Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (392 page)

   Platelet satellitosis (platelets form rosettes around white cells).

   Platelet cold agglutinins.

   Giant platelets missed by automated counters.

   Very elevated RBC count.

   Artifacts due to inappropriate technique in blood collection (clotted blood, overfilling vacuum tubes).

Suggested Readings

Bussel J. Diagnosis and management of the fetus and neonate with alloimmune thrombocytopenia.
J Thromb Haemost.
2009;7(Suppl 1):253–257.

Pouplar C, Gueret P, Fouassier M, et al. Prospective evaluation of the “4Ts” score and particle gel immunoassay specific to heparin/PF4 for the diagnosis of heparin-induced thrombocytopenia.
J Thromb Haemost.
2007;5:1373–1379.

Warkentin TE, Sheppard JI, Moore JC, et al. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassay.
J Thromb Haemost.
2008;6: 1304–1312.

   
DISORDERS OF PLATELET FUNCTION: INHERITED AND ACQUIRED

Disorders of platelet function are also referred as thrombocytopathies. The platelets’ major physiologic role is in hemostasis, where they arrest bleeding in small blood vessels. To perform this function optimally, the platelets’ number as well as function must be normal. Thrombocytopathies can be congenital, but more commonly, they are acquired. In most acquired thrombocytopathies, the platelet counts are normal. In some of the congenital disorders, the platelet count is reduced as well. Individuals who present with recent or life-long mucocutaneous bleeding should be suspected. Because thrombocytopathies and most von Willebrand disease cases have similar presentations, workup for the two conditions should be initiated simultaneously.

INHERITED THROMBOCYTOPATHIES

Defects in platelet–platelet interaction (aggregation defects)

   
Glanzmann thrombasthenia
is the most common inherited (autosomal recessive) disorder of platelet function. Affected patients have a lifelong hemorrhagic syndrome, mostly mucocutaneous, although their platelet count and size are normal. The bleeding severity differs considerably between patients. It depends in part on the severity of the genetic defect (absence or reduction of the platelet integrin receptor GPIIb-IIIa [α
_2b
β
₃
]). Affected genes coding for this integrin have been identified. The genotypic/phenotypic, that is, bleeding, do not correlate entirely. Moreover, the severity of bleeding declines with age. Bleeding results from the platelets’ inability to bind fibrinogen. There is absence, or reduction in aggregation with all agonists, but platelets agglutinate normally with ristocetin (Table
9-4
). There is normal release with strong agonists, such as thrombin. Complete absence of clot retraction was described in the severe type of disease.

   Afibrinogenemia: In the absence of fibrinogen, platelet cannot adhere resulting in lack of aggregation.

   Disorders of secretion and signal transduction include storage pool deficiencies of platelet granules, or granule contents, as well as primary transduction defects. The bleeding is usually mild.

   In the
gray platelet syndrome
, platelets are deficient in α granules. Platelet aggregation studies have produced variable results. Aggregation induced by ADP, epinephrine, arachidonic acid, and agglutination with ristocetin is normal (or only mildly impaired), but aggregation with collagen has been reported to be decreased or absent. Platelet count varies from 20,000 to 150,000/μL. On the peripheral blood smear (PBS), platelets are large and appear gray or gray-blue, are vacuolated, or look ghost-like. These patients have a tendency to develop myelofibrosis, splenomegaly, and progressive thrombocytopenia.