Hematol Oncol Clin N Am 21 (2007) 647–661

HEMATOLOGY/ONCOLOGY CLINICS
OF NORTH AMERICA
Acquired Platelet Dysfunction
Yu-Min P. Shen, MD*, Eugene P. Frenkel, MD
The University of Texas Southwestern Medical Center at Dallas,
5323 Harry Hines Boulevard, Dallas, TX 75390-8852, USA

A
cquired platelet dysfunction is encountered frequently in clinical prac-
tice. The usual clinical presentation is that of mucosal bleeding, epi-
staxis, or superficial epidermal bleeds; in general, the bleeding is
modest in degree. Often, the dysfunctional platelets are related to a medication
or a systemic disorder. Normally, when platelets are exposed to damaged
endothelium, they adhere to the exposed basement membrane collagen and
change their shape from smooth disks to spheres with pseudopodia. Then, they
secrete the contents of their granules, a process referred to as the release reac-
tion. Additional platelets form aggregates on those platelets that have adhered
to the vessel wall. As a result, the primary hemostatic plug is formed, and
bleeding is arrested. This article reviews the various forms of acquired platelet
dysfunction that result in decreased platelet aggregation, adhesion, or secretion.
Please refer to the article elsewhere in this issue for a comprehensive review of
the laboratory assessment for platelet function. These tests are appropriate and
important when the bleeding is significant or persistent and is not clearly ex-
plained by the clinical and drug causes defined in this article.
In addition to the classic mechanisms of platelet dysfunction resulting in
decreased function of the platelets, platelet defects with gain-of-function abnor-
mality are being recognized increasingly as a clinical entity. For instance, hep-
arin-induced thrombocytopenia results in a transient, but highly thrombogenic,
condition that is due to ‘‘hyperfunction’’ of platelets. The hyperactive platelet
syndrome (or sticky platelet syndrome) is an uncommon, but well-described,
entity that results in thrombosis of arterial or venous systems as well as com-
plications during pregnancy. These gain-of-function platelet abnormalities are
reviewed elsewhere in this issue.

PLATELET DYSFUNCTION ASSOCIATED WITH SYSTEMIC

DISEASE
Uremia
Uremic patients have complex hemostatic defects that include thrombocytope-
nia, coagulation abnormalities, and platelet dysfunction. Clearly, platelet

*Corresponding author. E-mail address: yu-min.shen@utsouthwestern.edu (Y-M.P. Shen).

0889-8588/07/$ – see front matter ª 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.hoc.2007.06.001 hemonc.theclinics.com
648 SHEN & FRENKEL

dysfunction is the most consistent and clinically relevant change. Commonly,

patients in renal failure have prolonged bleeding times that actually correlate
better with the degree of anemia than with the expected platelet numbers [1].
The basis of the dysfunction seems to be complex; however, increased con-
centrations of L-arginine and cyclic guanosine monophosphate, as well as
increased nitric oxide production by uremic platelets, seem to provide the
most important pathophysiologic mechanism and pose a possible role for nitric
oxide in uremic bleeding [2]. In addition, abnormal platelet adhesion to the sub-
endothelial surface has been demonstrated [3]. A variety of studies has impli-
cated other mechanisms, but the findings have been inconsistent and difficult
to assess. For instance, the amount of von Willebrand factor (VWF), as well
as its multimer pattern, antigen to activity ratios have been described as normal
and abnormal [4]. Similarly, platelet glycoprotein (GP) Ib/IX receptor number
and function have been shown to be normal and reduced [5]. Platelets from
uremic patients show reduced shear-induced platelet aggregation with high
shear rates [6], possibly due to increased proteolysis by ADAMTS13 VWF
metalloprotease. Defective activation-dependent receptor function of GP IIb/
IIIa for binding fibrinogen and VWF in uremic patients has been reported,
even though the number of receptors was normal [5]. In the laboratory, the
classic evaluation examines aggregation with exogenous agents (collagen,
ADP, and epinephrine); this is reduced in most uremic patients, with a higher
threshold minimum concentration needed to induce platelet aggregation [7].
Indeed, altered aggregation is used commonly as the laboratory documentary
test. Finally, defective platelet secretion of ADP has been reported with
increased platelet concentrations of adenylate cyclase and cyclic adenosine
monophosphate, as well as a diminished increase in platelet cytosolic calcium
concentration [8,9]. Thus, a dazzling array of multiple abnormalities in various
aspects of platelet function has been described. There is no unifying pathophys-
iologic mechanism that accounts for all of the recognized platelet defects that
are seen in uremic patients, nor is there a crisp relationship of these findings
to the bleeding diathesis.
Therapy for uremic platelet dysfunction with bleeding is hemodialysis or
peritoneal dialysis, despite a transient worsening of platelet function immedi-
ately after dialysis [10]. The clear role of dialysis has led to the legendary ex-
ploration of the many soluble factors discussed above. The relevance of such
factors has been emphasized further by the observation that platelet function
returns to normal 8 weeks after renal transplant [11]. The rheologic effect
from transfusion of packed red blood cells or improvement of anemia by eryth-
ropoietin therapy also is associated with decreased uremic bleeding, shortening
of the bleeding time, and increased platelet adhesiveness [12,13]; however, cau-
tion must be exercised when instituting erythropoietin therapy, because an
increase in fistula thrombosis was observed in a placebo-controlled trial [14].
The administration of cryoprecipitate or 1-desamino-8d-arginine vasopressin
(DDAVP) shortens the bleeding time and is temporarily effective in the control
of uremic bleeding in some patients [15,16], which may relate to improvement
ACQUIRED PLATELET DYSFUNCTION 649

in platelet adhesion and enhanced VWF activity [17]. Reduction in the severity
of uremic bleeding was reported after administration of conjugated estrogens
[18], but a single perioperative dose did not improve hemostasis [19].
Liver Disease
Often, platelet dysfunction is overlooked in patients who have acute or chronic
liver disease with a bleeding diathesis. As in uremia, platelet dysfunction asso-
ciated with liver disease is multifactorial. Aggregation studies demonstrated
blunted aggregation to collagen, thrombin, and ristocetin and absent secondary
aggregation waves after aggregation with ADP and epinephrine [20]. Altered
platelet membrane palmate and stearate metabolism also may contribute to
the platelet dysfunction [20]. Ingestion of alcohol may worsen the observed
underlying dysfunction by inducing a storage pool–type defect with decreased
ADP and ATP, as well as inhibition of thromboxane A2 synthesis [21].
Increased fibrin split products that are due to a primary activation of the fibri-
nolytic system—compounded by decreased clearance—interfere with the func-
tion of platelet surface glycoproteins and result in clinically significant
platelet dysfunction [22]. If platelet dysfunction is documented in a bleeding
patient who has liver disease, platelet concentrates should be given along
with careful use of DDAVP [23].

Paraproteinemia
Bleeding diathesis often complicates paraproteinemia because of multiple mye-
loma, Waldenström’s macroglobulinemia, monoclonal gammopathy of un-
determined significance, or polyclonal hypergammaglobulinemia [24–26].
Proposed mechanisms include thrombocytopenia, qualitative platelet dysfunc-
tion, inhibitors to plasma coagulation factors, enhanced clearance of plasma
coagulation factors, and hyperviscosity syndrome [24]. Bleeding is more com-
mon in patients who have IgA myeloma and macroglobulinemia and usually is
limited to purpura and mucous membrane bleeding [27]. Abnormalities in
bleeding time and other platelet function tests have been documented. The
platelet dysfunction is believed to result from nonspecific binding of the immu-
noglobulins to the platelet surface [28], although specific antigen–antibody
interactions have been reported in a few patients [29]. Plasmapheresis is an
effective therapeutic approach for clinically significant bleeding. Platelet trans-
fusion likely is not beneficial unless the paraproteinemia is well controlled.
Myeloproliferative Disorders
Chronic myeloproliferative disorders (CMPD) are characterized by thrombotic
and hemorrhagic complications. Patients frequently present with ecchymoses,
epistaxis, gastrointestinal bleeding, and a propensity for serious hemorrhage
after trauma or even minor surgical procedures. Often, the laboratory abnor-
malities demonstrated are inconsistent, and the correlation with severity of
the bleeding diathesis is poor [30]. The platelet dysfunction in CMPD seems
to be determined at the level of the committed megakaryocyte [31]. The abnor-
malities described include defective aggregation and release reaction, deficient
650 SHEN & FRENKEL

lipid peroxidation and responses to thromboxane A2, subnormal serotonin up-

take and storage, abnormal expression of Fc receptors, and a combined defect
in membrane expression and activation of GP IIb/IIIa complexes [32–37].
Acquired storage pool disorder [38] and platelet dysfunction that are due to a
reduction in the high molecular weight forms of plasma and platelet VWF [39]
are well-characterized defects in CMPD. The VWF-like defect is believed to
result from increased proteolysis of the high molecular weight VWF that is
due to increased binding to platelets and, thus, enhanced proteolysis by
ADAMTS13 [40]. In support of this hypothesis, VWF multimer analysis nor-
malizes with the reduction in the cell counts [41]. Platelet function studies are
prudent in patients who have CMPD and are suffering from excessive bleeding
(or clotting, which can happen with gain-of-function defects [42]).
Myelodysplastic Syndrome
Patients who have the myelodysplastic syndrome (MDS) often have a bleeding
diathesis that is due to thrombocytopenia or chronic disseminated intravascular
coagulation; however, as a result of dysplastic megakaryopoiesis, specific plate-
let dysfunction also may contribute to the bleeding manifestations of the patient
who has MDS. Often, the megakaryocytes are small with decreased lobation
and decreased granularity [43,44]. Ultrastructural studies with electron micros-
copy demonstrate dilated canalicular system and abnormal microtubular for-
mation [45]. Changes in granules are variable and can be reduced or giant
granules may form by the fusion of several single granules [46]. An acquired
membrane defect with abnormal glycoprotein expression occurs [32]. The
delineation of platelet dysfunction in MDS is difficult to define because of
the frequent presence of thrombocytopenia; however, platelet numbers do
not explain the bleeding diathesis well because the bleeding time commonly
is prolonged well out of proportion to the platelet count, and multiple platelet
aggregation defects can be documented [47].
Antiplatelet Antibody Lesions
Normally, about 100 IgG molecules are found on the surface of platelets [48].
Most tests evaluating increased IgG on the platelet surface do not distinguish
between pathogenic autoantibodies and nonspecific antibodies. Thus, despite
reports of increased antibody binding to platelets in immune-mediated throm-
bocytopenic purpura, systemic lupus erythematosus, and platelet alloimmuni-
zation, it is difficult to assess the potential adverse effects of these antiplatelet
antibodies. In most instances, the surviving platelets function normally; in a mi-
nority of patients with antiplatelet antibodies, the degree of bleeding manifesta-
tion is clearly out of proportion to the decreases in platelet count [49].
Most antibodies specific for platelet antigens are directed against the GP IIb/
IIIa complex [50]; antibodies against GP Ib/IX/V [51], GP Ia/Iia [52], and GP
IV [50] have been described as well. These antibodies interfere with the normal
functions of the respective target antigens to result in platelet dysfunction that
is due to impaired aggregation. Platelet aggregation studies demonstrated
decreased aggregation in response to ristocetin, ADP, epinephrine, or collagen
ACQUIRED PLATELET DYSFUNCTION 651

[53,54]. In addition, acquired storage pool deficiency may result from antibody-
induced platelet activation by way of Fc receptors or from interference with
uptake of substances into platelet granules during megakaryopoiesis [55,56].
Patients who have storage pool defects are expected to have absent second
wave aggregation or decreased ATP secretion on lumiaggregation study.
Treatment is directed at the underlying autoimmune process.

Disseminated Intravascular Coagulation

In addition to a bleeding diathesis from the consumption of coagulation factors
and platelets, patients who have disseminated intravascular coagulation experi-
ence qualitative platelet defects with reduced platelet aggregation and an
acquired storage pool deficiency [57]. These result from in vivo platelet activa-
tion by thrombin or other agonists. Also, fibrin and fibrinogen degradation
products interfere with platelet function as has been shown in ex vivo studies
with purified low molecular weight fibrinogen degradation products; however,
the true clinical relevance is uncertain, because a significantly high concentra-
tion of fibrinogen degradation products is unlikely to occur in vivo [58]. Typ-
ically, the significance of platelet dysfunction in disseminated intravascular
coagulation is overshadowed by the hemostatic defects resulting from the
thrombocytopenia and consumptive coagulopathy.

PLATELET DYSFUNCTION ASSOCIATED

WITH CARDIOPULMONARY BYPASS
Patients undergoing cardiopulmonary bypass may experience a variety of
hemostatic problems, including thrombocytopenia, hyperfibrinolysis, and qual-
itative platelet defects. The platelet dysfunction induced by the bypass circuit is
manifested as a prolonged bleeding time, abnormal ex vivo platelet aggregation
in response to several agonists, decreased platelet agglutination in response to
ristocetin, and deficiency of a and dense granules [59–62]. The severity of these
abnormalities correlates with the duration of extracorporeal bypass, and the ab-
normalities resolve within 2 to 24 hours after the patient comes off bypass [63].
The bypass-induced platelet defects likely result from platelet activation and
fragmentation [64,65] that are due to hypothermia, contact with fibrinogen-
coated synthetic surfaces, contact with blood–air interface, damage caused by
blood suctioning, and exposure to traces of thrombin, plasmin, ADP, or com-
plement [66,67]. Drugs (eg, heparin, protamine, and aspirin) and production of
fibrin degradation products can be expected to impair platelet function further
[68–70].
The therapy for bypass-induced platelet dysfunction includes DDAVP, pros-
tacyclin or its analog Iloprost, protease inhibitor aprotinin, and antifibrinolytic
agents, such as e-aminocaproic acid and tranexamic acid. DDAVP can shorten
the bleeding time, but trials in patients who have undergone bypass have
shown contradictory results [71,72]. With the assumption that the platelet dys-
function results from platelet activation, activation inhibitors (eg, prostacyclin
and prostaglandin E2) have been studied in human and animal models;
652 SHEN & FRENKEL

however, randomized trials with prostacyclin and Iloprost did not show a clear
benefit, perhaps limited by significant toxicities [73,74]. Aprotinin and the anti-
fibrinolytic agents can reduce or inhibit the hyperfibrinolysis that is seen with
cardiopulmonary bypass, thus reducing the fibrin degradation products present
[75,76]. After a careful evaluation for surgical causes of bleeding, judicious
transfusion of platelets and plasma is appropriate. If the bleeding manifestation
is that of platelet dysfunction with mucocutaneous bleeding, DDAVP should
be considered. If excessive wound bleeding is observed after initial hemostasis
to suggest hyperfibrinolysis, aprotinin or -aminocaproic acid and tranexamic
acid should be considered.

PLATELET DYSFUNCTION ASSOCIATED WITH DRUGS

Drug-induced qualitative platelet dysfunction is clearly the most common cause
of acquired platelet dysfunction. The list of medications or dietary supplements
that are associated with platelet dysfunction is long and growing (Box 1). These
include aspirin and other nonsteroidal anti-inflammatory drugs, thienopyri-
dine, antibiotics, cardiovascular drugs, psychotropic drugs, and dietary items,
such as herbal supplements, among others. In a healthy individual, drug-
induced platelet dysfunction is usually of no clinical significance; however, in
a patient who has coagulation disorders, uremia, or thrombocytopenia and
in patients who are undergoing surgery or anticoagulation therapy, impairment
of platelet function by drugs may lead to serious bleeding. Some drugs may
lead to prolonged bleeding time without clinical bleeding, whereas others
only cause dysfunction when added to platelets in vitro.

Aspirin
Acetylsalicylic acid is a potent and irreversible inhibitor of the platelet cycloox-
ygenase (COX-1 > COX-2), the enzyme responsible for the conversion of
arachidonic acid into prostaglandins, in particular, thromboxane A2 [77]. Con-
sequently, the platelet release reaction is inhibited—an event that occurs within
15 to 30 minutes after ingestion with doses as low as 40 to 80 mg—and persists
as long as the affected platelet survives (8–10 days). Thus, a single small dose of
aspirin impairs the release reaction for up to 96 hours [78]. Although prostacy-
clin synthesis by endothelial cells also is inhibited by aspirin, the endothelial cell
with a nucleus is able to replenish the cyclooxygenase. With the incomplete
inhibition of prostacyclin production by endothelial cells, coupled with the
complete irreversible inhibition of thromboxane A2 synthesis by platelets, the
overall result is an antithrombotic effect [78].
The effect of aspirin on platelet function is highly variable, with a significant
minority of the population considered resistant to aspirin [79]. Aspirin-induced
platelet dysfunction results from interference with platelet aggregation rather
than adhesion. Aspirin-treated platelets adhere normally when perfused
through denuded arterial segments; however, they do not interact with one
another [80]. Aggregometry tracings from aspirin-treated platelets show
absence of arachidonic acid–induced aggregation, impaired collagen-induced
ACQUIRED PLATELET DYSFUNCTION 653

Box 1: Common drugs affecting platelet function

Analgesics
Aspirin
Nonsteroidal anti-inflammatory drugs
Thienopyridines
Ticlopidine
Clopidogrel

b-Lactam antibiotics
Penicillins
Cephalosporins
Cardiovascular
Nitrates
Calcium channel blockers
Quinidine
GP IIb/IIa antagonists
Abciximab
Tirofiban
Eptifibatide

Psychotropic
Antidepressants
Phenothiazines
Herbal supplements
Fish oil
Garlic
Black tree fungus
Ginkgo biloba
Cumin
Turmeric

aggregation, and the absence of the secondary wave of aggregation induced by

epinephrine and ADP. Aspirin-treated platelets also fail to release normal
amounts of ADP, ATP, and serotonin [81].
Aspirin has a dose-dependent toxic effect on the gastrointestinal mucosa,
with a predictable blood loss from ingestion of aspirin [82]. Studies have shown
that aspirin primarily affects surgical bleeding in patients who are undergoing
surgery in areas of increased fibrinolytic activity (oral cavity or genitourinary
tract) or in patients with other coexisting coagulopathy [83]. In general, aspirin
654 SHEN & FRENKEL

should be avoided before cardiothoracic, plastic, and neurosurgical procedures

in which the limits of tolerable bleeding are narrow [84]. Infusion of DDAVP
has been effective in correcting a prolonged bleeding time that is due to aspirin
[85]. In more emergent cases of hemorrhage, platelet transfusion should be
given.
Nonsteroidal Anti-Inflammatory Drugs
Nonsteroidal anti-inflammatory drugs, such as ibuprofen, indomethacin, nap-
roxen, phenylbutazone, and sulfinpyrazone, also inhibit prostaglandin synthe-
sis by inhibition of COX [86]. In contrast to aspirin, their inhibition of COX-1
is reversible and generally short acting. The exception is piroxicam, which has
a long half-life measured in days [81]. These drugs may cause a transient pro-
longation of the bleeding time that usually is clinically insignificant. In fact, ibu-
profen can be given safely to hemophiliacs [87]. The COX-2 inhibitors interfere
with COX without affecting platelet function [88], whereas acetaminophen,
salicylate, and narcotics do not inhibit COX [87].
Thienopyridines
Ticlopidine and clopidogrel are antithrombotic agents that are used extensively
in the treatment of arterial diseases. They are more effective than aspirin in the
secondary prevention of cerebrovascular and cardiovascular events [89]. The
thienopyridines are additive with aspirin in preventing thrombotic complica-
tions after coronary artery stent placement [90]. The effects of ticlopidine
and clopidogrel on platelet aggregation and the bleeding time may be seen
within 24 to 48 hours of the first dose but do not reach maximum for 4 to 6
days. The effects on platelet function may last for 4 to 10 days after the drugs
have been discontinued, suggesting that the megakaryocytes also may be
affected [89].
The thienopyridines interfere with platelet function through a noncompeti-
tive inhibition of ADP binding to its low-affinity receptor, P2Y12 [91]. Platelet
aggregation studies demonstrated decreased aggregation to low concentrations
of many agonists, particularly ADP. Because ADP released from platelet-dense
granules and red blood cells at the site of injury plays a major role in the plate-
let responses to the other agonists, interference with the ADP effect by thieno-
pyridine may account for the observed effect on platelet aggregation. The
antithrombotic effect of thienopyridine results from impaired fibrinogen bind-
ing to GP IIb/IIIa, which is uncoupled from the ADP receptor [92].
Antibiotics
b-Lactam antibiotics can produce platelet dysfunction in vitro and ex vivo.
Patients receiving b-lactam antibiotics may have prolonged bleeding time
with a propensity for bleeding, especially if they have renal insufficiency or
are undergoing surgical procedures. The effect can be well documented by
aggregation studies, which demonstrate a dose-dependent reduction in aggrega-
tion in response to ADP, epinephrine, and collagen. Ristocetin-induced platelet
agglutination also is reduced, providing evidence that platelet adhesion also is
ACQUIRED PLATELET DYSFUNCTION 655

impaired [93]. These drugs seem to bind to and modify the platelet membrane,
resulting in decreased agonist binding and decreased calcium influx [94]. These
effects can be observed after several days of antibiotic treatment and may not
resolve for 7 to 10 days after discontinuation of the drugs. From these obser-
vations, it can be inferred that the antibiotic effects are irreversible or that
the megakaryocyte membrane is similarly affected. Penicillins and cephalospo-
rins that have an a-carboxy group adjacent to the b-lactam ring are most likely
to produce platelet dysfunction and clinical bleeding [95].
Glycoprotein IIb/IIIa Antagonists
GP IIb/IIIa antagonists are antithrombotic agents that are used extensively in
the setting of ischemic coronary artery disease and interventions [96]. Because
the absence or defective GP IIb/IIIa results in the inherited bleeding disorder
Glanzmann thrombasthenia, it is not surprising that patients receiving the
GP IIb/IIIa antagonists can have a bleeding diathesis with mucocutaneous
bleeding [97]. In addition to qualitative platelet dysfunction, a small percentage
of patients receiving these drugs may develop moderate to severe thrombocy-
topenia [98]. These must be differentiated from drug-induced platelet clumping
and heparin-induced thrombocytopenia. The risk for bleeding can be
decreased by using a lower dose of heparin and avoiding treatment of patients
who are receiving warfarin at therapeutic doses [99]. The platelet dysfunction is
reversed rapidly by platelet transfusion. Examples of GP IIb/IIIa inhibitors in
clinical use include abciximab (chimeric human-murine anti-GP IIb/IIIa mono-
clonal antibody Fab fragment), tirofiban, and eptifibatide (synthetic low molec-
ular weight GP IIb/IIIa inhibitors).

Cardiovascular Drugs
Several vasodilators in clinical use have been shown to decrease platelet aggre-
gation and secretion ex vivo. These include nitroprusside, nitroglycerin, nitric
oxide [100], and propranolol [101]. Calcium channel blockers, such as verapa-
mil, nifedipine, and diltiazem, also can inhibit platelet aggregation at high con-
centrations. This effect is seen primarily with epinephrine-induced aggregation
and does not seem to be related to calcium channel blockade. At therapeutic
doses, calcium channel blockers do not prolong the bleeding time, although
nisoldipine was reported to inhibit agonist-induced calcium transients and
platelet aggregation after 10 days of oral administration [102–104]. In addition,
at high concentration, quinidine was reported to cause a mild prolongation of
the bleeding time and potentiate the effect of aspirin [105].
Psychotropic Drugs
Patients receiving antidepressants or phenothiazines may exhibit impaired ag-
gregation responses attributed to a direct effect of the drugs on the phospho-
lipid bilayer and by inhibition of arachidonic liberation from platelet
membranes [106]. Inhibition of intracellular signaling molecules, such as pro-
tein kinase C, also is described [107]; however, this usually is not associated
with bleeding. Fluoxetine, one of the most popular antidepressants available,
656 SHEN & FRENKEL

does not seem to impair in vitro platelet aggregation and only rarely has been
associated with clinical bleeding [108].
Herbal Supplements
With the ever-increasing popularity of herbal or natural supplements for their
healing properties, the effect of these supplements on platelet function must be
considered. Fish oils containing x3 fatty acids cause a slight prolongation of the
bleeding time. These fatty acids reduce the platelet content of arachidonic acid
and compete with arachidonic acid for COX [109]. Black tree fungus and gar-
lic, used commonly in Chinese cooking, contain substances that can inhibit
platelet function [110,111]. Onion, Gingko biloba, cumin, and turmeric are com-
mon supplements and spices that have been shown to inhibit platelet aggrega-
tion and eicosanoid biosynthesis [112–114].

SUMMARY
Acquired platelet dysfunction, with or without clinically significant bleeding, is
observed frequently and is associated with a plethora of pathogenic mechanisms
affecting platelet adhesion, aggregation, or secretion. In many cases it can be
traced to commonly prescribed and over-the-counter medications. With the pop-
ularity of herbal or natural supplements, a careful drug history is essential for the
evaluation of a patient who has mucocutaneous bleeding that is suggestive of
platelet dysfunction. Astute evaluation for the associated systemic disorders
should be conducted. Judicious use of an experienced hemostasis laboratory
and close liaison with the coagulation specialist to facilitate the definition of
the platelet dysfunction facilitates the proper diagnosis and management.
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