GOOD MORNING! Thursday, July Heidi Murphy, MD Leslie Carter-King, MD
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1 GOOD MORNING! Thursday, July Heidi Murphy, MD Leslie Carter-King, MD
2 PREP QUESTION Almost all infants experience a transient increase in bilirubin concentrations known as physiologic jaundice during the first week after birth. Among the following, which is most likely to contribute to the development of this condition: A. B. C. D. E. Decreased enterohepatic circulation Increased bilirubin conjugation Decreased erythrocyte survival Increased ligandin levels Decreased erythrocyte volume
3 THE CASE 18 month old female with bruising
4 THE CASE Past Medical History Full term baby, vaginal delivery without complications Birth weight: 8 lb. 1 ounce No medical problems Family History No history of bleeding disorders No history of cancers No current medications No known drug allergies Immunizations up to date
5 PHYSICAL EXAM Weight: 10.8 kg (40%) Height: 83 cm (>95%) HC: 43 (>95%) T: 97.9 P: 158 RR: 30 BP: 121/78 GEN: HEENT: CV: RESP: ABD: EXT: DERM: Awake. Alert. NAD. Well hydrated. MMM. No signs of bleeding from nose/oropharynx - clear. RRR without murmurs/rubs/gallops. CTA bilaterally. Soft. NTND. + BS Warm. 2+ distal pulses. Bruising diffusely involving proximal upper extremities, bilateral lower extremities and low back along spine- all bruises of various ages. Scattered petechiae.
6 LABS WBC 15 H/H 13.5/39.5 Platelets: 18 Segs 43 Lymphs 51 Monos 2 Eos 1 Atypical lymphs 3 CMP- within normal limits Uric Acid 2.2 LDH 377 Ig GAME- within normal limits **Thrombocytopenia is defined as a platelet count >150,000!!
7 DIFFERENTIAL DIAGNOSIS
8
9 THROMBOCYTOPENIA & ITP Idiopathic thrombocytopenic purpura Immune thrombocytopenic purpura
10 PLATELETS Life span 7-10 days Removed from circulation by monocyte/macrophage system When needed, bone marrow can increase platelet production 10 fold! Primary hemostasis Secondary hemostasis Normal range 150, ,000 Thrombocytopenia Mild: k Moderate: 30-50k Severe: <30k
11
12 IMMUNE THROMBOCYTOPENIA Platelet count <100,000 Primary or Secondary Increase platelet destruction Immune-mediated Platelet activation/consumption Mechanical platelet destruction Platelet sequestration Decreased platelet production Infection Congenital heart disease Bone marrow failure Genetically-impaired thrombopoiesis **Normal or increased platelet production in bone marrow!!
13 IMMUNE THROMBOCYTOPENIA Annual incidence: 1-6.4/100,000 children Peak incidence between: 2-5 year olds Adolescence Males > Females Especially in younger ages Seasonal fluctuations Spring and early summer
14 PATHOGENESIS Auto-antibodies against Glycoprotein IIb/IIIa T-cell mediated cytotoxicity Act against megakaryocytes in the bone marrow 60% patients found to have history of preceeding infection in past month Some develop ITP after MMR vaccination
15 SIGNS AND SYMPTOMS Dry Purpura Cutaneous bleeding Petechiae, purpura, ecchymoses Found in 60% of patients with ITP *Thrombocytopenia rarely causes deep muscle or joint bleeding!! Wet Purpura Mucosal bleeding Nasal passages, buccal mucosa, gingiva, GI tract, vaginal tract Found in 40% of patients with ITP Much more common when platelets < 10,000 *Common presenting symptom is increased bruising!!
16 *Distinguish between bleeding/bruising in a healthy, active child vs. child with thrombocytopenia!!
17 CLINICAL MANIFESTATIONS Serious hemorrhage Epistaxis, gastrointestinal bleeding, intracranial hemorrhage requiring hospitalization or blood transfusion Incidence of ICH in ITP % ICH has a 25% mortality rate *Severe or persistent headache may be a sign of ICH in patients with ITP!!
18 WORK-UP CBC with differential Consider repeat if needed to r/o lab error Reticulocyte count Red blood cell indices DAT (direct Coombs) +/- Immunoglobulins
19
20 DIAGNOSTIC CRITERIA Platelet count <100,00 In presence of otherwise normal CBC and retic Normal blood smear No signs or symptoms of other conditions associated with thrombocytopenia Unequivocal response to ITP-specific treatments
21 DRUGS ASSOCIATED WITH ITP Heparin Phenytoin Carbamazepine Valproate Vancomycin Sulfonamides Rifampin Betalactamse antibiotics *History of medications should be taken in any child with thrombocytopenia!!
22 LABORATORY STUDIES 80% of patients with ITP will have platelet count < 20,000 44% of patients with ITP will have platelet count < 10,000 If anemia is present, should be microcytic secondary to bleeding May consider confirming patient had previously normal platelet count Peripheral blood smear
23 DISEASE COURSE Newly-diagnosed: 3 months duration 50-70% of patients Persistent: 3-12 months duration Chronic: >12 months duration 20-30% of pateints Recovery defined as platelet count >150,000 *Most children recover in < 1 year without treatment!!
24 TREATMENT OPTIONS: ITP Goal- Maintain a safe platelet count to prevent significant bleeding Treatment only necessary in patients with severe thrombocytopenia Except if has pre-existing/concomitant bleeding risk *Appropriate management of child with ITP!!
25 *Splenectomy is not an appropriate treatment option at the onset of ITP if there is no major bleeding problem present!! *Steroids and IVIg typically increase platelet count but do not alter natural course of disease!!
26 PRECAUTIONS Contact sports *Must avoid aspirin and other drugs that interfere with platelet function!! (NSAIDs) Prior to surgical interventions/dental surgery, ensure platelet count > 50,000 Significant bleeding risk, ensure platelets >100,000\ Reassurance!
27 MONITORING Newly diagnosed- Outpatient setting 1-2 x weekly depending on severity Once platelets >150,000, space labs Continue to monitor for 1-2 months to ensure stability of platelet count. Recurrence in <1% Chronic- Spontaneous remission in 1/3 of patients Uncommon to have platelets <10,000
28 WHEN TO WORRY?
29 ULTIMATELY: OTHER LABS HIV: negative EBV IgG/IgM: negative CMV IgG/IgM: negative ANA IgG: none detected Target Platelet Antibodies: Target Platelet 1 IgG negative IgM positive Target Platelet II IgG/IgM: negative
30 ULTIMATELY Flow cytometry Normal Bone Marrow aspirate Trilineage hematopoiesis Thrombocytopenia with megakaryocyte hyperplasia No increased abnormal blast forms FISH negative (No assay specific abnormalities detected) 46XX Positive antiplatelet antibodies!
31 FISH
32 BONE MARROW BIOPSY INDICATIONS Atypical clinical/lab features concerning for malignancy Failure to respond to glucocorticoids, IVIg, or anti-d Loss of response to typical ITP therapies that were previously effective Controversial!! Prior to starting steroids Prior to planned splenectomy Chronic ITP patients that have never been treated or never responded to treatment Considering thrombopoietic agent??
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