Utilization of a surgical database to provide care and assess perioperative treatment and outcomes in patients with bleeding disorders.

OBJECTIVES: To describe the Indiana Hemophilia and Thrombosis Center (IHTC) surgical database, its key components, and exploratory analyses of surgeries conducted between 1998 and 2019. METHODS: Surgical data across bleeding disorders collected retrospectively (1998-2006) and prospectively (2006-2019) were analyzed. Perioperative hemostasis, complications, and surgical plan deviations were compared by bleeding disorder diagnosis and data collection period. RESULTS: Within the 21-year period, 3246 procedures were conducted in 1413 patients with a diagnosis of von Willebrand disease (vWD), hemophilia A (HA), hemophilia B (HB), and other bleeding disorders. Majority of the procedures were minor (63.3%), and median number of surgeries per patient was 1 (range: 1-22). Adequate perioperative hemostasis was achieved in 90.9%, complications occurred in 13.6%, and surgical plan deviations occurred in 31.3% of procedures. Inadequate perioperative hemostasis and surgical plan deviations occurred more frequently in procedures involving HB compared with other bleeding disorders. Complications were not significantly different across bleeding disorders (p = .164). The prospective data collection period was associated with higher rates of hemostatic efficacy (92.4% vs. 88.3%; p < .001), complications (14.3% vs. 12.3%; p < .001), and plan deviations (34.2% vs. 25.1%; p < .001). CONCLUSION: The surgical database is an important resource in surgical management in patients with bleeding disorders. Further evaluation will facilitate use for the development of predictive models and principles of care.

Management of people with haemophilia A undergoing surgery while receiving emicizumab prophylaxis: Real-world experience from a large comprehensive treatment centre in the US.

INTRODUCTION: Surgery is frequently required in persons with haemophilia A (PwHA). Emicizumab, a bispecific, humanized monoclonal antibody, bridges activated factor (F) IX and FX. Management of patients undergoing surgery while receiving emicizumab is of clinical interest due to paucity of data. AIM: Review real-world experience of PwHA with/without FVIII inhibitors who required surgery while receiving emicizumab prophylaxis. METHODS: Data regarding peri-operative management, including type of surgery, haemostatic agent use and bleeding complications, were collected for PwHA receiving emicizumab undergoing surgery between 25/10/18 and 31/12/19 at the Indiana Hemophilia and Thrombosis Center. Analyses were exploratory and descriptive. RESULTS: Twenty minor and five major surgeries were performed in 17 and five patients, respectively. Overall, 9/20 minor surgeries were planned to occur with emicizumab as the sole haemostatic agent; of these, four required additional coagulation factor (2 due to haematomas following port removals, 1 due to oozing at port removal site, 1 due to bleeding following squamous cell carcinoma removal). Three of the 11 minor surgeries with planned additional coagulation factor resulted in non-major bleeds; all were safely managed with additional coagulation factor. All five major surgeries were planned with additional haemostatic agents; there was 1 bleed in a patient undergoing elbow synovectomy with nerve transposition, likely triggered by physical/occupational therapy. There were no major bleeds, thrombotic events or deaths. CONCLUSIONS: Additional haemostatic agent use is safe in PwHA undergoing surgery while receiving emicizumab. Additional data are needed to determine the optimal dosing/length of treatment of additional haemostatic agents to lower bleeding risk.

Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 35 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT05045820.

Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 37 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies.

Medical Education and Training: Building In-Country Capacity at All Levels.

Poorly trained workers and limited workforce capacity contribute immensely to barriers in cancer control in low- and middle-income countries (LMICs). Because of an increasing disease burden and the gap in trained personnel, it is critical that LMICs must develop appropriate in-country training programs at all levels to adequately address their cancer-related outcomes. The training in LMICs of cancer health personnel should address priority cancer diseases in the specific country by developing caregivers, trainers, researchers, and administrators at all levels of health care and all cadres of staff, from the community level to the national level. The Academic Model of Providing Access to Health care is a representative model of how a public tertiary hospital like the Moi Teaching and Referral Hospital in an LMIC setting can leverage its resources, collaborate with partners from high-resource countries, and assist in the development of a training center to spearhead a sustainable education program.

Perioperative management of von Willebrand disease in dermatologic surgery.

BACKGROUND: Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting an estimated 0.1% to 1% of the population. It is caused by a qualitative or quantitative defect of von Willebrand factor. Primary manifestations include intractable mucocutaneous bleeding after surgery or trauma. OBJECTIVE: The objective was to review the pathophysiology and clinical features of VWD and to propose a perioperative management strategy for patients with this condition undergoing dermatologic surgery. METHODS AND MATERIALS: Literature is reviewed. RESULTS: The various types and clinical manifestations of this condition are reviewed, and a perioperative strategy is presented for managing patients with VWD who undergo cutaneous oncologic or cosmetic surgical procedures. CONCLUSIONS: In most cases, dermatologic surgery can be safely performed in patients with VWD. The use of appropriate therapeutic prophylaxis in conjunction with a hematologist is indicated in high-risk, nonelective procedures.

The role of blood component removal in essential and reactive thrombocytosis.

An elevated platelet count is now a common finding in both hospitalized and ambulatory patients with the advent of automated complete blood cell counters. Clinicians may be called upon to make a distinction between a reactive process and a primary hematologic disorder as the cause of a thrombocytosis and to determine whether treatment is indicated. Essential thrombocythemia and other myeloproliferative disorders may present with marked increases in the platelet counts and may be associated with thrombohemorrhagic complications. Reactive thrombocytosis can be caused by iron deficiency and a variety of inflammatory conditions, infections, malignancy, bleeding or hemolysis, splenectomy, and drugs. Acute therapy for all of these disorders has included blood component removal, specifically plateletpheresis. The role of plateletpheresis in current management of thrombocytosis is considered, based on current knowledge of pathophysiology and a review of the literature.

Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures.

BACKGROUND: Hereditary antithrombin (AT) deficiency is associated with a significant risk of venous thromboembolism. Patients with this disorder frequently require long-term anticoagulation. Discontinuation of anticoagulation for childbirth or surgery may carry a substantial thrombotic risk. For this reason, replacement with AT concentrate has been used when anticoagulation is interrupted. A new recombinant human AT concentrate, produced using transgenic technology, has recently been developed. STUDY DESIGN AND METHODS: Human recombinant AT (rhAT) was provided by GTC Biotherapeutics, Inc. on a compassionate-use basis for five patients with hereditary AT deficiency who underwent six surgical procedures. Patients were treated perioperatively. Dosing was determined individually by the investigators with a goal of maintaining an AT activity of 80 to 150 percent. RESULTS: There was no clinical evidence of thrombosis or bleeding. Four of the five patients had postoperative duplex ultrasound studies of the lower extremities, which showed no evidence of acute thrombosis. Four patients were tested for antirecombinant rhAT antibodies postoperatively and were negative. CONCLUSION: These case reports indicate that rhAT can provide effective support for AT-deficient patients who undergo surgery. Further study of this product is needed to define optimal dosing and further assess clinical response.