Cardiovascular Consequences of Sickle Cell Disease.

Background: Sickle cell disease is an inherited blood disorder which can lead to severe complications, particularly in the cardiovascular and respiratory systems, potentially resulting in arrhythmias, pulmonary hypertension (PH), and cardiomegaly. This study aims to investigate the risk of PH and arrhythmias in adult SCD patients. Methods: Retrospective analysis of medical records from King Abdulaziz University Hospital (KAUH) for patients with SCD aged 15 and above between 2009 and 2021. The study included 517 patients, with echocardiograms and electrocardiograms assessed according to the European Society of Cardiology/the European Respiratory Society (ESC/ERS) guidelines for categorizing PH risk (low, moderate, high) and detecting arrhythmias. Data analysis employed the Statistical Package for the Social Sciences (SPSS), utilizing quantitative and qualitative data representation. Multivariate logistic regression identified independent risk factors with odds ratios at a 95% confidence interval (CI). Results: Among participants, 50.3% were male, with a total sample average age of 34.45 ± 9.28 years. Results indicated that 1.4% of patients experienced arrhythmias, 3.7% had a moderate PH risk, and 3.3% were classified as high PH risk. Logistic regression revealed significant independent risk factors for PH and arrhythmia in patients with SCD, with chronic kidney disease (CKD) carrying the highest odds (26.4 times higher odds of PH and 15.36 times higher odds of arrhythmias). Conclusion: Patients with SCD are at risk for developing PH and various arrhythmias but are often underdiagnosed. Key risk factors for PH included CKD, liver cirrhosis, and pre-existing cardiac conditions. Arrhythmias were significantly associated with CKD and pre-existing cardiac conditions. To mitigate these risks, we recommend involving a multidisciplinary healthcare team in the care of adult patients with SCD. Future prospective studies are advised for early detection of PH and arrhythmias in hemoglobinopathy patients, potentially reducing mortality.

Finding Waldo: Sonographic systematic approach to localize the appendix in children.

OBJECTIVES: To describe a systematic scanning approach using anatomical landmarks followed by an assessment of radiology trainees' ability to identify the normal appendix in healthy children. METHODS: Uncontrolled pre and post study assessing radiology residents' sonographic skills in detecting the normal appendix in healthy children. Initial questionnaire for the trainees' demographics, perceptions and experiences in detecting the appendix with ultrasound in children followed by a precourse test on healthy volunteers. Hands-on training was conducted by describing a systematic sonographic approach to identify the appendix using anatomical landmarks, and then a postcourse test was carried out. The primary outcome was unprompted ability to identify the appendix. Subjective self-scoring of confidence was also recorded. RESULTS: A three-hour hands-on workshop was conducted. Sixteen radiology trainees participated and were randomly distributed to four stations, each with different ultrasound machines and healthy volunteers. Fifteen had a precourse assessment, and 12 completed the postcourse assessment. Before the course, 3/15 (20%) identified the appendix, while 10/12 (83%) identified the appendix afterward. After the course, participants perceived finding the appendix easier than before. There was no statistically significant difference in the participants' perceived confidence in detecting the appendix. CONCLUSIONS: With the described scanning technique, most of the participants were able to identify the normal appendix after receiving short hands-on training. This highlights the importance of targeted training of radiology trainees and nonradiologists.

Predisposing Factors and Incidence of Venous Thromboembolism among Hospitalized Patients with Sickle Cell Disease.

Though patients with sickle cell disease (SCD) are at risk of developing venous thromboembolism (VTE), clear estimates of its incidence and predisposing factors in hospitalized SCD patients are not available. Therefore, this issue was addressed to facilitate an early diagnosis and initiate appropriate prophylactic and treatment strategies. A retrospective observational study was conducted on patients with SCD who were admitted to an academic center in Saudi Arabia over a 10-year period. We identified 1054 admissions of 394 patients with SCD. Of the 3% of patients identified with VTE, 50% experienced pulmonary embolism (PE), 34.3% exhibited deep vein thrombosis (DVT), 6.3% exhibited cerebral vein thrombosis, and 9.4% showed other forms of VTE. In pregnant SCD patients, 6.4% developed a VTE event during their hospital admission. Of the risk factors, high white blood cell count, length of stay, and presence of any additional risk factor for VTE was associated significantly with higher risk of VTE. In our study, this risk seems to be much lower, which is likely attributed to the use of VTE prophylactic strategies implemented in our center. Nevertheless, further studies are needed to establish the ideal prophylactic strategy in patients with SCD.

Is a Higher Body Mass Index a Risk Factor for Developing Antiphospholipid Antibody Syndrome?

BACKGROUND:  Antiphospholipid antibodies (aPLs) are antibodies directed against components of the cell membrane and can be associated with clinical features or be asymptomatic in 1-5% of the population. OBJECTIVE: The objective of this study is to investigate the frequency of aPL positivity based on body mass index (BMI). METHODS:  This is a retrospective analysis of all aPL testing done in a tertiary center between 2010 and 2020. The difference between patients with BMI <25, BMI 25-30, and BMI>30 is calculated using chi-square or Fisher's exact test as appropriate for categorical variables and a two-sample t-test for numerical variables. Unadjusted then multivariable logistic regression models were conducted to evaluate the effect of BMI on aPL positivity adjusting for age, thrombosis history, pregnancy complications history, and presence of autoimmune disease. Sex was included as an effect modifier. RESULTS:  Among 312 patients, the outcome (any positive aPL) was detected in 26 (20.8%), 13 (13.0%), and 16 (18.4%) patients with BMI groups: BMI <25, BMI 25-30, and BMI > 30, respectively. A multivariable logistic regression showed that those with BMI 25-30 had a lower risk of aPL positivity when compared to patients with BMI <25 (OR of 0.55 CI 0.25 - 1.14, p=0.116), and patients with BMI >30 also carried a lower risk compared with patients with BMI<25 (OR of 0.76, 95% CI 0.36 - 1.56, p=0.46); these results were not statistically significant. INTERPRETATION:  The results suggest that a higher BMI was not a risk factor for aPL positivity. A better understanding of the complex interactions between antiphospholipid antibodies and obesity should be further investigated.

Acquired Hemophilia A Masquerading as Bleeding on Anticoagulation: A Case Report Including Key Laboratory Considerations.

We report a case of a patient with recurrent hematomas while on anticoagulation for a pulmonary embolism and a prolonged hospital stay due to a delayed diagnosis for acquired hemophilia A. Acquired hemophilia A is a rare autoimmune bleeding disorder with autoantibodies directed against coagulation factor VIII (FVIII), leading to an acquired FVIII deficiency. A prolonged isolated activated partial thromboplastin time (aPTT) in a bleeding patient warrants workup for acquired hemophilia A. This is specifically challenging in patients with thrombosis on anticoagulation and can lead to significant delays in diagnosis and associated morbidities. The case highlights the need for further awareness of this disease, potential laboratory pitfalls when conducting and interpreting coagulation assays, and the management considerations in a patient with a simultaneous thrombotic and hemorrhagic condition.

Antiphospholipid Antibody Testing: An Audit on Testing Practices in a Public Tertiary Care Center.

BACKGROUND: Antiphospholipid antibodies (aPLs) are antibodies directed against cell membrane components and can be associated with clinical features or be asymptomatic. Testing and interpreting these antibodies is associated with many challenges and pitfalls in clinical practice. OBJECTIVE: To review all antiphospholipid antibody testing and describe the testing practices, indications for testing and interpretation of results to infer local challenges with aPL testing and subsequently address ways to overcome those challenges. METHODS: This is a retrospective analysis of all aPL testing done in a tertiary center between 2014 and 2018. Characteristics of study patients collected through chart review were described using the mean and standard deviation for continuous variables and proportion for categorical variables. Group differences were compared between patients with any aPL-positive result and those with no positive result using chi-square or Fisher's exact test as appropriate for categorical variables and a simple regression model for numerical variables. RESULTS: Among 414 patients undergoing aPL testing, mainly adult females, 62 (14.9%) patients had at least one positive antibody, of those, 26 (42%) had repeat testing done. Testing was mostly done for obstetric indication (107, 25.8%), with 36 patients having one or two early pregnancy losses <10 weeks as their testing indication. A total of 27 (6.5%) patients were labeled with APS/possible APS based on chart review, but on review of the testing of those patients according to classification criteria, only nine patients satisfied the criteria for APS. CONCLUSION: This study highlights the clinical challenges associated with aPL testing, including the controversies around indication for testing, the low rates of repeat testing to confirm persistence, and the common misinterpretation of results. Having an aPL testing profile, explicit reference ranges, results commentary, and close interaction between ordering physicians and laboratory staff might be starting points to overcome these challenges.

Venous and Arterial Thrombosis in Ambulatory and Discharged COVID-19 Patients: A Systematic Review and Meta-analysis.

Introduction Venous and arterial thromboses are frequently observed complications in patients with severe novel coronavirus disease 2019 (COVID-19) infection who require hospital admission. In this study, we evaluate the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge patients with COVID-19 infection. Materials and Method EMBASE and MEDLINE were searched up to July 21, 2021, in addition to other sources. We included studies that assessed the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge COVID-19 patients. Results A total of 16 studies (102,779 patients) were identified. The overall proportion of venous thromboembolic events in all patients, that is, ambulatory and postdischarge, was 0.80% (95% confidence interval [CI]: 0.44-1.28), 0.28% (95% CI: 0.07-0.64), and 1.16% (95% CI: 0.69-1.74), respectively. Arterial events occurred in 0.75% (95% CI: 0.27-1.47) of all patients, 1.45% (95% CI: 1.10-1.86) of postdischarge patients, and 0.23% (95% CI: 0.019-0.66) of ambulatory patients. The pooled incidence rate estimates per 1,000 patient-days for VTE events were 0.06 (95% CI: 0.03-0.08) and 0.12 (95% CI: 0.07-0.19) for outpatients and postdischarge, respectively, whereas for arterial events were 0.10 (95% CI: 0-0.30) and 0.26 (95% CI: 0.16-0.37). Conclusion This study found a low risk of venous and arterial thrombi in ambulatory and postdischarge COVID-19 patients, with a higher risk in postdischarge patients compared with ambulatory patients. This suggests that regular universal thromboprophylaxis in these patient populations is probably not necessary.

Reflex factor coagulation testing in patients with an unexplained prolonged aPTT: An institutional retrospective review.

BACKGROUND: We aim to determine the clinical utility of reflex coagulation investigations (RCI) for prolonged lupus insensitive activated partial thromboplastin time (aPTT) at our institution. METHODS: We retrospectively reviewed all potential RCI (lupus insensitive aPTT of ≥32s) from April 2014 to June 2019. Our diagnostic algorithm requires completion of RCI only if samples had no interfering medications to explain a prolonged aPTT and were either from a preoperative sample or from a patient presenting with unexplained bleeding. Appropriate RCI samples undergo further investigations with one-stage factor activity testing for factors 8(FVIII), 9(FIX), and 11(FXI) reflexively. Data were obtained through electronic medical records to capture clinical characteristics, laboratory findings, prophylactic hemostatic replacement, and bleeding outcomes. RESULTS: Three thousand and three hundreds seventeen samples from 2940 distinct patients were considered as potential RCI during the study period. 263/3317 (8%) samples had RCI completed. Of those, 55/263 (21%) had abnormal factor testing, with the majority from preoperative setting (43/55; 78%). 5/43 (12%) patients were referred to hematology for preoperative evaluation. 5/43 patients received preoperative hemostatic support. A total of 5 patients (5/43) developed postop bleeding. Six patients (6/55) had RCI for unexplained bleeding, and five patients (83%) had a newly identified clinically significant bleeding disorder. CONCLUSION: Reflex coagulation investigations benefited patients presenting with unexplained bleeding as this expedited the diagnosis and management of clinically significant bleeding disorders. RCI for preoperative evaluation infrequently led to additional hemostatic support/referral to hematology. The lack of additional workup for an abnormal factor activity level suggests laboratory alert fatigue as a potential contributory factor.

Venous Thromboembolism in Hospitalized Critical and Noncritical COVID-19 Patients: A Systematic Review and Meta-analysis.

Introduction Venous thromboembolism (VTE) has been observed as a frequent complication in patients with severe novel coronavirus disease 2019 (COVID-19) infection requiring hospital admission. Aim This study was aimed to evaluate the epidemiology of VTE in hospitalized intensive care unit (ICU) and non-ICU patients. Materials and Methods PubMed was searched up to November 13, 2020, and updated in December 12, 2020. We included studies that evaluated the epidemiology of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19. Results A total of 91 studies reporting on 35,017 patients with COVID-19 was included. The overall frequency of VTE in all patients, ICU and non-ICU, was 12.8% (95% confidence interval [CI]: 11.103-14.605), 24.1% (95% CI: 20.070-28.280), and 7.7% (95% CI: 5.956-9.700), respectively. PE occurred in 8.5% (95% CI: 6.911-10.208), and proximal DVT occurred in 8.2% (95% CI: 6.675-9.874) of all hospitalized patients. The relative risk for VTE associated with ICU admission was 2.99 (95% CI: 2.301-3.887, p <0.001). DVT and PE estimated in studies that adopted some form of systematic screening were higher compared with studies with symptom-triggered screening. Analysis restricted to studies in the 5th quintile of sample size reported significantly lower VTE estimates. Conclusion This study confirmed a high risk of VTE in hospitalized COVID-19 patients, especially those admitted to the ICU. Nevertheless, sensitivity analysis suggests that previously reported frequencies of VTE in COVID-19 might have been overestimated.

A case of congenital prothrombin deficiency with two concurrent mutations in the prothrombin gene.

Congenital prothrombin deficiency is an extremely rare, autosomal recessive bleeding disorder with a prevalence of 1 in 2 million individuals. Here, we report a case of congenital prothrombin deficiency with two concurrent mutations in the prothrombin gene (F2), affecting the heavy B chain. The patient presented with a history of multiple bleeding events in his youth that are mostly trauma associated, with a family history of prothrombin deficiency. Laboratory analysis showed a prolonged activated partial thromboplastin time and a prothrombin activity level of 5%. Genetic analysis of the F2 gene identified two heterozygous variants; one is a previously reported pathogenic deletion (c.1814_1815del; p.His605Argfs*13), and the other is a novel missense variant (c.1147C>T; p.Arg383Trp). In silico analysis predicted that p.Arg383Trp is likely to be disease causing, as it affects one of the anion-binding exosites-I of the B chain. This case highlights the significance of molecular findings in confirming the diagnosis of patients with congenital prothrombin deficiency.