Long-term safety outcomes of prekillikrein (Fletcher factor) deficiency: A systematic literature review of case reports

2019 ◽  
Author(s):  
Antonio Girolami ◽  
Catherine Rolland ◽  
Dan Sexton ◽  
Moshe Vardi ◽  
Jonathan A. Bernstein
Keyword(s):  
Lupus Erythematosus ◽  
Partial Thromboplastin Time ◽  
Case Reports ◽  
Activated Partial Thromboplastin Time ◽  
Plasma Kallikrein ◽  
Excessive Bleeding ◽  
Factor Deficiency ◽  
Fletcher Factor ◽  
The Impact

Background: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications.Objective: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reportedcomorbidities in patients with hereditary prekallikrein deficiency.Methods: We searched several medical literature databases for publications that reported data from patients with hereditaryprekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubationtime). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted.Results: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) wereincluded. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and onewith systemic lupus erythematosus).Conclusion: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

Long-term safety outcomes of prekallikrein (Fletcher factor) deficiency: A systematic literature review of case reports

2020 ◽  
Vol 41 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Antonio Girolami ◽  
Catherine Rolland ◽  
Dan Sexton ◽  
Moshe Vardi ◽  
Jonathan A. Bernstein
Keyword(s):  
Lupus Erythematosus ◽  
Partial Thromboplastin Time ◽  
Case Reports ◽  
Activated Partial Thromboplastin Time ◽  
Plasma Kallikrein ◽  
Time Data ◽  
Factor Deficiency ◽  
Fletcher Factor ◽  
The Impact

Background: Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. Objective: We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reported comorbidities in patients with hereditary prekallikrein deficiency. Methods: We searched several medical literature databases for publications that reported data from patients with hereditary prekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubation time). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Results: Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) were included. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and one with systemic lupus erythematosus). Conclusion: This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

The Activated Seven Lupus Anticoagulant Assay Detects Clinically Significant Antibodies

2008 ◽  
Vol 14 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Gary W. Moore ◽  
Savita Rangarajan ◽  
Geoffrey F. Savidge
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
Anticardiolipin Antibodies ◽  
Activated Partial Thromboplastin Time ◽  
Systemic Lupus ◽  
Lupus Anticoagulants ◽  
Russell’S Viper ◽  
Clinically Significant

Lupus anticoagulants are a heterogeneous group of autoantibodies detected by their effects on phospholipid-dependent coagulation assays. Persistent lupus anticoagulants are associated with thrombotic disease, but not all are clinically significant. Antibody heterogeneity and reagent and test variability dictate that at least 2 tests, of different types, should be used to screen lupus anticoagulants. The objective of this study was to investigate whether the activated seven lupus anticoagulant assay detects clinically significant antibodies. Eighty-two patients with antiphospholipid syndrome (APS) and 32 with systemic lupus erythematosus + positive for activated seven lupus anticoagulant and who were without thrombosis, who were positive by activated seven lupus anticoagulant assay, were investigated for lupus anticoagulants by dilute Russell's viper venom time, dilute activated partial thromboplastin time, and Taipan snake venom time, and for anticardiolipin antibodies. Fifty-seven of the APS patients were positive for lupus anticoagulants in multiple assays, 25 in activated seven lupus anticoagulant alone. Fourteen of the latter group were previously positive in other antiphospholipid antibodies assays, and 11 had only been positive for lupus anticoagulants by activated seven lupus anticoagulant. Twenty-eight had elevated anticardiolipin antibodies, 6 of whom were from the group that was positive in activated seven lupus anticoagulant only. Eight of the systemic lupus erythematosus + lupus anticoagulants (without thrombosis) patients were positive for lupus anticoagulant by activated seven lupus anticoagulant alone and had only been positive in activated seven lupus anticoagulant previously, and none had elevated anticardiolipin antibodies. The remaining 24 patients were lupus-anticoagulant positive in multiple assays, and 9 had elevated anticardiolipin antibodies. Dilute Russell's viper venom time and Dilute activated partial thromboplastin time are widely used to detect lupus anticoagulants and are considered to detect clinically significant antibodies. Activated seven lupus anticoagulant detected antibodies in APS patients who were positive by these assays and also lupus anticoagulants undetectable by the dilute Russell's viper venom time/dilute activated partial thromboplastin time reagents used, demonstrating its utility as a first-line or second-line assay.

Topics of spirituality in neonatology – Results from a systematic literature review

2016 ◽  
Vol 5 (4) ◽  
pp. 303-310 ◽  
Author(s):  
Michael Thiel
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Medical Staff ◽  
Case Reports ◽  
Meta Analysis ◽  
Long Term Outcomes ◽  
Difficult Situation ◽  
Study Designs ◽  
The Impact

AbstractIntroductionThe prognosis of preterms and ill newborns has improved substantially during the last decades. Besides conventional methods, additional interventions play an important role in this development. Managing parents' needs under the circumstances of intensive care can be a crucial aspect of dealing with this difficult situation. But data on this group has not been systematically evaluated so far.MethodWe performed a systematic literature review following the PRISMA criteria. Keywords were neonates, neonatology, newborn, preterm, parents, and spirituality. All study types in English and German were included.ResultsAfter evaluating the abstracts of the initial search results, we considered 33 studies eligible for analysis. Study types are surveys, interviews (qualitative studies), case reports, and reviews. Topics were parents, ethnical differences, medical staff, and palliative care.DiscussionThere is a variety of studies on spirituality in neonatology with a broad spectrum of study types. A meta-analysis is difficult, especially because of the heterogeneity of the study designs, patient numbers and questionnaires used. Although the studies are promising, short-term and long-term outcomes have not been evaluated yet. Interesting endpoints such as the influence on mortality, morbidity and duration of hospital stay cannot be stated. Thus it is too early to derive practical recommendations for the medical staff from these studies.ConclusionAlthough there is a body of data on spirituality in neonatology that addresses several important aspects, even more studies on the impact of parents' needs and the consequences for the medical staff are required.

One-step chromogenic equivalent of activated partial thromboplastin time evaluated for clinical application

1991 ◽  
Vol 37 (7) ◽  
pp. 1235-1244 ◽  
Author(s):  
Gabriëlle E Ponjee ◽  
Huib L Vader ◽  
Net J de Wild ◽  
Ger W T Janssen ◽  
Fedde van der Graaf
Keyword(s):  
Partial Thromboplastin Time ◽  
Clinical Laboratory ◽  
Intrinsic Factor ◽  
Activated Partial Thromboplastin Time ◽  
Factor Vii ◽  
Factor Deficiency ◽  
One Step ◽  
The One

Abstract We evaluated the clinical usefulness of a recently developed semi-automated one-step chromogenic equivalent of activated partial thromboplastin time (APTT; Behring). This simple test is easily adaptable for automation. Generally, the results with this chromogenic one-step APTT were at least as precise as those obtained with comparative coagulometric methods. The chromogenic one-step APTT showed, both in vitro and in vivo, adequate sensitivity to congenital intrinsic factor deficiency but no sensitivity to Factor VII deficiency. Unlike a two-step coagulometric APTT (Dade), the one-step chromogenic APTT seemed sensitive to activation products of the contact system, which are present in immunoadsorbed factor-deficient plasma. The in vitro sensitivity of the chromogenic APTT to heparin was comparable with that of a coagulometric APTT, but the sensitivity to heparin in patients' samples differed slightly. The chromogenic APTT is relatively insensitive to anomalies in the fibrinogen-fibrin conversion. Finally, we observed discrepancies between the chromogenic and coagulometric APTT results for plasma of patients with disseminated intravascular coagulation. We conclude that this one-step chromogenic APTT warrants further evaluation for possible use as a routine test for the clinical laboratory.

scholarly journals Low prevalence of bone mineral density testing in patients with systemic lupus erythematosus and glucocorticoid exposure

Lupus ◽  
2020 ◽  
pp. 096120332097973
Author(s):  
JB Boone ◽  
Lee Wheless ◽  
Alex Camai ◽  
S Bobo Tanner ◽  
April Barnado
Keyword(s):  
Bone Mineral Density ◽  
Systemic Lupus Erythematosus ◽  
Bone Mineral ◽  
Lupus Erythematosus ◽  
Race And Ethnicity ◽  
Mineral Density ◽  
Systemic Lupus ◽  
Bmd Testing ◽  
The Impact

Summary Patients with systemic lupus erythematosus (SLE) have an increased risk of developing osteoporosis and fractures due to systemic inflammation and glucocorticoids (GCs). Professional organizations recommend bone mineral density (BMD) testing in SLE patients on GCs, especially within 6 months of initiation. Using a validated algorithm, we identified SLE patients in an electronic health record cohort with long-term GC exposure (≥90 days). Our primary outcome was ever BMD testing. We assessed the impact of patient and provider factors on testing. We identified 693 SLE cases with long-term GC exposure, 41% of whom had BMD testing performed. Only 18% of patients had BMD testing within 6 months of GC initiation. In a logistic regression model for BMD testing, male sex (OR = 0.49, 95% CI 0.27 – 0.87, p = 0.01) was associated with being less likely to have BMD testing after adjusting for race and ethnicity. In contrast, older age (OR = 1.04, p < 0.001) and nephritis (OR = 1.83, p = 0.003) were associated with being more likely to have BMD testing after adjusting for race and ethnicity. Bone health in SLE patients remains an area in need of improvement with attention to patients who are younger and male.

scholarly journals Plasma prothrombin time and activated partial thromboplastin time as predictors of bleeding manifestations during dengue hemorrhagic fever

2009 ◽  
Vol 49 (2) ◽  
pp. 69
Author(s):  
I. N. Budastra ◽  
B. N. P. Arhana ◽  
IB. Mudita
Keyword(s):  
Cohort Study ◽  
Partial Thromboplastin Time ◽  
Cox Regression ◽  
Hemorrhagic Fever ◽  
Massive Bleeding ◽  
Activated Partial Thromboplastin Time ◽  
Regression Analyses ◽  
Cox Regression Analysis ◽  
The Impact ◽  
The Relationship

Background  Massive bleeding and shock are complications  ofdengue  hemorrhagic  fever (DHF)  that  are associated withhigh mortality. Impaired hemostasis, especially coagulopathy,contributes  to  bleeding manifestations in DHF. Parameters suchas  activated partial thromboplastin time (APTT)  and  plasmaprothrombin  time (PPT) indicate  the  impact  of  coagulationsystem.Objective  To  determine the relationship between  APTT  and PPTlevels with bleeding manifestations in  DHF  patients.Methods  A prospective  cohort  study was applied to subjectsdiagnosed with  DHF  at  the  Infection  and  Tropical DiseasesDivision, Department  of  Child Health, Medical School, UdayanaUniversity, Sanglah Hospital, Denpasar, Indonesia. Laboratorytests  to  determine  APTT  and  PPT  were carried  out  on  thethird, fourth,  and  fifth day after  the  onset  of  fever. Bleedingmanifestations were examined in patients during their hospitalstay. Univariate  and  Cox regression analyses were performedto examine relationship between  APTT  and  PPT  values withbleeding manifestations in  DHF  patients.Results  Forty-three children were enrolled in this study.  Therewas a significant relationship between increases in  APTT  valuewith bleeding manifestations in  DHF  patients [RR 2.79 (95%CI1.68 to 4.69), P <0.01]. Cox regression analysis showed  that  onlyincreased  APTT  values correlated with bleeding manifestations[RR 2.05 (95%CI 1.92 to 3.90), P  =  0.02].Conclusion  APTT  values may be used  as  a predictor for bleedingmanifestations  in  DHF.

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