HEMATOLOGY CONFERENCE

1. HEMATOLOGY CONFERENCE Cruz, Kristen, Cruz, Riza, Cudal, Beinjerinck Ivan, Dancel, Jonathan Carlo, Dans, Kunny, Daquilanea, Michee Grace

2. General Data • S.G • 4year old • Female • Birthday: • Novaliches Q.C • Informant: Mother • Reliability: Fair

3. Chief Complaint PALLOR

4. HISTORY OF PRESENT ILLNESS

5. HISTORY OF PRESENT ILLNESS

6. HISTORY OF PRESENT ILLNESS ADMISSION

7. Review of systems No weight loss No pruritus, cyanosis no easy fatigability No abdominal pain, no constipation No dysuria, oliguria No loss of consciousness, seizures, alteration in mental status

8. Maternal History Gestational History • Born to a 35 year old G4-P3, 3-0-0-2 • (+) prenatal check-up since 1st month AOG • Hepatitis and gestational diabetes screening was not done • denies of any exposure to infections and roentgen studies. • Vitamins: Ferrous Sulfate, Multivitamins • UTZ: (7th , 9th month)

9. Neonatal History • Birth • Patient was born term • AGA unrecalled, BW 4 lbs • unrecalled APGAR but claimed to be generally stable. • No Newborn screening

10. Feeding History Feeding - Birth- 1 year: exclusively breast feeding - 8 months: complementary feeding - 1year : chocolate drink - eats everything except vegetables

11. Personal History • Past Illnesses • Sept. 2009 – Dengue Fever, PICU • No history of trauma nor prior injuries. • No history of prior surgeries.

12. Personal History • Immunizations • BCG • Hepa B • DTP • OPV • Measles • Hib • MMR • Varicella • Typhoid

13. Growth and Development • Developmental milestones • Social smile – more than 4 months • Head control – more than 4 month old • Sits alone – more than 5 months • Roll over – 4 months • Walks alone – 1 year • Runs – 2 years • Feeds self with crackers – 6 months • First words – 11 months • Toilet train: 3 years • Scribbles: 2 years • Present assessment:

14. Family Profile

15. Family History (+) Hypertension (+) Cardiac disease – grandmother (+) Asthma – father side β- Thalassemia – sister (-) bleeding disorders (-) PTB (-) Diabetes mellitus (-) Kidney Disease

16. Socio-economic Profile • The patient lives in a bungalow, owned, made of wood with her parents and siblings. • The father is the breadwinner while the mother is the primary caregiver. • Water source for drinking is NAWASA • They don’t have any pets but there are stray dogs, chicken and a piggery in their neighborhood. • The garbage is collected twice a week and they practice waste segregation.

17. Physical examination Awake, alert, ambulatory, no signs of dehydration, not in cardiorespiratory distress, well-nourished, well-developed BP 90/50 HR100 bpm, reg RR24 cpm T36.3C, wt 14.7kg (z=-1), ht 94.5cm (Z=below -2) Warm moist skin, pale, no jaundice, no cyanosis, no rashes Atraumatic head, normocephalic, frontal bossing Pale palpebral conjunctivae, anicteric sclera, pupils 2-3mm ERTL

18. Physical examination • Nasal septum midline, no nasal congestion, no tragal tenderness, (-) aural discharge • Moist buccal mucosa, midline uvula, nonhyperemic posterior pharyngeal wall, tonsils not enlarged • Supple neck, thyroid not enlarged, (+)cervical lymphadenopathy • Symmetrical chest expansion, no retractions, clear breath sounds

19. Physical examination • Adynamic precordium, no murmurs • Globular abdomen, NABS, soft, nontender, no palpable masses, liver span 12cm, (+)splenomegaly • Straight spine, no deformities • No edema, no cyanosis, no clubbing • Pulses full and equal on all extremities, pale nail beds

20. Neurologic Examination Cerebrum: Awake, alert, GCS 15 Cranial nerves: I – XII intact Motor: 5/5 on all extremities,No tremors, atrophy, fasciculations Reflexes: DTR’s 2+, (-) Babinski Meningeal signs: No nuchal rigidity

21. PRESENTING MANIFESTATIONS • Low hemoglobin • Low hematocrit • (+)splenomegaly • Pallor • (+) family history

22. Approach to Diagnosis • Signs and Symptoms or Laboratory findings pathognomonic of a disease • Signs and Symptoms or Laboratory findings pointing to an organ or part of an organ system • Signs and Symptoms or Laboratory findings pointing to a group of diseases • Signs and Symptoms or Laboratory findings whose mechanism is well understood • Signs and Symptoms or Laboratory findings found in the least number of disease

23. Harrison’s Principle of Internal Medicine 17th edition

25. b-Thalassemia minor (heterozygous b-Thalassemia major (homozygous) severe hypochromic anemia with microcytosis anisocytosis, and poikilocytosis by 12 months. Mild ↑serum indirect bilirubin Hb electrophoresis shows only Hb F and A2 • mild hypochromic anemia • normal serum iron • increased red cell number • Ratio of mean red cell volume (MCV) to red cell count is <13 • Increased HgA2

26. COURSE IN THE WARDS On admission 2nd HD Applied to SAGIP Given Deferroxamine 500mg/vial OD x 5 days Reconstitute 1 vial of Desferroxamine with 2 ml sterile water. Once dissolved add 8ml PNSS to make 10mL solution then give per subcutaneous infusion over 12 hours • CBC requested • Pre-BT medications: • Paracetamol 250mg/5ml (3ml) • Diphenhydramine 12.5mg/5ml (10ml) • Transfused with properly typed and crossmatched 1’u’ pRBC divided into 2 satellite bags

27. COURSE IN THE WARDS 3rd and 4th HD 5th HD • Patient was stable

28. Laboratory Results

29. Laboratory Results

30. TREATMENT • Before chronic transfusions are initiated, the diagnosis of β0-thalassemia should be confirmed and the parents counseled about this lifelong therapy. • Initiating transfusion and chelation therapy can be difficult for parents to face early in their child's life. • Before transfusion therapy is begun, a red cell phenotype is obtained; blood products that are leukoreduced and phenotypically matched for the Rh and Kell antigens are required for transfusion. • If there is the possibility of a bone marrow transplant, the blood should be negative for cytomegalovirus and irradiated.

31. TREATMENT • Transfusion therapy promotes general health and well-being and avoids the consequences of ineffective erythropoiesis. • A transfusion program generally requires monthly transfusions, with the pretransfusion hemoglobin level >9.5 and <10.5 g/dL. • In patients with cardiac disease, higher pretransfusion hemoglobin levels may be beneficial. Some blood centers have donor programs that pair donors and recipients, decreasing the exposure to multiple red cell antigens.

32. TREATMENT • Transfusionalhemosiderosis causes many of the complications of thalassemia major. • Transfusionalhemosiderosis can be prevented by the use of deferoxamine (Desferal). • Accurate assessment of excessive iron stores is essential to optimal therapy. • The serum ferritin level is useful in assessing iron balance trends, but does not accurately predict quantitative iron stores. • Undertreatment or overtreatment of presumed excessive iron stores can occur when a patient is managed based on the serum ferritin level alone. • Measurement of the iron level by liver biopsy is the standard method for accurately determining the iron store. • Although quantitative liver iron measurement accurately guides the use of iron chelators, it may not reflect cumulative changes in cardiac iron.

33. TREATMENT • A ferritometer and specialized MRI software are emerging alternatives for liver biopsies. • Patients can have cardiac iron overload at the time of a safe liver iron measurement. • Many thalassemia centers monitor cardiac iron with T2 weighted MRI imaging, but routine application of this technology has not been implemented across all sites.

34. TREATMENT • Deferoxaminechelates iron and some other divalent cations, allowing their excretion in urine and stool. • Deferoxamine is given subcutaneously over 10–12 hr, 5–6 days a week. • Side effects include ototoxicity with high-frequency hearing loss, retinal changes, and bone dysplasia with truncal shortening. • The number of hours deferoxamine is used daily is more important than the daily dose. • High-dose, short-term infusions increase toxicity with little efficacy. P • lasma non-transferrin-bound iron (NTBI) is most likely responsible for the serious iron injury. When deferoxamine is infusing, it binds NTBI. • The 24 hr deferoxamine infusion has been shown to reverse cardiomyopathy in patients with excessive iron stores in the heart that result in symptomatic congestive heart failure.

35. TREATMENT • Deferiprone is a new iron chelator approved by the U.S. Food and Drug Administration for children >2 yr of age (see Chapter 462.1 ). • Deferiprone may not be as effective as deferoxamine in total body iron chelation, but may be more effective in removing cardiac iron. • Side effects include neutropenia, and weekly blood counts are needed. • Other iron chelators are being studied for oral and subcutaneous use. • ICL670 is an oral chelator that appears effective in phase III trials and may be approved for use in the U.S. in the near future. • Bone marrow transplantation has cured >1,000 patients who have thalassemia major. • Most success has been in children younger than 15 yr of age without excessive iron stores and hepatomegaly who have HLA-matched siblings. • All children who have an HLA-matched sibling should be offered the option of bone marrow transplantation.

36. DISCUSSION

37. Thalassemias -genetic disorders in globin chain production -β-thalassemia- either a complete absence of β-globin gene production (β0-thalassemia) or a partial reduction (β+-thalassemia) - α-thalassemia - α-globin gene production is either absent or partially reduced

38. EPIDEMIOLOGY Approximately 20 common alleles constitute 80% of the known thalassemias worldwide 3% of the world's population carries genes for β-thalassemia Southeast Asia, 5–10% of the population carries genes for α-thalassemia

39. THALASSEMIA • autosomal recessive blood disease. • the genetic defect results in reduced rate of synthesis of one of the globin chains that make up hemoglobin. • Reduced synthesis of one of the globin chains can cause the formation of abnormal hemoglobin molecules, thus causing anemia,

40. Overview Hemoglobin • oxygen-carrying component of the red blood cells • consists of two different proteins • alpha • beta.

41. Alpha Thalassemia • Four genes (two from each parent) are needed to make enough alpha globin protein chains. • commonly found in Africa, the Middle East, India, Southeast Asia, southern China, and occasionally the Mediterranean region. • types • Silent Carrier State. • Alpha Thalassemia Trait or Mild Alpha Thalassemia. • Hemoglobin H Disease. • Hemoglobin H-Constant Spring. • HydropsFetalis or Alpha ThalassemiaMajor Cooley's Anemia Foundation, Inc. 

42. PATHOGENESIS OF Alpha THALASSEMIA • relatively fewer α-globin • an excess of β- and γ-globin chains. • These excess chains form • Bart's hemoglobin (γ4) in fetal life • Hb H (β4) after birth. • Prenatally, a fetus with α-thalassemia may become symptomatic because Hb F requires sufficient α-globin gene production, • whereas postnatally, infants with β-thalassemia become symptomatic because Hb A requires adequate production of β-globin genes.

43. Inheritance Pattern for Alpha Thalassemia

44. Beta Thalassemias • People whose hemoglobin does not produce enough beta protein • It is found in people of Mediterranean descent, such as Italians and Greeks, Arabian Peninsula, Iran, Africa, Southeast Asia and southern China.

45. Pathogenesis of Beta Thalassemia • Inadequate β-globin gene production • leading to decreased levels of normal hemoglobin (Hb A) • imbalance in α- and β-globin chain production.

46. Types of Beta Thalassemia

47. Types of Beta Thalassemia

48. Inheritance Pattern for Beta Thalassemia

49. CLINICAL MANIFESTATIONS • If not treated, children usually become symptomatic as a result of progressive hemolytic anemia, • with profound weakness and cardiac decompensation during the 2nd 6 mo of life. • Most infants and children have cardiac decompensation when the hemoglobin is 4.0 g/dL or less.

50. Summary