Immune thrombocytopenic purpura as a predictor of postoperative complications in total knee arthroplasty: A nationwide cohort study

Aruni S. Areti; Paul Gudmundsson; Vinayak Perake; Senthil N. Sambandam

doi:10.1016/j.jor.2025.05.041

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68 (); 137-142

doi:

10.1016/j.jor.2025.05.041

Immune thrombocytopenic purpura as a predictor of postoperative complications in total knee arthroplasty: A nationwide cohort study

Aruni S. Areti^a,, Paul Gudmundsson^b, Vinayak Perake^c, Senthil N. Sambandam^b

a Baylor College of Medicine, 1 Baylor Plz, Houston, TX, 77030, USA

b UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA

c Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA

⁎Corresponding author: Aruni S. Areti. aruni.areti@bcm.edu

Received: 2025-4-7, Accepted: 2025-5-22, Published: 2025-5-27

Professor P K Surendran Memorial Education Foundation

Disclaimer:
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Total knee arthroplasty (TKA) is one of the most common joint replacement procedures in the United States, with increasing use among medically complex populations. Immune thrombocytopenic purpura (ITP), a rare autoimmune disorder marked by low platelet counts, may increase the risk of adverse postoperative outcomes.

We conducted a retrospective cohort study using the TriNetX Research Network, which includes de-identified electronic health records from over 74 million U.S. patients. Patients undergoing primary total knee arthroplasty (TKA) between 2005 and 2023 were identified using CPT code 27447. Immune thrombocytopenic purpura (ITP) was defined using ICD-9 code 287.3 and ICD-10 code D69.3 within one year prior to surgery. ITP patients were compared to non-ITP controls before and after 1:1 propensity score matching. Postoperative complications were identified using ICD codes. Odds ratios (ORs) and 95 % confidence intervals (CIs) were reported; p < 0.05 was considered significant.

We identified 3817 ITP patients and 233,543 non-ITP controls, with 3817 matched pairs in the final analysis. ITP was associated with increased odds of several postoperative complications. Infectious outcomes included higher rates of wound dehiscence (OR = 2.77), periprosthetic joint infection (OR = 5.40), and pneumonia (OR = 2.44) (all p < 0.001); deep surgical site infection was elevated pre-matching. Hematologic and cardiovascular complications included blood loss anemia (OR = 2.58), acute renal failure (OR = 2.67), and myocardial infarction (OR = 4.20). VTE events were more common, including deep vein thrombosis (OR = 2.44) and pulmonary embolism (OR = 2.90). Mechanical complications included periprosthetic fracture (OR = 3.18) and mechanical failure (OR = 4.20) (all p ≤ 0.002).

ITP was a significant risk factor for complications following TKA, underscoring the need for preoperative risk stratification and tailored perioperative management in this high-risk population.

Keywords

Immune thrombocytopenic purpura

Total knee arthroplasty

Postoperative complications

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1 Introduction

Total knee arthroplasty (TKA) is the most commonly performed joint replacement procedure in the U.S., primarily addressing advanced knee osteoarthritis to relieve pain and improve function.¹ The annual volume of TKAs has steadily increased, with over 670,000 procedures performed annually by 2012. Demand is projected to rise significantly, reaching 3.48 million procedures per year by 2030, with an estimated 855 % increase by 2050.² Additionally, the proportion of younger patients undergoing TKA is growing, particularly those under 55 years, who are expected to be the fastest-growing cohort by 2030, reflecting a broader demographic shift toward younger recipients.³ Therefore, as TKA candidacy expands to a more diverse and often medically complex population, it is critical to examine risk factors that may contribute to poor postoperative outcomes to optimize patient selection and perioperative management.

Despite extensive research identifying risk factors for poor outcomes following total knee arthroplasty (TKA), the impact of immune thrombocytopenic purpura (ITP) remains underexplored. ITP is an autoimmune disorder characterized by a low platelet count due to increased platelet destruction and impaired platelet production, leading to a variable risk of bleeding.⁴ Its effects have been studied in other surgical contexts, including total hip arthroplasty (THA), where patients with ITP have been shown to have higher transfusion requirements and an increased risk of bleeding.⁵ This is particularly concerning, as studies have shown that increased transfusion requirements and higher bleeding risk are associated with greater rates of surgical site infections (SSI), prolonged hospitalization, and a higher likelihood of ICU admission.⁶^,⁷

Ultimately, our study leverages a large cohort of patients to evaluate the impact of ITP on postoperative outcomes in TKA. By identifying potential risks associated with ITP, our findings aim to guide physicians in optimizing patient selection and perioperative management, particularly as the demand for TKA continues to grow exponentially.

2 Methods

2.1

2.1 Database Description

This retrospective cohort study utilized the TriNetX Research Network (https://trinetx.com, Cambridge, MA, USA). The data used in this study were collected on December 20, 2023, from the TriNetX Research Network, which provides access to electronic medical records, including diagnoses, procedures, medications, laboratory values, and genomic information, from approximately 74 million patients across 82 U S. healthcare organizations. TriNetX complies with the Health Insurance Portability and Accountability Act (HIPAA) and is ISO 27001:2013 certified, ensuring data protection and privacy.

2.2

2.2 Data acquisition

This study was Institutional Review Board exempt as it involved a secondary analysis of de-identified data, with no human subject interaction or intervention, per Section 164.514(a) of the HIPAA Privacy Rule. In this study, patients who underwent primary total knee arthroplasty (TKA) were identified using Current Procedural Terminology (CPT) code 27447 for surgeries performed between 2005 and 2023. Patients with a prior diagnosis of immune thrombocytopenic purpura (ITP) were identified using ICD-9 code 287.3 and ICD-10 code D69.3 up to one year before TKA. These patients comprised the ITP-positive TKA group, while those without ITP were included in the non-ITP control group.

Preoperative variables analyzed included sex, race, ethnicity, marital status, White race, Black race, Hispanic race, age over 65, diabetes, obesity, and smoking status. Postoperative outcomes assessed included deep surgical site infection (DSSI), wound dehiscence, periprosthetic infection, superficial surgical site infection (SSSI), acute renal failure, blood loss anemia, cardiac arrest and ventricular fibrillation, deep vein thrombosis (DVT), periprosthetic mechanical complications, myocardial infarction, pulmonary embolism (PE), periprosthetic fracture, pneumonia, and blood transfusion requirements.

2.3

2.3 Data analysis

The date of TKA was designated as the index event, from which the follow-up period began. Demographic information about patients was initially compiled using descriptive statistics. Independent samples t-tests were employed to examine continuous variables, while chi-squared tests were used to analyze categorical variables. Fisher's exact tests were applied when incidence values were less than five. To address baseline differences between the ITP and control cohorts, a 1:1 propensity score matching analysis was conducted. Patients were matched on the basis of age ≥65 years, sex, diabetes status, obesity, race, and smoking status using nearest-neighbor matching without replacement. For all tests, a p-value of less than 0.05 was regarded as statistically significant. The ratio of the incidence of medical and surgical complications in the ITP-positive group to the incidence in the non-ITP group was reported as odds ratios, along with their corresponding 95 % confidence intervals.

2.4

2.4 Software employed for statistical analysis and data visualization

Data compilation was performed using the TriNetX Live platform. Data management and statistical analysis were conducted using SPSS version 29 (IBM), while Microsoft Excel was employed for additional statistical analysis and data visualization.

2.5

2.5 Data integrity and ethical considerations

The TriNetX platform complies with HIPAA and GDPR regulations, ensuring data security and patient privacy by using only de-identified, aggregate data. This study was Institutional Review Board exempt as it involved a secondary analysis of de-identified data, with no human subject interaction or intervention, per Section 164.514(a) of the HIPAA Privacy Rule.

3 Results

Among patients undergoing TKA, 3817 were identified as Immune Thrombocytopenia (+), while 233,543 were included in the Control group. Table 1 summarizes the demographic characteristics of these groups. Patients in the Immune Thrombocytopenia (+) group were significantly older than those in the control group, with a mean age of 68.64 years compared to 66.97 years (p < 0.001).

Table 1 Patient demographic characteristics of immune thrombocytopenia (+) and control group.

Variable		Experiemental Group (n = 3817)	Control Group (n = 233543)	Significance
Age		68.64	66.97	<0.001∗
Sex (Males)		2011 (52.69 %)	87107 (37.30 %)	<0.001∗
Sex (Females)		1613 (42.26 %)	137393 (58.83 %)	<0.001∗
Marital Status
	Married	962 (25.20 %)	69548 (29.78 %)	<0.001∗
	Single	586 (15.35 %)	39422 (16.88 %)	<0.001∗
	Unknown	2269 (59.44 %)	124573 (53.34 %)	<0.001∗
Diabetes		1176 (30.81 %)	46012 (19.70 %)	<0.001∗
Smoking		1082 (28.35 %)	45989 (19.69 %)	<0.001∗
Obesity		1714 (44.90 %)	80699 (34.55 %)	<0.001∗
	American Indian or Alaska Native	16 (0.42 %)	628 (0.27 %)	<0.001∗
	Asian	67 (1.76 %)	4834 (2.07 %)	<0.001∗
	Black or African American	273 (7.15 %)	22828 (9.77 %)	<0.001∗
	Native Hawaiian or Other Pacific Islander	4 (0.10 %)	475 (0.20 %)	<0.001∗
	Other Race	81 (2.12 %)	5690 (2.44 %)	<0.001∗
	Hispanic	435 (11.40 %)	24392 (10.44 %)	<0.001∗
	White	2941 (77.05 %)	174696 (74.80 %)	<0.001∗
Ethnicity
	Ethnicity - Hispanic or Latino	187 (4.90 %)	12157 (5.21 %)	<0.001∗
	Ethnicity - Not Hispanic or Latino	2783 (72.91 %)	175317 (75.07 %)	<0.001∗

Sex differences were significant, with more males in the Immune Thrombocytopenia (+) group (52.69 % vs. 37.30 %) and fewer females (42.26 % vs. 58.83 %) (both p < 0.001). Marital status differed as well—fewer thrombocytopenic patients were married (25.20 % vs. 29.78 %) or single (15.35 % vs. 16.88 %), while more had an unknown status (59.44 % vs. 53.34 %) (all p < 0.001).

Several comorbid conditions were significantly more prevalent among patients with Immune Thrombocytopenia (+). Immune Thrombocytopenic patients had higher rates of diabetes (30.81 % vs. 19.70 %), smoking (28.35 % vs. 19.69 %), and obesity (44.90 % vs. 34.55 %) (p < 0.001).

Racial and ethnic distributions varied between groups. The Immune Thrombocytopenia (+) group had a greater proportion of American Indian or Alaska Native patients (0.42 % vs. 0.27 %) and a lower proportion of Black (7.15 % vs. 9.77 %) and Asian (1.76 % vs. 2.07 %) patients (p < 0.001 for all comparisons). The proportion of White patients was higher in the Immune Thrombocytopenia (+) group (77.05 % vs. 74.80 %, p < 0.001). Regarding ethnicity, the Immune Thrombocytopenia (+) group had a slightly lower proportion of Hispanic or Latino patients (4.90 % vs. 5.21 %), while the majority in both groups were non-Hispanic (72.91 % vs. 75.07 %) (p < 0.001).

Postoperative complications among patients with and without thrombocytopenia are summarized in Table 2 (unmatched cohort) and Table 3 (post-propensity matched cohort).

Table 2 Outcome analysis of immune thrombocytopenia (+) and control group prior to propensity matching.

Variable	Experiemental Group (n = 3817)	Control Group (n = 233543)	Odds Ratio	Significance
Superficial Surgical Site Infection	7 (0.18 %)	208 (0.09 %)	2.06 (0.97–4.38)	0.055
Deep Surgical Site Infection	3 (0.08 %)	25 (0.01 %)	7.35 (2.22–24.34)	<0.001∗
Wound Dehiscence	52 (1.36 %)	1194 (0.51 %)	2.69 (2.03–3.55)	<0.001∗
Periprosthetic Infection	111 (2.91 %)	1815 (0.78 %)	3.82 (3.15–4.64)	<0.001∗
Pneumonia	61 (1.60 %)	1414 (0.61 %)	2.67 (2.06–3.45)	<0.001∗
Acute Renal Failure	292 (7.65 %)	4382 (1.88 %)	4.33 (3.83–4.90)	<0.001∗
Blood Loss Anemia	634 (16.61 %)	14902 (6.38 %)	2.92 (2.68–3.19)	<0.001∗
Blood Transfusion	6 (0.16 %)	99 (0.04 %)	3.71 (1.63–8.47)	<0.001∗
Cardiac Arrest and Ventricular Fibrillation	8 (0.21 %)	99 (0.04 %)	4.95 (2.41–10.19)	<0.001∗
Myocardial Infarction	22 (0.58 %)	479 (0.21 %)	2.82 (1.84–4.33)	<0.001∗
Deep Vein Thrombosis	131 (3.43 %)	2882 (1.23 %)	2.84 (2.38–3.40)	<0.001∗
Pulmonary Embolism	96 (2.52 %)	1902 (0.81 %)	3.14 (2.55–3.87)	<0.001∗
Manipulation Under Anesthesia <4 Months	89 (2.33 %)	6610 (2.83 %)	0.82 (0.66–1.01)	0.065
Periprosthetic Mechanical Complication	22 (0.58 %)	817 (0.35 %)	1.65 (1.08–2.52)	0.019
Periprosthetic Fracture	30 (0.79 %)	528 (0.23 %)	3.50 (2.42–5.06)	<.001∗

Table 3 Outcome analysis of immune thrombocytopenia (+) and control group post propensity matching.

Variable	Experiemental Group (n = 3817)	Control Group (n = 3624)	Odds Ratio	Significance
Superficial Surgical Site Infection	7 (0.18 %)	7 (0.19 %)	0.95 (0.33–2.71)	0.923
Deep Surgical Site Infection	3 (0.08 %)	0 (0.00 %)	–	0.091
Wound Dehiscence	52 (1.36 %)	18 (0.50 %)	2.77 (1.62–4.74)	<0.001∗
Periprosthetic Infection	111 (2.91 %)	20 (0.55 %)	5.40 (3.35–8.71)	<0.001∗
Pneumonia	61 (1.60 %)	24 (0.66 %)	2.44 (1.52–3.92)	<0.001∗
Acute Renal Failure	292 (7.65 %)	109 (3.01 %)	2.67 (2.13–3.35)	<0.001∗
Blood Loss Anemia	634 (16.61 %)	260 (7.17 %)	2.58 (2.21–3.00)	<0.001∗
Blood Transfusion	6 (0.16 %)	3 (0.08 %)	1.90 (0.48–7.60)	0.356
Cardiac Arrest and Ventricular Fibrillation	8 (0.21 %)	2 (0.06 %)	3.80 (0.81–17.92)	0.069
Myocardial Infarction	22 (0.58 %)	5 (0.14 %)	4.20 (1.59–11.09)	0.002∗
Deep Vein Thrombosis	131 (3.43 %)	52 (1.43 %)	2.44 (1.77–3.38)	<0.001∗
Pulmonary Embolism	96 (2.52 %)	32 (0.88 %)	2.90 (1.94–4.33)	<0.001∗
Manipulation Under Anesthesia <4 Months	89 (2.33 %)	84 (2.32 %)	1.01 (0.74–1.36)	0.969
Periprosthetic Mechanical Complication	22 (0.58 %)	5 (0.14 %)	4.20 (1.59–11.09)	0.002∗
Periprosthetic Fracture	30 (0.79 %)	9 (0.25 %)	3.18 (1.51–6.71)	0.001∗

In the unmatched cohort (Table 2), SSSI was higher in the thrombocytopenic group (0.18 %) compared to controls (0.09 %), though this difference was not statistically significant (OR = 2.06 [0.97–4.38], p = .055). DSSI was significantly higher in the thrombocytopenic group compared to controls (0.08 % vs. 0.01 %; OR = 7.35 [2.22–24.34], p < .001). Wound dehiscence (1.36 % vs. 0.51 %; OR = 2.69 [2.03–3.55], p < .001), periprosthetic infection (2.91 % vs. 0.78 %; OR = 3.82 [3.15–4.64], p < .001), and pneumonia (1.60 % vs. 0.61 %; OR = 2.67 [2.06–3.45], p < .001) were significantly higher in the thrombocytopenic group.

Hematologic and cardiovascular complications, including acute renal failure (7.65 % vs. 1.88 %; OR = 4.33 [3.83–4.90], p < .001), blood loss anemia (16.61 % vs. 6.38 %; OR = 2.92 [2.68–3.19], p < .001), blood transfusion (0.16 % vs. 0.04 %; OR = 3.71 [1.63–8.47], p < .001), cardiac arrest and VF (0.21 % vs. 0.04 %; OR = 4.95 [2.41–10.19], p < .001), and MI (0.58 % vs. 0.21 %; OR = 2.82 [1.84–4.33], p < .001), were significantly more frequent among thrombocytopenic patients.

VTE complications, specifically DVT (3.43 % vs. 1.23 %; OR = 2.84 [2.38–3.40], p < .001) and PE (2.52 % vs. 0.81 %; OR = 3.14 [2.55–3.87], p < .001), were significantly higher in thrombocytopenic patients.

Mechanical and periprosthetic complications, including periprosthetic mechanical complications (0.58 % vs. 0.35 %; OR = 1.65 [1.08–2.52], p = .019) and periprosthetic fractures (0.79 % vs. 0.23 %; OR = 3.50 [2.42–5.06], p < .001), were significantly higher in the thrombocytopenic group. Manipulation under anesthesia within 4 months was not significantly different between groups (2.33 % vs. 2.83 %; OR = 0.82 [0.66–1.01], p = .065).

In the post-propensity matched cohort (Table 3), SSSI was not significantly different between the two groups (0.18 % vs. 0.19 %; OR = 0.95 [0.33–2.71], p = .923). DSSI was observed only in the thrombocytopenic group (0.08 % vs. 0.00 %), but this difference did not achieve statistical significance (p = .091). Wound dehiscence (1.36 % vs. 0.50 %; OR = 2.77 [1.62–4.74], p < .001), periprosthetic infection (2.91 % vs. 0.55 %; OR = 5.40 [3.35–8.71], p < .001), and pneumonia (1.60 % vs. 0.66 %; OR = 2.44 [1.52–3.92], p < .001) remained significantly higher in thrombocytopenic patients.

Hematologic and cardiovascular complications remained significantly elevated post-matching for acute renal failure (7.65 % vs. 3.01 %; OR = 2.67 [2.13–3.35], p < .001), blood loss anemia (16.61 % vs. 7.17 %; OR = 2.58 [2.21–3.00], p < .001), and MI (0.58 % vs. 0.14 %; OR = 4.20 [1.59–11.09], p = .002). Blood transfusion (0.16 % vs. 0.08 %; OR = 1.90 [0.48–7.60], p = .356) and cardiac arrest and VF (0.21 % vs. 0.06 %; OR = 3.80 [0.81–17.92], p = .069) were not significantly different post-matching.

VTE complications remained significantly higher post-matching for DVT (3.43 % vs. 1.43 %; OR = 2.44 [1.77–3.38], p < .001) and PE (2.52 % vs. 0.88 %; OR = 2.90 [1.94–4.33], p < .001).

Mechanical and periprosthetic complications, including periprosthetic mechanical complications (0.58 % vs. 0.14 %; OR = 4.20 [1.59–11.09], p = .002) and periprosthetic fractures (0.79 % vs. 0.25 %; OR = 3.18 [1.51–6.71], p = .001), remained significantly increased post-matching. Manipulation under anesthesia within 4 months remained not significantly different between groups post-matching (2.33 % vs. 2.32 %; OR = 1.01 [0.74–1.36], p = .969).

4 Discussion

Thrombocytopenia, broadly defined as a platelet count below 150 × 10³/μL, has been linked to adverse surgical outcomes such as bleeding, infection, poor wound healing, and prolonged hospital stays.^8–11 However, immune thrombocytopenic purpura —a distinct and clinically relevant subset of thrombocytopenia—has not been previously examined in the context of total knee arthroplasty (TKA). Our study is the first to evaluate this specific population, and using the largest cohort of ITP patients undergoing TKA to date, we found that ITP was associated with significantly increased risk across four major complication categories: (1) infectious complications, (2) hematologic and cardiovascular complications, (3) venous thromboembolism (VTE) and related events, and (4) mechanical and periprosthetic complications.

Among infectious complications, ITP patients demonstrated significantly higher odds of wound dehiscence, periprosthetic joint infection, and postoperative pneumonia, with deep surgical site infection also notably elevated prior to matching—highlighting their heightened susceptibility to both local and systemic infections. This vulnerability may stem in part from the critical role platelets play in both hemostasis and immune defense. In the setting of ITP, impaired platelet plug formation at sites of vascular injury compromises wound healing and tissue repair, thereby increasing the risk of wound dehiscence and secondary infection.¹² Supporting this, Greig et al. demonstrated that platelet deficiency in a mouse model led to increased bacterial burden and severity of PJI, underscoring the importance of platelet-mediated antimicrobial defense.¹³ Zhu et al. further identified wound dehiscence as a significant risk factor for PJI, emphasizing the need for meticulous wound care in this population.¹⁴ Beyond their role in clot formation, platelets also actively modulate innate immune responses. They interact with monocytes to regulate gene expression, enhance leukocyte recruitment, serve as a source of antimicrobial proteins, and engage with neutrophils to augment bactericidal activity.^15–17 Taken together, these findings suggest that both impaired hemostasis and immune dysregulation contribute to the elevated infectious complication rates observed in ITP patients undergoing TKA.

Our study found that ITP patients had an increased risk of blood loss anemia, which is well-established in the current literature as a key driver of transfusion requirements—a relationship that was also observed in our unmatched cohort, where blood transfusions were significantly more common among ITP patients.⁷^,¹² Platelets are key to the initial formation of a hemostatic plug at sites of vascular injury. When platelet counts are low, the ability to form these plugs is compromised, leading to increased bleeding risk during surgery, requiring increased blood transfusions.¹⁶^,¹⁸ These increased risk of blood transfusions may serve as a modulatory factor contributing to the increased risk of postoperative infection.⁹^,¹⁹ This is further supported by prior work, including a study by Xu et al., which identified perioperative transfusions as an independent risk factor for postoperative infections.²⁰

Despite being characterized by thrombocytopenia, ITP paradoxically promotes a chronic prothrombotic state, which may underlie the increased rates of thrombotic complications—such as myocardial infarction, acute renal failure, deep vein thrombosis (DVT), and pulmonary embolism (PE)—observed in our study as well as others.⁸^,¹⁰^,¹⁸ Autoantibody-mediated platelet destruction triggers compensatory megakaryopoiesis, releasing immature, hyperreactive platelets with heightened thrombotic potential.²¹ Concurrently, systemic immune activation involving T cells, macrophages, and elevated cytokines such as IL-6 and TNF-α contributes to endothelial dysfunction.²² Activated endothelial cells express adhesion molecules (e.g., ICAM-1, VCAM-1) and procoagulant factors such as tissue factor, which may ultimately promote the development of microthrombi within the microvasculature of vital organs, including the kidneys, heart, and lungs.^23–25 In parallel, this prothrombotic environment increases susceptibility to macrovascular events such as DVT and PE, particularly in the setting of immobility or surgical stress.²⁶ Surgery acts as a potent pro-inflammatory and pro-coagulant stimulus, compounding the existing vascular dysregulation and precipitating acute thrombotic events in patients already primed by chronic immune and endothelial activation.

However, it is important to recognize that complications such as acute renal failure (ARF) in patients with ITP likely have a multifactorial etiology. Direct mechanisms include autoimmune platelet activation and endothelial dysfunction, both of which contribute to a prothrombotic environment that may impair renal microcirculation.¹⁸ Indirect mechanisms may involve perioperative factors such as the administration of therapies like anti-D immunoglobulin, which has been associated with hemolysis and subsequent renal impairment.²⁷ Additionally, increased transfusion requirements may exacerbate renal dysfunction through inflammatory responses, immune modulation, or volume overload.²⁸^,²⁹ In addition, several studies have found that increased perioperative blood transfusions are also a significant risk factor for cardiac complications, suggesting a modulatory role in patients with ITP.⁷^,³⁰ For example, Whitlock et al. demonstrated that even a single unit of perioperative packed red blood cells was linked to a higher risk of ischemic stroke and myocardial infarction, with risk escalating with additional units transfused.³¹

Our study identified an increased risk of periprosthetic fracture and mechanical complications in patients with ITP following surgery—an underrecognized complication in this population. While not specific to periprosthetic fractures, Mannering et al. demonstrated that patients with ITP are at elevated risk for fractures overall. This increased fracture risk is likely multifactorial, with corticosteroid therapy—commonly used in the treatment of ITP—playing a significant role.³² Supporting this, Tantawy et al. found that children and adolescents with chronic ITP receiving corticosteroids had significantly lower bone mineral density (BMD) at the spine and hip, along with elevated markers of bone resorption compared to healthy controls.³³ In addition, Haft et al. demonstrated that patients on chronic corticosteroids had higher risks of fragility fractures and periprosthetic joint infections following TKA, which can undermine the stability of the prosthesis.³⁴ Together, these findings emphasize the importance of recognizing and mitigating fracture risk—including periprosthetic fractures—in the perioperative care of ITP patients undergoing orthopedic procedures.

Given these findings, clinicians should approach total knee arthroplasty in patients with ITP with heightened vigilance. Preoperative optimization—including platelet monitoring and hematology consultation when appropriate—may help mitigate bleeding and infection risks. Surgeons should maintain a high index of suspicion for wound healing complications, periprosthetic infection, and thrombotic events in the perioperative period. Additionally, our results underscore the importance of counseling patients with ITP regarding their elevated risk for postoperative complications, including blood loss anemia, infectious events, and mechanical failures such as periprosthetic fracture. Close postoperative monitoring, careful transfusion decision-making, and multidisciplinary coordination may improve outcomes in this unique patient population.

4.1

4.1 Limitations

This study also has several important limitations. First, clinical granularity was limited, as data on disease severity, platelet counts, and specific ITP treatments were unavailable, preventing stratification by disease burden or therapeutic response. This lack of granularity is particularly relevant given the heterogeneity of immune thrombocytopenia, as outcomes may significantly differ depending on treatment modalities (such as steroid use or splenectomy), duration and severity of disease, or refractory status—factors that are typically unavailable in administrative databases. Additionally, corticosteroid exposure—a known contributor to both fracture risk and infection—was not quantified in terms of dose or duration, limiting our ability to directly assess its impact. Furthermore, reliance on ICD codes alone to identify ITP may introduce substantial misclassification bias, as some patients labeled with ITP may have had transient thrombocytopenia or a different underlying cause altogether. There is also potential for confounding by indication, as patients with ITP may have received different perioperative management or had comorbid conditions not fully captured in the dataset. Finally, the generalizability of our findings may be limited, as national databases often underrepresent certain racial, ethnic, and socioeconomically disadvantaged populations and may not reflect outcomes in lower-resource or non-hospital settings.

5 Conclusion

In one of the largest cohort studies to date examining immune thrombocytopenic purpura (ITP) in the context of total knee arthroplasty (TKA), we identified significantly increased risks of infectious, hematologic, thromboembolic, and mechanical complications among ITP patients. As TKA utilization grows among medically complex populations, clinicians should carefully consider ITP in preoperative risk stratification. Future research should focus on evaluating perioperative platelet thresholds, optimizing transfusion strategies, and assessing the impact of ITP treatment regimens—such as corticosteroid tapering or thrombopoietin receptor agonist use—on surgical outcomes to inform evidence-based guidelines for this high-risk group.

CRediT authorship contribution statement

Aruni S. Areti: Investigation, Formal analysis, Visualization, Project administration, Writing – original draft. Paul Gudmundsson: Writing – review & editing. Vinayak Perake: Methodology, Writing – review & editing. Senthil N. Sambandam: Data curation, Software, Supervision.

Ethical approval and patient consent

Not applicable.

Declaration of patient consent

Not applicable.

Funding

This research did not receive any specific grant from public, commercial, or not-for-profit funding agencies.

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