Pediatric Urology- Gynecology

Pediatric Urology- Gynecology
By:Keith Wilkinson, MD FACEP

Anatomy
Shaft
Corpus Cavernosum (two)
* Two large columns on penile dorsum
* Columns separated by septum of fibers
Corpus spongiosum
* Located on ventral side (underside) of penis
* Does not contribute to penile rigidity
* Contains urethra
Tunica albuginea
* Bands together the two columns of corpus cavernosa
Lacunar space (Space of Smith)
* Surrounds tunica albuginea
* Intralacunar smooth muscle found within space

Anatomy
Glans
Innervation-
Sensation-
Pudendal nerve supplies dorsal nerves to penis
Erectile function- Nerves course through corpus cavernosa
Parasympathetic input (excitatory)- “Point”
Nervi erigentes runs adjacent to prostate gland
Sympathetic input (inhibitory)- “Shoot”
Sympathetic nerves supplied by thoracolumbar plexus
Vascular Supply of the Penis
Arterial inflow
Branches of deep internal pudendeal arteries

Hypospadias
* Incomplete development of the anterior urethra
o Anterior- (50 %)- Distal 1/3rd ventral shaft
o Middle- (20 %) percent of cases)- Middle 1/3rd
o Posterior hypospadias (30%)- Proximal 1/3rd
* More common in caucasians (esp Italians, Jews)
* Hypospadias, chordee associated with undescended testes and inguinal hernia (9- 17%)
o Abnormalities of the higher urinary tract are infrequent
* Treatment
o Single stage repair at age 6-18 months

Phimosis
* Previously retractable foreskin no longer retractable or foreskin retraction doesn’t occur by puberty
* Most retract by 1 year with 80% by age 4
* Rare in children
* Circumcision, repeated trauma, infections, poor hygiene, or chemical irritation
* Kids more likely to have obstruction
o Adults present with pain
* Surgery for obstruction of urinary stream, recurrent UTI or bouts of balanoposthitis

Phimosis
* Treatment
o Rare- only required for retention, possible prepuce abscess
o Urinary retention
+ Tub urination
+ Place feeding tube
+ Suprapubic aspiration safe, temporary
o Dorsal slit
+ Dorsal block or collar block
+ Double hemostat crush swollen prepuce
+ Incise between hemostats
+ Close open ends with absorbable suture
* Inability to extend foreskin back over glans
* Less common than phimosis
* Much more common in adults than kids
* More pressing than phimosis
* Often iatrogenic
* Therapy
o Pain management-
+ Topical 2% lidocaine gel or EMLA (eutectic mixture of local anesthetics cream [2.5% prilocaine, 2.5% lidocaine]
+ Systemic analgesia, dorsal penile nerve block, ring block
+ 1-5 cc lidocaine without epi
# 1/2 at 10:00 and 2:00 position at shaft base
# Inject between Buck’s fascia and corpora
o Control of edema-
+ Granular sugar to the surface of the swollen foreskin, cover with a condom or a finger of a rubber glove
+ Cool, compressive 1-in Surgical Cling dressings wrapped distal to proximal
+ Cooled with ice water-filled latex examination gloves
* Therapy
o Direct circumferential manual compression
o Hyaluronidase
+ 1 mL of hyaluronidase (150 U/cc Wydase) injected via TB syringe directly into several sites of the edematous foreskin
+ Breaks down hyaluronic acid in connective tissue, enhances fluid diffusion between tissue planes
+ Almost immediate decreased swelling
o Manual reduction
+ Distal traction of the foreskin using index and third fingers
+ Thumbs push the glans penis back through the paraphimotic ring of the foreskin
o Dorsal slit

Balanitis
Inflammation of the glans
* More common in men than boys
* Causes

Uncircumcised, poor hygiene
Chemical irritants (soap, petroleum jelly)
Drug allergies (tetracycline, sulfonamide)
Morbid obesity
Candidal species
Group A and B streptococci, Staph.,
Trichomonal species
Herpes Simplex
* Recurrent bouts can lead to phimosis

Balanitis
* Testing
o Serum glucose
o Culture of discharge
o Wet mount for Candida
o Syphilis serology test if STD suspected
o Herpes PCR swab
o Gonorrheal, chlamydia in adolescent, suspicion of abuse
* Treatment
o Retract the foreskin daily and soak in warm water to clean penis and foreskin
o Apply Bacitracin (not Neosporin)
o Apply topical clotrimazole for probable candidal balanitis

Balanoposthitis
* Inflammation of the glans and foreskin
* Etiology- uncircumcised, usually preschoolers
o Infection-
+ Grp A Strep (thin, purulent discharge; rapid strep positive), Staph, Candida, rarely gram negatives, syphilis (adolescents)
o Chronic friction, zipper injuries, and contact dermatitis, or a fixed drug eruption (TCN, or clotrimazole)
o Chronic- Balanitis xerotica obliterans
* Treatment-
o Local hygiene (sitz baths, cleaning)
o 0.5% hydrocortisone cream to the affected parts
o Antimicrobial topical ointments
+ Utility is unproved
o Oral antibiotics
+ 5 to 7 days of amoxicillin or cephalexin in recalcitrant cases or with more advanced cellulitis
+ Recurrence raises suspicion of DM, immunocompromise, Balanitis xerotica obliterans

Pearly Papules
* Common- seen in 30%
o Most common in young, uncircumcised African- Americans
* Empty hair follicules on the corona
* Benign- Do not warrant treatment
o Don’t resolve with circumcision
* Can be confused with (genital warts)

Meatal Stenosis
* Circumcised males
* Follows inflammatory reaction around meatus
o Usually diaper rash
* Significant when sprays or dorsally deflects stream
* Obstruction, dysuria, UTI uncommon
o Tub voids, urologic consultation
o Foley catheter, urethral meatotomy
Priapism
* Can occur in any age group
o Peaks at age 5-10 years, 20-50 years
* Causes
o Erectile dysfunction drugs most common causes of adult priapism (0.05-6% of users)
o Sickle cell most common cause in children
+ Causes 2/3rd of all cases
+ Occurs in 27% male children, 89% male adults
+ Highest aged 19-21 years
* Duration of symptoms most important factor affecting outcome
o Up to 92% with priapism for less than 24 hours remained potent
o Only 22% with priapism that lasted longer than 7 days remained potent
* Erection-smooth muscle relaxation and increased arterial flow into the corpora cavernosa
o Engorgement of the corpora cavernosa causes compression of the venous outflow tracts (ie, subtunical venules), resulting in blood trapping within the corpora cavernosa.
o Nitric oxide- major neurotransmitter controlling erection
+ Corpora cavernosa endothelium lining secretes nitric oxide

* Priaprism - failure of detumescence
+ Underregulation of arterial inflow (ie, high flow)
+ Failure of venous outflow (ie, low flow)- more common
# Excessive release of neurotransmitters
# Blockage of draining venules (eg, mechanical interference in sickle cell crisis, leukemia, or excessive use of IV TPN
* Treatment
o Impotence uncommon
o Need for surgical decompression uncommon
o Most low- flow, resolves spontaneously
o Hydration, analgesia
* Sickle cell disease
o Analgesics, hydration
o Exchange transfusion
+ Aim for reduction of Hgb S to 30- 35%
+ Aim for HCT > 30%
o Medical therapy successful up to 37%Alpha, beta agonists
o Oral pseudoephedrine or oral beta-agonists- (terbutaline) little efficacy
* Penile nerve block
o Bupivicaine without epi
* Intercavernosal phenylephrine (Neo-Synephrine)- drug of choice
o Nearly pure alpha agonist
o Intracavernosal injection
o 1 mL:1000 mcg diluted with an additional 9 mL NS
o Inject 0.3-0.5 ml using a 29-gauge needle into the corpora cavernosa
o Compress area of injection
o Wait 10-15 minutes between injections

Penile decompression
* Repeated aspirations or irrigations and sympathomimetic injections over several hours might be necessary
* Resolution of ischemic priapism following sympathomimetic injection with or without irrigation has been shown to occur in 43-81%
* Aspiration- 16- to 18-gauge angiocath into the lateral aspect of the corpus cavernosum
o Unilateral approach usually adequate because of the vascular channels between the 2 corpora cavernosa
o May be difficult because of the sludging of blood within the corpus cavernosum
o Saline irrigation and repeated aspirations may improve flow dynamics
* Surgical decompression
* Phenylephrine irrigation
o 1000 mcg phenylephrine in 100 mL of normal saline (10 mcg/mL)
o Infuse 10-20 mL at a time
o If unable to infuse, inject phenylephrine directly in 200- to 500-mcg aliquots
o Maximum dose of 1500 mcg
o Compression must be applied
o Epinephrine can also be used

Penile Trauma
* Zipper injury
o Local anesthetic
o Cute median bar with wire cutters
* Corporal rupture
o Adolescents, teens, adults
o Palpable, audible snap
o Acute bending of the penis
o Acute pain, immediate detumescence
o Delayed presentation common
o Treatment
+ Exploration
* Shaft laceration
o Exclude corporal, uretheral injuries
o Close with absorbable suture
* Toilet seat most common
o Corporal, urethral injury uncommon
o Meatal blood warrants consultation, consideration for retrograde urethrogram

Scrotal Pain by Age
* Acute scrotal pain seen in the ED
o Torsion of an appendage was the most common diagnosis (46%)
+ Especially age 3- 13
o Epididymitis next (35%)
+ Most common after age 13
o Testicular torsion (16%)
+ Most common cause in first year (86%)

Testicular Torsion
* Failure of fixation between enveloping tunica vaginalis and posterior scrotal wall
o Inappropriately high attachment of the tunica vaginalis
o Bell clapper deformity- found in up to 12% of males
* Left testicle more common
o Bilateral in 10%
* Most aged 12-18 years (peak age 14)
o Smaller peak also occurs in neonatal period in undescended or incompletely descended testes
* Most testes torse lateral to medial
o Typically takes 720 degree turn for ischemia
* Approximately 5-10% of torsed testes spontaneously detorse

Testicular Torsion
* Pain usually sudden, severe
o Scrotum, inguinal region, lower abdomen
* History of physical activity, or trauma
o Fair number occur during sleep
* Up to 50% of patients have prior episodes of intermittent testicular pain
o Nausea and vomiting (20-30%)
o Abdominal pain (20-30%)
o Fever (16%)
o Urinary frequency (4%)
* Elevated, horizontal lie of the testicle- (Brunzel sign)-
o Best seen in upright position
* Skin pitting at scrotal base- (Ger sign)
* Enlargement and edema of the testicle, scrotum
* Scrotal erythema
* Ipsilateral loss of the cremasteric reflex
o As high as 100% in some series
* Abnormal contralateral testicle

Testicular Torsion
* Diagnosis
o Urinalysis- usually normal
+ WBCs can be seen in up to 30%
o CBC-
+ Mildly elevated in most (60%)
o Doppler US/ nuclear scan
+ Sensitivity of 86%, specificity of 100%, accuracy of 97% when presence of intratesticular flow is the sole criterion
+ Nuclear scan- nearly identical sensitivity (80- 90 %), specificity (75- 95 %)
Testicular Torsion
* Treatment
o Surgical exploration
o Manual detorsion
+ Manual detorsion is successful in 30-70% of patients
+ “Open the book” -

Testicular/ Epididymal Appendage Torsion
* Appendages have no known function
o Appendage testes seen in 92%, epididymal 25%
* Most common cause of acute scrotum
* Peak age 7- 14 (mean 10.6)
* Pain is more intense near the head of the epididymis or testis
* Isolated tender nodule may be palpated
* “Blue dot sign” pathognomonic- 21%
* Treatment-
o Testicular doppler US if unsure
o Most will calcify or degenerate over 10 to 14 days and cause no harm

Epididymitis
* Pain usually more gradual than torsion
o Gradual onset, teens, older kids
* Causes-
o Congenital anomalies of the lower urinary tract
o Retrograde reflux of urine
o STDs in sexually active > 15
+ Neisseria gonorrhoeae, Chlamydia trachomatis
+ Escherichia coli with reflux disease
+ Klebsiella pneumoniae, Pseudomonas aeruginosa in neurogenic bladder, CP
* Presentation-
o Epididymal tenderness
+ Sterile pyuria, especially in first 15 cc void
o Cremasteric reflex preserved
o Prehn’s sign of low utility
* Diagnosis- Ultrasound
o Enlarged epididymis
o Increased flow
o Flow to testicle
* Treatment-
o Outpatient management
o Oral antibiotics for 10 to 14 days
+ Sexually active
# Need to cover GC, chlamydia, ureaplasma, mycoplasma
# Ceftriaxone, azithromycin
# Consider test for syphilis in sexually active
+ Suspected bacterial
# E. Coli usual pathogen
# Ampicillin, ceftriaxone, gentamicin if toxic
# Amoxicillin, TMP-SX if non-toxic
Mumps
* Most common cause of primary orchitis
* Droplet spread
o As contagious as influenza
* Symptoms 2- 3 weeks after exposure
o Up to 20% asymptomatic
* Uneventful recovery in 2 weeks
* Complications
o Orchitis- Occurs in 20% of symptomatic
+ Swelling of one or both testicles
+ Painful, but rarely leads to sterility
+ Typically unilateral
o Pancreatitis- upper abdominal pain, N/V
o Encephalitis/ meningitis- rare
o Ovarian inflammation- fertility unaffected
o Hearing loss- rare, usually permanent

Orchitis
* Rare
* Bilateral testicular tenderness and swelling over a few days´ duration
* Occurs in conjunction with systemic diseases
o Mumps- occurs on 20% prepubertal (rarely postpubertal)
+ Follows the development of parotitis by 4-7 days
+ Unilateral in 70% of cases
+ Described with MMR vaccine
o Other viral illnesses-
+ Coxsackie virus, infectious mononucleosis, varicella, and echovirus.
o Bacterial orchitis rare
+ Almost always associated with spread from epididymitis
+ Nearly always in sexually active - Neisseria gonorrhoeae, Chlamydia trachomatis, Escherichia coli
+ Unilateral testicular edema occurs in 90% of cases.
* Treatment-
o Symptomatic if concurrent with virus (mumps, mononucleosis)
+ Unilateral testicular atrophy occurs in 60% of patients with orchitis, sterility rare
o Urology evaluation, ultrasound if toxic, diagnosis unclear, suspicion of bacterial orchitis

Undescended Testes
* Testes start descent from inguinal ring at 7th month, complete by birth
* Retractile testes more common
o Cremasteric muscle pulls testicle up
o Should be able to be drawn down into scrotum
+ “Catcher’s position”
o Typically resolves by adolescence
* True, undescended seen in 4% newborn males
o More common in preemies
o Decreases to 0.8% by 1 year
+ Increased risk torsion, trauma, malignancy, infertility
+ Should be corrected if not in normal position by age 1
Scrotal Problems
* Hydroceles
o Incomplete or abnormal obliteration of the processus vaginalis
o Scrotum communicates with abdominal cavity
+ Can lead to diagnostic confusion with appendicitis
o Painless, apparent in neonatal period, disappear by 1 year of age
o Non or minimally compressible scrotal fullness that transilluminates
o US for pain, inability to find testicle, possibility of intratesticular tumor
o Compressibility suggests communicating hydrocele- concurrent inguinal hernia
* Varicoceles-
o Dilated network of veins of pampiniform plexus
o Consequence of spermatic venous valvular incompetence
o Often not noticed until puberty
* Found on the left side (85- 90 %)
o Left spermatic vein drains directly into renalvein
o “Bag of worms” mass posterior, lateral, and superior to the testis extending up the spermatic cord
* Significance
o Untreated can reduce fertility
+ Smaller, softer testicle
o Acute onset, persistence of varicocele when child lies down can suggest rare acute increase in IVC or renal vein pressure (Wilm’s tumor)
* Spermatoceles and Epididymal Cysts
o Sperm-containing cysts of the rete testis or efferent ducts (spermatoceles) or the epididymis (epididymal cysts)
o Painless scrotal masses
+ Located superior and posterior to the testes
+ Transilluminate well
o US shows anechoic mass without disruption of testicle parenchyma
o Treatment-
+ Reassurance- no impact on fertility
+ NSAIDS

Idiopathic Scrotal Edema
o Painless scrotal erythema, induration
+ Nontender, may itch
+ Can extend to portions of the penis, abdomen, and groin
+ No fever
o Occurs in 2- 11 year olds
o Two-thirds of cases unilateral
o No cause known
+ Differential includes cellulitis, local contact dermatitis, insect bite, fixed drug eruption
o Management-
+ US if unable to examine testes
+ U/A, WBC normal
+ No benefit from steroids, antihistamines, antibiotics
+ Usually resolves in 1- 4 days
+ Recurrence rate up to 20%
Kidney Stones
* Children <16 constitute ~ 7 % of all cases of stones
* 1:1 sex distribution
* Can present at any age- most common age 8-10
* 20- 30 % of children may have only painless hematuria
* Incidence higher in southeast US, hot climates, family history
* Types
o Calcium with phosphate or oxalate (57%)
o Struvite (24%)- associated with infection
o Uric acid (8%)
o Cystine (6%)
* Diagnosis
o Hematuria
+ Spot urine for Spot urinalysis and culture, including ratio of calcium, uric acid, oxalate, cystine, citrate, and magnesium to creatinine
o Helical CT still performs well (97% sensitive, 96% specific)
o Ultrasound better in kids than adults
+ Can be used as first study but still not as good as CT
* Disposition
o Urologic consult
o Admit infants, infected stones, lone kidney, intractable pain, abnormal kidney function, larger stones

Gynecologic Problems
* Labial Adhesions
o Also called vulvar synechiae, gynatresia, vulvar or labial fusion, labial coalescence, agglutination
o Usually seen in girls 3 months to 6 years of age
o Common-
+ Accounts for nearly 50 % of prepubertal gynecologic outpatient complaints
+ Usually asymptomatic
# May have urethritis, UTI
* Labial Adhesions
o Appearance
+ Fusion thin, affects labia minora, doesn’t involve clitoris
+ If thick, may be midline fusion of the labioscrotal folds (median raphe) seen in ambiguous genitalia
o Management
+ Requires no treatment (resolves spontaneously during puberty)
+ Topical estrogen cream (0.1% conjugated estrogen vaginal cream) twice daily for 2 to 4 weeks

* Lichen Sclerosis Atrophica
o Uncommon in prepubertal girls
o Presents with itch, irritation, dysuria, perineal and/or perianal pain, and
bleeding
o May be a coexistent vaginal discharge
o Characteristic appearance- white, atrophic, finely wrinkled vulva
+ Ulcerations, blisters, excoriations, and
inflammation are seen over the vulva, perineum, and perianal area
+ Hourglass or figure-eight pattern
* Lichen Sclerosis Atrophica
o Management
+ Removal of all perineal irritants
+ Systemic antipruritics
+ Local application of an emollient ointment, such as A & D ointment
+ Topical steroids- 2- to 3-month course of treatment with a low-potency topical
steroid cream, such as 2.5% hydrocortisone cream, applied two
to three times daily, is often useful
+ Topical antifungal creams, systemic antibiotics for superinfection
* Urethral prolapse
o Uncommon disorder
o Circular eversion of urethral mucosa through the urethral meatus
o Almost all (90- 100 %) cases occur in black girls
o Etiology unclear
o Typically presents with painless “vaginal”
bleeding
o Doughnut-shaped mass originating from and encircling the urethral meatus, protrudes through the vulva
+ Edematous and friable, often ulcerated
* Urethral prolapse
o Treatment
+ Identify the urethral meatus with certainty
# Observing the child voiding her bladder or by catheterization
+ Don’t confuse with sexual abuse
+ Mild prolapse
# Sitz baths, topical antibiotics, topical steroids, topical estrogen cream (0.1% conjugated estrogen cream to the prolapsed urethra 2-3 times daily for 2 weeks)
# Urologic referral
# Simple manual reduction and urethral catheterization for 1-2 days have been effective in minor cases of urethral prolapse; however, recurrence rates are high
* Urethral foreign bodies
o Bloody urine combined with infection and slow, painful urination should
suggest a possible foreign body in the lower urinary tract
o Management-
+ X- ray of the bladder and urethral areas may show opaque foreign body
+ Endoscopic removal
+ Retrograde urethrography or endoscopic confirmation of an intact, nontraumatized urethra is indicated after removal

Gynecologic Problems Vaginitis
* Affects vulva predominantly in prepubertal girls
* Atrophy from estrogen lack, acidic pH, lack of lactobacilli, poor hygiene
* Most nonspecific- negative cultures or mixed flora
* Group A beta-hemolytic streptococci (GABHS) occasionally causes a beefy red, painful vulvovaginitis
* Shigella also described
o Up to 18% in one study
* Pinworm infection with Enterobius vermicularis is common in prepubertal children
o May present with significant vulvar pruritus, more familiar anal pruritus.
* Candida albicans most frequent fungal
* Noninfectious etiologies- chemical irritation from lotions and bubble baths
* Systemic skin disorders- seborrhea, lichen sclerosis, psoriasis, eczema, and contact dermatitis
* Treatment
o Need to suspect vaginal foreign body
o Supportive care for nonbacterial
+ Wiping front to back
+ Avoidance of tight-fitting garments
* Neonatal vaginal bleeding
o Usually occurs at 3 to 5 days
o Caused by withdrawal of transplacental estrogens
o No treatment except reassurance of parents.

* Hydrocolpos
+ Uterine distension from imperforate hymen, transverse vaginal septum, or atretic vagina
+ Bulging, shiny, pearly gray “mass” is seen covering the introitus
+ Palpable abdominal mass
+ Possible urinary retention
o Diagnosis
+ US- nonmobile, midline, cystic mass behind the bladder
o Treatment
+ aspiration and drainage

Pediatric UTI
* Neonatal period-
o UTI in 4- 7% of febrile infants
o Hematogenous seeding of kidneys
* Postneonatal period-
o UTI in 2% of age 1-5
o 3-5% of school aged girls
o Retrograde migration of perineal flora
* Congenital urinary tract anomalies-
o vesicoureteral reflux, urolithiasis
associated with a higher incidence
* Bacteria-
o Escherichia coli accounts for vast majority
o Klebsiella, Proteus, Enterobacter species
o Enterococcus species, Staphylococcus aureus, and group B streptococci
+ Most frequently isolated gram-positives
+ More likely to be causative organisms in the
neonatal period
o Coagulase-negative staphylococcal UTI occurs in teens and young adults
o Other agents
+ Adenovirus cystitis occurs more commonly in young boys
* Testing
o Urine culture gold standard
o Sensitivities of a positive leukocyte esterase or nitrite or a positive urine culture result < 50%
o Combined presence of pyuria (more
than five WBC/ hpf) and bacteriuria
improves sensitivity to 65%
o Positive predictive value of UA is 81 %
* Treatment- 10- to 14-day course in children
* Disposition
o Inpatient management for any child less than 3 months of age with a febrile UTI; significant dehydration, appear toxic, pyelonephritis, urinary stents or other urinary foreign bodies, renal insufficiency, immunocompromise

Pediatric UTI
* Imaging- (IVP, U/S, voiding cystourethrogram)
o all girls less than 5 years of age
o all boys regardless of age
o children with evidence of pyelonephritis
o any female >5 years of age with recurrent UTIs
o those not responding to antibiotics
o Evidence for these recommendations is only fair
o Study all patients with culture-proven UTIs with a voiding cystourethrogram (VCUG) and a renal and bladder ultrasound

Sexual Assault
* Presentation
o Most often, several years have elapsed
* Symptoms
o Disclosure-
o GU symptoms- vaginal discharge, vaginal bleeding, dysuria, urinary tract infections, urethral discharge
o Behavior disturbances- excessive masturbation, genital fondling, sexually provocative behavior, encopresis, regression, nightmares
o Unrelated complaints in 15%- abdominal pain, asthma, sore throat
* Assailant known to the child in > 90 % of cases
* Definite physical findings are present in only about 50% to 60%
o True in cases of known penetration
* Hymen-
o Most often annular, crescentic, and
smooth edged
o Variation in orifice based on age, size,
position, degree of relaxation
* Hymenal trauma
o Notches, also referred to as concavities or clefts
+ Concavities at the 6:00 position associated with prior penetrating trauma
o Scarring- marked alteration in the vascular pattern (white areas or swirling vascularity) suggests healed injury
o Erythema is not specific for abuse

Sexual Abuse
* Genital examination can be confined to a careful inspection of genitalia, perianal area unless older adolescent or perforating vaginal trauma
* Exam, data collection useful up to 72 hours
* Position- seated parent’s lap, supine in frog leg, knee chest
* Toluidine blue dye applied to the genital area may also detect subtle acute
injuries
* Hymen- fine reddish-orange, thin-edged
* Thickness, color of the hymen vary with age
o Normally thick during infancy, again with the onset of puberty
o In between, thinner, usually annular or crescentic, smooth edged
o Wide variation in hymenal orifice size
+ vaginal opening greater than 4- 5 mm is suggestive of abuse
o Erythema is not specific for abuse

Normal Hymen
* Traumatic hymenal changes-
o Hymenal notches or concavities especially at 6:00 position
o Gaping openings
o Irregular contour with deep notches
o Scarring with marked alteration in the vascular pattern (white areas or swirling
vascularity
o Absence of physical findings does not preclude abuse
Abnormal Hymen
Sexual Abuse
* Genital exam in young boy typically normal
* Anal exam may be completely normal in the case of either acute or chronic
sodomy
o May see fissures, abrasions, hematomas, thickened rugae, lichenification of anal skin, changes in tone, fingerprint bruises on iliac wing, inner thigh
Abnormal Anus
STD Protection

* Cultures of the throat, vagina (or urethra), and rectum for gonorrhea
* Culture from the vagina (or urethra) for Chlamydia
o Rapid antigen assays are not considered reliable in prepubescent children
* VDRL for syphilis indicated if clinical evidence of syphilis, history of syphilis in assailant, or presence of another STD
* HIV testing should only be done after counseling and if there is reason to suspect infection
Pediatric Genitourinary
* Conclusions
o Obtain culture on all kids less than teen years
o Always examine the testicles in boys with abdominal pain
o Consider ketamine if need exam, repair in ER

Pediatric Urology- Gynecology.ppt

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Clinical Objectives of Surgical Treatment in OSA

Clinical Objectives of Surgical Treatment in OSA
By:Ho-Sheng Lin, MD
Associate Professor
Department of Otolaryngology/
Head and Neck Surgery

SCS Educational Day
Clinical Objectives
* Positive Airway Pressure, not surgery, is the first line of treatment for OSA
o Safe and effective
* Compliance rate for CPAP is about 50% (40-80%)
o Kribbs et al. (based on objective measures)
+ 25% use CPAP on a full time basis
+ 46% use CPAP > 4 hrs/night on 70% of nights monitored
* 35% of pts failed to show up following PSG (Lost to followup)
* 15% of pts never received machine
o May not be a problem in Canada/European countries, but a major problem here due to insurance hassles
* 15% are compliant w/ PAP Tx
o Compliance defined as
+ Use > 4 hrs/night
+ Use > 5 nights/wk (70%)
* 35% of pts who are prescribed PAP Tx are compliant and “adequately” treated
Clinical Objectives
Preop & Postop PSG
Other Measures of Surgical Success in OSA
* Quality of life
* Function / Performance
* Motor vehicle accident risk
* Cardiovascular disease risk
* Mortality risk
Quality of life
Minor Symptoms Evaluation Profile
Cardiovascular Dz
Overall Mortality
UPPP
CPAP
Adjusted Hazard Ratio of Death
CPAP v UPPP
Conclusion
* Positive Airway Pressure, not surgery, is the first line of treatment for OSA
* However, in patients noncompliant with PAP, surgery is better than no surgery
* Goal of Surgery
o Improve PAP compliance
+ Offer surgical treatments to alleviate physical discomfort such as nasal obstruction
+ Offer surgical treatments, such as tonsillectomy for pts w/ obstructing tonsils, to decreased positive pressure required & increase comfort
o Provide surgical alternatives by offer multi-level surgical procedures based on the level of airway obstruction
+ Surgical Response (AHI >50% and AHI<20)
+ Improved tolerance and compliance with PAP
+ ? Improved daytime symptoms and nighttime
* Hypothetical pt
o AHI of 40
o Sleep 8 hrs/night
o Total AH = 320/night w/out Tx
* 2 scenarios considered “treatment success”:
o 1)Patient underwent UPPP and his AHI went down to 20
+ His total number of AH per night is now 160
o 2)Patient started on CPAP treatment, w/ average use of 4 hrs/night every night.
+ Assuming that while on CPAP, his AHI went down to 0.
+ His total number of AH per night would also be 160.
+ 0 AH/hr x 4 hrs + 40 AH/hr x 4 hrs = 160.
* Both of the above “success scenarios” result in equal number of apnea and hypopnea per night
* Is one scenario better than the other?
* Is it better to have mediocre sleep all night (UPPP) or have good sleep half night and poor sleep the other half of the night (CPAP)?
* Both scenarios are clearly not “ideal”

Final Thought
Redefining Improvement for Patients Who Fail CPAP
CPAP
Success
Treatment

Clinical Objectives of Surgical Treatment in OSA.ppt

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Spine Trauma

Spine Trauma – Part A
By:Keith Wilkinson MD FACEP
Keith Wilkinson MD FACEP
St. John Hospital and Medical Center

Spinal Cord Injury
* Background:
o 8,000 -10,000 new cases expected annually
o Young men- mean age 33.5
o More frequently on weekends, holidays, during summer months
* Greater than half of cord injuries occur in the cervical spine region, a third in the thoracic region, and the remainder in the lumbosacral area
* Most cases of spine injury do not involve permanent cord injury
* Majority (90%) caused by blunt
trauma
o Majority from MVCs > falls, gunshot wounds, sports/ recreational activities
Bony Anatomy
Vertebral Anatomy
Anatomy
* Spinal cord occupies:
o ~35% of canal at the level of the Atlas
o ~ 50% of the canal in the lower cervical region (C2-7), thoracolumbar spine
Ventral- front
Dorsal- back
Ascending Spinal Cord Tracks
Dorsal column- medial lemniscus
Ipsilateral loss of tactile discrimination, vibration, joint and muscle proprioception
Leg fibers medial, arms lateral
Crosses just below level of medulla
Dorsal spinocerebellar tract
Transmits unconscious proprioceptive information to cerebellum
Fine coordination of posture
An uncrossed tract
Ipsilateral leg dystaxia
Ventral spinocerebellar tract

Unconscious proprioceptive information to cerebellum
Posture of lower extremities
Crossed tract
Contralateral leg dystaxia
Ascending Spinal Cord Tracks
Lateral spinothalamic tract
Pain and temperature
Crossed tract
Contralateral loss of pain and temperature sensation one segment below lesion
Ventral white commissure
Bilateral loss of pain and temperature
Dorsal Horn
Ipsilateral segmental anesthesia and areflexia
Descending Spinal Cord Tracks
Lateral corticospinal tract
Also called pyramidal system
Volitional motion
90% crossed in medulla
Ipsilateral spastic paresis with pyramidal signs
Ventral corticospinal tract
Mild contralateral muscle weakness
Proximal muscles more affected

Ventral horn
Ipsilateral flaccid paralysis
Dermatome Distribution
Spinal Level Muscle Innervation
Muscle Strength Grading
* 0 Flaccid
* 1 Flicker of muscle contraction
* 2 Full range of motion, gravity excluded
* 3 Full range of motion against gravity only
* 4 Full range of motion against gravity and some external resistance
* 5 Normal

Stability of Spine Fractures
* Three columns-Disruption of 2/3 unstable
A.Anterior column- anterior vertebral body, the anterior annulus fibrosus, anterior longitudinal ligament
B.Middle column-posterior vertebral body wall,posterior annulus fibrosus, posterior longitudinal ligament
C.Posterior column-posterior vertebral arch, posterior ligamentous complex
* Degree of compression
+ Vertebral body compressions > 50 %
generally considered unstable

Spine Fracture Types
* Compression fractures
o Result from axial loading and flexion,
o Failure of the anterior column
o Middle, posterior columns intact
o Usually stable unless > 50% height
o Unlikely to be directly responsible for neurologic damage

Burst Fractures
* Axial load
* Both anterior and middle columns fail
* Retropulsion of bone and disk fragments into the canal
* May cause spinal cord compression

Fracture Dislocations
* Fracture-dislocations
o Most damaging of injuries
o Failure of all three columns
o Compression, flexion, distraction, rotation, or shearing forces

Flexion- distraction
* Seat belt–type injuries
o Particularly where lap belts alone are used
* Failure of both the posterior and middle columns
o Intact anterior column prevents subluxation
* Radiographic findings:
o Increased height of the posterior vertebral body
o Fracture of posterior wall of the vertebral body
o Posterior opening of the disk space.


Clinical Clearance of the Cervical Spine
Cervical spine injury is highly unlikely if the patient has

1) No neck pain or tenderness
2) No neurologic signs or symptoms
3) No loss of consciousness
4) Normal mental status
5) No distracting injury

Cervical spine series
* Sensitivities for a cross table lateral demonstrating all 7 cervical vertebra vary (77- 90%)
* Sensitivity of full three view series (lateral, AP and odontoid views) increases to 80% to 100%
o Odontoid 10%, AP 1%
* If cervical fracture found:
o 50% have fx at adjacent level
o 15% have fx in another part of cervical spine
o 10% have fx in thoracic/lumbar spine

Interpreting Cervical Spine X-rays
* True lateral identifies 80- 90% of significant bony or ligamentous lesions
o Adequate films
+ Full visualization of all seven vertebrae
+ C7-T1 injuries are not common, seen with swimmer's view
* Open-mouth odontoid view identifies most of the remaining 10% of significant lesions
o Look for normal alignment and equal spacing between C2 and the lateral masses of C1
* AP or oblique views rarely identifies injury not already suspected

Cervical Spine Radiographs
* Most missed fractures due to inadequate films of the cervico-cranium, C7- T1 junction
* Cervical CT should be used to assess C1-C2 in victims of severe head trauma (GCS < 10, intracranial hemorrhage, skull fractures), when unable to obtain an open mouth or anteroposterior odontoid view
* The open mouth odontoid view is unreliable in unconscious intubated patients missing nearly 16% of injuries
* Up to 15% of cervical spine injuries are missed when the lateral view alone is used to clear patients
* Addition of CT increases sensitivity to 95-100%

Cervical Spine Radiology and the Unconscious Patient

Cervical Spine Radiology
Dens view
Fuchs view
Cervical Spine Radiology
Swimmer’s View
Cervical Spine Radiology
* Look for
o Normal atlanto-occipital alignment
o Predental space 3 mm or less
o Prevertebral soft tissue space less than 5 mm anterior to C3
o Spinal canal plain film anteroposterior diameter 13 mm or greater
o Any horizontal translation of one vertebra on the next
o Fanning of the space between spinous processes
o Fracture of any bone

3 Rules of 3
* The predentate space should be < 3mm
* The prevertebral soft tissue at C3 is usually 3 mm
* Anterior wedging of 3mm or more suggests a fx
Flexion/ extension views
o Used carefully to demonstrate spinal column stability if the initial three views raise a question but would predict a stable spinal column
+ Small chip fracture of the anterior-inferior margin of the vertebral body
+ 1 to 2 mm with no other noted abnormalities
o Used when the initial three views are normal but the pain seems out of proportion, suggesting greater occult ligamentous damage
o Requires awake, cooperative patient
o Abnormal if there is more than a 3.7-mm step-off of one vertebra on the next or if there is an 11° or greater angulation between vertebral segments
* Flexion-extension views
o No urgency
o Fluoroscopic examination of the unconscious patients has a specificity of about 99% and a sensitivity of 92%
o 625 patients with two suffering neurological deterioration, one with complete quadriplegia

Spine Imaging
* CT/ MRI
o The incidence of unstable spinal injury in the unconscious intubated patient is about 10%
o MRI not as sensitive as CT for imaging bone injuries
o MRI- Superb at defining neurologic, muscular, and soft tissue injury
+ MRI may also be used to identify ligamentous injury
+ Indicated in all patients with neurologic symptoms or physical findings but no clear explanation on plain films and/or CT
CT
* Excellent for upper spine anatomy, rotational injuries, degenerative vs. acute subluxations, subtle compressions
o High incidence of upper cord injury with ICH, GCS < 8
* 3-d reconstructions add improved detail

MRI
Unstable Cervical Spine Fractures
* Jefferson fracture
* Hangman’s fracture
* Teardrop fracture
* Bilateral locked facets

C spine Mechanism of Injury
HYPERFLEXION INJURY (46-79%)
* odontoid fracture
* simple wedge fracture (stable)
* tear drop fracture
* anterior subluxation
* bilateral locked facets (unstable)
* anterior disc space narrowing
* widened interspinous distance
* clay shoveler’s fracture
HYPEREXTENSION INJURY (20-38%)
* anteriorly widened disc space
* prevertebral swelling
* tear drop fracture
* neural arch fracture of C1
* subluxation (anterior/posterior)
* hangman’s fracture
Unstable Cervical Spine Fractures
* FLEXION:
o bilateral interfacetal dislocation
o flexion teardrop fracture (usually C5 or C6)
* EXTENSION:
o extension teardrop (usually C2 or C3)
o hangman’s fracture
o extension-dislocation
o extension-fracture-dislocation
o odontoid fracture
* VERTICAL COMPRESSION:
o Jefferson burst fracture

Spine Trauma – Part A
Spine Trauma – Part B

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Morbidity and Mortality

Morbidity and Mortality
by:Randy Hoover MD

Eponyms: Livedo reticularis associated with stroke-like episodes is known as?
* Sly’s Syndrome
* Sneddon’s Syndrome
* Riley-Day Syndrome
* Shwachman’s Syndrome
* Richter’s Syndrome
73 year old woman presents to an outside acute care clinic with a chief complaint of back pain.
* Upper-thoracic region
* Described as a “bunch,” mild in severity
* Constant, no radiation or change with position, not respirophasic
* Similar to recent transient episodes

History of Present Illness
* Associated with fatigue and malaise
* Night prior to presentation, unable to get comfortable; sweats and nausea
* Recent nose bleeds
* No fevers or rigors
* No chest pain, SOB or abdominal pain
* No bowel or bladder symptoms

Past Medical History
* Chronic A.Fib
o Anticoagulated on warfarin
* H/O Atypical Chest Pain
o Cath 12/00, normal
* Chronic Low Back Pain
* HTN
* CRI
o Baseline Creatinine 1.5
* COPD
* Chronic Diarrhea
* Temporal Lobe epilepsy
* S/P Appendectomy, herniated bowel repair

Medications
* Diltiazem CD 360 mg po qd
* Losartan 50 mg po qd
* Triamterene 50 mg po qd
* Warfarin 5 mg po qhs
* Metoprolol XL 50 mg po qd
* Amlodipine 5 mg po qd

ADR’s: Morphine, ACE Inhibitors
Social History
* Widowed mother of 2
* Consumes a glass of sherry and of cognac daily
* Current 2 ppd smoker
o Approx 100 pk year history
* Lives alone and functions independently

Physical Exam
Gen: 73 yowf, pleasant, NAD, who appeared older than her stated age
T=97.9 P=89 R=18 BP=126/90
Heent: EOMI, PERLA, OP pink and moist. Sclera anicteric
Neck: Supple, JVP =6 cm
Lungs: Poor air movement but otherwise clear
CV: Irreg Irreg no MRG and variable S1
AB: + Bs, soft, non-tender, non-distended, no masses, no hepatosplenomegaly
Back: Tender in the mid-dorsal region. Pain could be reproduced. No paravertebral or bony tenderness. No muscular spasm
Ext: No c/c/e
Labs
Initial Radiology
* RUQ Ultrasound: Multiple gallstones, no
wall thickening, no free fluid or dilated ducts
* CT Abdomen: Gallbladder is distended, no gallstones, slightly enlarged common hepatic and common bile ducts

Further Evaluation
* 2 weeks later: Seen by general surgery at DHMC for possible symptomatic cholelithiasis
o Pt extremely reluctant to undergo surgery
o “ I’ve not been significantly bothered by this”
o Referred to GI for possible ERCP
* 1 month later: Seen by GI
o Persisently elevated alk phos and amylase
o Thought secondary to etoh vs stone passage

-Management Options-
What would you do next?
* Ursodeoxycholic acid
* HIDA scan
* MRCP
* ERCP
* Recommend Surgery
* Watchful waiting

-Test Characteristics-
Magnetic Resonance Cholangiopancreatography (MRCP)
MRCP (Thin Slab)
* ERCP
o Could only cannulate pancreatic duct
o Dye injected into pancreatic duct showed local dilatation
o Brushings of pancreatic duct
o Sent to IR for transhepatic cholangiogram
* Percutaneous Transhepatic Cholangiogram
o Mildly distended intra/extrahepatic ducts
o Narrowing of distal common bile duct
o No dye spilling into duodenum, cholecystostomy tube placed

Admitted for monitoring
Physical Exam
Labs
Assessment and Plan
* Hypertensive urgency
o EKG without signs of ischemia. Pt with lethargy and + proteinuria
o IV Labetalol PRN until SBP decreased < 180
o Restart oral antihypertensive agents: diltiazem, losartan, metoprolol, and amlodipine
* Ductal dilatation s/p ERCP and PTC
o Hydrate
o Monitor LFTs and for signs of post-ERCP pancreatitis
o Cefotetan for prophylaxis
o F/U on Brushings
Post-ERCP Pancreatitis
* Serum amylase elevated in 75% of patients
* 5% have clinical pancreatitis
* MOST mild/moderate, rarely (0.4%) severe
* Usually with therapeutic (versus diagnostic)
* Prediction rules
o Amylase < 276, lipase < 1000 @ 2 hours
* Prevention
o Technical, stents, pharmacologic
+ Antibiotics, calcitonin, glucagon, nifedipine, C1-inhibitors, secretin, anticoagulation, corticosteroids, somatostatin, octreotide, gabexate mesilate, IL-10
Hospital Days 2-4
* Hypertension/A.fib
o Improved with oral agents
* Post ERCP pancreatitis
o Amylase 600
o Lipase 3780
o NPO, pain control, continue IV Hydration
* Cholecystostomy tube falls out
o IR contacted: recommend monitoring LFTs
* Day 4
o Feeling much better, tolerating clear liquids, LFTs stable at baseline
Hospital Day 5
* C/o Increasing RUQ pain, worsening abdominal distention, and nausea
* Labs:
* Plan: NPO, adequate pain management, follow LFTs, place PICC line and begin TPN
Hospital Day 6
* Worsened abdominal pain and distention.
* New rhonchi bilateral lung bases
* Labs:
* CT Abdomen and Pelvis

Hospital Day 7
* Worsening abdominal pain and distention
* Return to IR
o Attempted to drain bile pool around liver, but unable to do so
o Replace cholecystostomy tube
* Somnolent and short of breath
o ABG: 7.25/50/77 on 2 L, oxygen increased to 4 liters
o CXR: CHF
o Lasix 20 mg IV
o Appeared to stabilize

Hospital Day 8
* Somnolent and unarousable
* Acute Abdomen
o Absent bowel sounds, + guarding and rebound
o Urgent surgical consultation
* Exploratory Laparatomy
o Bile Leak from right medial lobe of liver at previous puncture site, cultures sent
o Cholecystectomy: gallbladder full of stones, signs of chronic cholecystitis
o T-Tube inserted
o No masses noted
* Transferred to ICU on ventilator

Hospital Day 9-13
* Fever spikes
o Peritoneal fluid growing Enterococci
o Hospital acquired pneumonia
* Brushings Returned:
Bile Duct: negative for malignancy, + inflammation
Pancreatic Duct: ATYPICAL; atypical ductal epithelial cells. Metaplastic and benign mucosal cells present
Hospital Day 14
* Defervesced
* Oliguric, rising BUN/CR
* Increased ventilatory requirements
* Increasing LFTs
Family Meeting
* Family Meeting
o Daughter indicated that her mother would not want her life prolonged by aggressive measures
o Family requested to withdraw support
o Pt made DNR/DNI
* Support withdrawn
o Pt died peacefully 3 hours later
* Family refused autopsy
Haunting Questions
At what point did this go wrong?
What was her diagnosis?

Morbidity and Mortality.ppt

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Lupus Anticoagulant

Lupus Anticoagulant
By:Jennifer Kirkland (Lambe)

Antiphospholipid
Antibody Syndrome
* Antibodies to phospholipids or plasma proteins bound to phospholipids
o Lupus anticoagulant antibodies
o Anticardiolipin antibodies
o Anti-ß2- glycoprotein I antibodies
* Other antibodies: prothrombin, annexin V, phosphatidylserine, phosphatidylinositol
o These antibodies are not standardized for clinical use and their clinical utility is not well characterized

Lupus anticoagulant
* Lupus anticoagulant
o Describes a group of antibodies which react with cardiolipins, other phospholipids, ß2-glycoprotein I, or proteins other than ß2-glycoprotein I
-AND-
o possess “lupus anticoagulant” activity

What is lupus anticoagulant activity?

* Ability to interfere with coagulation testing (in particular, the tests which are phospholipid dependent) leading to prolonged values
* Despite the “anticoagulant effect” in vitro, these antibodies actually cause coagulation in vivo, in the form of arterial and venous thromboses

Lupus anticoagulant:
Actually a Misnomer
* Associated with clotting, not anticoagulation
* More than one antibody is associated with lupus anticoagulant activity
* Only about 50% of individuals with a lupus anticoagulant meet the American College of Rheumatology criteria for the classification of lupus (SLE)

Definitions
* Cardiolipin= mitochondrial phospholipid
o Causes a biologic false positive test for syphilis
* ß2-glycoprotein I -(not a phospholipid but a plasma phospholipid binding protein)
o In early 1990s, discovery that some anticardiolipin antibodies require the presence of ß2-glycoprotein I in order to bind to cardiolipin
o Patients with SLE or the antiphospholipid syndrome require ß2-glycoprotein I in order to bind to cardiolipin
o Most ß2-glycoprotein I-dependent anticardiolipin antibodies recognize ß2-glycoprotein I equally well whether bound to cardiolipin or bound to other anionic phospholipids

Additional info on LAs
* Anticardiolipin antibodies and Anti-ß2- glycoprotein I antibodies may not possess lupus anticoagulant properties
* Specificity of anticardiolipin antibodies for antiphospholipid syndrome increases with titer and is higher for the IgG than for the IgM isotope
* There is no definitive association between specific clinical manifestations and particular subgroups of antiphospholipid antibodies


Effects of antiphospholipid antibodies on coagulation
* Actually has opposing effects on coagulation
Procoagulant Effects
* Inhibits activated protein C pathway
* Up-regulates TF pathway
* Inhibits antithrombin III activity
* Disrupts annexin V shield on membranes
* Inhibits anticoagulant activity of ß2-glycoprotein I
* Inhibits fibrinolysis
* Activates endothelial cells
* Activates and degranulates neutrophils
* Enhances expression of adhesion moleculres by endothelial cells and adherence of neutrophils and leukocytes to endothelial cells
* Potentiates platelet activation
* Enhances platelet aggregation
* Enhanced binding of ß2-glycoprotein I to membranes
* Enhanced binding of prothrombin to membranes
Anticoagulant Effect
* Inhibits activation of factor IX
* Inhibits activation of factor X
* Inhibits activation of prothrombin to thrombin
o “Microenvironment of cell membranes in vivo may promote greater inhibition of anticoagulant pathways and therefore thrombosis.”
o Ultimately, we don’t really know the mechanism by which thrombosis is promoted over anticoagulation

Criteria for detection of lupus anticoagulant antibodies
* Lupus anticoagulant
1. Must prolong coagulation in at least one phospholipid-dependent coagulation assay with the use of platelet poor plasma
+ Extrinsic (dPT)
+ Intrinsic (aPTT, dilute aPTT, KCT, colloidal silica clotting time)
+ Final common pathway (dRVVT, Taipan venom time, Textarin and Ecarin time)

2. Failure to correct the prolonged coagulation time by mixing the patient’s plasma with normal plasma (1:1)
3. Correction of the prolonged coagulation time after addition of excess phospholipid or platelets that have been frozen and then thawed (they release phospholipids)
4. Rule out other coagulopathies with the use of specific factor assays if the confirmatory test is negative or if a specific factor inhibitor is suspected

To rule out a lupus anticoagulant antibody
* Two or more assays that are sensitive to these antibodies must be negative (one should be based on low phospholipid concentration and they should evaluate distinct portions of the coagulation cascade)

Diagnosis of antiphospholipid antibody syndrome
* Clinical Criteria
o Vascular thrombosis (Venous or arterial: blood vessels, brain, kidneys, lung GI tract, placenta etc)
o 1 or more deaths of normal fetuses at or after 10th week of gestation,or 1 or more premature births at or before the 34th week of gestation; or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation

* Laboratory criteria
o Anticardiolipin antibodies
+ Anticardiolipin IgG or IgM antibodies present at moderate or high levels in the blood on two or more occasions at least 6 weeks apart
o Lupus anticoagulant antibodies
+ LA detected in the blood on 2 or more occasions at least 6 weeks apart (?12 weeks)

Antiphospholipid syndrome
* Primary
o No other evidence of another autoimmune disease
* Secondary
o Associated with autoimmune or other diseases, most commonly SLE
* Sneddon’s syndrome: clinical triad of stroke, livedo reticularis, and hypertension may represent undiagnosed antiphospholipid syndrome.


Epidemiology
* Antiphospholipid antibodies are found among young, apparently healthy control subjects at a prevalence of 1 to 5% for both anticardiolipin antibodies and lupus anticoagulant antibodies
o Meta-analysis
+ LA= 11.1 Odds ratio for venous thrombosis compared with 3.21 with anticardiolipin Ab
o Multivariant analysis
+ Odds ratio for venous and arterial thromboembolism is 4.4 with LA and 1.2 with anticardiolipin
* Prevalence increases with age

Prevalence of LAs in patients with SLE
* Anticardiolipin antibodies= 12-30%
* Lupus anticoagulant antibodies= 15-34%
* B2glycoprotein I antibodies=20%
o Antiphospholipid syndrome may develop in 50 to 70% of patients with both SLE and antiphospholipid antibodies after 20 years of follow-up
o Up to 30% of patients with SLE and anticardiolipin antibodies lacked any clinical evidence of the antiphospholipid syndrome over an average follow-up of seven years

Prospective study
* In a recent prospective study involving individuals with antiphospholipid antibodies, the incidence of thrombosis per year was:
o 1% in individuals with no history of thrombosis
o 4% in patients with systemic lupus erythematosus
o 5.5% in patients with a history of thrombosis
o 6% in individuals with high titer IgG anticardiolipin antibody (>40 units).

Functional Assays of Lupus Anticoagulants
* aPTT
o Some manufacturers offer aPTT reagent which contains a low amount of phospholipid, therefore it is more sensitive for lupus anticoagulant
o Conditions causing acute phase reactants associated with increased fibrinogen and factor VIII, may shorten the aPTT and mask a weak LA
* Prothrombin Time:
o patients with LA will have a normal PT unless they are receiving oral anticoagulants or they develop an inhibitor to prothrombin (PT reagents contain more phospholipids than PTT reagents)

* DRVVT (screening)
o Activates factor X which in the presence of PL, calcium, and factor V activates prothrombin, leading to the formation of a fibrin clot
o Dilution of the venom yields a clotting time in which concentration of the PL reagent is the rate limiting step (there is low amount of phospholipids)
o Inhibition by LA leads to prolongation
o After positive screen, perform the mixing study- if does not correct then:
* DRVVT (confirm)
o Adds a higher amount of phospholipids to neutralize the lupus anticoagulant
o Ratio is derived from the screen clotting time divided by the confirmatory clotting time
o If ratio exceeds the established cutoff, then lupus anticoagulant is in the specimen

Tissue thromboplastin inhibition test (TTI)
o Modified PT assay
o Thromboplastin, which is rich in phospholipid, can be diluted so that its concentration becomes the rate limiting step
o Inhibition of prothrombinase by a LA will cause prolongation of the PT assay
o Due to the various PL and its concentration in the reagent, the test varies in its sensitivity and specificity

STACLOT LA: Hexagonal II Phase Phospholipid Assay
* Two part aPTT screening assay for LA
* Patient’s plasma is mixed with buffer (screening test) or hexagonal phase phosphatidyl ethanolamine (confirmatory test) to neutralize any lupus anticoagulant present
* Mixtures are incubated with normal plasma to correct any coagulation factor deficiency
* Measure aPTT in both mixtures
* If specimen contains LA, the aPTT of the confirmatory test will be significantly shorter than that of the screening test

Staclot-LA
* Phospholipid antibody positive= difference in the clotting times between the two tubes is greater than + 8.0 seconds.
* The aPTT reagent in this assay contains a heparin inhibitor which makes the test system insensitive to heparin levels up to 2.0 U/mL.
* False positive results may occur in patients with high titer Factor VIII inhibitors

Summary
* Lupus anticoagulant causes thrombosis
* Lupus anticoagulant is a group of antibodies that bind to phospholipids or phospholipid binding proteins
* Due to the heterogeneity of the phospholipid antibody, there is no single test that is confirmatory for all phospholipid dependent antibodies.

References

* Kaolin clotting time
o Sensitive for LA when no additional PL is used
o LA is identified when the KCT fails to correct after the addition of even large amounts of plasma
o Problems with the KCT, owing to the particular nature of kaolin, is that it is unsuitable for some photo-optical devices, which makes full automation difficult
* Taipan (Oxysuranus scutellatus) venom activates prothrombin in the presence of PL and Ca2+
* Textarin (Pseudonaja textiles) acts similarly but requires the presence of factor V
* Specificity of both of the above tests can be improved by mixing tests and/or confirmation with the use of ecarin, an enzyme purified from the venom of Echis carinatus, in conjunction with the Textarin test

Lupus Anticoagulant.ppt

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Antiphospholipid Antibody Syndrome in Children

Antiphospholipid Antibody Syndrome in Children
By:Jill Glassberg Azok
Grand Rounds
January 23, 2009

Case: OL

* HPI: 2 yo female with Trisomy 21, Tetralogy of Fallot
o 7/9/08: surgical repair of TOF
o 7/31: re-exploration of surgical wound due to wound dehiscense, cultures +pseudomonas
o 7/31: developed rash on buttocks, trunk, described as “red, circular spots”; initially thought to be Candida
+ Over the next 2 wks, developed petechiael rash of her trunk, feet
+ Rash became diffuse erythroderma with resolution of petechiae
o 8/15: returned to OR for exploration of sternal wound due to fever, respiratory distress, and rash; no evidence of infection
o 8/22: returned to OR sternal non-union
+ cultures +corynebacterium and enterococcus facaelis


* PMHx
o DOL 3: TE fistula repair
o DOL 9: modified BT shunt
o Post-op course complicated by thrombus in iliac and aorta, requiring thrombectomy
o Hypothyroidism
o Trisomy 21
o Tetralogy of Fallot with pulmonary atresia
o Chronic lung disease requiring tracheostomy and ventilator
Labs
* Lupus anticoagulant: positive
* Russel viper venom test: negative
* Cardiolipin antibody: positive
o IgM: indeterminate, IgA/IgG: negative
* Beta-2-Glycoprotein-I
o IgM: negative, IgA/IgG: positive
* Phosphatidylserine antibodies
o IgA, IgG, IgM-negative
* Skin biopsy
o Marked hemorrhage in the superficial dermis; prominent fibrin thrombi with white blood cells occluding the vessels of the superficial vascular plexus.
o Given the occlusion and lack of inflammation around the vessels, we favor the extravasation of red blood cells is secondary to the occlusion and not secondary to a vasculitis.

Hospital Course
* Diagnosed with Catastrophic Antiphospholipid Antibody Syndrome: Treated with IVIG 5mg/kg
* 8/26: Decreased perfusion, increased lactate, decreased urine output, firm abdomen, guaic positive stools
o KUB: pneumatosis with possible portal venous gas formation
o Taken To OR for concern for necrotizing enterocolitis;
o Exploratory laparotomy and ileocolic resection
o Small intestine had diffuse areas of necrotizing enterocolitis with poor perfusion
o Right colon and the transverse colon were distended with evidence of full-thickness injury and vessel thrombosis
o Returned to CICU on inotropic support, broad spectrum antibiotics, both chest and abdomen were open
* 8/28 worsened clinically: Back to OR
o Small bowel was necrotic with multiple areas of full-thickness injury.
o The remaining portion of the colon down to the level of the rectus was also necrotic.
o Thrombi in the distal vessels and at the end branches of the mesenteric vessels
o She had a complete colectomy with resection of most of her small bowel
* 8/29: family decided to withdraw care: patient expired
* Autopsy: Cause of death listed as catastrophic antiphospholipid antibody syndrome

Antiphospholipid Antibody Syndrome
* Multisystem autoimmune disease
* Most common cause of acquired thrombophilia
* History
o 1906: antiphospholipid antibody discovered in patients with syphilis, complement-fixing antibody that reacted with extracts from bovine hearts
o 1952: Conley and Hartmann described circulating anticoagulant in patients with Lupus
o 1963: Bowie associated the anticoagulant with thromboembolic events
* Epidemiology
o Most common in young to middle-age adults
o Can occur in children and elderly
o More common in females

* Diagnosis
o At least one antiphospholipid antibody
o At least one clinical manifestation
* May be primary or secondary


CLINICAL CRITERIA
1. Vascular thrombosis: One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ.
2. Pregnancy morbidity

A. One or more unexplained deaths of a morphologically normal fetus at or beyond the tenth week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus, or

B. One or more premature births of a morphologically normal neonate at or before the thirty-fourth week of gestation because of severe preeclampsia or eclampsia, or severe placental insufficiency, or

C. Three or more unexplained consecutive spontaneous abortions before the tenth week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded


LABORATORY CRITERIA

1. aCL of IgG and/or IgM isotype in blood, present in medium or high titer, on two or more occasions at least 6 weeks apart, measured by a standardized ELISA for β2-GPI–dependent aCL.

2. Lupus anticoagulant present in plasma, on two or more occasions at least 6 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Hemostasis (Scientific Subcommittee on Lupus Anticoagulant/Phospholipid-Dependent Antibodies), in the following steps:

A. Prolonged phospholipid-dependent coagulation demonstrated on a screening test (eg, activated partial thromboplastin time [aPTT], kaolin clotting time, dilute Russell's viper venom time, dilute prothrombin time, Texarin time)

B. Failure to correct the prolonged coagulation time on the screening test by mixing with normal platelet-poor plasma

C. Shortening or correction of the prolonged coagulation time on the screening test by the addition of excess phospholipid

D. Exclusion of other coagulopathies (eg, factor VIII inhibitor or heparin) as appropriate

Clinical Manifestations
* Vascular thrombosis: arterial and venous
* Skin: Levido reticularis
* Recurrent pregnancy loss
* Neurologic: TIA, stroke, migraine, chorea, seizures, optic neuritis
o Sneddon Syndrome: stroke, levido reticularis, hypertension
* Cardiac: Coronary artery disease, premature atherosclerosis, vegetations
* Renal: thrombotic microangiopathy, renal vein thrombosis, renal infarction, renal artery stenosis with hypertension, increased allograft vascular thrombosis, and reduced survival of renal allografts
* Pulmonary: PE, pulmonary hypertension
* GI: Budd-Chiari syndrome, intestinal ischemia and infarction, colonic ulceration, esophageal necrosis and perforation, hepatic infarction, acalculous cholecystitis with gallbladder necrosis, and mesenteric and portal vein thrombosis
* Hematologic: thrombocytopenia, TTP/HUS, hemolytic anemia

Antiphospholipid antibodies
* Antiphospholipid antibodies present in young, healthy controls
o Studies of healthy blood donors
+ Lupus anticoagulant in 8%
+ IgG anticardiolipin in 6.5%
+ IgM anticardiolipin in 9.4%
+ <2% of healthy blood donors with elevated anticardiolipin antibody still had elevated level 9months later
o Incidence increases with age and coexisting chronic disease
* Among patients with thrombosis, prevalence of antiphospholipid antibodies is 4 to 21%
* Increasing risk of thrombosis among those with higher antibody titers

* Lupus anticoagulant: most specific
o Functional assay, measures ability to prolong clotting time
o aPTT, Russel viper venom test, kaolin clotting time
o Meta-analysis showed the odds ratio of lupus anticoagulant for stroke: 11 compared to 1.6 for anticardiolipin
* Anticardiolipin antibodies- most sensitive
* Anti-b2 Glycoprotein I antibodies
* Other antibodies of unclear significance: prothrombin, annexin V, phosphatidylserine, phosphatidylinositol, phosphatidylcholine
* Some anti-cardiolipin antibodies require presence of the plasma phospholipid-binding protein b 2-glycoprotein I in order to bind to cardiolipin
* People with syphilis or infectious diseases, antibodies bind directly to anticardiolipin, independent of /inhibited by b 2-glycoprotein-I
* Autoimmune anticardiolipin antibodies directed against phospholipid-binding protein, not phospholipid itself

Pathogenesis Theories
* Interfere with phospholipid-binding proteins involved in the regulation of the clotting cascadeprocoagulant
* Activation of endothelial cellsincreased expression of cell-surface adhesion molecules and increased secretion of cytokines and prostaglandins
* Oxidant-mediated injury of vascular endothelium
* Platelet activation

Drug Induced aPLs
* Mediations reported
o Phenothiazines
o Phenytoin
o Hydralazine
o Procainamide
o Quinidine
o Dilantin
o Ethosuximide
o Alpha-interferon
o Amoxicillin
o Chlorothiazide
o Oral contraceptives
o Propranolol
* Usually transient
* Associated with IgM
* Rarely associated with thrombosis
* Mechanism unknown

Significance of aPLs
* No history of thrombosis and positive aPL: Risk of new thrombosis <1%
* History of thrombosis and positive aPL: Risk of new thrombosis >10% in first year if anticoagulation stopped within 6 months

A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies
Ruiz-Irastorza G Database of Abstracts of Reviews of Effects 2008

* Sixteen studies were included (n=1,740)
* Thrombosis recurrence rates among untreated patients: 19 to 29% per year
* Rates of major bleeding varied widely, ranging from 0.57 to 10% per year. Seventy-four per cent of bleeding episodes occurred in patients with an INR ≥3.0
* Eighteen deaths were reported to be directly related to recurrent thromboses and one due to bleeding. Ten patients in one study died as a result of the presenting thrombosis
* Patients with definite APS and arterial and/or recurrent thrombosis are at high risk of recurrent events. Most thrombotic events in patients on warfarin occur at an INR <3; recurrences are infrequent among those with an INR of 3.0 to 4.0. Patients with venous embolism or stroke and a single positive aPL that does not persist are at relatively low risk of recurrent thrombosis.
* Recommendations: after a first venous thrombosis, patients with APS should be treated with warfarin at an INR of 2.0 to 3.0; those with arterial or secondary thrombosis should be treated with warfarin at an INR >3.0. Patients with venous thrombosis or stroke and a single positive aPL test should be retested, and should be treated no differently from other patients unless the antibody persists.

Pediatric Antiphospholipid Syndrome: Clinical and Immunologic Features of 121 Patients in an International Registry
* 121 cases of antiphospholipid antibody syndrome in children in the European registry
o Mean age of onset: 10.7 years
o Slightly more common in females, 1.2:1
o 60 (49.5%) had underlying autoimmune disease
o 72 (60%) had venous thrombosis
o 39 (32%) had arterial thrombosis
o 81% had positive anticardiolipin antibodies
o 67% had positive anti-b2-glycoprotein I antibodies
o 72% had positive Lupus anticoagulant

Unique to Pediatric Population
* Lack of prothrombotic risk factors which are present in adults, ie cigarette smoking
o Frequency of vascular thrombosis lower
* Increased incidence of infection-related antiphospholipid antibodies
o Parvovirus B19, cytomegalovirus, varicella-zoster virus, HIV, streptococcal and staphylococcal infections, gram negative bacteria, mycoplasma pneumoniae
* Higher frequency of Evan’s syndrome, Raynaud’s, migraines, and chorea
* Decision-making for long term anticoagulation

Neonatal APS
* Due to transplacental passage of maternal aCL, disappear over 6months
* In pediatric age group, neonatal period highest risk for thrombosis
o Decreased Protein C, Protein S, and antithrombin
o Elevated Factor VIII and von Willebrand factor
* Despite this, very low risk of thrombosis

Catastrophic APS
* Multiple, simultaneous vascular occlusions throughout body
o Widespread microthrombi in multiple vascular bedsMassive thromboembolism
o Clinical involvement of at least 3 organ systems over days to weeks
o Histopathologic evidence of occlusions of small and large blood vessels
o Most common organs: kidney>lung>CNS>heart>skinmultiorgan failure
o DIC in 25%
o Respiratory failure, stroke, abnormal liver enzymes, renal insufficiency/failure, adrenal insufficiency, cutaneous infarcts
* Precipitating factor in 55%: Most common is infection
* Usually primary APS
* Treatment
o Treat precipitating factor if present
o Anticoagulation
o Steroids
o IVIG
o Plasma exchange
* Mortality > 50%

Antiphospholipid Antibody Syndrome in Children .ppt

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