Society guidelines on interventional spine procedures (ISPs) provide evidence-based recommendations for periprocedural management of patients on anticoagulation or antiplatelet therapy or those with common bleeding disorders.1,2 However, there are no specific guidelines or advisories concerning unique coagulopathies like Quebec platelet disorder (QPD). QPD is a rare, autosomal-dominant, qualitative platelet disorder implicated in delayed-onset bleeding (12 hours to 4 days) after minor or major hemostatic challenges.3 Periprocedural management of QPD patients undergoing ISP require careful planning and coordination of care to minimize the risk of postprocedural bleeding complications (PPBCs).
The patient provided written Health Insurance Privacy and Portability Act (HIPAA) authorization to publish this case report.
A 59-year-old woman presented to our tertiary pain clinic for treatment of chronic left-sided nonradiating neck pain with profoundly limited unilateral range of motion that had worsened gradually over 5 years. She was diagnosed with QPD at 48 years of age, following unusual perioperative hemorrhages. She had previously undergone a C6–7 anterior discectomy and fusion followed by a C5–6 discectomy and foraminotomy, 21 years and 16 years before clinic presentation, respectively. Both surgeries were complicated by postoperative hemorrhage requiring emergency decompression surgery and transfusion of blood products. On another occasion, she developed right thigh compartment syndrome after a soft tissue contusion while water-skiing, requiring decompressive fasciotomy at 37 years of age. On a different occasion, she developed a large hematoma at the surgical tourniquet site while undergoing knee arthroscopy 4 weeks before planned pain management interventions. The patient reported receiving prophylactic platelet transfusion for the knee arthroscopy.
She described her neck pain as moderate to very severe, and on examination, there was limited cervical rotation limited to 5°, but without sensorimotor deficits or pathologic reflexes. Spine imaging confirmed cervical facet arthropathy. She failed to note improvement in her pain with multimodal analgesia and physical therapy, and was deemed a high-risk surgical candidate due to her platelet disorder and bleeding histories.
We suggested diagnostic left third occipital nerve and C3–C5 medial branch nerve blocks (MBNBs) to assess candidacy for radiofrequency ablation (RFA). We consulted with her hematologist for guidance on the management of her bleeding disorder for ISP. She was instructed to take 1300 mg of tranexamic acid, an antifibrinolytic oral agent (AFOA), on the morning and evening of the procedures. She was also transfused 2 units of platelets immediately before each procedure. She underwent a fluoroscopy-guided MBNB (25-gauge Whitacre needles) with a report of >80% pain relief, and 5 weeks later, she underwent fluoroscopy-guided RFA (22-gauge thermocouple with a 5-mm active tip, 80°C for 60 seconds at each nerve). She was observed closely in recovery, and neither procedure resulted in PPBC. The patient was evaluated in clinic on the day following each procedure to evaluate for evidence of hematoma. One month after the RFA, she reported nearly complete resolution of neck pain with improved cervical range of motion, and follow-up 6 months later revealed continued nearly complete pain relief.
QPD is a rare platelet disorder that results in accelerated rates of fibrinolysis.3 The mechanism is a >100-fold increase in urokinase plasminogen activator (uPA) within alpha granules of platelets.3 uPA is a serine protease that converts inactive zymogen plasminogen into active plasmin.4,5 In turn, plasmin then triggers the proteolytic cascade, and creates an imbalance between the coagulation and fibrinolysis cascades favoring excessive bleeding (Figure).4,5 QPD patients usually only respond to treatment with AFOA.3,6 Therefore, performing ISP in QPD patients poses a treatment challenge and requires careful planning and coordination of care to minimize the risk of bleeding complications.
As there is limited literature on QPD, and the diagnosis is often made after surgical or procedural interventions in which PPBCs are identified, the prevalence of the disease is truly unknown. Much of what is known about the presentation of QPD is based on a study that utilized a standardized bleeding history questionnaire in 127 relatives in a large family with QPD to assess bleeding risks and common clinical manifestations of this platelet disorder.6 Commonly reported symptoms included bleeding that led to lifestyle changes (such as decreasing exposure to high-impact sports), bleeding for >24 hours after dental work or deep lacerations, frequent ecchymosis, and bruising disproportionate to an inciting trauma.6
The diagnosis of QPD is definitive with genetic testing, specifically identifying a mutation of PLAU, the uPA gene in chromosome 10.3,7 Family history is important, but no specific ethnic groups have been identified as higher risk for carrying the genetic mutation. Laboratory studies may show reduced to low-normal platelet counts, decreased platelet aggregation responses to epinephrine, and significantly increased expression of uPA in platelets, but not in plasma.4
The only known treatment for QPD is AFOA-like tranexamic acid or epsilon-aminocaproic acid.3,4,6 Both medications are synthetic analogs of lysine, an amino acid that inhibits plasminogen from binding to fibrin and thus prevents conversion to plasmin (Figure).8 At higher doses, tranexamic acid can also directly inhibit plasmin activity.8 Tranexamic acid is more commonly used because it is 10 times more potent at inhibiting fibrinolysis than epsilon-aminocaproic acid.3,8 The recommended dosage for oral tranexamic acid is typically either 25 mg/kg body weight every 8 hours in those with normal renal function or 15–20 mg/kg body weight every 8 hours in those who have renal insufficiency.3 It is suggested that those with recurrent bleeding episodes after hemostatic challenges take prophylactic treatment at the standard dose but at a reduced frequency (once or twice daily).3 The recommended duration of treatment also varies depending on the indication, largely based on prior case reports wherein QPD patients experienced excessive bleeding when AFOA was or was not used before hemostatic challenges.3,4,6 No treatment is necessary for spontaneous hematuria or uncomplicated vaginal childbirth.3 Three to 4 days of treatment is recommended for minor bleeding or minor surgeries like biopsies, 5 to 7 days for those undergoing major surgeries, 10 to 14 days for those experiencing intracranial bleeding, and up to several weeks to months as prophylaxis for those with joint bleeding.3 Unfortunately, there are no data to facilitate dosing of patients undergoing ISP. In this case, the patient (body mass index [BMI] 23.6 kg/m2, weight 72.6 kg) prophylactically received 1300 mg of tranexamic acid on the morning and evening of MBNB and RFA. In comparison to minor surgeries, the tissue trauma with cervical MBNB and subsequent RFA procedures is low and most significant at the time of the procedure; therefore, we chose to follow the hematologist’s recommendations. The patient was also transfused 2 units of platelets before each procedure. Although platelet transfusion is not effective in the treatment of excessive bleeding in QPD patients, there are general recommendations to limit spinal or peripheral joint injections on patients with history of spontaneous bleeding and platelet dysfunction only to those with normal platelet counts.2 Our patient had a baseline platelet count of 167 K/uL, which was borderline low (reference range 140–390 K/uL). Hence, this was an additional precautionary approach by our team.
We found no studies showing whether QPD patients are protected against arterial and venous thrombosis. One QPD patient from the previously mentioned questionnaire study did experience pulmonary embolism while receiving AFOA to control postoperative hematoma after a cesarean delivery in preeclampsia.6 The risks and benefits of AFOA treatment must be carefully weighed and individualized for each patient. Tranexamic acid is specifically contraindicated in patients with a history of thromboembolic disease or severe renal failure.9
To our knowledge, this is the first report of a patient with QPD undergoing ISP, specifically a cervical MBNB and RFA, wherein bleeding risk was minimized and PPBC was prevented by incorporating a systematic approach (Table). While cervical MBNB and RFA are typically classified as intermediate risk, we considered this case high risk given the patient’s extensive history of PPBC.1 Such stratification is consistent with the society guideline to consider upgrading patients with certain comorbidities like severe renal or hepatic dysfunction or coagulopathies to a higher-risk category.1 This prompted our team to consult with a hematologist to develop an individualized plan for this patient’s interventions. Although double comparative MBNBs decrease the false-positive rate and are correlated with more favorable RFA outcomes,10 we opted to proceed with a single diagnostic MBNB to further minimize the risk of bleeding. One might also argue to proceed directly to RFA to reduce the overall number of invasive procedures.
Summary of Approach to ISP in a Patient With QPD
|Obtain detailed medical and surgical histories.
|Check platelet counts to assess indication for platelet transfusion before ISP.
|Consult with hematologist to develop individualized plan for management of bleeding for ISP.
|Consider recommending prophylactic administration of tranexamic acid, dosing 15–25 mg/kg body weight once to twice daily based on renal function and prior bleeding histories.
|Consider platelet transfusion to normalize platelet count as necessary.
|Educate patient on signs and symptoms of bleeding, including neurological changes such as altered mental status or lightheadedness, and instruct to seek medical attention immediately if any concerns.
|Closely monitor patient with serial clinic visits starting on postprocedure day 1 to assess for postprocedural bleeding complications.
bbreviations: ISP, Interventional spine procedures; QPD, Quebec platelet disorder.
While the current evidence-based society guidelines for ISP focus on patients with common bleeding disorders or those taking anticoagulation or antiplatelet therapy,1,2 these should facilitate providers in developing individualized approaches for patients with rare coagulopathies. We recommend that interventionalists be cognizant of unique bleeding disorders like QPD and utilize appropriate resources to maximize patient safety for these procedures.
Name: Debbie Lee, MD.
Contribution: This author helped gather the data and prepare the manuscript.
Name: David R. Walega, MD, MSCI.
Contribution: This author helped conduct the case study and prepare the manuscript.
This manuscript was handled by: Mark C. Phillips, MD.
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