Endoscopic sinus surgery (ESS) and septoplasty are commonly performed otolaryngologic procedures and are standard surgical treatments for chronic rhinosinusitis and septal deviation [1]. Although these intranasal procedures are generally considered safe, postoperative epistaxis remains their most common complication because the nasal mucosa is highly vascular.

Most postoperative bleeding occurs immediately or within 24 hours after surgery (early postoperative bleeding) and is mainly attributable to local vascular injury or incomplete hemostasis at the surgical site. In most cases, it can be controlled with local measures, such as nasal packing or electrocautery [2]. By contrast, delayed hemorrhage occurring more than 24 hours after surgery, particularly when it develops several days postoperatively, is uncommon. Its potential etiologies are diverse and include infection, vascular lesions (e.g., pseudoaneurysm), and systemic coagulation disorders; therefore, a careful diagnostic approach is required [3,4]. In patients without a prior hematologic history, unexplained delayed massive hemorrhage may indicate an underlying systemic disorder rather than an isolated surgical complication [5,6].

Immune thrombocytopenia (ITP), formerly known as idiopathic thrombocytopenic purpura, is an acquired autoimmune disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production. Patients typically present with petechiae, purpura, and mucosal bleeding. When the platelet count falls below 20–30×10³/μL, the risk of life-threatening intracranial hemorrhage or major internal bleeding increases markedly [7]. ITP is usually diagnosed on the basis of characteristic cutaneous manifestations or spontaneous bleeding. However, postoperative onset of ITP presenting as delayed massive hemorrhage with an abrupt decline in platelet count despite normal preoperative blood test results is exceedingly rare.

We report the case of a 46-year-old man with no prior hematologic history who developed life-threatening delayed epistaxis 5 days after ESS and septoplasty. Diagnostic evaluation revealed severe acute ITP, and the patient responded well to treatment. This case underscores that otolaryngologists should consider rare hematologic emergencies such as ITP, in addition to local causes, in the differential diagnosis of otherwise unexplained delayed severe postoperative hemorrhage. We also discuss diagnostic and therapeutic strategies for managing such cases.

A 46-year-old man was transferred to our emergency department (ED) because of uncontrolled epistaxis. His medical history was notable for diabetes mellitus. In 2008, he was scheduled to undergo surgery for chronic rhinosinusitis at an outside hospital, but the procedure was aborted when he developed vasovagal syncope during anesthetic induction. In 2010, he underwent septoplasty for septal deviation under local anesthesia.

He later underwent revision septoplasty and bilateral ESS at a private otolaryngology clinic for severe rhinitis symptoms. Preoperative blood tests performed 9 days before surgery showed a hemoglobin level of 15.2 g/dL, a platelet count of 271×10³/μL, and normal coagulation profiles, including prothrombin time (PT) and activated partial thromboplastin time (aPTT). His postoperative course was initially uneventful, and he was discharged on postoperative day (POD) 1 after removal of the nasal packing. However, he was readmitted to the clinic on POD 5 because of uncontrolled epistaxis. Despite repeated nasal packing and application of local hemostatic agents, the bleeding could not be controlled, and he was transferred to our institution on POD 6.

On arrival, the patient was in hypovolemic shock, with a blood pressure of 50/30 mm Hg. Initial laboratory testing revealed severe anemia (hemoglobin, 6.9 g/dL) and profound thrombocytopenia (platelet count, 5×10³/μL). Immediate resuscitation for hemorrhagic shock was initiated, including rapid intravenous fluid administration and transfusion of 3 units of packed red blood cells and 16 units of platelet concentrates. After partial hemodynamic stabilization, the nasal cavity was examined, and persistent oozing was noted despite the existing packing (Fig. 1A and B). Bilateral nasal packing was then replaced with Vaseline gauze to provide compression of the nasal cavity while minimizing additional mucosal trauma.

Follow-up laboratory testing showed that the hemoglobin level increased from 6.9 g/dL to 9.0 g/dL, indicating partial correction of the anemia. In contrast, the platelet count decreased from 5×10³/μL to 4×10³/μL, a finding consistent with platelet transfusion refractoriness (Table 1). Peripheral blood smear (PBS) showed marked thrombocytopenia, neutrophilic leukocytosis, and normocytic normochromic anemia. Importantly, no microscopic evidence of platelet clumping was observed, confirming true thrombocytopenia and excluding EDTA-dependent pseudothrombocytopenia. In addition, no schistocytes suggestive of microangiopathic hemolysis were identified, making thrombotic thrombocytopenic purpura (TTP) unlikely.

The disseminated intravascular coagulation (DIC) profile showed elevated D-dimer (12.85 μg/mL) and fibrin/fibrinogen degradation products (34.61 μg/mL), yielding an International Society on Thrombosis and Haemostasis (ISTH) DIC score of 5 (Table 2). However, the fibrinogen level remained within the normal range (222 mg/dL), and PT and aPTT were only minimally prolonged. These findings were interpreted as secondary to acute hemorrhage rather than overt consumptive coagulopathy. On the basis of a working diagnosis of severe acute ITP, treatment was started immediately with intravenous immunoglobulin (IVIG) 1 g/kg and high-dose corticosteroids (prednisolone 60 mg).

Autoimmune screening, including antinuclear antibody, lupus anticoagulant, and anti-platelet antibodies, was unremarkable. Tests for hemolysis, including the direct antiglobulin test (Coombs test), haptoglobin, and lactate dehydrogenase, were also negative. In addition, screening for Helicobacter pylori and measurement of serum immunoglobulin levels showed no abnormalities. Drug-induced immune thrombocytopenia (DITP) was also considered because the patient had been exposed to multiple perioperative medications, including antibiotics (levofloxacin and clindamycin), analgesics (acetaminophen and tramadol), and other agents (bepotastine, montelukast, pseudoephedrine, and esomeprazole). However, the severity of thrombocytopenia accompanied by hypovolemic shock was atypical for DITP, which usually follows a milder clinical course. Although DITP could not be definitively excluded, the overall clinical course and laboratory findings favored ITP over a drug-induced etiology. Accordingly, secondary causes of thrombocytopenia were considered unlikely, and the overall findings were consistent with severe acute primary ITP.

During the ED stay, the patient developed melena and gross hematuria in addition to epistaxis, suggesting ongoing systemic bleeding. Because of persistent severe thrombocytopenia and continued bleeding tendency, he was admitted to the intensive care unit (ICU) for close monitoring and management. On ICU admission, the corticosteroid regimen was escalated from oral prednisolone to intravenous methylprednisolone (125 mg). Mycophenolate mofetil (MMF; 500 mg twice daily) was added as a steroid-sparing immunosuppressive agent because of concern for corticosteroid-refractory ITP and the need for sustained immunosuppression. Ceftriaxone (2 g) was administered concomitantly for prophylactic purposes. Intensive immunosuppressive therapy was continued, and a cumulative IVIG dose of 2 g/kg was completed by hospital day (HD) 2. Despite additional platelet transfusions, the platelet count remained critically low at 1–4 ×10³/μL, consistent with persistent platelet transfusion refractoriness.

On HD 3, the platelet count increased to 26×10³/μL, representing the first meaningful rise since admission. IVIG was discontinued, whereas intravenous methylprednisolone and MMF were continued. To support platelet recovery, an additional 16 units of platelet concentrates were transfused on the same day. Because a prompt platelet response became evident from HD 3 onward, bone marrow examination was deferred, consistent with current guidelines that do not recommend routine biopsy in newly diagnosed ITP when there is an adequate response to first-line therapy. On HD 4, the platelet count increased further to 96×10³/μL, and the patient was transferred to the general ward. That same day, bilateral nasal packing was removed, and no further active bleeding was observed. The nasal vestibules were kept moist to prevent mucosal dryness. From HD 5 onward, intravenous corticosteroids were transitioned to oral prednisolone (65 mg), whereas MMF was continued. The platelet count continued to increase (Fig. 2). On HD 9, the day of discharge, nasal endoscopy showed favorable healing at the surgical site without evidence of bleeding. The platelet count had normalized to 201×10³/μL.

After discharge, oral corticosteroids were tapered gradually over approximately 2 months while the platelet count remained stable and were then discontinued. Nasal mucosal wound healing was comparable to the usual postoperative course after ESS and septoplasty, and recovery was uneventful, with no recurrent epistaxis or other notable findings (Fig. 1C and D). At the last follow-up, he remained in good health without evidence of ITP relapse.

This case describes a rare presentation in which severe acute ITP was identified as the cause of delayed massive epistaxis occurring 5 days after ESS and septoplasty in a patient with no prior hematologic history.

In most patients, postoperative epistaxis after rhinologic surgery occurs immediately or within 24 hours (primary hemorrhage) and is usually related to local factors, such as inadequate hemostasis at the operative site [2,8]. In contrast, delayed hemorrhage occurring several days after surgery is uncommon and is more often attributed to premature sloughing of crusts, infection, or rupture of an aneurysm [3–5,9].

In the present patient, no obvious local source of bleeding was identified, and the abrupt decline in platelet count to <5×10³/μL appeared to be the principal cause of the delayed hemorrhage, an extremely unusual clinical scenario [10,11]. Acute ITP in adults is most commonly associated with antecedent viral infection, medication exposure, or lymphoproliferative disorders [7]. However, this patient had a normal preoperative platelet count (271×10³/μL) and no history of preceding infection that might have triggered ITP. These findings raise the possibility that the surgical procedure itself may have served as the precipitating event.

We therefore hypothesize that the surgical procedure itself may have acted as a precipitating factor for the onset of ITP. Surgical stress and tissue injury can promote a systemic inflammatory response characterized by cytokine release, including interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha, together with transient immune dysregulation. These changes may in turn precipitate an abnormal platelet-directed immune response [12,13]. Although the precise pathogenesis of postoperative ITP has not been fully elucidated, similar postoperative immune-mediated thrombocytopenic presentations have been reported in other surgical fields [7]. Notably, several of these cases were characterized by normal preoperative platelet counts, suggesting that the surgical insult itself may serve as the inciting event. Acute acquired ITP has been described after cardiac surgery, in which diagnosis required extensive workup to exclude other causes of immune-mediated platelet destruction, and prompt treatment with corticosteroids and IVIG was essential for recovery [14]. Acute-onset thrombocytopenia with presumptive ITP has also been described after mastectomy and axillary lymph node dissection, presenting as early as POD 2 in the absence of any identifiable secondary etiology [15]. In addition, severe immune-mediated thrombocytopenia refractory to conventional therapy but responsive to thrombopoietin receptor agonists has been described after revision arthroplasty [16]. Collectively, these reports support the biological plausibility that perioperative inflammatory perturbations may, in rare cases, precipitate severe autoimmune thrombocytopenic syndromes.

In the diagnostic workup of severe postoperative thrombocytopenia, a timing-based approach is essential because the differential diagnosis broadens substantially in late-onset thrombocytopenia, particularly when it occurs on or after POD 5. Under these circumstances, it is critical to distinguish ITP from other life-threatening hematologic conditions, including DIC, TTP, and DITP [11,17–20].

In the present case, true thrombocytopenia was first confirmed because PBS showed no microscopic evidence of platelet clumping, thereby effectively ruling out EDTA-dependent pseudothrombocytopenia. Subsequently, despite profound hypotension and massive hemorrhage at presentation, coagulation studies, including PT and aPTT, remained within normal limits, arguing against consumptive coagulopathy such as DIC. In addition, no schistocytes were identified on PBS, making TTP unlikely. Although the patient had been exposed to multiple perioperative medications, DITP was considered unlikely on several clinical grounds. First, the severity of thrombocytopenia accompanied by hemodynamic instability is atypical for DITP, which generally follows a milder clinical course [19]. Second, in classic DITP, platelet counts usually recover within days after discontinuation of the offending agent; in this case, however, thrombocytopenia persisted and remained refractory despite discontinuation of all suspected medications [21]. Third, and most importantly, the prompt and robust platelet recovery after IVIG and corticosteroid treatment is more consistent with a primary autoimmune mechanism than with a drug-dependent antibody-mediated process, in which immunomodulatory therapy would not be expected to produce such a definitive response [7,22]. Taken together, these findings strongly favored acute primary ITP over DITP. Furthermore, bone marrow examination was deferred in accordance with current guidelines because the patient had classic isolated thrombocytopenia without atypical findings on PBS and showed a rapid response to first-line therapy [7]. Overall, the presence of isolated thrombocytopenia in the absence of coagulopathy supported a prompt diagnosis of severe acute ITP and enabled timely initiation of appropriate immunomodulatory therapy [7,11]. This case underscores that comprehensive laboratory evaluation at presentation, including coagulation studies in addition to a complete blood count, is essential for establishing an accurate diagnosis in severe postoperative thrombocytopenia [11,17].

The primary goal of ITP treatment is to achieve hemostasis by raising the platelet count to a safe level [7]. Current guidelines recommend combined therapy with IVIG, high-dose corticosteroids, and platelet transfusion for patients with life-threatening bleeding [7,23].

A particularly notable finding in this case was the minimal increment in platelet count, which remained at 4×10³/μL even immediately after transfusion of 16 units of platelet concentrates. This pattern is consistent with platelet transfusion refractoriness in ITP, in which circulating autoantibodies rapidly destroy transfused platelets. Although the numerical response was negligible, platelet transfusion was still considered necessary to provide temporary hemostatic support during active bleeding. Sustained platelet recovery was achieved only after immunomodulatory therapy with IVIG and corticosteroids.

In conclusion, otolaryngologists should not regard delayed severe postoperative epistaxis, particularly after discharge, solely as a local complication. Even when preoperative laboratory findings are normal, serious systemic hematologic disorders such as ITP may develop unexpectedly in the postoperative period, and early recognition is critical to prevent catastrophic outcomes [7,11,24,25]. Accordingly, clinicians should promptly perform a comprehensive laboratory evaluation, including a complete blood count with PBS and coagulation studies, to identify potential systemic causes and exclude other life-threatening conditions [7,11,25]. Timely multidisciplinary management, particularly rapid hematology consultation and initiation of appropriate immunomodulatory therapy, remains essential when ITP is suspected or confirmed [7,24,25].

This case highlights the critical importance of prompt systemic hematologic evaluation in patients presenting with unexplained severe bleeding after routine nasal surgery, even when preoperative findings are normal.