von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis

Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:A

A rare presentation of Austrian syndrome with septic arthritis in an immunocompetent female

BACKGROUND: Austrian syndrome, which is also known as Osler\u27s triad, is a rare aggressive pathology consisting of pneumonia, endocarditis, and meningitis caused by Streptococcus pneumoniae and carries drastic complications. CASE PRESENTATION: A case of a 68-year-old female with a past medical history of hypertension and had a recent viral influenza is presented. She developed bacterial pneumonia, endocarditis with mitral and aortic vegetations and perforation, meningitis, and right sternoclavicular septic arthritis. Two prior case reports have described sternoclavicular septic arthritis as part of Austrian syndrome. Our case is the third case; however, it is the first case to have this tetrad in an immunocompetent patient with no risk factors, i.e., males, chronic alcoholism, immunosuppression, and splenectomy. CONCLUSIONS: Clinicians should maintain a high index of suspicion for the possibility of sternoclavicular joint septic arthritis as a complication of Austrian syndrome in immunocompetent patients

Coronary Fistula between Left Anterior Descending Artery (LAD) and Pulmonary Artery (PA) Leading to Sudden Cardiac Death: Case Report with Literature Review

Coronary artery fistulas (CAF) are inappropriate connections between a coronary artery and a major vessel or a cardiac chamber. These fistulas may or may not present with symptoms, but they need to be detected as early as possible in order to decide on the most appropriate treatment methodology (i.e. surgery versus conservative management). We report the case of a 67-year-old female with no modifiable cardiovascular risk factors who had an unwitnessed sudden death at home during her ongoing evaluation of a fistula detected incidentally between the left anterior descending artery (LAD) and the pulmonary artery (PA). This case highlights that early diagnosis and treatment of symptomatic CAF is crucial to minimize the risk of sudden cardiac death. Although symptomatic fistula of LAD to PA has been reported in the literature multiple times, it has been rarely reported that this fistula can result in sudden cardiac death

Cardiogenic shock in autoimmune rheumatologic diseases: an insight on etiologies, management, and treatment outcomes

Autoimmune rheumatological disorders are known to have an increased risk for cardiovascular diseases including coronary artery disease (CAD), myocarditis, pericarditis, valvulopathy, and in consequence cardiogenic shock. Data on cardiogenic shock in rheumatological diseases are scarce; however, several reports have highlighted this specific entity. We sought to review the available literature and highlight major outcomes and the management approaches in each disease. Systematic literature search, including PubMed, Ovid/Medline, Cochrane Library, and Web of Science, was conducted between January 2000 and December 2009. We reviewed all cases reporting cardiogenic shock with rheumatologic conditions, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Takayasu\u27s arteritis (TA), granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), and antiphospholipid syndrome (APS). We selected 45 papers reporting a total of 48 cases. Mean age was 39 ± 7.3 years and 68.8% were females. Most common rheumatologic conditions associated with cardiogenic shock were SLE (31%), GPA (23%), TA (14.6%), APA (10.4%), and RA (8.3%). Cardiogenic shock was found to be caused by eosinophilic myocarditis in 58% of cases, CAD in 19% of cases, and valvulopathy in 6% of cases. Most patient required high-dose steroids and second immunosuppressant therapy. Mechanical circulatory supported was required in 23 cases, IABP in 16 cases, and ECMO in 12 cases. Complete recovery occurred in 37 patients while 9 patients died and 2 required heart transplant. Responsible for two-thirds of cases, eosinophilic myocarditis should be suspected in young cardiogenic shock patients with underlying rheumatologic conditions. Lupus and GPA are the two most common conditions

Spontaneous Biliary Pericardial Tamponade: A Case Report and Literature Review

BACKGROUND: Biliary pericardial tamponade (BPT) is a rare form of pericardial tamponade, characterized by yellowish-greenish pericardial fluid upon pericardiocentesis. Historically, BPT reported to occur in the setting of an associated pericardio-biliary fistula. However, BPT in the absence of a detectable fistula is extremely rare. CASE PRESENTATION: A 75-year-old Hispanic male presenting with dyspnea and diagnosed with cardiac tamponade. Subsequent pericardiocentesis revealed biliary pericardial fluid (bilirubin of 7.6 mg/dl). Patient underwent extensive workup to identify a potential fistula between hepatobiliary system and the pericardial space, which was non-revealing. The mechanism of bile entry into the pericardial space remains to be unidentified. LITERATURE REVIEW: A total of six previously published BPT were identified: all were males, mean age of 53.3 years (range: 31-73). Mortality was reported in two out of the six cases. The underlying etiology for pericardial tamponade varied across the cases: incidental pericardio-biliary fistula, traumatic pericardial injury, and presence of associated malignancy. - Conclusion: Biliary pericardial tamponade is a rare form of tamponade that warrants a prompt workup (e.g., Hepatobiliary Iminodiacetic Acid - HIDA scan) for an iatrogenic vs. traumatic pericardio-biliary fistula. As a first case in the literature, our case exhibits a biliary tamponade in the absence of an identifiable fistula

Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at .0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of .0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures

Bleeding assessment tools in the diagnosis of von Willebrand disease: systematic review & meta-analysis of test accuracy.

Background Von Willebrand Disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. Objective We systematically reviewed diagnostic test accuracy results of bleeding assessment tools (BATs) to screen patients for VWD. Methods We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. Results The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval [CI] 66%-83%) and 54% (29%-77%), respectively. Certainty of evidence varied from moderate to high. Conclusion This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates will influence patient management</p

Laboratory assays of VWF activity and use of desmopressin trials in the diagnosis of VWD: a systematic review and meta-analysis.

Von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of any VWF activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR , VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appears to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with VWD suspected of type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD

Von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis.

Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:Ag <0.30 IU/mL, VWF sequence variants were detected in 75-82% of patients in 2 studies, and for VWF:Ag between 0.30-0.50 IU/mL, VWF sequence variants were detected in 44-60% of patients in 3 studies. A sensitivity of 0.90 (95% CI: 0.83 to 0.94), and a specificity of 0.91 (95% CI: 0.76 to 0.97) were observed for a platelet-dependent VWF activity /VWF:Ag ratio of <0.7 in detecting type 2 VWD (moderate certainty in the test accuracy results). VWF antigen and platelet-dependent activity are continuous variables with an increase in bleeding risk with decreasing levels. This systematic review shows that using a VWF activity/VWF:Ag ratio of <0.7 versus lower cutoff levels in patients with an abnormal initial VWD screen is more accurate for the diagnosis of type 2 VWD