A Case Presentation:

Clues from the Bruise

By: PGI Ryan Abutazil

Objectives:
1. To be able to present an actual case of immune thrombocytopenic purpura 2. To be able to discuss the pathologic process of the disease 3. To present therapeutic options for ITP 4. To be able to present updates on ITP

Clinical History
o o o o o J.P.H. 2 years old Male Islam Manlubal, R.T. Lim, Zamboanga Sibugay

Chief Complaint: spontaneous bruise formation

Clinical History
1. Twelve days PTA (+) raised non-erythematous, nontender, non-pruritic skin lesions (+) fever (+) decrease in appetite (+) weight loss

Clinical History

2. Nine days PTA (+) spontaneous formation of P5 coin-size bruises, non-tender (+) pin point petechial rashes (-) fever (-) bleeding diathesis

Clinical History
(+) consult at Ipil Provincial Hospital, was given HEMARATE and was referred to this institution. 3. Three days PTA (+) consult at the OPD Dept. of ZCMC (+) laboratory work up was requested

Clinical History
CBC with platelet

Hct WBC Diff. Count

0.35 5.2

0.29

Peripheral Blood Smear

SMEARS SHOW NORMOCHROMIC RBCs WITH MODERATE ANISOPOIKILOCYTOSIS. THE CELLS IN THE WBC SERIES ARE MATURED. PLATELETS ARE INADEQUATE IN NUMBERS

Segmenters 0.60 Lymphocyte s 0.08 Eosinophils 0.03 Monocytes Platelet Count 108

Clinical History
4. On the night PTA (+) had an onset of epistaxis, spontaneously resolved (-) meds taken, (-) vomiting, (-) abdominal pain (-) cyanosis, (-) pallor (-) jaundice

Clinical History
(-) allergies to food and medication (-) previous hospitalization (-) past exposure to radiation or chemicals (-) Heredofamilial diseases such as leukemia or anemia or other blood dyscrasia.

Clinical History
Born to a G1P1 mother, delivered institutionally full term via NSVD; compliant to prenatal check up (-) maternal illness (+) immunization (+) Bottlefed since birth (NESTOGEN)

Physical Exam
At the ER, patient was seen -awake -ambulatory -irritable -NICRD Vital signs: BP- 90/60mmHg Temp- 36.2 PR- 116 RR- 35

Physical Exam
Weight: 11 kg. Height: 82 cm.

Skin: Ecchymoses at the left lateral portion of the trunk and anterior areas of both legs below the knees; Petechiae on the areas of the forehead, left cheek and lower lips (-) pallor (-) jaundice (-) cyanosis

Physical Exam

EENT: Pink Palpebral Conjunctiva, Anicteric sclerae, midline nasal septum with no signs of trauma or bleeding, moist oral mucosa, (-) lymphadenopathy,

Physical Exam
Chest and Lungs: ECE, (-) IC & subcostal retractions, (-) chest indrawings, (-) crackles, (-) rales, (-) adventitous breathe sounds

Physical Exam

Heart: adynamic precordium with normal rate and regular rhythm, (-) murmurs

Physical Exam
Abdomen: flat, nondistended, normoactive bowel sounds, soft, non tender, no palpable mass, no organomegaly Extremities: good, equally strong pulses with good CRT

Admitting Impression
Immune Thrombocytopenic Purpura (ITP)with mild symptoms

Basis for Diagnosis

History: - 2 years old - male - a preceding infection (raised, nonerythematous, non-tender skin lesions and fever) - abrupt onset of spontaneous bruises on the trunk and legs and pin point rashes on the face - CBC results with PBS - Epistaxis

Basis for Diagnosis

Physical Exam: - Skin: Ecchymoses at the left lateral portion of the trunk and anterior areas of both legs below the knees; Petechiae on the areas of the forehead, left cheek and lower lips - no lymphadenopathy - no organomegaly

Differential Diagnosis
RULED IN RULED OUT

Leukemia

spontaneous bruising, petechiae, weight loss spontaneous bruising, petechiae, weight loss spontaneous bruising, petechiae, weight loss

(-) lymphadenopathy (-) splenomegaly (-) bone tenderness (-) WBC derangements

Hemolytic Uremic Syndrome

(-) signs of hypertension (-) renal impairement (-) Neurologic manifestations include alteration in mental status, seizures, hemiplegia, paresthesias, visual

Thrombotic Thrombocytopenic purpura

Differential Diagnosis
RULED IN RULED OUT

Wiskott-Aldrich Syndrome

Male, unusual bruising, occurs primarily in children spontaneous bruising, petechiae, epistaxis, purpura

Absence of atopic symptoms like eczema (-) pancytopenia in CBC (-) congenital birth defects

Fanconis anemia

Differential Diagnosis
RULED IN RULED OUT

Drug-induced thrombocytopenia

spontaneous bruising, petechiae, epistaxis, purpura spontaneous bruising, petechiae, epistaxis, purpura spontaneous bruising, petechiae, epistaxis, purpura

Absence of history of drug intake

Aplastic anemia

Thrombocytopeni a with absent

radii

Other than thrombocytopenia, CBC result is normal Age of onset is 1st week of life; (-) gross physical abnormalities

Course in the Ward:

May 9, 2011 12:00PM (+) awake, comfortable (-) afebrile (+) ecchymosses (+) petechiae (-)
organomegaly

     

(+) good pulses Acute ITP with mild symptoms May 9, 2011 10:00PM

    

Admitted to Ward 8 (ISO) Secure consent TPR q 4 hours DAT Insert IV heplock Lab work-up 1. CBC, platelet, Blood typing - done 2. Peripheral Blood Smear - done For BMA tomorrow in the morning Secure consent For repeat CBC, Platelet, and PBS tomorrow morning I and O q shift and record Refer for any untoward event

 NPO post breakfast at 6:00 AM  Start D 5.3 NaCl 500 cc at MR once on NPO  Refer accordingly

1st Hospital Day

Date S O A P May 9, 2011  Comfortable  Not irritable  No bleeding episodes  Good appetite  Good activity         Temp: 37.0 PR: 105 RR: 27 Awake (+) ecchymoses and petechaie PPC Nondistended abdomen (-) organomegaly Good pulses Acute ITP with  TPR q 4 hours mild  DAT symptoms  Lab work-up 1. CBC, platelet, Blood typing 2. Peripheral Blood Smear  For BMA tomorrow in the morning  Secure consent  For repeat CBC, Platelet, and PBS tomorrow morning  I and O q shift and record

2nd Hospital Day

Date S O A P May 10, 2011 Rpt CBC Plt: Hgb 123 Hct 0.39 RBC 5.36 WBC 13.0 Seg 0.33 Lymph 0.57 Mono 0.10 Platelet 38 MCV 72.4 MCH 22.9 MCHC 31.7 PBS RBCs are moderately hypochromic; WBC series are unaltered; Platelets are diminished  Comfortable  Not irritable  No bleeding episodes  Good appetite  Good activity  Afebrile with normal PR and RR  Awake, playing  (+) ecchymoses and petechaie  PPC  CBS, (-) crackles  Nondistended abdomen  (-) organomegaly  Good pulses  (-) cyanosis Acute ITP  For BMA: with mild secure symptoms materials and consent from watcher  Monitor V/S without fail  S/P BMA: maintain flat on bed for 6 hours refer if site is bleeding continuously  Start Prednisone 10mg per 5mL, 10 mL once a day per orem.

3rd Hospital Day

Date S O A P May 11, 2011 Rpt CBC Plt: Hgb 123 Hct 0.37 RBC 5.36 WBC 8.0 Seg 0.64 Lymph 0.35 Mono 0.01 Platelet 98  New areas with petechial rashes on the face and neck  No epistaxis  No melena      Comfortable Acute ITP Asleep with mild Temp: 37.3 symptoms PR 111 RR 25 (+) petechial rashes & ecchymoses Ppc, (-) epistaxis, (-) gum bleeding (-) lymphadenopath y ECE, clear breath sounds with no crackles or wheezes NRRR (-) murmur Same abdominal  IVF to consume then terminate  For repeat CBC, Platelet  Continue V/S monitoring

PBS None

 

4th Hospital Day

Date S O A P May 12, 2011  Comfortable  Not irritable  No bleeding episodes  Good appetite  Good activity  Temp: 36.9  PR: 98 RR: 21  Awake, wellnourished  (+) ecchymoses and petechaie  PPC  Nondistended abdomen  (-) organomegaly  Good pulses Acute ITP with  Terminate IVF mild  MGH symptoms  Continue Prednisone Oral medication at home  Ff up scheduled

Final Diagnosis:

Acute ITP with mild symptoms

What is ITP?
 Immune

 Thrombocytopenic  Purpura

What happens in normal hemostasis?

What happens in normal hemostasis?

What Occurs in ITP?

 Increased peripheral destruction of platelets  Humoral Immunity is involved primarily
a. production of antibodies that identifies the platelet

surface proteins as foreign. b. These antibodies work in two ways: OPSONIZATION, a process where the antibody coats the platelet for optimum recognition and subsequent phagocytosis by macrophages and polymorphonuclear neutrophils, and COMPLEMENT PATHWAY ACTIVATION, which when activated destroys platelet wall integrity, resulting in cell lysis.

What Occurs in ITP?

 Eventually, immune destruction of platelets is more than its production, which results to depletion of platelets peripherally below 100,000.  Depleted platelets could not hold a solid platelet plug to prevent bleeding at the site of vascular injury.  The problem is primarily on platelet destruction, and not on platelet production.

Clinical Manifestations
Acute ITP Children > adults (2-6 years old) Chronic ITP Adults mainly (30-50 years old)

Females = Males Females > males Self-limiting Post viral Lasts within 6 months Spontaneous remission in 85% Chronic in most No preceding illness Lasts >6 months

Spontaneous remissions 2%

Clinical Manifestations
Chronic Infantile ITP Age Onset Preceding Infection Platelet Count Response to Therapy Incidence of Chronicity 4-24 months Abrupt Unusual <20,000 poor 30% Male/Female ratio 3:1 Chronic Childhood ITP > 24 months 1:3 Insidious Frequent 40,000-80,000 Temporary 10-15%

Clinical Manifestations
 Abrupt onset of bruises and petechial rashes on an apparently well child  Mucosal membrane bleeding, e.g. epistaxis or gum bleeding episodes  Gross hematuria or gastrointestinal bleeding

 A history of a viral illness 1 to 3 weeks prior to the onset of the rashes  There is normal spleen and liver size

Diagnosis
 The diagnosis of Immune Thrombocytopenic Purpura is established once you have excluded other possible factors for the thrombocytopenia, such as leukemia, myelodysplasia, aplastic anemia, or adverse drug reactions.

 CBC results will show no abnormalities in the RBC and WBC counts, unless prolonged bleeding has occurred.

 Peripheral Blood Smear of ITP is non-specific since other thrombolytic thrombocytopenias also show larger platelets with increased platelet diameters.

Diagnosis
Bone Marrow Aspiration: - the presence of megakaryocytes in normal or increased numbers confirms that the thrombocytopenia is thrombolytic and not a problem of production - absence of leukemic infiltrates rules out malignancy as the cause of the platelet decrease. - Eosinophils may be abundant in BMA of ITP patients

Patient Management
 When do we treat?

a. Treatment is indicated if there has been prolonged mucosal bleed such as epistaxis or gum bleeding b. If possible intracranial bleed is imminent c. Still, the physicians clinical judgement is of utmost importance in deciding whether to treat a child with ITP, since oral corticosteroids also carry several side effects that would affect the patient in the long term.

Pharmacological Patient Management

 Corticosteroids : oral prednisone at a dose of 1 to 2 mg per kg per day (60 to 80 mg maximum). In giving this, vascular stability is increased and the endothelial abnormalities are resolved. Side effects: growth retardation, osteoporosis, cataracts, hypertension, acne, psychosis and cushingoid facie.

1. Prolongs platelet survival from splenic destruction by inhibiting phagocytosis 2. Improves platelet preservation and economy by increasing capillary resistance 3. Suppresses immune response against platelet

Indication:
1.Excessive bleeding from the mucous membrane 2.Extensive purpuric lesions especially on the head and neck 3.Thrombocytopenia of more than 5 weeks. 4.Recurrent Thrombocytopenia 5.Platelet count of less than 30,000

Pharmacological Patient Management

 High dose IV gammaglobulin 1. blocks Fc Receptors of the RES 2. Protection of platelets and or megakaryocytes from platelet antibody 3. Also acts as an antiviral.  Indications: 1. infants less than 2 years old who are refractory to steroid therapy

2. This is a valid alternative for steroid therapy

Beneficial Effects: 1. it actually decreases bleeding episodes compared to steroid treatment 2. increases platelet production more significantly than steroid therapy Toxic Effects: 1. Fever and chills in 1-3% of patients 2. Anaphylaxis in IgA-deficient patients.

Pharmacological Patient Management

Anti-Rh D Therapy Infusion of Anti-Rh D in patients with Rh positive will mount an immune response againts the patient s RBC s which will result to a transient hemolytic anemia. Coincident to the clearance of the antibody-coated RBC s is the increase in the platelet survival in the patients with ITP. This is due to the blocking of the Fc receptors of the reticuloendothelial system.

Pharmacological Patient Management

Vinblastine Danazol Cyclophosphamide Azathioprine Cyclosporine Alpha- interferon

 Platelet transfusion- (+) active neurologic signs Splenectomy- for severe acute ITP with acute life threatening bleeding, with a non-responsive medical treatment

Laparoscopic splenectomy for immune thrombocytopenic purpura at a teaching institution. Zheng CX, Zheng D, Chen LH, Yu JF, Wu ZM. Source
Department of General Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China (Email: zhengchaoxu@yahoo.com).

BACKGROUND: High anatomic location, fragility, and generous blood supply of the spleen makes laparoscopic splenectomy (LS) difficult to master, and few patients need splenectomy for benign disorders. The aim of this research was to assess operative outcomes and hematological results of a large series of patients treated with LS for chronic immune thrombocytopenic purpura (ITP) and to determine which clinical variables predict favorable hematological outcome.

METHODS: LS was successfully performed for 154 patients with chronic ITP from September 1999 to April 2009 at the First Affiliated Hospital of Sun Yat-sen University. Operative outcomes were assessed retrospectively. Long-term follow-up data were obtained from outpatient medical records and phone interviews. Clinical and laboratory variables (including gender, age, disease duration before surgery, previous response to steroids, preoperative platelet count, and postoperative peak platelet count) were evaluated by univariate analysis to identify potential predictors of hematological outcome. Multivariate Logistic regression model was used to determine independent predictors of hematological outcome.

RESULTS: One patient died from subphrenic abscess and postoperative sepsis. The overall major morbidity rate was 8.4%. None of the patients required a second surgery for complications. Of the 127 patients available for a mean follow-up of 43.6 months (range 9 114 months), the overall initial response (i.e., at two months after LS) and long-term response to LS were achieved in 89.0% and 80.3%, respectively. Five patients (3.9%) developed pneumonia 3 - 35 months after LS. Univariate analysis showed a significant difference in mean age between responders (29.1 years) and nonresponders (38.8 years; P < 0.05). Patients who responded to steroid therapy had better hematological outcome than those who did not respond (P < 0.05). Compared to nonresponders, responders to LS had a significantly higher postoperative peak platelet count (404 10(9)/L versus 213 10(9)/L, P < 0.001).

CONCLUSIONS: LS is a safe and effective treatment for chronic ITP. Postoperative peak platelet count may serve as a major predictor of long-term response.