Abdulelah Nuqali Intern

Causes Red cell membrane disorders ( hereditary spherocytosis ) Red cell enzyme disorders ( G6PD deficiency ) Hemoglobinopathies ( SCD, Thalassemia ) Auto-immune

Hemolysis lead to Anemia Reticuloenothelial hyperplasia ( hepatomegaly, splenomegaly ) Elevated unconjugated bilirubin Exess urinary urobilinogen

The diagnosis clue to hymolysis are Raised reticulocytes count Unconjugated bilirubinemia – increased urinary urobilinogen Abnormal appearance of RBCs on a blood film ( e.g. spherocytes, sickle shaped, or very hypochromic ) Increased erythropoiesis in the bone marrow

-X-lined recessive, different variants of the disease -Enzyme deficient red blood cells -Higher prevalence in Mediterranean's, Blacks, Orientals -Presents with acute hemolytic anemia with jaundice and dark urine -Diagnosis- G6PD assay, Blood film- Heinz bodies Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

-Management is supportive: hydration, transfusion, phototherapy -Prevention of acute episodes: Avoid known oxidants (e.g. fava beans, ASA, antimalarials, sulfonamides

Sickle cell Anemia

Definition Sickle cell anaemia (sickle cell disease, SCD) is caused by an autosomal-recessive single gene defect in the beta chain of haemoglobin (HbA), which results in production of sickle cell haemoglobin (HbS). It is the most common genetic disorder in children in many countries.

Pathophysiology Irreversibly sickled red cells may be trapped in the microcirculation, resulting in thrombosis and therefore ischemia in an organ or bone.

Pathophysiology Sickle disease is fundamentally an inflammatory state, with activation of the endothelium, probably through proximate effects of reperfusion injury physiology and chronic molestation by adherent red cells and white cells. The disease also involves enhanced angiogenic propensity, activation of coagulation, disordered vasoregulation, and a component of chronic vasculopathy. Sickle cell anemia is truly an endothelial disease. The Endothelial Biology of Sickle Cell Disease: Inflammation and a Chronic Vasculopathy, 2010, Microcirculation Journal

Clinical Presentation Newborn usually without symptoms ; development of hemolytic anemia over first 2-4 months ? ; By the 6 month, may have functional asplenia ( by age 5 years, almost all will )

Clinical Presentation First presentation usually hand-foot syndrome ( Acute dactylitis )

Clinical Presentation Acute painful crises : Younger – most extremities With increasing age – head, chest, back, abdomen Precipitated by ; illness, fever, hypoxia, acidosis

Clinical Presentation More extensive vaso-occlusive crises –> ischemic damages : Skin ulcer Retinopathy Avascular necrosis Infarction of bone and marrow ( Increase risk of salmonella osteomyelitis ) Splenic auto-infarction

Clinical Presentation More extensive vaso-occlusive crises –> ischemic damages : Pulmonary – Acute chest syndrome ( along with sepsis, are most common cause of mortality ) Stroke ( peak at 6 – 9 years of age ) Priapism, especially in adolescent

Clinical Presentation Acute splenic sequestration ( peak age 6 months to 3 years ) ; can lead to rapid death Altered splenic function -> incresed susceptibility to infection, especially with encapsulated bacteria ( S.pneumonae, H.influenzae, N.meningitidis )

Clinical Presentation Aplastic crises : After infection with parvovirus B19 Absence of reticulocytes during acute anemia

Labs Increased reticulocytes Mild to moderate anemia Normal MCV Nucleated RBCs If sever anemia : ( smear : target cell, sickle RBCs )

Diagnosis Confirm diagnosis with Hb electrophresis

Management Prophylaxis : Treatment of acute crises : Treatment of chronic problems :

Management Prophylaxis : Full immunization Twice daily penicillin Daily oral folic acid’ Avoiding exposure to : cold, dehydration, excessive exercise, stress or hypoxia

Management Treatment of acute crises : Oral or IV analgesia Good dehydration Antibiotics Oxygen Exchange transfusion ( for acute chest syndrome, stroke and priapism )

Management Acute Pain Management – NIH guidelines  Initiate analgesic therapy within 15 minutes  Pt with known crisis history  use opioid and dose known to be effective for that pt  Otherwise, give loading dose of IV morphine 5 to 10mg or IV hydromorphone 1.5mg  Reassess and Redose Q min prn with ¼ to ½ loading dose until pain relieved  Start scheduled opioid dosing with breakthrough prn or PCA pump  Coadminister scheduled NSAIDs

Management Treatment of chronic problems : Hydroxyurea ( a drug which increase their HbF production and helps protect against further crises ) BMT

Beta-thalassaemia

Key Factors Mediterranean, Southeast Asian, Middle Eastern ethnicity family history asymptomatic

Clinical Presentation lethargy abdominal distension failure to gain weight low height and weight pallor

Clinical Presentation skeletal changes large head chipmunk facies ( due to extramedullary hemopoiesis -> maxillary over growth, skull bossing ) misaligned teeth hepatosplenomegaly jaundice

Clinical Presentation

Diagnosis CBC peripheral smear reticulocyte count LFTs haemoglobin analysis plain x-rays of skull abdominal ultrasonography plain x-rays of long bones

Management Regular transfusion Iron monitoring + chelation Splenectomy Assessment for stem cell transplantation

Management Regular transfusion The decision to start regular transfusions is clear when the initial hemoglobin level is well below 6 g/dL OR patients with a hemoglobin level less than 7 g/dL with growth impairment, marked skeletal changes, or extramedullary hematopoiesis. Standards of Care Guidelines for Thalassemia, 2012, Children’s hospital & research center oakland

Management Iron monitoring + chelation Iron overload is the major cause of morbidity for thalassemia patients. Chelation therapy should be started after about one year of chronic transfusions. Standards of Care Guidelines for Thalassemia, 2012, Children’s hospital & research center oakland

x ray Standards of Care Guidelines for Thalassemia, 2012, Children’s hospital & research center oakland

Management Splenectomy The use of splenectomy in thalassemia has declined in recent years. This is partly due to a decreased prevalence of hypersplenism in adequately transfused patients. There is also an increased appreciation of the adverse effects of splenectomy on blood coagulation. In general, splenectomy should be avoided unless absolutely indicated. Standards of Care Guidelines for Thalassemia, 2012, Children’s hospital & research center oakland

Management Splenectomy Splenectomy is indicated in the transfusion- dependent patient when hypersplenism increases blood transfusion requirement and prevents adequate control of body iron with chelation therapy. An enlarged spleen— without an associated increase in transfusion requirement—is not necessarily an indication for surgery. Standards of Care Guidelines for Thalassemia, 2012, Children’s hospital & research center oakland