Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening reaction to heparin. It occurs when a patient develops antibodies against a heparin-platelet factor 4 (PF4) complex, leading to platelet activation. This process results in thrombocytopenia and an increased risk of venous and arterial thrombosis, affecting up to 50% of untreated patients.
Diagnosing and treating HIT can be particularly challenging, especially in patients requiring systemic anticoagulation in the perioperative context of cardiac or vascular surgery.
This study aimed to determine the incidence, risk factors, and complications associated with HIT in post-cardiac surgery patients, as well as to analyze the healthcare resource consumption it entails at the hospital level. A retrospective analysis was conducted in the United States (Maryland) from 2012 to 2020. Among 33,583 cardiac surgery patients identified through the Maryland Health Services Cost Review Commission’s database, 184 (0.55%) were diagnosed with postoperative HIT. This incidence remained stable throughout the study period. Patients aged 18 years and older with diagnoses identified via ICD-9 and ICD-10 codes were included. Postoperative complications (e.g., hemorrhages, stroke, thromboembolic events), length of hospital stay, mortality, readmission rates, and relevant costs (both for the initial surgery admission and subsequent readmissions) were compared between patients with and without HIT.
Patients with HIT were older (> 80 years; p < .001) and presented more severe illness at admission (p < .001). Additionally, HIT patients had higher mortality rates (13.6% vs. 2.3%; p < .001), longer hospital stays (21 vs. 7 days; p < .001), higher hospital costs ($123,160 vs. $45,303; p < .001), greater risk of bleeding complications (7.6% vs. 1.1%; p = .002), and thromboembolic events (9.8% vs. 1.1%; p < .001), even after propensity score analysis. HIT patients exhibited a higher readmission rate than non-HIT patients, bordering statistical significance (63.4% vs. 53.3%; p = .05). However, there were no differences in the median number of readmissions or in total costs incurred by both patient groups during readmission periods.
The authors concluded that patients with HIT not only experience worse outcomes and more complications during the postoperative period following cardiac surgery but also generate higher costs during the initial hospital stay. Given these findings, the authors emphasized the need to implement strategies aimed at minimizing the risk of HIT in these patients.
COMMENTARY:
As previously mentioned, HIT is a rare complication; however, considering the risk factors associated with its occurrence—advanced age, surgery, female sex, prior use of unfractionated heparin (particularly at therapeutic doses), renal failure, and ultrafiltration therapies—it has a higher prevalence (1–3%) in patients with cardiovascular conditions, especially those requiring surgical intervention.
It is essential to understand that there is no dose of heparin low enough to completely prevent the development of HIT. Even heparin flushes or heparin-coated catheters may be sufficient to trigger it. Additionally, HIT can occur with exposure to any form of heparin, regardless of the administration route or exposure duration. However, diagnosis requires a marked thrombocytopenia (a sudden or ≥ 50% decrease from baseline counts) and a positive test for PF4-heparin antibodies, without other apparent causes for thrombocytopenia. This point is critical given the broad differential diagnosis of thrombocytopenia in these patients (e.g., hemorrhage, sepsis, DIC, extracorporeal circulation-related consumption). The isolated presence of these antibodies does not increase thromboembolic risk, and current guidelines do not recommend routine antibody screening. This represents one of the study’s main limitations, as the method used for HIT diagnosis and heparin exposure route is unclear. Additionally, both HIT and other diagnoses relied on whether they were coded using the ICD. Furthermore, the ICD code for thrombotic events does not specify when these events occurred. These factors may have introduced unmeasured variables that could confound the identified associations.
HIT typically occurs 5–10 days after heparin exposure, which explains the prolonged hospital stays and delayed discharges observed in this study, even in the absence of other surgical complications. On the other hand, the lack of statistically significant differences in the average number of readmissions and associated hospital costs between the two patient groups suggests that the major implications of this condition concerning morbidity and mortality occur during the acute phase. Therefore, it is during this period that attention should be focused.
The first thing to recognize is that the evidence available to guide management in this context is limited. This is due not only to the low incidence of HIT but also to the diagnostic challenges it presents, especially when urgent surgery is required, leaving insufficient time for a comprehensive preoperative evaluation. Moreover, avoiding intraoperative heparin exposure entirely may not always be feasible.
According to current guidelines, the cornerstone of treatment is to avoid unnecessary heparin exposure and ensure close monitoring for bleeding and thromboembolic complications, along with appropriate clinical and platelet count surveillance. Many hospital laboratories do not perform functional PF4-heparin antibody tests, and sending these tests to external facilities can take several days. This underscores how therapeutic decisions can vary significantly depending on the urgency of the surgery.
In urgent cases, a presumptive diagnosis is necessary. This can be established using a validated scoring system, known as the 4Ts, which evaluates the degree of thrombocytopenia, timing of onset in relation to heparin administration, presence of thrombosis, and other potential causes of thrombocytopenia. If a high probability of HIT is determined in a patient requiring urgent surgery, they should be managed as if HIT were present until definitive test results are available. The therapeutic options in such scenarios include:
- Performing plasmapheresis or administering intravenous immunoglobulin before surgery if heparinization cannot be avoided.
- Using alternative anticoagulants, such as bivalirudin, argatroban, or fondaparinux, depending on the clinical context and anticoagulation requirements.
- Co-administering an antiplatelet agent with heparin, such as a glycoprotein IIb/IIIa receptor antagonist (e.g., tirofiban).
- Administering epoprostenol alongside heparin.
All of these approaches are reasonable for managing HIT, although the level of supporting evidence is low, and no clear preference for one over another has been established. Generally, the choice depends on the clinician’s expertise, institutional experience, and resource availability.
In cases of elective surgery, the management algorithm is more defined, as it is often possible to refine the diagnosis and, as recommended, delay surgery whenever feasible. Ideally, surgery should be postponed until PF4-heparin antibodies are no longer detectable, which typically takes approximately three months (up to 100 days).
In both surgical scenarios, and regardless of the chosen preoperative or intraoperative management strategy, postoperative anticoagulation—whether therapeutic or prophylactic—in a patient diagnosed with HIT must be performed using a heparin-free agent. However, restarting anticoagulation specifically for HIT in patients re-exposed to heparin is not indicated unless recurrent thrombocytopenia due to HIT reoccurs.
Gathering evidence on this topic confirms that HIT has a significant negative impact on patient prognosis. Nonetheless, the uncertainty surrounding the understanding and management of this condition remains a challenge, underscoring the need for vigilance in monitoring all patients with significant thrombocytopenia following cardiovascular surgery.
REFERENCE:
Yesantharao LV, Etchill EW, Canner J, Alejo D, Choi CW, Lawton JS, et al. Heparin-Induced Thrombocytopenia After Cardiac Surgery-A Statewide Review of Health Care Utilization. Ann Thorac Surg. 2024 Jan;117(1):221-228. doi: 10.1016/j.athoracsur.2022.07.049.
