Pediatric Examination and Board Review (161 page)

6.
(D)
The history of an upper respiratory infection is most consistent with the diagnosis of acute ITP, and a bone marrow evaluation is not required for those patients with characteristic features of ITP. The presence of fever, other cytopenias, lymphadenopathy, or organomegaly is more likely to be associated with other diagnoses, such as acute leukemia, and therefore patients with these features should undergo a bone marrow evaluation.

7.
(B)
The peak age of onset of ITP is 2-6 years old. It is much less common in infants younger than 1 year of age and in adolescents. About 80-90% of pediatric ITP cases are self-limited and have complete recovery of platelet counts within 6 months, independent of the type of treatment used. ITP that occurs in patients younger than 1 year of age or in those older than 10 years of age is more likely to be chronic, with persistent and possibly lifelong thrombocytopenia that is often less responsive to treatment. Children with chronic ITP can also have other associated autoimmune diseases or immunodeficiencies, such as systemic lupus erythematosus or common variable immunodeficiency, with immune-mediated thrombocytopenia as the presenting feature.

8.
(C)
Platelet disorders with thrombocytopenia or platelet dysfunction are associated with petechiae, purpura, and mucocutaneous bleeding, including epistaxis, gingival hemorrhage, and GI bleeding (see
Figure 92-1
). Spontaneous intracranial hemorrhage is a rare but severe complication of ITP, with an estimated incidence between 0.1 and 0.5% of ITP cases. Joint bleeding is a common complication of clotting factor deficiencies such as factor VIII or factor IX deficiency (hemophilia A and B, respectively) but is almost never seen in patients with platelet disorders.

FIGURE 92-1.
Idiopathic thrombocytopenic purpura. Nonpalpable purpura in ITP. (Reproduced, with permission, from Knoop KJ, Stack LB, Storrow AS, et al. Atlas of Emergency Medicine, 3rd ed. New York: McGraw-Hill; 2010:362. Photo contributor: Lawrence B. Stack, MD.)

9.
(A)
The most frequently used initial treatment for ITP is either intravenous immune globulin (IVIG) or anti-Rho-D immune globulin. Corticosteroids can also be effective, but bone marrow evaluation should be performed before steroid use to rule out the presence of underlying leukemia. Platelet transfusions are generally not indicated for ITP treatment because the platelets will be rapidly destroyed by the immune-mediated platelet consumption occurring in ITP. Nonsteroidal anti-inflammatory medications, such as ibuprofen, should also be avoided, because they inhibit platelet function. Anti-Rho-D immune globulin acts via binding to red blood cells and inducing red blood cell sequestration in the spleen, thereby displacing platelets to be released back into the bloodstream. Therefore, one of the side effects of anti-Rho-D treatment is anemia, and its use should be avoided in patients who are anemic before treatment. The mechanism of IVIG action is poorly understood.

The use of IVIG, anti-Rho-D, or corticosteroids will not have any effect on the natural course of the disease but can temporarily increase the platelet count to reduce the incidence of bleeding complications. Because approximately 80-90% of cases of ITP resolve spontaneously regardless of the treatment used, careful observation can also be a therapeutic option, with later intervention as needed. For emergent cases with severe bleeding unresponsive to other therapies, splenectomy can reduce platelet consumption and sequestration and lead to an increased platelet count but should not be used as the primary therapy. Splenectomy is generally reserved for cases of chronic ITP unresponsive to other therapies with reduced quality of life because of bleeding complications.

10.
(C)
Wiskott-Aldrich syndrome is a rare X-linked disorder that is characterized by neutropenia, thrombocytopenia, and an eczematous skin rash (see
Figure 92-2
). Anemia is not a feature of the syndrome. The immune deficiency of Wiskott-Aldrich syndrome results in increased infections of all types, including viral, bacterial, and fungal. The thrombocytopenia is characterized by small platelets and an increased risk of bleeding, with a significant risk of intracranial hemorrhage. Wiskott-Aldrich syndrome can also be associated with other autoimmune disorders such as Coombs positive hemolytic anemia, arthritis, and vasculitis. Patients with Wiskott-Aldrich syndrome have more than a 100-fold increased risk of malignancies, including lymphomas and brain tumors. Splenectomy can result in an increased platelet count, reduced risk of bleeding complications, and increased patient survival, but bone marrow transplantation is the only currently available curative therapy.

FIGURE 92-2.
Severe atopic dermatitis in a boy with WiskottAldrich syndrome. Note the serosanguineous crusting. (Reproduced, with permission, from Wolff K, Goldsmith LA, Katz SI, et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill; 2008: Fig. 144-7.)

11.
(A)
Neonatal thrombocytopenia is a relatively common finding and can be the result of a variety of underlying conditions. Maternal antibodies can cross the placenta to cause alloimmune thrombocytopenia in the fetus, and maternal use of certain medications can also cause neonatal thrombocytopenia. Neonatal infections, sepsis, DIC, and thrombosis can all also be associated with thrombocytopenia.

Neonates with large hemangiomas or vascular malformations can have associated consumptive coagulopathy with DIC and thrombocytopenia, termed the Kasabach-Merritt syndrome. Other congenital causes of thrombocytopenia include syndromes such as TAR syndrome, congenital amegakaryocytic thrombocytopenia, Bernard-Soulier syndrome, and Wiskott-Aldrich syndrome. Fanconi anemia is an autosomal recessive, aplastic disorder associated with chromosomal instability that can have isolated neonatal thrombocytopenia or pancytopenia as well as skeletal anomalies. However, the most common age of onset of cytopenias in patients with Fanconi’s anemia is 3-14 years of age, with only 5% of cases diagnosed in infancy. Neonates with a chromosomal disorder such as trisomy 13, 18, or 21 can also frequently have isolated thrombocytopenia of unknown etiology. Glanzmann thrombasthenia is a rare autosomal recessive disorder associated with defective platelet adhesion and bleeding but with normal platelet counts.

12.
(C)
Factor VIII deficiency, or hemophilia A, is inherited in an X-linked pattern. Factor IX deficiency, or hemophilia B, is also X-linked, whereas factor XI deficiency (sometimes called hemophilia C) is inherited in an autosomal recessive manner. Hemophilia A occurs in approximately 1 in 4000 newborn boys; hemophilia B occurs in approximately 1 in 30,000. Both are associated with an increased risk of bleeding. Possible neonatal complications include umbilical stump bleeding, bleeding from circumcision sites, and intracranial hemorrhage. Children with hemophilia can have mucocutaneous bleeding and purpura, but deep soft tissue hemorrhages and intra-articular joint hemorrhages (termed
hemarthroses
) are the hallmarks of the disease. Hemarthrosis can occur at any age but most commonly occurs with increased (but still uncoordinated) ambulation in late infancy and early toddlerhood. Hemarthroses are characterized by acute joint warmth, swelling, and tenderness, and, if recurrent, can result in chronic arthritis and joint destruction. Other bleeding complications in patients with hemophilia include oral hemorrhages (particularly after dental procedures), GI bleeding, and hematuria.

The severity of bleeding symptoms is related to the level of factor in the blood, with mild cases having more than 5% of factor levels, moderate cases having 1-5% normal factor levels, and severe cases having less than 1% normal factor levels. Normal factor levels range from 60% to 150%, with female heterozygotes having levels between 20% and 50% of normal with no bleeding symptoms.

13.
(B)
Placement of central lines or arterial lines, lumbar punctures, intramuscular injections, and any surgical procedures should be avoided in patients with hemophilia (severe factor VIII or IX deficiency) until after factor replacement therapy has been given. Peripheral venipuncture can be done, although repeated traumatic efforts should be avoided. Hemophilia patients who have suffered head trauma should receive factor replacement therapy
before
any brain imaging is performed because any intracranial hemorrhage that has occurred will continue bleeding until factor replacement is given.

14.
(B)
Factor VIII deficiency results in a prolonged PTT, with a normal PT and thrombin time. Fibrin time is not a true test. Factor VIII is involved in the intrinsic coagulation cascade, which is initiated by factor XII interaction with high molecular weight kinins or kallikrein. This interaction results in serial activation of factors XI and IX. Factor VIII acts as a cofactor with activated factor IX for activation of factor X. The PTT measures the function of the intrinsic cascade and is therefore prolonged in cases of factor VIII or IX deficiency. The PT measures the extrinsic clotting cascade, with factor VII interacting with tissue factor to activate factor X. Activated factor X can then activate factor V, which then activates thrombin (factor II). Thrombin cleaves fibrinogen to form fibrin. Factor XIII is then required for fibrin cross-linking to form a stable blood clot.

15.
(B)
Therapy for bleeding in a patient with hemophilia B, or factor IX deficiency, includes local control measures such as ice and direct pressure but can also include topical thrombin and oral aminocaproic acid, an antifibrinolytic agent. For more severe bleeding, replacement of the deficient factor is required. With mild mucocutaneous bleeding, the goal of factor replacement should be to increase the factor level to approximately 20-30%. With more severe bleeding, the target factor level is much higher. Patients with hemarthroses should receive factor replacement to attain a 60-80% factor level; patients with suspected or documented intracranial hemorrhages should attain a 100% factor level. The replacement factor used is specific for the underlying defect because factor VIII will not suffice for treatment of patients with factor IX deficiency and vice versa. However, for patients with hemophilia who have developed inhibitory antibodies against the replacement factor treatments, the need for replacement factor can be bypassed with the use of preactivated downstream clotting proteins, such as activated factor VII, which directly activates factor X and promotes clot formation in the absence of either factors VIII or IX.

16.
(D)
vWD is characterized by deficiencies or dysfunction of von Willebrand factor (vWF), a large serum protein involved in platelet interactions with each other and with the forming blood clot. vWD can be divided into 3 types, depending on the underlying defect in von Willebrand factor. Type 1 vWD is caused by decreased amounts of von Willebrand factor, type 3 is caused by its complete absence. Type 2 is composed of 4 subtypes, each a result of a different mutation that affects the function of the protein. Each type of vWD is associated with increased bleeding, particularly bleeding from mucous membranes (epistaxis and menorrhagia) and postoperative bleeding after surgical procedures such as dental extraction or tonsillectomy/adenoidectomy. Chronic blood loss can be severe enough to cause iron deficiency anemia, and vWD should always be suspected in older children or adolescents who develop iron deficiency anemia.

17.
(A)
Type 1 vWD is caused by decreased production of vWF, which is produced and stored in both platelets and vascular endothelial cells, and DDAVP can stimulate the release of available vWF in most patients to increase the serum levels and assist in clot formation. Side effects of DDAVP include hyponatremia. Serum sodium levels should be monitored in patients receiving frequent DDAVP doses. FFP has very small amounts of vWF and would not be an effective therapy for severe bleeding. Cryoprecipitate, however, contains large amounts of vWF and can be used for replacement. Endogenous vWF in the bloodstream is bound to factor VIII and protects factor VIII from degradation. So the best treatment option for bleeding patients with decreased vWF, or for those who do not respond to DDAVP, is replacement with partially purified factor VIII products, which also contain large amounts of vWF. Recombinant factor VIII products are composed solely of purified factor VIII and do not contain any vWF. Except in cases of type IIB vWD that are associated with thrombocytopenia, platelet counts are generally normal in vWD patients, and so transfusions would not be of benefit to control bleeding.