Hematology



Hematology


Nirali Shah

Eric F. Grabowski



Anemia


Definition



  • A reduction of RBC volume or hemoglobin conc < range of nml in healthy pts


  • Hematologic parameters vary w/ age (interpret using age-specific indices)


  • Microcytic anemia is the most common category of anemia in children


Clinical Manifestations



  • Can be asymptomatic or w/ fatigue, irritability, dyspnea


  • History: Diet Hx: Nutritional iron def is primary cause of microcytic anemia in children


  • Pica, Pagophagia (Craving and eating ice; common with iron deficiency)


  • FHx: Eval hemoglobinopathy in African Americans, Mediterranean region/southeast Asia


  • Signs or symptoms of blood loss: Hematochezia, melena, heavy menses


  • Exam: Pallor, tachycardia/flow murmur, assess for splenomegaly


Diagnostic Studies



  • CBC, MCV, retic, hemolysis labs (Coombs, bilirubin, haptoglobin, LDH), smear


  • Hemoglobin and mean corpuscular volume by age. (J Pediatr 1979;94:26)



    • Ex: 6 mo MCV nml range 71–94 fL, 18 yo MCV nml range 78–98 fL




image


Microcytic Anemia

(Pediatr Rev 2007;28:5; N Engl J Med 1999;341:1986)



  • Mentzer index (MCV/RBC): >13 consistent w/ iron def; <13 with beta-thal trait


  • Iron studies:



    • Iron deficiency: ↓ Iron ↑ TIBC ↓ Ferritin


    • Chronic disease: ↓ Iron ↓ TIBC ↑ Ferritin


    • Thalassemia/lead: ↑-Nml Iron ↓ TIBC ↑ Ferritin


  • Iron deficiency anemia: Most common form of microcytic anemia



    • Rx: 6 mg/kg elemental Fe ×6 wk in 2–3 divided doses, IV iron in severe def, blood transfusion. Vitamin C increases absorption of iron.


    • Tea, phytates (e.g., in corn) diminish iron absorption.


    • Typically improvement in reticulocyte count, MCV, and hemoglobin in 1–4 wk


  • Anemia of chronic disease: Can be microcytic or normocytic. (N Engl J Med 2005;352:1011); hepcidin (↑ w/ inflam) blocks Fe release



    • Treat underlying disorder (i.e., epo for renal disease)



Normocytic Anemia

(Pediatr Rev 1988;10:77)



  • Low retic: Diamond-Blackfan, trans erythroblastopenia of childhood, aplastic crisis


  • High retic: Hemolysis (including autoimmune), G6PD, hereditary spherocytosis


Macrocytic Anemia

(Ped Rev 1988;10:77; N Engl J Med 1999;341:1986)



  • Vit B12 deficiency: Rare in kids, 2/2 pernicious anemia and ileal disease (Crohns)



    • Assoc w/ pancytopenia w/ macrocytosis, hyperseg PMNs


    • Exam: Glossitis and decreased vibration and position senses


    • Neuro manifestations → can be irreversible if untreated


    • Rx: Oral or parenteral Vitamin B12 supplementation


  • Folate deficiency: Rare 2/2 ↑ in folate supplementation for pregnancy



    • Found in malabsorption syndromes, EtOH use, chronic hemolysis, drugs (MTX)


    • R/o Vit B12 def (folate supps fix RBC parameters; B12 def can be missed)


Hemoglobinopathies


Sickle Cell Disease (SCD)

(Pediatr Rev 2007;28:259)



  • Definition: Chronic hemolytic anemia; includes Hgb variants SS, SC, S-beta thal, SO Arab, SD, and other rare S-Hb genotypes


  • SS dz: Both β-globin genes w/ mutation (valine for glutamate at AA 6 on β-chain)



    • SC dz: 1 β-globin chain w/ mutation (lysine for glutamate at AA 6)


    • CC disease: Relatively mild, mild microcytic anemia


    • Sickle-β-thal: 1 β-globin gene w/ S mut, other nonfxnl. Similar course as SS dz


  • Pathophysiology:



    • Nucleotide sub (GTG for GAG; codon 6) of β-globin gene (chromo 11); valine for glut acid; HbS polymerizes on deoxygenation, distorts RBC into crescent


    • Sickled cells less deformable and ↑ adherence to vasc endothelium; lead to vascular occlusion, organ ischemia, and chronic end organ damage.


  • Epidemiology:



    • African American: 1 in 375, 9% carrier prev in U.S.; Hispanics: 1 in 1200


  • Clinical manifestations: Appear in first yr as fetal Hb concentrations decline



    • Fetal Hb protective because it inhibits deoxy-Hb S polymerization in the RBCs


    • Those w/ persistence of fetal Hb (HbF >30%) have mild or no symptoms


    • See later in chapter


  • Diagnostic studies: Newborn screening (NS) performed in 44 states and DC



    • If NS not offered, high risk infants tested by electrophoresis before 3 mo


    • Sickledex (rapid test based on solubility) inappropriate in newborns


  • Prophylaxis: PCN, pneumococcal vaccine, hydroxyurea



    • Transcranial Doppler (TCD): If flow velocity >200 cm/sec, ↑ risk for stroke. Chronic transfxn therapy ↓ 1° stroke 10×’s in Hb-SS and Hb-S-β.



      • Screening all kids w/ Hb-SS and Hb-S-β btw 2–16 yo. D/c of Rx after 36 mo of Rx resulted in reversion to abn TCD velocity or stroke in 45% of pts.


    • Recs for indefinite transfusion Rx for pts who have abn TCD findings


  • Complications and Management














































































Complication Features Evaluation & Treatment
Infection Fever >101.5 CBC/diff, retic, U/A, pan cx, CXR. CFTX, +/- Vanco
Outpt if: well appearing, >6 mo, WBC <25, nl CXR, no UTI, Tm <103, and reliable f/u
– S. pneumo sepsis Children <5 Ceftriaxone (CFTX)
– Osteomyelitis Salmonella, Staph. Aureus Hard to differentiate from VOC (see below), ESR, blood and bone aspirate
– Parvo B19 Aplastic crisis Transfusion. Reticulocytopenia 7–10 d. Immunity is lifelong.
Splenic sequestration Hb-SS <3 yr; Hb-SC, S-β-thal any age. Sudden splenomegaly and >2 g/dL ↓ Hgb from baseline w/ ↑ retics. CBC/diff, monitor spleen tip.
Transfusion as needed
Pulmonary Features (N Engl J Med 2008;359:2254)
Acute chest syndrome 50% pts (#2 cause of admission). Defined by CXR w/ new pulmonary infiltrate w/ fever &/or resp sx’s.
Hypoxia not necessary for dx.		 CFTX/Azithro, xfuse w/ pRBC if O2 <95%, or Hct <18%, do not exceed Hct >35% 2/2 viscosity. IV hydrate NOT more than 1 × maintenance, IS, albuterol nebs
Pulmonary HTN 30% of adults who have Hb-SS Optimal management still under investigation
Vaso-Occlusive pain crisis (VOC) 70% of all patients; 5% (Hb-SS) account for 30% of admissions (#1 cause of hospitalizations) NS bolus 20 cc/kg and hydrate at 1.5 × M (unless ACS); morphine PCA, Toradol, Incent spir (IS), bowel reg
Anemia Tranfuse w/ Sickle negative, CMV safe, leukoreduced, extended phenotype cross matched Transfuse for Hgb <5; falling Hct with low retic; ACS w/O2 requirement; stroke; splenic sequestration
Neurologic Features
Overt stroke 11% of Hb-SS by age 20 yr Xfuse if fixed or evolving deficit, focal szr, exchange xfusion, or RBC pheresis if >20 kg to ↓ HBS <30%
Silent infarction MRI 22% of Hb-SS children  
Osteonecrosis—Femoral/humoral head 50% of Hb-SS (increased with alpha-thalassemia); 60% of Hb-SC  
Retinopathy 50% of Hb-SC adults Routine ophthalmology visits
Renal insufficiency 5%–20% of Hb-SS adults  
Cholelithiasis 42% by adolescence  
Leg ulcers 10%–25% of Hb-SS adults  
Priapism 10%–40% of Hb-SS males Urology consult



Thalassemias

(Pediatr Rev 2002;23:75; Pediatr Rev 2007;28:5)



  • Nml Hgb (Hgb A) composed of 2 β-chains and 2 α-chains.


  • Fetal Hgb (Hgb F) composed of 2 γ-chains and 2 α-chains.


  • Consider dx w/ hypochromic, microcytic anemia, and in pts of appropriate ethnic background


Beta-Thalassemia Trait



  • AR, β-chains controlled by two genes on chromosome 11; no Rx needed


  • Diminished production of nml β-globin chains → hypochromic, microcytic anemia


  • Characterized by mild anemia (hemoglobin 9.5–11) and MCV <80


  • Basophilic stippling often seen on blood smear


Beta-Thalassemia Major

(Cooley Anemia)



  • Little to no production of beta-chains, and subsequently hemoglobin A (alpha2, beta2)


  • Usually evident beyond 6 mo of age when fetal hemoglobin production falls


  • Severe hypochromic, microcytic anemia requires chronic transfusion


  • Enlargement of liver and spleen because of extramedullary hematopoiesis


  • Long-term complications those of iron overload; BMT from matched donor curative


Alpha-Thalassemia



  • Normal: 4 functional genes for alpha-chain (on chromosome 16)


  • Silent carrier: 3 functional genes


  • α-thalassemia trait: 2 functional genes, typically asymptomatic w/ ↓ Hgb


  • Hgb H: 1 functional gene. Hgb H composed of tetrad of β-chains 2/2 paucity of available α-chains. Characterized by chronic hemolytic anemia w/ splenomegaly.


  • Bart Hgb: 0 functional genes. Bart Hgb: tetrad of four γ-chains, leading to catastrophic anemia, hydrops fetalis, and fetal or neonatal loss.


Platelet Disorders


Thrombocytopenia

(Pediatr Rev 2005;26:401)

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Aug 18, 2016 | Posted by in PEDIATRICS | Comments Off on Hematology

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