Purpose: Glanzmann’s thrombasthenia (GT) is a rare bleeding disorder caused by a mutation in the αIIbβ3 integrin essential for optimal platelet function and hemostasis. The aim of this study was to identify the burden of GT on patients and caregivers through better understanding of the management and psychosocial impact of this disorder. Patients and Methods: Participants for this online survey were recruited using a rare disease specialty recruiter from Comprehensive Health Education Services. Data were collected from January 31 through March 12, 2019. The questionnaire was designed to collect information regarding demographics, diagnosis, treatment, and psychosocial impact. Results: Of the 45 respondents (24 patients and 21 caregivers), the majority were female (58%), white (64%), and employed full-time (53%) and had no family history of GT (64%). Many patients reported significant bruising at birth (76%), and the mean age at diagnosis was 2.6 years. About half of the patients experienced 1 bleed per day, and 13% had over 500 bleeds of any severity per year. Most bleeds were skin bruising or mouth bleeds, but patients also reported joint/muscle and gastrointestinal bleeds. Most patients reported receiving a platelet transfusion (82%), and some had developed platelet refractoriness (38%) or antibodies (32%). Common treatments were antifibrinolytics (82%) and recombinant activated factor VII (rFVIIa) (42%), likely due to the presence of antibodies. Many (58%) patients experienced issues with excessive bleeding at school; 38% reported missing school as a result. Female patients struggled to find a gynecologist with knowledge of the management of GT. Most patients were satisfied with the support they receive from their current partner (65%) and their friends (76%). Conclusion: Most patients with GT are diagnosed early. Patients experience considerable psychosocial impact. Patient and physician education concerning treatment alternatives and the support of the GT community are critical.
Purpose: Congenital factor VII (FVII) deficiency is a rare bleeding disorder of variable phenotype with predominantly mucocutaneous bleeding. The aim of this study was to identify the burden of FVII deficiency on patients and caregivers through a better understanding of the management and psychosocial impact of this disease. Materials and Methods: A rare disease specialty recruiter from Comprehensive Health Education Services recruited participants for this online survey, which was conducted from January 31 to March 12, 2019. A moderator-assisted questionnaire was used to collect data on demographics, diagnosis, treatment, and psychosocial impact. Results: Of the 45 respondents (25 patients and 20 caregivers), the majority were female (56%). Respondents reported a wide variety of initial bleeding symptoms, including bruising (58%), epistaxis (56%), and menorrhagia (36% of females). Because symptoms varied between individuals and were not always severe, diagnosis was often delayed. Mean time to obtain a diagnosis was 6.5 years and mean age at first diagnosis was 12.9 years. One-quarter (24%) of the respondents reported more than 100 bleeds of any severity over the previous year. When treating bleeds, 44% of patients reported using antifibrinolytics, and 42% reported using recombinant activated factor VII. Almost 31% of respondents reported missing schooldays as children, and 16% reported losing or resigning from a job in adulthood as a direct result of their disease. Notably, 29% of caregivers and 10% of their partners had also experienced issues with employment. Forty percent of respondents reported not participating in contact sports during childhood, and 22% continued to avoid contact sports in adulthood. Conclusion: Overall, FVII deficiency has a substantial psychosocial impact, but most patients are satisfied with their disease management and are optimistic about their future. Patients desire additional educational, social, and financial support.
We evaluated the utility of left atrial volume index (LAVI) and markers of coagulation and hemostatic activation (MOCHA) in cryptogenic stroke (CS) patients to identify those more likely to have subsequent diagnosis of atrial fibrillation (AF), malignancy or recurrent stroke during follow-up.Consecutive CS patients who met embolic stroke of undetermined source (ESUS) who underwent transthoracic echocardiography and outpatient cardiac monitoring following stroke were identified from the Emory cardiac registry. In a subset of consecutive patients, d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex and fibrin monomer (MOCHA panel) were obtained ≥2 weeks post-stroke and repeated ≥4 weeks later if abnormal; abnormal MOCHA panel was defined as ≥2 elevated markers which did not normalize when repeated. We assessed the predictive abilities of LAVI and the MOCHA panel to identify patients with subsequent diagnosis of AF, malignancy, recurrent stroke or the composite outcome during follow-up.Of 94 CS patients (mean age 64 ± 15 years, 54% female, 63% non-white, mean follow-up 1.4 ± 0.8 years) who underwent prolonged cardiac monitoring, 15 (16%) had new AF. Severe LA enlargement (vs normal) was associated with AF (P < .06). In 42 CS patients with MOCHA panel testing (mean follow-up 1.1 ± 0.6 years), 14 (33%) had the composite outcome and all had abnormal MOCHA. ROC analysis showed LAVI and abnormal MOCHA together outperformed either test alone with good predictive ability for the composite outcome (AUC 0.84).We report the novel use of the MOCHA panel in CS patients to identify a subgroup of patients more likely to have occult AF, occult malignancy or recurrent stroke during follow-up. A normal MOCHA panel identified a subgroup of CS patients at low risk for recurrent stroke on antiplatelet therapy. Further study is warranted to evaluate whether the combination of an elevated LAVI and abnormal MOCHA panel identifies a subgroup of CS patients who may benefit from early anticoagulation for secondary stroke prevention.
Reports of thrombotic complications in patients with COVID-19 are increasingly prominent, and these reports include patients receiving therapeutic anticoagulation.1, 2 At our institution, multiple occurrences of anticoagulation failure prompted us to search for alternative aetiologies contributing to refractory hypercoagulability. Here we describe COVID-19-associated hyperviscosity, a potentially severe consequence of infection with severe acute respiratory syndrome coronavirus 2, in 15 patients tested to date. This work was done ethically in accordance with institutional review board approval.
Background: Platelet function testing to monitor antiplatelet therapy is important for reducing thromboembolic complications, yet variability across testing methods remains challenging. Here we evaluated the agreement of four different testing platforms used to monitor antiplatelet effects of aspirin (ASA) or P2Y12 inhibitors (P2Y12-I). Methods: Blood and urine specimens from 20 patients receiving dual antiplatelet therapy were analyzed by light transmission aggregometry (LTA), whole blood aggregometry (WBA), VerifyNow PRUTest and AspirinWorks. Result interpretation based on pre-defined cutoff values was used to calculate raw agreement indices, and Pearson's correlation coefficient determined using individual units of measure. Results: Agreement between LTA and WBA for P2Y12-I-response was 60% (r = 0.65, high-dose ADP; r = 0.75, low-dose ADP). VerifyNow agreed with LTA in 75% (r = 0.86, high-dose ADP; r = 0.75, low-dose ADP) and WBA in 55% (r = 0.57) of cases. Agreement between LTA and WBA for ASA-response was 45% (r = 0.09, high-dose collagen WBA; r = 0.19, low-dose collagen WBA). AspirinWorks agreed with LTA in 60% (r = 0.32) and WBA in 35% (r = 0.02, high-dose collagen WBA; r = 0.08, low-dose collagen WBA) of cases. Conclusions: Overall agreement varied from 35 to 75%. LTA and VerifyNow demonstrated the highest agreement for P2Y12-I-response, followed by moderate agreement between LTA and WBA. LTA and AspirinWorks showed moderate agreement for aspirin response, while WBA showed the weakest agreement with both LTA and AspirinWorks. The results from this study support the continued use of LTA for monitoring dual antiplatelet therapy, with VerifyNow as an appropriate alternative for P2Y12-I-response. Integration of results obtained from these varied testing platforms with patient outcomes remains paramount for future studies.
Measurement of a single marker of coagulation may not provide a complete picture of hemostasis activation and fibrinolysis in patients with chronic cardiovascular diseases. We assessed retrospective orders of a panel which included prothrombin fragment 1.2 (PF1.2), thrombin: antithrombin complexes, fibrin monomers, and D-dimers in patients with heart assist devices, cardiomyopathies, atrial fibrillation and intracardiac thrombosis (based on ordering ICD-10 codes). During 1 year there were 117 panels from 81 patients. Fifty-six (69%) patients had heart assist devices, cardiomyopathy was present in 17 patients (21%) and 29 patients (36%) had more than 1 condition. PF1.2 was most frequently elevated in patients with cardiomyopathy (61.1%) compared to those with cardiac assist devices (15.7%; P = 0.0002). D-dimer elevation was more frequent in patients with cardiac assist devices (98.8%) compared to those patients with cardiomyopathy (83.3%; P = 0.014). Patients with cardiomyopathy show increases of PF1.2 suggesting thrombin generation. In contrast, elevations of D-dimers without increase in other coagulation markers in patients with cardiac assist devices likely reflect the presence of the intravascular device and not necessarily evidence of hemostatic activation.
Background: The objective of this study was to evaluate if anticoagulation therapy reduces recurrent stroke in embolic stroke of undetermined source (ESUS) patients with left atrial enlargement (LAE) or abnormal markers of coagulation and hemostatic activity (MOCHA) compared to antiplatelet therapy. Methods: ESUS patients from January 1, 2017, to June 30, 2019, underwent outpatient cardiac monitoring and the MOCHA profile (serum d-dimer, prothrombin fragment 1.2, thrombin–antithrombin complex, and fibrin monomer). Anticoagulation was offered to patients with abnormal MOCHA (≥2 elevated markers) or left atrial volume index 40 mL/m2. Patients were evaluated for recurrent stroke or major hemorrhage at routine clinical follow-up. We compared this patient cohort (cohort 2) to a historical cohort (cohort 1) who underwent the same protocol but remained on antiplatelet therapy. Results: Baseline characteristics in cohort 2 (n = 196; mean age = 63 ± 16 years, 59% female, 49% non-White) were similar to cohort 1 (n = 42) except that cohort 2 had less diabetes (43 vs. 24%, p = 0.01) and more tobacco use (26 vs. 43%, p = 0.04). Overall, 45 patients (23%) in cohort 2 initiated anticoagulation based on abnormal MOCHA or LAE. During mean follow-up of 13 ± 10 months, cohort 2 had significantly lower recurrent stroke rates than cohort 1 (14 vs. 3%, p = 0.009) with no major hemorrhages. Conclusions: Anticoagulation therapy in a subgroup of ESUS patients with abnormal MOCHA or severe LAE may be associated with a reduced rate of recurrent stroke compared to antiplatelet therapy. A prospective, randomized study is warranted to validate these results.
The much-anticipated arrival of andexanet alfa, a recombinant factor Xa decoy protein that rapidly reverses the anticoagulant effects of direct oral factor Xa inhibitors (FXai) like apixaban and rivaroxaban,1 has many hospital systems wondering how to manage patients who may benefit from reversal but fall outside clear indications. For example, patients with delayed drug clearance due to renal failure may experience major bleeding or require emergent surgery. A recent perspective article in Blood provides an excellent overview of FXai testing and highlights both the limited availability and clinical need for drug-specific FXai testing in critical situations.2 While development of rapid drug-specific assays is underway, methods to quantitate FXai concentrations quickly, especially given the high cost of antidote, are needed right now. Herein, we provide data suggesting that conventional heparin-calibrated anti-Xa tests, performed using standard coagulometers in many U.S. hospitals, may help guide appropriate and cost-effective use of FXai antidote.
Objectives: Patients with coronavirus disease 2019 (COVID-19) have thromboembolic complications. Assessment of coagulation and other markers could be useful to understand their coagulopathy. Methods: We performed a retrospective study of inflammatory and coagulation parameters, including prothrombin fragment 1.2 (PF1.2), thrombin-antithrombin complexes (TATs), fibrin monomers, and D-dimer, in hospitalized patients with COVID-19. We compared the markers in patients with thrombosis, admission to the intensive care unit (ICU), and poor outcome. Results: Of the 81 patients, 9 (11%) experienced an acute thrombotic event (4 with pulmonary embolism, 3 with venous thrombosis, and 2 with stroke). PF1.2 was elevated in 32 (39%) patients, TATs in 54 (67%), fibrin monomers in 49 (60%), and D-dimer in 76 (94%). Statistically significant elevation in PF1.2 and TATs was seen in patients admitted to the ICU, while D-dimer and fibrin monomers were significantly elevated in patients with poor outcomes. The presence of multiple abnormal coagulation parameters was associated with ICU admission. Other parameters with statistically significant results included abnormal WBC counts and elevated C-reactive protein, which were associated with ICU admission and poor outcomes. Conclusions: Our data demonstrate that abnormalities of biomarkers of hemostasis activation and inflammatory markers are associated with poor outcomes in patients with COVID-19.
Background: 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.
Methods: 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.
Main results: 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.
Conclusions: 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.