Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025;13(5):291-298.
doi: 10.22038/ABJS.2025.80206.3661.

Anti-PF4/ Heparin Antibodies Early Seroconversion in Hip Fracture Patients Receiving Low Molecular Weight Heparin Prophylaxis: a Pilot Study of 100 Consecutive Patients

Markos Psifis  1 , Christos Koutserimpas  2 , Ioannis Stavrakakis  1 , Chrysostomos Tsatsoulas  1 , Vasiliki Danilatou  3 , Kalliopi Alpantaki  1
Affiliations

Anti-PF4/ Heparin Antibodies Early Seroconversion in Hip Fracture Patients Receiving Low Molecular Weight Heparin Prophylaxis: a Pilot Study of 100 Consecutive Patients

Markos Psifis et al. Arch Bone Jt Surg. 2025.

Abstract

Objectives: Heparin-induced thrombocytopenia (HIT) represents a serious adverse reaction triggered by antibodies (anti-PF4/H) in heparin regimens. It is not clear if different low-molecular weight heparins (LMWHs) prompt distinct immunogenic responses in anti-PF4/H production and if these antibodies correlate with thrombocytopenia, thrombotic events, and early postoperative mortality. This pilot prospective study investigates the early output of anti-PF4/ H in elderly patients undergoing proximal femoral nailing for an intertrochanteric hip fracture surgery.

Methods: A total of 100 consecutive patients (72 females) with surgically treated intertrochanteric hip fractures were prospectively included. Ninety-four patients were available for the final follow-up. Twenty-seven patients received bemiparin, 42 enoxaparin and 25 tinzaparin. The levels of anti-PF4/H using the semi-quantitative latex-enhanced immunoassay; HemosIL® HIT-Ab(PF4-H) and platelets (PLT) levels were measured on the admission day and on day 5 following LMWH administration. Patients were followed up for at least 3 months for major thrombotic events and all-cause mortality.

Results: No patient developed clinically evident HIT, while 6 (6.4%) experienced thrombotic complications, and 22 (23.4%) passed away within 3 months after surgery. None of the patients with thrombotic complications tested positive for anti-PF4/H. Upon evaluating patients' seroconversion by day 5, six out of 94 (6.4%) patients tested positive for anti-PF4/H. Among them, three patients received bemiparin, two tinzaparin, and one enoxaparin. No statistically significant variance was observed in anti-PF4/H seroconversion between different types of LMWHs (p-value = 0.545) or in PLT count deviations (p-value = 0.990).

Conclusion: This pilot prospective study investigated anti-PF4/H production in older patients with hip fractures receiving different LMWHs. Preliminary results suggest that all tested anticoagulants have similar immunogenicity profiles in terms of PF4/H sensitization. These findings highlight the overall safety of LMWHs in elderly hip fracture patients. Moreover, the presence of anti-PF4/H appears unrelated to PLT fluctuations, subsequent VTE events and early postoperative mortality.

Keywords: Anti/ PF4; Femoral nail; HIT; Heparin; Hip fracture; LMWH.

PubMed Disclaimer

Conflict of interest statement

The authors do NOT have any potential conflicts of interest for this manuscript.

Figures

Figure 1
Figure 1
Box plots of the PF4-H antibody Δ-parameter between day 1 and 5 for each one of the LMWH studied
Figure 2
Figure 2
Box plots of PLT Δ-parameter between day 1 and 5 for each one of the LMWH studied
Figure 3
Figure 3
Nonlinear regression model for the correlation of the anti-PF4/H difference to the PLT difference
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Koster A, Nagler M, Erdoes G, Levy JH. Heparin-induced Thrombocytopenia: Perioperative Diagnosis and Management. Anesthesiology. 2022;136:336–344. - PubMed
    1. Arepally GM, Cines DB. Pathogenesis of heparin-induced thrombocytopenia. Transl Res. 2020;225:131–140. - PMC - PubMed
    1. Arepally GM. Heparin-induced thrombocytopenia. Blood. 2017;129:2864–2872. - PMC - PubMed
    1. Lubenow N, Hinz P, Thomaschewski S, et al. The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. Blood. 2010;115:1797–803. - PubMed
    1. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006;4:759–65. - PubMed

LinkOut - more resources