General anesthesia with nerve blocks for a patient with femoral fracture and essential thrombocythemia: a case report

Abstract

Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm characterized by an abnormal increase in platelets. We report a female patient with a severe femoral fracture and ET who underwent the femoral intramedullary fracture fixation procedure. Her past medical history included hypertension and ET. On the second day of hospitalization, her platelet count was 922 × 10⁹/L. In our case, general anesthesia combined with a femoral nerve block and a lateral femoral cutaneous nerve block were used when the platelet count was within normal range. After surgery, the platelet count increased to 979 × 10⁹/L despite using anticoagulant drugs and hydroxyurea. The postoperative recovery went well after the follow-up of this patient. In this case report, we provide our experience of anesthesia management and review the progress of relevant literature to provide some reference.

Introduction

Thrombocytosis occurs when the platelet count exceeds 450 × 10⁹/L and has an annual incidence in the United States of 2.5 per 100 000. ¹ According to its etiology, it can be divided into essential thrombocythemia (ET) and secondary thrombocythemia.

Platelets are the primary cell type involved in hemostasis, and current data suggest that different anesthetics impact on hemostatic function and surgical bleeding. ² Therefore, the high platelet count of patients with ET causes concerns for anesthesiologists during surgery. However, because few studies have used thromboelastography platelet mapping or platelet aggregation assays to determine the effects of anesthetics on platelets, the results of studies that investigated the impact of regional versus general anesthesia were mixed. ³

Femoral comminuted fracture with ET is rare. In this case, we used general anesthesia combined with nerve blocks because of the high possibility of thrombotic and hemorrhagic complications during a femoral intramedullary fracture fixation procedure. The reporting of this study conforms to CARE guidelines ⁴ and we obtained signed consent to publish from the patient.

Case report

A 69-year-old female patient (height, 160 cm; weight, 70 kg) who had an accidental fall sustained a right femoral fracture and was admitted to hospital. X-ray examination confirmed a comminuted fracture of the lower femur, which required surgery. The patient was taking controlled-release nifedipine tablets (30 mg/day) for her 5-year history of hypertension. Additionally, she had a 4-year history of ET and used aspirin (100 mg/day) and hydroxyurea (500 mg twice a day) to manage her platelet count.

Blood analysis revealed her platelet count to be higher than 922 × 10⁹/L. Echocardiography showed reduced left ventricular diastolic function and thickening of the basal segment of the interventricular septum (ejection fraction, 61%); preoperative arteriovenous ultrasound of the lower limbs showed venous tendon thrombosis. The thromboelastogram (TEG) showed her thrombodynamic potential index to be 202.7 (normal range, 5–90). Furthermore, D-dimer levels were 2.24 mg/L (normal range, 0–0.5 mg/L), indicating that her blood was hypercoagulable. Using risk stratification, we reviewed the patient’s medical history and considered her at high risk for ET thrombosis because of her severe femoral fracture, hypertension, lower limb venous thrombosis, and age over 60 years. ⁵ Her orthopedist prescribed nadroparin calcium and rivaroxaban for coagulopathy melioration. Because of her ET and venous thrombosis, the attending surgeon carried out a multi-disciplinary treatment involving hematopathology, anesthesiology, and medical intervention. Plateletpheresis is recommended before surgery for high-risk patients,^5,6so after discussion, we performed it twice using the automated blood cell separator to reduce the number of platelets. Following this, she experienced muscle twitches, which subsided after receiving a calcium gluconate injection. Finally, her platelet count was reduced the day before surgery to 252 × 10⁹/L. The presence of leukocytoses, especially those exceeding 11 × 10⁹/L, is another risk factor for thrombosis in patients with ET.^7,8 Fortunately, the leukocytosis level for this patient was within normal range.

Following 10 days of preoperative preparation, she was readied for intramedullary fracture fixation, aiming to minimize surgical trauma. General anesthesia was our preferred anesthetic method, so we administered an ultrasound-guided femoral nerve block and lateral femoral cutaneous nerve block, considering enhanced recovery after surgery. The routine intravenous anesthetic induction was performed using etomidate, fentanyl, atracurium, and midazolam. Once the anesthesia was at an appropriate depth, we inserted an endotracheal tube in the patient’s throat using a video laryngoscope. Then, we blocked the femoral nerve and the lateral femoral cutaneous nerve using an in-plane technique and 0.3% ropivacaine (20 mL for the femoral nerve block and 10 mL for the lateral femoral cutaneous nerve block) under ultrasonography.

We used dexmedetomidine, sevoflurane, and remifentanil to carry out the procedure while anesthesia was maintained. There were no obvious hemodynamic changes during surgery, and her endotracheal tube was successfully removed after waking up at the end of surgery. Her platelet count increased to 370 × 10⁹/L on the first day after surgery. Blood count changes during initial admission are described in Table 1. She continued taking oral hydroxyurea (500 mg twice a day) and rivaroxaban (10 mg/day) to regulate her platelet count and prevent thrombosis. Additionally, she received treatment to promote fracture healing, reduce swelling, and relieve pain. She was discharged 7 days after the fixation procedure and was instructed to return for a follow-up visit to the orthopedics clinic after 1 month. Three months after the procedure, X-ray showed her femoral fracture to have healed correctly (Figure 1), and a lower-extremity vascular ultrasound found no thrombosis.

Table 1.

Changes in blood counts during initial admission.

Blood counts	Day 2	Day 4	Day 7	Day 8	Day 9	Day 11	Day 13	Day 16
Platelets (× 109/L)	922	879	905	360	252	370	614	979
Red blood cells, RBC (×109/L)	2.8	2.8	2.7	2.6	2.6	2.3	2.2	2.4
White blood cells, WBC (×109/L)	6.2	6.6	6.7	4.8	4.7	7.9	5.4	5
Hemoglobin, Hgb (g/L)	108	110	105	102	101	90	85	93
Platelet distribution width, PDW (fL)	15.6	15.7	8.6	16	9	16	15.8	15.7
Mean platelet volume, MPV (fL)	7.7	7.8	8.7	7.8	9	8.2	7.9	7.6
Plateletcrit, PCT (%)	0.7	0.7	0.8	0.3	0.2	0.3	0.5	0.7

Figure 1.

Perioperative X-ray of the femur. The photographs show the femoral fracture healing process.

Discussion

ET is a specific myeloproliferative disease with low incidence, which is often associated with mutations in Janus kinase 2, calreticulin, or thrombopoietin receptor genes. ⁹ However, the patient in this study did not undergo genetic analysis during her treatment. A major diagnostic criterion for ET is proliferation and loose clustering of bone marrow megakaryocytes, ¹⁰ but unfortunately our patient had not received a bone marrow biopsy before surgery. There may also be a temporary increase in platelet count reactivity under specific conditions, such as infection, inflammatory irritation, or a state of stress ¹¹ ; however, this increase usually represents a laboratory anomaly and can return to normal levels after the trigger is removed.

Because ET is a rare chronic myeloproliferative disease, physicians treating patients should be aware of potential complications, which include vasomotor, hemorrhagic, and thrombotic events, with a particularly high incidence of arteriovenous thrombosis during the perioperative period. ⁶ Platelet dysfunction may underlie the thrombotic and hemorrhagic tendency rather than its quantity. ¹²

Although a retrospective study showed that more than half of patients with ET received general anesthesia, ¹³ the use of general anesthesia combined with peripheral nerve block has not been reported for such patients. Moreover, most past studies on the use of anesthesia for ET are case reports. For example, Hiyoshi et al reported the treatment of an ET patient with laparoscopic ileocecal resection under general anesthesia, ¹⁴ while another case report documented an 81-year-old woman with ET who underwent laparoscopic right hemicolectomy. ¹⁵

General anesthesia or intravertebral anesthesia are typically available for femoral fractures under standard conditions, but intervertebral anesthesia should only be used if platelet counts and aggregation tests are within normal ranges. ¹⁶ The patient’s coagulation status must be evaluated prior to intervertebral anesthesia to minimize the risk of epidural hematoma because intraspinal hematoma or other deep hematoma may cause serious consequences such as paraplegia or nerve damage. Patients with ET also have a high risk of perioperative thrombotic attacks in the cardiovascular and cerebrovascular system because of their impaired hemostatic system. ¹⁷ Thus, the risk of thrombosis should be reduced during general anesthesia by using graduated compression stockings and maintaining hemodynamic stability. Our patient had no airway difficulties or abnormal pulmonary functions. Moreover, we chose not to perform intraspinal anesthesia to avoid the change in position necessary for back puncture.

Bleeding complications are the main concern during epidural or subarachnoid anesthesia for patients with ET. ¹⁸ A previous case report of ET documented the use of a labor epidural and Plateletworks assay to detect the absolute values of active thrombocytes for hemostasis. ¹⁹ Here, we used TEG to analyze the coagulation function prior to surgery. We also used rivaroxaban, an efficient quick-acting direct Xa factor inhibitor, to combat the hypercoagulable blood state and prevent perioperative thrombosis. Rivaroxaban is a promising alternative to heparin and warfarin, with comparable efficacy and safety to traditional anticoagulants. Indeed, a noninferiority trial found that rivaroxaban was more effective than enoxaparin at preventing venous thromboembolic events after surgery. ²⁰ In 2020, Tobias et al found that FXa triggered platelet activation through protease-activated receptor 1, independently of thrombin. ²¹ This pathway is inhibited by rivaroxaban, which therefore reduces platelet activation, aggregation, and thrombosis using a dose-dependent mechanism of action. Although a 10-year retrospective study reported aspirin, hydroxyurea, heparin, and warfarin as the most common perioperative treatment of ET in 25 cardiac surgery patients, ⁶ heparin resistance was documented in patients with ET. ²² Ours is the first known patient with ET to receive rivaroxaban perioperative anticoagulant therapy. In the third month after surgery, arteriovenous ultrasound of the lower limbs revealed no thrombosis, indicating a successful therapeutic outcome. Future studies should further explore the efficacy and safety of rivaroxaban for surgical patients with ET.

Selective ultrasound-guided nerve blocks can quickly numb the surgical area while avoiding complications from intraspinal anesthesia. Furthermore, real-time ultrasound monitoring shows the needle and anesthetic diffusion, minimizing relative puncture complications. In a previous report of lower-extremity surgery, the accuracy and validity of the nerve blocks contributed to effective analgesia and tolerable passive rehabilitation training after surgery. ²³ In our case, femoral nerve block and lateral femoral cutaneous nerve block provided effective analgesia for this older patient, particularly during early postoperative passive movement.

In conclusion, this is the first known case to use general anesthesia combined with a femoral nerve block and lateral femoral cutaneous nerve block for a femoral fracture fixation procedure with ET. Our experience in anesthesia management from lower limb surgery with ET could be helpful. In the future, we should consider various factors when these patients with ET need surgery and explore an appropriate anesthesia plan.