eMedicine Specialties > Pediatrics: General Medicine > Hematology
Thrombasthenia: Treatment & Medication
Updated: Nov 18, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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.
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
Coadministration with estrogens may cause increase in clotting factors, leading to hypercoagulable state
Documented hypersensitivity; evidence of active intravascular clotting process; DIC; use of IV product in newborns; hematuria (relative contraindication because urinary obstruction may result)
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.
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
Coadministration with demeclocycline and lithium decreases effects; fludrocortisone and chlorpropamide increase effects of desmopressin
Documented hypersensitivity; platelet-type vWD
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.
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
None reported
Documented hypersensitivity
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.
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
None reported
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
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.
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
None reported
Documented hypersensitivity to drug or material of bovine origin
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
More on Thrombasthenia |
| Overview: Thrombasthenia |
| Differential Diagnoses & Workup: Thrombasthenia |
 Treatment & Medication: Thrombasthenia |
| Follow-up: Thrombasthenia |
| References |
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References
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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].
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Further Reading
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
