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Sickle Cell Disease and Trait: What Every Primary Care Physician Needs to Know

Objectives
• • • • Pathophysiology of sickle cell disease Inheritance of sickle cell disease Health maintenance for sickle cell disease Management of acute illness

The Management of a child with sickle cell disease is best when overseen by a comprehensive sickle cell disease center. If unavailable, care should be provided in consultation with a pediatric hematologist.

Sickle Cell Disease
Patho hysiolo!y

What "s Sickle Cell Disease#
• n inherited disease of red blood cells • ffects hemoglobin • Polymeri!ation of hemoglobin leads to a cascade of effects decreasing blood flow • Tissue hypo"ia causes acute and chronic damage

Why Do Cells Sickle# • #lutamic acid is substituted for valine • llowing the polymeri!ation of sickle hemoglobin when deo"ygenated .

Normal $s% Sickle &ed Cells Normal • $isc%&haped • $eformable • 'ife span of ()* days Sickle • &ickle%&haped • +igid • 'ives for )* days or less .

.Hemolysis and . blocking local blood flow to a microscopic region of tissue. The result is pain. or hemolysis. and the degree of anemia varies widely between patients. these episodes produce tissue hypo"ia.aso%occlusion )emolysis: The anemia in &. $aso'occl(sion: -ccurs when the rigid sickle shaped cells fail to move through the small blood vessels. mplified many times. The production of red cells by the bone marrow increases dramatically. but is unable to keep pace with the destruction.$ is caused by red cell destruction. and often damage to organs.

ardiomegaly and functional murmurs Hyposthenuria and enuresis Proteinemia .holelithiasis $elayed growth and se"ual maturation +estrictive lung disease2 Pulmonary Hypertension2 vascular necrosis Proliferative retinopathy 'eg ulcers Transfusional hemosiderosis2 • • • • • • 2Potential cause of mortality . including papillary necrosis .hronic Manifestations/ • • • • • • • • • • • • • • • nemia 0aundice &plenomegaly 1unctional asplenia .hest &yndrome2 &troke2 Priapism Hematuria.risis2 cute .Hemolysis and . muscoskeletal or abdominal pain5 &plenic &e6uestration2 plastic .aso%occlusion 4continued5 cute Manifestations/ • • 3acterial &epsis or meningitis2 +ecurrent vaso%occlusive pain 4dactylitis.

< • ).Sickle Cell Disease SCD *enoty e #enotype #enotype prevalence • &ickle cell anemia 4&&5 • &ickle Hb .5 • &ickle S beta plus 4&78 thalassemia 5 • &ickle 3eta !ero 4&79 thalassemia5 • :. disease 4&.< • =< • )< .

)istorical Distrib(tion o+ )emo!lobin $ariants )emo!lobin S )emo!lobin C )emo!lobin D )emo!lobin E Malarial +egions of frica and sia lpha thalassemia occurs in all these regions as well .

$ is ( in ?@.&.** siansB and ( in ).::@ for &ickle beta%thalassemia.aucasiansB ( in (..*** Hispanics 4western states5B ( in ((.(** Hispanics 4eastern states5B ( in ?).*** . the prevalence of sickle cell disease is ( in .$ • In frican% mericans the incidence of &.@** Cative mericans . populations. ( in () frican% mericans are carriers for the disorder • In other A. for Hb&&. for Hb&.Prevalence>Incidence of &. In addition. and ( in (. ( in =?.=.

Sickle Cell Pedi!ree • • • • Parents with sickle cell trait/ hemoglobin & Probability of child with hemoglobin / ).< Probability of child with sickle cell trait &/ .< .*< Probability of child with sickle cell disease &&/ ).

Sickle Cell Disease Newborn Screenin! .

and comprehensive care markedly reduces morbidity and mortality in infancy and childhood. and the . Puerto +ico.Newborn Screenin! +or Sickle Cell Disease • D@ states.irgin Islands provide mandatory universal newborn screening • &pecimen must be drawn prior to transfusion • Prevention of pneumococcal septicemia • Farly $etection and treatment of splenic se6uestration 'inkage to timely diagnostic. Eashington $.. parental education. .

&olubility testing should never be used for confirmation. and>or high performance lipid chromatography."nter retin! Newborn Screenin! &es(lts Sickle )emo!lobino athies Screenin! &es(lts. & G8 thalassemia & Hemoglobin F & . isoelectric focusing.ariant -ssociated Disorder && or &79thalassemia &. . 1& 1&.ariant 2. 1& 1&F 1& .onfirmatory testing re6uires hemoglobin separation by electrophoresis 4cellulose acetate and citrate agar5.

ell Trait Hb .arrier Hb F .ariant . . F .ariant -ssociated Carrier State &ickle ."nter retin! Newborn Screenin! &es(lts )emo!lobino athy Carriers Newborn Screenin! &es(lt 1 1 1 1 & .arrier .arrier Hb .

ana!ement .aintenance -nd .Sickle Cell Disease )ealth .

.ana!ement • • • • • Health maintenance Infection prevention Pain management &ickle emergencies .hronic disease management .

)ealth .aintenance • 1re6uent visits/ every ? to : months • Immuni!ations H +outine immuni!ations H Hib% : months and older H )? valent Pneumova" at five years • Penicillin prophyla"is beginning no later than two months • Cutrition and fluids H 1olate supplementation is controversial .

malocclusion from increased bone marrow activity. Iaundice. with differential and reticulocyte count.)ealth .aintenance • Physical e"am with attention to/ H #rowth and development. delayed puberty • 'ab evaluations/ H .3. liver>spleen si!e. renal J liver function . heart murmur of anemia. urinalysis.

aintenance &pecial studies • 3rain% Transcranial doppler ultrasonography.)ealth . Fcho cardiogram for pulmonary hypertension • Ceurologic% neuropsychological testing . M+I>M+ • 'ungs% Pulmonary function tests.

* mg P.C(rrent &ecommendations • Penicillin Prophyla"is/ &&.3I$ • Ehen to discontinue is controversial • Penicillin Prophyla"is/ &. years • +outine use in infants and children is controversial • &pecial . and &β8 Thalassemia H &.3I$ H -ver ? years/ ).ircumstances H History of repeated sepsis. &βKThalassemia H ) months to ? years/ (). warrants penicillin prophyla"is similar to && H &β8 Thalassemia/ penicillin prophyla"is can be safely discontinued at . surgical splenectomy . mg P.

. H Incidence ?< in && &ea 1an • nnual evaluation after age (* years by ophthalmologist H 'aser photocoagulation for vessel disease &almon Patch/ &.Eye E/amination • +etinal vessel disease H Incidence ??< in hemoglobin &.

Emer!encies • • • • • • • 0ever1in+ection -c(te chest syndrome Eye tra(ma 2hy hema3 Pria ism Stroke S lenic se4(estration Severe ain .

antibiotics IMMF$I TF'M if child appears ill or temperature L D*9. urinalysis. antibiotics/ %. with differential and reticulocyte count.3. chest "%ray • Indications for hospitali!ation J I.hild appears ill % ny temperature L D*9. % bnormal laboratory values • &tart I. 4(*(915 is an FMF+#FC.0ever and "n+ection • 1ever L ?=. and throat cultures..M • 3asic laboratory evaluation/ H . blood.9 . urine.C-T E IT 1-+ ' 3&5 . 4$.

respiratory symptoms.auses H Infection H 1at emboli H 'ung infarct &ince you cannot distinguish between acute chest syndrome and pneumonia clinically there is no change in treatment. new infiltrate on chest "%ray . .linically/ cute onset of fever.-c(te Chest Syndrome leading cause of death in sickle cell disease .

omplications if untreated/ %glaucoma. %retinal artery blockage .Eye Tra(ma Fye trauma is an emergency in '' sickle conditions 4including sickle trait5 #et sickle prep %rapid test% if sickle status unknown . %optic nerve atrophy.

ommonly occurs in children and adolescents with && or &.Pria ism . Treatment is difficult H -pioid pain medication H Intravenous fluids H spiration and irrigation of the corpus cavernosum H &urgery H 3lood Transfusions • Impotence with severe disease or recurrent episodes Urethra Corpus cavernosum .

• Historically = to (*< of children with && • N&ilent &trokeO in ))< of children with hemoglobin && Treatment/ .Stroke ny acute neurologic symptom other than mild headache.hronic transfusion therapy to maintain sickle hemoglobin at or below ?*< . even if transient. re6uires urgent evaluation.

S lenic Se4(estration • &udden trapping of blood within the spleen • Asually occurs in infants under ) years of age with && • &pleen enlarged on physical e"am. may not be associated with fever. or other symptoms • .irculatory collapse and death can occur in less than thirty minutes •+ecurrence very common 4. pain. respiratory.*<5 • ssociated with high mortality 4)*<5 .

< • Hemoglobin &.P years • .an occur in adolescence and adulthood • Incidence about . H Incidence increased/ ) and (@ years • Mean age =.S lenic Se4(estration • Hemoglobin && H Incidence increased/ : and ?: months • -verall incidence about (.< .

autious blood transfusion H Treat anemia.Treatments 0or S lenic Se4(estion • Intravenous fluids H Maintain vascular volume • . se6uestered blood can be released from spleen • &pleen removal or splenectomy H If indicated .

holelithiasis Priapism vascular necrosis +ight upper 6uadrant syndrome .Pain .ana!ement cute pain • • • • • • • • Hand%foot syndrome 4dactylitis5 Painful episodes/ vasoocculsion &plenic se6uestration cute chest syndrome .

times maintenance unless acute chest syndrome suspected • ssess pain level and treat H $o not withhold opioids H 1re6uently reassess pain control • ssess for cause of pain>complications .Pain ..ana!ement Pain is an emer!ency Hospital evaluation/ • Hydration/ (.

ana!ement Mild%moderate pain • -cetamino hen H Hepatoto"ic • Non'steroidal anti'in+lammatory a!ents 2NS-"Ds3 %.ontraindicated in patients with gastritis>ulcers and renal failure %Monitor renal function if used chronically .Pain .

an"iolytics5 • May increase efficacy of analgesics .Pain .ana!ement • Moderate%severe pain H -pioids are first%line treatment H Morphine sulfate or hydromorphone H Meperidine C-T recommended • 4Metabolite causes sei!ures J renal to"icity5 • Moderate or less severe pain H cetaminophen or C& I$Qs in combination with opioids H -ther adIuvant medications 4sedatives.

)and 0oot Syndrome ' Dactylitis • Farly complication of sickle cell disease • Highest incidence : months to ) years • Painful swelling of hands and feet • Treatment involves fluids and pain medication • 1evers treated as medical emergency .

proteinuria.&enal Disease • +enal findings H H H H H $ecreased ability to concentrate urine $ecreased ability to e"crete potassium Inability to lower urine pH normally Hematuria > papillary necrosis nemia. hematuria • +isk factors for progressive renal failure .

hronic hepatitis . leading to bleeding disorders or liver failure • Iron overload H $ue to chronic transfusions • .*all 5ladder and 6iver • #all stones and biliary sludge H Monitor by ultrasound every (%) years • .holestasis H May progress.

onservative • C& I$Rs and : weeks of rest off affected limb • Physical therapy .5one Disease Dia!nosis and Treatment • vascular necrosis of hips and shoulders H Inde" of suspicion • Persistent hip or shoulder pain • Plain film or M+I • Treatment H .

/ 1ilm #rade ./ 1ilm H Co grade for .Screenin! -$N • vascular Cecrosis H Hip 1ilms H Hip M+I H #rading of .C • • • • • #rade I/ M+I #rade II/ 1ilm>M+I #rade III/ 1ilm #rade I.C of the shoulder .

retinal detachment5 'eg ulcers .Chronic Com lications • • • • • • • nemia>0aundice 3rain $amage>&troke Sidney failure $ecreased lung function Fye disease 4bleeding.hronic pain management .

-nemia 7 8a(ndice • .ommon and starting in the first year of life • $ecreased lifespan of sickle red cells H Hemolysis H nemia H Hyperbilirubinemia H +eticulocytosis .

isual%spatial impairment • Impaired memory • Poor impulse control .Stroke • Intracranial hemorrhage H More common in adults • &e6uela overt and Nsilent strokesO H Paralysis/ overt stroke H Ceuropsychologic changes/ both overt and silent strokes • .

. increased M. and increased leukocyte count • +enal failure common in adults ..< H Increased incidence with age H Increased with anemia..$ patients with nephrotic syndrome develop end%stage renal disease • -ccurs in T )*< of all patients • -ccurs in D.&enal Disease • Proteinuria>Cephrotic syndrome • D*< of &.< of all pediatric patients% increased in hemoglobin && to :..

6e! 9lcers • -ccurs in about ).< of all hemoglobin && patients • Predominantly males H Incidence increased with • ge • $ecreased hemoglobin H Incidence decreased with alpha thalassemia • +ecurrence rate is T @.< .

hronic Pain • Pain lasting L? to : months • Patients should receive comprehensive psychologic and clinical assessment • Treatment H H H H H nalgesics Hydro"yurea TFC& units +ela"ation techni6ues Physical and occupational therapy ..

are • Moung adults 4L)* years5 with fre6uent pain crises at greatest risk for early death • 3arriers to care for young adults H 'ack of adult &. denial of chronic illness5 H Ineffective coping skills 4passive versus active5 .$ providers H 'oss of medical coverage H $evelopmental 4level of independence.dolescents and Transition of .

support groups • Plan gradual transition 4start ( year before5 • . school>vocational staff. social work.are • $evelop e"plicit plan for transition • Team approach% pediatric and adult providers.dolescents and Transition of .ontinue communication between pediatric J adult providers after transition .

ontent should include/ %#enetic basis. variability>unpredictability of disease.ounseling • Eho should receive counselingU %Parents of newborns with sickle disorders or traits %Pregnant women> prenatal counseling • Ehat is the purpose of counselingU %Fducation %Informed decision%making • . average life span . chances of disease or trait 4potential pregnancy outcome5. family planning. disease%related health problems.#enetic .

nih.gov>health>prof>blood>sickle>scVmngt.pdf .nhlbi.Information about sickle cell disease can be found through the merican cademy of Pediatrics or from the Cational Institute of Health on line at/ http/>>www.