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.

Association of Genetic Variant FVIII Gene and Factor VIII: A Pilot Study Among Hemophilia A Female Relatives in Saudi Arabia.

Hemophilia A (HA) is an X-linked recessive disorder that results from mutations in the factor VIII gene (FVIII). Most affected patients are males due to the inheritance of mutations in the FVIII gene from their mothers. Females are mostly found to be carriers unless they inherited the mutation from both parents. Obligate carriers of HA are mothers whose sons are affected with HA, or daughters who inherit the mutation from their affected fathers. A possible carrier of HA could be any female who has one or more affected relatives with HA in her family. Hemophilia A carriers (HACs) could present with similar symptoms to affected patients, including low factor VIII level, and risk of bleeding especially after surgical procedures or postpartum hemorrhage. OBJECTIVES:  Assessing the phenotype of possible HAC and its association with genetic variants in the FVIII gene for better screening methods for HAC. METHODS: From the period between 25 June and 25 October 2021, the study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. We recruited seven mothers whose sons were affected with HA, and 18 possible HAC who are relatives to sever affected patients with HA. All 25 candidates were assessed for the FVIII level, activated partial thromboplastin time (APTT), and bleeding risk and sequenced a part of Exon14 in their FVIII gene. RESULTS: Twenty-five percent of the participants show a low level of FVIII, however, none of them have prolonged bleeding nor suffer from bleeding tendency. We also identified two missense variants in six of the candidates, but the clinical significance of these variants has not been determined previously. CONCLUSION: This pilot study is the first to explore the phenotype of several HAC in Saudi Arabia. A larger scale study with more HA patients and their female relatives is needed to understand the correlation between phenotype and genotype for better screening for HAC.

Incidence and Risk Factors of Infections Among Diffuse Large B-cell Lymphoma and Classical Hodgkin's Lymphoma Patients in a Tertiary Care Center in Saudi Arabia: A Retrospective Cohort Study.

INTRODUCTION:  Non-Hodgkin's lymphoma (NHL) ranked fourth among all cancer types in Saudi Arabia, as reported by the Saudi Health Council in 2015. Diffuse large B-cell lymphoma (DLBCL) is the most common histological type of NHL. On the other hand, classical Hodgkin's lymphoma (cHL) ranked sixth and had a modest tendency to affect young men more frequently. Over recent decades, DLBCL patients were treated with cyclophosphamide, doxorubicin hydrochloride, oncovin, and prednisolone (CHOP) alone. Adding rituximab (R) to the standard regimen (CHOP) shows significant improvement in overall survival. However, it also has a considerable effect on the immune system, impacting complement-mediated and antibody-dependent cellular cytotoxicity and causing an immunosuppressive state through modulating T-cell immunity via neutropenia, which can let the infection spread. AIMS AND OBJECTIVES:  This study aims to evaluate the incidence and risk factors associated with infections in DLBCL patients in comparison to patients with cHL treated with doxorubicin hydrochloride (Adriamycin), bleomycin sulfate, vinblastine sulfate, and dacarbazine (ABVD). MATERIALS AND METHODS:  This study is a retrospective case-control study that included 201 patients acquired between January 1st, 2010, and January 1st, 2020. Sixty-seven patients had a diagnosis of cHL and had received ABVD, and 134 had DLBCL and had received rituximab. Clinical data were obtained from the medical records. RESULTS:  During the study period, we enrolled 201 patients, of whom 67 had cHL, and 134 had DLBCL. DLBCL patients had a higher serum lactate dehydrogenase upon diagnosis than cHL (p = 0.005). Both groups have similar response rates with complete remission/partial remission. Compared to cHL, patients with DLBCL were more likely to have advanced disease when they first presented (stage III/IV, DLBCL: 67.3 vs. cHL: 56.5; p = 0.005). DLBCL patients had an increased risk of infection as compared to cHL patients (DLBCL: 32.1 % vs. 16.4%; p = 0.02). However, patients with a poor response to treatment had an increased risk of infection compared to patients with a favorable response regardless of the type of disease (odds ratio: 4.6; p = <0.001). When using multivariate analysis, it is revealed that unfavorable therapeutic response continues to be the only predictor raising the probability of infection in the population (odds ratio: 4.2; p = 0.003). CONCLUSIONS:  Our study explored all potential risk factors for the occurrence of infection in DLBCL patients who received R-CHOP versus cHL. The most reliable predictor of an increased risk of infection during the follow-up period was having an unfavorable response to medication. To assess these results, additional prospective research is required.

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.

Primary Central Nervous System Burkitt Lymphoma, Presenting with Long-Term Fluctuating Level of Consciousness: A Case Report and Literature Review on Challenges in Diagnosis and Management.

BACKGROUND Burkitt lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) rarely affecting the central nervous system (CNS) as a primary disease. Over the past years, only a few cases of primary CNS Burkitt lymphoma were reported. There is a challenge in early recognition and diagnosis of this type of brain lymphoma. Furthermore, there is no specific treatment protocols for primary CNS Burkitt lymphoma, which adds to the difficulty in managing those patients. We introduce a case of a 65-year-old who presented with fluctuating memory disturbance diagnosed as cerebral Burkitt lymphoma. CASE REPORT A 65-year-old man developed a gradual decrease in his level of consciousness over a span of 4 days, associated with fluctuating memory disturbances. A CT scan showed a hyperdense mass in the region of the trigon of the left lateral ventricle and marked obstructive hydrocephalus involving the temporal, occipital horns, and the left lateral ventricle, with no evidence of other suspicious lesions. A brain biopsy of the lesion revealed features of encephalitis initially, but the patient presented later with worsening symptoms, and a repeated brain biopsy showed features of Burkett lymphoma, with normal pan-CT scan. CONCLUSIONS Primary CNS Burkitt lymphoma (PCNSBL) is a rare disease with no clear evidence in the literature of how to deal with it. Reporting such cases provides a better understanding of how to approach such unusual presentations. Treatment of PCNSBL is challenging and even with the currently adopted approaches, the disease still has a very poor outcome.

Immunogenicity of The BNT162b2 COVID-19 mRNA and ChAdOx1 nCoV-19 Vaccines in Patients with Hemoglobinopathies.

INTRODUCTION: Studies assessing immune responses following Pfizer-BioNTech BNT162b2 mRNA COVID-19 (Pfizer) and ChAdOx1 nCoV-19 AZD1222 (AstraZeneca) vaccines in patients with hemoglobinopathy are non-existent in the literature despite being thought at high risk of infection. METHODS: Prospectively, we collected serum from patients with hemoglobinopathies at least 14 days post vaccine and measured neutralizing antibodies (nAb) in addition to binding antibodies using in-house assays. RESULTS: All 66 participants mounted a significant binding antibody response (100%), but nAbs were detected in (56/66) post-vaccine with a rate of 84.5%. Age, gender, vaccine type, spleen status, hydroxyurea use, and hyperferritinemia did not affect the rate significantly. While 23/32 (71.8%) patients receiving only one dose of the vaccine were able to mount a positive response, 33/34 (97.05%) of those who had two doses of any vaccine type had a significant nAbs response. Patients who had anti-nucleocapsid (N), signifying asymptomatic infection in the past, were able to produce nAbs (31/31). No nAbs were detected in 10/35 (28.5%) patients with no anti-N antibodies. CONCLUSION: Our results provide supportive data when advising patients with hemoglobinopathy to receive COVID-19 vaccines and ensure booster doses are available for better immunity. Whenever available, measurement of nAb is recommended.

Low clinical utility of testing for anti-platelet factor 4 in asymptomatic individuals after ChAdOx1 nCoV-19 vaccine.

INTRODUCTION: The development of anti-platelet factor 4 (PF4) antibodies is linked to a rare thrombotic complication described now as vaccine-induced immune thrombotic thrombocytopenia (VITT). This clinical syndrome with thrombosis and thrombocytopenia was reported after exposure to the Oxford-AstraZeneca COVID-19 vaccine, ChAdOx1 nCoV-19 vaccine (AZD1222), and Ad26.COV2.S vaccine (Janssen/Johnson & Johnson). In the absence of the clinical features, the incidence of positive anti-PF4 antibodies in asymptomatic individuals post-vaccination is unclear. METHODS: The aim of this study was to evaluate the development of anti-PF4 antibodies in asymptomatic individuals 14-21 days after receiving the first dose of ChAdOx1 nCoV-19 vaccine (AZD1222) and BNT162b2 vaccine. Prospectively, we collected serum from individuals before and after ChAdOx1 nCoV-19 vaccine and BNT162b2 vaccine and measured anti-PF4 antibodies using the Asserachrom HPIA IgG ELISA (Stago, Asnieres, France). RESULTS: We detected positive anti-PF4 antibodies in 5 of 94 asymptomatic individuals post-vaccine with a rate of 5.3% with low titers (OD 0.3-0.7). Four of 5 individuals who tested positive after the vaccine had also positive anti-PF4 antibodies before the vaccine, which indicates that a majority of the positive results are due to preexisting anti-PF4 antibodies. We did not find a relation between the development of anti-PF4 antibodies and the immune response to the vaccine, status of prior COVID-19 infection, and baseline characteristics of participants. None of the participants developed thrombosis nor thrombocytopenia. CONCLUSION: Our results provide new evidence to guide the diagnostic algorithm of suspected cases of VITT. In the absence of thrombosis and thrombocytopenia, there is a low utility of testing for anti-PF4 antibodies.