eMedicine Specialties > Pediatrics: General Medicine > Hematology

Thrombasthenia

Noah C Federman, MD, Assistant Professor of Pediatrics, Division of Pediatric Hematology/Oncology, Mattel Children's Hospital, David Geffen School of Medicine; Director, Pediatric Bone and Soft Tissue Sarcoma Program, University of California at Los Angeles
Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA; Mark E Green, MD, Chief, Department of Emergency Medicine, Emergency Medicine, Gateway Medical System; Lawrence S Frankel, MD, Director of Pediatric Hematology/Oncology, Scott and White Clinic; Professor, Department of Pediatrics, Division of Hematology/Oncology, Texas A&M University School of Medicine

Updated: Nov 18, 2008

Introduction

Background

Glanzmann, a Swiss pediatrician, initially described thrombasthenia in 1918 when he noted purpuric bleeding in patients with normal platelet counts.¹ The term thrombasthenia means weak platelets. Glanzmann thrombasthenia (GT) is one of several inherited disorders of platelet function, which also include Bernard-Soulier syndrome, as well as deficiencies of platelet adhesion, aggregation, and secretion.² Each of these disorders is characterized by a lifelong bleeding tendency.

As in most individuals with hereditary hematologic disorders, thrombasthenia is typically diagnosed at an early age. Pediatricians must be aware of its existence and, when confronted with a complicating coagulopathy, consider thrombasthenia in the differential diagnosis.

Pathophysiology

GT is a rare autosomal recessive disorder whereby the production and assembly of the platelet membrane glycoprotein (GP) IIb-IIIa is altered, preventing the aggregation of platelets and subsequent clot formation.

Review of platelet function

Platelets adhere to sites of endothelial injury and then activate, aggregate, and secrete various chemicals designed to promote further platelet recruitment and aggregation. von Willebrand factor (vWF) binds the exposed collagen and binds GP Ib-IX-V complex on the surface of the platelet. This binding adheres platelets to the site of injury. Fibrinogen and vWF bind to the GP IIb-IIIa complex exposed on the activated platelet's surface. This allows crosslinking of platelets and formation of a clot.

Specific deficiency

The platelet integrin GP IIb-IIIa (also referred to as a IIb-b) is a calcium-dependent heterodimer complex that can bind fibronectin, fibrinogen, vWF, and vitronectin. Approximately 80,000 GP IIb-IIIa receptors are present on the surface of each platelet. GP IIb and GP IIIa have their own separate genes on the long arm of chromosome 17. Abnormalities in either gene or in the assembly of the complex result in an abnormal or deficient receptor and, consequently, in disease. Specific genetic abnormalities of each GP include missense mutations, nonsense mutations, splice site mutations, deletions, and point mutations. More than 70 mutations have been described. These mutations are widely distributed over the 2 genes that encode GP IIb and IIIa present at chromosome band 17q.21-23.³ Small deletions, insertions, splicing defects, and nonsense and missense mutations are common. A database of these mutations can be reviewed at the Samuel Bronfman Department of Medicine's Glanzmann Thrombasthenia Database.

GT is an autosomal recessive disorder and heterozygous individuals are asymptomatic. Typically, one of the GPs is not properly formed, leaving the other unpaired in the endoplasmic reticulum, where it is degraded. Platelet aggregation, which requires the entire complex, is therefore deficient or completely absent. Binding sites for thrombin are preserved in thrombasthenic platelets, allowing the platelets to be activated for aggregation.⁴ Although granule release still occurs, crosslinking as described is disabled.

The deficiency is uniformly present throughout the platelet population and is present in endothelial cells and precursor megakaryocytes. Patients with GT are classified as having type 1, type 2, or variant type based on the degree of GP IIb-IIIa deficiency, fibrinogen binding, and clot retraction.⁴ Patients with type 1, the most severe form of the disease, have less than 5% of the normal amount of GP IIb-IIIa present on their platelets. Additionally, they have absent fibrinogen binding and clot retraction. Individuals with type 2 have 10-20% of GP IIb-IIIa, can bind fibrinogen, and have normal–to–moderately deficient clot retraction capability. Persons with the variant type of thrombasthenia have more than 50% of the normal amount of GPIIb-IIIa; however, fibrinogen binding and clot retraction widely vary.

Frequency

United States

Over 500 cases of thrombasthenia have been reported in the international literature. Although GT predominates among certain ethnic groups, an estimate of worldwide incidence and prevalence has not been reported.

International

As stated above, international frequency data are unknown. However, particularly high carrier rates have been reported in certain ethnic groups, such as Arab populations, specifically Jordanian nomadic tribes, Iraqi Jews, French gypsies, and individuals from southern India. The incidence rate also appears to be increased in families in which marriage to close relatives is accepted.⁵

Mortality/Morbidity

The probability of death following bleeding is estimated at approximately 5-10%. Most of these cases are related to occurrence of severe unprovoked intracranial or GI hemorrhages.

Race

High carrier rates of GT mutations have been reported in Jordanian nomadic tribes, Iraqi Jews, French gypsies, and individuals from southern India. A report of 382 patients with GT in Iran may suggest that this hereditary hemorrhagic disorder may be more common than initially believed in the Arab population.⁶

Sex

The disease is inherited as an autosomal recessive disorder. No differences appear to occur based on sex. Men present more frequently with gingival bleeding, whereas women present more frequently with menorrhagia.

Age

Patients with GT are typically diagnosed in infancy or early childhood. However, age of diagnosis can range from birth to adulthood. Neonatal purpura typically suggests type 1 thrombasthenia. Epistaxis and GI bleeding are frequent presenting signs of GT and are more severe in children, especially those aged 4-10 years. Menorrhagia may be a presenting sign of GT in adolescent females and can be a critical problem. The severity and frequency of bleeding usually decreases with age.

Clinical

History

• Initially, patients present with mucocutaneous bleeding in the neonatal period or with bleeding following circumcision.
• Children with thrombasthenia may have purpura, epistaxis, gingival bleeding, GI bleeding, and menorrhagia.
• The occurrence of most minor bleeding decreases with age.
• Severe menorrhagia is a common problem that requires careful observation and treatment with oral contraceptive pills. It is usually associated with an excessively proliferative endometrium that reflects estrogen dominance.⁵
• Additional presenting symptoms include GI bleeding and hematuria.
• Excessive bleeding following parturition and postsurgical bleeding represent a significant risk.
• Although uncommon, hemarthrosis and deep hematomas more characteristic of hemophilias can occur.
• Posttraumatic bleeding may be severe in patients not prepared with normal platelets.
• Clinical bleeding does not always correlate with the amount of GP IIb-IIIa present.
• Because the Glanzmann thrombasthenia (GT) trait is recessive, the absence of a family history should not delay a workup for thrombasthenia.

Physical

• Most patients with thrombasthenia present with signs of purpura or bleeding.
• The initial physical examination should focus on assessing hemodynamic stability.
• The diagnosis is made in patients with refractory hemorrhage and appropriate findings on the diagnostic laboratory studies (see Laboratory Studies).
• Other than identification of hemorrhage, physical examination findings are of limited use.

Causes

• Trauma is the most frequent cause of bleeding in persons with thrombasthenia. This includes surgical procedures (eg, dental extractions) in which bleeding can be severe. Pregnancy and delivery are also common causes of severe bleeding in this disorder.
• Spontaneous bleeding typically decreases in adolescence and adulthood.
• GI bleeding requires an investigation as to cause.
• Unprovoked intracranial and GI bleeding can occur and is, for the most part, responsible for the 5-10% mortality in GT.

Differential Diagnoses

Other Problems to Be Considered

Disseminated intravascular coagulation
Idiopathic thrombocytopenic purpura
Gray platelet syndrome (a -granule deficiency)
Hermansky-Pudlak syndrome
Pseudo-von Willebrand disease (vWD)
Scott syndrome
Quebec platelet syndrome
Chédiak-Higashi syndrome
Medication-induced (aspirin) platelet inhibition

Workup

Laboratory Studies

• A history of prolonged bleeding, a prolonged bleeding time, and failure of platelets to aggregate in response to L-epinephrine, adenosine 5'-diphosphate (ADP), collagen, and arachidonic acid are diagnostic of thrombasthenia. Note that response to ristocetin in platelet aggregation studies is normal.
• The platelet function assay PFA-100 (Dade-Behring; Miami, Fla) can replace bleeding times and may aid in the diagnosis of Glanzmann thrombasthenia (GT). The PFA-100 measures the time to closure when blood is passed through a collagen filter. This time is prolonged in patients with GT.⁷
• A CBC count and peripheral smear may also be helpful to suggest the degree of bleeding and rule out other potential causes. Patients who are thrombasthenic have platelet counts within the reference range and, on blood smear findings, normal platelet morphology.
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are within reference ranges.
• A urinalysis may reveal proteinuria and microscopic hematuria.
• The diagnosis of GT should always be confirmed by documenting the deficiency of GP IIb-IIIa using flow cytometry or immunoblot analysis.

Imaging Studies

• Perform head CT scanning in patients with a history of the disease and head trauma.

Treatment

Medical Care

• Refractory bleeding in individuals with thrombasthenia requires the transfusion of normal platelets. Use human leukocyte antigen (HLA)–matched platelets whenever possible to prevent alloimmunization complications.
• Epistaxis can be controlled with nasal packing or application of gel foam soaked in topical thrombin. E-aminocaproic acid may be used to control bleeding in patients with severe epistaxis or after dental extraction.
• Menorrhagia can be severe in patients affected with Glanzmann thrombasthenia (GT). It usually results from excessive estrogen secretion, which causes a highly proliferative endometrium. Acute menorrhagia can be treated with high doses of progesterone followed by maintenance therapy with oral contraceptive pills.
• Iron deficiency anemia can develop in patients with chronic gingival bleeding, GI bleeding, or menorrhagia and may require oral iron supplementation.
• Recombinant factor VIIa (rFVIIa) has been successfully used to achieve hemostasis in patients with GT, particularly in patients who have developed isoantibodies to the GP IIb-IIIa complex and who are thus refractory to platelet transfusions.⁸ rFVIIa appears to enhance endothelial deposition of GP IIb-IIIa–deficient platelets. Combined with antifibrinolytic therapy, rFVIIa further stabilizes the newly formed clot.⁵ rFVIIa has been approved by the European Union for use in patients with GT and platelet refractoriness due to antibodies. The use of rFVIIa continues to be investigated in the setting of GT. It is currently not approved by the US Food and Drug Administration (FDA) for patients with GT, and its use in children with thrombasthenia remains controversial. Optimal dosing has yet to be defined in both pediatric and adult patients with GT. A dose of 90 mcg/kg given every 2 hours for 3 or more doses has been used with success.⁸
• HLA-matched sibling allogeneic stem cell transplantation (SCT) has been successfully performed in patients with GT and platelet isoantibodies that cause severe refractory bleeding. Although curative, this treatment is not recommended in routine cases of thrombasthenia because of the potential complications associated with SCT. The decision to pursue SCT as a potential treatment for GT should be made on a case-by-case basis. Reduced intensity conditioning regimens with SCT have been used in small series with excellent results.⁹  This raises the possibility of curative therapy with reduced adverse late effects.

Surgical Care

• Treatment with platelet transfusions is often necessary prior to surgical or dental procedures. Aminocaproic acid may also be used postsurgically to control bleeding. Recombinant factor VIIa has been used in invasive surgical procedures or high-risk surgical procedures such as cardiothoracic surgery and spinal/neurosurgery. For dental extractions, molded plastic splints can aid in achieving hemostasis.
• Pregnancy and especially delivery can be a major challenge for patients with GT and their care providers. HLA-matched platelet transfusions should be given prior to delivery and are usually required for a week postpartum.⁵ rFVIIa has been used successfully to treat severe bleeding at delivery.

Consultations

• Consultation with a hematologist is strongly suggested.

Diet

• No special diet is required. However, patients with GT should avoid consuming excessive quantities of foods and substances that further interfere with platelet function. This includes excessive quantities of garlic, onions, ginger, and ginseng, as well as food products with quinine and aspirin.

Activity

• Any degree of trauma in a patient with thrombasthenia can be severe.
• Advise persons with thrombasthenia to take appropriate limitations and precautions with sports and other activities.

Medication

The goal of thrombasthenia therapy is to compensate (partly) for defective platelet function.

Antifibrinolytic agents

These agents inhibit fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. The thrombus that forms during treatment is not lysed as rapidly. Effectiveness is uncertain.

Aminocaproic acid (Amicar)

Synthetic competitive inhibitor of plasminogen activation. Preparations include 250 mg/mL PO syr, 500-mg and 1000-mg PO tab, and IV susp.

Dosing

Adult

Loading dose: Infuse 4-5 g IV over 30 min
Maintenance dose: 1 g/h PO/IV until bleeding stops; not to exceed 30 g/d

Pediatric

100-200 mg/kg PO initially, followed by 100 mg/kg PO q6h; not to exceed 30 g/d
Alternatively, 100 mg/kg (3 g/m²) IV initially, followed by 33 mg/kg/h (1 g/m²/h) IV; not to exceed 18 g/m²/d

Interactions

Coadministration with estrogens may cause increase in clotting factors, leading to hypercoagulable state

Contraindications

Documented hypersensitivity; evidence of active intravascular clotting process; DIC; use of IV product in newborns; hematuria (relative contraindication because urinary obstruction may result)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution with impaired liver and kidney function (adjust dose) and coronary artery disease; rapid IV administration may cause hypotension, bradycardia, or arrhythmias; doses used are for vWD, although no studies have determined optimal dosing in thrombasthenia; because aminocaproic acid can be fatal in patients with DIC, differentiate between hyperfibrinolysis and DIC; do not use IV product in newborns (contains benzyl alcohol)

Vasopressin analogs

These agents act like antidiuretic hormone (ADH) to increase factor VIII levels (transiently). They also have direct and local effect on vessel walls that produces increase in platelet adhesion. In part, this local hemostatic action of desmopressin may account for the clinical observation that desmopressin shortens the bleeding time, bleeding episodes, or both.

Desmopressin (DDAVP, Stimate)

Synthetic vasopressin analog used to control severe bleeding.

Dosing

Adult

0.3 mcg/kg IV over 15-30 min; may repeat once if necessary
<50 kg: 150 mcg (1 spray) intranasally as single dose
>50 kg: 300 mcg (1 spray each nostril) intranasally as single dose
Use high-concentration nasal spray (ie, 150 mcg/spray)

Pediatric

<3 months: Not established
>3 months: Administer as in adults

Interactions

Coadministration with demeclocycline and lithium decreases effects; fludrocortisone and chlorpropamide increase effects of desmopressin

Contraindications

Documented hypersensitivity; platelet-type vWD

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hyponatremia, fluid and electrolyte imbalance, and coronary artery disease; avoid overhydration in patients using desmopressin to gain benefit from its hemostatic effects; doses used are for vWD; no studies have determined optimal dosing in thrombasthenia

Clotting factors

Hemostasis is the physiologic response to bleeding. Injury and factors released by platelets initiate the coagulation cascade, which is mediated by blood clotting factors. This results in formation of an insoluble fibrin clot, reinforcing the initial platelet plug.

Coagulation factor VIIa, recombinant (NovoSeven)

Vitamin K–dependent GP that promotes hemostasis by activating extrinsic pathway of coagulation cascade. Data for refractory severe bleeding in the setting of platelet allosensitization are limited. Reports of efficacy in refractory severe bleeding in pregnancy and in the perioperative period. Not approved by the FDA for treatment of GT associated bleeding.

Dosing

Adult

90-110 mcg/kg IV bolus q90-120min for 4 doses; then q2h for 24 doses; then q3h until bleeding stopped.
Adjust dose to nearest 1.2-mg vial size

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for signs of thrombosis or activation of coagulation system; thrombotic events may increase in patients with advanced atherosclerotic disease, crush injury, sepsis, or DIC

Hemostatic agents, topical

These agents are used as an adjunct to achieve hemostasis.

Gelatin, topical absorbable (Gelfoam, Gelfilm)

Used to provide hemostasis in surgery. Can be used for PO and dental surgery and with topical thrombin to stop epistaxis. Available in sponges, dental packs, and sterile powder.

Dosing

Adult

Apply packs or sponges dry or saturated with normal saline; hold in place with direct pressure until hemostasis achieved

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Do not use as sole hemostatic agent in patients with severe bleeding or for closure of skin incisions; do not use in menorrhagia, postpartum bleeding, or in presence of infection

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Generally well tolerated; adverse effects may include increased incidence of infection; tissue compression due to fluid absorption, granuloma formation, or fibrosis

Thrombin, topical (Thrombin-JMI, Reothrom)

Used as an adjunct to achieve hemostasis. Topical thrombin catalyzes the conversion of fibrinogen to fibrin. Available as powder and lyophilized powder for reconstitution.

Dosing

Adult

Profuse bleeding: Apply 1000-2000 U of powder directly to the site of bleeding
Mild bleeding: Apply 100 U for mild skin or mucosal bleeding

Pediatric

Administer in adults

Interactions

None reported

Contraindications

Documented hypersensitivity to drug or material of bovine origin

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Only for external or topical use; do not use as only hemostatic agent in patients with severe bleeding; may develop bovine antibodies

Follow-up

Further Inpatient Care

• Patients with thrombasthenia who receive platelet transfusion warrant admission for close observation.
• Patients with significant blood loss may require close observation in a critical care setting.
• Human leukocyte antigen (HLA)-matched platelets should be requested on standby for rebleeding episodes.
• Avoid administering medications that interfere with platelet function (nonsteroidal anti-inflammatory drugs [NSAIDs]).

Deterrence/Prevention

• Actions taken to prevent minor trauma are strongly suggested.

Complications

• Alloimmunization is a possible complication of treating patients without matched blood.
• Some patients have developed antibodies to the glycoprotein (GP) IIb-IIIa receptor.

Prognosis

• If patients receive timely platelet transfusions, the prognosis is very good.
• Individuals with thrombasthenia and GI bleeding have the worst prognosis (see Mortality/Morbidity).

Patient Education

• Advise patients with thrombasthenia to avoid contact sports or activities that may result in even minor trauma.
• Encourage avoiding causes of GI bleeding (ie, alcohol, NSAIDs).

Miscellaneous

Medicolegal Pitfalls

• Failure to administer human leukocyte antigen (HLA)-specific platelets can result in significant complications throughout the life of a patient with thrombasthenia because of the formation of antibodies to platelets and, possibly, isoantibodies to GP IIb-IIIa receptor.
• Administering nonmatched platelets when matched platelets are available makes the provider vulnerable to litigation. However, if the patient has life-threatening bleeding and matched platelets are not available, nonmatched platelets are warranted.

References

1. Glanzmann E. Hereditare hamorrhagische thrombasthenie. Ein Beitrag zur Pathologie der Blutplattchen. J Kinderkranken. 1918;88:113.

2. Nathan DG, Orkin SH. Nathan and Oski's Hematology of Infancy and Childhood. 6^th ed. Philadelphia, PA: WB Saunders.

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4. Lee GR, Foertser J, Lukens J, Paraskevas F. Wintrobe's Clinical Hematology. 10^th ed. Philadelphia, PA: Williams & Wilkins; 1999.

5. Nurden AT. Glanzmann thrombasthenia. Orphanet J Rare Dis. 2006;1(1):10. [Medline]. [Full Text].

6. Toogeh G, Sharifian R, Lak M, et al. Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran. Am J Hematol. 2004;77:198-199. [Medline].

7. Buyukasik Y, Karakus S, Goker H, Galantino G. Rational use of PFA-100 device for screening of platelet function disorders and von Willebrand disease. Blood Coag Fibrinolysis. 2002;13:349-353. [Medline].

8. Poon MC. The evidence for the use of recombinant human activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders. Transfus Med Rev. Jul 2007;21(3):223-36. [Medline].

9. Connor P, Khair K, Liesner R, Amrolia P, Veys P, Ancliff P. Stem cell transplantation for children with Glanzmann thrombasthenia. Br J Haematol. Mar 2008;140(5):568-71. [Medline].

10. Arvin AM, Behrman RE, Kliegman R, eds. Nelson Essentials of Pediatrics. 3^rd ed. Philadelphia, PA: WB Saunders; 1998.

11. Bellucci S, Damaj G, Boval B, et al. Bone marrow transplantation in severe Glanzmann's thrombasthenia with antiplatelet alloimmunization. Bone Marrow Transplant. Feb 2000;25(3):327-30. [Medline].

12. Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood. Oct 15 2008;112(8):3011-25. [Medline].

13. Hoffman R, McGlave P, Shattil SJ, et al. Hematology: Basic Principles and Practice. 3^rd ed. New York, NY: Churchill Livingstone; 1999.

14. Kashyap R, Kriplani A, Saxena R, Takkar D, Choudhry VP. Pregnancy in a patient of Glanzmann's thrombasthenia with antiplatelet antibodies. J Obstet Gynaecol Res. Jun 1997;23(3):247-50. [Medline].

15. Katzung B. Basic and Clinical Pharmacology. 6^th ed. Norwalk, CT: Appleton & Lange; 1994.

16. Linden MD, Frelinger AL, Barnard MR, et al. Application of flow cytometry to platelet disorders. Seminars in Thrombosis and Hemostastis. 2004;30:501-511. [Medline].

17. Martin I, Kriaa F, Proulle V, et al. Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann's thrombasthenia and anti-glycoprotein IIb-IIIa antibodies. Br J Haematol. Dec 2002;119(4):991-7. [Medline].

18. Nair S, Ghosh K, Kulkarni B, Shetty S, Mohanty D. Glanzmann's thrombasthenia: updated. Platelets. Nov 2002;13(7):387-93. [Medline].

19. Poon MC, D'Oiron R, Von Depka M, et al. Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann's thrombasthenia: results of an international survey. J Thromb Haemost. Jul 2004;2(7):1096-103. [Medline].

20. Poon MC, Demers C, Jobin F, Wu JW. Recombinant factor VIIa is effective for bleeding and surgery in patients with Glanzmann thrombasthenia. Blood. Dec 1 1999;94(11):3951-3. [Medline]. [Full Text].

21. Sassetti B, Lajmanovich A, Vazquez A, et al. Glanzmann thrombasthenia in children from Argentina. J Pediatr Hematol Oncol. Feb 1996;18(1):23-8. [Medline].

Keywords

thrombasthenia, Glanzmann thromboasthenia, GT, Glanzmann disease, constitutional thrombopathy, hereditary hemorrhagic thrombopathy, Bernard-Soulier syndrome, hereditary hemorrhagic disorder, menorrhagia, epistaxis, purpura, circumcision, gingival bleeding, dental extraction, head trauma, iron deficiency anemia, stem cell transplantation, SCT

Contributor Information and Disclosures

Author

Noah C Federman, MD, Assistant Professor of Pediatrics, Division of Pediatric Hematology/Oncology, Mattel Children's Hospital, David Geffen School of Medicine; Director, Pediatric Bone and Soft Tissue Sarcoma Program, University of California at Los Angeles
Noah C Federman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, and Connective Tissue Oncology Society
Disclosure: Nothing to disclose.

Coauthor(s)

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Mark E Green, MD, Chief, Department of Emergency Medicine, Emergency Medicine, Gateway Medical System
Mark E Green, MD is a member of the following medical societies: American College of Emergency Physicians and American Medical Association
Disclosure: Nothing to disclose.

Lawrence S Frankel, MD, Director of Pediatric Hematology/Oncology, Scott and White Clinic; Professor, Department of Pediatrics, Division of Hematology/Oncology, Texas A&M University School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

J Martin Johnston, MD, Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital
J Martin Johnston, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Department of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

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