Patient-centric care in primary immune thrombocytopenia (ITP): shared decision-making and assessment of health-related quality of life.

ABSTRACTImmune thrombocytopenia (ITP), an autoimmune disease characterized by low platelet counts and increased bleeding risk, can impair health-related quality of life (HRQoL), impacting patients' daily lives and mental health. A number of patient-reported outcome (PRO) measures (both generic and specific to ITP) can be used to understand the impact of ITP on HRQoL and generate evidence to guide disease management. As well-developed PRO tools could help in HRQoL assessment, their optimization could help to solidify a patient-centric approach to ITP management. Shared decision-making is a collaborative process between a patient and their healthcare professional in making decisions about care. Treatment decisions based on this shared process between physician and patient are recommended by clinical guidelines. The goal of this narrative review is to discuss treatment decisions with regards to patient-centric ITP management, with a focus on the impact of PRO measures and the process of shared decision-making in practice.

Risk-based and individualised management of bleeding and thrombotic events in adults with primary immune thrombocytopenia (ITP).

Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; <20-30 × 109 /L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient- and disease-related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient-centric approach. Currently, evidence-based recommendations and validated tools are lacking to support decision-making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk-based and individualised management of bleeding and thrombosis risk in adults with primary ITP.

Avatrombopag treatment response in patients with immune thrombocytopenia: the REAL-AVA 1.0 study.

Background: Thrombopoietin-receptor agonists (TPO-RAs) are used to treat immune thrombocytopenia (ITP), a disorder characterized by prolonged low platelet counts (PCs) that pose a risk of serious bleeding episodes. Avatrombopag (AVA) is the most recently approved TPO-RA for the treatment of chronic ITP. A high proportion of patients responded to AVA in clinical trials, and treatment was well-tolerated; however, limited real-world effectiveness data have been reported to date. Objectives: To describe demographic and clinical characteristics, treatment patterns, and outcomes following the initiation of AVA in patients with ITP in the United States. Design: This is a retrospective study using administrative claims data from the Komodo Healthcare Map (1 February 2017 to 28 February 2022) linked with PC laboratory data. Methods: Patients with ⩾1 diagnosis of ITP, ⩾1 paid prescription for AVA (index date), and ⩾1 month of pharmacy coverage after AVA initiation were selected. Baseline characteristics and follow-up steroid, immunosuppressant, and rescue medication use were described. The percentage of patients achieving clinically meaningful PC thresholds (⩾30 × 109/l) were assessed among patients with ⩾1 PC following AVA initiation and prior to AVA discontinuation/switch (effectiveness subgroup). Results: A total of 205 patients met eligibility criteria and 49% reported TPO-RA use in the prior 6 months. Approximately 70% and 93% of patients did not require use of steroid or immunoglobulin rescue medication during follow-up, respectively. Among patients with concomitant steroid (n = 75) or immunosuppressant (n = 7) use at AVA initiation, 35% and 57% discontinued those treatments, respectively. Of the 21 patients in the effectiveness subgroup, 81% achieved clinically meaningful PC thresholds. Conclusion: A high proportion of evaluable patients with ITP in this real-world study achieved clinically meaningful PCs, without requiring rescue medication during AVA treatment, with many able to discontinue baseline concomitant steroid or immunosuppressant utilization. Despite limited availability of PC data, these results are consistent with results from the AVA pivotal clinical trials.

Electronic health record risk-stratification tool reduces venous thromboembolism events in surgical patients.

Background: Venous thromboembolism is a preventable cause of morbidity and mortality after surgery. To ensure that patients receive appropriate venous thromboembolism chemoprophylaxis, a nonmandatory risk-stratification tool based on patient clinical condition was implemented through the electronic health record to stratify patient risk and recommend chemoprophylaxis. We hypothesized that implementing this tool would reduce postoperative venous thromboembolism events in general surgery as well as across all surgical services. Methods: All adult patients undergoing inpatient surgical operations (January 2012-December 2019) at a single quaternary care center and Level 1 trauma center were abstracted from institutional electronic health record database and stratified into patients admitted before and after venous thromboembolism risk-stratification tool implementation. Bivariable analyses compared venous thromboembolism chemoprophylaxis prescription and venous thromboembolism events with implementation and screening among all surgical patients as well as in general surgery patient subset. Results: A total of 64,377 adults underwent operations: 27,819 preimplementation and 36,558 postimplementation. A significant reduction in venous thromboembolism events occurred from pre- to post-tool implementation for all cases (0.77% vs 0.47%, P < .001). General surgery patients (n = 15,723) had a significant increase in chemoprophylaxis prescription (81.9% vs 86.0%, P < .001) and a significant reduction in venous thromboembolism events (1.41% vs 0.59%, P < .001). After tool implementation, use of extended postdischarge chemoprophylaxis was greater among general surgery patient subset than the entire patient cohort (46.7% vs 29.6%, P < .001). Conclusion: The integration of a nonmandatory electronic health record risk-stratification tool was associated with a significant reduction in venous thromboembolism events. Extended chemoprophylaxis was prescribed in nearly half of general surgery patients at very high risk for postdischarge events.

Avatrombopag Effectively Maintained Platelet Counts in a Patient with Immune Thrombocytopenia Who Was Intolerant to Tyrosine Kinase Inhibitor Therapy.

BACKGROUND First-line treatments for patients with immune thrombocytopenia include corticosteroids, intravenous immunoglobulin, and anti-D. These may be followed by second- and third-line options, including thrombopoietin receptor agonists and the tyrosine kinase inhibitor fostamatinib. These treatments have different mechanisms and divergent adverse event profiles. We show that fostamatinib-associated adverse events can be mitigated with fostamatinib dose reduction and the introduction of avatrombopag, and that response can be maintained with avatrombopag monotherapy. CASE REPORT A 61-year-old woman with a history of chronic refractory immune thrombocytopenia since 2006 had previously received steroids, rituximab, splenectomy, and eltrombopag without achieving platelet count stability. The patient reported flu-like symptoms in February 2020, with platelet counts ranging from 25×109/L to 50×109/L and isolated occurrences <10×109/L. Platelet counts did not respond to eltrombopag 75 mg/day, 2 courses of rituximab, or multiple courses of prednisone. Within 2 weeks of starting fostamatinib 150 mg twice daily, she reached a platelet count of 523×109/L. She experienced new-onset diarrhea associated with fostamatinib, so the dose was reduced to 75 mg twice daily, and avatrombopag 20 mg/day was added to augment platelet recovery. Platelet levels remained in the supratherapeutic range. She was transitioned to avatrombopag 40 mg/day monotherapy and then 20 mg/day owing to continued supratherapeutic platelet counts. CONCLUSIONS Avatrombopag can be used in combination with fostamatinib to augment platelet response and reduce the severity of adverse events associated with fostamatinib, while maintaining adequate therapeutic response in chronic immune thrombocytopenia. Avatrombopag 40 mg/day monotherapy was quite effective in achieving and maintaining high platelet counts.

Risk of Major Bleeding with Ibrutinib.

BACKGROUND: The Bruton tyrosine kinase inhibitor, ibrutinib, is an effective therapy against mature B-cell malignancies. Although generally well tolerated, serious bleeding emerged during developmental clinical trials as an unexpected, although uncommon, adverse event. As the use of ibrutinib increases outside of the clinical trial setting and in patients with more comorbidities, the rate of major bleeding could be greater. MATERIALS AND METHODS: A retrospective analysis the data from all patients at our center and its regional clinics who had been prescribed ibrutinib from January 2012 to May 2016 were reviewed for demographic data, comorbid illnesses, bleeding events, and concurrent medications. RESULTS: We identified 70 patients. Bleeding of any grade occurred in 56% of patients, mostly grade 1 to 2 bruising and epistaxis. Major bleeding, defined as grade ≥ 3, occurred in 19% of patients, greater than previously reported. Anemia (hemoglobin < 12 g/dL; hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.4-18.2; P = .02) and an elevated international normalized ratio (> 1.5; HR, 9.5; 95% CI, 2.7-33.5; P < .01) at ibrutinib initiation were associated with an increased risk of major bleeding. Of those with major bleeding, most patients were also taking an antiplatelet agent (70%), an anticoagulant (17%), or a CYP 3A4 inhibitor (7%), with 13% taking both antiplatelet and anticoagulant medications. The use of both antiplatelet and anticoagulant therapy significantly increased the risk of a major bleed event (HR, 19.2; 95% CI, 2.3-166.7; P < .01). CONCLUSION: The results of the present study have demonstrated a greater rate of major bleeding with ibrutinib use in a standard clinical setting than previously reported. Patients with anemia or an elevated international normalized ratio or requiring anticoagulant and/or antiplatelet medications during ibrutinib therapy have a significantly increased risk of major bleeding. Careful consideration of the risks and benefits for this population is needed. The combination of antiplatelet and anticoagulation medications with ibrutinib therapy is of particular concern.

Safety and effectiveness of apixaban compared to warfarin in dialysis patients.

Background: The use of apixaban for stroke prophylaxis or for the treatment of venous thromboembolism in end stage renal disease (ESRD) patients maintained on dialysis is based on one single-dose pharmacokinetic study. There is a deficiency of clinical evidence supporting safety in this population.Objective: The purpose of this study was to determine the safety and efficacy of apixaban compared with warfarin in dialysis patients.Patients/methods: This is a retrospective cohort study conducted at the University of Virginia Medical Center. A total of 124 ESRD patients maintained on dialysis who either received apixaban (n = 74) or warfarin (n = 50) between January 1, 2014 and October 31, 2016 were included in the study. We used multivariable logistic regression to compare the likelihood of patients experiencing a bleeding event based on anticoagulant therapy.Results: The apixaban group experienced fewer overall bleeding events than the warfarin group (18.9% vs 42.0%; P = .01); this significant difference persisted in adjusted analysis (OR = 0.15; 95% CI = 0.05-0.46; P = .001). Major bleeding events were less frequent in the apixaban group compared with patients on warfarin (5.4% vs 22.0%; P = .01). There were no recurrent ischemic strokes in either groups. A lower, non-significant, incidence of recurrent VTE was found in patients on apixaban compared with warfarin (4.4% vs 28.6%; P = .99).Conclusion: Compared to warfarin, our findings suggest that apixaban is a safe and effective alternative in patients with ESRD maintained on dialysis, with apixaban patients experiencing fewer bleeding events than warfarin patients.

Thrombosis and Thromboprophylaxis in Gynecology Surgery.

Gynecologic surgery offers unique challenges, as pelvic surgery places patients at an increased risk of venous thromboembolism (VTE). Prevention of VTE is a goal of patients, policy makers, and surgeons. In this review, we address the current research and recommendations for VTE prophylaxis.

Bleeding Risk and Management in Interventional Procedures in Chronic Liver Disease.

The coagulopathy of liver disease is distinctly different from therapeutic anticoagulation in a patient. Despite stable elevated standard clot-based coagulation assays, nearly all patients with stable chronic liver disease (CLD) have normal or increased clotting. Common unfamiliarity with the limitations of these assays in CLD may lead to inappropriate and sometimes harmful interventions, including blood product transfusions before a procedure. Knowledge of the distinct hemostatic alterations in CLD can allow identification of the small subset of patients with clinically significant coagulopathy who can benefit from hematologic optimization before invasive procedures.

Direct Oral Anticoagulants in Cirrhosis.

OPINION STATEMENT: The risk of thrombosis in patients with chronic liver disease is increasingly recognized. As patients with cirrhosis develop indications for anticoagulation therapy (e.g., venous thromboembolism, portal vein thrombosis, or atrial fibrillation), providers are left to make difficult decisions when selecting therapeutics with little evidence to rely on. Current practice supports the use of low molecular weight heparin or vitamin K antagonists in select patients with cirrhosis requiring anticoagulation. While traditional anticoagulants may be safe and effective in select patients with compensated cirrhosis, the use of direct oral anticoagulants (DOAC) is more controversial. DOAC are desirable as they do not require routine monitoring and can be taken orally. Unfortunately, patients with chronic liver disease were excluded from clinical trials that demonstrated efficacy and safety when compared to traditional anticoagulation. Data are now emerging that support the use of DOAC in well-compensated cirrhosis patients. However, further study is needed with all (traditional and DOAC) anticoagulation medications in patients with cirrhosis to better ensure safety and further understand pharmacologic properties in this challenging population.

IVC agenesis: a rare cause of deep vein thrombosis.

We present the case of a healthy, young Caucasian female who presented to an outside hospital with phlegmasia cerulea dolens of both lower extremities. Computed tomography angiography revealed inferior vena cava (IVC) occlusion. She was initiated on heparin infusion and transferred to University of Virginia Medical Center. Our evaluation revealed aplasia of the IVC from the infrahepatic segment to the confluence of the common iliac veins and acute bilateral iliac vein thromboses. An extensive network of collateral veins was noted. These findings were consistent with IVC agenesis. She was not pregnant or using contraception. Primary thrombophilia workup was negative. She underwent bilateral iliac vein thrombolysis and was started on anticoagulation. While IVC agenesis is rare, it carries risk for development of thrombotic sequelae and bears consideration when evaluating young patients with unexplained deep vein thrombosis, especially if extensive and bilateral.