Cheryl Cummings Stegbauer, CFNP, PhD
Clinical Case Report Editor
AZ, a 19-year-old obese female, presented to her primary care provider complaining that her menses was longer than usual. She described a prolonged, heavy menstrual flow with increased cramping over the past 8 days. This was unlike her normal menses, which were regular in the past.
Menorrhagia is a common complaint. Approximately 5% of females seek medical attention for this condition.1 Menorrhagia is defined as cyclic menstrual bleeding producing more than 80 mL of blood and/ or bleeding for more than 7 consecutive days.1-5 Most individuals cannot accurately quantify the amount of menstrual bleeding in mL.6 Therefore, it is often helpful to ask the patient how the menses is disrupting her lifestyle.7
Most women have a consistent pattern of menstrual bleeding from month to month. When there is an excessive amount of bleeding during the expected menstrual cycle, an underlying organic or hematologic etiology must be considered.3
Since the definition of heavy menstrual bleeding varies, it is important to have guidelines for menstrual bleeding. A normal menstrual pattern occurs every 21 to 35 days8 and lasts from 2 to 7 days. The average woman loses approximately 30 to 40 cc of blood each cycle, which represents eight soaked pads or tampons per menses.2
* Obtaining Patient History
It is most important to obtain a detailed obstetric and gynecologic history. By comparing how the patient’s current menstrual cycle differs from her normal menstrual cycles in relation to duration, frequency, and intensity, the nurse practitioner (NP) can gain insight into the severity of bleeding.9-11
Further details should be obtained if the patient reports any of the following situations: menses lasting 3 or more days longer than usual; bleeding between each cycle; decreased intervals between the menses by 4 or more days; sudden increase of two or more sanitary pads or tampons per day; the interval between each menses is less than 21 days; each menses lasts longer than 7 days; passage of significant clots or flooding.10,12 The patient’s sexual history, use of birth control, possible pregnancy, and prior gynecologic surgeries must also be noted.
Nurse practitioners should explore the patient’s past medical history. It is important to know if the patient has a known bleeding or clotting disorder, thyroid disorder, chronic liver disease, or renal disease.11,13 The identification of renal disease is significant because patients with chronic renal disease frequently have excessive heavy menses.14 The NP should also ask about any over- the-counter medications, prescription drugs, or herbal remedies.
AZ had a medical history of obesity, migraine headaches, asthma, depression, and dyslipidemia. Her history was negative for thyroid disease, liver abnormalities, chronic renal disease, and bleeding or clotting disorders. There was no significant past surgical history. Her medications included: norethindrone/ ethinyl estradiol (Ortho- Novum 7/7/7), ibuprofen 800 mg tid prn or naproxen prn, fluticasone bid, and albuterol prn.
AZ reached menarche at age 12, and reported a regular menses approximately every 28 days, which usually lasted 7 days. During her most recent menstrual cycle however, she described a heavy menses; she changed a saturated pad every hour for 12 consecutive days. She had never been pregnant.
AZ believed that because she was taking norethindrone/ethinyl estradiol consistently, she did not need to use condoms. She had been sexually active with her current partner for 4 years. She had no history of a sexually transmitted infection and her Papanicolaou smear 6 months prior was normal.
The patient’s family history should be explored in detail as well. AZ’s family history revealed that her sister also experienced heavy, prolonged menstrual bleeding. She also had lupus. Oral contraceptive pills controlled her sister’s menses.
AZ’s mother, who was in the end stages of metastatic cancer, had a long history of heavy menses with clotting. Her mother’s heavy menses was never evaluated. AZ also reported that her maternal grandmother had a history of heavy menses. Although this family history was significant, there were no reports of any specific hmatologie disorders.
* Review of Systems
To determine if the patient is hemodynamically stable, ask about shortness of breath, fatigue, lightheadeddness, dizziness, presyncopal or syncopal events,>5 nausea, vomiting, or fever.
A thorough bleeding history should also be taken, particularly mucocutaneous bleeding. This includes prolonged epistaxis, easy bruising, gingival bleeding, or heavy menses.11 Severe abnormal bleeding (e.g., development of iron deficiency anemia requiring a blood transfusion; hemoglobin less than 10gm/dL) that is recurrent or that affects different anatomical sites are strong possibilities for an underlying systemic coagulopathy.16,17 Heavy bleeding associated with tooth extraction, surgery, postpartum, prolonged bleeding with superficial cuts, or reports of a heavy prolonged menses since menarche are also highly predictive of a bleeding disorder18 but the history may be subtle.
Heavy menstrual bleeding may be the only clinical manifestation of an inherited bleeding disorder.1,16,17,19,20 Finally, the NP should ask about any dyspareunia, vaginal discharge, or dysuria.
Upon questioning, AZ reported intermittent epistaxis and bruising easily as a teenager. She denied any gum bleeding or other sources of bleeding.
There was no history of shortness of breath, dizziness, fatigue, or presyncopal or syncopal events. AZ reported no significant history of nausea or vomiting, and no vaginal or urinary complaints.
* The Physical Examination
The patient’s hemodynamic status must be evaluated. In examining the patient’s skin, note petechiae and ecchymosis, which may be indicative of a hematologic disorder.10,21
In addition, it is important to check for any virilization including hirsutism,11 striae, or acanthosis nigricans. Next, the NP should examine for thyromegaly and abdominal tenderness, rigidity, or masses. A thorough gynecological and bimanual exam is needed to verify the bleeding site. Foreign bodies and discharge, as well as uterine or adnexal tenderness or masses, should be assessed.10 Inspection of the urethra, vagina, cervix, and rectum, including a Hemoccult test, is imperative to determine the source of bleeding.9
AZ was 5’6” and weighed 262 pounds, with a body mass index of 42. Her vital signs were as follows: left arm blood pressure (BP) was 128/90 (sitting) and right arm BP (sitting) was 128/88; pulse at 76 per minute; temperature 99.8 orally. There were no orthostatic changes with position change.
She exhibited no striae or acanthosis nigricans. Ecchymosis and petechiae were not observed. Her thyroid was not palpable. Her heart had normal S^sub 1^ S^sub 2^ heart sounds without murmur. Her abdomen was tender throughout with no masses, splenomegaly, rebound, or rigidity.
Her genital exam was normal, showing no external or internal lesions. She had an active bloody discharge per the cervical os. There was no foreign body detected, nor was there presence of any abnormal discharge. The bimanual exam was normal without any cervical motion, uterine, or adnexal tenderness. There were no masses palpated. The rectal exam was normal and the hemoccult test was negative.
* Laboratory Data
Initial laboratory work included a beta human chorionic gonadotropin, complete blood count with differential, platelet count, reticulocyte count, and cultures for chlamydia and Neisseria gonorrhoeae. If a bleeding disorder is suspected, obtain a prothrombin time, partial prothrombin time (PTT), and bleeding time.5,19
AZ’s beta human chorionic gonadotropin quantitative was negative, her white blood cell count was normal, hemoglobin and hematocrit were slightly down at 13.7 and 38.3 respectively.
Her platelet count was normal and prothrombin time was normal. The PTT and reticulocyte count were elevated at 33.6 seconds (normal 20.8 to 32.8) and 2.9 respectively. Additionally, AZ recently had a normal thyroid-stimulating hormone, blood urea nitrogen, creatinine, fasting blood sugar, iron profile, and urinalysis.
* The Initial Management Plan
The initial management plan was to increase AZ’s norethindrone/ ethinylestradiol dosage to twice a day until the bleeding stopped, and then resume a once-daily dosing. She was also given an antiemetic to use every 12 hours as needed and was told to return to the clinic in 3 days.
Iron supplements to treat anemia and antiprostaglandin medications such as ibuprofen or naproxen are also often recommended. To prevent heavy bleeding, combination oral contraceptives are recommended. If the patient cannot take oral contraceptives due to contraindication, progesterone can be given for 10 days starting on either day 11 or 14 of the menstrual cycle.22
One considerable concern is the risk for a venous thromboembolism, which is often related to an inherited defect such as factor V Leiden mutation.22 This mutation interferes with protein C-protein S anticoagulant pathway and is a risk with the increased oral contraceptive dose.8
* The Diagnosis
In AZ’s case, a coagulation disorder was suspected due to her heavy cyclic menstrual bleed,history of easy bruising and epistaxis, the prolonged PTT, and her significant family history of heavy menses.
Consequently, the PTT, hemoglobin, and hematocrit were repeated, and a von Willebrand (vWD) panel and bleeding time were obtained. A pelvic ultrasound was also ordered to rule out any fibroids, tumors, or cysts.
The vWD panel usually includes a factor VIII complex activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and a ristocetin cofactor activity (vWF:RCo). In mild cases of vWD, the FVIILC is usually normal or slightly reduced. Nevertheless, in severe vWD, the FVIII:C may be less than 5% to 10% of normal. In severe cases, hemarthrosis and hematomas are noted secondarily to markedly low concentrations of factor VIII.16,17,23,24
Patients with mild forms of vWD usually have approximately 30% to 50% of normal vWF:Ag.16,17,23 The vWF:RCo measures how well the vWF is functioning. In Type 1 vWD, the vWF:Ag and vWF:RCo are usually reduced.23
Abbreviations
The bleeding time can be normal with a congenital bleeding disorder. The accuracy and reliability of the bleeding time is decreased in mild cases of vWD. However, it has been useful in demonstrating the bleeding tendency in severe cases of vWD.25 Overall, test results can vary depending on the administration technique. Moreover, cutaneous scarring can occur on the tested individual.18
AZ’s results revealed a mild drop in the hemoglobin and hemotocrit of 13.2 and 36.4 respectively. The PTT remained elevated at 33.6 seconds, the bleeding time was normal at 6.30 minutes, and the FVIII:C was normal at 71%. The vWF:Ag (normal = 43% to 150%) and the vWF:RCo (normal = 47% to 150%) were depressed at 28% and 31% respectively. Her pelvic ultrasound was normal. After these results were obtained, a hematologist ordered further testing, including vWF multimers. The vWF multimers are a qualitative measure of the structure of the vWF molecule and are only necessary if the vWF:Ag and vWF:RCo are abnormal. Conversely, it is not necessary if Type 3 vWD is known.26
Adolescents with menorrhagia are at a higher risk of having a bleeding disorder, especially once pregnancy and a pelvic pathology have been ruled out.4,5,27 Von Willebrand disease should be suspected in women with menorrhagia, other mucosal bleeding, excessive bruising without petechiae, heavy bleeding with tooth extraction, surgery, or postpartum. It should also be suspected in women who have a family history of heavy bleeding with menses or surgical procedures.8,13
The vWF can be falsely elevated if the patient is pregnant or experiencing other hormonal fluctuations, under a lot of stress, in a postoperative period, has an infection, or an inflammatory response. This can result in a normal laboratory value.28 In order to help prevent an inaccurate result due to hormonal fluctuations, it is recommended that testing for vWD be done on days 1 through 3 of the menstrual cycle.19 If there is a strong history suggestive of vWD, repeat testing may be necessary.16,17,29
The patient’s blood type affects results.16,17 If a patient is type O, generally the person will have lower vWF:Ag levels (36 to 160 u/dL). Types A, B, and AB have higher levels.13,19
AZ’s menorrhagia was secondary to vWD Type 1. Von Willebrand disease is the most common, autosomal dominant, congenital bleeding disorder affecting 0.5% to 1% of the general population.13,18,30,31 Menorrhagia is often the first symptom in women with vWD.32 This disease stems from the decreased production of vWF, a plasma protein necessary for normal blood clotting.18 When blood vessels are injured, platelets do not adhere properly. As a result, it takes longer for the bleeding to stop.
Once a patient is diagnosed, it is important to consider other family members. Recall that AZ’s sister had lupus and a history of heavy menses, and she responded favorably with oral contraceptive therapy. It is possible that acquired vWD can present in females with systemic lupus erythematosus, with the production of anti-von Willebrand factor antibody.33 Therefore, a response to hormonal therapy should not prevent a further diagnostic workup for a bleeding disorder.34 In this case, AZ’s sister should also be tested for vWD.
Acquired vWD may be found in patients with no family history, as well as in association with another disorder, such as leukemia, systemic lupus erythematosus, lymphoma, congenital heart disease, and hypothyroidism.35
However, this deficiency may appear when neither parent has the abnormality. In that case, it would be a new mutation and vWD could be passed on to future children.
* Treatment
For AZ, desmopressin acetate (DDAVP) nasal spray (Stimate) was chosen to help control her menorrhagia. Desmopressin acetate is the treatment of choice for vWD Type I.13,36 Desmopressin maybe given intravenously or intranasally, however, the intranasal spray is equally efficacious and more convenient.36
Patients should also use desmopressin acetate prophylactically before minor outpatient gynecological surgeries, as well as for other mucosal or dental procedures. Desmopressin acetate promotes the release of normal functioning vWF from the blood vessel’s endothelial cell lining.13,18,30 It strengthens hemostasis by decreasing the bleeding time, and increasing levels of factor VIII and the vWF.31,37,38
The NP must watch the patient’s sodium levels, since desmopressin acetate can cause hyponatremia.2031 To prevent this from occurring, the patient is instructed to limit fluid intake 18 hours after taking desmopressin acetate.30,39
Other side effects include mild tachycardia, headache, and flushing, which are related to the vasomotor effects of the medication. These symptoms are usually mild and transient.31,36,40 Lastly, desmopressin acetate is usually contraindicated with vWD Type 2B, due to the possibility of worsening effects of bleeding diathesis and thrombocytopenia.18,38 If the patient has less than 10% of the vWF:Ag, then desmopressin acetate will be ineffective.13,18,31,41
* Education
After AZ’s condition was diagnosed, her NP made sure she was thoroughly educated about vWD. She was instructed to report any breakthrough bleeding or irregular menses. Women with vWD have heavier menses. If menstrual bleeding occurs at other times, then another source must be ruled out.
AZ was instructed to report headaches, muscle weakness, nausea, vomiting, and seizures, because these can be signs of hyponatremia.36,42 The patient must avoid aspirin as well as nonsteroidal anti-inflammatory drugs, due to the risk of further defects in platelet function. AZ was instructed to inform all providers of her new diagnosis of vWD, especially before surgical procedures to the mucous membranes (mouth, nose, throat, gastrointestinal, gynecological, and urinary tract).
Additionally, AZ was advised about potential pregnancies. In patients with vWD Type 1, the vWF: Ag, and FVIII:C increase during pregnancy. Hence, bleeding during pregnancy is relatively uncommon.16,17,30,31,43 in addition, sex hormones increase during pregnancy and prevent postpartum hemorrhage.39 Bleeding during pregnancy is noted for patients with severe disease, such as those with undetectable levels of vWF.43
New precautions for traveling were also discussed. AZ was instructed to carry an identification bracelet that indicates she has vWD Type 1 and is using desmopressin acetate.
Since the definition of heavy menstrual bleeding varies, it is important to have guidelines for menstrual bleeding.
Differential Diagnosis of Menorrhagia
Pregnancy/ectopic pregnancy/ trophoblastic disease/spontaneous or incomplete abortion
Infection: chlamydia/gonorrhea/ trichomonas
Trauma/sexual abuse
Foreign body
Medication induced: medroxyprogesterone acetate, oral contraceptive, acetylsalicylic acid, anticoagulants, nonsteroidal antiinflammatory drugs, steroids, major tranquilizers, tricyclic antidepressants
Other gynecological pathology or structural anomaly
Endocrine disorders: hyperthyroidism, hypothyroidism, polycystic ovarian syndrome
Underlying systemic disorders: von Willebrand disease, liver disease, thrombocytopenia, idiopathic thrombocytopenic purpura, severe sepsis, leukemia, aplastic anemia, hypersplenism
Dysfunctional uterine bleeding
The patient’s sexual history, use of birth control, possible pregnancy, and prior gynecologic surgeries must be noted.
Heavy menstrual bleeding may be the only clinical manifestation of an inherited bleeding disorder.
The vWF can be falsely elevated if the patient is pregnant or experiencing other hormonal fluctuations.
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ACKNOWLEDGEMENTS
The author would like to thank Jennifer Cironi, APRN and Ivy Alexander, APRN, Yale University, for their thorough review of this article.
Karen A. Stemler, MS, RN, APRN, FNP
ABOUT THE AUTHOR
Karen Stemler holds a joint appointment as a Program Instructor at Yale University School of Nursing and as a Family Nurse Practitioner in an internal medicine practice in New Haven, Conn.
Copyright Springhouse Corporation Dec 2004
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