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2046 Part XII: Hemostasis and Thrombosis Chapter 120: Hereditary Qualitative Platelet Disorders 2047

approximately 50 percent but did not alter function. A series of pre- Laboratory Features
diction tools indicated that somewhere between 45 and 74 percent of Table 120–3 provides characteristic laboratory findings in GT. Patients
the 114 novel missense mutations may be deleterious. Thus, perhaps have normal platelet counts and morphology, prolonged bleeding
approximately 0.6 percent of individuals in the general population is times, decreased or absent clot retraction, and abnormal platelet aggre-
a silent carrier for a GT variant that profoundly affects structure and/ gation responses to physiologic stimuli. The initial slope of high-dose
or function. In addition, some of the rare individuals in the healthy ristocetin-induced aggregation is normal (or near normal), reflecting
population with levels of integrin α β receptor expression intermedi- the normal plasma VWF and the normal platelet GPIb/IX content; at
IIb 3
ate between those of obligate GT carriers and normal individuals may lower doses of ristocetin, however, where GPIb/IX–mediated activation
reflect heterozygosity for “hypomorphic” variants that partially affect of integrin α β (Chap. 112) normally contributes to the aggregation
IIb 3
receptor expression, but not function. 112 response, patients have decreased second wave aggregation. GT plate-
116
lets undergo normal shape change in response to ADP and thrombin,
demonstrating their ability to undergo metabolic and cytoskeletal
Clinical Features changes in response to these agents. Similarly, high doses of thrombin
Table 120–2 summarizes the clinical manifestations of 177 patients and collagen produce normal release of dense body and α-granule con-
with GT obtained from two reviews. 22,33 Menorrhagia occurs in nearly tents 18,20,117 ; the decreased secretion observed with lower doses of these
all female patients. Purpura can be present immediately after birth but agents reflect the lack of augmentation of the release reaction normally
often is not dramatic. Petechiae of the face and subconjunctival hem- produced by platelet aggregation. 18,116,118–120
orrhage associated with crying may be the first symptoms in neonates Platelets in whole blood or platelet-rich plasma adhere to glass
and babies. Spontaneous hemarthroses and central nervous system because fibrinogen first becomes deposited on the glass and the platelets
bleeding are very rare. The hemorrhagic diathesis in patients with GT then adhere to the immobilized fibrinogen. 121,122 Platelets from patients
is notable for its variability and the lack of correlation between the
biochemical platelet abnormalities and clinical severity. Even within
22
groups of patients such as the Iraqi Jews, most of whom share the same
genetic α or β subunit abnormalities, there is a wide spectrum of TABLE 120–3. Laboratory Features of Glanzmann
IIb
3
clinical severity. 33,39 Moreover, the severity of bleeding symptoms can Thrombasthenia
vary significantly during the lifetime of individual patients. GT does not I. Platelet count: Normal
appear to protect against the development of atherosclerosis as judged
by the carotid artery intima-to-media ratio. Carriers of GT are usually II. Bleeding time: Markedly prolonged
113
asymptomatic or only mildly symptomatic and generally have normal III. Tests of platelet function
results in platelet function tests. 22,33,112,114,115 A. Platelet aggregation
1. Epinephrine—no observable response
2. ADP and thrombin—shape change, but no aggregation
3. Collagen—shape change followed by variable increase
TABLE 120–2. Bleeding in Patients with Glanzmann in light transmission most likely from progressive adhe-
Thrombasthenia sion to collagen fibers (pseudoaggregation)
4. Ristocetin—normal initial slope of aggregation; at low
No. of Affected Frequency doses, inhibition of second wave; at high doses, cyclical
Patients (%) aggregation–disaggregation
SYMPTOMS B. Aperture closure time (PFA-100): Prolonged
Menorrhagia 54/55 98 C. Clot retraction: Absent or reduced
Easy bruising, purpura 152/177 86 D. Platelet release reaction: Decreased with epinephrine and
low-dose adenosine diphosphate (ADP), thrombin, and
Epistaxis 129/177 73 collagen; normal with high-dose thrombin and collagen
Gingival bleeding 97/177 55 E. Interaction with glass (platelet retention test): Absent or
Gastrointestinal hemorrhage 22/177 12 reduced
F. Platelet coagulant activity: Variably abnormal
Hematuria 10/177 6
G. Microparticle formation: Variably abnormal
Hemarthrosis 5/177 3
H. Ex vivo interaction with deendothelialized blood vessels in
Intracranial hemorrhage 3/177 2 flow chambers: Marked abnormality in platelet thrombus
Visceral hematoma 1/177 1 formation and defective platelet spreading; decreased
platelet adhesion at high shear rates
SEVERITY IV. Tests of α β and α β receptors: Number and functional
Requirement for red cell transfusions integrity IIb 3 V 3
Patients from literature* 32/48 67 A. α β content: Reduced or absent, except in variants
IIb 3
Paris patients 54/64 84 B. α β content: Reduced or absent in patients with β 3
V 3
defects; normal or increased in patients with α defects
IIb
*Data are from 177 patients reviewed by George and colleagues of C. Platelet binding of fibrinogen and other adhesive glyco-
22
whom 113 were from the literature and 64 were studied in Paris. proteins to α β : Reduced or absent
IIb 3
Reproduced with permission from Coller BS. Inherited disorders of D. Platelet fibrinogen content: Markedly reduced, except in
platelet function. In: Bloom AL, editor. Hemostasis and Thrombosis. some variants
UK: Churchill Livingstone p. 721–766, 1992.

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