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At a Glance
Thromboxane synthetase (synthase) deficiency is a mild to moderate bleeding disorder in which the primary defect is a quantitative deficiency of thromboxane synthetase leading to reduced thromboxane production.
Thromboxane synthetase deficiency is characterized by mucocutaneous, gastrointestinal (GI), or surgical bleeding.
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. Thromboxane production provides positive feedback to granule secretion and assists in platelet aggregation through not fully elucidated mechanisms.
Thromboxane synthetase deficiency is extremely rare with less than ten cases reported and without an associated syndrome. The mode of transmission is unknown but presumed to be autosomal recessive.
The diagnosis of thromboxane synthetase deficiency can be made by demonstration of impaired secondary wave aggregation to low dose adenosine diphosphate (ADP), impaired aggregation to collagen, thrombin, and epinephrine, and absent aggregation to arachidonic acid using 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 thromboxane synthetase deficiency, then it is recommended to first rule out other bleeding disorders prior to verification of this rare diagnosis. A reasonable screening hemostatic evaluation should include the following labs: complete blood count (CBC) with differential, peripheral blood smear, platelet function analyzer-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 mucocutaneous bleeding symptoms.
There are no associated cytopenias, and the platelets have a normal morphological appearance under light microscopy. Screening PT/PTT and fibrinogen activity will be normal. The closure time in a PFA-100 will demonstrate prolongation of the closure time in the collagen/epinephrine cartridge.
If all the screening labs are normal, except for the PFA-100, then a reasonable next consideration is platelet aggregometry.(Table 1)
Table 1.
| PFA-100 | Platelet aggregometry |
|---|---|
| Prolonged closure time in the collagen/epinephrine cartridge | Impaired secondary wave aggregation to low dose ADP |
| Impaired aggregation to collagen, thrombin and epinephrine | |
| Absent aggregation to arachidonic acid |
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 non-steroid anti-inflammatory drugs (NSAIDs) or aspirin use (within the previous 7-8 days) can lead to false-positive results. In addition, there are herbal medications and certain foods (garlic and fatty foods) that can prolong the closure time in the collagen/epinephrine cartridge.
What Lab Results Are Absolutely Confirmatory?
In the absence of recent aspirin or NSAID use, demonstration of impaired secondary wave aggregation to low dose ADP, impaired aggregation to collagen, thrombin, and epinephrine, and absent aggregation to arachidonic acid using platelet aggregometry is the gold standard.
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
The PFA-100 alone cannot be used to rule out a thromboxane synthetase deficiency; therefore, if there is a strong clinical suspicion, platelet lumiaggregometry is recommended.
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?
Patients taking medications that include aspirin have a similar PFA-100 and platelet aggregometry pattern, thus, stopping all aspirin/NSAID containing products 8 days prior to testing is crucial.
The PFA-100 and platelet lumiaggregometry pattern is similar to Cyclooxygenase deficiency, thus, consideration of this diagnosis is crucial with quantification of Cyclooxygenase enzyme activity necessary to differentiate.
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