LabMed

Platelet Storage Pool Disease – Congenital Alpha Granule Deficiency

At a Glance

Alpha-Storage Pool Deficiency, or gray platelet syndrome, is a mild to moderate bleeding disorder in which the primary defect is a deficiency in platelet alpha granules.

Alpha-Storage Pool Deficiency is a rare autosomal recessive disorder characterized by mucocutaneous bleeding (particularly epistaxis), surgical bleeding, and ecchymosis.

The prevalence of Alpha-Storage Pool Deficiency is unknown, since it has only been described since 1971.

After platelets adhere to the damaged endothelium, mediated through von Willebrand factor (VWF), and aggregate, mediated through fibrinogen, the recruited platelets activate and liberate their stored granules. Normal platelets contain alpha granules that store factor V, fibronectin, VWF, thrombospondin, platelet factor-4, Beta-thromboglobulin, HMWK, and platelet-derived growth factor.

The diagnosis can be made by visual demonstration of deficient platelet alpha granules with either electron microscopy or light microscopy and supported by an impaired aggregation to collagen, adenosine diphosphate (ADP), and thrombin with platelet aggregometry.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

If there is clinical suspicion for Alpha-Storage Pool Deficiency, it is recommended to first rule out other bleeding disorders in addition to verification of this diagnosis. A reasonable screening hemostatic evaluation should include the following labs: complete blood count (CBC), peripheral blood smear, platelet function analyser-100 (PFA-100), Prothrombin time (PT), Partial Thromboplastin time (PTT), and fibrinogen activity.

Direct evaluation for von Willebrand disease by VWF antigen, Ristocetin cofactor assay, and FVIII activity should be considered upfront, especially if there are mucocutaneous bleeding symptoms.

Review of the peripheral blood smear and demonstration of mild thrombocytopenia and gray appearance of the platelets are suggestive of this disorder. Screening PT and PTT will be normal, and PFA-100 closure times will be variably prolonged.

Electron microscopy of mounted platelets is definitive with demonstration of the absence of alpha granules (Table 1).

Table 1.

Test Results Indicative of the Disorder
PFA-100 Platelet aggregometry Electron microscopy
Variable closure time prolongation in both cartridges Variable impaired aggregation to most agonists Absence of alpha granules on mounted platelets

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

A thorough drug history is recommended prior to performing a PFA-100 or other platelet studies, since recent NSAID or aspirin use (within 7-8 days) can lead to false-positive results. In addition, there are herbal medications and certain foods that can prolong the closure time mostly in the collagen/epinephrine cartridge.

What Lab Results Are Absolutely Confirmatory?

Demonstration of significant reduction of alpha granules of mounted platelets utilizing electron microscopy associated with mild thrombocytopenia and a grayish appearance under light microscopy confirms the diagnosis.

What Confirmatory Tests Should I Request for My Clinical Dx? In addition, what follow-up tests might be useful?

Unfortunately, the PFA-100 shows variable prolongation of both agonist-coated cartridges and, in some cases, can be normal. Similarly, platelet aggregometry cannot be solely relied on to make a definitive diagnosis.

What Factors, If Any, Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

The PFA-100 can be affected by a low hematocrit (<28%), low platelet count (<100,000), and low VWF (as with VWD) and, thus, in cases of mild thrombocytopenia without Alpha-Storage Pool Deficiency, there can be a prolonged PFA-100.

Type 2B VWD, Bernard-Soulier Syndrome, and idiopathic thrombocytopenic purpura (ITP) may all be confused for Alpha-Storage Pool Deficiency but should be considered clinically. The major identifier of Alpha-Storage Pool Deficiency being visual deficiency of granularity under light microscopy compared to the former diagnoses.

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