Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin‐dependent antibodies

Abstract

Summary Cardiopulmonary bypass (CPB) induces the release of platelet factor 4 (PF4) and patients are at risk of heparin‐induced thrombocytopenia (HIT). This study was aimed to determine whether an abnormal evolution in platelet count (PC) after CPB is predictive of the development of HIT antibodies. Two abnormal PC patterns were defined: pattern P1, characterized by a decrease in PC following previous correction of thrombocytopenia occurring during CPB, and pattern P2, defined as a persistent low PC in the days following CPB. PC was evaluated for 10 d in 305 consecutive patients before and after CPB. Serotonin release assay (SRA) was carried out between days 8 and 10 to detect pathogenic heparin‐dependent antibodies. Moreover, antibodies to heparin–PF4 (H–PF4) complexes were assayed by enzyme‐linked immunosorbent assay. PC evolution after CPB was normal in 300 patients although antibodies to H–PF4 were frequently present (53·4%). Changes in PC were abnormal in five patients with pattern P1 (n = 4) or P2 (n = 1). As SRA was positive in four of the five cases, the positive predictive value of abnormal PC pattern for pathogenic HIT antibodies was 80%. Careful follow‐up of PC after CPB makes it possible to predict with high specificity (99%) for those patients who develop pathogenic HIT antibodies.

Early‐onset and persisting thrombocytopenia in post‐cardiac surgery patients is rarely due to heparin‐induced thrombocytopenia, even when antibody tests are positive

“…The high positive predictive value of this clinical profile (3/3, 100%) was in marked contrast to the overall low risk of HIT in patients simply testing HIPA-positive (3/71, 4.2%) or EIA-IgG-positive (3/304, 1%), irrespective of the clinical context. This confirms the findings of others [9,13], and provides further evidence that a 50% or greater platelet count decline that begins between days 5 and 10 post-cardiac surgery is highly predictive for HIT and should prompt a change in anticoagulation even before the results of antibody tests become available.…”

“…profile 1 ([a platelet count fall by > 50% (from the postoperative peak) between days 5 and 10 postsurgery] [12], and profile 2 (early-onset and persisting thrombocytopenia) [9,13]. Early-onset and persisting thrombocytopenia was defined as platelet counts that decreased within the first 4 days after surgery and remained below 100 · 10 9 L )1 until at least the seventh postoperative day.…”

“…However, only a minority of these patients develop clinically evident HIT, characterized by a second episode of thrombocytopenia beginning within a narrow ÔwindowÕ between postoperative days 5 and 10 (the ÔP1 patternÕ reported by Pouplard et al [9]). And third, in some patients, the early-onset thrombocytopenia persists beyond the first 5 days, and thus extends into the period in which HIT typically occurs -the so-called ÔP2 patternÕ described by Pouplard et al [9]. Particularly when this last group of patients tests positive for anti-PF4-heparin antibodies, the crucial issue becomes whether the patient has developed ÔtrueÕ HIT or whether a preceding -and persisting -surgeryrelated non-HIT thrombocytopenic disorder is simply associated with incidental and clinically irrelevant seroconversion [10].…”

“…Second, as many as 25-70% of patients develop anti-platelet factor 4 (PF4)-heparin antibodies detectable by immunoassays, and 4-20% test positive by platelet activation assay, during the first 10 days post-cardiac surgery [4][5][6][7][8]. However, only a minority of these patients develop clinically evident HIT, characterized by a second episode of thrombocytopenia beginning within a narrow ÔwindowÕ between postoperative days 5 and 10 (the ÔP1 patternÕ reported by Pouplard et al [9]). And third, in some patients, the early-onset thrombocytopenia persists beyond the first 5 days, and thus extends into the period in which HIT typically occurs -the so-called ÔP2 patternÕ described by Pouplard et al [9].…”

Traitement antithrombotique en chirurgie cardiaque

“…101 Low molecular weight heparin, which is not commonly used during heart surgery because of its long half-life and poor neutralization by protamine, carries a lower risk of HIT than UFH. 102 A proportional fall in platelet count of more than 30 to 50% from the highest preoperative value, five to ten days after heart surgery, with or without thrombosis, suggests HIT. 103,104 Significant levels of HIT antibodies usually occur only after the fifth postoperative day or later, so thrombocytopenia during the first four postoperative days is only rarely attributable to HIT.…”