You are in: eMedicine Specialties > Pediatrics: General Medicine > Hematology Bernard-Soulier SyndromeArticle Last Updated: Jul 31, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: John D Geil, MD, Associate Professor of Pediatrics, Division of Hematology/Oncology, University of Kentucky College of Medicine; Consulting Staff, Department of Pediatric Hematology/Oncology, University of Kentucky Children's Hospital John D Geil is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology Editors: Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Gary D Crouch, MD, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences; David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville; Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Department of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine Author and Editor Disclosure Synonyms and related keywords: Bernard-Soulier syndrome, BSS, hereditary platelet disorder, bleeding disorder, coagulation disorder, giant platelets, thrombocytopenia, bleeding tendency, May-Hegglin anomaly, gray platelet syndrome, von Willebrand factor, vWF INTRODUCTIONSection 2 of 10
  BackgroundBernard-Soulier syndrome (BSS) was first described in 1948 as a congenital bleeding disorder characterized by thrombocytopenia and large platelets. The disorder was recognized to be familial and inherited in an autosomal recessive manner. In the 1970s, the molecular defect was shown to involve the absence of a platelet membrane glycoprotein. BSS is one of a group of hereditary platelet disorders characterized by thrombocytopenia, giant platelets, and a tendency toward bleeding. Other disorders in this category are the May-Hegglin anomaly and gray platelet syndrome. PathophysiologyThe underlying biochemical defect is the absence or decreased expression of the glycoprotein Ib/IX/V complex on the surface of the platelets. This complex is the receptor for von Willebrand factor (vWF), and the result of decreased expression is deficient binding of vWF to the platelet membrane at sites of vascular injury, resulting in defective platelet adhesion. This is demonstrated by the lack of aggregation of platelets in response to ristocetin, an antibiotic that normally causes platelets to aggregate. The end result is the lack of formation of the primary platelet plug and increased bleeding tendency. The cause of the thrombocytopenia is not definitely known, but it is probably related to a decreased platelet life span. FrequencyUnited StatesThis syndrome is rare, with an estimated occurrence of less than 1 case per million population. Mortality/MorbidityBleeding tendency is variable in severity. Bleeding can be severe with injury or surgery. RaceBSS is a rare disorder described primarily in Caucasians of European ancestry, as well as in the Japanese population. However, prevalence in other ethnic groups is unknown. SexMales and females are affected with equal frequency. AgeBleeding due to BSS may begin in infancy and may continue with varying severity throughout life. CLINICALSection 3 of 10
HistorySymptoms are consistent with low or dysfunctional platelets and include easy bruising, nosebleeds, mucosal bleeding, menorrhagia, and, occasionally, gastrointestinal bleeding. The severity of symptoms may be widely variable. PhysicalThe physical examination findings are consistent with low or dysfunctional platelets and may include increased bruising and mucosal bleeding. CausesBernard-Soulier syndrome is inherited in an autosomal recessive fashion, so males and females are affected with equal frequency. Heterozygotes usually have no bleeding manifestations. DIFFERENTIALSSection 4 of 10
May-Hegglin Anomaly Von Willebrand Disease
|
| Drug Name | Aminocaproic acid (Amicar) |
|---|---|
| Description | Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. The main problems are that the thrombi that form during treatment are not lysed and effectiveness is uncertain. |
| Adult Dose | 30 g/d PO/IV in divided doses q3-6h; not to exceed 30 g/d |
| Pediatric Dose | Loading dose: 100-200 mg/kg PO/IV Maintenance dose: 100 mg/kg/dose q4-6h; not to exceed 30 g/d |
| Contraindications | Documented hypersensitivity; evidence of active intravascular clotting process; disseminated intravascular coagulopathy (differentiate between disseminated intravascular coagulopathy and hyperfibrinolysis because aminocaproic acid can be fatal in patients with disseminated intravascular coagulation) |
| Interactions | Coadministration with estrogens may cause increase in clotting factors, leading to a hypercoagulable state |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Do not administer unless a definite diagnosis of hyperfibrinolysis has been made; caution with cardiac, hepatic, or renal disease; avoid rapid IV administration because this may induce hypotension, bradycardia, and/or arrhythmia |
| Drug Name | Tranexamic acid (Cyklokapron) |
|---|---|
| Description | Alternative to aminocaproic acid. Inhibits fibrinolysis by inhibiting plasminogen activators. |
| Adult Dose | 25 mg/kg PO tid/qid for 2-8 d |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Thrombolytics antagonize effect; anti-inhibitor coagulant complex or factor IX complex may increase thrombosis risk |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Caution in renal dysfunction or upper urinary tract bleeding and history of thromboembolic disease or DIC |
Desmopressin stimulates factor VIII, prostaglandins, and plasminogen release, but the mechanism of action is not clear and may not be common to all 3 substances. These agents possess effect on vessel walls that produces an increase in platelet adhesion. This local hemostatic action may account for its hemostatic properties.
| Drug Name | Desmopressin acetate (DDAVP, Stimate) |
|---|---|
| Description | Used to decrease bleeding time in some, but not all, patients with BSS. It may be useful for minor bleeding episodes. The exact mechanism for this is unknown, but it may relate to increased levels of von Willebrand factor binding to some residual glycoprotein Ib in patients without an absolute deficiency. |
| Adult Dose | IV (DDAVP): 0.3 mcg/kg IV Intranasal (Stimate 1.5 mg/mL): <50 kg: 150 mcg (1 spray in one nostril) intranasally >50 kg: 300 mcg (1 spray in each nostril) intranasally |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; platelet-type von Willebrand disease |
| Interactions | Coadministration with demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects of desmopressin |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Avoid overhydration in patients using desmopressin to benefit from its hemostatic effects; restrict free water intake to avoid hyponatremia; mild facial flushing and headache are possible |
Hemostasis is the physiological response to bleeding. Injury and factors released by platelets initiates the coagulation cascade, which is mediated by blood clotting factors. This results in formation of an insoluble fibrin clot, thus reinforcing the initial platelet plug. Clotting factors (ie, antihemophilic factor [factor VIII], factor VII, or IX) function as cofactors in the blood coagulation cascade.
| Drug Name | Antihemophilic factor, recombinant (Factor VII, Kogenate) |
|---|---|
| Description | Experience with the use of recombinant activated factor VII is limited in patients with congenital platelet disorders. Safety and efficacy still are being evaluated. |
| Adult Dose | 70-110 mcg/kg IV |
| Pediatric Dose | Not established, limited data exist; administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Not evaluated adequately |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus |
| Precautions | Monitor patients for signs or symptoms of activation of the coagulation system or thrombosis; because of limited experience, use caution with prolonged dosing; risk of thrombotic adverse events after treatment is unknown |
Bernard-Soulier Syndrome excerpt
Article Last Updated: Jul 31, 2007
