Pediatric Examination and Board Review (160 page)

(E) prolonged PTT

3.
The most likely diagnosis for this child is

(A) ALL

(B) ITP

(C) von Willebrand disease (vWD)

(D) thrombocytopenia with absent radii (TAR) syndrome

(E) Wiskott-Aldrich syndrome

4.
Which of the following tests is not indicated in the initial evaluation of a patient with a suspected bleeding disorder?

(A) platelet function analysis

(B) direct Coombs test

(C) PTT

(D) complete blood count

(E) international normalized ratio (INR) test

5.
Which of the following medications is not associated with immune-mediated thrombocytopenia?

(A) erythromycin

(B) penicillin

(C) trimethoprim-sulfamethoxazole

(D) chloroquine

(E) ceftazidime

6.
Which of the following is not an indication for a bone marrow evaluation in cases of thrombocytopenia?

(A) fever

(B) concurrent neutropenia

(C) hepatosplenomegaly

(D) history of upper respiratory infection

(E) concurrent anemia

7.
The most common age range for the presentation of acute ITP is

(A) 0-1 years

(B) 2-10 years

(C) 10-15 years

(D) 15-20 years

(E) older than 20 years

8.
Which of the following is the least common complication of ITP?

(A) intracranial hemorrhage

(B) epistaxis

(C) intra-articular hemorrhage

(D) melena

(E) gingival hemorrhage

9.
Which of the following is the best initial treatment for patients with ITP?

(A) intravenous immune globulin

(B) ibuprofen

(C) splenectomy

(D) platelet transfusion

(E) FFP

10.
Which of the following is not a feature of Wiskott-Aldrich syndrome?

(A) eczematous rash

(B) thrombocytopenia

(C) anemia

(D) recurrent infections

(E) small platelet size

11.
Which of the following syndromes is not associated with an increased incidence of neonatal thrombocytopenia?

(A) Glanzmann thrombasthenia

(B) Kasabach-Merritt syndrome

(C) Down syndrome

(D) Fanconi anemia

(E) TAR syndrome

12.
What is the inheritance pattern for factor VIII deficiency?

(A) autosomal recessive

(B) autosomal dominant

(C) X-linked

(D) mitochondrial

(E) autosomal dominant with variable penetrance

13.
Which of the following procedures is contraindicated in a patient with uncorrected severe factor IX deficiency?

(A) peripheral intravenous line placement

(B) femoral central line placement

(C) antecubital venous blood draw

(D) brain CT scan

(E) blood cultures

14.
Laboratory findings associated with hemophilia A include which of the following?

(A) prolonged PT

(B) prolonged PTT

(C) prolonged thrombin time

(D) prolonged fibrin time

(E) prolonged INR

15.
Which of the following is not a useful treatment option for control of bleeding in a patient with hemophilia B?

(A) recombinant factor IX

(B) recombinant factor VIII

(C) activated factor VII

(D) aminocaproic acid

(E) topical human recombinant thrombin

16.
Which of the following is the least likely to occur in patients with vWD?

(A) gingival hemorrhage

(B) menorrhagia

(C) prolonged epistaxis

(D) hemarthrosis

(E) bleeding with central line placement

17.
Which of the following is the best treatment for a patient with severe bleeding and type 1 vWD?

(A) intranasal desmopressin (DDAVP)

(B) FFP

(C) recombinant factor VIII

(D) platelet transfusion

(E) recombinant factor IX

18.
Which of the following statements regarding vWD is true?

(A) incidence of vWD is higher in males than in females

(B) vWD is the most common hereditary bleeding disorder in the United States

(C) vWD is characterized by frequent bleeding into joints

(D) type 3 vWD is the most common subtype

(E) there are 5 hereditary types of vWD

ANSWERS

1.
(C)
Petechial rashes are uncommon in pediatrics but are a presenting symptom of severe systemic illness. The differential diagnosis of acute-onsetpetechiae includes infectious and noninfectious causes. Infections caused by the meningococcus, rickettsia, and several congenital infections, for example, toxoplasmosis, rubella, CMV, herpes simplex, and sepsis from any organism causing DIC can be associated with petechial rashes. Infectious mononucleosis is generally not associated with petechiae. Noninfectious causes of petechial rashes include ITP, a common cause of acute thrombocytopenia and petechiae, as well as drug-induced immune thrombocytopenia, HUS, and Henoch-Schönlein purpura. Bone marrow suppression of platelet production in diseases such as ALL and aplastic anemia also can be associated with thrombocytopenia and petechiae.

2.
(A)
Petechiae are the result of capillary hemorrhages and/or abnormal platelet function, caused by either decreased platelet number or intrinsic platelet dysfunction. Abnormal platelet function or number can also be associated with purpura, easy bruising, and mucocutaneous bleeding such as epistaxis and menorrhagia. Therefore, in the patient with petechiae, the most likely abnormality is thrombocytopenia. Although abnormal PTs and PTTs are associated with bleeding disorders, the symptoms generally do not include petechiae. Low factor VIII or IX levels in particular are associated with intraarticular and deep muscle hemorrhages rather than petechiae. An increased level of fibrin degradation products is associated with activation of the coagulation cascade, such as that which occurs in deep venous thromboses or DIC, and it is not directly related to the presence or absence of petechiae.

3.
(B)
The most likely diagnosis for an otherwise healthy child with the acute onset of petechiae with thrombocytopenia is ITP, particularly in toddlers with a history of a recent upper respiratory infection and no family history of other disorders. ITP is generally associated with a history of a viral illness 1-3 weeks before the onset of thrombocytopenia. Characteristically, children have diffuse petechiae with purpura and ecchymoses, but they are otherwise well, with no fevers, weight loss, bone pain, organomegaly, with an otherwise normal physical examination and no history of medication use. Other less common bleeding complications of ITP include epistaxis, GI hemorrhage, and hematuria. Less than 1% of cases experience an intracranial hemorrhage, but the associated morbidity and mortality from intracranial hemorrhage is significant. The peripheral smear will show characteristic scant, large platelets, with the remainder of the complete blood count and peripheral smear being normal.

ALL occurs in children in the same age range as ITP but is associated with other findings such as fever, organomegaly, and other abnormalities in the complete blood count. vWD generally is not associated with petechiae, although type 2B, a rare subtype, is associated with thrombocytopenia and can present with petechiae. In general, vWD does not have an acute onset and most commonly is associated with a positive family history. TAR syndrome is a rare autosomal recessive syndrome characterized by congenital thrombocytopenia, with neonatal onset of petechiae and purpura and associated limb anomalies, including absent radii bilaterally but normal thumbs. The normal thumbs distinguish TAR syndrome from Fanconi anemia, which can also have cytopenias and limb anomalies but is associated with abnormal thumbs.

4.
(B)
The initial evaluation of a child with easy bruising, bleeding, and/or petechiae should include a complete blood count with differential and evaluation of the peripheral smear to assess the platelet count and morphology. In addition, the PT and PTT should be measured to assess the function of the coagulation cascade. The result of a PT determination performed on a normal individual will vary depending on what type of analytical system is used. This is due to the differences between batches of manufacturer’s tissue factor used in the reagent to perform the test. The INR was devised to standardize the results. Each manufacturer assigns an ISI (International Sensitivity Index) value for any tissue factor they manufacture. The ISI value indicates how a particular batch of tissue factor compares with an internationally standardized sample. The ISI is usually between 1.0 and 2.0. The INR is the ratio of a patient’s PT to a normal (control) sample, raised to the power of the ISI value for the analytical system. A screening test for platelet function such as a platelet function analysis is also indicated. A bleeding time should not be performed as a screening test in children for possible bleeding disorders because of the limited expertise in correctly performing the test and the poor sensitivity and specificity of the results. The thrombin time can be useful in addition for evaluating a patient for a fibrinogen defect. A direct Coombs test will not be helpful in assessing the status of the coagulation system. Further testing can then focus on any abnormalities found in the initial screen, such as measuring factor levels in patients with prolonged PT or PTT or platelet aggregation studies for patients with abnormal platelet function analyses.

5.
(A)
Many types of medications, including many antimicrobials, can induce immune-mediated thrombocytopenia. Some medications, such as valproic acid and chemotherapeutic agents, cause thrombocytopenia via myelosuppression in a dosedependent fashion. Other types of medications, including antibiotics such as the penicillins, sulfonamides, and quinines, as well as nonsteroidal anti-inflammatory medications, anticonvulsants, diuretics, and acetaminophen, are associated with immune-mediated thrombocytopenias. Macrolides such as erythromycin do not generally cause these immune-mediated reactions. Other medications associated with immune-mediated thrombocytopenia include heparin and gold, which can both be associated with the development of antiplatelet antibodies.

Medications that induce immune-mediated thrombocytopenia can do so via 2 mechanisms. Heparin and gold induce antibodies in 1-3% of uses, and the antibodies act through platelet activation, leading to platelet consumption and a combination of thrombosis from platelet activation and bleeding from thrombocytopenia. Other medications, such as chloroquine, can induce antibodies that bind to platelet surface proteins only in combination with the drug itself. These antibody-drug coated platelets could then be sequestered in the reticuloendothelial system, resulting in severe thrombocytopenia and potentially severe bleeding.