AUTHOR INFORMATION

Section 1 of 11

Authored by Noah Federman, MD, Department of Pediatrics, Fellow, Division of Pediatric Hematology/Oncology, Mattel Children's Hospital at UCLA, David Geffen School of Medicine at U

Coauthored by Kathleen Sakamoto, MD, Professor, Department of Pediatrics, Division of Hematology-Oncology and Pathology and Laboratory Medicine, Mattel Children's Hospital, David Geffen School of Medicine, University of California at Los Angeles; 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

Noah Federman, MD, is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, and Connective Tissue Oncology Society

Edited by J Martin Johnston, MD, Consulting Staff, Department of Pediatrics, Division of Hematology-Oncology, St Luke's Mountain States Tumor Institute; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; James L Harper, MD, Associate Chair for Medical Education in Pediatrics, Associate Professor of Pediatric Hematology-Oncology, University of Nebraska Medical Center; 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; and Robert J Arceci, MD, PhD, King Fahd Professor, Division of Pediatric Oncology, Johns Hopkins University School of Medicine

Author's Email:	Noah Federman, MD
Editor's Email:	J Martin Johnston, MD

eMedicine Journal, November 30 2006, VOLUME 7, Number 11

INTRODUCTION

Section 2 of 11

Background: Glanzmann, a Swiss pediatrician, initially described thrombasthenia in 1918 when he noted purpuric bleeding in patients with normal platelet counts. 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 (Nathan, 2003). 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 cross-linking of platelets and formation of a clot.

Specific deficiency

The platelet integrin GP IIb-IIIa (also referred to as aIIb-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 (Nurden, 2005). 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 (Lee, 1999). Although granule release still occurs, cross-linking 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 (Lee, 1999). 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 are extremely variable.

Frequency:

• In the US: 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.

• Internationally: 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 (Nurden, 2006).

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 recent 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 (Toogeh, 2004).

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

Section 3 of 11

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 (Nurden, 2006).



• 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 Lab 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 rate in GT.

DIFFERENTIALS

Section 4 of 11

Abdominal Trauma
Bernard-Soulier Syndrome
Birth Trauma
Child Abuse & Neglect: Physical Abuse
Epistaxis
Gastrointestinal Bleeding: Surgical Perspective
Head Trauma
Hematuria
Hemolytic-Uremic Syndrome
Meckel Diverticulum
Neonatal Sepsis
Von Willebrand Disease

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

Section 5 of 11

Lab 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 (Buyukasik, 2002).



• 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 demonstrate 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

Section 6 of 11

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 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 are thus refractory to platelet transfusions. Recombinant factor VIIa appears to enhance endothelial deposition of GP IIb-IIIa–deficient platelets. Combined with antifibrinolytic therapy, recombinant factor VIIa further stabilizes the newly formed clot (Nurden, 2006). Recombinant factor VIIa has been approved by the European Union for use in patients with GT and platelet refractoriness due to antibodies. The use of recombinant factor VIIa 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.



• HLA-matched sibling allogeneic stem cell transplantation (SCT) has been successfully performed, albeit very infrequently, 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 and only after all other options are considered. With the advent of novel techniques of removing GP IIb-IIIa isoantibodies such as protein A Sepharose immunoadsorption, the use of SCT as a therapy for GT may become even less frequent (Martin, 2002).

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 (Nurden, 2006). Recombinant factor VIIa 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

Section 7 of 11

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

Drug Category: 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.

Drug Name	Aminocaproic acid (Amicar) -- Synthetic competitive inhibitor of plasminogen activation. Preparations include 250 mg/mL PO syr, 500 mg PO tab, and IV susp.
Adult Dose	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 Dose	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
Contraindications	Documented hypersensitivity; evidence of active intravascular clotting process; DIC; use of IV product in newborns; hematuria (relative contraindication because urinary obstruction may result)
Interactions	Coadministration with estrogens may cause increase in clotting factors, leading to hypercoagulable state
Pregnancy	C - Safety for use during pregnancy has not been established.
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)

Drug Category: 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.

Drug Name	Desmopressin (DDAVP, Stimate) -- Synthetic vasopressin analog used to control severe bleeding.
Adult Dose	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 Dose	<3 months: Not established >3 months: Administer as in adults
Contraindications	Documented hypersensitivity; platelet-type vWD
Interactions	Coadministration with demeclocycline and lithium decreases effects; fludrocortisone and chlorpropamide increase effects of desmopressin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
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

Drug Category: 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.

Drug Name	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.
Adult Dose	110 mcg/kg IV bolus q90min for 4 doses; then q2h for 24 doses; then q3h for 20 doses Adjust dose to nearest 1.2-mg vial size
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Category: Hemostatic agents, topical -- These agents are used as an adjunct to achieve hemostasis.

Drug Name	Gelatin, topical absorbable (Gelfoam, Gelfilm) -- Used to provide hemostasis in surgery. Can be used for oral and dental surgery and with topical thrombin to stop epistaxis. Available in sponges, dental packs, and sterile powder.
Adult Dose	Apply packs or sponges dry or saturated with normal saline; hold in place with direct pressure until hemostasis achieved
Pediatric Dose	Administer as in adults
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
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Generally well tolerated; adverse effects may include increased incidence of infection; tissue compression due to fluid absorption, granuloma formation, or fibrosis

Drug Name	Thrombin, topical (Thrombostat, Thrombogen, Thrombinar) -- Used as an adjunct to achieve hemostasis. Topical thrombin catalyzes the conversion of fibrinogen to fibrin.
Adult Dose	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 Dose	Administer in adults
Contraindications	Documented hypersensitivity to drug or material of bovine origin
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Section 8 of 11

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.



• 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 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

Section 9 of 11

Medical/Legal Pitfalls:

• Failure to administer 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.

TEST QUESTIONS

Section 10 of 11

CME Question 1: Which of the following is unlikely to be confused with Glanzmann thrombasthenia?

A: Bernard-Soulier syndrome
B: Thrombocytopenia purpura
C: Gray platelet syndrome
D: Hemophilia B
E: None of the above (all are in differential)

The correct answer is D: Hemophilia B is caused by a deficiency of coagulation factor IX and is not a platelet-related deficiency. The bleeding of persons with thrombasthenia (and the other platelet disorders listed) is purpuric in nature, whereas hemarthrosis is more typical in individuals with hemophilias.

CME Question 2: Which of the following laboratory values is correct for the patient with thrombasthenia?

A: Increased activated partial prothrombin time
B: Decreased platelet counts
C: Increased bleeding time
D: Increased platelet size
E: None of the above

The correct answer is C: Normal platelet morphology and number and increased bleeding time are diagnostic of thrombasthenia.

Pearl Question 1 (T/F): Corticosteroids are the mainstays of therapy for a bleeding patient with thrombasthenia.

The correct answer is False: Corticosteroids have not been demonstrated to be efficacious in treating patients with thrombasthenia.

Pearl Question 2 (T/F): Transfusion of platelets is the only therapy consistently demonstrated to stop bleeding in individuals with thrombasthenia.

The correct answer is True: Bleeding in individuals with thrombasthenia requires the transfusion of normal platelets. Use human leukocyte antigen (HLA)–matched platelets to prevent alloimmunization complications.

Pearl Question 3 (T/F): Patients with thrombasthenia should receive human leukocyte antigen (HLA)–matched platelets.

The correct answer is True: Platelet transfusions can cause sensitization to HLAs, with resulting platelet destruction. Because they are likely to require multiple transfusions, patients with thrombasthenia should receive antigen-matched platelets. However, in the setting of severe bleeding without availability to HLA-matched platelets, platelet transfusion is still warranted.

Pearl Question 4 (T/F): The worst form of thrombasthenia is type 2.

The correct answer is False: Type 1 is the most severe form of the disease; patients with type 1 thrombasthenia have less than 5% of reference range glycoprotein (GP) IIb-IIIa levels.

BIBLIOGRAPHY

Section 11 of 11

• Arvin AM, Behrman RE, Kliegman R, eds: Nelson Essentials of Pediatrics. 3rd ed. Philadelphia, Pa: WB Saunders; 1998.
• Bellucci S, Damaj G, Boval B, et al: Bone marrow transplantation in severe Glanzmann's thrombasthenia with antiplatelet alloimmunization. Bone Marrow Transplant 2000 Feb; 25(3): 327-30[Medline].
• 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].
• Glanzmann E: Hereditare hamorrhagische thrombasthenie. Ein Beitrag zur Pathologie der Blutplattchen. J Kinderkranken 1918; 88: 113.
• Hoffman R, McGlave P, Shattil SJ, et al: Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 1999.
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• Lee GR, Foertser J, Lukens J, Paraskevas F: Wintrobe’s Clinical Hematology. 10th ed. Philadelphia, Pa: Williams & Wilkins; 1999.
• Lee TH, ed: Epocrates [computer program]. Version 4.0(B1). ePocrates Inc; 1999.
• 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].
• 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 2002 Dec; 119(4): 991-7[Medline].
• Nathan DG, Orkin SH: Nathan and Oski's Hematology of Infancy and Childhood. 6th ed. Philadelphia, Pa: WB Saunders.
• Nurden AT: Qualitative disorders of platelets and megakaryocytes. J Thromb Haemost 2005 Aug; 3(8): 1773-82[Medline].
• Nurden AT: Glanzmann thrombasthenia. Orphanet J Rare Dis 2006; 1(1): 10[Medline][Full Text].
• Poon MC, Demers C, Jobin F, Wu JW: Recombinant factor VIIa is effective for bleeding and surgery in patients with Glanzmann thrombasthenia. Blood 1999 Dec 1; 94(11): 3951-3[Medline][Full Text].
• Sassetti B, Lajmanovich A, Vazquez A, et al: Glanzmann thrombasthenia in children from Argentina. J Pediatr Hematol Oncol 1996 Feb; 18(1): 23-8[Medline].
• 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].

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