More Than Menorrhagia
VIIA D. ANDERSON, APRN HEMATOLOGY NURSE PRACTITIONER
JANE GEYER, APRN, WHNP-BC GYNECOLOGY NURSE PRACTITIONER
Objectives
Summarize menstrual physiology
Define heavy menstrual bleeding (HMB)
Explain common bleeding disorders associated with HMB
Describe the evaluation process of HMB and Iron Deficiency Anemia (IDA)
Introduce common pharmacologic agents used to control HMB and IDA
Explain the TCH referral process for patients with HMB and IDA 13 yo obese female presents to PCP for annual visit
History of migraines (with aura) well controlled with prn Imitrex
History of epistaxis, but epistaxis occurring more frequently since starting softball Case Study: Last nosebleed 1 month ago while at the movies with her boyfriend Tiffany Menarche attained 6 months ago
Menses occurs 1-2 times/month
Menses 10 days in duration
Temp 37C, HR 101, RR 18, BP 100/62
Pallor
Fatigue
Lab Normal Ranges Result WBC 4.5-13 6.49 Hemoglobin 12-16 gm/dl 7.5 gm/dl MCV 78-95 fl 69 fl Platelet 150-450 563 Lab Absolute Retic 0.042-0.065 0.026 Count UPT Negative Results PT 10.5-15.7 seconds 11 seconds PTT 25.2-33.2 seconds 38 seconds TSH 0.5-4.3 mIU/L 0.81 mIU/L Vwf antigen 56-176% 38% Vwf activity 50-150% 34% Factor 8 47-169% 35% Von Willebrand ratio 0.7-1.2 0.9
If you encounter abnormal labs you are not sure how to interpret…………
Refer, Refer, Refer!
We’re here to help! The Menstrual Phase 1: Follicular Phase Phase 2: Luteal Phase Cycle • Begins day 1 of the menstrual • Begins on the day of the LH cycle Surge • Ovarian follicle present typically The first day of menses represents the first day of a menstrual cycle. present on ovary approximately 26 hours following ovulation. The menstrual cycle is divided into 2 phases: • Low serum estradiol and • Endometrial lining thickens progesterone hormones trigger • The subsequent decrease in a negative feedback response estradiol/progesterone levels in which GnRH pulse following ovulation causes frequency is increased, which regression or resolution of causes an increase in FSH. follicle/corpus luteum. • The increase in FSH causes a • Regression of corpus lutem rise in estradiol production, and causes loss of endometrial a formation of a dominant blood supply and ultimately, GnRH: gonadotropin releasing hormone follicle. Ovulation occurs. sloughing of the uterine lining, or • Estradiol peaks mid cycle, then onset of menses. GnRH: gonadotropin releasing hormone mid cycle surge causes positive feedback loop activation, and FSH: follicle stimulating hormone a rise in LH levels. Normal Menstrual Cycles
Average age of menarche in the US: currently 12 years (12.8 in NHC females, and 12.2 in AA females)
More cycle variability in menstrual cycles within the first 5 – 7 years following menarche.
By year 1 following menarche, up to 65% of females will have a regular menstrual cycle of at least 10 periods per year.
For females that reach menarche at age 13 will likely achieve regular menses at a slower rate. Approximately 50% of this population will have regular menses within 4.5 years of menarche. Normal Menstrual Cycles in Adolescents Vs Adults
Adolescents: Adults: Menstrual cycle length: 21-45 days Menstrual cycle length: 28-35 days
Duration of menstrual bleeding: 2-7 Duration of menstrual bleeding: 4-6 days days
Median blood loss: 30ml Median blood loss: 30 ml (approximately 3 – 6 pads per day) (approximately 3 – 6 pads per day) Abnormal Uterine Bleeding
Amenorrhea or lack of menses
Abnormal intervals of menses
Excessive volume or duration of flow
**Heavy menstrual bleeding only applies to patients with heavy menses with regular, ovulatory cycles** Pictorial blood loss assessment chart (PBAC)
The PBAC generates a score based on number of pads/tampons changed, percentage of saturation, and passage of blood clots.
A score of >= 100 has been associated with heavy menstrual bleeding (HMB). Causes of AUB in adolescents
Most common cause of AUB in adolescents within 1-2 years of menarche is anovulatory bleeding.
Up to 20-30% of patients with heavier than usual menstrual bleeding will be found to have an underlying bleeding disorder, such as von Willebrand disease.
Other differential diagnoses:
Pregnancy, polycystic ovarian syndrome (PCOS), thyroid disorders, hypothalamic dysfunction (due to obesity, low BMI, stress, excessive exercise) and/or sexually transmitted infections (STIs). Initial Gynecological Workup
Other considerations may include CBC Iron Panel • Gonorrhea/Chlamydia TSH • Urine Pregnancy Test von Willebrand Panel (includes von Willebrand antigen, von • Pelvic Ultrasound Willebrand activity, factor VIII • Androgen levels levels, and aPTT) • Prolactin levels Fibrinogen • Estradiol/LH/FSH PT/INR Treatment options
Hormonal treatments: Hemostatic treatments: Combined hormonal contraceptives: Tranexamic Acid pills, patch, vaginal ring Aminocaproic Acid Progestin only contraceptives: pills, Desmopressin (Stimate) injection, subdermal implant, intrauterine device Factor therapy Platelet transfusion Combined hormonal contraceptive pills Side effects: • Nausea when first initiated. Taking the Combined birth control pills (COCs) pills at night with food may help. contain two hormones, estrogen and • Irregular bleeding patterns when first progestin. initiated, which improve within 3 The combined pills are typically used for months of use. 21-24 days at a time, with a hormone • Mild headaches when first initiated. free interval of 4-7 days. This should improve within 3 months of Menstrual bleeding should occur during use. the hormone-free interval of the pill • COCs do not cause mood changes or pack. weight gain. COCs may be contraindicated in • Risk of a stroke or a blood clot! certain medical conditions, please refer Remember ACHES to CDC recommendations. Combined Hormonal Contraceptive Patch
The patch contains two hormones, Side effects: estrogen and progestin. • Skin irritation. The patient should rotate The transdermal patch can be applied placement sites to help decrease topically to the buttock, abdomen, upper arm, or upper torso. irritation. • Irregular bleeding patterns when first The patch should be changed every 7 initiated, which improve within 3 days on the same day of each week for 3 consecutive weeks. months of use. • The patch does not cause mood The patch should then be removed for 7 changes or weight gain. days for a hormone-free interval. A new patch should be placed following • Stroke or blood clot risk! Remember the 7 days. ACHES Combined Hormonal Vaginal Ring
The vaginal ring contains two Side effects: hormones; estrogen and progestin. • Irregular bleeding when first initiated. The vaginal ring is inserted intravaginal This should improve within 3 months of (with or without a tampon applicator). use. • The ring should not cause weight gain The ring stays inside the vagina for 21 or mood changes. days, and is then removed for 7 days for a hormone-free interval. • Risk of stroke or blood clot: Remember A new vaginal ring should be inserted ACHES! after 7 days. Progestin Only Contraceptive pill
Referred to as the “mini-pill” contains only one Side effects: hormone called norethindrone. • Irregular bleeding - typically most The POP comes in a pack with 28 days of active common within first 3 months of use hormones and does not contain a “hormone free” pill. • Amenorrhea - considered normal with perfect use. This pill is less effective as contraception and is typically used in patients with contraindications to • The POP does not cause weight gain. estrogen containing contraceptives. • Not as effective as contraception.
The POP should be taken daily at the same time. If the pill is taken >3 hours late from scheduled time, it is considered a missed dose. The patient should take the missed dose as soon as it is remembered, and continue with the rest of the pills as scheduled. Progestin only injection
Contains one progestin hormone. Side effects:
The shot is typically given every 11-13 • Weight gain weeks, but the interval between doses • Decreased bone mass density (BMD) may be adjusted based on patient • Irregular menstrual bleeding specific needs. Can be given Q 1 • Mood changes? month if needed for suppression. Can be given up to Q 15 weeks if needed for contraception.
It can be given intramuscularly or subcutaneously. Progestin only subdermal implant
Subdermal contraceptive implant: Side effects: Contains a progestin only hormone, etonorgestrel Side effects: Subdermal rod inserted in the arm. Lasts for up to 5 years for contraception but is currently FDA Irregular menstrual bleeding patterns (as approved for 3 years. highlighted above) Not considered first tier for menstrual suppression Does not effect BMD A study on bleeding patterns in Nexplanon users Weight gain in 12% of users. Mean weight revealed 22% of patients have amenorrhea, 34% had fewer than 3 spotting/bleeding episodes in gain was 3kg in 36 months. 90 days, and the remainder of patients had prolonged or more frequent menses.1 Approximately 50% likelihood of reduced menstrual bleeding Intrauterine devices (IUDs)
The levonorgestrel IUD is currently FDA Side effects: approved for heavy menstrual bleeding. • Irregular bleeding The IUD is a t-shaped device inserted into the uterine cavity. • Cramping following insertion • Spotting It is typically placed in the office as an outpatient procedure. In special • Expulsion of the device circumstances, the IUD may be inserted in the operating room or a special procedure room, to allow for more advanced bleeding precautions. About 80% of females notice less menstrual bleeding or amenorrhea after 1 year of use.
Hematology Role
Perform a clinical and laboratory evaluation for underlying bleeding disorder
Identify and manage iron deficiency anemia
Provide input regarding the management of HMB, especially in patients with hemostatic abnormalities HISTORY QUESTIONS
Family Bleeding disorders, women with heavy menstrual bleeding; unexpected surgical hemorrhage, easy bruisability; mucosal, GU, rectal bleeding, epistaxis, anemia, connective tissue disorders
Birth Birth complications, preterm (IVH), umbilical stump bleeding, cephalohematoma, bleed post circumcision
Hematological Anemia, bruising, splenomegaly, jaundice, fever, night sweats, weight loss, bone pain, joint pain, headaches HPI Medications Current and past medications; NSAIDs, aspirin, antiepileptic meds
Illness Other medical condition/ co morbidities (systemic illness/autoimmune disorders)
Surgery Surgical bleeding (dental extractions, T&A)
Menstrual Age at menarche, duration of menses, frequency of menses, pads/tampons used per day, clotting during menstrual flow, dysmenorrhea, nausea, flooding HISTORY QUESTIONS
Family Bleeding disorders, women with heavy menstrual bleeding; unexpected surgical hemorrhage, easy bruising; mucosal bleeding, epistaxis, anemia, connective tissue disorders
Birth Birth complications, preterm (IVH), umbilical stump bleeding, cephalohematoma
Hematological Anemia, bruising, splenomegaly, jaundice, fever, night sweats, weight loss, bone pain, joint pain, headaches HPI Medications Current and past medications; NSAIDs, aspirin, antiepileptic
Illness Other medical condition/ co morbidities (systemic illness/autoimmune disorders), joint disease
Surgery Surgical bleeding (dental extractions, T&A)
Menstrual Age at menarche, duration of menses, frequency of menses, pads/tampons used per day, clotting during menstrual flow, dysmenorrhea, nausea, flooding Hemostasis Evaluation
Hemostasis
Vessel Fibrin clot Injury
https://www.msdmanuals.com/home/blood-disorders/blood-clotting-process/how-blood-clots Primary Hemostasis
Initiated by endothelial damage
Vasoconstriction
Platelet adhesion
Platelet activation
Platelet aggregation
Leads to the formation of primary platelet plug
Mannucci, P. (2004). Treatment of von willebrand’s disease, New England Journal of Medicine, 351, 683-694. Secondary Hemostasis
Strengthening of plug with fibrin to form thrombus
Involves clotting factors Laboratory Evaluation
CBC
Retic
Peripheral smear
PT
PTT
Von Willebrand profile
Fibrinogen
Lupus anticoagulant
Platelet aggregation studies Lab Normal Ranges Result WBC 4.5-13 6.49 Hemoglobin 12-16 gm/dl 7.5 gm/dl MCV 78-95 fl 69 fl Platelet 150-450 550 Lab Absolute Retic 0.042-0.065 0.026 Count UPT Negative Results PT 10.5-15.7 seconds 11 seconds PTT 25.2-33.2 seconds 39 seconds TSH 0.5-4.3 mIU/L 0.81 mIU/L Vwf antigen 56-176% 38% Vwf activity 50-150% 34% Factor 8 47-169% 45% Von Willebrand ratio 0.7-1.2 1.1
Von Willebrand Disease (vWD)
Ratio of V WF:RCo V WF:Ag Mediates platelet adhesion and Ty pe FVIII V WF:RCo/ (IU/dL) (IU/dL) binds/stabilizes factor 8 V WF:Ag
Most commonly inherited bleeding Type 1 <30* <30* ↓ or Normal >0.5–0.7 disorder (AD/AR) Type 2A <30* <30–200*† ↓ or Normal <0.5–0.7 May be acquired Type 2B <30* <30–200*† ↓ or Normal Usually <0.5–0.7 Up to 20-30% women with HMB have vWD Type 2M <30* <30–200*† ↓ or Normal <0.5–0.7 Incidence ~ 1-2% of population Type 2N 30–200 30–200 ↓↓ >0.5–0.7
Type 3 <3 <3 ↓↓↓(<10 IU/dL) Not applicable
https://www.cdc.gov/ncbddd/vwd/inherited.htmlNormal 50–200 50–200 Normal >0.5–0.7 Most common
•Factor VIII, IX (hemophilia carrier) Other •Factor XI
Bleeding Rare Disorders •Factor XIII (occurs 1 in 5 million births) •Factor V, VII •Major platelet function defects Non-Hormonal Treatment Options
Tranexamic Acid (Lysteda) Aminocaproic Acid (Amicar) DDAVP Factor replacement Platelet transfusion Antifibrinolytics
Inhibit plasmin in the endometrium Suppress fibrinolysis Only taken during menses Does not regulate menstrual cycle Not indicated for dysmenorrhea May be used alone or in conjunction with hormonal treatment options to control menstrual bleeding Reduce menstrual blood flow and improve quality of life Drug accumulation in patients with reduced renal function Murray, V., Norrving, B., Sandercock, P. A. G., Terént, A., Wardlaw, J. M., & Wester, P. (2010). The molecular basis of thrombolysis and its clinical application in stroke. Journal of Internal Medicine, 267(2), 191–208. Antifibrinolytics
Tranexamic Acid Aminocaproic Acid 1300 mg TID po no more than 5 50 mg/kg po every 6 hours prn consecutive days Tabs and liquid formulation available IV formulation available IV formulation available Binding affinity to plasmin and plasminogen is 6-10x more potent Side effects: nausea, vomiting, than aminocaproic acid abdominal pain, diarrhea Side effects: nausea, emesis, diarrhea, color blindness Risk for thrombosis? Synthetic analogue of anti-diuretic hormone
Increases plasma concentration of VWF, & factor VIII; and enhance platelet adhesiveness
To control bleeding for patients with mild hemophilia A and low von Willebrand factor /type 1 von Stimate Willebrand disease Nasal spray
DDAVP challenge must be done prior to prescribing
Risk tachyphylaxis Side effects: headache facial flushing, fluid retention, hyponatremia/seizures, BP changes Treatment is given pre-operatively with surgery/dental work or bleeding episodes or during menses to control HMB
Desmopressin (DDAVP®)/Stimate
Factor replacement (ex. vWF: FVIII Patient concentrate (Humate P® ) Antifibrinolytics Education Platelet transfusion
Avoid NSAIDS/aspirin products
Management of nosebleeds
Vaseline, saline spray/saline gel, Afrin, Stimate (for vwd, platelet defects) Iron Deficiency Lab Definition Result Anemia Serum Iron Circulating iron in the blood Low (normal or high if eaten) Total Iron Binding Measure of Elevated Iron is essential for the Capacity (TIBC) transferrin/available iron production of RBCs binding sites Inadequate supply of Ferritin Iron stores in liver Low iron leads to low hgb and Transferrin Serum iron/TIBC Low low iron stores saturation Hemoglobin RBC protein transport O2 Low MCV RBC size Low RDW RBC variation High Retic / Retic hgb Immature RBC Low Etiology of IDA
Blood Loss
Systemic Ineffective Disease red cell production
RBC Destruction Kidney Disease
Nutritional Dizziness
Fatigue
Weakness
Signs and General malaise Symptoms of Pallor Pica
Iron Poor concentration Deficiency Shortness of breath on exertion Anemia Increasing cardiac output leads to: rapid heart beat
Palpitations
sweating
murmur Treatment of Iron Deficiency Anemia
Oral Iron Supplementation Dietary changes Elemental iron 1-3mg per kg •Ferrous sulfate •Iron polysaccharide complex given 1-2 times/day •Ferric iron supplement Take with citrus juice, not milk Retic count should rise in 5-10 days Intravenous Iron supplementation Hgb rise in 2-3 weeks
•Ferric Carboxymaltose Intravenous Iron supplement •IV Iron Dextran Severe anemia (hgb <5gm/dl) with hemodynamic instability
Blood Transfusion Drug Pros Cons
IV Iron • Compliance is • Potential for assured allergic reactions • More rapid (increased w/ correction of iron dextran) anemia • Low phosphorus Comparison • Skin staining • Cost of • Intravenous Oral • Easily available • Duration of Treatment Iron • Cost treatment • Low risk serious • Palatability side effects • GI upset • Constipation, nausea, vomiting • Inadequate in certain GI conditions Case Study: Tiffany
Presented for referral to HAT/GYN clinic 2 weeks after PCP visit Hemoglobin 7.3 gm/dl at presentation Non-compliance with oral iron (causing constipation) Diagnosed with low VWF Education on VWF and treatment Plan to start progesterone only contraceptive Scheduled follow up visit for IV iron infusion Will consider Stimate challenge at later date if progesterone is not effective The Young Women’s Hemostasis & Thrombosis Program within the Hematology Clinic of Texas Children’s Hospital receives multiple referrals for heavy menstrual bleeding
The Young Women's HAT program has Referral clinic on the 2nd Thursday, 3rd Thursday and 4th Tuesday each month on the Clinic 14th floor of Mark Wallace Tower Submit referral request to HAT/GYN clinic:
Epic
Phone 832-822-4362
Fax 832-825-4362 Viia D. Anderson APRN [email protected]
THANK YOU! Jane Geyer, APRN, WHNP-BC [email protected] References
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