Coroner Issues Warning After 2 Young Women Die From Taking Oral Contraceptives

The risk of developing a blood clot increases substantially in women with the Heterozygous Factor V Leiden mutation who take oral contraceptives. areeya_ann/shutterstock

A New Zealand coroner has issued a warning about the risks of oral contraceptives after two women died from blood clots in the same circumstances in the same month.

A 24-year-old Auckland-based make-up artist, Georgia O’Neill, was found “unresponsive” in her bedroom on the afternoon of Sept. 20, 2021, after complaining that she was “not feeling well” and “had a lot of pain in her lower back” earlier in the day. Ms. O’Neill had sent a text message to her father and flatmate.

Ms. O’Neill was at the time prescribed an oral contraceptive, Ginet, according to the Coroner’s report (pdf).

Upon receiving the text message, Ms. O’Neill’s flatmate replied three times but did not receive a response.

The flatmate then went back to their home to find Ms. O’Neill unresponsive, where she was later pronounced dead by attending paramedics.

A post-mortem examination found Ms. O’Neill had thrombosis in the right pulmonary artery, as well as a heterozygous Factor V Leiden mutation.

The Heterozygous Factor V Leiden mutation is inherited in about 1-5 percent of people with European ancestry, with that figure growing to 10-20 percent in people with underlying venous thromboembolism.

Add in an oral contraceptive, and the risk of developing a blood clot increases substantially, with around five and seven in every thousand affected annually.

Dr. Merriman, clinical director of haematology and lead thrombosis clinician at Te Whatu Ora Waitematā, said that women with Factor V Leiden have an approximately 35-fold increased risk of developing a deep venous thrombosis (DVT) or pulmonary embolism (PE) compared with women without Factor V Leiden.

Coroner Alexander Ho said that had Ms. O’Neill been more aware of the risks of developing DVT while she took the contraceptive pill, Ginet, she would have been wary about attributing symptoms to a “pre-existing back condition.”

Ginet is not recommended in women solely for contraception and is only available via prescription, according to the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) (pdf).

Ginet is also used to treat women with acne, hair loss, or increased growth of facial and body hair if these conditions are the result of over-production of male-type hormones called androgens, the medical authority said.

“GINET can also be used to treat polycystic ovary syndrome, a hormone imbalance that can cause irregular or absent periods, acne, excessive hair growth, infertility, recurrent miscarriage, and obesity,” Medsafe said.

“However, women starting the combined oral contraceptive pill should be counselled that there is an increased risk of venous thromboembolism and advised to seek immediate medical attention if they develop symptoms of DVT or PE,” Mr. Ho said.

While Ms. O’Neill did take the Pfizer Comirnaty vaccine on Sept. 7, 2021, the coroner found “no evidence” to suggest that this played a role in causing her death.

Teenager Dies in Similar Circumstances

In a similarly eerie set of circumstances, 17-year-old Isabella Alexander, who also took an oral contraceptive while having the pre-existing Heterozygous Factor V Leiden mutation, died from blood clots on Sept. 9, 2021.

The Year 13 student collapsed while walking with her father on Muriwai Beach, reported NZ Herald.

Blood clots were found in her lungs and legs on the morning of her death, according to the coroner’s report.

The coroner found the death was caused directly by pulmonary thromboembolism and indirectly by the heterozygous Factor V Leiden mutation, which was made worse by the use of oral contraceptives.

Similar to Ms. O’Neill, Ms. Alexander had also taken the Pfizer Comirnaty vaccine earlier, but the coroner found “no evidence” to suggest that this played a role in causing her death.

The coroner said that Ms. Alexander’s death “is a reminder that widely used, and relatively safe, medications still have risks.”

The coroner added that even healthy young people, who appear to have no obvious risk factors, can be affected.

The coroner suggested that all prescribers of the combined oral contraceptive pill and other hormone-related medications should ensure that they access a patient’s comprehensive clinical history, and inform them about the risks of venous thromboembolism, the seriousness of the condition, and the symptoms to look out for.

Symptoms to Look Out For

The coroner recommends keeping alert for the following symptoms:

• For Deep Venous Thrombosis (DVT):
  - Leg pain or tenderness in the thigh or calf
  - Leg swelling (oedema)
  - Skin that feels warm to the touch
  - Reddish discolouration and streaks
• For Pulmonary Embolism (PE):
  - Unexplained shortness of breath
  - Rapid breathing
  - Chest pain anywhere under the ribcage
  - Fast heart rate
  - Light headedness and passing out

Combined Oral Contraceptives and Factor V Leiden Mutation Pose ‘Multiplicative’ Risk Factors for DVT: Study

According to a 2020 study published in Research and Practice in Thrombosis and Haemostasis (RPTH), the combination of oral contraceptives and factor V Leiden mutation are “multiplicative” risk factors for venous thromboembolism.

The study found that women who took oral contraceptives are at increased thrombotic risk, which is due to increased levels of fibrinogen (protein that is important in blood clotting) and coagulation factors, and a decrease in antithrombin and protein S (which prevents proteins from making too many blood clots).

Those who have the Factor V Leiden Mutation have resistance to Activated Protein C (important in regulating anticoagulation, inflammation, and cell death), and therefore have increased blood clot risk.

Additionally, the study found that thrombin generation improved greatly after the discontinuation of combined oral contraceptives.