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1996 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 1997

Complications (EPIC), Evaluation of Percutaneous Transluminal Cor- pseudothrombocytopenia concerns conditions with which it is con-
onary Angioplasty to Improve Long-term Outcome of c7E3 GPIIb-IIIa fused rather than any pathology associated with the condition. It is
Receptor Blockade (EPILOG), and Evaluation of Platelet IIb/IIIa Inhib- important that this syndrome be recognized promptly to avoid unnec-
itor for Stenting (EPISTENT). In these studies, pseudothrombocytope- essary diagnostic tests and treatment.
nia accounted for more than one-third of low platelet counts in patients
undergoing coronary interventions and treated with abciximab. These INHERITED PLATELET DISORDERS
studies demonstrated that pseudothrombocytopenia is a benign labora-
tory condition not associated with increased bleeding, stroke, transfu- Megakaryopoiesis and thrombopoiesis are regulated by a number of
sion requirements, or the need for repeat revascularization. hematopoietic growth factors and transcription factors (Chap. 113).
Any genetic defect affecting platelet production, function or morphol-
MISCELLANEOUS ASSOCIATIONS ogy may cause inherited platelet disorders (IPDs; Chap. 121). In recent
Some studies suggest that platelet agglutinins occur more frequently in decades, knowledge of normal megakaryocyte and platelet physiology
has grown enormously, aided in part by the study of IPDs.
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52,53
hospitalized patients and in association with medical conditions such as IPDs are a very heterogeneous group of disorders. Some dis-
autoimmune diseases, malignancy, liver disease, and sepsis. 25,43–46 How- orders, such as Bernard-Soulier syndrome, appear to be restricted
ever, others found no association with any particular pathology or with to platelets, whereas others appear as a part of a complex pathol-
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use of specific drugs. 30 ogy, as seen in thrombocytopenia with absent radii (TAR) syndrome
One study showed that antibodies from patients with pseudoth- (Fig. 117–2). In some IPDs, the platelet count may be normal despite
rombocytopenia can induce agglutination of donor platelets in the pres- severely impaired platelet function, such as in Glanzmann throm-
ence of EDTA. This agglutination was prevented by warming the donor basthenia. Other disorders are accompanied by abnormal platelet
platelets to 37°C or by pretreating the platelets with aspirin, prostaglan- numbers, usually thrombocytopenia. Table 117–2 summarizes the
din E , apyrase, and monoclonal antibodies against integrin α β that inherited thrombocytopenias.
IIb 3
1
block the binding site for fibrinogen and von Willebrand factor (VWF), Severe forms of IPDs that present as a bleeding tendency early in
or arg-gly-asp (RGD) peptide, which binds the site on integrin α β childhood are rare. IPD patients usually present with mucocutaneous
IIb 3
that recognizes cytoadhesive proteins. Whether the same reaction bleeding, such as with purpura, epistaxis, and/or gingival bleeding.
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occurs in vivo is not known, but in that case the antibodies should have Menorrhagia and bleeding during pregnancy and labor are common
a slow reactivity, or else bleeding would sometimes occur. problems in female patients. Spontaneous life-threatening bleeding is
rare, including intracranial hemorrhage, massive gastrointestinal or
MANAGEMENT OF THE PATIENTS WITH genitourinary bleeding. Recent molecular investigations of IPD patients
PSEUDOTHROMBOCYTOPENIA and their families with bleeding diathesis demonstrated that most IPDs
cause mild bleeding tendencies, and IPDs may be more prevalent than
An (unexpected) low platelet count reported by automated cell count- previously thought. In these milder cases, a bleeding diathesis may
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ers should be confirmed by microscopic examination of the blood film. only be diagnosed after an episode of excessive bleeding, such as during
Automated cell counters identify platelets merely based on their small surgery or following trauma.
volumes in comparison to those of other blood cells, generally defined Diagnosis of IPD presents a significant challenge because of the
as volumes between 2 and 20 fL. Because platelet clumps tend to exceed heterogeneity of clinical and laboratory findings of the patients with
20 fL, the clumps may be counted as leukocytes, and even if counted the same disorder, even in the same family. IPD patients with isolated
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as platelets, several platelets are counted as one. Thus, pseudothrom- macrothrombocytopenia share common clinical and basic laboratory
bocytopenia may be accompanied by pseudoleukocytosis. 5,21,24,47 The features with certain acquired platelet disorders and are sometimes mis-
greater the delay in processing of anticoagulated blood, the greater is diagnosed. It is very important to distinguish IPD patients from those
the degree of platelet clumping and the greater the potential for arti- with acquired platelet disorders, such as ITP, to avoid unnecessary or
fact. Platelet clumping can be prevented by collecting the sample in potentially harmful treatments. Helpful in this regard is information
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EDTA and maintaining its temperature at 37°C. Even with these mea- obtained during the history, including a family history of bleeding and
sures, however, clumping will still occur in approximately 20 percent consanguinity in the family, because the majority of IPDs are inherited
of cases. 30 as autosomal recessive traits. Because some IPDs are associated with
Another alternative is use of sodium citrate, which chelates cal- increased risk of developing myeloid malignancies, the patient and fam-
cium more weakly than does EDTA but still causes platelet clumping in ily should be asked about a family history of myeloid malignancies. The
approximately 10 to 20 percent of cases with EDTA-induced clumping. presence of skeletal, facial, ocular, audiologic, neurologic, renal, cardiac,
In some patients, an accurate platelet count can be obtained only by and immune problems associated with platelet disorders may also sug-
sampling blood directly into ammonium oxalate and manually count- gest IPD. 51,56
ing the platelets using a Bruker chamber. Flow cytometry may help for Laboratory evaluation of a potential IPD should start with a
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determining exact platelet number by immunostaining of the platelets. careful blood film investigation, which could be helpful for patients
Platelet agglutinins are not associated with bleeding or throm- with MYH9-related diseases (giant platelets and Döhle-like inclusion
bosis, so they appear to have no clinical implications, except that they bodies within leukocytes; Fig. 117–3), Bernard-Soulier syndrome
may lead to unnecessary therapy because of misdiagnosis. Trans- (macrothrombocytopenia), Gray platelet syndrome (pale platelets),
placental transmission of agglutinins has been documented, but the and sitosterolemia (giant platelets surrounded by a circle of vacuoles,
pseudothrombocytopenia induced by these antibodies in the neonate stomatocytosis). Platelet function analyzer (PFA-100) occlusion times
resolves spontaneously. 48,49 No complications have been reported when are usually found to be prolonged. The skin bleeding time is not recom-
platelet agglutinins are discovered during pregnancy. 48,50 Transfu- mended for screening, because it is invasive and poorly reproducible.
sion of blood products from patients with pseudothrombocytopenia Although the PFA-100 test is very sensitive in detecting Bernard-Soulier
produces an acceptable corrected count increment in the recipient, syndrome and platelet-type von Willebrand disease (VWD), it may be
again supporting its benign nature. Thus, the clinical importance of normal in patients with variant forms of these disorders, or patients
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Kaushansky_chapter 117_p1993-2024.indd 1996 9/21/15 2:31 PM