Factor XIII in the Acute Care Setting and Its Relevance in Obstetric Bleeding.

Background: Major hemorrhage is one of the main causes of preventable mortality in either severe trauma, high-risk surgical patient, or the obstetric population. As underlined by the cell-based coagulation model, a resistant and stable clot is essential to prevent or to stop an ongoing bleeding. Coagulation factor XIII (FXIII) stabilizes the newly formed clot by cross-linking the fibrin monomers into a three-dimensional network and by impeding fibrinolysis. Thus, FXIII is an essential coagulation factor in the acutely bleeding patient. Summary: Acquired FXIII deficiency is much more common than the inherited form. On the basis of acute tissue injury which leads to major bleeding, acquired FXIII deficiency is traditionally considered to be secondary to consumption. However, recent evidence in the field of obstetrics and high-risk surgery suggests that it might be an associated factor rather than a consequence of the bleeding, which would mean that early replacement of FXIII could potentially improve outcomes. However, FXIII measurement is not universally available. Assessing FXIII through viscoelastic assays seems feasible, though likely it is not yet accurate. Moreover, the target population at risk and the aimed FXIII level required to achieve hemostasis in each condition are yet to be defined. Key Messages: FXIII should be assessed and replaced if necessary in the acutely bleeding patient. We recommend FXIII to be included in an escalating scheme of hemostatic therapies in the acute care setting.

Peripartum Haemorrhage: Haemostatic Aspects of the Updated Peripartum Haemorrhage Guideline of the German-Speaking Countries.

Background: Peripartum haemorrhage (PPH) is a potentially life-threatening complication. Although still rare, the incidence of peripartal haemorrhage is rising in industrialised countries and refractory bleeding remains among the leading causes of death in the peripartal period. Summary: The interdisciplinary German, Austrian, and Swiss guideline on "Peripartum Haemorrhage: Diagnostics and Therapies" has reviewed the evidence for the diagnostics and medical, angiographic, haemostatic, and surgical treatment and published an update in September 2022 . This article reviews the updated recommendations regarding the early diagnosis and haemostatic treatment of PPH. Keystones of the guideline recommendations are the early diagnosis of the bleeding by measuring blood loss using calibrated collector bags, the development of a multidisciplinary treatment algorithm adapted to the severity of bleeding, and the given infrastructural conditions of each obstetric unit, the early and escalating use of uterotonics, the therapeutic, instead of preventative, use of tranexamic acid, the early diagnostics of progressive deficiencies of coagulation factors or platelets to facilitate a tailored and guided haemostatic treatment with coagulation factors, platelets as well as packed red blood cells and fresh frozen plasma when a massive transfusion is required. Key Messages: Essential for the effective and safe treatment of PPH is the timely diagnosis. The diagnosis of PPH requires the measurement rather than estimation of blood loss. Successful treatment of PPH consists of a multidisciplinary approach involving surgical and haemostatic treatments to stop the bleeding. Haemostatic treatment of PPH starts early after diagnosis and combines tranexamic acid, an initially ratio-driven transfusion with RBC:plasma:PC = 4:4:1 (when using pooled or apheresis PC) and finally a goal-directed substitution with coagulation factor concentrates for proven deficiencies. Early monitoring of coagulation either by standard parameters or viscoelastic methods facilitates goal-directed haemostatic treatment.

The Impact of Prepartum Platelet Count on Postpartum Blood Loss and Its Association with Coagulation Factor XIII Activity.

Background: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality worldwide. Contradictory information exists regarding the relevance of prepartum platelet count on postpartum hemorrhage. We have shown prepartum coagulation factor XIII to be associated with postpartum blood loss; however, little is known about the association of platelet count with factor XIII activity. Our objectives were, first, to evaluate the impact of prepartum platelet count on measured postpartum blood loss in the context of prepartum measurements of coagulation factors I, II, and XIII and, second, to evaluate the association of platelet count with coagulation factor XIII, both pre- and postpartum. Material and Methods: This is a secondary analysis of a prospective cohort study (PPH 1,300 study) which analyzed the impact of prepartum blood coagulation factors on postpartum blood loss in 1,300 women. Blood loss was quantified using a validated technique. The impact of prepartum platelet count on measured blood loss was assessed by continuous outcome logistic regression; the association of platelet count with factor XIII activity by Spearman rank correlation. Results: Prepartum platelet count was significantly associated with measured postpartum blood loss: every one unit (G/L) increase in prepartum thrombocytes was associated with an odds ratio of 1.002 (95% confidence interval, 1.001-1.004, p = 0.005) to keep blood loss below any given cut-off level. This means that the probability of postpartum hemorrhage decreases with increasing prepartum platelet levels. Moreover, a significant association of platelet count with factor XIII activity was shown (Spearman rank correlation coefficient for prepartum values 0.228, p < 0.001, and for postpartum values 0.293, p < 0.001). Discussion/Conclusion: The significant association of prepartum platelet count and postpartum blood loss as well as the association of platelet count with blood coagulation factor XIII activity support the likely role of platelets in preventing postpartum hemorrhage and support the new guidelines for the treatment of postpartum hemorrhage in Germany, Austria, and Switzerland, which calls for optimizing platelet counts peripartally in case of postpartum hemorrhage. A possible effect of platelets on the level of circulating factor XIII cannot be ruled out and should prompt further investigation.

The associations between alcohol intake and cardiometabolic risk in African-origin adults spanning the epidemiologic transition.

BACKGROUND: Cardiometabolic (CM) risk affects approximately 25% of adults globally, and is diagnosed by meeting 3 out of 5 of the following CM risk factors: elevated blood pressure, high triglycerides, elevated blood sugar, low high-density lipoprotein (HDL) level, and abdominal obesity. Adults with CM risk are approximately 22% more likely to have higher mortality rates, and alcohol consumption may be associated with higher CM risk. While previous studies have investigated this potential connection, the majority of them did not include African-origin adults. Therefore, the study aimed to explore the association between alcohol intake and CM risk in 5 African-origin cohorts, spanning the epidemiologic transition in Ghana, South Africa, Jamaica, Seychelles and the United States of America. METHODS: Measurements included clinical measures for CM risk and self-reported alcohol consumption. Each participant was categorized into one of three drinking categories: non-drinker, light drinker (1-3 drinks daily for men and 1-2 drinks daily for women) and heavy drinker (4 or more drinks every day for men and 3 or more drinks per day for women). Using non-drinker status as the reference, the association between alcohol consumption status and prevalence of each of the five CM risk factors and overall elevated CM risk (having 3 out of 5 risk factors) was explored, adjusting for site, age and sex. Associations were explored using logistic regression and significance was determined using odds ratios (OR) and 95% confidence intervals. RESULTS: Neither light nor heavy drinking was associated with increased odds for having higher CM risk compared to nondrinkers (OR = 1.05, p = 0.792 and OR = 1.11, p = 0.489, respectively). However, light drinking was associated with lower odds for having low high density lipoproteins (HDL) cholesterol (OR = 0.69, p = 0.002) and increased risk for high triglycerides (OR = 1.48, p = 0.030). Heavy drinking was associated with elevated blood pressure (OR = 1.59, p = 0.002), high triglycerides (OR = 1.73, p = 0.006) and decreased risk of low HDL-cholesterol (OR = 0.621, p < 0.0005). Finally, country-specific analyses indicated that the relationship between heavy drinking and elevated CM risk varied widely across sites. CONCLUSION: While several CM risk factors were associated with alcohol consumption, the associations were inconsistent and varied widely across five international cohorts of African-origin. Future studies should focus on understanding the individual site-related effects.

Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER).

Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.

THROMBOTECT - a randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during induction therapy of acute lymphoblastic leukemia in children and adolescents.

Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively compared the efficacy and safety of antithrombotic interventions in the consecutive leukemia trials ALL-BFM 2000 and AIEOP-BFM ALL 2009. Patients with newly diagnosed acute lymphoblastic leukemia (n=949, age 1 to 18 years) were randomized to receive low-dose unfractionated heparin, prophylactic low molecular weight heparin (enoxaparin) or activity-adapted antithrombin throughout induction therapy. The primary objective of the study was to determine whether enoxaparin or antithrombin reduces the incidence of thromboembolism as compared to unfractionated heparin. The principal safety outcome was hemorrhage; leukemia outcome was a secondary endpoint. Thromboembolism occurred in 42 patients (4.4%). Patients assigned to unfractionated heparin had a higher risk of thromboembolism (8.0%) compared with those randomized to enoxaparin (3.5%; P=0.011) or antithrombin (1.9%; P<0.001). The proportion of patients who refused antithrombotic treatment as allocated was 3% in the unfractionated heparin or antithrombin arms, and 33% in the enoxaparin arm. Major hemorrhage occurred in eight patients (no differences between the groups). The 5-year event-free survival was 80.9±2.2% among patients assigned to antithrombin compared to 85.9±2.0% in the unfractionated heparin group (P=0.06), and 86.2±2.0% in the enoxaparin group (P=0.10). In conclusion, prophylactic use of antithrombin or enoxaparin significantly reduced thromboembolism. Despite the considerable number of patients rejecting the assigned treatment with subcutaneous injections, the result remains unambiguous. Thromboprophylaxis - for the present time primarily with enoxaparin - can be recommended for children and adolescents with acute lymphoblastic leukemia during induction therapy. Whether and how antithrombin may affect leukemia outcome remains to be determined.

NOACs in Anesthesiology.

BACKGROUND: Due to increasing use of new oral anticoagulants (NOACs), clinicians are faced more and more frequently with clinical issues related to these drugs. OBJECTIVE: The objective of this publication is to make practical suggestions for the perioperative management of NOACs as well as for their handling in overdoses and bleedings. RECOMMENDATIONS: In elective surgery and creatinine clearance ≥ 50 ml/min, a NOAC should be discontinued 24-36 h before the intervention, and even earlier in case of reduced kidney function. In emergency interventions that cannot be delayed, the management is dependent on the NOAC plasma levels. With levels ≤ 30 ng/ml, surgery can be performed. With levels >30 ng/ml, reversal agents should be considered. In low bleeding risk surgery, NOACs can be re-started 24 h after the intervention, which is prolonged to 48-72 h after surgery with high bleeding risk. In case of NOAC overdose and minor bleedings, temporary discontinuation and supportive care are usually sufficient to control the situation. In severe or life-threatening bleedings, nonspecific and specific reversal agents should be considered.

Independent association of resting energy expenditure with blood pressure: confirmation in populations of the African diaspora.

BACKGROUND: Obesity is a major risk factor for hypertension, however, the physiologic mechanisms linking increased adiposity to elevations in blood pressure are not well described. An increase in resting energy expenditure (REE) is an obligatory consequence of obesity. Previous survey research has demonstrated that REE is an independent predictor of blood pressure, and eliminates the co-linear association of body mass index. This observation has received little attention and there have been no attempts to provide a causal explanation. METHODS: At baseline in an international comparative study on obesity, 289 participants aged 25-44 were recruited from communities in the US, the Seychelles, Ghana and South Africa and had REE measured with indirect calorimetry. All participants were thought to be free of major illness. RESULTS: In multivariate regression models, both systolic and diastolic blood pressure were positively associated with REE (p < 0.01), while body mass index and fat mass were negatively correlated with systolic blood pressure (p < 0.01, and p < 0.05 respectively), but not diastolic blood pressure. CONCLUSIONS: These data confirm previous reports and suggest that a common physiologic abnormality links REE and blood pressure. Elevated catecholamines, a putative metabolic characteristic of obesity, is a possible candidate to explain this association. The direct role of excess adipose tissue is open to question.

Neurodegenerative cerebrospinal fluid biomarkers tau and amyloid beta predict functional, quality of life, and neuropsychological outcomes after aneurysmal subarachnoid hemorrhage.

Cerebrospinal fluid (CSF) biomarkers might be useful in predicting outcome after aneurysmal subarachnoid hemorrhage (aSAH). It was the aim to determine whether tau and amyloid beta CSF concentrations predict functional, health-related quality of life (hrQoL), and neuropsychological outcomes after aSAH. Ventricular CSF was obtained from n = 24 aSAH patients at admission (D0), day 2 (D2), and day 6 (D6). CSF total (t)Tau, phosphorylated (p)Tau(181P), and amyloid beta(1-40 and 1-42) (Aß40/Aß42) levels were compared between patients with favorable and unfavorable functional (modified Rankin Scale (mRS)), hrQoL (Euro-Qol (EQ-5D)), and neuropsychological outcomes at 3 (3 m) and 12 months (12 m). Patients with unfavorable functional (mRS 4-6) and hrQoL outcome (EQ-5D z-score ≤ - 1.0) at 3 and 12 m had higher CSF tTau/pTau and lower Aß40/Aß42 at D0, D2, and D6 with varying degrees of statistical significance. In terms of predicting neuropsychological outcome, CSF pTau showed a statistically significant correlation with the z-scores of executive function (r = - 0.7486, p = 0.008), verbal memory (r = - 0.8101, p = 0.002), attention (r = - 0.6498, p = 0.030), and visuospatial functioning (r = - 0.6944, p = 0.017) at 3 m. At 12 m, CSF pTau had statistically significant correlations with the z-scores of verbal memory (r = - 0.7473, p = 0.008) and visuospatial functioning (r = - 0.6678, p = 0.024). In conclusion, higher tTau/pTau and lower Aß40/Aß42 CSF levels predict unfavorable long-term functional and hrQoL outcomes. Neuropsychological deficits correlate with increased CSF tTau and pTau concentrations.

The Potential Close Future of Hemophilia Treatment - Gene Therapy, TFPI Inhibition, Antithrombin Silencing, and Mimicking Factor VIII with an Engineered Antibody.

Summary Hemophilia is one of the best researched monogenic diseases. Hemophilia A will affect approximately 1:5,000 male live births. In recent decades, great progress has been made with the introduction of recombinant proteins in the 1990s for therapy and prophylaxis, securing adequate availability and, with the introduction of the prophylaxis concept, reducing the negative impact of hemophilia on morbidity (especially arthropathy). Despite this progress, there are still challenges to overcome to secure adequate prophylaxis and treatment: for the time being, causal pharmacological hemophilia prophylaxis and therapy requires repeated i.v. application on a regular basis. Although this approach leads to a reduced comorbidity, it does not yet represent an optimized approach with continuous reversal of the hemophilic defect, which would be the ideal solution. This review summarizes the very new treatment strategies for the treatment of hemophilia A and B.

Peripartum Haemorrhage: Haemostatic Aspects of the New German PPH Guideline.

Summary Peripartum haemorrhage remains one of the main causes of maternal mortality world-wide. The German, Austrian and Swiss Societies of Gynaecology and Obstetrics have updated the current guidelines for the treatment of peripartum haemorrhage together with the German Society of Anaesthesiology and Intensive Care Medicine and the Society of Thrombosis and Haemostasis Research. The recommendations have been the result of a thorough review of the available scientific literature and a consensus process involving all members of the guideline group. A key element of the anaesthesiological and haemostatic management is the development of a multidisciplinary standard operating procedure combining surgical as well as medical and haemostatic treatments depending on the severity of bleeding. The guideline underscores the value of clinical and laboratory diagnostics of peripartum haemorrhage as early as possible, even pre-emptively. This allows for an early identification of causes of bleeding and a specific treatment. The guideline comprises evidence-based recommendations for the use of uterotonics, tranexamic acid and blood products such as factor concentrates, fresh frozen plasma, platelet concentrates, packed red blood cells, recombinant activated factor VII and desmopressin. In addition, recommendations for blood conservation strategies involving the use of cell salvage, permissive hypotension and transfusion triggers are given.

Cardiovascular risk status of Afro-origin populations across the spectrum of economic development: findings from the Modeling the Epidemiologic Transition Study.

BACKGROUND: Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. METHODS: In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25-45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. RESULTS: The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. CONCLUSIONS: These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event.

Thrombosis in Inherited Fibrinogen Disorders.

Although inherited fibrinogen disorders (IFD) are primarily considered to be bleeding disorders, they are associated with a higher thrombotic complication risk than defects in other clotting factors. Managing IFD patients with thrombosis is challenging as anticoagulant treatment may exacerbate the underlying bleeding risk which can be life-threatening. Due to the low prevalence of IFD, there is little information on pathophysiology or optimal treatment of thrombosis in these patients. We searched the literature for cases of thrombosis among IFD patients and identified a total of 128 patient reports. In approximately half of the cases, thromboses were spontaneous, while in the others trauma, surgery, and parturition contributed to the risk. The true mechanism(s) of thrombosis in IFD patients remain to be elucidated. A variety of anticoagulant treatments have been used in the treatment or prevention of thrombosis, sometimes with concurrent fibrinogen replacement therapy. There is no definite evidence that fibrinogen supplementation increases the risk of thrombosis, and it may potentially be effective in the treatment and prevention of both thrombosis and hemorrhage in IFD patients.

Factor XIII Deficiency and Thrombocytopenia Are Frequent Modulators of Postoperative Clot Firmness in a Surgical Intensive Care Unit.

OBJECTIVE: Fibrinogen and factor XIII (FXIII) have been shown to critically influence clot firmness in the intraoperative setting and thus likely influence intraoperative bleeding. We were interested to identify potential modulators of postoperative clot firmness in a tertiary care hospital surgical intensive care unit setting, independent of their clinical course during surgery. METHODS: 272 day-shift consecutive patients were evaluated for whole blood clot firmness evaluated by the ROTEM® EXTEM thrombelastometric assay and various potential modulators of clot firmness upon arrival at the surgical intensive care unit (SICU). RESULTS: Maximum clot firmness on the SICU was found to be independently influenced by the amount of colloids given during surgery as well as by platelet count, fibrinogen concentration, and FXIII activity at the time of SICU admission. In patients with lowest clot firmness, FXIII activity was the most important independent modulator of clot firmness; in patients with the highest clot firmness, platelet count and fibrinogen concentration were the most important modulators of clot firmness. Deficiencies (i.e., results below normal range) of these modulators of clot firmness were most prevalent for FXIII (activity < 70%: 45% of cases), which was significantly more frequent than thrombocytopenia (<150 × 109/l: 32%) or fibrinogen deficiency (<1.5 g/l: 6%). CONCLUSIONS: Postoperative clot firmness as evaluated by whole blood thrombelastometry (ROTEM EXTEM assay) is independently and frequently modulated though FXIII activity and the platelet count, while fibrinogen concentration is also an independent but much less frequent modulator. Different modulators show different influences, depending on the clot firmness being present. Colloids infused during surgery also independently modulate postoperative clot firmness. Based on our data, strategies can be developed to improving postoperative care of patients with bleedings or at risk for bleeding.

In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a New Ecarin-Based Thromboelastometry Test.

BACKGROUND: An increasing number of oral anticoagulants has been approved, including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the diluted thrombin time measured with Hemoclot® has shown reliable results. So far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM assay uses ecarin to initiate the coagulation cascade at the step of thrombin generation and measures the clotting time (CT) by thromboelastometry. METHODS: This study investigated the correlation of the EcaTEM with standard laboratory assays in dabigatran-treated patients. Ten patients undergoing total hip or knee arthroplasty were included in the study. DE for thromboprophylaxis was started 4 h after surgery. Blood samples were taken before surgery as well as 2, 6 and 12 h after ingestion on the 3rd postoperative day. Dabigatran concentration (Hemoclot), activated partial thromboplastin time, thrombin time and CT EcaTEM were measured. RESULTS: Only CT EcaTEM and Hemoclot showed a correlation > 0.75 for all measurements. CONCLUSION: CT EcaTEM appears a valid PoC method parameter to detect thrombin inhibition and thus the presence of dabigatran beside diluted thrombin time at different concentration levels. This may represent an opportunity to identify the presence of dabigatran, e.g., in emergency situations.

Clinical Outcomes of Venous Thromboembolism in Patients with and without Cancer: The SWIss Venous ThromboEmbolism Registry (SWIVTER).

Background The association between cancer and venous thromboembolism (VTE) in producing adverse clinical outcomes requires further investigation. Methods In the Swiss Venous ThromboEmbolism Registry (SWIVTER), we compared adverse clinical outcomes between 493 patients with cancer-associated VTE and 1,569 VTE patients without cancer, and identified independent predictors of 90-day mortality. Results Among cancer patients, 351 (71%) had active disease at the time of VTE diagnosis and 232 (47%) had metastatic disease. Cancer patients more frequently had asymptomatic VTE (13 vs. 4%; p < 0.001), iliofemoral deep vein thrombosis (42 vs. 32%; p = 0.017), and upper extremity deep vein thrombosis (16 vs. 7%; p < 0.001). Cancer was associated with an increased risk of cumulative 90-day mortality (13.0 vs. 2.2%; hazard ratio [HR], 6.27; 95% confidence interval [CI], 4.13-9.50; p < 0.001), recurrent VTE (4.7 vs. 2.3%; HR, 2.05; 95% CI, 1.21-3.45; p = 0.007), and bleeding requiring medical attention (5.7 vs. 3.3%; HR, 1.80; 95% CI, 1.13-2.86; p = 0.013). Among cancer patients, the strongest factor associated with mortality was metastatic disease (HR, 4.86; 95% CI, 2.68-8.81; p < 0.001), whereas it was pulmonary embolism among noncancer patients (HR, 4.96; 95% CI, 1.50-16.45; p = 0.009). Symptomatic as compared with asymptomatic VTE predicted neither mortality (12.6 vs. 15.9%; HR, 0.76; 95% CI, 0.39-1.49; p = 0.42) nor recurrent VTE (4.7 vs. 4.8%; HR, 0.98; 95% CI, 0.29-3.31; p = 0.98) in cancer patients. Conclusion In SWIVTER, early mortality of cancer-associated VTE was mainly driven by the extent of cancer disease and not by VTE symptoms or severity.

The social patterning of risk factors for noncommunicable diseases in five countries: evidence from the modeling the epidemiologic transition study (METS).

BACKGROUND: Associations between socioeconomic status (SES) and risk factors for noncommunicable diseases (NCD-RFs) may differ in populations at different stages of the epidemiological transition. We assessed the social patterning of NCD-RFs in a study including populations with different levels of socioeconomic development. METHODS: Data on SES, smoking, physical activity, body mass index, blood pressure, cholesterol and glucose were available from the Modeling the Epidemiologic Transition Study (METS), with about 500 participants aged 25-45 in each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States). RESULTS: The prevalence of NCD-RFs differed between these populations from five countries (e.g., lower prevalence of smoking, obesity and hypertension in rural Ghana) and by sex (e.g., higher prevalence of smoking and physical activity in men and of obesity in women in most populations). Smoking and physical activity were associated with low SES in most populations. The associations of SES with obesity, hypertension, cholesterol and elevated blood glucose differed by population, sex, and SES indicator. For example, the prevalence of elevated blood glucose tended to be associated with low education, but not with wealth, in Seychelles and USA. The association of SES with obesity and cholesterol was direct in some populations but inverse in others. CONCLUSIONS: In conclusion, the distribution of NCD-RFs was socially patterned in these populations at different stages of the epidemiological transition, but associations between SES and NCD-RFs differed substantially according to risk factor, population, sex, and SES indicator. These findings emphasize the need to assess and integrate the social patterning of NCD-RFs in NCD prevention and control programs in LMICs.

Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data.

BACKGROUND: Plasma-derived factor XIII (FXIII) concentrate is an effective treatment for FXIII deficiency. We describe adverse drug reactions (ADRs) reported during pharmacovigilance monitoring of Fibrogammin®/Corifact® and review published safety data. METHODS: Postmarketing safety reports recorded by CSL Behring from June 1993 to September 2013 were analyzed. Clinical studies published during the same period were also reviewed. RESULTS: Commercial data indicated that 1,653,450,333 IU FXIII concentrate were distributed over the review period, equivalent to 1,181,036 doses for a 70 kg patient. 75 cases were reported (one/15,700 standard doses or 22,046,000 IU). Reports of special interest included 12 cases of possible hypersensitivity reactions (one/98,400 doses or 137,787,500 IU), 7 with possible thromboembolic events (one/168,700 doses or 236,207,200 IU), 5 of possible inhibitor development (one/236,200 doses or 330,690,100 IU), and 20 of possible pathogen transmission (one/59,100 doses or 82,672,500 IU). 19 pathogen transmission cases involved viral infection; 4 could not be analyzed due to insufficient data, but for all others a causal relationship to the product was assessed as unlikely. A review of published literature revealed a similar safety profile. CONCLUSION: Assessment of ADRs demonstrated that FXIII concentrate carries a low risk of ADRs across various clinical situations, suggesting a favorable safety profile.

[The new German guideline on postpartum haemorrhage (PPH): essential aspects for coagulation and circulatory therapy]. / Die neue deutsche Leitlinie zur peripartalen Hämorrhagie - Wichtige Aspekte für die Gerinnungs- und Kreislauftherapie.

Worldwide, post-partum haemorrhage (PHH) remains one of the leading causes for maternal mortality. The German Society of Gynaecology and Obstetrics, the German Midwifes' Society, the German Society of Thrombosis and Haemostasis and the German Society of Anaesthesiology and Intensive Care updated the former guideline. The resulting recommendations are the results of a structured literature search and a formal consensus process and contain all aspects of PPH including diagnosis, causes, risk factors and therapy. Key aspect of the anaesthesiological and haemostatic therapies is the development of an interdisciplinary standard operating procedure containing medical options related to the bleeding's cause and severity as well as the surgical option. For suspected PPH, this guideline emphasizes clinical and laboratory-based diagnostics, as only those will enable an early identification of the bleeding's causes and the resulting causative therapy. Recommendations cover evidence-based application of uterotonics for atony as well as tranexamic acid, calcium, factor concentrates and blood products. Additionally, recommendations are given on the topics of cell salvage, controlled hypotension and restrictive transfusion triggers.