Sticky Platelet Syndrome

On 10-4-23 Mayukh Sarker, PhD asked, “At the October 4–6 Mayo conference someone asked. ‘what is sticky platelet syndrome, and can it be defined and diagnosed?’ The consensus was no, it was an “old school” thought but it currently can’t be diagnosed clinically or by the laboratory. What are your thoughts on this?”

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On 10-5-23 Emmanuel Favaloro, PhD, responded; well, there are three camps:
1. One camp has a passionate belief in the existence of SPS and believes that diagnosis is possible by assessing platelet responses to ADP and epinephrine.
2. One camp has a passionate disbelief in the existence of SPS, but if you challenge them, most of them will have to admit that they have not ever systematically tested for SPS.
3. One camp keeps an open mind. I’m in this camp; I even wrote a ‘blog’ on it [cited below].
I don’t get why people can accept the existence of hereditary platelet dysfunction [reduced = bleeding] but refuse to believe the plausibility of hereditary platelet hyper-aggregability [increased = thrombosis risk]. We can certainly detect platelet hyper-aggregability in some of our patients, although the vast majority will represent acquired hyper-aggregability. That’s why patients are put on anti-platelet agents.
We had a few hyper-aggregable patients even show false 2B/platelet-type VWD patterns [see citation below]. These patients also showed enhanced reactivity against low-dose ADP or epinephrine.
However, the assessment of hereditary association for platelet hyper-aggregability requires dedicated systematic assessment. Our lab never went down that path, although my former boss was one of those with hyper-aggregable platelets. He passed away too young, as did his father. Perhaps he had SPS? We’ll never know.
There are other conditions where camps exist: hematidrosis [“sweating blood”] is one; a hematologist will never believe hematidrosis exists until they encounter it! Oh, I wrote a ‘blog’ on that too! [cited below]

On the same day, Bob Gosselin responded: “As with Dr. Favaloro, I am in camp 3, sans the blog…however it’s unclear why the agonists for SPS would be limited to ADP and epinephrine if one were to look for increased platelet function, as collagen response is to a different receptor [GP VI], as well as other agonists. Spontaneous platelet aggregation [SPA] is also rumored to be an event, but again, without a consistent “pattern,” that too has become another folklore item.
“Since PLT response includes WBC interaction [aggregates], we may be missing that linkage to thrombotic risk.  Unfortunately, our evaluation of coagulation stuff is in isolation [plasma, PRP, etc] we are likely missing a whole lotta stuff that may be leading to thrombotic risk, and perhaps to a lesser degree, bleeding risk.
“We need to get some smart engineers to figure out a better way to evaluate the whole package, including plasma proteins, WBCs, RBCs, and endothelium…a gang outta TN and GA [if I recollect correctly] have created an artificial endothelium model that seems promising but decades from practical use.
“Although I did PLT aggregation for 20+ years at my old haunts, except for a collection of study samples from a weight loss facility, I  do not recollect a single time a PLT agg was ordered for thrombosis or thrombotic risk.
“That’s my ‘blog’…long on opinion, short on data or experience, but I shan’t be encumbered by facts!

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I [Geo] responded: One barrier is that many of us remain wedded to heavily manipulated LTA when we have 25 years of impedance-based whole blood lumiaggregometry experience where WBCs and RBCs exert their in vivo-like influences. Epinephrine is ineffective in WBLA as well in 20% of patients’ platelets in PRP, but ADP, collagen, and arachidonic acid can be calibrated to test for hyperaggregability.

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Bob Gosselin did both methods…each has their plus/minuses. ADP and epinephrine on WB were kinda worthless, esp with luminescence release.

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Still October 5, George responded that Mammen and Frenkel’s publications in the 1990s associated SPS with several thrombotic conditions. Their articles were downplayed as “anecdotal.” An open mind and RCTs were and are needed. When I worked at Colorado Coagulation Consultants in the early 2000s, we offered an SPS assay for locals using LTA. One man’s platelets aggregated spontaneously [SPA] before we could add an agonist. He had heart disease.

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Dr. Favaloro responded, “Yes, Mammen was a great believer in SPS [Camp 1], but was ridiculed by his medical colleagues [Camp 2], and had great difficulty publishing in the mainstream journals.”

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Dave McGlasson wrote, “George and I performed a study on ASA response comparing WBA vs LTA  several years ago and used AA and collagen for the aggregometry. Unlike Bob, I did have a few VA subjects in whom we looked for PLT hyperreactivity with low concentrations of aggregating agents. These subjects were on anti-fungal agents for cryptococcus. Short collagen lag phases and large responses to AA. For what it’s worth. consistency in platelet aggregations is still an issue.”

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Dr. Favaloro’s response on 10-6-23: I can’t recall the specifics of the cases we eventually did aggregation studies on and found heightened responses, but could have derived from the short PFA-100 closure times we observed, and then maybe the clinicians wanted further studies to explain the finding; they also tended to have high VWF levels; so, a “powder keg ready to explode;” I hope they were put on anti-platelet meds! I can’t say they had SPS in the congenital sense, but they certainly had ’sticky platelets’!

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On 10-6-23 I spoke with Larry Brace, PhD, who resides in camp 3 with some publications in the 1990s.

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Selected References

• Click Seminars in Thrombosis and Hemostasis Commentaries Volume  45 for Dr. Favaloro’s SPS editorial.
• Click Seminars in Thrombosis and Hemostasis Commentaries Volume 44 for Dr. Favaloro’s hematidrosis editorial.