SUSPECT THALASSEMIA , MALNUTRITION AND PERICARDIAL EFFUSION

Presenter : Sasikala S. Balakrishnan Yeoh Shu Ting

Supervisor : Dr. Tina Christina L. Tobing, SpA (K)

Background
Thalassaemia is a group of inherited disorders of hemoglobin synthesis characterized by a reduced or absent one or more of the globin chains of adult hemoglobin . Genetic autosomal recessive blood disease.

Currently, there are approx. 1000 patients with severe thalassemia in the US The incidence of thalassemia trait within the ethnic groups involved ranges from 3% to 5% 50-100/1000 in southeast Asia 30/1000 worldwide 150-300/1000 in Italy, Greece, and among Americans of Italian or Greek descent

Pericardial effusion defines the presence of an abnormal amount and/or character of fluid in the pericardial space. It can be caused by a variety of local and systemic disorders, or it may be idiopathic. Pericardial effusions can be acute or chronic, and the time course of development has a great impact on the patient's symptoms.

Thalassemia
Mediterranean Anemia- 1st published in 1925 May be either homozygous defect or heterozygous defect.

Demographics: Thalassemia
Found most frequently in the Mediterranean, Africa, Western and Southeast Asia, India and Burma

GeneticTypes of Thalassaemia :
There are TWO basic groups of thalassaemia. Alpha ( )Thalassaemia Beta ( )Thalassaemia

Alpha Thalassemia
Alpha Thalassemia: deficient/absent alpha subunits
Excess beta subunits Excess gamma subunits newborns /

Five types:
Silent Carrier Trait (Minor) Hemoglobin H Disease Major (Hemoglobin Bart s) Hemoglobin Constant Spring

/ /

Genetic basis of Alpha Thalassemia

Encoding genes on chromosome 16 (short arm) Each cell has 4 copies of the alpha globin gene
Each gene responsible for production of alpha globin

4 possible mutation states:

Loss of ONE gene silent carrier Loss of TWO genes thalassemia minor (trait) Loss of THREE genes Hemoglobin H
Accumulation of beta chains Association of beta chains in groups of 4 Hemoglobin H

Loss of FOUR genes Hemoglobin Barts

NO alpha chains produced only gamma chains present Association of 4 gamma chains Hemoglobin Barts

Classification & Terminology

Alpha Thalassemia
/ - / -/- --/ Hb H disease --/- Barts hydrops fetalis --/- Normal Silent carrier Minor

Beta Thalassemia
Beta Thalassemia: deficient/absent beta subunits
Commonly found in Mediterranean, Middle East, Asia, and Africa

Three types:
Minor Intermedia Major (Cooley anemia)
May be asymptomatic at birth as HbF functions

Genetic basis of Beta Thalassemia

Encoding genes on chromosome 11 (short arm) Each cell contains 2 copies of beta globin gene
beta globin protein level = alpha globin protein level

Suppression of gene more likely than deletion

2 mutations: beta-+-thal / beta-0-thal

Loss of ONE gene thalassemia minor (trait) Loss of BOTH gene complex picture
2 beta-+-thal thalassemia intermedia / thalassemia major 2 beta-0-thal thalassemia major beta-+-thal / beta-0-thal thalassemia major

Excess of alpha globin chains

Classification & Terminology Beta Thalassemia

Normal Minor Intermedia / /0 / + 0 / + +/+ 0 / 0 +/+ 0 / +

Major

Pathophysiology
Disturbance of ratio between Alpha & non alpha globin chain synthesis then absent or decrease production of one or more globin chains Formation of abnormal Hb structures Ineffective erythropoiesis Excessive RBCs Destruction Iron Overload Extra-medullary hematopoiesis

 Silent carriers
asymptomatic normal

Clinical Manisfestation of Alpha Thalassemia

Alpha Thalassemia minor (trait)

no anemia microcytosis -unusually small red blood cells due to fewer Hb in RBC normal

Alpha Thalassemia intermedia (Hemoglobin H )

microcytosis & hemolysis (breakdown of RBC) - results in severe anemia bone deformities splenomegaly (enlargement of spleen) severe and life threatening

Clinical Manisfestation of Beta Thalassemia

Beta Thalassemia minor (trait)
asymptomatic microcytosis minor anemia

Beta Thalassemia intermedia

symptoms similar to Cooley Anemia but less severe

Beta Thalassemia major (Cooley Anemia)

most severe form moderate to severe anemia intramedullary hemolysis (RBC die before full development) peripheral hemolysis & splenomegaly skeletal abnormalities (overcompensation by bone marrow) increased risk of thromboses pulmonary hypertension & congestive heart failure

Signs & Symptoms

Thalassaemia Minor : Usually no signs or symptoms except for a mild anemia. Thalassaemia Major : 1. Paleness, Jaundice or yellow coloured skin. 2. Growth retardation. 3. Bony abnormalities specially of the facial bones. 4. Enlarged spleen and liver.

DIAGNOSIS

PERIPHERAL BLOOD FILM

Hypochromasia,microcytosis,hypochromic macrocytes that represent polychromatophilic cells,nucleated RBC, basophilic stippling, immature leukocytes

Supra vital stain in hemoglobin H disease that reveals heinz bodies(golf ball appearance)

Increased erythropoiesis in the bone marrow of patients with thalassemia major expands the marrow cavity producing the typical hair-on-end appearance as seen on this radiograph of the skull of a boy with -thalassemia.

 Bone Marrow aspiration Liver biopsy ECG and echocardiography HLA typing Eye examinations, hearing tests, renal function tests, frequent blood counts

DIFFERENTIAL DIAGNOSIS

Iron deficiency anemia Acute leukemia Malaria Rhesus incompatibility

TREATMENT
Blood

transfusion Chelation Bone marrow transplant Splenectomy should be considered when: Annual blood requirements exceed 200 cc/kg/yr. Splenic enlargement is accompanied by symptoms such as left upper quadrant pain or early satiety. Leucopenia or thrombocytopenia causing clinical problems (e.G. Recurrent bacterial infection or Bleeding).

Guidelines to begin transfusion..

(i)Confirmed

laboratory diagnosis of thalassaemia major;

(ii) Laboratory criteria: Hb < 7g/dl on 2 occasions, > 2 weeks apart (excluding all other contributory causes such as infections) or (iii) Laboratory and clinical criteria, including:

- Hb > 7g/dl with: - Facial changes - Poor growth - Fractures, and - Extramedullary haematopoiesis

Transfusion programs
Recommended treatment for thalassaemia major involves: lifelong regular blood transfusions, administered every two to five weeks, to maintain the pre-transfusion hemoglobin level above 9-10.5 g/dl. A higher target pre-transfusion hemoglobin level of 11-12 g/dl appropriate for patients with heart disease or other medical conditions.

IRON CHELATORS:
Desferioxamine (Desferal) Deferiprone (Feriprox) Deferasirox (Exjade, Icl670)

COMPLICATION
iron

overload Repeated transfusions- blood-borne diseases(hepatitis B and C),pyrexia High-output cardiac failure Osteoporosis Hyperbilirubinemia, gallstones long-term increased red-cell turnover Gout Desferrioxamine- local reaction, high frequency hearing loss

PROGNOSIS
Quality of life can drastically improve by supertansfusion and chelation therapy Bone marrow transplant, if possible, is curative.

MALNUTRITION

Theoretical framework of Nutrition Problems. Nutrition problems

Food intake

causes

Infect Disease
Health
causes

direct

Food availability Mother & child in household caring service

indirect

POOR FAMILY & EDUCATION, FOOD STUFF & JOB OPPORTUNITY

main problem

ECONOMIC & POLITIC CRISIS

problem

core

Three level of determinants lead to nutrition status Immediate : Immediate :

Inadequacy of dietary Inadequacy of dietary intake intake manifested :: manifested -PEM - PEM - Micronutr.deficiency - Micronutr.deficiency - Diarrhea& &worm worm disease - Diarrhea disease - ARI - ARI Supply && coverage immuniz Supply coverage immuniz

Intervention programs Supply side :

- access : health care facilities - supplementation of food & micronutr. - immunization - quality: providersskill - information system: coverage of suplpement., fortification, surveillance, etc.

Underlying :
- Household food security - Access to PHC - Community of awareness & care for children & women

Basic :
- Socio-economic conditions (poverty & crisis) - Political factors - Traditional practices (infant feeding) - Environment & sanitation

Demand side:
- empowerment - family awareness of nutrition - subsidies / health insurance

Health & Nutrition Status of Children

PERMASALAHAN MEP :
t merupakan primadona masalah kesehatan gizi
t berperan pd. morbiditas & mortalitas anak t deteksi dini dan tatalaksananya penting sebagai

upaya pencegahan melanjutnya MEP

t MEP berat perlu perawatan di intensif di RS t Berdampak jangka panjang thd. kualitas SDM

MEP.

Klasifikasi Gizi Buruk :

1. GOMEZ (195..) : BB/U : Klinis + laboratoris

2. MacLarren (196..)

3. The Wellcome : Klinis + antropometris Trust Party (1970) 4. Waterlow 5. WHO

(1973)

: BB/TB
:

(1999)

Klinis + antropometris

MEP.

Klasifikasi Gizi Buruk :

Wellcome classification of severe forms of protein-energy malnutrition
Percentage of standard weight for age Oedema present Oedema absent

60-80

Kwashiorkor Marasmic

Undernourishedhment

<60

kwashiorkor

Nutritional marasmus

MEP.

Klasifikasi Gizi Buruk (WHO,1999) :

Gizi kurang Edema
simetris

Gizi buruk + (oedematous

--

malnutrition)

BB/TB

(70-79%)

-3< Z-score <-2

(<70%) (severe wasting)

< -3 Z-score < -3 Z-score

TB/U

(85-89%)

-3< Z-score <-2

(<85%) (severe stunting)

Clinical Feature of Marasmus and Kwashiorkor

Feature Growth failure Wasting Oedema Hair changes Mental changes Dermatosis, flaky-paint Appetite Anaemia Subcutaneous fat Face Fatty infiltration of liver

Kwashiorkor Present Present Present (mild) Common Very common Common Poor Severe (sometimes) Reduced but present May be oedematous Present

Marasmus Present Present, marked Absent Less common Uncommon Does not occur Good Present, less severe Absent Drawn in, monkey-like Absent

Pericardial Effusion

What is it?
Fibrous sac surrounding heart-dense network of collagen fibres Serous membrane two continuous layers separated by a small amount of fluid lubricant (10-20mls straw coloured) Layers are called visceral and parietal
Visceral is inner layer (epicardium) Parietal is continuous with diaphragm and outer walls of great arteries

Where is it?
Surrounds the heart Continuous with the great arteries and the diaphragm

What is it s function?
Stabilises the position of the heart within the chest Prevents friction between the moving heart and adjacent structures Allows for small acute changes in size and shape but limits ventricular filling (not the case in chronic setting)

Pericardial Effusion
Normal: 15-50 ml of thin serous fluid Sudden increase: up to 200 ml: OK between 200 and 300 ml: can be fatal Slow increase: up to 2 liters: OK

Normal heart and Pericardial effusion

Symptoms
exercise intolerants Dull chest pain dyspnea at rest ascites pallor mucosa anorexia cough Weakness

Signs Tachycardia Hypotension Signs of shock Jugular venous distension

Diagnosis & Laboratorium Studies

The following lab studies may be performed in patients with suspected pericardial effusion. Electrolytes - Metabolic abnormalities (eg, renal failure) CBC count with differential - Leukocytosis for evidence of infection, as well as cytopenias, as signs of underlying chronic disease (eg, cancer, HIV) Cardiac enzymes Pericardial fluid analysis

Imaging Studies
Chest radiography

enlarged cardiac silhouette (so-called water-bottle heart)

Image is from a patient with malignant pericardial effusion. Note the "water-bottle" appearance of the cardiac silhouette in the anteroposterior (AP) chest film.

Echocardiography
is the imaging modality of CHOICE for the diagnosis of pericardial effusion, as the test can be performed rapidly and in unstable patients. Most importantly, the contribution of pericardial effusion to overall cardiac enlargement and the relative roles of tamponade and myocardial dysfunction to altered hemodynamics can be evaluated with echocardiography

Differential diagnosis
Cardiac Tamponade Pericarditis, Constrictive-Effusive Cardiomyopathy, Dilated Pericarditis, Uremic Myocardial Infarction Pulmonary Edema, Cardiogenic Pericarditis, Acute Pulmonary Embolism Pericarditis, Constrictive

Treatment
Medication Aspirin/nonsteroid anti inflammatory agents(NSAIDS) Most acute idiopathic or viral pericarditis occurrences are self-limited and respond to treatment with aspirin or another NSAID. Aspirin may be the preferred nonsteroidal agent to treat pericarditis after myocardial infarction because other NSAIDs may interfere with myocardial healing. Indomethacin should be avoided in patients who may have coronary artery disease.

 Antibiotics In patients with purulent pericarditis, urgent pericardial drainage combined with intravenous antibacterial therapy (eg, vancomycin 1 g bid, ceftriaxone 1-2 g bid, and ciprofloxacin 400 mg/d) is mandatory. Irrigation with urokinase or streptokinase, using large catheters, may liquify the purulent exudate, but open surgical drainage is preferable.

 The initial treatment of tuberculous pericarditis should include isoniazid 300 mg/day, rifampin 600 mg/day, pyrazinamide 15-30 mg/kg/day, and ethambutol 15-25 mg/kg/day. Prednisone 1-2 mg/kg/day is given for 5-7 days and progressively reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential.

Surgical Care
Subxiphoid pericardial window with pericardiostomy Thoracotomy Video-assisted thoracic surgery

Consultations
A CARDIOLOGIST should be involved in the care of patients with pericardial effusion.

Complication
Pericardial tamponade Can lead to severe hemodynamic compromise and death. Heralded by equalization of diastolic filling pressures. Treat with expansion of intravascular volume (small amounts of crystalloids or colloids may lead to improvement, especially in hypovolemic patients) and urgent pericardial drainage. Avoid positive-pressure ventilation if possible, as this decreases venous return and cardiac output. Vasopressor agents are of little clinical benefit. Chronic pericardial effusion Effusions lasting longer than 6 months. Usually well tolerated.

PROGNOSIS
Most patients with acute pericarditis recover without sequelae. Predictors of a WORSE OUTCOME include the following: fever greater than 38C, symptoms developing over several weeks in association with immunosuppressed state, traumatic pericarditis, pericarditis in a patient receiving oral anticoagulants, a large pericardial effusion (>20 mm echo-free space or evidence of tamponade), or failure to respond to NSAIDs. Patients with symptomatic pericardial effusions from HIV/AIDS or cancer have high short-term mortality rates.

Discussion & Summary

Thank you