Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study

Miyoshi, Takekazu; Oku, Hisato; Asahara, Saiko; Okamoto, Akira; Kokame, Koichi; Nakai, Michikazu; Nishimura, Kunihiro; Otsuka, Fumiyuki; Higashiyama, Aya; Yoshimatsu, Jun; Miyata, Toshiyuki

doi:10.1007/s12185-019-02633-x

Cited by 8 publications

(2 citation statements)

References 38 publications

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“…Moreover, the activity and antigen levels of PS are both known to decrease when COCs are taken, and the VTE risk including pregnancy is elevated. 64 In a reported gene analysis of thrombophilia associated with pregnancy-related DVT in Japan, DVT occurred in the first and second trimesters of pregnancy with both PS deficiency and PC deficiency, while there was no occurrence in the third trimester or postpartum period. 32 Considering from the above that DVT may occur from the first trimester, the carriers of PS p.K196E need careful management starting from early pregnancy.…”

Section: Commentarymentioning

confidence: 99%

Clinical guidance for peripartum management of patients with hereditary thrombophilia

Kobayashi

Morishita

Tsuda

et al. 2021

J of Obstet and Gynaecol

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Hereditary thrombophilia is a condition in which individuals are susceptible to the formation of thrombi due to a hereditary deficiency in anticoagulant factors, antithrombin (AT), protein C (PC), or protein S (PS). Many Japanese thrombophilia patients have PS deficiency, especially PS p.K196E (also called as PS Tokushima), which is exclusive to the Japanese population, and thrombosis sometimes occurs during pregnancy. At present, no management guidelines for pregnancy and delivery in thrombophilia patients have been developed. The Study Group for Hereditary Thrombophilia, one of the research groups of blood coagulation abnormalities in the Research Program on Rare and Intractable Diseases supported with the Research Grants of the Ministry of Health, Labour and Welfare Science, has therefore developed this clinical guidance to provide healthcare workers with necessary information on safe pregnancy, parturition and neonatal management, adopting a format of responses to seven clinical questions (CQ). At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

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Section: Commentarymentioning

confidence: 99%

Clinical guidance for peripartum management of patients with hereditary thrombophilia

Kobayashi

Morishita

Tsuda

et al. 2021

J of Obstet and Gynaecol

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“…The higher levels and activity of coagulation factors in females are likely partially driven by circulating sex hormone levels, with shorter clotting times in women on in vitro fertilization treatment during high estrus 22 and increased coagulation factors in both women on oral contraceptive pills 56 and females during peak estrus of the menstrual cycle 57 . Interestingly, oral contraceptives not only promote thrombin formation in females by upregulation of coagulation factors but also via decreased antithrombin levels 58 which further drive thrombin generation. These in vivo changes can be recapitulated in vitro such that blood from healthy volunteers spiked with physiologic concentrations of estradiol displays pronounced hypercoagulability, with shorter time to clot formation and increased thrombin generation 57 …”

Section: Introductionmentioning

confidence: 99%

Sex dimorphisms in coagulation: Implications in trauma‐induced coagulopathy and trauma resuscitation

Coleman,

Gumina,

Hund

et al. 2024

American J Hematol

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Trauma‐induced coagulopathy (TIC) is one of the leading causes of preventable death in injured patients. Consequently, it is imperative to understand the mechanisms underlying TIC and how to mitigate this mortality. An opportunity for advancement stems from the awareness that coagulation demonstrates a strong sex‐dependent effect. Females exhibit a relative hypercoagulability compared to males, which persists after injury and confers improved outcomes. The mechanisms underlying sex dimorphisms in coagulation and its protective effect after injury have yet to be elucidated. This review explores sex dimorphisms in enzymatic hemostasis, fibrinogen, platelets, and fibrinolysis, with implications for resuscitation of patients with TIC.

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Sequential multiple retinal vein occlusions and transient ischemic attack inMTHFRpolymorphism and protein S deficiency

Cho¹,

Ragi²,

et al. 2020

Molec Gen & Gen Med

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BackgroundThe C677T variant of the MTHFR (5,10‐Methylenetetrahydrofolate reductase) gene is associated with increased susceptibility to homocystinuria (OMIM#236250), neural tube defects (OMIM#601634), schizophrenia (OMIM#181500), thromboembolism (OMIM#188050), and vascular diseases. Protein S deficiency is also associated with an increased risk of thromboembolism from reduced thrombin generation. In this report, we describe the case of a patient who presented with multiple retinal vein occlusions likely caused by an underlying combination of a homozygous MTHFR C677T variant and protein S deficiency.MethodsWe performed 8 years of continuous ophthalmic follow‐up of one patient diagnosed with central retinal vein occlusion. Peripheral blood was collected for metabolic evaluation and hypercoagulability assessment. Targeted gene sequencing was used for genetic diagnosis. Examination of the retinal vasculature was performed through dilated funduscopic examination, digital color fundus and ultrawide‐field color fundus photography, spectral domain optical coherence tomography, and fluorescein angiography.ResultsSequential retinal vein occlusions and a transient ischemic attack were observed during the follow‐up period. Targeted gene sequencing by PCR identified the homozygous MTHFR C677T variant. The metabolic profile indicated low‐protein S activity, high levels of vitamin B6, and LDL cholesterol consistent with her hypercoagulable state. Prescription of low‐dose aspirin and atorvastatin for hypercholesterolemia resulted in no further neovascularization, leakage, or vein occlusion.ConclusionRetinal vein occlusions associated with the MTHFR C677T variant and protein S deficiency may signal impending systemic thromboembolic episodes and warrant aggressive preventative measures.

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Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study

Cited by 8 publications

References 38 publications

Clinical guidance for peripartum management of patients with hereditary thrombophilia

Clinical guidance for peripartum management of patients with hereditary thrombophilia

Sex dimorphisms in coagulation: Implications in trauma‐induced coagulopathy and trauma resuscitation

Sequential multiple retinal vein occlusions and transient ischemic attack inMTHFRpolymorphism and protein S deficiency

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