heme update for disability determination (vonwillebrand and sickle cell) jennifer m pearce md...
TRANSCRIPT
Heme Update for Disability Determination(vonWillebrand and Sickle cell)
Jennifer M Pearce MDSeptember 2010
vonWillebrand Disease• What is it?
--vW protein important for start of clot—attracts platelets and helps them stick to bleeding site--Type I vW disease is most common—make the protein but have reduced (not absent) quantities making clotting difficult--Type II vW—make an abnormally functioning protein--Type III vW—no protein made and have severe bleeding
Clinical Manifestations of vW
• In general bleeding is not severe enough to cause disability• Don’t have joint bleeds or spontaneous bleeding • Primarily mucosal bleeding
--nosebleeds--gum bleeding/dental work--bleeding with tonsillectomy etc
• Menorrhagia--can be incapacitating but that is rare--can cause significant iron deficiency
Treatment of vW
• Use of DDAVP as IV or intranasal to raise vW levels
• Use of antifibrinolytics• Infusion of blood derived vW protein• Hormonal control of menses
Is vW a reason for Disability?
• Essentially NO unless there are unusual extenuating circumstances
Sickle Cell Disease
Sickle Cell Disease• With all the variants affects 1:600 African
Americans, 1:12 are carriers• Can also occur in other ethnic groups: India,
Italy, Spain, Saudi Arabia, Greece• Variants: SS, SC, S-Beta Thal, SD
--but in all S is the primary hemoglobin--SS have, in general, more problems
Lifespan in Sickle Cell
• Used to be quoted in 20s because of overwhelming infectious deaths in early childhood
• Now in 40s and death is usually from endstage heart, kidney or lung disease or hemorrhagic stroke
Sickle Cell Trait• One Beta chain has sickle and the other is normal• 8% of African-Americans, 0.5% Hispanics, 0.2%
Caucasians in United States• Only sickle in extreme circumstances– Increased risk exertional rhabdomyolysis,
spenic infarction and renal medullary carcinoma
– 10-30x increase of exercise induced death—recent NCAA ruling
• Generally have no symptoms or issues except in extreme and avoidable situations
Hemoglobin• Normal is 2 alpha chains
and 2 beta chains floating in red cell as a foursome—they don’t stick to another foursome
• In Sickle cell the beta chains have a mutation that, when the hemoglobin unloads oxygen normally, allows the tetramers to stack together in a polymer
Oxygenated to Deoxygenated
The red cell
• Red cells unload their oxygen in the capillaries
• Capillary diameters are smaller than a red cell
• When sickle cells deoxygenate their shapes change and if they are still in the capillaries they get stuck
Vaso-occlusive crisis• Essentially deep pain from tissue death in the
region where blood flow occluded– Often extremities but can be anywhere
• Precipitated by anything that slows blood flow through the capillaries or increases rate of deoxygenation
• Can happen any time and can last from hours to days—episodic, unpredictable, last from a day to a week
• Prolonged pain often requires narcotics• Addiction rare, respiratory depression rare
Dactylitis
What leads to a crisis?
• Anything that leaves the pliant red cell in the capillary long enough to undergo shape change and get stuck
• Causes oxygen to unload more quickly (increased tissue demand, acidosis)
• Slows blood flow (cold, vessel constriction, dehydration)
Factors that precipitate a crisis
• Physical Cold—a few degrees of change, warmth of clothing, heat in house, swimming
• Hypoxia—high altitudes, asthma, sleep apnea• Acidosis—don’t go for the “burn” • Dehydration—and kidneys can’t concentrate• Weather changes• Another illness—URI etc• Hormonal—menstrual cycle
Treatment of a crisis
• Pain relief and anti-inflammatoriesStart with Tylenol and Ibuprofen, then codeine and on up to morphine/narcotic
• Hydration—oral or intravenous• Heat • Rest• Correct inciting factors
Other Issues=Anemia
• Stiff damaged cells are removed rapidly from circulation--normal non sickle red cell lives 120 days--normal sickle cell lives 20 days
• Marrow can’t keep up so usually hemoglobin is 6.5-9gm/dl instead of >10
• impacts growth and development: increased caloric needs of marrow “machine”
Other Issues=Overwhelming sepsis
• Primarily in the younger child; starts at 4 months of age --15% incidence without penicillin prophy--30-50% mortality (2/3 of deaths within 8 hours)
• Mostly from ineffective spleen which is gradually “killed off” by sickling
• Try to prevent with vaccines and prophylactic penicillin
• Rapid intervention with fevers
Other Issues=Stroke• 10% of kids, peak age for ischemic=7• Older adolescents/young adults: hemorrhagic
stroke=50% fatal• 2/3 incidence of recurrence unless transfused• Screen with TCD and MRI/MRA• Stroke
--Often silent--Thrombotic in kids, hemorrhagic in adults--?reason for learning problems in kids--mandates transfusions/bone marrow transplant
Other Issues=Cardiac
• Pump wears out faster: cardiomegaly and LVH• Pulmonary hypertension, cor pulmonale• Iron overload with cardiomyopathy
Other Issues=Acute chest
• Pneumonia vs vaso-occlusive crisis in chest– Or a bit of both
• Rapid progression of symptoms• Major cause of death
Other issues=Chronic lung disease
• Concurrent asthma• Progress to pulmonary fibrosis• Pulmonary arterial hypertension (PAH)– Puts additional stress on heart, pumping against
higher pressure– 30% of adults who were screened– 75% on autopsy– 40-50% 2 year mortality when severe PAH
Renal
• Inability to concentrate urine– Happens early in life– Become dehydrated more easily
• Hematuria/proteinuria• Nephrotic syndrome• Renal failure
Avascular necrosis
• SC and SS• “death” of femoral/humeral head• Pain and disability
Other Issues=Vision
• Develop retinopathy as age (starts in teens)• Can seriously affect vision
Other Issues=miscellaneous
• Aplastic crisis• Gallbladder disease• Skin ulcers: poor healing• Splenic sequestration– In 5-24 mo of age, rapid onset with severe
anemia– Life threatening
Lifestyle in Sickle Cell
• Uncertainty always about tomorrow--makes education and employment tough
--average 24 days/year in the hospital --many days at home unable to work or be in
school--parents lose work days
• Some patients more affected clinically than others—why?
• Social stigma re narcotic use even if very appropriate
Sickle Cell “Cure”
• Bone Marrow Transplant--difficulties with finding donors--post transplant complications--New group of disabling/chronic conditions
• Gene therapy--?? the future
Sickle cell treatment
• Chronic transfusion therapy--iron overload--red cell sensitization
• Hydroxyurea—can be wonder drug – Increases fetal hemoglobin levels which interfere
with sickling– Improves anemia, decreases organ damage,
decreases incidence/severity of VOC