Anemia s. Troy Lund MSMS PhD MD

Transcription

1 Anemia s Troy Lund MSMS PhD MD lundx072@umn.edu

2 Hemoglobinopathy/Anemia IOM take home points. 1. How do we identify the condtion? Smear, CBC Solubility Test (SCD) 2. How does it present clincally? 3. How do we treat it? Give iron, blood, etc. 4. How do we prevent it? Avoid the cold Avoid dehydration! Avoid infections Troy Lund, Dr. Carol Diamond, UW - Madison

3 Hemoglobinopathy SOUTHEAST ASIA alpha-thalassemia beta-thalassemia hemoglobin E hemoglobin Constant Spring

4 Geography of Hemoglobinopathies

5 Hemoglobin synthesis 25% 25% 0.5% 1.5% 48% α α γ δ β α α γ δ β 25% 25% 0.5% 1.5% 48% Chromosome 16 Chromosome 11

6 Hemoglobins in normal adults α β α γ α δ β α γ α δ α HbA HbF HbA 2 98% ~1% <3.5%

7 THALASSEMIA Diminished or absent synthesis of normal globin chains (α or β); genetically heterogeneous Heterozygous state protects from malaria, hence more common in southern European, African, Asian peoples Unbalanced globin chain synthesis causes microcytosis, ineffective erythropoiesis and hemolysis All roads lead to anemia

8 Thalassemia

9 Single α- globin gene missing normal CBC Two α-globin genes missing: microcytosis, minimal anemia One β-globin gene missing: microcytosis, mild anemia Three α- globin genes missing: microcytosis, hemolysis, moderate to severe anemia Two β-globin genes missing: transfusiondependent anemia Decreasing globin chain production Four α- globin genes missing: fetal demise Increasing globin chain imbalance causing: ineffective erythropoiesis (precipitated α chains) hemolysis (β tetramers or Hb H) Red cells have shorter half-life Worsening anemia

10 Alpha thalassemia * * * αα /αα αα /α αα / α / / Normal Mild microcytosis Mild microcytosis Hemoglobin H disease Hemoglobin Barts Hydrops Fetalis (no fetal Hgb, only gamma chains that precipitate) * Particularly important in SE Asia

11 Hgb H disease H Hgb H inclusions (supravital stain) Hemoglobin H, consisting of beta chain tetramers, is an unstable hemoglobin which forms precipitates just below the red blood cell membrane. This precipitated hemoglobin inclusion can be observed when red blood cells are stained with Brilliant Cresyl Blue (BCB). Hemoglobin H bodies are seen as faint blue inclusions.

12 Hydrops fetalis (note gross edema) Hydrops fetalis (These are precipitated gamma-chains)

13 Beta thalassemia major No beta chain produced (no HbA) Severe microcytic anemia occurs gradually in the first year of life (as gamma chain production stops) Marrow expansion Iron overload Growth failure and death

14 Beta thalassemia major

15 Thalassemia

16 Beta thalassemia major Male 18 years

17 Beta thalassemia major treatment Transfusion Iron chelation Stem cell transplant

18 Β-Thalassemia Minor β/ β 0 or β/ β + Microcytosis, target cells Mild anemia often asymptomatic Decreased HbA production Increased proportion of Hb A 2

19 Β-Thalassemia Intermedia β + / β 0 (small amount of β chain production) Chronic anemia Splenomegaly Often transfusion-dependent

20 Hemoglobin E β mutation (glutamine lysine at amino acid 26) Altered mrna splicing, unstable mrna Heterozygous in 30% of SE Asians Homozygous Hb E: microcytosis, hypochromia, little or no anemia Hemoglobin E / β thal causes thalassemialike phenotype

21 Clinical Features of Sickle Cell Anemia Painful episodes Pneumococcal disease Acute chest syndrome Splenic infarction Splenic sequestration Stroke Osteonecrosis Priapism Retinopathy Leg ulcers Gallstones Renal abnormalities Osteopenia Nutritional deficiencies Placental insufficiency Pulmonary hypertension

22 Complications of Sickle Cell Disease Skin ulcer Pneumonia Stroke Osteonecrosis

23 Sickle Cell Dactylitis

24 Sickle Cell: Pathophysiology Deoxygenation of mutant Hb leads to K + efflux cell density / dehydration polymerization Sickled cells adhere to endothelial cells Endothelial factors vasoconstriction Blood flow promotes vaso-occlusion Vicious cycle with decreased blood flow, hypoxemia / acidosis, increased sickling Some cells become irreversibly sickled

25 Diagnosis

26 Iron Deficiency Anemia Severe Image ID: Authors: ASH Image Collection Category: Underproduction Anemias > Iron Deficiency Copyright 2017 American Society of Hematology. Copyright restrictions may apply.

27 Sickle Cell

28 Megaloblastic anemia caused by severe B12 deficiency in a breastfed infant. Image ID: Authors: Volodymyr Shponka, MD;Maria Proytcheva, MD Category: Underproduction Anemias > Megaloblastic Anemia > B12 / folate Copyright 2017 American Society of Hematology. Copyright restrictions may apply.

29 Another reasopn for a peripheral smear BLASTS

30 New Point of Care

31 Solubility Test

32 Solubility Test Sensitivity: 40-90% in the real word Specificity: 90-95%

33 Hemoglobin Electrophoresis Separation of various hemoglobins with electrophoresis on cellulose acetate, ph 8.6. Hemolysates represented are AA (normal adult), SC (hemoglobin SC disease), SSF (homozygous sickle disease, SS, with increased F), AS (sickle trait), and AC (C trait).

34 Iron Deficiency vs thalassemia Remember to look at the CBC MCV (small) RBC count (high in thalassemia) RDW

35 Sickle Cell Anemia - treatment Opiates and hydration for painful crises Pneumococcal vaccination Transfusion for serious manifestations (eg stroke); exchange transfusion Hydroxyurea Retinal surveillance Stem cell transplant

36 Other Anemia Treatment Suspect Iron deficiency Trial of Iron (8 12 weeks), (unlikely to hurt anyone) Thalassemia Blood for those severely affected.

37 Oxygen Saturation Interpretation We treat anemia and lower saturations to increase oxygen carrying capacity -> to alleviate symptoms (SOB, tachycardia, elevated cardiac output)

38 A Slide on Air Travel (a cold, stressful, dehydrating, low oxygen situation) 1. Hgb up to 10 g/dl 2. No recent crisis (5 6 weeks) 3. Medical Supplies 4. Keep hydrated, warm, and do not forget medicines.

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