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Study offers ‘intriguing’ insights into post-cardiac surgery thrombocytopenia
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I suspect every hematologist has been faced with the difficult task of evaluating a patient with thrombocytopenia following open-heart surgery.
Is this the frightening precursor of heparin-induced thrombocytopenia (HIT) or simply the usual post-pump consumption of platelets that will repair spontaneously within a couple of days?
The diagnostic problem is compounded by the fact that more than half of these patients have positive but unimportant enzyme-linked immunosorbent assays (ELISA) — assays that detect antibodies against platelet factor 4 (PF4) bound to heparin, or less so to enoxaparin, that may cause HIT.
The relatively frequent occurrence of HIT following cardiac surgery and knee arthroplasty is suggested to reflect marked release of potentially antigenic PF4 by activated/damaged platelets in the extracorporeal apparatus, or by stagnation in the tourniqueted leg in the latter case.
However, a study led by researchers at Albert Einstein College of Medicine shed a newer intriguing light on post-pump thrombocytopenia.
In their paper, published in Nature Medicine, Bruns and colleagues show that megakaryocytes modulate their own production of platelets by suppressing marrow stem cells, and they do so by secreting PF4.
Their studies followed their 3-D whole-mount imaging of mouse bone marrow, which demonstrated nonrandom, close association of megakaryocytes with hematopoietic stem cells.
This led to an ASH presentation that selective depletion of marrow megakaryocytes provokes stem cell division and maturation.
Moreover, they now report that injection of the mega product, PF4, suppresses stem cell activation and numbers. Conversely, animals genetically deficient in PF4 are enriched in maturing stem cell numbers.
Thus, one can hypothesize that at least some post-pump thrombocytopenia is due to released PF4 that suppresses stem cell maturation, resulting in decreased platelet production. Tidy pathophysiology, but not much help to the befuddled hematologist evaluating the post-pump thrombocytopenic patient.
My own suggestion to cardiac surgeons is to avoid heparin after surgery and use fondaparinux, particularly if the 4Ts score for HIT is evocative. Argatroban is “evidence-based,” but its use is a bit unruly.
Lest one only finds PF4 a treacherous substance, be reminded that it is likely beneficial in bacterial defense and intriguingly has been demonstrated by Chinese investigators to have remarkable radioprotective properties. In that study, Chen and colleagues found hematopoietic mesenchymal stem cells to be protected from otherwise lethal irradiation by PF4 both in vitro and in intact animal models.
References:
Bruns I, et al. Nat Med. 2014;doi:10.1038/nm.3707.
Bruns I, et al. Abstract 3. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2013; New Orleans.
Chen JJ, et al. Br J Radiol. 2014;doi:10.1259/bjr.20140184.
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Harry S. Jacob, MD, FRCPath(Hon), is HemOnc Today’s Founding Chief Medical Editor and its Consulting Editor for Hematology. He can be reached at jacob002@umn.edu. Disclosure: Jacob reports no relevant financial disclosures.