LabMed

Platelet Storage Pool Disease – Congenital Delta Granule Deficiency

At a Glance

Delta-Storage Pool Deficiency is a mild to moderate bleeding disorder in which the primary defect is a deficiency of dense or delta granules. Delta-Storage Pool Deficiency is characterized by mucocutaneous bleeding (particularly epistaxis), surgical bleeding, and ecchymosis.

The diagnosis is supported by demonstration of a ratio greater than 2:1 of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) in the platelets as measured by HPLC, visual deficiency of platelet dense granules with electron microscopy or mepacrine-labeled fluorescence microscopy, impaired serotonin release by the 14C serotonin release assay or impaired secondary wave aggregation to low dose ADP, and epinephrine but variable impaired aggregation to collagen, arachidonic acid, and ristocetin using platelet aggregometry.

After platelets adhere to the damaged endothelium, mediated through von Willebrand factor (VWF) and aggregate, mediated through fibrinogen, the recruited platelets then activate and liberate their stored granules. Normal platelets contain 3-8 dense granules that store serotonin, ADP, ATP, calcium, and magnesium.

Delta-Storage Pool Deficiency is associated with two rare congenital disorders, Chediak Higashi Syndrome and Hermansky Pudlak Syndrome.(Table 1)

Table 1.

Delta-Storage Pool Deficiency Associated Syndromes
Chediak Higashi Syndrome Hermansky Pudlak Syndrome
Autosomal recessive DisorderOculocutaneous albinismNeurologic DysfunctionGiant cytoplasmic leukocyte inclusionsSevere immunodeficiency Autosomal recessive disorderCommon in NW Puerto RicoOculocutaneous albinismRotary nystagmusLipofuscinosisPulmonary fibrosis

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 Delta-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) with differential, peripheral blood smear review, platelet function analyser-100 (PFA-100) , prothrombin time (PT), Partial thromboplastin time (PTT), and fibrinogen activity. Direct evaluation for von Willebrand disease (VWD) by VWF antigen, Ristocetin cofactor assay, and FVIII activity should be considered upfront, especially if there are reported mucocutaneous bleeding symptoms.

There are no associated cytopenias with normal platelet morphology and normal screening coagulation tests (PT, PTT, and fibrinogen activity). The closure time with a PFA-100 will be variably prolonged.

If all of the screening hemostatic tests are normal, except possibly the PFA-100, then consideration for either platelet lumi-aggregometry, platelet nucleotide ratio analysis (ATP:ADP), mepacrine-labeled fluorescence microscopy, serotonin release assay, or electron microscopy should be considered based on what is best available locally.(Table 2)

Table 2.

Tests Results indicitive of the Disorder
PFA-100 Serotonin Release Assay Platelet Aggregometry
Variably prolonged closure times in both cartridges Impaired serotonin release Impaired secondary aggregation to low dose ADP/epinephrine
Variable impaired aggregation to collagen, arachidonic acid and ristocetin

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 (e.g., garlic and fatty foods) that can prolong the closure time in the collagen/epinephrine cartridge. It is recommended to avoid these foods/herbals prior to platelet testing.

What Lab Results Are Absolutely Confirmatory?

Demonstration of significant reduction of dense granules on mounted electron microscopy and absence of secondary wave aggregation in the presence of low dose ADP and epinephrine are the gold standard tests.

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

Light transmission aggregometry (LTA) testing is often poor at detecting the dense granule defect, and often the modified version of LTA, called lumiaggregometry, is more sensitive.

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?

In myeloproliferative disorders, disseminated intravascular coagulation (DIC), following cardiopulmonary bypass, Thrombotic Thrombocytopenic Purpura (TTP), and Hemolytic Uremic Syndrome (HUS), there is an acquired form of Delta-Storage Pool Deficiency that resolves with correction of these clinical disorders.

Rarely, patients can have a combined Alpha/Delta-storage pool deficiency.

Up to 25% of patients with Delta-Storage Pool Deficiency can have normal platelet aggregation responses to epinephrine, ADP, and collagen.

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