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The following case study focuses on a four-year-old boy who has a two-year history with intermittent epistaxis. Test your knowledge by reading the background information below and making the proper selection.

Nosebleeds last approximately 20 to 30 minutes and occur approximately three to four times a month. The mother reports some mild-moderate bruising with vaccines in the past. She occasionally noticed bruising on his extremities but reports that he is a very active child, and she thought this was normal. His birth and developmental history are normal. Exam is normal. His mother is very concerned because recently her son had his tonsils removed and had significant post-operative bleeding, prompting a referral to a hematologist. Family history is unremarkable, and there are no known bleeding disorders in the family. He has one sister who is six years old and healthy. Laboratory exam yields a normal CBC, normal PT/PTT/INR, and a normal peripheral smear.

You remain concerned about a potential bleeding disorder given his past medical history.

1) The lab test that is most likely to lead you to the diagnosis of a potential bleeding disorder would be:

1. Von Willebrand panel
2. Bleeding time
3. Electron microscopy looking for a platelet granule defect
4. Factor VIII/IX levels
5. Platelet aggregation test

2) The best method of treatment if this patient is sent to the ER for bleeding is:

1. Factor VIII infusion
2. Desmopressin (DDAVP) 
3. Emergent platelet transfusion and possible rFVIIa
4. A blood transfusion

Answers

Question 1: E; Question 2: C

Explanation

This patient has Glanzmann’s thrombasthenia, a rare autosomal recessive congenital disorder associated with severe platelet dysfunction. Clinically, patients present with increased mucosal bleeding (epistaxis, menorrhagia, and/or post-op bleeding complications). The platelet morphology and size are usually normal on peripheral blood smear. Platelet count is usually normal. PT/PTT/Thrombin are normal. The bleeding time is markedly prolonged. Platelet aggregation studies are classic for diagnosing Glanzmann’s and show abnormal aggregation with all agonists except ristocetin, because ristocetin agglutinates platelets and does not require a metabolically active platelet. Glanzmann’s is caused by a deficiency of the platelet fibrinogen receptor GPIIb-IIIa present on the platelet surface and undergoes conformational change when platelets are activated. Fibrinogen binds to GIIb-IIIa and causes platelets to aggregate, thus a defect in this receptor predisposes to bleeding. Glanzmann’s can be distinguished from other platelet function disorders such as Bernard–Soulier syndrome, a congenital disorder characterized by thrombocytopenia with giant platelets and is caused by a deficiency in the GPIb complex (vWF receptor) on the platelet surface. Other less common platelet function disorders such as Gray platelet syndrome are caused by absence of platelet α-granules, causing platelets to appear gray on Wright stain of peripheral blood. Gray platelet syndrome exhibits an absence of aggregations and secretion with most agonists other than thrombin and ristocetin, and electron microscopy will clinch the diagnosis (i.e., absent α granules).Treatment for Glanzmann’s thrombasthenia is platelet transfusion, which may be life-saving. In cases of severe life-threatening bleeding, rVIIa (recombinant Factor VIIa) has also been used. Stem cell transplantation is the only curative option. A medical alert bracelet is recommended, and adequate education for the family is essential.

Case study submitted by Robyn Dennis, MD, Texas Children’s Cancer Center, Houston, TX.