Table 6.

Study results on the prevalence or incidence of heavy menstrual bleeding.

Author, year	Study design	Overall risk of biasa	Antiplatelet drug type and dose	Menorrhagia: definitionand assessment method	Intervention	Comparison
Wun et al. [26], 2013	Randomized double-blind controlled phase 2 trial	No information	Prasugrel 5 mg daily	Menorrhagia not further specified Either events requiringmedical attention or recorded in retrospect during study visits by interviewing patients	Prasugrel	Placebo
					60 d incidence of menorrhagia in patients with SCD: 2/21 (9.5%)	60 d incidence of menorrhagia in patients with SCD: 0/9
Cuadrado et al. [27], 2014	Randomized open-label controlled trial	Serious	Aspirin 75-125 mg	Menorrhagia not further specified Assessed by questionnaire at study visits or from eneral physician/hospital reports	Aspirin	Aspirin + low-intensity VKAb
					aPL-positive patients, median FU 3 y: 0/80 reported menorrhagia	aPL-positive patients, median FU 3 y: 10/80 (12.5%) reported menorrhagia
Kawamatsu et al. [32], 2021	Retrospective cohort study	Serious	Not reported	Menorrhagia not further specified Based on data collected from electronic medical records	Antiplatelet	DOAC	VKA		Antiplatelet + anticoagulant
					Patients with Fontan circulation: 2/28 (7.1%) menorrhagia	Patients with Fontan circulation: 1/16 (6.3%) menorrhagia	Patients with Fontan circulation: 4/16 (25%) menorrhagia		Patients with Fontan circulation: 5/10 menorrhagia
Rodpetch et al. [33], 2021	Cross-sectional study	Serious	Aspirin 81 mg, clopidogrel 75 mg	Using the subjective definition of HMB as the gold standard, an MBQ score of ≥21.5 wasused to define HMB (sensitivity 82.9%; specificity 83.1%)	Antiplatelet (N = 16)	VKA (N = 29)		DOAC (N = 4)
					25.0% (95% CI, 7.0-52.0)	27.6% (95% CI, 12.7-47.0)		25.0% (95% CI, 0.6-80.0)
Matsushita et al. [34], 2022	Prospective cohort study	Serious	Not reported	HMB is defined as the usual rate of changing pads during full flow higher than 8 times daily Based on a structured questionnaire	Antiplatelet	Anticoagulant		Combination
					Women with Fontan circulation: 3/8 HMB	Women with Fontan circulation: 2/8 HMB		Women with Fontan circulation: 2/2 HMB

aPL, antiphospholipid antibodies; DOAC, direct oral anticoagulant; FU, follow-up; HMB, heavy menstrual bleeding; MBQ, menstrual bleeding questionnaire; SCD, sickle cell disease; VKA, vitamin K antagonist.

^aOverall risk of bias judgments based on the Risk of Bias in Non-randomised Studies - of Interventions assessment tool.

^bTarget international normalized ratio, 1.5 (range, 1.3-1.7).