Treatment of patients with hemophilia A and B has undergone significant advances during the past 2 decades. However, despite these advances, the development of antibodies that inhibit the function of ...infused clotting factor remains a major challenge and is considered the most significant complication of hemophilia treatment. This chapter reviews current tools available for the care of patients with inhibitors and highlights areas where progress is imminent or strongly needed. For management of bleeding, bypassing agents remain the mainstay of therapy. Recombinant factor VIIa and activated prothrombin complex concentrates are similarly effective in populations of patients with hemophilia and inhibitors; however, individuals may show a better response to one agent over another. Recent studies have shown that prophylaxis with bypassing agents can reduce bleeding episodes by ∼50%-80%. The prophylactic use of bypassing agents is an important tool to reduce morbidity in patients before they undergo immune tolerance induction (ITI) and in those with persistent high titer inhibitors, but cost and lack of convenience remain barriers. Because of the significant burden that inhibitors add to the individual patient and the health care system, inhibitor eradication should be pursued in as many patients as possible. ITI is an effective tool, particularly in patients with severe hemophilia A and good risk profiles, and leads to a return to a normal factor VIII response in ∼60% of patients. However, for the group of patients who fail to respond to ITI or have hemophilia B, new and improved tools are needed.
Emicizumab binds to activated factor IX and factor X, reproducing the bridging function of the missing factor VIII. In a trial of emicizumab prophylaxis, emicizumab every 1 or 2 weeks led to a lower ...bleeding rate than no prophylaxis.
ABSTRACTThe coronavirus disease (COVID-19) pandemic has threatened millions of lives worldwide with severe systemic inflammation, organ dysfunction, and thromboembolic disease. Within our ...institution, many critically ill COVID-19 positive patients suffered major thrombotic events, prompting our clinicians to evaluate hypercoagulability outside of traditional coagulation testing.We determined the prevalence of fibrinolysis shutdown via rotational thromboelastometry (ROTEM, Instrumentation Laboratories, Bedford, MA) in patients admitted to the intensive care unit (ICU) over a period of 3 weeks. In 21 patients who had a ROTEM test, we found that eleven (52.4%) met the criteria for fibrinolysis shutdown. Nine patients (42.9%) were diagnosed with venous thromboembolic (VTE) events during their admission. Eight of 9 (89%) of the VTE patients met criteria for fibrinolysis shutdown.Given the high rate of fibrinolysis shutdown in these patients, our data support using viscoelastic testing to evaluate for the presence of impaired fibrinolysis. This may help identify patient subsets who might benefit from the administration of fibrinolytics.
Immune tolerance induction (ITI) is the only treatment to eradicate inhibitors in people with severe haemophilia A with inhibitors. Since the risk of inhibitor development is greater among Black and ...Hispanic persons, it has been hypothesized that race and ethnicity may influence ITI success. Limited studies have evaluated this hypothesis.
To examine the success of ITI according to race and ethnicity.
Participants who entered the Community Counts (CC) Registry between 2013 and 2017, were aged ≥3 years at study entry, and received ITI were included (n = 559). The proportion of participants with successful ITI was examined with adjusted prevalence ratios (aPRs) and corresponding 95% confidence intervals (95% CIs).
Among 559 participants, 56.9%, 19.1%, 18.1% and 4.3% were Non-Hispanic (NH) White, NH Black, Hispanic and Asian, respectively, and 1.7% were coded as other or missing. Approximately 80% of Hispanic, NH Black and NH White participants had good/very good prognosis, defined as having a pre-ITI peak inhibitor of < 200 Bethesda Units per millilitre. Nearly 60% of participants (59.7%) achieved successful ITI, 20.7% and 19.5% experienced partially successful or failed ITI, respectively. Successful ITI was non-significantly lower in NH Black (54.2%; aPR = 0.95, 95% CI 0.62-1.44) and Hispanic (55.4%; aPR = 0.89, 95% CI 0.71-1.13) relative to NH White participants (62.6%).
In this study, 60% of participants in the CC Registry had successful ITI, consistent with previous studies. The proportion with successful ITI was generally comparable across racial and ethnic groups with similar prognosis. These findings do not support the hypothesis that ITI response varies according to race or ethnicity.
Management of comorbidities in haemophilia Kempton, Christine L.; Makris, Michael; Holme, Pål Andre
Haemophilia : the official journal of the World Federation of Hemophilia,
February 2021, 2021-Feb, 2021-02-00, 20210201, Letnik:
27, Številka:
S3
Journal Article
Recenzirano
Odprti dostop
With the introduction of clotting factor concentrates in the early 1970s, significant improvements in quality of life and life expectancy of persons with haemophilia (PWH) were realized. ...Unfortunately, as a result of transmission of HIV and hepatitis C virus (HCV) by contaminated concentrates in the 1980s, many of these gains were lost. Now with four decades of PWH unexposed to contaminated factor products and current treatments capable of suppressing and eliminating HIV and HCV, respectively, the survival rate is once again increasing. In addition to the usual comorbidities associated with advanced age in the general population, several specific issues occur in patients with bleeding disorders. This manuscript explores the incidence and management of the comorbidities of the ageing PWH with a focus on cardiovascular disease and osteoporosis.
There is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19 patients at risk for ...thrombotic events and other complications.
Hospitalized patients with confirmed SARS-COV-2 from four Atlanta hospitals were included in this observational cohort study and underwent admission testing of MOCHA parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer). Clinical outcomes included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, access line thrombosis, ICU admission, intubation and mortality.
Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American), 45 (16%) had a thrombotic endpoint. Each MOCHA parameter was independently associated with a thrombotic event (p<0.05) and ≥ 2 abnormalities was associated with thrombotic endpoints (OR 3.3, 95% CI 1.2-8.8) as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6) and ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only ≥ 2 MOCHA abnormalities were associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4). MOCHA and D-dimer cutoffs were not associated with mortality. MOCHA with <2 abnormalities (26% of the cohort) had 89% sensitivity and 93% negative predictive value for a thrombotic endpoint.
An admission MOCHA profile is useful to risk-stratify COVID-19 patients for thrombotic complications and more effective than isolated d-dimer for predicting risk of ICU admission and intubation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hemophilia A is a congenital X-linked bleeding disorder caused by coagulation factor VIII (FVIII) deficiency. Routine infusion of factor replacement products is the current standard of care; however, ...the development of alloantibodies against FVIII remains a challenge. The treatment of hemophilia has undergone major advances over the past century to improve safety, effectiveness, manufacturing, and convenience of factor products. Major recent advances in the treatment of hemophilia A include the emergence of extended half-life products, factor VIII orthologs, and gene therapy products. Extended half-life products were designed to decrease the frequency of infusions, but only modest half-life extension is achieved. Factor VIII orthologs featuring lower cross-reactivity with anti-FVIII antibodies may be less susceptible to inactivation by inhibitors. Meanwhile, gene therapy may potentially provide a cure for hemophilia A, thus abrogating the need for protein-based factor replacement. This review aims to discuss current and emerging FVIII replacement products for hemophilia A.
Introduction
In chronic diseases, disease‐related distress can impact disease outcomes. Distress and haemophilia‐related distress has been demonstrated in people with haemophilia (PwH). The ...association of haemophilia‐related distress on disease outcomes among PwH is unknown.
Aim
To study the association of haemophilia‐related distress with haemophilia specific outcomes, including adherence to prophylactic therapy, the presence of a target joint, healthcare utilization and work‐impairment.
Methods
In a cross‐sectional study, adults with haemophilia A or B were enrolled in a study to validate the haemophilia‐related distress questionnaire (HRDq). In this planned analysis, univariate and multivariate associations between the HRDq total score and disease outcomes were explored.
Results
The 114 participants in this analysis were male, mostly with haemophilia A (92%) and severe disease (52%) with a median age of 31.9 years. On univariate analysis, HRDq total score (5‐point change) was associated with the presence of a target joint (P = .002), high healthcare utilization (P = .011), poor adherence (P = .033) and work‐impairment (P ≤ .001). After adjustment for age, race, severity and other potential confounders, adherence (aβ 0.33, 95% CI .17, .49) and work‐impairment (aβ 4.69, 95% CI 3.27‐6.1) remained statistically significantly associated with HRDq total score.
Conclusion
Haemophilia‐related distress is associated with poor adherence to factor prophylaxis and work‐impairment. The direction of the association (causation) is yet to be determined and requires future study.
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