Navigating hemostasis: anesthetic challenges in a pituitary tumor with type 2 von Willebrand disease—case report

Introduction

von Willebrand disease (VWD) is the most common hereditary bleeding disorder and represents a considerable proportion of coagulopathies diagnosed worldwide. It is estimated that approximately one quarter of individuals with coagulopathies have VWD, surpassing in prevalence other disorders such as hemophilia A or B (1). In Colombia, epidemiological records report a crude prevalence of 5.31 cases per-100,000 inhabitants, making it an underdiagnosed disease despite its clinical relevance (2).

The anesthetic management of patients with hematologic disorders represents a significant perioperative challenge, especially in cases of VWD, due to the high risk of bleeding, which is further increased when the surgery involves critical structures such as brain tumors. This risk depends on factors such as plasma levels of von Willebrand factor (VWF), bleeding history, and response to prior treatments (3). Clinical manifestations vary according to the type and severity of the deficit, ranging from mild forms with recurrent epistaxis, menorrhagia, or spontaneous bruising to severe presentations with disproportionate intraoperative or postoperative hemorrhage (4).

From a pathophysiological standpoint, VWD is characterized by deficiency or dysfunction of VWF, a glycoprotein essential for hemostasis, facilitating platelet adhesion and aggregation at sites of vascular injury and serving as a carrier protein for FVIII. Its deficiency leads to an ineffective platelet plug and decreased clot stability (5). Three main types of VWD are recognized: types 1 and 3, due to partial or complete quantitative deficiency of VWF, and type 2, due to a qualitative alteration of its function. The is subdivided into four distinct subtypes (2A, 2B, 2M, and 2N), each characterized by specific functional abnormalities affecting different aspects of VWF biology (4–6).

Pituitary neuroendocrine tumor (PitNET) account for 10%–15% of all intracranial tumors and are the second most common primary brain tumors (7). Transsphenoidal surgery (TSS) remains the gold standard treatment for PitNETs meeting surgical indications (7). However, their proximity to critical neurovascular structures—such as the cavernous sinuses and internal carotid arteries—increases the risk of intraoperative and postoperative hemorrhage (8, 9).

In this context, the anesthetic management of patients with VWD undergoing TSS requires an interdisciplinary strategy focused on bleeding prevention, advanced hemodynamic monitoring, and individualized hemostatic replacement. This case report describes the process from the selection of the anesthetic technique, prioritizing hemodynamic stability, to intraoperative hemostatic control and prevention of postoperative complications, all framed within perioperative planning based on international guidelines (4, 8).

Case report

A 42-year-old male patient with a history of type 2 VWD and hypothyroidism on oral levothyroxine 100 mcg daily presented with a one-year history of intense headache associated with diplopia and progressive decrease in visual acuity, compatible with bilateral compressive optic neuropathy and bitemporal hemianopsia. On physical examination, corrected visual acuity was 20/100 in the right eye and 20/20 in the left eye. No signs of ophthalmoparesis or cavernous sinus syndrome.

Brain magnetic resonance imaging showed a pituitary tumor with characteristics of PitNET Knosp grade 3A, considering the extension of the lesion in relation to the lateral intracavernous carotid line, with compression of the third ventricle and the hypothalamic–chiasmatic region (Figure 1). The patient's preoperative hormonal profile was within the normal limits. Consequently, the lesion was classified as a non-functioninal PitNET (NF-PitNET), indicating that the clinical and neurosurgical management would focus on mass decompression with a TSS resection.

Hematologic laboratory studies revealed a complete blood count within normal ranges as well as adequate coagulation parameters. The preoperative VWD parameters showed a VWF Antigen (VWF:Ag)/Activity (%) at 0.6, VWF:RCo 35.8%, and FVIII at 52%. Thyroid function was normal (TSH: 1.33 µIU/mL; free T4: 6.9 µg/dL) and the electrocardiogram was unremarkable.

Preoperative assessment

The patient was evaluated by anesthesiology and hematology and classified as American Society of Anesthesiologists (ASA) III, with a Revised Cardiac Risk Index (RCRI) < 1% and a Johns Hopkins (JH) score of 4/5.

The surgical procedure was authorized, and preoperative levels of VWF:Ag, VWF:RCo, and FVIII were requested, in addition to baseline thromboelastography (TEG) 24 h before the surgical incision.

The diagnosis of type 2 VWD in this patient was re confirmed based on the qualitative discrepancy between VWF:Ag and functional VWF activity. The preoperative VWF:Ag/Activity ratio was significantly reduced at 0.6, which, alongside a VWF:RCo of 35.8% and FVIII of 52%, confirms a qualitative defect rather than a purely quantitative one (Table 1).

Table 1. Perioperative hemostatic and hematologic profile evolution. The table details the dynamic changes in coagulation factors, TEG parameters, complete blood count, and standard coagulation times across the preoperative, intraoperative, and postoperative phases.

VWD, von Willebrand Disease; VWF, von Willebrand Factor; VWF:Ag, VWF Antigen; VWF:RCo, VWF Ristocetin Cofactor; FVIII, Factor VIII; TEG, Thromboelastography; R-time, Reaction time; K-time, Clot kinetics; MA, Maximum amplitude; PT, Prothrombin Time; aPTT, activated Partial Thromboplastin Time; INR, International Normalized Ratio; v, reference value.

Note the baseline preoperative characteristic of type 2 VWD (VWF:Ag/Activity ratio of 0.6) and the normalization of intraoperative and postoperative parameters after the targeted VWF/FVIII concentrate replacement (VWF:Ag/Activity ratio of 0.9% and 1.1%, respectively).

Intraoperative monitoring

Standard monitoring was performed with noninvasive blood pressure (NIBP), electrocardiography, pulse oximetry, capnography, and temperature, as well as invasive monitoring with a radial arterial line, right subclavian central venous catheter under ultrasound guidance, urinary catheter, processed four-channel electroencephalography (SedLine), and regional cerebral oximetry (O₃) by near-infrared spectroscopy (NIRS) (Figure 2).

Advanced hemodynamic monitoring with the FloTrac™ (Edwards Lifesciences, Irvine, CA, EE. UU.) reported: cardiac index 3.0 L/min/m², stroke volume index (SVI) 69 mL/beat/m², central venous pressure (CVP) 10 mmHg, and systemic vascular resistance (SVR) 948 dyn·s/cm⁵, requiring norepinephrine at 0.02–0.04 µg/kg/min (Figure 2). A total of 1,200 mL of balanced crystalloids (600 mL of 0.9% saline and 600 mL of Ringer's lactate) were administered, guided by a goal-directed resuscitation strategy.

Induction and maintenance of anesthesia

The patient weighed 70 kg and measured 1.81 m in height. Total intravenous anesthesia (TIVA) was delivered using target-controlled infusion (TCI). Propofol was administered according to the Schnider model, with an effect-site concentration (Ce) of 6.0 µg/mL for induction and 4.5 µg/mL for maintenance. Remifentanil was delivered using the Minto model, with a Ce of 6.0 ng/mL during induction and 4–5 ng/mL during maintenance, titrated according to SedLine monitoring [Patient State Index (PSI) 34–38] and bilateral near-infrared spectroscopy (NIRS; O₃ average 73%–75%). A dexmedetomidine infusion was administered (Ce 0.7 ng/mL), and neuromuscular blockade was achieved with rocuronium 30 mg IV, followed by orotracheal intubation with a 7.5-mm endotracheal tube.

Prior to the initial incision for transsphenoidal surgery (TSS), local infiltration of the nasal mucosa was performed to optimize hemostatic stability and surgical field visualization. A total of 5 mL of 1% lidocaine with epinephrine (1:200,000) was infiltrated into the nasal septum and turbinates.

Mechanical ventilation was maintained using a protective strategy, with a tidal volume of 480 mL, respiratory rate of 17 breaths/min, FiO₂ of 40%, PEEP of 7 cmH₂O, plateau pressure of 22 cmH₂O, and driving pressure of 12 cmH₂O.

The total duration of anesthesia was 342 min. The estimated total doses administered were 2,714.2 mg of propofol and 4,047 µg of remifentanil, corresponding to average infusion rates of 6.8 mg/kg/h and 0.17 µg/kg/min, respectively.

Hemostatic management

One hour before anesthetic induction, plasma-derived VWF/FVIII concentrate (Wilate® 500 IU in 5 mL; OCTAPHARMA PHARMACEUTICALS) was administered intravenously with the goal of achieving plasma levels between 80% and 100%. These values were verified by quantification of VWF and FVIII four hours after the start of surgery, as well as by intraoperative TEG performed one hour after the incision, with parameters remaining within normal ranges (Figure 2). This was complemented with tranexamic acid (bolus of 10 mg/kg followed by continuous infusion at 2 mg/kg/h) and administration of hydrocortisone 50 mg IV after induction, given the potential risk of panhypopituitarism.

Total blood loss was 500 mL, with sustained hemodynamic stability and blood gas parameters within target ranges: pH: 7.36, PaO₂: 148 mmHg, PaCO₂: 32 mmHg, Hb: 12.4 g/dL, HCO₃: 18.2 mmol/L, and lactate: 1.3 mmol/L. Intraoperative urine output was 1,200 mL (5.3 mL/kg/h), with a negative fluid balance of 200 mL.

Analgesia and extubation

Multimodal analgesia was implemented with paracetamol 1 g IV, hydromorphone 0.4 mg IV, and local infiltration. Postoperative nausea and vomiting prophylaxis included dexamethasone 4 mg IV, ondansetron 4 mg IV, and haloperidol 1 mg IV. Given the adequate neurological, hemostatic, hemodynamic, and ventilatory evolution, safe extubation was performed, and the patient was transferred to the intensive care unit (ICU) for monitoring and follow-up.

Postoperative follow-up

Four hours after surgery, VWF and FVIII levels were 80.9% and 76%, respectively, justifying administration of a new dose of 500 IU/500 IU. During the ICU stay, VWF and FVIII levels were maintained >50%, with a replacement scheme of 500 IU every 12 h until day 4, then every 24 h until day 6, and subsequently every 48 h until completing 10 days.

During this period, the patient presented polyuria (7.3 mL/kg/h), without criteria for neurogenic diabetes insipidus (urine osmolality: 315.78 mOsm/kg; serum osmolality: 280.39 mOsm/kg), and without electrolyte disturbances.

Clinical evolution was favorable, without postoperative bleeding or endocrine dysfunction. The patient was discharged from the ICU on postoperative day 4 and from the hospital on postoperative day 7, with complete neurological recovery and no complications. The clinical significance of these diagnosis was discussed with the patient, and proactive family screening was recommended to ensure safety in future anesthetic exposures for first-degree relatives.

Discussion

A TSS for a PitNET in the presence of type 2 VWD requires a coordinated multidisciplinary approach involving hematology, anesthesiology, and neurosurgery to optimize perioperative hemostasis and minimize bleeding risk (3, 5, 10).

Sequential evaluation of plasma levels of VWF and FVIII in the preoperative, intraoperative, and postoperative phases is essential, allowing hemostatic replacement to be guided based on quantitative measurements and dynamic intraoperative monitoring using TEG. This tool provides key information on coagulation time (R), clot kinetics (K), and maximum clot strength (MA), all of which are essential indicators for achieving hemostatic therapeutic goals in VWD.

Surgical planning begins with scheduling the case as the first procedure of the day, facilitating resource availability and timely monitoring of plasma levels. According to current recommendations, quantification of VWF, VWF:Ag, VWF:RCo, and FVIII is established 24 h before the surgical incision and again 4 h after the start of the procedure, complemented by baseline TEG and a new TEG one hour after the beginning of surgery (4).

Replacement with VWF/FVIII concentrate is calculated using the validated formula:With the goal of achieving plasma levels of 80%–100% (80–100 IU/dL) VWF:RCo and FVIII activity before the surgical incision aligns with guideline recommendations for major surgery (peak levels >100 IU/dL are advised to ensure normal hemostasis) (4, 6). Thereafter, periodic monitoring of VWF:RCo, VWF:Ag, and FVIII levels is performed to maintain values above 50% during the first 72 h, by administering 500 IU of VWF/FVIII concentrate every 12 h, adjusted to laboratory results. Based on these doses, the regimen is progressively modified: from day 4 to 6 every 24 h, and from day 7 to 10 every 48 h (4). This approach enables personalized, dynamic, and safe replacement according to plasma levels and clinical evolution.

Dose(IU)=(desiredincreaseinVWF–IR)×weight(kg)

In addition to factor replacement as a hemostatic strategy, antifibrinolytic coadjuvants such as tranexamic acid are used, as recommended by the ASH-ISTH-NHF-WFH guidelines for patients with VWD (4). In parallel, continuous, real-time hemodynamic assessment and minimally invasive technologies such as the FloTrac™ are integrated for advanced hemodynamic monitoring, helping to avoid abrupt changes in preload, afterload, and cardiac output, which could compromise both cardiovascular stability and cerebral perfusion. Furthermore, neuromonitoring tools such as SedLine and NIRS are implemented, which are essential for real-time detection of alterations in cerebral autoregulation and for adjusting anesthetic depth (11).

The use of intraoperative TEG in TSS in type 2 VWD represents a real-time, point-of-care assessment of global hemostatic function between platelets and fibrinogen that complements standard VWF/FVIII monitoring (3, 12–13). Specific parameters such as K-time and the maximal rate of thrombus generation (MRTG) are sensitive indicators of VWF deficiency (14).

In the neurosurgical setting, TEG is essential for the real-time identification of bleeding disorders and for guiding intraoperative factor replacement, ensuring that the desired hemostatic effect is achieved before surgical incision (13).

Finally, in the postoperative period, close surveillance of plasma VWF and FVIII levels is crucial to prevent both delayed bleeding and thrombotic events, adjusting replacement doses in an individualized manner. This comprehensive strategy demonstrates the importance of combining biochemical assessment, dynamic monitoring of hemostasis, and targeted factor replacement, together with multidisciplinary support, for successful management of patients with VWD undergoing neurosurgery, while simultaneously developing research hypotheses for TEG-guided dosing of VWF/FVIII concentrates.

Potential pitfalls in the perioperative management

Despite a successful outcome, the perioperative management of type 2 VWD in neurosurgery carries significant pitfalls that clinicians must anticipate. The first major risk is the over-correction and accumulation of FVIII. While the administration of plasma-derived VWF/FVIII concentrate is essential to achieve surgical hemostasis, the half-life of FVIII (approximately 12–15 h) is longer than that of VWF (approximately 8–10 h) (6, 15). During perioperative treatment with plasma-derived VWF/FVIII concentrate, FVIII levels rise while VWF:RCo declines (15). A pharmacokinetic study demonstrated that in the presence of therapeutic VWF levels (average 1.23 IU/mL), FVIII clearance decreased from 460 mL/h to 264 mL/h, and FVIII half-life increased from 6.6 to 11.4 h. This protective effect of VWF on FVIII clearance, combined with continuous endogenous FVIII synthesis, explains why FVIII can accumulate to supraphysiologic levels (≥150–200 IU/dL) during prolonged treatment (6, 15).

Repeated and unmonitored dosing can lead to supraphysiologic FVIII plasma levels (≥150–200 IU/dL), which increases the risk of postoperative venous thromboembolism (VTE) (16, 17).

A second pitfall involves errors in the TEG interpretation in the context of in type 2 VWD. While TEG provides valuable real-time data on global hemostasis strength, standard TEG assays are primarily driven by thrombin generation, fibrinogen, and FVIII levels, making them relatively insensitive to the direct qualitative defects of VWF seen in type 2 VWD (18, 19). Consequently, if FVIII levels are adequate, a patient with a severe qualitative VWF defect might present with a false sense of hemostatic adequacy with a “normal” standard TEG. Thus, TEG must be interpreted strictly as a complementary tool to confirm overall intraoperative hemostasis post-replacement, rather than a standalone diagnostic monitor for cases with type 2 VWD (3, 18, 19).

Limitations

Several limitations must be acknowledged in this report. First, its nature as a single case report inherently limits the generalizability of our clinical findings and management protocol to a broader surgical population with coagulopathies. Second, although the diagnosis of type 2 VWD was supported by a reduced VWF:Ag/functional activity ratio, advanced laboratory phenotyping, such as VWF multimer analysis or genetic testing, was unavailable to precisely identify the specific subtype (2A, 2B, 2M, or 2N). Third, our intraoperative hemostatic assessment relied on standard TEG, which is primarily sensitive to thrombin generation and factor VIII levels rather than direct qualitative VWF defects; thus, a normal TEG profile must be interpreted with caution and strictly as a complementary tool. Fourth, the study's retrospective design made it entirely dependent on existing medical records and laboratory studies, limiting our ability to control for external variables or standardize molecular measurements at identical time points. Finally, the lack of long-term post-discharge follow-up beyond the immediate postoperative period prevents the evaluation of delayed endocrinological or late-onset thromboembolic complications.

Conclusions

The coexistence of type 2 VWD and a pituitary tumor poses a complex anesthetic–hemostatic challenge that requires rigorous planning and multidisciplinary management. The application of institutional protocols based on the ASH-ISTH-NHF-WFH (2021) guidelines allowed targeted VWF/FVIII replacement, optimizing perioperative hemostasis. Neurological and hemodynamic monitoring, together with the use of antifibrinolytic coadjuvants, ensured intraoperative hemostasis, hemodynamic stability, and an uneventful postoperative course. This case underscores the importance of individualized perioperative management, intraoperative TEG, continuous monitoring of coagulation factors, and the integration of specialized teams to reduce morbidity and mortality in high–hemorrhagic-risk surgeries.

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Footnotes

Edited by: Fridtjof Schiefenhövel, University Hospital Rechts der Isar, Technical University of Munich, Germany

Reviewed by: Maribel Diaz-Ricart, Hospital Clinic of Barcelona, Spain

César Alejandro Martínez-de Los Santos, Monterrey Institute of Technology and Higher Education (ITESM), Mexico

Abbreviations ASA, American Society of Anesthesiologists; NIRS, near-infrared spectroscopy; PitNET, pituitary neuroendocrine tumor; JH, Johns Hopkins; TEG, thromboelastography; TSS, transsphenoidal surgery; RCRI, revised cardiac risk index; VWD, von Willebrand disease; VWF, von Willebrand factor; VWF:Ag, von Willebrand factor Antigen.