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Open access

Maja Hjelm Lundgaard, Allan Carlé, Ulla Birgitte Christiansen, Anne Sørensen, Søren Risom Kristensen, and Stine Linding Andersen

Introduction

Thyroid disorders have been linked to abnormalities in the coagulation system, and a hypocoagulant state has been proposed in hypothyroidism. The assessment of thyroid function is, however, not routinely recommended as part of the assessment for coagulation disorders.

Case presentation

We present a 32-year-old woman who had no history of thyroid disease and who recently gave birth preterm because of severe preeclampsia and intrauterine growth restriction. Due to severe placental dysfunction, she underwent a routine biochemical assessment of the coagulation system 6 months postpartum, and a prolonged activated partial thromboplastin time (APTT) (43 s) was identified along with a low level of coagulation factor VIII (0.44 IU/mL), and a low level of von Willebrand factor (vWF) antigen (0.35 IU/mL), vWF activity (0.38 IU/mL) as well as reduced generation of thrombin. The assessment of thyroid function in the patient identified autoimmune, overt hypothyroidism with a thyroid-stimulating hormone (TSH) concentration of 139 mIU/L, low levels of the peripheral thyroid hormones (total thyroxine: 43 nmol/L, total triiodothyronine: 0.9 nmol/L), and high levels of thyroid peroxidase antibodies (296 U/mL) as well as thyroglobulin antibodies (927 U/mL).

Conclusion

In this case, prolonged APTT provided a diagnostic clue for the assessment of thyroid function in a young woman with a recent history of severe placental dysfunction. The identification of autoimmune, overt hypothyroidism emphasizes that measurement of TSH may be of clinical importance in cases of unexplained prolonged APTT or other biochemical signs of abnormalities in the coagulation system.

Established facts

  • Hypothyroidism has been associated with alterations of the coagulation system suggesting a hypocoagulant state.

  • At present, measurement of thyroid-stimulating hormone is not routinely recommended as part of the assessment for coagulation disorders.

Novel insights

  • In this case, biochemical assessment of the coagulation system was routinely performed following a pregnancy complicated by severe placental dysfunction.

  • Overt hypothyroidism of autoimmune origin was identified secondary to prolonged activated partial thromboplastin time (APTT) postpartum along with low levels of coagulation factor VIII, von Willebrand factor, and thrombin generation.

  • Measurement of thyroid-stimulating hormone may be considered in cases of unexplained prolonged APTT.

Open access

Stine Linding Andersen, Niels Henrik Bruun, Peter Astrup Christensen, Simon Lykkeboe, Aase Handberg, Annebirthe Bo Hansen, Maja Hjelm Lundgaard, Louise Knøsgaard, Nanna Maria Uldall Torp, Allan Carlé, Jesper Karmisholt, Inge Bülow Pedersen, Peter Vestergaard, and Stig Andersen

Objective

Thyroid disease in women of reproductive age is mainly of autoimmune origin, and thyroid peroxidase antibodies (TPO-Ab) as well as thyroglobulin antibodies (Tg-Ab) are key markers. Adding to this, much focus in pregnancy is on euthyroid women who are thyroid antibody positive. Evidence to substantiate the cut-offs for the definition of thyroid autoantibody positivity in early pregnant women is warranted.

Methods

Stored serum samples from 14,030 Danish pregnant women were used for the measurement of TPO-Ab, Tg-Ab, TSH, and free thyroxine (ADVIA Centaur XPT, Siemens Healthineers). Among all women, a reference cohort of 10,905 individuals was identified for the establishment of antibody cut-offs. Percentile cut-offs for TPO-Ab and Tg-Ab were determined using regression on order statistics (the reference cohort). The established cut-offs were then applied (the full cohort), and frequencies of early pregnancy as well as later diagnosis of hypothyroidism were evaluated.

Results

The highest established cut-offs (95th, 97.5th, and 99th percentiles) were 59, 68, and 81 U/mL for TPO-Ab and 33, 41, and 52 U/mL for Tg-Ab. When the cut-offs were applied in the full cohort, 11.0, 10.2, and 9.7% were TPO-Ab positive, whereas 13.3, 12.3, and 11.2% were Tg-Ab positive. Antibody-positive women (TPO-Ab and/or Tg-Ab) had higher median TSH and were more likely to have hypothyroidism in early pregnancy and to be diagnosed with hypothyroidism during follow-up.

Conclusions

This large study established and evaluated pregnancy-specific cut-offs for TPO-Ab and Tg-Ab. The findings are important regarding the classification of exposure in pregnancy and assessment of thyroid autoimmunity per se.