What are the possible causes of large menstrual clots in a reproductive‑age woman?

Large Menstrual Clots: Causes and Evaluation

Large menstrual clots (≥1 inch diameter) are a hallmark sign of heavy menstrual bleeding and indicate excessive blood loss that overwhelms normal endometrial hemostatic mechanisms, requiring systematic evaluation for structural, hormonal, and coagulation abnormalities. 1

Understanding the Mechanism

Large clots form when menstrual blood loss exceeds the endometrium's capacity for normal hemostasis. During physiological menstruation, progesterone withdrawal triggers bleeding that is controlled through platelet aggregation, fibrin deposition, and thrombus formation, while fibrinolysis prevents clot organization within the uterine cavity. 2 When this delicate balance is disrupted—whether by excessive bleeding volume, impaired coagulation, or enhanced fibrinolysis—large clots develop as the body attempts to control hemorrhage. 2

Systematic Evaluation Using PALM-COEIN Framework

The ACOG PALM-COEIN classification provides the algorithmic structure for identifying causes: 3

Structural Causes (PALM)

• Polyps: Endometrial polyps protruding into the uterine cavity cause irregular or heavy bleeding with clot formation. 4

• Adenomyosis: Frequently coexists with fibroids, presenting with heavy menstrual bleeding, dysmenorrhea, and dyspareunia, most commonly in women in their 40s. 5

• Leiomyoma (fibroids): Submucosal fibroids that project into the uterine cavity are strongly associated with heavy menstrual bleeding and large clots, typically presenting with an enlarged, irregular uterus on palpation. 4, 5

• Malignancy/hyperplasia: Endometrial hyperplasia and malignancy must be excluded, especially in women with risk factors (obesity, unopposed estrogen, age >45 years), as these represent serious etiologies. 4, 5

Nonstructural Causes (COEIN)

• Coagulopathy: Up to 20% of women with heavy menstrual bleeding have an underlying inherited bleeding disorder, with von Willebrand disease being the most common (affecting 13% of adolescents with abnormal uterine bleeding). 6, 7 Women on anticoagulation have dramatically increased risk—70% experience heavy menstrual bleeding, with NOACs like rivaroxaban causing rates of 27% versus 8.3% with warfarin. 5, 8

• Ovulatory dysfunction: The most common cause of abnormal uterine bleeding in otherwise healthy women, resulting from anovulation or oligo-ovulation. 3, 7 This includes PCOS (affecting 4-6% of women), hypothalamic amenorrhea, and perimenopausal transition. 5

• Endometrial disorders: Primary endometrial disorders involve molecular deficiencies in endometrial hemostasis—abnormalities in tissue factor, thrombin, plasminogen activators, or their inhibitors—representing intrinsic problems independent of hormonal or structural factors. 4, 2

• Iatrogenic: Progestin-only contraceptives (pills, DMPA, implants) frequently induce irregular bleeding patterns. 5 Antiepileptic drugs (carbamazepine, phenobarbital, phenytoin) induce hepatic metabolism of sex hormones, reducing their bioavailability. 5

• Not yet classified: Encompasses causes that don't fit within the framework. 4

Diagnostic Algorithm

Immediate Assessment

1. Rule out pregnancy first in all reproductive-age women—this is mandatory before proceeding. 4, 5

2. Assess bleeding severity using specific predictors:

   • Clots ≥1 inch diameter 1
   • "Flooding" (changing pad/tampon more frequently than hourly) 1
   • Low ferritin indicating iron deficiency 1

3. Screen for bleeding disorders when:

   • Flooding and/or prolonged menses present 1
   • Personal or family history of bleeding exists 1
   • Heavy menstrual bleeding since menarche 7
   • This warrants hematology referral 1

Laboratory Evaluation

• Serum TSH: Evaluate for thyroid dysfunction (both hypo- and hyperthyroidism cause menstrual irregularities). 4, 5

• Serum prolactin: Assess for hyperprolactinemia from pituitary adenomas, hypothyroidism, or medications (antipsychotics, antiepileptics). 4, 5

• Complete blood count: Document anemia severity. 1

• Coagulation studies: When bleeding disorder suspected based on history—include von Willebrand panel, platelet function testing. 6, 1

Imaging Strategy

• Transvaginal ultrasonography is first-line imaging for structural causes. 4 Avoid in virgins; use transabdominal approach instead. 3

• Saline-infusion sonohysterography or hysteroscopy provides superior detection of endometrial polyps and submucosal fibroids compared with standard ultrasound. 4

• Hysteroscopy enables direct visualization and can identify focal lesions missed by blind endometrial sampling. 4

Endometrial Sampling

• Endometrial biopsy is preferred over dilation and curettage—it's less invasive, safer, and lower cost for diagnosing hyperplasia or cancer. 3 However, sensitivity varies with lesion characteristics (focal vs. diffuse, size, location). 3

• Indications: Age >45 years, obesity, unopposed estrogen exposure, failed medical treatment, or persistent irregular bleeding. 3

Critical Pitfalls to Avoid

• Never perform digital pelvic examination in pregnant women with vaginal bleeding until placenta previa and vasa previa are excluded—this can cause catastrophic hemorrhage. 4

• Don't dismiss heavy menstrual bleeding since menarche as "normal"—this pattern strongly suggests an underlying bleeding disorder requiring hematologic evaluation. 7

• Don't initiate hormonal treatment for unexplained bleeding without evaluation—progestin-only contraceptives might mask symptoms of underlying pathology including pelvic malignancy. 5

• Don't assume all heavy bleeding is hormonal—endometrial biopsy sensitivity is imperfect and can miss focal lesions, so if medical treatment fails, further investigation with hysteroscopy is indicated. 3

• Recognize that women on anticoagulation require specialized management—70% experience heavy menstrual bleeding, and successful treatment may require modification of the anticoagulation regimen in addition to hormonal or hemostatic therapy. 8