for vWD

• Platelet count—measured by automated methods

• PTT—measures anticoagulant portion of the factor VIII molecule

• Bleeding time—measures adhesion of platelets to site of injury

• vWF activity—measured by ristocetin-induced platelet aggregation (RIPA)

• Platelet count—measured by automated methods

• PTT—measures anticoagulant portion of the factor VIII molecule

• Bleeding time—measures adhesion of platelets to site of injury

• vWF activity—measured by ristocetin-induced platelet aggregation (RIPA)

• vWF antigen—measured by immunoassay

Most patients will have variable test results. It is recommended that this test profile be performed multiple times within a time period to aid in diagnosis.

Type 1

Type 2

Type 3

Genetics Autosomal Autosomal Autosomal dominant dominant recessive

Bleeding time T or N T T

vWF agn. i 4 Absent

*Secondary vWD variants include types 2A, 2B, 2M, and 2N: these are not discussed.

in Chapter 15, platelet glycoproteins play a significant role in hemostasis. The receptor for vWf is GP Ib-IX. This complex, Ib-IX, serves as a site for thrombin binding as well as regulating platelet shape and reactivity.18 GP IIb and IIIa are receptors for fibronectin (an adhesive protein for platelets), vWF, fibrinogen, and factors V and VIII. BSS is inherited as an autosomal recessive disorder, with near normal amounts of GPIb in heterozygotes. If the disorder is inherited homozygously, however, moderate or severe bleeding may occur. Epistaxis, gingival bleeding, menorrhagia, and purpura are the usual bleeding manifestation. Additionally, there is a thrombocytopenia with giant platelets observed on the peripheral smear. Ristocetin-induced platelet aggregation is absent in BSS patients since there are no receptors to bind to vWF, a key ingredient in ristocetin induced platelet aggregation. Platelet aggregation with other agents such as epinephrine, thrombin, and collagen appears normal. The bleeding time test is prolonged.

Platelet transfusions are the treatment of choice for active bleeding but they should be used prudently to prevent the stimulation of platelet antibodies. To date, over 30 mutations of the glycoproteins involved in the GP Ib-IX complex have been described.19

Glanzmann's Thrombasthenia

Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder, first described in 1918, most often associated with consanguinity. Homozygous individuals may experience variable bleeding patterns. When bleeding does occur, it is usually from birth as umbilical cord or circumcisional bleeding and may proceed to gingival bleeding, purpura, or prolonged bleeding from minor cuts or childhood events. The defect in GT is a deficiency or abnormality of GP lib and Ilia. These glycoproteins serve as the intermediary for fibrinogen binding to platelets, a necessary step in platelet aggregation. Aggregation cannot occur if GP Ilb/IIIa is absent or if there is an absence of fibrinogen or calcium.20 Patients with GT will have a prolonged bleeding time, normal platelet count and morphology, and abnormal aggregation with all aggregating agents except ristocetin. Ristocetin-induced aggregation depends upon the interaction of vWF and platelet GP Ib. The GP IIb/IIIa complex does not play a role in this type of aggregation. Treatment in GT depends upon the severity of the bleeding episode. Platelet transfusions may be considered but HLA-matched or ABO-matched transfusion may reduce the possibilities of platelet alloimmunization. Oral contraceptives may be used to control menorrhagia, and agents such as ethyleneaminocaproic acid (EACA) are effective topical thrombin-inducing agents for procedures such as tooth extractions.21

Platelet Release Defects

Once platelets adhere to an injured surface, the contents of the platelets are released. Platelets contain alpha and dense granules, which are highly metabolic substances containing procoagulant materials, vasoconstrictors ATP and ADP. The disorders that are described are inherited, usually have abnormal secondary phases of platelet aggregation, and show postoperative bleeding combined with menorrhagia and easy bruisability. In most of these disorders, the bleeding time is abnormal, but the platelet count may be normal.

Hermansky-Pudlak syndrome: An autosomal recessive disorder characterized by a severe deficiency of dense granules. Patients show albinism and may have hemorrhagic events.

Chediak-Higashi syndrome: An autosomal recessive disorder, in which patients show albinism and giant lysosomal granules in neutrophils. Not only are the white cells in these patients qualitatively flawed, but platelet release is impaired. Patients show frequent infections because of impaired phagocytic ability and death usually occurs in childhood. Patients manifest throm-bocytopenia and increased liver and spleen.

Wiskott-Aldrich syndrome: This is an X-linked recessive disorder in which patients show severe eczema, recurrent infections, immune defects, and thrombocytopenia.

Thrombocytopenia with absent radii (TAR): A rare disorder of the skeletal system in which patients have no radial bones and other skeletal and cardiac abnormalities. Thrombocytopenia is seen in most patients.

Gray platelet syndrome: Platelets show a lack of alpha granules and are noted in the peripheral smear as appearing larger, having a gray or blue-gray color. Patients may show thrombocytope-nia, bleeding tendencies, and bruisability

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