DISCUSSION

Adenomyosis is a benign gynecologic condition, described as the presence of ectopic endometrial glands and stroma within the myometrium which commonly presents as cyclic menstrual
pain, large uterus and abnormal uterine bleeding.² A causal
relationship between VTE and adenomyosis has not yet been established and it is not known whether there is a direct link between the two conditions. In this patient with intermediate to high-risk severity of pulmonary embolism (sPESI score of 1), right ventricular dysfunction and positive troponin test, hospitalization and monitoring is needed due to the risk of early hemodynamic decompensation and circulatory collapse. Immediate anticoagulation is necessary with consideration of rescue perfusion if with clinical deterioration.³ In the 2019 ESC guideline for Acute Pulmonary Embolism, it is reasonable to leave patients with intermediate-high risk PE on LMWH anticoagulation over the first 2 – 3 days and ensure the patient remain stable before switching to oral anticoagulation. Although warfarin was the traditional gold standard for anticoagulation among patients with pulmonary embolism, NOAC are now considered non-inferior to warfarin with lesser bleeding risk profile. The 2019 ESC guidelines, now recommends NOAC in preference to a vitamin K antagonist among eligible patients with no contraindications.³ Considering that the more common risk factors for venous thromboembolism were absent in this patient, such as advanced age, major surgery, immobilization, cancer or a previous COVID-19 infection, work up for any hypercoagulable state was deemed necessary.⁴

In this patient with underlying protein C deficiency who presented with pulmonary embolism (PE) and deep vein thrombosis, the appropriate management is the use of anticoagulation, However, considering that the patient was also diagnosed with diffuse adenomyosis with abnormal uterine bleeding, use of anticoagulation may worsen menstrual bleeding and aggravate the patient’s anemia. In a retrospective study of Hong et al in 2017, they evaluated the incidence of venous thromboembolism with concomitant adenomyosis. Of the 41 patients included in the study, five had associated venous thromboembolism (all five had pulmonary embolism). Three had worsening bleeding following anticoagulation which gonadotropin releasing hormone analogs were effective in controlling. Four of the five patients eventually underwent hysterectomy for long term management of adenomyosis.¹ Treatment of these patients remain challenging. In the setting of an active VTE, common management options for menstrual bleeding such oral contraceptive pills are usually contraindicated. All patients in the study of Hong et al were treated with GnRH analogs inducing a sustained period of amenorrhea, hence, preventing hemorrhagic episodes while ongoing anticoagulation treatment and until the thrombus has resolved.¹

All patients with pulmonary embolism should receive at least 3 months of anticoagulation. Extended oral anticoagulation therapy reduces the risk for recurrent VTE by < 90%, but this benefit is partially offset by the risk of bleeding. However, in this patient with persistent risk factor for venous thromboembolism, extended duration of anticoagulation is recommended using NOAC Apixaban or Rivaroxaban weighing the risk for increased bleeding.³

The patency of the pulmonary arterial bed is restored in the majority of PE survivors within the first few months following the acute episode; therefore, no routine follow-up CTPA imaging is needed. However, in some patients, thrombi become persistent and organized, which in rare cases may result in Chronic Thrombo-embolic pulmonary hypertension (CTEPH), a potentially life-threatening obstructing vasculopathy. The diagnosis of CTEPH is based on findings obtained after at least 3 months of effective anticoagulation, to distinguish this condition from acute PE hence the recommended follow up is after 3 months to assess symptom recurrence, bleeding risk and early 2D echocardiogram.³ The aims of an efficient follow-up strategy should be to provide appropriate care such as exercise rehabilitation, treatment of comorbidity, behavioral education, and modification of risk factors and to ensure early detection of CTEPH for further diagnostic workup and specific treatment.³

In conclusion, occurrence of venous thromboembolism in patients with adenomyosis is uncommon and several treatment dilemmas may be encountered, however it can be managed successfully with careful multidisciplinary planning, timely intervention and meticulous monitoring. Efficient follow-up strategy after pulmonary embolism should be provided together with continuous gynecologic treatment and monitoring to prevent recurrence and adverse side effects of anticoagulation treatment.

Keywords
Venous thromboembolism, Protein C deficiency, Pulmonary
embolism, Adenomyosis

ACKNOWLEDGMENTS

The authors would like to acknowledge all attending physicians involved in the management of the case, your invaluable
contribution has made this case a success. Special thanks to our beloved The Medical City Cardiology Department and our cardiology consultants for their unwavering support and provision of inspiration, nothing else but much gratitude.