Introduction: Sickle cell trait (SCT) has been associated with ischemic stroke in some, but not a... more Introduction: Sickle cell trait (SCT) has been associated with ischemic stroke in some, but not all, epidemiologic cohorts. Heterogeneity of the association may be related to differences in demographic subgroups or midlife risk factors. Methods: The ARIC study is an observational cohort based on 4 US communities. Participation has included 6 clinical visits and ongoing surveillance of acute cardiovascular events. Black participants were genotyped for SCT, excluding any with sickle cell anemia or hemoglobin SC disease. Global genetic ancestry was determined from whole genome variation. Midlife factors were ascertained at ARIC visit 1 (1987-1989), or if missing imputed from visit 2 (1990-1992). Acute ischemic stroke was classified by physician review of the medical record. Associations between SCT and ischemic stroke were analyzed using repeat-events Cox regression with robust estimators, counting all occurrences of ischemic stroke per participant. Models were adjusted for sex, age, global genetic ancestry, and midlife factors (smoking, hypertension, hyperlipidemia, diabetes, chronic kidney disease, and previous myocardial infarction). Effect modification was tested by the multiplicative interaction of SCT with each midlife factor. Results: Our population was composed of 3,827 black adults with complete midlife data (32 [0.8%] excluded). SCT was identified in 255 (7%). The mean age at visit 1 was 53 years; the median follow-up time was 26 years. Most (63%) were women. At midlife, individuals with SCT had a greater prevalence of hyperlipidemia (32% vs. 26%; P =0.04) and chronic kidney disease (20% vs. 13%; P =0.003). From 1987-2016, 579 ischemic strokes occurred in 456 individuals. SCT was more strongly associated with ischemic stroke in participants with chronic kidney disease [HR=2.01 (1.13 - 3.60)] than those without [HR=1.10 (0.77 - 1.57)], P for interaction = 0.05, Figure 1 . Conclusions: The association between SCT and ischemic stroke is heterogeneous and appears to be stronger in those with chronic kidney disease.
The recommended dose of recombinant factor VIIa (rFVIIa, NovoSeven®) is 90 mcg/kg every 2–3 hours... more The recommended dose of recombinant factor VIIa (rFVIIa, NovoSeven®) is 90 mcg/kg every 2–3 hours. The Home Treatment Study demonstrated an average of 2.2 doses of 90 mcg/kg were required to treat mild to moderate bleeds. Since it is recognized that a single dose administered shortly after a bleed, if equally effective, would be more convenient and possibly could reduce bleeding morbidity, this study examined the experience registered with the use of single rFVIIa doses in the United States. The HTRS database contains patient data relating to hemophilia treatment and related disorders, and in particular the treatment of acute bleeding episodes in individuals with hemophilia complicated by anti-factor VIII (FVIII) or IX (FIX) alloantibody inhibitors. Between January 2004 and March 2008, the database contained information on over 5,000 bleeding episodes. The data for patients receiving only a single bolus intravenous dose of rFVIIa and no additional treatment were evaluated. The parameters assessed included patient demographics, bleed location, bleed type (specifically joint and muscle bleeds), and dose. Of 2,532 patients who received rFVIIa, 70 with congenital hemophilia A (n=63) or B (n=7) and inhibitors experienced 508 bleeding episodes that were treated solely with a single dose of rFVIIa. The mean (median, range) age at the time of bleed was 12.7 years (8.2, 0.6–60.4). Mean titers for anti-FVIII and anti-FIX were 62.2 BU (15.0, 0–1408) and 6.8 BU (1.3, 0–31.7), respectively. The bleed sites recorded were joints (271 bleeds [53%], including 55 in target joints [20.2% of joint bleeds]), muscle (78, 15%), mucosal (45, 9%), intracranial (25, 5%), and subcutaneous (21, 4%). Joint bleeds occurred primarily in the ankles (124 bleeds), elbows (61 bleeds) and knees (53 bleeds). For 508 bleeds treated with a single dose of rFVIIa, the mean (median, range) dose was 119.5 mcg/kg (100, 25–500) with 20 of those doses ≥270 mcg/kg. Patients with joint bleeds were treated with 123.1 mcg/kg (100, 25–500), target joint bleeds with 155.3 (140, 50–393), and those with the muscle bleeds received 120.1 mcg/kg (100, 50–500). The most common single dose regimen overall and for the joint and muscle bleeds was 90 mcg/kg rFVIIa. The majority of bleeds (424, 82.7%) were treated at home, but bleeds were also treated at Hemophilia Treatment Centers (61, 12.0%) and in the emergency room (15, 3.0%). Overall, physician reported “bleeding stopped” in 97% of the 494 bleeds, 97% of hemarthroses, 96% of target joint hemarthroses and 96% of muscle bleeds. For the remaining 14 episodes, although documentation did not indicate “bleeding stopped”, no other medications were recorded. There were no serious adverse drug reactions. Registry data can only demonstrate the treatment reported in selected bleeds captured, and the analysis here specifically examined bleeds treated with only a single dose either because of bleed resolution or by physician/patient choice. The data analyzed here demonstrate single doses of rFVIIa of up to 500 mcg/kg (mean 119 mcg/kg) for mild to moderate bleeds effectively resolved bleeds in 97%, including hemarthrosis, target joints hemarthrosis, and muscle bleeds. These data support the possibility that rFVIIa can be administered in a single bolus dose with equivalent or superior efficacy as multiple lower doses for bleeding episodes treated as part of a home therapy regimen. While 3 randomized trials have examined the equivalence of a single dose of 270 mcg/kg with 3 doses of 90 mcg/kg, these data suggest that single doses of rFVIIa therapy in the real world often were empirically titrated on a patient specific basis, according to the severity and site of the bleeding episode. These registry data provide justification for prospective, randomized, single dose titration trials of rFVIIa or future analogues.
Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular d... more Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular disease (CVD). Traditional cardiovascular risk factors do not fully explain the high CVD risk in this population. During hemodialysis, blood interacts with the biomaterials of the hemodialysis circuit. This interaction can activate the complement system and the factor XII-driven contact system. FXII activation triggers both the intrinsic pathway of coagulation and the kallikrein-kinin pathway, resulting in thrombin and bradykinin production, respectively. The complement system plays a key role in the innate immune response, but also contributes to the pathogenesis of numerous disease states. Components of the complement pathway, including mannose binding lectin and C3, are associated with CVD risk in people with end-stage kidney disease (ESKD). Both the complement system and the factor XII-driven contact coagulation system mediate proinflammatory and procoagulant responses that could contribute to or accelerate CVD in hemodialysis recipents. This review summarizes what is already known about hemodialysis-mediated activation of the complement system and in particular the coagulation contact system, emphasizing the potential role these systems play in the identification of new biomarkers for CVD risk stratification and the development of potential therapeutic targets or innovative therapies that decrease CVD risk in ESKD patients.
Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired auto-antib... more Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired auto-antibodies to endogenous Factor VIII (FVIII) resulting in decreased FVIII activity. AHA can lead to life-threatening bleeding, with effective treatment requiring both immunosuppressive therapy (IST) and bypassing agents such as recombinant activated Factor VII (rFVIIa) or activated prothrombin complex concentrates (APCC) (Tiede et al. Haematologica 2020). Some, including our group, have begun using emicizumab as well (Knoebl et al. Blood 2020). IST is required for inhibitor eradication, but regimens are heterogenous and have not been systematically compared in the literature. While there is no standard of care IST in these patients, most patients in the literature receive multiple agents, including corticosteroids, mycophenolate mofetil, cyclosporine, and/or rituximab in combination. We report in a prospective cohort that for IST, rituximab monotherapy is an effective strategy. An updated tre...
IntroductionHaemophilia A patients require perioperative clotting factor replacement to limit exc... more IntroductionHaemophilia A patients require perioperative clotting factor replacement to limit excessive bleeding. Weight‐based dosing of Factor VIII (FVIII) does not account for inter‐individual pharmacokinetic (PK) variability, and may lead to suboptimal FVIII exposure.AimTo perform an external validation of a previously developed population PK (popPK) model of perioperative FVIII in haemophilia A patients.MethodsA retrospective chart review identified perioperative haemophilia A patients at the University of North Carolina (UNC) between April 2014 and November 2019. Patient data was used to externally validate a previously published popPK model proposed by Hazendonk. Based on these validation results, a modified popPK model was developed to characterize FVIII PK in our patients. Dosing simulations were performed using this model to compare FVIII target attainment between intermittent bolus (IB) and continuous infusion (CI) administration methods.ResultsA total of 521 FVIII concent...
Qualitative platelet defects are a heterogeneous group of disorders characterized by abnormal pla... more Qualitative platelet defects are a heterogeneous group of disorders characterized by abnormal platelet function. Currently available laboratory assays lack sensitivity and specificity for detecting Storage Pool and Platelet Secretion defects. The Gray Platelet Syndrome (GPS) is an autosomal recessive disorder characterized by a decrease or absence of alpha granule contents. The Quebec Platelet Disorder (QPD) results from proteolysis of alpha granule proteins due to increased amounts of platelet urokinase. A decrease or deficiency of multimerin is characteristic. Proteomics is a rapidly developing field with great promise in the study of pathophysiology and biomarker development. Recent advances have made measurement of relative protein abundance in multiple samples feasible. We used one such approach, “isotope Tagging for Relative and Absolute Quantitation” (iTRAQ) to characterize the platelet proteome of healthy volunteers and patients with GPS and QPD. iTRAQ allows analysis of up ...
Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired autoantibo... more Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired autoantibodies to endogenous Factor VIII (FVIII) decrease FVIII activity. AHA can lead to serious bleeding, with effective treatment requiring both immunosuppressive therapy (IST) and bypassing agents such as recombinant activated Factor VII (rFVIIa) or activated prothrombin complex concentrates (APCC). Disadvantages to bypassing agents include the inability to monitor response with standard lab assays, inconsistent hemostatic efficacy, and thrombosis (Astermark et al. 2007). Recombinant porcine FVIII (rpFVIII) ), by virtue of its incomplete homology in the A2 and C2 domains of the FVIII molecule, has decreased reactivity with anti-human FVIII (hFVIII) inhibitors (Mulliez et al. 2014), enabling its use in AHA. It also has the advantage of laboratory monitoring of FVIII activity levels and hemostatic efficacy after failure of bypassing agents (Trautmann-Grill et al. 2018). Between July 2015 and Apr...
Introduction and Rationale: The development of alloantibodies to factor VIII remains a challengin... more Introduction and Rationale: The development of alloantibodies to factor VIII remains a challenging and significant complication in the treatment of patients with congenital hemophilia A (HA). Inhibitor development is more common in severe HA than in non-severe HA (NSHA). Incidence of inhibitors in NSHA is approximately 3-13%, and even with attempted immune tolerance induction and immunosuppression, inhibitors have been reported to persist long-term in about 40% of NSHA patients (Hay 1998). Inhibitors in patients with NSHA can have variable kinetics, causing clinical characteristics similar to patients with acquired hemophilia A (AHA), with observable type 2 kinetics and inhibition of exogenous and endogenous FVIII activity (d'Oiron et al. 2006). Optimal treatment regimens have yet to be established for these patients, in terms of inhibitor eradication and choice of agent for control of bleeding episodes, with known thrombotic side effects when using bypassing agents, including i...
Background: Compared to Whites, Black-Americans may have a 40% higher incidence of idiopathic VTE... more Background: Compared to Whites, Black-Americans may have a 40% higher incidence of idiopathic VTE. However, whether other VTE characteristics vary by race is uncertain. Objective: To compare demographic and baseline characteristics among White- and Black-Americans with VTE. Methods: Using a standardized data-collection form, demographic and baseline characteristics were prospectively collected from consecutive consenting patients enrolled in seven Thrombosis and Hemostasis Centers from August 2003 to March 2008. For patients with objectively diagnosed VTE, demographic and baseline characteristics were compared among White- and Black-American VTE patients, both overall, and by age and gender. Results: Among 1960 White- and 368 Black-Americans with VTE, compared to Whites, Blacks had significantly less isolated DVT (73.9% vs. 86.5%, p<0.001) and significantly more PE ± DVT (45.1 vs. 39.6%, p=0.05). Blacks and Whites did not differ in mean age (43.4 vs. 44.3 years), but a significan...
Introduction: Sickle cell trait (SCT) has been associated with ischemic stroke in some, but not a... more Introduction: Sickle cell trait (SCT) has been associated with ischemic stroke in some, but not all, epidemiologic cohorts. Heterogeneity of the association may be related to differences in demographic subgroups or midlife risk factors. Methods: The ARIC study is an observational cohort based on 4 US communities. Participation has included 6 clinical visits and ongoing surveillance of acute cardiovascular events. Black participants were genotyped for SCT, excluding any with sickle cell anemia or hemoglobin SC disease. Global genetic ancestry was determined from whole genome variation. Midlife factors were ascertained at ARIC visit 1 (1987-1989), or if missing imputed from visit 2 (1990-1992). Acute ischemic stroke was classified by physician review of the medical record. Associations between SCT and ischemic stroke were analyzed using repeat-events Cox regression with robust estimators, counting all occurrences of ischemic stroke per participant. Models were adjusted for sex, age, global genetic ancestry, and midlife factors (smoking, hypertension, hyperlipidemia, diabetes, chronic kidney disease, and previous myocardial infarction). Effect modification was tested by the multiplicative interaction of SCT with each midlife factor. Results: Our population was composed of 3,827 black adults with complete midlife data (32 [0.8%] excluded). SCT was identified in 255 (7%). The mean age at visit 1 was 53 years; the median follow-up time was 26 years. Most (63%) were women. At midlife, individuals with SCT had a greater prevalence of hyperlipidemia (32% vs. 26%; P =0.04) and chronic kidney disease (20% vs. 13%; P =0.003). From 1987-2016, 579 ischemic strokes occurred in 456 individuals. SCT was more strongly associated with ischemic stroke in participants with chronic kidney disease [HR=2.01 (1.13 - 3.60)] than those without [HR=1.10 (0.77 - 1.57)], P for interaction = 0.05, Figure 1 . Conclusions: The association between SCT and ischemic stroke is heterogeneous and appears to be stronger in those with chronic kidney disease.
The recommended dose of recombinant factor VIIa (rFVIIa, NovoSeven®) is 90 mcg/kg every 2–3 hours... more The recommended dose of recombinant factor VIIa (rFVIIa, NovoSeven®) is 90 mcg/kg every 2–3 hours. The Home Treatment Study demonstrated an average of 2.2 doses of 90 mcg/kg were required to treat mild to moderate bleeds. Since it is recognized that a single dose administered shortly after a bleed, if equally effective, would be more convenient and possibly could reduce bleeding morbidity, this study examined the experience registered with the use of single rFVIIa doses in the United States. The HTRS database contains patient data relating to hemophilia treatment and related disorders, and in particular the treatment of acute bleeding episodes in individuals with hemophilia complicated by anti-factor VIII (FVIII) or IX (FIX) alloantibody inhibitors. Between January 2004 and March 2008, the database contained information on over 5,000 bleeding episodes. The data for patients receiving only a single bolus intravenous dose of rFVIIa and no additional treatment were evaluated. The parameters assessed included patient demographics, bleed location, bleed type (specifically joint and muscle bleeds), and dose. Of 2,532 patients who received rFVIIa, 70 with congenital hemophilia A (n=63) or B (n=7) and inhibitors experienced 508 bleeding episodes that were treated solely with a single dose of rFVIIa. The mean (median, range) age at the time of bleed was 12.7 years (8.2, 0.6–60.4). Mean titers for anti-FVIII and anti-FIX were 62.2 BU (15.0, 0–1408) and 6.8 BU (1.3, 0–31.7), respectively. The bleed sites recorded were joints (271 bleeds [53%], including 55 in target joints [20.2% of joint bleeds]), muscle (78, 15%), mucosal (45, 9%), intracranial (25, 5%), and subcutaneous (21, 4%). Joint bleeds occurred primarily in the ankles (124 bleeds), elbows (61 bleeds) and knees (53 bleeds). For 508 bleeds treated with a single dose of rFVIIa, the mean (median, range) dose was 119.5 mcg/kg (100, 25–500) with 20 of those doses ≥270 mcg/kg. Patients with joint bleeds were treated with 123.1 mcg/kg (100, 25–500), target joint bleeds with 155.3 (140, 50–393), and those with the muscle bleeds received 120.1 mcg/kg (100, 50–500). The most common single dose regimen overall and for the joint and muscle bleeds was 90 mcg/kg rFVIIa. The majority of bleeds (424, 82.7%) were treated at home, but bleeds were also treated at Hemophilia Treatment Centers (61, 12.0%) and in the emergency room (15, 3.0%). Overall, physician reported “bleeding stopped” in 97% of the 494 bleeds, 97% of hemarthroses, 96% of target joint hemarthroses and 96% of muscle bleeds. For the remaining 14 episodes, although documentation did not indicate “bleeding stopped”, no other medications were recorded. There were no serious adverse drug reactions. Registry data can only demonstrate the treatment reported in selected bleeds captured, and the analysis here specifically examined bleeds treated with only a single dose either because of bleed resolution or by physician/patient choice. The data analyzed here demonstrate single doses of rFVIIa of up to 500 mcg/kg (mean 119 mcg/kg) for mild to moderate bleeds effectively resolved bleeds in 97%, including hemarthrosis, target joints hemarthrosis, and muscle bleeds. These data support the possibility that rFVIIa can be administered in a single bolus dose with equivalent or superior efficacy as multiple lower doses for bleeding episodes treated as part of a home therapy regimen. While 3 randomized trials have examined the equivalence of a single dose of 270 mcg/kg with 3 doses of 90 mcg/kg, these data suggest that single doses of rFVIIa therapy in the real world often were empirically titrated on a patient specific basis, according to the severity and site of the bleeding episode. These registry data provide justification for prospective, randomized, single dose titration trials of rFVIIa or future analogues.
Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular d... more Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular disease (CVD). Traditional cardiovascular risk factors do not fully explain the high CVD risk in this population. During hemodialysis, blood interacts with the biomaterials of the hemodialysis circuit. This interaction can activate the complement system and the factor XII-driven contact system. FXII activation triggers both the intrinsic pathway of coagulation and the kallikrein-kinin pathway, resulting in thrombin and bradykinin production, respectively. The complement system plays a key role in the innate immune response, but also contributes to the pathogenesis of numerous disease states. Components of the complement pathway, including mannose binding lectin and C3, are associated with CVD risk in people with end-stage kidney disease (ESKD). Both the complement system and the factor XII-driven contact coagulation system mediate proinflammatory and procoagulant responses that could contribute to or accelerate CVD in hemodialysis recipents. This review summarizes what is already known about hemodialysis-mediated activation of the complement system and in particular the coagulation contact system, emphasizing the potential role these systems play in the identification of new biomarkers for CVD risk stratification and the development of potential therapeutic targets or innovative therapies that decrease CVD risk in ESKD patients.
Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired auto-antib... more Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired auto-antibodies to endogenous Factor VIII (FVIII) resulting in decreased FVIII activity. AHA can lead to life-threatening bleeding, with effective treatment requiring both immunosuppressive therapy (IST) and bypassing agents such as recombinant activated Factor VII (rFVIIa) or activated prothrombin complex concentrates (APCC) (Tiede et al. Haematologica 2020). Some, including our group, have begun using emicizumab as well (Knoebl et al. Blood 2020). IST is required for inhibitor eradication, but regimens are heterogenous and have not been systematically compared in the literature. While there is no standard of care IST in these patients, most patients in the literature receive multiple agents, including corticosteroids, mycophenolate mofetil, cyclosporine, and/or rituximab in combination. We report in a prospective cohort that for IST, rituximab monotherapy is an effective strategy. An updated tre...
IntroductionHaemophilia A patients require perioperative clotting factor replacement to limit exc... more IntroductionHaemophilia A patients require perioperative clotting factor replacement to limit excessive bleeding. Weight‐based dosing of Factor VIII (FVIII) does not account for inter‐individual pharmacokinetic (PK) variability, and may lead to suboptimal FVIII exposure.AimTo perform an external validation of a previously developed population PK (popPK) model of perioperative FVIII in haemophilia A patients.MethodsA retrospective chart review identified perioperative haemophilia A patients at the University of North Carolina (UNC) between April 2014 and November 2019. Patient data was used to externally validate a previously published popPK model proposed by Hazendonk. Based on these validation results, a modified popPK model was developed to characterize FVIII PK in our patients. Dosing simulations were performed using this model to compare FVIII target attainment between intermittent bolus (IB) and continuous infusion (CI) administration methods.ResultsA total of 521 FVIII concent...
Qualitative platelet defects are a heterogeneous group of disorders characterized by abnormal pla... more Qualitative platelet defects are a heterogeneous group of disorders characterized by abnormal platelet function. Currently available laboratory assays lack sensitivity and specificity for detecting Storage Pool and Platelet Secretion defects. The Gray Platelet Syndrome (GPS) is an autosomal recessive disorder characterized by a decrease or absence of alpha granule contents. The Quebec Platelet Disorder (QPD) results from proteolysis of alpha granule proteins due to increased amounts of platelet urokinase. A decrease or deficiency of multimerin is characteristic. Proteomics is a rapidly developing field with great promise in the study of pathophysiology and biomarker development. Recent advances have made measurement of relative protein abundance in multiple samples feasible. We used one such approach, “isotope Tagging for Relative and Absolute Quantitation” (iTRAQ) to characterize the platelet proteome of healthy volunteers and patients with GPS and QPD. iTRAQ allows analysis of up ...
Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired autoantibo... more Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired autoantibodies to endogenous Factor VIII (FVIII) decrease FVIII activity. AHA can lead to serious bleeding, with effective treatment requiring both immunosuppressive therapy (IST) and bypassing agents such as recombinant activated Factor VII (rFVIIa) or activated prothrombin complex concentrates (APCC). Disadvantages to bypassing agents include the inability to monitor response with standard lab assays, inconsistent hemostatic efficacy, and thrombosis (Astermark et al. 2007). Recombinant porcine FVIII (rpFVIII) ), by virtue of its incomplete homology in the A2 and C2 domains of the FVIII molecule, has decreased reactivity with anti-human FVIII (hFVIII) inhibitors (Mulliez et al. 2014), enabling its use in AHA. It also has the advantage of laboratory monitoring of FVIII activity levels and hemostatic efficacy after failure of bypassing agents (Trautmann-Grill et al. 2018). Between July 2015 and Apr...
Introduction and Rationale: The development of alloantibodies to factor VIII remains a challengin... more Introduction and Rationale: The development of alloantibodies to factor VIII remains a challenging and significant complication in the treatment of patients with congenital hemophilia A (HA). Inhibitor development is more common in severe HA than in non-severe HA (NSHA). Incidence of inhibitors in NSHA is approximately 3-13%, and even with attempted immune tolerance induction and immunosuppression, inhibitors have been reported to persist long-term in about 40% of NSHA patients (Hay 1998). Inhibitors in patients with NSHA can have variable kinetics, causing clinical characteristics similar to patients with acquired hemophilia A (AHA), with observable type 2 kinetics and inhibition of exogenous and endogenous FVIII activity (d'Oiron et al. 2006). Optimal treatment regimens have yet to be established for these patients, in terms of inhibitor eradication and choice of agent for control of bleeding episodes, with known thrombotic side effects when using bypassing agents, including i...
Background: Compared to Whites, Black-Americans may have a 40% higher incidence of idiopathic VTE... more Background: Compared to Whites, Black-Americans may have a 40% higher incidence of idiopathic VTE. However, whether other VTE characteristics vary by race is uncertain. Objective: To compare demographic and baseline characteristics among White- and Black-Americans with VTE. Methods: Using a standardized data-collection form, demographic and baseline characteristics were prospectively collected from consecutive consenting patients enrolled in seven Thrombosis and Hemostasis Centers from August 2003 to March 2008. For patients with objectively diagnosed VTE, demographic and baseline characteristics were compared among White- and Black-American VTE patients, both overall, and by age and gender. Results: Among 1960 White- and 368 Black-Americans with VTE, compared to Whites, Blacks had significantly less isolated DVT (73.9% vs. 86.5%, p<0.001) and significantly more PE ± DVT (45.1 vs. 39.6%, p=0.05). Blacks and Whites did not differ in mean age (43.4 vs. 44.3 years), but a significan...
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