... already after two weeks most ... disappeared." — [15:51]

• Dr. Blondin (future of the field):

  "I think where the field should be going is trying to identify really the safest preparation. ... and also a better personalized prediction on which women is more likely to get this side effect." — [19:13]

Key Timestamps

• 00:50–04:00: Dr. Langer explains her clinical inspiration and knowledge gap around beta thalassemia minor in pregnancy.
• 05:03–07:22: Discussion of anemia statistics, measurement method, iron supplementation, and pitfalls in therapy.
• 08:51–09:27: Maternal-fetal outcomes and generalizability of findings.
• 12:22–13:02: Findings on postpartum hemorrhage and implications for counselling and future research.
• 13:19–16:53: Dr. Blondin summarizes the rationale, methods, and strikingly rapid fall-off in thrombosis biomarker levels after stopping estrogen.
• 16:57–19:13: Clinical implications, international guidelines, importance for perioperative and VTE management, future research vision.

Conclusion

This episode highlights pressing clinical gaps and actionable insights in maternal hematology:

• Beta thalassemia minor is more clinically significant in pregnancy than often believed, with up to a third of pregnancies experiencing significant anemia without fetal risk but some increased postpartum hemorrhage—a call for greater clinical awareness and nuanced management.
• The risk of estrogen-associated thrombosis after stopping combined hormonal contraceptives drops far more quickly than previously thought, clarifying safe management intervals for both thrombosis and surgical scenarios and underscoring the drive toward safer, more personalized contraceptive choices.