Sickle Cell AnemiaIlene Claudius

iaclaudius@gmail.com

• No disclosures

Sickle Cell Anemia

•Genetic Hb beta-chain abnormality

•SS and S/B-thal (Hb 6-9 g/dL)

•SC and S/B-thal = SCA (Hb 9-14 g/dL)

•Sickle Cell Trait

Pathophysiology of Sickle Cell

•Deoxygenation

• Cellular dehydration

• RBC death

• Vaso-occlusion ischemia

VOC: Pain

• Typically sudden

• Low grade fever

• Extremities, chest, back

• Recurrent

• >3 hospitalizations for pain crisis/ year = early death

VOC: NSAIDS

•Analgesia within 30 minutes of triage

•NSAIDS for mild to moderate pain

•AKI in 8-17% peds admissions

•1 dose vs 0 doses ketorolac No difference AKI

•Multiday high-dose ketorolac Increase AKI

VOC: Opioids

• Parenteral morphine

• Opioid naïve: 0.1 mg/kg (max 10 mg) per dose

• Opioid tolerant: 10% of total equivalent morphine daily dose (3 PO = 1 IV)

• Reassess in 15-30 minutes

• If pain not decreased by 50%, repeat or escalate dose 25%

• Decreased GFR

• Hydromorphone 0.015 mg/kg every 15-30 minutes

• Consider trial of oral morphine for moderate pain

• IN fentanyl in smaller kids (dose 2 mcg/ kg)

VOC: Pain

•Use non-pharmacologic therapies: heat, distraction

•Consider ketamine 0.3 mg/kg

•Oral antihistamines every 4-6 hours

• Incentive spirometry every 2-4 hours

• Ineffective treatment: Fluids, oxygen, steroids, transfusion

VOC: Dactylitis

• Often first presentation

• Typically <2 years

• Metacarpals/tarsals

• Tender, painful, swollen hands and feet

• Low-grade temperature elevation

• Treat as vaso-occlusive pain crisis

• Lasts days to weeks

Acute Chest Syndrome

• Leading cause of death

• Sudden onset

• Cough, SOB, retractions, rales

• New infiltrate on CXR

• Etiology: chlamydia #1, mycoplasma #2, RSV #3, fat embolism, ischemia (including PE), atelectasis, pulmonary edema, or ???

ACS: Who gets it?

•Most common < 10 years

•1-3 days after admission for VOC crisis

•Parvovirus bony infarct fat embolism

Acute Chest Syndrome

• IV cephalosporin

• Oral macrolide

• Oxygen to maintain saturation of 95% (only if hypoxemia)

• Incentive spirometry

• Bronchodilators for wheezing

ACS: Transfusion

• Simple transfusion of 10-20 mL/kg PRBCs

• Hb is decreased by 1 g/dL or more

• Hb is <9 g/dL

• Transfuse up to 9-11 g/dL

• Exchange transfusion (1-1.5X patients RBC volume)

• Oxygen sat <90% or paO2 < 60 mmHg (with O2)

• Increasing respiratory distress

• Progressive pulmonary infiltrates

• Declining Hb in spite of transfusion

Anemia

•Anemia = 2 g/dL decline in Hb (or <6 if unknown)

Reticulocyte count

High: Get LDH/ AST/ bili

Low: Splenic Sequestration

High: Hemolysis

Low: Aplastic

Aplastic Anemia

•Low Hb, low reticulocyte count

•80% parvovirus

•Simple transfusion

•Dispo home

•Recheck labs in 7-10 days

Splenic Sequestration

• Low Hb + high reticulocyte count +/- low platelets

• Age 1-4 years

• Sudden enlargement of spleen + anemia

• Abd pain not reliable

• Simple transfusion up to Hb = 8 g/dL (use 5-10 mL/kg transfusions)

• Admit

• Multiple episodes splenectomy

Stroke

• 10% children with HbSS

• Sudden weakness, aphasia, seizures, coma

• CT MRI, MRA

• Exchange transfusion

• OK to give simple transfusion while waiting (NICE)

• To Hb of 10 g/dL

• Wait > 6 hours

• Prioritize exchange transfusion over tPA

Priapism

• Unwanted erection lasting more than 4 hours

• Stuttering priapism can be recurrent shorter episodes

• 35% of men with SCA

• Vigorous hydration and analgesia

• Oral pseudoephedrine OK

• Corporal aspiration/ irrigation with alpha-adrenergics

• Transfusion not indicated

Bacteremia

• Splenic impairment from 2-3 months on

• Pre-pneumococcal vaccination, 10% <3y were bacteremic

• Penicillin prophylaxis to 5 years

• PCV 13 PCV 23 at 2 years and 5 years; meningococcal vaccines

• Bacteremia in 0.8 to 2.6% of febrile children with SCA

• 0.2% Invasive pneumococcal disease

Fever

• Increased risk bacteremia• Ill-appearing patients (8.5X)

• WBC >30,000/mcL

• Hypotension

•Procalcitonin <0.5 ng/mL helpful in excluding bacteremia

Fever

• Temperature >39.5C or ill appearance = admit for IV Abx and observation

• Temperature >38.5C• CBC with differential, retic count, blood cx, urine cx

• Parenteral antibiotics

• Outpatient OK if well appearing

Fever

•Influenza• Increased complication rate

•56X higher admission rate

•Osteomyelitis•Salmonella bacteremia

Hepatobiliary

• Acute Intrahepatic Cholestasis:

• Tender enlarged liver

• Hyperbilirubinemia (conjugated, unconjugated)

• Coagulopathy, variable liver enzymes, low platelets

• High untreated mortality (30%) from hepatic failure, bleeding

• Simple or exchange transfusion

Hepatobiliary

• Gallstones• 12% preschool age

• 70-75% adults

• Rarely sx

• 10% cholecystitis; 5% choledocholithiasis

• Hepatic Sequestration: painful liver enlargement, drop in Hb of 2g/dL

They grow up so fast…

• Pulmonary hypertension

• Pulmonary arterial hypertension in 10%

• SOB during routine activity, lethargy, chest pain, syncope, palpitations

• Higher risk of embolic disease

• PE

• Organ infarction

• Leg ulcers (22% by 30s)

• Renal complications

• CKD (4-18%)

• Hyposthenuria: inability to concentrate urine dehydration

Chronic Therapies

•Transfusion

•Hydroxyurea: Increases HbF

Complications of Therapy

• Chronic transfusion protocols

• Iron overload

• Cardiomegaly

• Liver dysfunction

• Thyroid and pituitary dysfunction

• 20-40% patients develop alloantibodies

• Hydroxyurea

• Leukopenia

• Skin, nail, hair issues

• Elevated creatinine

On the Horizon

• Oral L-glutamine just approved for 5 years and up

• Decrease• Pain crises (mean 4 for placebo, 3 for drug over 48w)

• Incidence ACS

• Time in hospital

L-glutamine Side Effects

• Constipation

• HA

• Pain in abd/ext/abd/back

• Poverty

• Annual cost: $40,515

BMT

•Curative

•Survival >90% if matched sibling donor

•40-50% rejection with unrelated donor

•<20% have matched sibling donor

I hate sickle cell disease

…and stupid Americans

Gene Therapy

• Vector-mediated addition of anti-sickling B-globulin gene to stem cells

• 8 patients

• Harvest stem cells

• Wipe out other cells with chemo

• Prolonged neutropenia

• $500,000-700,000

On the Horizon

•Crizanlizumab • Humanized monoclonal antibody

• Binds P-selectin, interfering with adhesion of cells to vascular endothelium

• Early studies show 45% decrease in annual VOC rate

• Received FDA Breakthrough Therapy designation in 1/2019

• SE: arthralgia, diarrhea, pruritis, chest pain