Endometriosis Part I: Evaluation and Diagnosis

Be sure to check out our previous episode on chronic pelvic pain with Dr. Eva Reina to round out your CPP diagnosis skills!

What is endometriosis? 

• Gynecologic condition where endometrial glands and stroma occur outside of the uterine cavity that can respond to hormonal shifts of the menstrual cycle.

  • Most within pelvis, but can occur elsewhere: bowel, diaphragm, and even in the pleural cavity 

  • Benign, but can cause dysmenorrhea, dyspareunia, chronic pain, and infertility 

• Incidence

  • Occurs in 6-10% of reproductive age women, but is present in 38% of women with infertility and 71-87% of women with chronic pelvic pain! 

  • No data to suggest that endometriosis is increasing, but it is likely more recognized and being diagnosed more often now.

  • There is a familial association - first degree relatives of someone with endometriosis are at higher risk for also developing it, but the inheritance is likely polygenic-multifactorial 

• Risk factors

  • Nulliparity, prolonged exposure to endogenous estrogen (ie. early menarche, late menopause)

  • Shorter menstrual cycles, heavy periods, obstruction of menstrual outflow

  • Increased height, lower BMI, and high consumption of trans unsaturated fats

    • This does not mean that you’re going to get endometriosis if you’re tall or have a low BMI! And you’re not going to treat it by stopping eating trans fats.

    • Association doesn’t equate to causation.

• Etiology 

  • Endometriosis occurs when ectopic endometrial tissue implants, grows, and elicits inflammatory response 

  • Inflammatory response: COX-2 activity, overproduction of prostaglandins, and then chronic inflammation → triggers pain and causes infertility

    • Also why those with endometriosis will usually have flares that coincide with their menstrual cycle.

  • Nerve growth factor is also highly expressed in endometriotic lesions → increase density off nerve fibers → can explain increased sensitivity and pain 

    • Can also be explained by central sensitization (lowering threshold of pain) 

    • Go back go our CPP episode to remember what all these things are! 

  • Sampson’s Theory of Retrograde Menstruation - most popular/common theory where endometrial cells flow backwards through the fallopian tubes into the peritoneal cavity during menses

    • But, up to 90% of women HAVE retrograde menstruation, and not everyone has endometriosis 

    • Likely, there is a multifactorial cause of endometriosis, where ectopic endmoetrial tissue interacts with alterned immunity, imbalance of cell proliferation/apoptosis, aberrant signalling, and genetic factors 

    • There are certain genes that are statistically associated with endometriosis 

  • Chronic inflammation and endometriotic lesions can distort the pelvic anatomy through adhesions, endometriomas, and other substances lilke cytokines and prostaglandins that are “hostile” to normal ovarian function, fertilization, and implantation 

How do we evaluate for endometriosis? 

• History and physical

  • Usually patient will present during reproductive years with pelvic pain (ie. dysmenorrhea or dyspareunia), infertility, or ovarian mass 

  • However, there are many people with endometriosis who are asymptomatic! 

  • Diagnosis is more likely to be made in people with symptoms 

    • Remember the “PPUBS” framework 

      • Pain - can you describe your pain? 

      • Periods - menstrual history; is the pain surrounding menstruation or line up with other parts of their menstrual cycle? 

      • Urinary symptoms - there can be endometriotic lesions on the bladder → frequency, urgency, pain with voiding 

      • Bowel - symptoms include diarrhea, constipation, dyschezia, and bowel cramping 

      • Sexual dysfunction - peritoneal or deeply infiltrating endometriosis can present with dyspareunia 

  • Physical exam: can be variable depending on location and size of implants

    • You may feel nodules in the posterior fornix, uterosacral ligaments,, adnexal masses, and immobility or lateral displacement of the cervix or uterus 

    • However, exam can be completely normal 

• Rule out other causes for pelvic pain 

  • Labs - no pathognomonic lab for endometriosis 

    • CA125 can be elevated, but it’s not routinely ordered because other diseases can also elevate CA-125 levels 

    • It’s not specific and not helpful for endometriosis

  • Imaging 

    • Ultrasound is usually all you need - can see things like endometriomas, nodules, etc. 

    • Sometimes, can consider MRI

    • Imaging can help to rule out other causes of pelvic pain (ie. fibroids)  

• Definitive diagnosis vs. presumptive diagnosis 

  • Presumptive diagnosis

    • Endometriosis is a pathologic diagnosis - meaning you need histology of a lesion biopsied during surgery 

    • Sometimes, if surgery is not desired or not yet possible, presumptive diagnosis can be made based on combination of signs, symptoms, and imaging findings 

    • Clinical diagnosis is enough to start therapy that is low risk and easily tolerated

    • If patients improve, can actually hold off on surgery 

  • Definitive diagnosis 

    • Surgery - usually indicated for persistent pelvic pain that does not respond to medical therapy, evaluation of severe symptoms that limit function, andd treatment of anatomic abnormalities 

    • Usually laparoscopy - can get definitive diagnosis and treatment 

      • Peritoneal lesions can appear like reddish or bluish irregularly shaped islands, “powder burn” lesions, white opacifications, translucent blebs

      • Allen-Masters syndrome = scarred or puckered peritoneal surface 

      • Dense fibrous disease 

      • Endometriomas 

  • Pathologic Categorizations 

    • Superficial peritoneal lesions 

    • Ovarian lesion (endometrioma) 

    • Deeply infiltrating - solid endometriosis situated more than 5 mm deep to the peritoneum 

  • Surgical Staging - this is to report operative findings. They do NOT correlate with presence or severity of symptoms. However, there are studies that have shown inverse correlation with advanced stages and prognosis for fertility treatment 

    • Stage I - minimal disease; ie. isolated implants, no significant adhesions 

    • Stage II - mild endometriosis with superficial implants that are < 5 cm in aggregate and are scattered on peritoneum and ovaries. NO significant adhesions 

    • Stage III - Moderate disease with multiple implants, both superficial and deeply invasive, peritubal and periovarian adhesions may be evidence  

    • Stage IV - severe disease; multiple superficial and deep implants, including large ovarian endometriomas. Filmy and dense adhesions are usually present

Hysteroscopy: The Basics, feat. Andrey Dolinko, MD

Today we’re joined for a first part of a two-part talk on hysteroscopy with special guest, Dr. Andrey Dolinko! Andrey was our co-resident at Brown and is currently a second-year fellow in reproductive endocrinology and infertility at the University of Pennsylvania.

What is hysteroscopy?

• Ancient Greek hustérā, “the womb” & Skopéō - to see 

• History (Rudic-Biljic-Erski et al 2019)

  • First developed in mid-19th century

    • Pantaleoni performed hysteroscopy on a 60yo woman to diagnose an endometrial polyp and treated it with silver nitrate. Used cystoscope developed by Desormeaux that used series of concave mirrors and light source

  • Early 20th century

    • Carbon dioxide used as first distention medium in 1925

    • 1926 - two-channel hysteroscopy (introduction and suction of distention media)

    • 1927 - operative channel introduced

    • 1928 - irrigation system

    • 1930s - fixed optic systems and fluid delivery systems

  • Second half of 20th century

    • Fiberoptic cable added to hysteroscope in 1965 (cold xenon light)

    • Operative hysteroscopy and use of different distention media takes off in 1970s

    • Videoendoscopy started in 1982

    • 1996 - Bettocchi office hysteroscope

    • 1990s - resectoscopes, first monopolar and then bipolar

  • 21st century

    • Morcellators - i.e., MyoSure

How does hysteroscopy work?

• Contraindications

  • Pregnancy

  • Cervicitis

  • Active PID

  • Comorbidities that may be exacerbated by intravascular volume expansion

• Timing

  • Reproductive-aged women: proliferative phase CD5-12, ideally not during active bleeding

  • Exclude pregnancy!

  • Post-menopausal-aged women: any time
    

• Positioning

  • Dorsal lithotomy position

  • Avoid steep trendelenburg because risk of air embolism

    • Causes negative pressure in pelvic veins

• Patient prep

  • Vaginal prep w/4% chlorhexidine gluconate soap or providone-iodine

• Antibiotics

  • not indicated

• Anesthesia (ranges)

  • None

  • Can do PO/IM/IV NSAIDs, benzos

  • Paracervical blocks

  • Regional anesthesia

  • IV sedation

  • General LMA

  • GETA

• Vaginal instruments

  • Speculums and retractors

  • Tenaculum

  • Dilators

  • Curettes

• Hysteroscope

  • Hysteroscope components

    • Scope

      • Eyepiece

      • Barrell

      • Objective lens

        • 0 to 70 degrees (typically 0 or 30)

    • Inner sheath w/inflow

    • Outer sheath w/outflow for operative scopes

    • Light source

      • Most-commonly Xenon or LED these days

    • Camera-head and video monitor

  • Diagnostic

    • Flexible

    • Rigid

  • Operative

    • Rigid operative scope

    • Scopes to be used with hysteroscopic tissue removal systems

    • Resectoscopes

  • Distention media

    • Fluid choice

      • Historical

        • Gas - CO2

        • High-viscosity 32% Dextra (Hyscon)

      • Current

        • Low viscosity

          • Electrolyte-rich

            • Saline

            • LR (rarely)

          • Electrolyte-poor

            • 5% Mannitol

            • 3% Sorbitol

            • 1.5% Glycine

    • Fluid deficit

      • A reflection of potnetial systemic fluid absorption

        • Surgical disruption of endometrium and myometrium provides direct access to sinus/vessels

          • If intrauterine pressure greater than vascular pressure → intravasation -> a fluid bolus!

      • Where else may the fluid be going?

        • Out the tubes

        • Out the vagina

        • Onto the floor

  • Fluid management systems help to determine deficit

    • Simple

      • Gravity

      • Pressure bag

    • Automated systems

      • Can set fluid deficits for automatic calculation

      • Uterine pressure setting

Prenatal Genetic Screening: An Update

One of our very first podcasts covered prenatal genetic screening and testing. Since then, ACOG has updated the former PB 163 to the new PB 226. For today, we’ll cover some changes/updates and get more into diagnostic testing, which we didn’t cover in depth on our previous episode. Diagnostic testing info remains well-covered by PB 162.

How do you provide genetic counseling to a patient? 

• Every pregnancy has a risk for genetic abnormality and review that this risk increases with increasing age

  • Average rate is 1/150 live births. There is also risk based on family history. 

    • Review family history of birth defects, genetic diagnoses in the family, etc. prior to discussion

  •  Risk of abnormalities based on age:

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• Review options for genetic screening for patients.

  • All types of genetic screening is limited, and all genetic screening tests detect fewer abnormalities than diagnostic tests with microarray. Diagnostic tests include CVS and amniocentesis.

• Screening and diagnostic testing should be discussed and offered to all patients early in pregnancy regardless of maternal age or baseline risk

What are the available tests?

• Preimplantation genetic testing/screening 

  • PGT-A (also called PGS previously) - preimplantation genetic testing for aneuploidies 

    • Biopsy of an embryo at the blastocyst stage, usually around day 5-6 of development 

    • Cells are taken from the outer layer of cells (trophectoderm) that will eventually become the placenta 

    • PGT-A just screens for aneuploidy, and the idea is to increase the chances of live birth by screening for embryos that have aneuploidy.

  • PGT-M - preimplantation genetic testing for monogenetic/single gene mutations

    • Same as above in terms of how the cells are gotten, but in this case, tests are done for monogenic disease or single gene mutations 

    • Can be used to choose embryos that do not have a genetic disease, like screening for embryos that do not have Huntington’s or cystic fibrosis 

    • Disease and mutation must be known beforehand — this is a highly targeted screening.

  • PGT-SR - preimplantation genetic testing for structural rearrangements 

    • Useful when there are parental structural chromosomal abnormalities.

    • Detects things like translocation, inversion, deletions, insertions, etc.

  • With PGT, because the cells biopsied are destined to become placenta, other forms of pregnancy genetic screening should still be offered due to risk of mosiacism - that is, different genetic material in different cell lines.

• Screening and Testing During Pregnancy 

  • Discuss that many screening tests are sensitive for T21, but may have less sensitivity for other chromosomal disorders. 

  • Review these tests cannot detect other genetic abnormalities like point mutations, deletions, translocations, etc. 

  • Types of screening tests: 

    • NIPT (cell free DNA) – test any time around 9-10 weeks to term. 99% detection rate for trisomy 21. It has the highest DR of all tests and lowest false positive rate, but also may detect maternal aneuploidy or disease. Highest sensitivity and specificity. Does NOT test for open neural tube defects.

      • Someone with a screen positive serum analyte test may choose cfDNA for follow up if they want to avoid a diagnostic test, but they should be informed that it is still a screening test, meaning it can still fail to identify some chromosomal abnormalities and may delay definitive testing if positive.

    • Integrated screen – two tests. First is at 10w-13w6d. Then 15-22w. DR for T21 is 96%, but you need two samples and no first trimester results. Method: NT + PAPP-A in first trimester, then quad screen (hCG, AFP, uE3, inhibin A)

    • Sequential – 10w-13w6d, then 15-22 w. 95% DR for T21. Still need two samples, with first trimester NT + BHCG, PAPP-A and +/- AFP. Then quad screen.

    • Quad screen – 15w-22w. 81% DR for T21. It’s a one-time test, but also has lower DR than integrated

    • Other options with lower detection rates: first trimester screen (NT+PAPP-A, bHCG, AFP), Serum integrated (Integrated just without NT), NT alone

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ACOG PB 226

Diagnostic Testing

• The gold standard for detecting genetic abnormalities and should be offered after abnormal genetic screening tests.

• Chorionic villi sampling – done between 10-13 weeks. 

  • Get placental villi transabdominally or transcervically. 

  • Pregnancy loss rate 1/500. Limb reduction defect is super low, around 6/10,000. 

  • Can cause spotting/bleeding. Also the tissue is placental, so there is still possibility of mosaicism (ie. placenta doesn’t have abnormalities, but fetus does). 

    • Because of this, sometimes after CVS can still recommend amnio.

• Amniocentesis – done between 15-20 weeks usually, but can be done any time later too. 

  • Reason not to do too early: amnion and chorion not fused, increasing anomalies/loss rate.

  • Rate of loss is about 1:300 – 1:750 depending on studies. 

  • Other complications include spotting or loss of fluid. 

  • Cells are from sloughed off fetal skin cells, so can actually get fetal DNA.

• Type of tests that can be sent from diagnostic testing - a question you might get: what are you sending it for? 

  • Karyotype

    • Detects aneuploidies, like trisomies, 45X, 47 XXY.

    • Need culturable cells, so takes longer (7-10 days).

    • Cannot usually be done on dead tissue (ie. stillbirth), because the cells likely won’t grow 

  • Microarray

    • Can find major aneuploidies and submicroscopic changes that you can’t see just with karyotype.

    • Can’t detect balanced translocations and triploidy.

    • Can be done on cultured cells or uncultured tissue.

    • Can also be done on copy number variants If done on uncultured cells.

    • Can be fast turn-around (3-7 days).

  • FISH

    • Uses probes for specific chromosomes or chromosomal regions (ie, can detect T21 but also can detect 22q11.2 deletion).

    • Can be done on uncultured cells, so can get results in as few as 2 days.

    • Good to use if someone screens positive for T21 or other aneuploidy on serum analytes or cfDNA and you want a quick results before you get the full karyotype/microarray results

    • Often start with FISH, then reflex to microarray if normal, or karyotype if abnormal (to confirm).

COVID-19 Update #3: Treating the Pregnant Patient

Prevention of COVID-19: More Updates on Vaccination

• Vaccination is the #1 thing folks can do to protect themselves and their fetuses!

• Since our last podcast, ACOG, SMFM, ASRM, ACNM, AABM (just to name a few) have all endorsed COVID-19 vaccination at any time for folks trying to conceive, who are pregnant, or postpartum and lactating!

• SMFM has released consensus guidance for healthcare providers regarding vaccine counseling:

  • Check out our previous episodes (#1 and #2) on vaccine effectiveness

  • We at CREOGs Over Coffee wholeheartedly recommend vaccination, especially with this stronger data regarding safety in reproduction, pregnancy, and lactation.

COVID and Pregnancy: What Options Are Available for Treatment?

We’re going to address the following major questions today:

• Does patient merit inpatient admission?

• If they can stay outpatient, does the patient qualify for any therapy?

• If they need to be inpatient, when to start therapeutics and what options are available? 

• When is delivery indicated for maternal benefit?

Decision to Admit:

COVID can be broken into asymptomatic disease, then mild, moderate, severe, and critical disease:

• Mild

  • Flu-like symptoms: fever, cough, myalgias

  • Anosmia

  • No dyspnea, shortness of breath, or abnormal chest imaging (if performed)

• Moderate:

  • Symptomatic dyspnea/shortness of breath, but able to maintain SpO2 > 94% on room air

  • Evidence of pneumonia on imaging

  • Refractory fever (>39C) to acetaminophen

• Severe:

  • Respiratory rate > 30

  • SpO2 < 94% on room air (so any O2 requirement!)

  • PaO2 / FiO2 < 300 

  • More than 50% lung area involvement of disease on imaging

• Critical:

  • Multiorgan failure or dysfunction, shock

  • Respiratory failure requiring high flow nasal cannula or mechanical ventilation

• Patients with mild disease or no symptoms can be safely monitored outpatient, with a 10-day self quarantine from positive test or onset of symptoms in accordance with CDC guidelines. 

• Patients with moderate disease will often require hospitalization in pregnancy, owing to risk of progression. However, this is an individualized decision, and non-pregnant folks might more typically stay outpatient in this scenario.

  • If patients remain outpatient, SMFM recommends ongoing check-ins from patients to their prenatal care providers to assess symptoms and ensure there is no concern for disease progression.

  • Also recommend a follow up visit (either in-person or via telemedicine) at least once within 2 weeks of diagnosis.

  • Necessary and indicated medical care should not be avoided due to a positive COVID status!

• Patients with severe or critical disease, obviously, will merit inpatient admission. 

• Patients with mild-moderate disease with other comorbidities may also be considered for hospitalization (i.e., patients with hypertension, diabetes, other maternal medical conditions), as these patients appear to be more prone to acute decompensation. 

Inpatient Care: Protocols and Hospital Disposition

• Vital signs and fetal monitoring as indicated when fetal intervention would be considered.

• ICU level of care should be considered with:

  • Rapidly increasing oxygen needs to maintain SpO2 >95%

  • Hypotension (MAP < 65) despite some measure of fluid resuscitation.

    • Owing to risk of pulmonary edema, SMFM recommends an initial 500-1000cc bolus of crystalloid to assess response, and conservative fluid management unless clearly hypovolemic.

  • Need for mechanical ventilation or intubation - 

    • Intubation is recommended if O2 requirements are >15L by NC or mask, >40-50L by high-flow NC, >60% FiO2 by Venturi mask, or altered mental status with inability to protect airway. 

  • Need for other end-organ support (i.e., hemodialysis)
    

• Prone positioning is possible in pregnancy! 

  • Proning in COVID (and other causes of acute respiratory distress syndrome) is well-studied

    • It is hypothesized to decrease ventilation-perfusion mismatch by bringing more blood to the more open anterior lung fields (rather than the often atelectasis-affected lower posterior lung).

  • Padding and support devices may need to be used for appropriate support in pregnancy.

  • In non-intubated patients, lateral-decubitus or full-prone positioning is also permissible and can help improve oxygenation.
    

• Thromboprophylaxis is generally recommended in at least hospitalized patients, given critical illness increases hypercoagulability risk further in pregnancy.

  • Prophylaxis is generally not recommended after discharge, unless other specific comorbidities exist.

    • SMFM offers use of a risk scale, the IMPROVE Risk Score, as well as deferring to clinical expertise to guide use of pharmacologic prophylaxis once discharged from the hospital.
      

• Extracorporeal membrane oxygenation (ECMO)

  • Allows for oxygenation of the lungs (VV ecmo) and possibly combining with pumping action (VA ecmo) in patients with severe ARDS refractory to other methods of therapy. 

    • It gets even more complicated than this, but that’s the basics!

  • ECMO is a significant intervention with its own set of morbidities and risks, and should be reserved for significant, severe cases of pregnancy where it may be helpful and delivery may not/cannot be considered at that present moment (i.e., previable or periviable gestation). 

  • These conversations are often very individualized by institution, so we’ll hold off on further discussion from here! 

Therapeutics and Indications

• Outpatient:

  • Monoclonal antibody therapy (i.e., Regeneron)

    • FDA Emergency Use Authorization indicated for patients over age 12 who have mild-to-moderate COVID-19, weigh at least 40kg, and are at high risk of progression to severe disease or hospitalization. The criteria are:

      • BMI > 35

      • Chronic kidney disease

      • Diabetes

      • Immunosuppresive therapy 

    • Data is limited on their use in pregnancy, but other monoclonal antibodies are generally well-tolerated with no fetal effects. Thus, they can be used in appropriate pregnant patients. 

• Inpatient:

  • Dexamethasone

    • Associated with decreased risk of mortality in those requiring mechanical ventilation

    • Also has small decrease in mortality for those requiring oxygen generally

      • (RECOVERY Trial)

    • Recommended dosing: 6mg IV or PO daily x 10 days.

      • NOT recommended in those who do not require oxygen

    • Dexamethasone does cross the placenta measurably: it is the alternative steroid to betamethasone for fetal lung maturity!

      • FLM dosing: 6mg IM q12h x 4 doses

      • Thus, it is appropriate to use in appropriate pregnant patients; FLM dosing should be given for the first 48h of therapy. 

  • Remdesivir

    • Associated with decreased duration of disease in patients requiring oxygen therapy (ACTT-1 Trial)

    • Recommended if SpO2 < 94% on mechanical ventilation or ECMO

    • No fetal toxicity is known, and can be used on an emergency / compassionate use basis.
      

When to deliver the hospitalized patient:

• SMFM recommends that in patients with refractory hypoxemia, delivery at/after 32 weeks is reasonable if it will allow for further care optimization given:

  • Low risk of neonatal mortality at 32 weeks (0.2%) and

  • Overall low risk of major morbidity (8.7% at 32 weeks). 

    • This also logistically is often more appropriate - controlled delivery is certainly more preferable to chaos! 

• In those who are critically ill, decision for delivery is certainly individualized.

  • Mechanical ventilation alone is not an indication for delivery.

  • Proning, ECMO, and other ventilator methods should be considered especially under 30-32 weeks. 

Blood Transfusion

What’s in blood anyway? 

• Whole Blood - blood that basically contains all the following components 

  • It contains everything! Most of the time, when we donate blood, we donate whole blood 

• Red blood cells (often called packed red blood cells) 

• Take whole blood and centrifuge it to separate out just the red blood cells. Usually, other additives will be placed in such as citrate, dextrose, and adenine to preserve the cells and keep them alive 

  • Usually can be kept refrigerated for up to 42 days in the US, but can be frozen for up to 10 years 

  • Usually 1 unit is from 1 donor, and the idea is that 1 unit should raise the HgB by 1 point 

  • Volume is anywhere between 220-340cc, and the reason this can be different is because it depends on the original HCT of the donor. Most of the time, it is about 250cc.

• Why do we use it? 

  • Because one needs blood!

    • Should be considered in patients who have acute blood loss anemia, who are symptomatic 

      • Usually can start to think about it if Hgb is <8 g/dL, when not at baseline for patient, and if they are symptomatic 

      • Would recommend if <7 g/dL if they are postpartum or postoperative or wound healing

  • In other cases (ie. sickle cell disease), transfuse to a threshold to prevent sickle crisis 

• Things to know before transfusion

  • Before transfusion, someone should be typed and crossed so that they get blood that matches their own 

  • If they don’t, their bodies can create antibodies against the donated blood, which can then lead to alloimmunization 

  • This is a problem for future pregnancies possibly! See our episodes on alloimmunization

  • The only exception: massive transfusion or exsanguination protocol when there is no time to type and crossmatch someone 

  • Some people will still have a fever or small allergic reaction to blood - which is why most people are predosed with Tylenol and Benadryl, but we’ll talk more about this in risks/benefits of blood transfusion 

• Different types of pRBC 

  • Irradiated red cells - indicated for patients at risk of transfusion-associated graft-versus host disease. Components are irradiated by gamma or X-rays within 14 days of donation. Shelf life is about 14 days after irradiation 

  • Washed red cells - for patients who have recurrent or severe allergic reactions to red cells. Also for patients with IgA deficiency with anti-IgA antibodies if red cells from IgA deficient donor is not available. Shelf life is 14 days from washing 

  • CMV negative red cells - only from donors who are known CMV negative. Required for newborn babies because CMV can be fatal 

• Platelets 

  • How do we get them? 

    • Whole blood donation → centrifuged and the buffy coats (between the red cells and plasma layers are pooled from a few donations to the plasma of one of the donors 

      • Usually, this will result in “pooled platelets” or “platelet packs” so when you transfusion a unit of platelets, it’s actually considered a “4 pack” or “6 pack” or even “10 pack” of platelets. Check with your institution. 

      • Usually, volume is about 300cc, and can be stored at room temperature (20-24 degrees C) with constant agitation 

      • Shelf life is about 5 days 

    • Apharesis donation - platelets come from 1 donor and is apheresed (separated) immediately

      • Will results in only 1 donor per pack of platelets 

      • Volume is around 200cc 

      • Again, can be stored at room temperature with agitation and lasts 5 days 

  • Why do we use it? 

    • Usually when there are low platelets 

    • Most places will have thresholds, ie. if platelets are <50K and patient needs urgent or emergent surgery or are actively bleeding 

    • Some places may put threshold for transfusion of <100k if CNS bleed

    • If not bleeding, generally consider if Plt <10k to prevent spontaneous bleed 

      • If coagulopathy but not bleeding, can consider higher threshold, around 20-30K 

  • Other things to know 

    • Platelets still need to be crossmatched to ABO and Rh antigens 

  • Different types of platelets 

    • Irradiated platelets - same reason to give these as irradiated red cells 

    • Human leucocyte antigen (HLA)-selected platelets 

    • Human platelet antigen (HPA) -selected patients 

      • Population to keep in mind: pregnant patients with neonatal alloimmune thrombocytopenia - where their antibodies attack baby’s platelets 

      • These types of platelets should be used to transfuse babies with NAIT 

• Plasma (sometimes referred to as fresh-frozen plasma) 

  • How do we get it? 

    • Plasma is from whole blood donation or component donation by apheresis 

    • Usually frozen soon after collection to maintain activity of blood-clotting factors 

    • Can be stored for up to 3 years 

    • Thawed FFP can be stored for 24 hours 

  • Why do we use it? 

    • Contains ALL clotting factors, but the amount will depend on the amount from the donor 

    • Volume of usually 250-300cc 

    • Can be given to patients who have coagulopathy, or whom are bleeding and need massive blood transfusion 

    • Should replace 1:1:1  

• Cryoprecipitate 

  • How do we get it? 

    • Thawing FFP to about 4 degrees C, which will produce a cryoglobulin rich in fibrinogen, Factor VIII, and von Willebrand Factor. It does NOT contain all clotting factors 

    • Usually single-donor packs or pools 

  • Why do we use it? 

    • Originally developed for treatment of hemophilia

    • It is more concentrated and lower volume than FFP. 1 pack is about 50cc 

    • Consider giving if patient is coagulopathic but also fluid overloaded 

  • Other things about it 

    • Should be stored frozen 

    • Shelf life of about 3 years 

• Granulocytes 

  • Not going to talk about this one as much, but essentially contains neutrophils 

  • Controversial but sometimes used for patients with life-threatening conditions where they have low neutrophil counts 

• Human albumin solution 

  • No clotting factors or blood group antibodies, so crossmatching not needed 

• Clotting factor concentrates 

  • Can be single factor concentrates 

  • Used for treatment of inherited coagulation issues (ie. for hemophilia A, can use recombinant Factor VIIIc) 

  • PCC or prothrombin complex concentrate (PCC) contains factors II, VII, IX, and X. 

• Immunoglobulin solutions

  • Usually manufactured from large pools of donor plasma

  • Contains antibodies to viruses that are common in the population (ie. IVIG) 

  • Specific immunoglobulins can be made from selected donors with high antibody levels (ie. Anti-D immunoglobulin or Rhogam!) 

Benefits, Risks, and Safety

• Benefits - and how to safely give blood 

  • As discussed before, blood transfusion can be life saving in many people, but we need to do this safely  

  • We already discussed: type and crossmatch blood 

    • Right patient, right blood, right time → correct patient identification, good documentation and communication, and monitoring of the patient 

    • Patient consent needs to be obtained 

    • Also, do not give more blood than is indicated!  

      • https://pubmed.ncbi.nlm.nih.gov/32652065/

        • Hamm et al reasoning for 1 u blood instead of 2 u in postpartum women with acute blood loss 

• Risks 

  • Mostly morbidity and mortality from blood transfusion is preventable, but can still occur, especially when wrong blood is given 

  • Non-infectious risks

    • Febrile non-hemolytic transfusion reactions (usually mild) - can sometimes be treated with benadryl/Tylenol pretreatment 

    • Allergic reaction - can be mild (ie. urticaria) to severe (angioedema or anaphylaxis) 

    • Acute hemolytic transfusion reaction - usually due to ABO incompatibility 

    • Bacterial contamination of blood - can lead to sepsis 

    • Transfusion-associated circulatory overload (TACO) - worsening pulmonary edema within 6 hours of transfusion 

    • Transfusion-related acute lung injury (TRALI) 

      • Caused by antibodies in donor blood reacting with patient’s neutrophils, monocytes, or pulmonary endothelium 

      • Can lead to leaking of plasma into lung alveolar spaces → cough with frothy sputum, shortness of breath, hypotension, fevers

      • Usually presents within 2 hours of transfusion 

      • CXR will show bilateral nodular shadowing in lungs 

      • Can be confused with acute heart failure, but should not be treated with diuretics 

      • May need to intubate. Supportive care for treatment 

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• What to do about acute reactions? 

  1. Stop the transfusion and undergo rapid assessment of vitals, and make sure to check patient ID and blood ID (does it match?) 

  2. Usual evaluation of ABC (airway, breathing, circulation) 

  3. If mild reactions (ie. isolated temperature of >38 degrees, pruritis, or rash), can consider treatment, but could continue transfusion 

  4. However, if increasing temperature >39, life-threatening changes (ie. allergic reaction with anaphylaxis), stop immediately and proceed to resuscitate as needed 

• Infectious risks 

  1. Viral infections - risks are incredibly low because every blood donation is screened for HBV, HCV, HIV, HTLV, syphilis, west nile virus, Zika

  2. Every first time donor is tested for Chagas disease 

  3. Creutzfeldt-Jakob Disease - prion disease that first appeared in the UK in 1996. People cannot donate if they have:

     1. Been in UK >3 months from 1980-1996.

     2. Diagnosed with vCJD, or

     3. Had blood transfusion in UK, France, or Ireland from 1980 to present.

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What if your patient declines blood transfusions?

• Respect the values, beliefs, and cultural backgrounds of all patients 

• Frank discussion with patients about blood transfusion and components of blood 

  • Jehovah’s Witness patients usually will refuse transfusion of whole blood and primary blood components (ie. red cells, platelets, white cells, and plasma) 

  • However, some may accept derivatives of primary blood components (ie. albumin, cryo, clotting factors, immunoglobulins) 

• Discussion of how to save blood cells and discuss other methods of decreasing likelihood of transfusion 

  • Intraoperative cell saver, apheres, dialysis, or cardiac bypass are usually ok 

  • Iron transfusions if needed prior to procedures, if there is time 

  • Discussion of autologous transfusion if possible 

• Signing advance decision documents (usually most hospital will have these) about which blood products are acceptable and which are not 

• Remember: 

  • Emergency or critically ill patients with temporary incapacity must be given life-saving treatment (including blood transfusion) unless there is clear evidence of prior refusal