Case Presentation by Amy Buth, MD
A 12 y/o G0P0 presents to the ED with her mother and grandfather with complaints of vaginal bleeding for the past 20 days. Four days prior, she developed a severe frontal headache with fatigue. This morning she felt nauseated and had one episode of nonbloody/nonbilious emesis. She also developed diffuse abdominal cramps with extreme fatigue, leading to her collapsing at home. Her mother therefore brought her daughter in to the ED right away. Per the mother, the patient has irregular heavy periods which last 7 -10 days. Menarche was December 2013. Last cycle was October 14-November 4, 2014. She missed her cycle in August and September of 2014. During the past 20 days, she has been using 10 pads/day and noticing clots. She is not sexually active and denies any trauma or abuse. She currently feels weak and dizzy. She denies any fevers, chills, chest pain, shortness of breath, dysuria, hematuria, increased urgency or frequency with urination, or diarrhea.
PMH: Asthma (resolved)
SurgH: Right inguinal hernia repair 2011
Gyn: G0P0. Began menstruating December 2013; typically as a 7 day cycle
Meds: Tylenol for pain PRN
FH: Denies family history of bleeding, bruising, thrombotic disease, breast/uterine/ovarian/colon cancer, hypertension, or diabetes
SH: denies alcohol, tobacco, illicit drug use. The patient is a Jehovah Witness
Vitals: Temp 37.0 oral, BP 120/66, HR 118, RR 20, 98% on RA. Positive orthostatics
Constitutional: Lethargic, poor eye contact, laying on the bed in mild distress.
Eye: PERRL, EOMI, no discharge, conjunctival pallor
Respiratory: Lungs CTA bilaterally, no cough, no wheezing, no cyanosis.
Cardiovascular: Tachycardia, regular rhythm, no chest pain, no palpitations, no peripheral edema, good pulses equal in all extremities
Gastrointestinal: Bilateral lower quadrant tenderness, no distension, no rebound tenderness, no palpable masses
Genitourinary: Pelvic exam: normal external genitalia, blood at the introitus, blood noted in the vaginal vault, there is slow active bleeding from the cervix. Bimanual exam: uterus is anteverted and normal in size, no adnexal masses or tenderness, no cervical motion tenderness
Integumentary: Warm, dry, pallor
Hematology/Lymphatics: No petechia or bruising
Neurologic: Symmetric face, decreased strength in all extremities bilaterally secondary to fatigue and poor effort
Pregnancy test: negative
CBC: 6.8>4.6/14.7<393 with 77% PMNs and 19% lymphs. MCV 75 and RDW 13.6
BMP: 137/3.8/103/24/11/0.52, glucose 98
TSH 6.149 (NL 0.210 – 4.940), T3 total 139 (NL 60 – 180), T3 free 3.9 (NL 1.4 – 4.4), total Thyroxine 8.7 (NL 6.2 – 14.6), free Thyroxine 1.1 (NL 0.8 – 1.8)
Prolactin 15.3 (NL 2.8 – 29.2)
von Willebrand activity 348 (NL 43-138), von Willebrand antigen 244 (60-153), Factor VIII 395.7 (63-150)
1) What is the patient’s most likely diagnosis?
c) Anovulatory bleeding
d) von Willebrand Disease
2) After placing the patient on a cardiac monitor and starting a fluid bolus, what would be the best next step?
a) Uterine packing
b) Order O negative blood
c) Order a stat transvaginal ultrasound
d) Consult pediatric gynecology
3) What is the typical treatment for this diagnosis?
a) Gonadotropin-releasing hormone agonists
b) Synthetic thyroid hormone therapy
c) High dose estrogen therapy
d) Desmopressin / DDAVP
4) BONUS: The patient and her family are Jehova’s Witnesses. You develop great rapport with the family and have a heart to heart discussion about the patient’s treatment and safety. The patient and her family are grateful for your recommendations but are refusing a blood transfusion. They are agreeable to discuss alternative treatment plans. The patient is tachycardic, lethargic, orthostatic, and actively bleeding with Hg 4.7. You again strongly encourage the importance of the blood transfusion. The family then asks to be discharged so they can go to another Children’s Hospital that has a Jehovah’s witness liaison for more direction. What do you do?
a) Follow the patient/family’s wishes and do not give a blood transfusion. Consider other options.
b) Discharge the patient so they can go to another facility of their choice
c) Contact the court to make a ruling
d) Call security to keep the patient and proceed to give the blood transfusion
Question 1: Perimenarchal adolescents who have abnormal uterine bleeding typically results from anovulation (C). During the anovulatory cycle, estrogen levels rise but in the absence of ovulation, a corpus luteum never forms. Therefore, progesterone is not produced, causing the endometrium to become hyperproliferative. Once the endometrium outgrows its estrogen supply, it leads to irregular sloughing and bleeding. Sometimes anovulation occurs from an abnormality in the hypothalamic-pituitary-ovarian axis. The hypothalamus secretes GnRH which stimulates the pituitary to produce FSH and LH which act on the ovarian follicles and ovarian theca cells respectively. If there is an alteration to the GnRH release, this will affect FSH and LH. Thus, if there is a decrease in GnRH such as with hypothyroidism (C), this leads to decreased FSH/LH that may result in amenorrhea. Increased prolactin can also lead to GnRH suppression and amenorrhea. Hyperthyroidism on the other hand would lead to menorrhagia. In this case, the patient had an elevated TSH but normal T3/T4 results which suggests subclinical hypothyroidism which would not cause the irregular heavy bleeding. She also had a normal prolactin level. Polyps, leiomyomas (A), and ovarian neoplasms leading to irregular bleeding are less frequent in this young adolescent group. If there is considerable bleeding around menarche enough to necessitate blood transfusions, coagulopathies like von Willebrand Disease (D) should be excluded. VWD is a common coagulation abnormality that arises from a deficiency of von Willebrand factor, a protein required for platelet adhesion, platelet-endothelial adhesion, and fibrin clot formation by acting as a carrier protein for factor VIII. In this patient, the von Willebrand activity (also known as the Ristocetin Cofactor) is elevated to 348 (normal 43-138), von Willebrand antigen is elevated at 244 (normal 60-153), and factor VIII is 395.7 (normal 63-150). Patients with VWD typically have normal to decreased levels of VWF antigen, VWF activity, and Factor VIII. A possible explanation for the elevated levels is that VWF is an acute phase reactant that could be elevated secondary to the patient’s clinical state.
Question 2: After running through ABCs and beginning fluid resuscitation, the patient should receive a blood transfusion (B) due to her Hg being 4.6 with tachycardia, lethargy, lightheadedness, fatigue, and positive orthostatics. This patient is symptomatic from her anemia secondary to vaginal bleeding. She is actively bleeding but not profusely bleeding due to a ruptured major vessel. Uterine packing (A) may be necessary in severe life-threatening blood loss. Specifically, a foley catheter can be placed in the cervix to tamponade the bleeding. Packing in light bleeding has increased risk of infection and is usually avoided. A transvaginal ultrasound (C) is needed, but should wait until the patient is stable for imaging. Pediatric gynecology (D) should be consulted but the patient is unstable and needs blood products first.
Question 3: The treatment for anovulatory bleeding in this patient is high dose estrogen therapy which should be initiated after OBGYN consultation and recommendations (C). If Hg >12 g/dL you can supplement with iron, NSAIDS to help reduce flow, and consider oral contraceptive pills if the patient is sexually active. If Hg 9-12 g/dL, OCP BID until bleeding stops and continue OCP QD for 21 days followed by 1 week of placebo pills. If Hg <9 g/dL, admit to hospital and transfuse based on degree of hemodynamic instability. OCP Q4H until bleeding slows and then OCP QID for 2-4 days followed by OCP TID for 3 days, and then OCP BID for total of 21 days or until HCT >30%. Gonadotropin-releasing hormone agonists (A) can be used for temporarily shrinking uterine fibroids and temporarily stop menstrual bleeding. Hormonal birth control can also be used to reduce bleeding, cramps, and pain for women with fibroids. Synthetic thyroid hormone therapy (B) is used for hypothyroidism. Desmopressin / DDAVP (D) is used for von Willebrand Disease. It is known to increase VWF and factor VIII levels.
Question 4: This is a tricky ethical question because the patient herself is refusing blood as well as her parents. She is a minor and cannot make decisions on her own at this point. In general, if a child needs blood to save his/her life, you must give blood (D) – even over the objection of the patient and parents. Parents do not have the right to refuse life saving treatment for a minor. It is important though to seek parental consent for their child even if they refuse. This may lead to a constructive conversation that could provide the family with a better understanding of why the patient needs the blood transfusion. In this particular case, the blood products were ordered, and the ED physicians and the family had a long conversation about the benefits and risks of the transfusion. The family kept refusing the transfusion. Hematology was consulted to see if there was any other option to treat the anemia. They said blood was necessary. Therefore, two services and two ED physicians were in agreement to the blood transfusion. By this time, the blood arrived, and the family tried to leave AMA. The ED physicians called a member of the ethics committee who agreed the patient’s safety takes over and a blood transfusion was necessary. Fortunately, good rapport was eventually made between the family and the physicians, and the family finally signed consent for a unit of packed red blood cells. OBGYN was involved and initiated Premarin.
Hoffman BL et al. Chapter 8. Abnormal Uterine Bleeding. Williams Gynecology, 2e. New York, NY: McGraw-Hill; 2012.
Morrison LJ, Spence JM. Chapter 99. Vaginal Bleeding in the Nonpregnant Patient. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7e.New York, NY: McGraw-Hill; 2011.
Rick, Margaret. Treatment of von Willebrand disease. UptoDate. Nov 1, 2013
Sass AE, Kaplan DW. Adolescence. CURRENT Diagnosis & Treatment: Pediatrics, 22e. New York, NY: McGraw-Hill; 2013.
Stewart, Elizabeth. Uterine Fibroids: Beyond the Basics. UpToDate. Oct 11, 2013
Image courtesy of ScienceBlogs: Pharyngula. http://scienceblogs.com/pharyngula/2006/04/06/why-the-wingnuts-hate-plan-b/.