Sickle Cell Disease/Acute Chest Syndrome Chairman’s Rounds August 13, 2010 David H. Rubin, MD Department of Pediatrics, St. Barnabas Hospital Professor

Sickle Cell Sickle Cell Disease/Acute Chest Disease/Acute Chest Syndrome Syndrome Chairman’s RoundsChairman’s RoundsAugust 13, 2010August 13, 2010

David H. Rubin, MDDavid H. Rubin, MDDepartment of Pediatrics, St. Barnabas Department of Pediatrics, St. Barnabas HospitalHospitalProfessor of Clinical Pediatrics, Professor of Clinical Pediatrics, Albert Einstein College of Medicine Albert Einstein College of Medicine

OBJECTIVESOBJECTIVES

Case presentationCase presentation History of sickle cell diseaseHistory of sickle cell disease PathophysiologyPathophysiology ComplicationsComplications TreatmentTreatment Competency Based SummaryCompetency Based Summary

CASE PRESENTATIONCASE PRESENTATION

12 month old SC patient with fever 12 month old SC patient with fever for 2 days; tmax 103for 2 days; tmax 103FF

+ rhinorrhea, no cough+ rhinorrhea, no cough Reduced oral intake and activityReduced oral intake and activity PE: T105.2PE: T105.2F, P198, R62, O2sat:97%F, P198, R62, O2sat:97%

• ChestChest reduced breath sounds R base reduced breath sounds R base Chest xray: R base infiltrateChest xray: R base infiltrate

HISTORY OF SICKLE CELL HISTORY OF SICKLE CELL DISEASEDISEASE

19101910 • First description (in western literature) First description (in western literature)

of sickle cell disease by Chicago of sickle cell disease by Chicago physician James B. Herrickphysician James B. Herrick

• Patient from West Indies with anemia Patient from West Indies with anemia characterized by unusual red cells: characterized by unusual red cells: “sickle shaped”“sickle shaped”

19271927• Hahn and Gillespie showed sickling of Hahn and Gillespie showed sickling of

red cells was related to low oxygen red cells was related to low oxygen


19481948 • Janet Watson (pediatric hematologist in Janet Watson (pediatric hematologist in

New York) noted newborn fetal hemoglobin New York) noted newborn fetal hemoglobin lacked abnormal sickle hemoglobin seen in lacked abnormal sickle hemoglobin seen in adults adults

• Linus Pauling and Harvey Itano showed that Linus Pauling and Harvey Itano showed that hemoglobin from patients with sickle cell hemoglobin from patients with sickle cell disease is different from normalsdisease is different from normals

• First disorder in which abnormality in First disorder in which abnormality in protein known to be at fault protein known to be at fault


1984 1984 • BBone marrow transplantation in a child with in a child with

sickle cell disease produced the first reported sickle cell disease produced the first reported curecure

• Transplantation was performed to treat acute Transplantation was performed to treat acute leukemia-child's sickle cell disease was cured leukemia-child's sickle cell disease was cured as a side-event as a side-event

1995 1995 • HydroxyureaHydroxyurea became the first (and only) became the first (and only)

drug proven to drug proven to preventprevent complications of complications of sickle cell disease in the sickle cell disease in the Multicenter Study of Multicenter Study of Hydroxyurea in Sickle Cell AnemiaHydroxyurea in Sickle Cell Anemia

HEMOGLOBIN HEMOGLOBIN MOLECULEMOLECULE

Hemoglobin - two pairs of non-Hemoglobin - two pairs of non-identical globin and polypeptide identical globin and polypeptide chains; each chain associated with chains; each chain associated with one heme groupone heme group

Four polypeptide chains (alpha, beta, Four polypeptide chains (alpha, beta, gamma and delta) in the globin gamma and delta) in the globin portion portion • HbA - 2 alpha and 2 beta chainsHbA - 2 alpha and 2 beta chains• HbF - 2 alpha and 2 gamma chainsHbF - 2 alpha and 2 gamma chains• HbA2 - 2 alpha and 2 delta chainsHbA2 - 2 alpha and 2 delta chains

Heme group - iron containing pigment Heme group - iron containing pigment responsible for oxygen transport responsible for oxygen transport

Hemoglobin A

SICKLE CELL DISEASESICKLE CELL DISEASE

The chain of colored boxes represent the first eight amino acids in the beta chain of hemoglobin. The sixth position in the normal beta chain has glutamic acid, while sickle beta chain has valine. This is the sole difference between the two.

SICKLE CELL DISEASESICKLE CELL DISEASE 1/400 African American infants1/400 African American infants 8% of African Americans are 8% of African Americans are

heterozygous carriers of the gene – they heterozygous carriers of the gene – they have traithave trait

Also found in: African, Mediterranean, Also found in: African, Mediterranean, Middle Eastern, Indian, or Caribbean Middle Eastern, Indian, or Caribbean ancestryancestry

Pathology directly related to Pathology directly related to polymerization of deoxygenated sickle polymerization of deoxygenated sickle hemoglobinhemoglobin• Distortion of erythrocyte morphologyDistortion of erythrocyte morphology• Reduced RBC life spanReduced RBC life span• Increased viscosityIncreased viscosity• Episodes of vasoocculsionEpisodes of vasoocculsion


Antenatal diagnosis by Antenatal diagnosis by amniocentesis or chorionic amniocentesis or chorionic villus DNA villus DNA

Hb S identified by Hb S identified by electrophoresis and solubility electrophoresis and solubility testingtesting• Affected newborns express small Affected newborns express small

quantities of Hb S – quantities of Hb S – even with even with predominance of Hb Fpredominance of Hb F


Clinical course: Clinical course: • ischemic changesischemic changes• intermittent “crises”intermittent “crises”

Anemia, increased reticulocyte Anemia, increased reticulocyte countcount

Splenomegaly in early Splenomegaly in early childhoodchildhood

High risk of bacterial sepsisHigh risk of bacterial sepsis

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

OXYGEN SATURATION CURVES in (a) 41 normals and (b) 53 subjects with sickle cell anemia. For any given pO2, the saturation for Hb SS cells is less than that for normal erythrocytes. (Johnson CS, Verdegem TV. Pulmonary complications of sickle cell disease. Semin Resp Med 1988;9:291)

LABORATORY FINDINGSLABORATORY FINDINGS

Hemoglobin: 5-9 g/dlHemoglobin: 5-9 g/dl Target cells, Target cells,

poikilocytes, sickled poikilocytes, sickled cellscells

Reticulocyte count 5-Reticulocyte count 5-15%15%

WBC count: 12-WBC count: 12-15,000/mm15,000/mm33

Platelet count Platelet count increasedincreased

Increased LFT’s, Increased LFT’s, bilirubinbilirubin

DIFFERENTIAL DIFFERENTIAL DIAGNOSISDIAGNOSIS

Surgical abdomenSurgical abdomen Rheumatic feverRheumatic fever Rheumatoid arthritisRheumatoid arthritis OsteomyelitisOsteomyelitis LeukemiaLeukemia

COMPLICATIONS ICOMPLICATIONS I Priapism - GU tract infarctionPriapism - GU tract infarction Retinopathy – sequestration Retinopathy – sequestration

of blood in conjunctival of blood in conjunctival vessels; retinal hemorrhagevessels; retinal hemorrhage

Cholelithiasis - chronic Cholelithiasis - chronic hemolysishemolysis

Osteonecrosis of femoral headOsteonecrosis of femoral head

COMPLICATIONS IICOMPLICATIONS II Hematuria, hyposthenuria, Hematuria, hyposthenuria,

renal failure - papillary renal failure - papillary necrosisnecrosis

Jaundice - hepatic infarctJaundice - hepatic infarct Stroke, seizures, weakness, Stroke, seizures, weakness,

sensory hearing loss - CNS sensory hearing loss - CNS ischemiaischemia

Respiratory distress - Respiratory distress - pulmonary infarctionpulmonary infarction

““ROUTINE” ROUTINE” TREATMENTTREATMENT

Maintain full immunization statusMaintain full immunization status Administer polyvalent Administer polyvalent

pneumococcal vaccine (pneumococcal vaccine (may be may be poorly immunogenic in children poorly immunogenic in children with Hb SS and < 5 yrs of age)with Hb SS and < 5 yrs of age)

Administer Administer H. influenzae H. influenzae vaccinevaccine Folic acid dailyFolic acid daily

““ROUTINE” TREATMENTROUTINE” TREATMENT

Prophylactic penicillin 4 mo- 5 Prophylactic penicillin 4 mo- 5 yrs (<5y: 125mg/12h; >5y: yrs (<5y: 125mg/12h; >5y: 250mg/12h)250mg/12h)

Aggressive ED approach to Aggressive ED approach to temperature >38.5temperature >38.5C: C: • laboratory studies (CBC, culture, laboratory studies (CBC, culture,

UA and culture, chest x-ray)UA and culture, chest x-ray)• admissionadmission• antibioticsantibiotics

SPECIFIC PROBLEMS IN SPECIFIC PROBLEMS IN SICKLE CELL PATIENTSSICKLE CELL PATIENTS

Bacterial sepsisBacterial sepsis• Other infectionsOther infections

Acute chest syndromeAcute chest syndrome Vasoocclusion crisesVasoocclusion crises Splenic sequestration crisesSplenic sequestration crises Aplastic crisesAplastic crises Hemolytic crisesHemolytic crises TreatmentTreatment

BACTERIAL SEPSISBACTERIAL SEPSIS Impaired immunologic function, Impaired immunologic function,

functional aspleniafunctional asplenia Increased risk fromIncreased risk from: :

streptococcus pneumoniae, H. streptococcus pneumoniae, H. influenzae, n. meningitidis, influenzae, n. meningitidis, salmonella, E. coli, mycoplasma salmonella, E. coli, mycoplasma pneumoniae, staphylococcus pneumoniae, staphylococcus aureusaureus

Greatest risk 6 months - 3 years Greatest risk 6 months - 3 years of ageof age

BACTERIAL SEPSISBACTERIAL SEPSIS Impaired immunologic functionImpaired immunologic function

• Loss of splenic activityLoss of splenic activity• Fulminant nature of illnessFulminant nature of illness• Most dangerous period: 6m-3y (protective Most dangerous period: 6m-3y (protective

antibodies limited with diminished splenic antibodies limited with diminished splenic function)function)

Risk of sepsis = 100X normal populationRisk of sepsis = 100X normal population Streptococcus pneumoniae, h. influenza Streptococcus pneumoniae, h. influenza

most common in young childrenmost common in young children E. coli and salmonella most common in E. coli and salmonella most common in

older childrenolder children

BACTERIAL SEPSISBACTERIAL SEPSIS Differentiating the patient with Differentiating the patient with

viral illness vs serious bacterial viral illness vs serious bacterial illness (SBI) difficultillness (SBI) difficult

ONLY a blood culture can identify ONLY a blood culture can identify difference – MUST obtain rapidly difference – MUST obtain rapidly and administer antibioticsand administer antibiotics

Clinical deterioration is VERY Clinical deterioration is VERY rapidrapid

Treat for septic shock EARLYTreat for septic shock EARLY

BACTERIAL SEPSISBACTERIAL SEPSIS Emergence of penicillin resistant Emergence of penicillin resistant

streptococcus pneumoniaestreptococcus pneumoniae Rapid blood work and IV ceftriaxone Rapid blood work and IV ceftriaxone

or cefotaxime and vancomycin (if area or cefotaxime and vancomycin (if area of high resistance)of high resistance)

If not acutely ill on physical exam (no If not acutely ill on physical exam (no pallor, rales, increased spleen, rales) pallor, rales, increased spleen, rales) with guaranteed follow-up within with guaranteed follow-up within 24H, may treat with ceftriaxone 50 24H, may treat with ceftriaxone 50 mg/kg, otherwise admitmg/kg, otherwise admit

BACTERIAL SEPSISBACTERIAL SEPSIS Short stay outpatient unit also Short stay outpatient unit also

appropriateappropriate If “low risk” for SBI, may give PO If “low risk” for SBI, may give PO

or IV antibiotics and or IV antibiotics and discharge….BUT MUST SEE discharge….BUT MUST SEE WITHIN 24 HRS for FOLLOWUPWITHIN 24 HRS for FOLLOWUP

Older child with any fever…may Older child with any fever…may not have high WBC and may not not have high WBC and may not have high fever….BEWARE – admit have high fever….BEWARE – admit for antibiotics and close for antibiotics and close observationobservation

BACTERIAL BLOOD BACTERIAL BLOOD CULTURES IN CHILDREN CULTURES IN CHILDREN WITH SCD WITH SCD (Rogovik 2009)(Rogovik 2009)

Retrospective chart review of 692 Retrospective chart review of 692 pediatric SCD patients with or without pediatric SCD patients with or without fever from 2005-2007 in Toronto Sick fever from 2005-2007 in Toronto Sick Children’s Hospital (inclusion in study Children’s Hospital (inclusion in study limited to 530 with blood cultures)limited to 530 with blood cultures)

77% of febrile children admitted; 7 77% of febrile children admitted; 7 positive cultures; 3 in febrile childrenpositive cultures; 3 in febrile children

No No s.pneumoniae s.pneumoniae species – “all species – “all identified microorganisms part of identified microorganisms part of normal skin or oral flora and could be normal skin or oral flora and could be contaminants…”contaminants…”• Thought to be due to 7-valent Thought to be due to 7-valent

pneumococcal vaccinepneumococcal vaccine

SEPTIC SEPTIC ARTHRITIS/OSTEOMYELITIARTHRITIS/OSTEOMYELITI

SS VERY difficult to diagnose VERY difficult to diagnose

clinically; similar to bone clinically; similar to bone infarctioninfarction

Diagnostic tests prior to Diagnostic tests prior to antibiotics: Gram stain and antibiotics: Gram stain and cultureculture• bone aspiration (osteomyelitis)bone aspiration (osteomyelitis)• joint aspiration (septic arthritis)joint aspiration (septic arthritis)

AntibioticsAntibiotics

INFLUENZA A (H1N1) AND INFLUENZA A (H1N1) AND SICKLE CELL DISEASESICKLE CELL DISEASE

(Inusa 2010)(Inusa 2010) Review of cases of H1N1 disease in Review of cases of H1N1 disease in

patients with SS disease in children in patients with SS disease in children in London: April–August 2009London: April–August 2009

21 positive cases among 2200 patients 21 positive cases among 2200 patients with SCD; 19 were admitted; 11 with SCD; 19 were admitted; 11 needed blood transfusions due to needed blood transfusions due to falling Hg and ACS (10 patients had falling Hg and ACS (10 patients had acute chest syndrome)acute chest syndrome)

All successfully treated with oseltamivirAll successfully treated with oseltamivir

ACUTE CHEST ACUTE CHEST SYNDROME SYNDROME (Vichinsky 2000)(Vichinsky 2000)

Defined as a new infiltrate on a Defined as a new infiltrate on a chest radiograph associated with chest radiograph associated with one or more symptoms such asone or more symptoms such as• FeverFever• CoughCough• Sputum productionSputum production• TachypneaTachypnea• DyspneaDyspnea• New onset hypoxiaNew onset hypoxia

ACUTE CHEST ACUTE CHEST SYNDROME SYNDROME (Vichinsky 2000)(Vichinsky 2000)

Clinical and radiological similarity Clinical and radiological similarity to bacterial pneumoniato bacterial pneumonia• Fever, leukocytosisFever, leukocytosis• Pleuritic chest painPleuritic chest pain• Pleural effusionPleural effusion• Cough with purulent sputumCough with purulent sputum

Clinical course is uniqueClinical course is unique• Multiple lobe involvement possibleMultiple lobe involvement possible• Duration of clinical illness and of Duration of clinical illness and of

radiologic clearing of infiltrates radiologic clearing of infiltrates prolonged (10-12 days)prolonged (10-12 days)

ACUTE CHEST ACUTE CHEST SYNDROME/PathophysiologySYNDROME/Pathophysiology Process may be initiated byProcess may be initiated by

• Microbial infectionMicrobial infection• In situ vaso-occlusionIn situ vaso-occlusion• Fat embolism from ischemic/necrosis Fat embolism from ischemic/necrosis

bone marrowbone marrow• ThomboembolismThomboembolism

?Activation of endothelium by ?Activation of endothelium by oxygen radicals of erythrocytes or oxygen radicals of erythrocytes or infection process that induces infection process that induces secretion of inflammatory cytokinessecretion of inflammatory cytokines

ACUTE CHEST ACUTE CHEST SYNDROMESYNDROME

Most cases are infectious Most cases are infectious originorigin

Difficult to identify organism Difficult to identify organism although more common although more common organisms areorganisms are•Mycoplasma pneumoniaeMycoplasma pneumoniae•S pneumoniaeS pneumoniae•Chlamydia trachomatisChlamydia trachomatis

ACUTE CHEST SYNDROME ACUTE CHEST SYNDROME Clinical PresentationClinical Presentation

(Johnson 2005)(Johnson 2005)

Fever > 38.5Fever > 38.5°C and cough most °C and cough most commoncommon – especially in children – especially in children compared with adolescentscompared with adolescents

Tachypnea and bronchospasm more Tachypnea and bronchospasm more common in childrencommon in children

HoweverHowever – – 35% of patients had 35% of patients had normal PEnormal PE; “additional data ; “additional data support unreliability of the physical support unreliability of the physical examination in the detection of examination in the detection of ACS…”ACS…”


SymptomsSymptoms: tachypnea, rales, ronchi, ?: tachypnea, rales, ronchi, ?lobar consolidationlobar consolidation

WorkupWorkup: oxygen saturation, CBC, blood : oxygen saturation, CBC, blood culture, chest x-ray (may be negative in culture, chest x-ray (may be negative in 50% of cases) 50% of cases)

TreatmentTreatment: : • Start antibiotics earlyStart antibiotics early• Initiate IV ampicillin or ceftriaxone (plus Initiate IV ampicillin or ceftriaxone (plus

erythromycin in young child); consider erythromycin in young child); consider streptococcus pneumoniae streptococcus pneumoniae or or MycoplasmaMycoplasma

• RBC transfusion or exchange transfusion for RBC transfusion or exchange transfusion for severe anemia (Hg < 5), hypoxia, radiographic severe anemia (Hg < 5), hypoxia, radiographic evidence of rapidly progressive diseaseevidence of rapidly progressive disease

• Therapy with steroids may prevent clinical Therapy with steroids may prevent clinical deterioration in ACSdeterioration in ACS

STEROIDS AND ACS STEROIDS AND ACS (Strouse 2008)(Strouse 2008)

Retrospective cohort study to examine Retrospective cohort study to examine risk factors for readmission and risk factors for readmission and prolonged hospitalization at Johns prolonged hospitalization at Johns Hopkins in patients < 22 yrs of age Hopkins in patients < 22 yrs of age 1998-20041998-2004

Identified 65 patients with 129 Identified 65 patients with 129 episodes of ACS (mean age 12.5 yrs)episodes of ACS (mean age 12.5 yrs)

Readmission strongly associated with Readmission strongly associated with use of corticosteroid (OR 20, p<.005) use of corticosteroid (OR 20, p<.005)

Suggest limited use of steroidsSuggest limited use of steroids

STEROIDS AND ACS STEROIDS AND ACS (Kumar 2010)(Kumar 2010)

Retrospective study of 63 patients Retrospective study of 63 patients with 78 episodes of ACS from 2005-with 78 episodes of ACS from 2005-2007 at SUNY Downstate2007 at SUNY Downstate

““Asthma Regimen” of prednisone Asthma Regimen” of prednisone used (2mg/kg/d max 80 mg in 2 used (2mg/kg/d max 80 mg in 2 divided doses for 5 daysdivided doses for 5 days

15% of 53 children receiving steroids 15% of 53 children receiving steroids and 8% of the 25 children who did not and 8% of the 25 children who did not receive steroids were readmitted (NS)receive steroids were readmitted (NS)

No significant readmission rate from No significant readmission rate from steroidssteroids

STEROIDS AND ACS STEROIDS AND ACS (Sieff 2010)(Sieff 2010)

““Therapy with steroids not Therapy with steroids not usually needed unless usually needed unless patient has a history of patient has a history of asthma and signs of asthma asthma and signs of asthma exacerbation….”exacerbation….”


(Kikiska 2004)(Kikiska 2004)

Increased incidence following Increased incidence following abdominal surgery (15-20%)abdominal surgery (15-20%)

ACS was associated withACS was associated with• Age (young Age (young vs old) vs old)• Weight (lighter Weight (lighter over heavier) over heavier)• Operative blood loss (more > Operative blood loss (more >

less)less)• Lower final temperatureLower final temperature

CAUSES OF ACUTE CHEST SYNDROME1. Hb S–Related *Direct consequences of Hb S

• Pulmonary vaso-occlusion (16.1%)• Fat embolism from bone marrow

ischemia/infarction (8.8%)• Hypoventilation secondary to

rib/sternal bone infarction or to narcotic use

• Pulmonary edema induced by narcotics or fluid overload

*Indirect consequences of Hb S • Infection

Atypical bacterialChlamydia pneumoniae (7.2%)Mycoplasma pneumoniae (6.6%)Mycoplasma hominis (1.0%)

CAUSES OF ACUTE CHEST SYNDROME*

•Bacterial •Staphylococcus aureus, coagulase-positive (1.8%)•Streptococcus pneumoniae (1.6%)•Haemophilus influenzae (0.7%)

•Viral •Respiratory syncytial virus (3.9%)•Parvovirus B19 (1.5%)•Rhinovirus (1.2%)

•2. Unrelated to Hb S •Fibrin thromboembolism •Other common pulmonary diseases (eg, aspiration, trauma, asthma) *Vichinsky et al., NEJM, 2000 and Johnson, Semin Resp Med, 1988

POOR PROGNOSIS/POTENTIAL INDICATIONS FOR POOR PROGNOSIS/POTENTIAL INDICATIONS FOR EXCHANGE TRANSFUSION IN ACUTE CHEST EXCHANGE TRANSFUSION IN ACUTE CHEST

SYNDROMESYNDROME(Vichinsky 2000, Johnson 1988, Fine 1997)

Altered mental status and other Altered mental status and other acute neurologic findingsacute neurologic findings

Persistent tachycardia >125/minPersistent tachycardia >125/min Persistent respiratory rate >30/min Persistent respiratory rate >30/min

or increased work of breathing or increased work of breathing (nasal flaring, use of accessory (nasal flaring, use of accessory muscles, sternal retractions)muscles, sternal retractions)

Temperature >40°CTemperature >40°C Hypotension compared with Hypotension compared with

baselinebaseline

POOR PROGNOSIS/POTENTIAL INDICATIONS POOR PROGNOSIS/POTENTIAL INDICATIONS FOR EXCHANGE TRANSFUSION IN ACUTE FOR EXCHANGE TRANSFUSION IN ACUTE

CHEST SYNDROMECHEST SYNDROME(Vichinsky 2000, Johnson 1988, Fine 1997)

Arterial pH <7.35Arterial pH <7.35 Arterial oxygen saturation persistently Arterial oxygen saturation persistently

<88%, despite aggressive ventilatory <88%, despite aggressive ventilatory supportsupport

Serial decline in pulse oximetry or Serial decline in pulse oximetry or increasing A-a gradientincreasing A-a gradient

Hemoglobin concentration falling by 2 g/dL Hemoglobin concentration falling by 2 g/dL or moreor more

Platelet count <200,000/μLPlatelet count <200,000/μL Evidence for multiorgan failureEvidence for multiorgan failure Pleural effusionPleural effusion Progression to multilobe infiltratesProgression to multilobe infiltrates

ASTHMA AND ACSASTHMA AND ACS(Boyd 2004)(Boyd 2004)

Does asthma increase the risk of Does asthma increase the risk of ACS in children with sickle cell ACS in children with sickle cell disease?disease?

Retrospective case control study Retrospective case control study (cases: ACS, controls: no ACS)(cases: ACS, controls: no ACS)

Cases of physician diagnosed Cases of physician diagnosed asthma 4 times (95% CI: 1.7, 9.5) asthma 4 times (95% CI: 1.7, 9.5) more likely to develop ACS and more likely to develop ACS and longer hospitalizationlonger hospitalization

ACS AND LUNG ACS AND LUNG FUNCTIONFUNCTION

(Sylvester 2006)(Sylvester 2006)

Hypothesis: children with sickle cell Hypothesis: children with sickle cell disease hospitalized with ACS have poor disease hospitalized with ACS have poor lung function compared with those with lung function compared with those with SCD not hospitalized with ACS SCD not hospitalized with ACS

ResultsResults• Higher resistance, TLC and RV in ACS groupHigher resistance, TLC and RV in ACS group• No difference in PFTs pre/post bronchodilator No difference in PFTs pre/post bronchodilator

therapy, but ACS group had lower FEVtherapy, but ACS group had lower FEV2525 and and FEFFEF7575 pre and lower FEF pre and lower FEF7575 post post

Conclusion – ACS hospitalized children Conclusion – ACS hospitalized children had significant differences in PFThad significant differences in PFT

VASOOCCLUSIONVASOOCCLUSION Infarction of bone, soft tissue, Infarction of bone, soft tissue,

and viscera by sickled red cellsand viscera by sickled red cells Young childrenYoung children: usually painful : usually painful

crises involve extremitiescrises involve extremities Older children/adolescentsOlder children/adolescents: head, : head,

chest, abdominal, back painchest, abdominal, back pain Intercurrent illness may Intercurrent illness may

precipitate crisisprecipitate crisis

HAND-FOOT HAND-FOOT SYNDROMESYNDROME

Acute sickle Acute sickle dactylitisdactylitis

11stst manifestation of manifestation of diseasedisease

Pain symmetrical Pain symmetrical swelling of hands swelling of hands and feet and feet

Ischemic necrosis of Ischemic necrosis of small bones; rapidly small bones; rapidly expanding bone expanding bone marrow chokes off marrow chokes off blood supplyblood supply

Radiographs helpful Radiographs helpful in chronic stagein chronic stage

VASOOCCLUSIONVASOOCCLUSION Occlusion of mesenteric vessels Occlusion of mesenteric vessels

vs. appendicitis; pain may mimic vs. appendicitis; pain may mimic acute surgical conditionacute surgical condition

Hepatic infarction - acute onset Hepatic infarction - acute onset of jaundice and abdominal pain of jaundice and abdominal pain (similar to hepatitis, cholycystitis (similar to hepatitis, cholycystitis and biliary obstruction)and biliary obstruction)

GU Tract - renal papillary GU Tract - renal papillary necrosis, priapismnecrosis, priapism• Antifibrinolytic drugs Antifibrinolytic drugs -aminocaproic acid or -aminocaproic acid or

tranexamic acid may cause ureteral clottranexamic acid may cause ureteral clot

VASOOCCLUSION/ VASOOCCLUSION/ TreatmentTreatment

Mild/Moderate PainMild/Moderate Pain• 11½½ maintenance with oral or IV fluids or maintenance with oral or IV fluids or

D5½NS or D5¼NSD5½NS or D5¼NS• Acetaminophen with or without codeineAcetaminophen with or without codeine• Admit if poor pain control, poor Admit if poor pain control, poor

hydration status, or repeated ED visitshydration status, or repeated ED visits Severe PainSevere Pain

• 11½½ maintenance with oral or IV fluids or maintenance with oral or IV fluids or D5½NS or D5¼NSD5½NS or D5¼NS

• Morphine 0.1-0.15 mg/kg IVMorphine 0.1-0.15 mg/kg IV• AdmitAdmit

CNS INFARCTIONCNS INFARCTION Spectrum of initial complaints: mild Spectrum of initial complaints: mild

symptoms of TIA to seizures, coma, symptoms of TIA to seizures, coma, hemiparesis, deathhemiparesis, death

Cortical infarction seen on MRI or CTCortical infarction seen on MRI or CT Immediately start 1½ - 2 volume Immediately start 1½ - 2 volume

exchange to reduce Hb S to < 30% of exchange to reduce Hb S to < 30% of total Hbtotal Hb• whole blood < 5 days old ORwhole blood < 5 days old OR• packed red cells < 5 days reconstituted with packed red cells < 5 days reconstituted with

fresh frozen plasmafresh frozen plasma Preserve pre-transfused sample for red Preserve pre-transfused sample for red

cell antigen identification cell antigen identification

PRIAPISMPRIAPISM

Admit with severe pain or persistent Admit with severe pain or persistent erectionerection

Hydration: 1½ - 2X maintenance for 24-Hydration: 1½ - 2X maintenance for 24-48 hours with IV fluids D5½NS or D5¼NS48 hours with IV fluids D5½NS or D5¼NS

If swelling does not decrease, transfuse If swelling does not decrease, transfuse with red cells to raise Hb to 9-10g/dlwith red cells to raise Hb to 9-10g/dl

If no improvement, exchange transfusion If no improvement, exchange transfusion to reduce Hb S to < 30% of total Hbto reduce Hb S to < 30% of total Hb

If no improvement, corporal aspiration If no improvement, corporal aspiration or surgical procedureor surgical procedure

SPLENIC SEQUESTRATION SPLENIC SEQUESTRATION CRISISCRISIS

SymptomsSymptoms: left upper quadrant : left upper quadrant pain, pallor, lethargypain, pallor, lethargy

SignsSigns: hypotension, tachycardia, : hypotension, tachycardia, enlarged and firm spleenenlarged and firm spleen

LaboratoryLaboratory: severe anemia, : severe anemia, thrombocytopenia, neutropenia, thrombocytopenia, neutropenia, increased reticulocytesincreased reticulocytes

TreatmentTreatment: Immediate volume : Immediate volume replacement, transfusion with replacement, transfusion with packed red cells or whole bloodpacked red cells or whole blood

APLASTIC CRISISAPLASTIC CRISIS SymptomsSymptoms: progressive pallor, : progressive pallor,

lethargy, may be caused by lethargy, may be caused by parvoviral infectionparvoviral infection

SignsSigns: absence of jaundice : absence of jaundice LaboratoryLaboratory: severe anemia, : severe anemia,

decreased reticulocytesdecreased reticulocytes TreatmentTreatment: transfusion with : transfusion with

packed red cells or whole packed red cells or whole bloodblood

HEMOLYTIC CRISISHEMOLYTIC CRISIS

SymptomsSymptoms: viral/bacterial : viral/bacterial infectioninfection

SignsSigns: sudden pallor, jaundice, : sudden pallor, jaundice, scleral icterus scleral icterus

LaboratoryLaboratory: severe anemia, : severe anemia, increased reticulocytes, active increased reticulocytes, active hemolysishemolysis

TreatmentTreatment: rarely needs : rarely needs transfusion; await resolution of transfusion; await resolution of infection infection

TREATMENT TREATMENT (Sieff 2010)(Sieff 2010)

Fluids Fluids • Primarily for vaso-occlusive crisisPrimarily for vaso-occlusive crisis• 11½½ maintenance with oral or IV fluids or maintenance with oral or IV fluids or

D5½NS or D5¼NS D5½NS or D5¼NS Pain managementPain management

• Mild/moderate: oral medications Mild/moderate: oral medications acetaminophen with codeine or acetaminophen with codeine or oxycodeineoxycodeine

• Severe: IV morphine or hydromorphine, Severe: IV morphine or hydromorphine, patient controlled analgesia, NSAIDs patient controlled analgesia, NSAIDs

TREATMENT TREATMENT (Sieff 2010)(Sieff 2010)

Sepsis – antibioticsSepsis – antibiotics• Due to emergence of resistant strains of s. Due to emergence of resistant strains of s.

pneumoniae, treat with 3pneumoniae, treat with 3rdrd generation generation cephalosporin (cefotaxime or ceftriaxone) cephalosporin (cefotaxime or ceftriaxone) and vancomycinand vancomycin

• Watch for secondary organ damage due to Watch for secondary organ damage due to sickling in presence of acidosis, stasis, and sickling in presence of acidosis, stasis, and hypoxia – consider transfusion (packed hypoxia – consider transfusion (packed RBC or exchange transfusions)RBC or exchange transfusions)

Acute chest syndromeAcute chest syndrome – cover for – cover for appropriate organismsappropriate organisms

TREATMENT TREATMENT (Roseff 2009)(Roseff 2009)

TransfusionTransfusion• Consider in patients with signs and Consider in patients with signs and

symptoms of anemiasymptoms of anemia• Increases patient hemoglobinIncreases patient hemoglobin• Dilutes Hg S with Hg ADilutes Hg S with Hg A

• RBC’s with Hg A - longer survival than Hg RBC’s with Hg A - longer survival than Hg SS

• Suppresses patient’s own Suppresses patient’s own erythropoiesiserythropoiesis


Simple transfusion (peripheral IV)Simple transfusion (peripheral IV)• Technical ease, low risk of exposure, Technical ease, low risk of exposure,

dilution of Hg Sdilution of Hg S• Increases viscosity, risk of Fe overloadIncreases viscosity, risk of Fe overload

Exchange transfusion (automated Exchange transfusion (automated machine)machine)• Rapid reduction in Hg S, no risk of Fe Rapid reduction in Hg S, no risk of Fe

overloadoverload• Requires large gauge catheter, expertise in Requires large gauge catheter, expertise in

special equipment, higher risk of exposurespecial equipment, higher risk of exposure


Indications for transfusionIndications for transfusion• Aplastic crisisAplastic crisis• Hemolytic crisis (extremely rare)Hemolytic crisis (extremely rare)• Splenic sequestrationSplenic sequestration• PriapismPriapism• Presurgical prophylaxisPresurgical prophylaxis• Acute chest syndromeAcute chest syndrome• StrokeStroke

OTHER TREATMENT OTHER TREATMENT (Sieff 2009, Steinberg 2010)(Sieff 2009, Steinberg 2010)

Stem cell transplantationStem cell transplantation HydroxyureaHydroxyurea

• Introduced 25 years ago based on ability Introduced 25 years ago based on ability to increase fetal hemoglobin (Hg F)to increase fetal hemoglobin (Hg F)

• Observational studies in children have Observational studies in children have shown benefits and safetyshown benefits and safety

• Often used for maintenance therapy in Often used for maintenance therapy in patients with strokepatients with stroke

• In long term study (17.5 years f/u) In long term study (17.5 years f/u) mortality reduced in those treated with mortality reduced in those treated with hydroxyureahydroxyurea

TRANSITION TO ADULT TRANSITION TO ADULT CARE CARE

(Hunt 2010)(Hunt 2010)

30 day rate of return to acute 30 day rate of return to acute care care • 10-17 yrs: 27.4%10-17 yrs: 27.4%• 18-30 yrs: 48.9%18-30 yrs: 48.9%

Why the increase?Why the increase?• Lack of insuranceLack of insurance• Poor follow-up contactsPoor follow-up contacts• Too much reliance on emergency Too much reliance on emergency

departments for ongoing caredepartments for ongoing care

SUMMARYSUMMARY Chronic hemolytic anemiaChronic hemolytic anemia CrisesCrises: vasoocclusive (any : vasoocclusive (any

organ, acute chest syndrome, organ, acute chest syndrome, stroke), hemolytic, stroke), hemolytic, sequestration, aplasticsequestration, aplastic

Watch for sepsisWatch for sepsis Continuity of care criticalContinuity of care critical: :

immunizations, antibioticsimmunizations, antibiotics

COMPETENCY COMPETENCY BASED OBJECTIVESBASED OBJECTIVES

Medical KnowledgeMedical Knowledge • knowledge about the established knowledge about the established

and evolving biomedical, clinical, and evolving biomedical, clinical, and cognate (epidemiological and and cognate (epidemiological and social-behavioral) sciences and social-behavioral) sciences and their application to patient caretheir application to patient care

• Diagnosis, management of sickle Diagnosis, management of sickle cell disease cell disease


Patient CarePatient Care • family centered patient care family centered patient care

developmentally and age developmentally and age appropriate compassionate and appropriate compassionate and effective for treatment of health effective for treatment of health care problems and promotion of care problems and promotion of healthhealth

• Medical home for treatment of Medical home for treatment of multispecialty diseasemultispecialty disease


Practice Based LearningPractice Based Learning • investigation and evaluation of investigation and evaluation of

patient care, and the assimilation patient care, and the assimilation of scientific evidenceof scientific evidence

Communication SkillsCommunication Skills • interpersonal and communication interpersonal and communication

skills resulting in effective skills resulting in effective information exchange and learning information exchange and learning with patients, families and with patients, families and professional associatesprofessional associates


System Based PracticeSystem Based Practice • understanding systems of health understanding systems of health

care organization, financing, and care organization, financing, and delivery, and the relationship of delivery, and the relationship of one’s local practice and these one’s local practice and these larger systemslarger systems

ProfessionalismProfessionalism • carrying out professional carrying out professional

responsibilities, adherence to responsibilities, adherence to ethical principles, and sensitivity ethical principles, and sensitivity to diverse patient populationsto diverse patient populations

REFERENCESREFERENCES Vichinsky et al., NEJM, 2000 Fine et al, NEJM 1997 Johnson CS. The acute chest syndrome.

Hematol Oncol CLin N am 19 (2005) 857-879. Sylvester KP et al. Impact of acute chest

syndrome on lung function of children with sickle cell disease. J Pediatr 2006;149:17-22.

Sylvester KP. Airway hyperresponsiveness and acute chest syndrome in children with sickle cell anemia. Pediatr Pulmonol 2007;42:272-276.

Sieff, CA. Hematologic emergencies. In Fleisher Ludwig. Pediatric Emerg Med 6th ed., Phila, Lippincott. 2010

REFERENCESREFERENCES Caboot JB and Allen JL. Pulmonary complications

of sickle cell disease in children. Curr Opin Pediatr 2008;20:279-287.

Boyd JH et al. Asthma and acute chest in sickle cell disease. Pediatr Pulmonol 2004;38:229-232.

Kumar R et al. A short course of prednisone in the management of acute chest syndrome of sickle cell disease. J Pediatr Hematol Oncol 2010;32:e91-e94.

Strouse JJ et al. Corticosteroids and increased risk of readmission after acute chest syndrome in children with sickle cell disease. Pediatr Blood Cancer 2008;50:1006-1012.

REFERENCESREFERENCES Inusa B et al. Pandemic influenza A (H1N1) virus

infections in children with sickle cell disease. Blood 2010;115;110:2329-2340.

Rogovik AL et al. Bacterial blood cultures in children with sickle cell disease. Amer J Emerg Med 2010:28:511-514.

Roseff SD. Sickle cell disease: a review. Immunohematol 2009;25:67-74.

Steinberg et al. Risks and benefits of long term use of hydroxyurea in sickle cell anemia; a 17.5 year followup. Am J Hematol 2010;85:403-408.

Hunt SE. Transition from pediatric to adult care for patients with sickle cell disease. JAMA 2010;304:408-409.

Documents

Sickle Cell Disease/Acute Chest Syndrome Chairman’s Rounds August 13, 2010 David H. Rubin, MD Department of Pediatrics, St. Barnabas Hospital Professor