Sickle Cell Disease 101. Objectives. What is SCD? 4/20/2016. Discuss the pathophysiology & genetics of Sickle Cell Disease (SCD).

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1 Sickle Cell Disease 101 Jennifer Young, RN, MS, CPNP-AC Sickle Cell & Thalassemia Nurse Practitioner Nationwide Children s Hospital Objectives Discuss the pathophysiology & genetics of Sickle Cell Disease (SCD). Discuss the common complications of SCD. Briefly discuss sickle cell trait. What is SCD? Disorder of the red blood cells. Normal red blood cells are disc shaped and very pliable. Sickle cells are sickle shaped, rigid and break very easily. Cold Fever/infection Dehydration Hypoxia (low oxygen saturation) Acidosis Sickle cells don t live as long as normal red blood cells which leads to anemia. 1

2 Who Gets SCD? An inherited autosomal recessive disorder. One affected gene is received from each parent. Each parent must have either sickle cell trait or sickle cell disease to have a child with sickle cell disease. Geographical Pattern Africa North and South America The Mediterranean Middle East India and Pakistan The Caribbean Incidence & Etiology 72,000 Americans have sickle cell disease Affects 1:500 African-Americans 1:1,000-1,4000 Hispanic-Americans #1 Inherited disorder in the United States Ohio Newborn Screening Ohio screens for 32 genetic diseases at birth. Since 1991 abnormal hemoglobin screening has been included. Ohio Department of Health is notified of abnormal hemoglobin screens. ODH then notifies Newborn Screening Coordinator. Primary Care Provider referral is necessary to be seen in clinic. Some Primary Care Providers choose to manage SCD on their own. 2

3 PATHOPHYSIOLOGY CAC GTG GTG CAC GAC TGA GGA CTC CTG ACT CCT GAG valine histidine leucine threonine proline glutmaic acid CTC GAG glutamic acid CAC GTG GTG GAC TGA GGA CAC CAC CTG ACT CCT GTG valine histidine leucine threonine proline valine CTC GAG glutamic acid Single amino acid substitution: valine replaces glutamic acid on the 6 th position of the ß chain Sickle HGB What Are The Odds? If both parents have sickle cell trait: 25% chance with each pregnancy of having a child with disease What Are The Odds? If one parent has sickle cell trait & one parent has sickle cell disease: 50% chance with each pregnancy of having a child with sickle cell disease. 3

4 SCD Genotypes Four common types with varying degrees of severity and associated complications. Hgb SS Hgb SBeta 0 Thalassemia Hgb SC Hgb SBeta + Thalassemia Not all children will have the same experience with pain and/or complications, in part due to different types of disease. Common complications Anemia Pain Infection Acute Chest Syndrome Stroke Splenic Sequestration Some are life threatening while others are life altering Manifestations of Sickle Cell 4

5 Anemia Caused by chronic destruction of red blood cells & shorter red cell lifespan. Degree of anemia will vary based on type of sickle cell. Important to know the patient s baseline! Anemia may worsen during times of: Infection Splenomegaly MAY be seen during times of painful episode. Degree of Anemia Normal Hgb g/dl Hgb SS/Hgb SBeta0Thal 6-9 g/dl Hgb SC 9-12 g/dl Hgb S Beta + Thal g/dl Reticulocyte count Indication of the bone marrow response to anemia Normal (outside of newborn period) 0.5-2% Typically increased in SCD Bilirubin likely increased in SCD due to release with red blood cell destruction. Pain Caused by clumping of sickle cells. Log jam effect. Can occur in any part of the body. Common sites: Bones Lungs Abdomen Joints Hands/feet- Dactylits common in infants and toddlers. Swollen hands/feet that are painful to the touch 5

6 Pain Prevention Warm clothing- layers Dry off after swimming Hydration!!! Reduce stress Prompt treatment of illness/injury Educating patients/families on prevention is key Outpatient Pain Management Early, aggressive management hours of scheduled oral regimen ibuprofen 10mg/kg/dose Q6 hours oral opioid- Hydrocodone w/ acetaminophen (Norco/Lortab) 0.15mg/kg/dose Q4-hours Oxycodone mg/kg/dose Q4-6 hours No longer using Tylenol with codeine Doses may need adjusting due to tolerance Inpatient Pain Management IV fluid hydration IV opioid via PCA pump Morphine or Dilaudid most commonly Consider home opioid regimen when determining opioid dosing Anti-inflammatory medications. Toradol 0.5mg/kg x1dose followed by ibuprofen Q6 hours. Non-pharmacological therapies: Heat Psychology Massage Therapy 6

7 Infection Children with SCD can become seriously ill very quickly due to infection. #2 cause of death in children with sickle cell!! Infection Prevention Oral penicillin twice daily (until 5 yrs of age) Most children died in infancy prior to penicillin. Pneumococcal and Meningococcal vaccines. Annual influenza vaccine. Can develop secondary complications from the flu; therefore, broad spectrum antibiotics necessary. Acute Chest Bacteremia Risk of Infection Splenic dysfunction: encapsulated organisms. Auto infarct spleen by 5-6 years of age. Neutrophil migration abnormality Vascular endothelial abnormality: increased adhesion Infection Management Temperature of o or higher is treated as emergent Requires evaluation in clinic or Emergency Department. CBC, retic, blood cx, Ceftriaxone CXR necessary if respiratory symptoms/chest pain are present. Can likely be managed at home after evaluation but may require inpatient management. T 103, WBC 30,000, noncompliance 7

8 Acute Chest Syndrome (ACS) Most common cause of acute death in children and adults with SCD. 10% hospital mortality in adults 2nd most common cause of hospitalization in patients with sickle cell disease. #1 most common complication of surgery and anesthesia in patients with SCD Definition of ACS Definition: new infiltrate on CXR + Fever Chest Pain Hypoxia Other respiratory symptoms. Causes: Fat embolism Atelectasis Infection Pathophysiology of ACS 1. Regional hypoxia/lung injury occurs causing cells to sickle d/t inability to reoxygenate. 2. Sticky/inflexible sickled cells clog up microvasculature of the lungs. 4. As a result further sickling, Occlusion, and pulmonary infarction occurs which leads to increased hypoxia and lung injury. 3. Sickled cells stick to the endothelium of the lungs causing inflammation & vascular stasis. 8

9 Signs & Symptoms of ACS Rapid respirations Nasal flaring Grunting Retractions Wheezing Low oxygen saturation Shortness of breath Fever may or may not present Management of ACS Inpatient management to monitor for respiratory deterioration Can see rapid decline in the first 48 hours. Continuous pulse oximetry & AGGRESSIVE incentive spirometry & pulmonary toilet. Incentive spirometry is the only intervention proven to prevent ACS. Oxygen therapy as needed to keep sats >92% in order to break the cycle of hypoxia. Management of ACS Antibiotics Ceftriaxone Streptococcus pneumoniae and Hemophilus influenza Azithromycin Mycoplasma pneumoniae and Chlamydia pneumoniae Bronchodilators- Albuterol Transfusion therapy Effective in improving oxygenation & lowering sickle hemoglobin concentration. Improvement in clinical condition with transfusion therapy has been well documented. 9

10 Stroke About 10% of children with sickle cell disease will have a stroke. More common in children with Hgb SS. Peak age 3-10 years of age. 30% of children with SCD have silent strokes Ischemic insult Signs & Symptoms of Stroke Altered mental status Severe headache Sudden onset of vomiting Visual changes Slurred or altered speech Weakness on one side of the body Personality changes Seizures Unable to arouse or coma Stroke Prevention & Management Prevention: Annual screening with Transcranial Doppler (TCD) ultrasound to identify children at highest risk Treatment: Early intervention is key!! Exchange transfusion (apheresis) Emergently then Q3-5 weeks indefinitely Decreases sickle concentration to prevent repeat stroke Long-term management of complications Weakness or altered mobility if present Academic challenges 10

11 Splenic Sequestration Vaso-occlusion of the spleen Most often in infants & toddlers with Hgb SS disease May be presents in setting of a febrile illness Can occur in older children Acute can be an EMERGENCY! Hgb and platelet count drops Chronic splenomegaly can lead to chronic thrombocytopenia. Splenic Sequestration Management Education for early detection is essential How to assess spleen size. s/s of worsening anemia Acute management: Monitoring for worsening sequestration leading to worsening anemia Can be done inpatient or outpatient depending on case and severity May require PRBC transfusion Splenic Sequestration Management Parental and Provider monitoring for recurrent/worsening sequestration Close outpatient follow-up to monitor CBC, retic and spleen size Chronic transfusion therapy may be necessary. May require splenectomy. If greater than 5 yrs of age patient will need to restart Penicillin VK 250mg BID life-long Increased risk of bacteremia in asplenia Pre-splenectomy immunizations are required. Encapsulated organisms 11

12 Disease Modifying Agents Hydroxyurea Daily oral medication given to: Initiate/increase fetal hemoglobin (hgb F) productive Decrease blood viscosity by decreasing white cells & platelets. NIH recommendation: Hgb SS & S Beta 0 Thalassemia 9 months of age and older. Close follow-up is necessary Adherence assessment Medication tolerance Monitoring for side effects neutropenia, thrombocytopenia, elevated renal and/or liver function studies Dose titration What About A Cure? Bone Marrow Transplant (BMT) Risk/Benefit Ratio to be considered Matched sibling donor HLA typing Cord Blood Banking 15-20% chance that a sibling would be match Matched unrelated donor match through National Marrow Donor Program Some difficulty in finding a match Close follow-up is necessary Sickle Cell Trait Definition: A hereditary condition in which an individual inherits one normal gene for hemoglobin (A) and one abnormal gene for hemoglobin (S) Prevalence: There are 1 million to 3 million Americans with sickle cell trait. 1:12 African Americans 12

13 Complications of Sickle Cell Trait Typically asymptomatic Complications may development in extreme conditions Physical exhaustion Athletic conditioning Military Management of Sickle Cell Trait Education- Family and patient education of trait status Family education with Newborn Screening Counselor in early childhood. Patient education: Prevent extreme conditions Inheritance pattern of SCD and risk of having a child with SCD Questions? 13