The D-dimer antigen is a unique marker of fibrin degradation that is formed by the sequential action of 3 enzymes: thrombin, factor XIIIa, and plasmin. First, thrombin cleaves fibrinogen producing fibrin monomers, which polymerize and serve as a template for factor XIIIa and plasmin formation. Second, thrombin activates plasma factor XIII bound to fibrin polymers to produce the active transglutaminase, factor XIIIa. Factor XIIIa catalyzes the formation of covalent bonds between D-domains in the polymerized fibrin. Finally, plasmin degrades the crosslinked fibrin to release fibrin degradation products and expose the D-dimer antigen. D-dimer antigen can exist on fibrin degradation products derived from soluble fibrin before its incorporation into a fibrin gel, or after the fibrin clot has IntroductionFibrinogen is a soluble plasma glycoprotein that is transformed into highly self-adhesive fibrin monomers after thrombin cleavage. 1 A detailed overview of the process of fibrin formation was recently published. 2 In brief, in the first step of D-dimer formation, thrombin cleavage exposes a previously cryptic polymerization site on fibrinogen that promotes the binding of either another fibrinogen or a monomeric fibrin molecule. 3 Fibrin monomers then bind to one another in an overlapping manner to form 2 molecule thick protofibrils ( Figure 1). 4,5 Plasma remains fluid until 25% to 30% of plasma fibrinogen is cleaved by thrombin, 6 allowing time for fibrin to polymerize while simultaneously promoting thrombin activation of plasma factor XIII. 7 Thrombin remains associated with fibrin, 8 and as additional fibrin molecules polymerize, it activates plasma factor XIII bound to fibrinogen. 9 The complex between soluble fibrin polymers, thrombin, and plasma factor XIII promotes the formation of factor XIIIa before a fibrin gel is detected. 6 In the second step of D-dimer formation, factor XIIIa covalently cross links fibrin monomers via intermolecular isopeptide bonds formed between lysine and glutamine residues within the soluble protofibrils and the insoluble fibrin gel. 10 D-dimer antigen remains undetectable until it is released from crosslinked fibrin by the action of plasmin. In the final step of D-dimer formation, plasmin formed on the fibrin surface by plasminogen activation cleaves substrate fibrin at specific sites ( Figure 1). 11 Fibrin degradation products are produced in a wide variety of molecular weights, including the terminal degradation products of crosslinked fibrin containing D-dimer and fragment E complex (Figure 1). 12,13 It is uncommon to detect circulating terminal fibrin degradation products (D-dimer-E complex) in human plasma, whereas soluble high-molecular-weight fragments that contain the "D-dimer antigen" are present in patients with DIC and other thrombotic disorders. 14 These fragments may be derived from soluble fibrin before it has been incorporated into a fibrin gel, or alternatively may be derived from high-molecular-weight complexes released from an insoluble clot (Figure 2). 15,16 "D-...

Department of Veterans Affairs.

No abstract

Background: Despite increasing emphasis on integration of palliative care with disease-directed care for advanced cancer, the nature of this integration and its effects on patient and caregiver outcomes are not well-understood. Aim: We evaluated the effects of integrated outpatient palliative and oncology care for advanced cancer on patient and caregiver outcomes. Design: Following a standard protocol (PROSPERO: CRD42017057541), investigators independently screened reports to identify randomized controlled trials or quasi-experimental studies that evaluated the effect of integrated outpatient palliative and oncology care interventions on quality of life, survival, and healthcare utilization among adults with advanced cancer. Data were synthesized using random-effects meta-analyses, supplemented with qualitative methods when necessary. Data sources: English-language peer-reviewed publications in PubMed, CINAHL, and Cochrane Central through November 2016. We subsequently updated our PubMed search through July 2018. Results: Eight randomized-controlled and two cluster-randomized trials were included. Most patients had multiple advanced cancers, with median time from diagnosis or recurrence to enrollment ranging from 8 to 12 weeks. All interventions included a multidisciplinary team, were classified as “moderately integrated,” and addressed physical and psychological symptoms. In a meta-analysis, short-term quality of life improved, symptom burden improved, and all-cause mortality decreased. Qualitative analyses revealed no association between integration elements, palliative care intervention elements, and intervention impact. Utilization and caregiver outcomes were often not reported. Conclusions: Moderately integrated palliative and oncology outpatient interventions had positive effects on short-term quality of life, symptom burden, and survival. Evidence for effects on healthcare utilization and caregiver outcomes remains sparse.

Key Points• Depression was found in 35.2% of adult SCD patients and was strongly associated with worse physical and mental quality-of-life outcomes.• Total health care costs for adult SCD patients with depression were more than double those of SCD patients without depression.Sickle cell disease (SCD) is a chronic, debilitating disorder. Chronically ill patients are at risk for depression, which can affect health-related quality of life (HRQoL), health care utilization, and cost. We performed an analytic epidemiologic prospective study to determine the prevalence of depression in adult patients with SCD and its association with HRQoL and medical resource utilization. Depression was measured by the Beck Depression Inventory and clinical history in adult SCD outpatients at a comprehensive SCD center. HRQoL was assessed using the SF36 form, and data were collected on medical resource utilization and corresponding cost. Neurocognitive functions were assessed using the CNS Vital Signs tool.Pain diaries were used to record daily pain. Out of 142 enrolled patients, 42 (35.2%) had depression. Depression was associated with worse physical and mental HRQoL scores (P , .0001 and P , .0001, respectively). Mean total inpatient costs ($25 000 vs $7487, P 5 .02) and total health care costs ($30 665 vs $13 016, P 5 .01) were significantly higher in patients with depression during the 12 months preceding diagnosis. Similarly, during the 6 months following diagnosis, mean total health care costs were significantly higher in depressed patients than in nondepressed patients ($13 766 vs $8670, P 5 .04). Depression is prevalent in adult patients with SCD and is associated with worse HRQoL and higher total health care costs. Efforts should focus on prevention, early diagnosis, and therapy for depression in SCD.