We read with great interest the paper “Heparin-Induced Thrombocytopenia in Cardiac
Surgery Patients” by Pishko and Cuker[1] and we found it very important with a view to clinical prevention. The authors reviewed
the epidemiology, clinical diagnosis, and laboratory diagnosis of heparin-induced
thrombocytopenia (HIT) in cardiac surgery patients and present a conceptual framework
for selecting intraoperative anticoagulation in patients with a history of HIT.
With reference to the findings reported in the paper, we would like to make the following
contribution to the discussion. We retrospectively analyzed data from 600 postcardiac
surgery patients to evaluate the incremental value of performing 4Ts test and EuroSCORE
(European System for Cardiac Operative Risk Evaluation) test in identifying patients
at a high risk of developing anti-PF4/heparin antibodies and thrombotic complications.
A secondary end point was thrombotic events during the 30-day follow-up.
Anti-PF4/heparin antibodies were tested in all patients using a commercial immunoassay
(Asserachrom Human PF4 ELISA [enzyme-linked immunosorbent assay] kits).[2]
[3]
[4] No functional HIT assay was performed. Preoperative ELISA HIT testing was not performed.
Of the 600 patients investigated, 131 (21.8%) were found to have anti-PF4/heparin
antibodies in the postoperative period (5–7 days from surgery). This group included
both patients who were seropositive prior to surgery and those who seroconverted after
surgery. This is a limitation of the study. A previous systematic review found that
preoperative antibodies were present in 5 to 22% of cardiac surgery patients.[5] We calculated the 4Ts score and the EuroSCORE for our patient cohort[6] using scoring as previously reported.[7]
[8] A high-probability 4Ts score was predictive of anti-PF4/heparin antibody formation
and thrombotic events ([Table 1]
[6]). The EuroSCORE did not add any more information in our cohort of patients ([Table 1]). The only parameter of the EuroSCORE that added information for stratification
was the left ventricular ejection fraction ([Table 2]). Reduced ejection fraction is a marker of severity of cardiac disease and is associated
with an increased risk of thrombosis.[9] Patients with reduced ejection fraction may be more likely to have been treated
with heparin, which might favor the development of anti PF4/heparin antibodies in
cardiac surgery patients preoperatively leading to possible “early onset” HIT.[10] This is a rare form of HIT characterized by early onset of thrombocytopenia, a confounding
factor in patients undergoing cardiac surgery.[10] In fact, in cardiac surgery patients, early onset and persisting thrombocytopenia
can be explained by several non-HIT factors (e.g., postoperative multiorgan system
failure).[10] Patients with a high probability 4Ts test and a reduced ejection fraction therefore
need a more careful evaluation. In these patients, a test for anti-PF4/heparin antibodies
would be useful to enable early diagnosis of HIT and, consequently, enable better
management of anticoagulant therapy in patients found to have pathological HIT. Patients
with HIT are at a high risk of thrombosis, and when pathological HIT is strongly suspected
or confirmed, heparin should be stopped according to the American College of Chest
Physicians guidelines.[9] Furthermore, appropriate alternative anticoagulant therapy should be promptly initiated
at therapeutic doses until the platelet count has recovered.
Table 1
Thrombotic events in patients stratified according 4Ts score and EuroSCORE
|
High score, n (%)
|
Intermediate score, n (%)
|
Low score, n (%)
|
|
4Ts score (n = 131 patients)
|
57 (43.5%)
|
36 (27.4%)
|
9 (6.8%)
|
|
EuroSCORE (n = 131 patients)
|
57 (43.5%)
|
33 (25.1%)
|
12 (9.1%)
|
Abbreviation: EuroSCORE, European System for Cardiac Operative Risk Evaluation.
Table 2
Association of thrombosis with 4Ts score in all patients who yielded intermediate
and high 4Ts score, in patients with a high EuroSCORE, and in patients with low ejection
fraction
|
4Ts score
|
|
Low
(reference)
|
Intermediate, HR (95% CI)
|
High, HR (95% CI)
|
|
Total population
(131 patients)
|
1
|
1.05 (0.76–1.01)
|
1.74 (0.9–2.2)[a]
|
|
Patients with a high EuroSCORE value (87 patients)
|
1
|
1.12 (0.34–1.15)
|
1.24 (0.42–1.56)
|
|
Patients with low ejection fraction
(55 patients)
|
1
|
0.98 (0.66–0.98)
|
2.0 (0.56–2.34)[a]
|
Abbreviations: CI, confidence interval; EuroSCORE, European System for Cardiac Operative
Risk Evaluation; HR, hazard ratio.
a
p < 0.05.
In patients with intermediate-to-high likelihood of complications, as predicted by
EuroSCORE, the addition of 4Ts score improved the prediction of events ([Table 1]). These patients need a more careful follow-up, and immunological tests for anti-PF4/heparin
antibodies, followed by functional HIT confirmation, could help prevent thrombotic
complications related to pathological HIT.[2]
[3]
[4]
[5]
[7]
[8]
[9]
[11]
[12] We agree with Pishko and Cuker that it is necessary to distinguish the common platelet
count fall associated with CPB and surgery from the much less common platelet count
fall associated with HIT. The 4Ts score and the EuroSCORE might help to identify high-risk
patients that need close follow-up to avoid thrombotic complications related to HIT.
