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