Clinical and Laboratory Diagnosis of Antiphospholipid Syndrome: A Review.

The antiphospholipid syndrome (APS) manifests through venous or arterial thrombosis, with or without pregnancy complication alongside the continuous presence of antiphospholipid antibodies (aPL). APS classification relies on three aPL subtypes: anticardiolipin (aCL), anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulants (LA) antibodies. Given that thrombosis and pregnancy issues are not unique to APS, the precise and reliable identification of aPL forms the basis for diagnosis. Semi-quantitative solid-phase assays identify two antibodies, aCL and anti-ß2GPI, while LA detection occurs through various phospholipid-dependent coagulation assays that are based on antibody behaviour. LA, specifically, is conclusively associated with thrombosis, prompting discussions around the serological criteria for APS. Despite advancements in LA detection, the standardisation of all aPL detection assays remains imperative. The combined presence of aCL and anti-ß2GPI with thrombosis inconsistently triggers concern. Initial presentations by APS patients commonly exhibit a heightened risk of stroke, miscarriages in the later stages of pregnancy, positive results of LA tests, and widespread thrombosis across multiple organs, often leading to adverse outcomes. Correctly diagnosing this condition is pivotal to avoid unnecessary long-term secondary thromboprophylaxis.

Hematological Profile of Hb Adana Among High School Students in Northeast Peninsular Malaysia.

Background Hb Adana is a non-deletional alpha (α)-thalassaemia variant resulting from mutations in α1- or α2-globin codon 59 (αCD59), leading to the production of unstable α-globin. Clinical manifestations can vary from silent carrier status to dependence on blood transfusions, hepatosplenomegaly, skeletal deformities, and spinal cord compression. Despite the significance of Hb Adana inheritance, studying this variant poses challenges due to the scarcity of molecular tests and the potential for routine diagnoses to be overlooked. This study aims to investigate the prevalence of Hb Adana among local high school students and assess the hematological parameters and hemoglobin analysis of Hb Adana in Malaysia. Methodology This retrospective study analyzed 13,721 blood samples collected from high school students participating in Malaysia's National Thalassaemia Screening Program at Hospital Raja Perempuan Zainab II (HRPZ II). Deletional α-thalassaemia was detected using multiplex gap-polymerase chain reaction (PCR), while common non-deletional α-thalassaemia was identified using multiplex amplification refractory mutation system (ARMS) PCR. Data were extracted from the HRPZ II database for analysis. Results Among the participants, 2327 individuals were found to have either common deletional (n=1037, 44.6%) or non-deletional (n=1290, 55.4%) α-thalassaemia. Hb Constant Spring was the most prevalent non-deletional α-thalassaemia, accounting for 53.03% of cases. Thirty-one participants (1.33%) exhibited αCD59α/αα, and one (0.04%) had αCD59α/-α3.7. Among the 32 subjects with Hb Adana, 87.5% were Malay, and 12.5% were Orang Asli. Additionally, seven cases of HbE/Hb Adana co-inheritance were identified. Hemoglobin levels in heterozygous Hb Adana individuals ranged from mild anemia to normal, between 95 g/L and 153 g/L. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were approximately 73 fL and 23 pg, respectively. Conclusion This study delineates the distribution of α-thalassaemia mutation patterns among high school students in Kelantan, Northeast Peninsular Malaysia. Our findings indicate that Hb Adana is rare in our region and co-inheritance with an α-gene deletion results in α+-thalassaemia and with HbE, α0-thalassaemia. All heterozygous Hb Adana individuals exhibited low MCVs and MCHs.

Haemostatic, Inflammatory, and Haematological Biomarkers Among Orthopaedic Patients With Prolonged Immobilization and the Risk of Hypercoagulable States.

Background Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with lower limb traumatic fractures. Orthopaedic patients who experience trauma in the lower limbs with prolonged immobilization may experience a hypercoagulable state, which could eventually lead to the development of VTE. Therefore, this study aims to evaluate the changes in hypercoagulable markers, including haemostatic, inflammatory, and haematological biomarkers in orthopaedic trauma patients with prolonged immobilization. Materials/method This prospective cohort study was conducted at Hospital Universiti Sains Malaysia from August 2020 to March 2022. Every patient with fractures in the lower limbs was screened for eligibility, and patients who required immobilization for more than five days without receiving anticoagulant prophylaxis were recruited for this study. The laboratory tests, including D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), erythrocyte sedimentation rate (ESR), and platelet count, were serially measured on day one and day five of hospitalization. The biomarkers were analyzed using a paired t-test, with a p-value <0.05 as a significant result. Results A total of 54 patients with fractures in the lower limbs, ages ranging from 12 to 50 years old, were involved in this study. The paired t-test analysis demonstrated that several biomarkers showed a significant increase in mean difference between day one and day five of immobilization, which included fibrinogen, ESR, and platelet count. The mean differences for each biomarker with fibrinogen were 0.66 g/L (p<0.001, 95% CI of mean difference: -1.04, -0.27), ESR increased by 17.98mm/hr (p<0.001, 95% CI of mean difference: -24.69, -11.27), and platelet count increased by 128.59×109/L (p<0.001, 95% CI of mean difference: -166.55, -90.64) on day five of immobilization. D-dimer was elevated in all patients on both post-trauma days; however, no significant difference was observed in this biomarker between day one and day five of immobilization. Conclusion In conclusion, our study found that fibrinogen, ESR, and platelet count levels were significantly increased in orthopaedic trauma patients with prolonged immobilization. The increase in these biomarkers indicates the body's reaction to tissue injury after trauma, which may contribute to the hypercoagulable states. Further research with a larger sample size is warranted to assess the viability of these biomarkers as potential diagnostic indicators for the development of VTE related to hypercoagulability.

Coagulation Status Using Clot Wave Analysis in Patients With Prolonged Immobilization.

Background Prolonged immobilization is widely recognized as a risk factor for thromboembolism. In this prospective study, we investigated the changes in clot waveform analysis (CWA) parameters in prolonged immobilized patients following lower limb trauma. CWA is an advanced method for assessing global coagulation that involves continuously monitoring changes in light transmittance, absorbance, or light scattering during routine clotting tests. Additionally, we also aim to determine the CWA parameters between day one and after day three of immobilization. Methods A total of 30 patients with prolonged immobilization were enrolled in this study. The plasma of these patients was collected on the first day of their admission and subsequently obtained again after day three of immobilization. Prothrombin time (PT)-based CWA and activated partial thromboplastin time (aPTT)-based CWA were performed using the ACL TOP 300 CTS (Werfen: Bedford, USA) coagulation analyzer, which utilizes the optical method for clot detection. Plasma samples for 20 normal controls were recruited from a healthy blood donor. The CWA parameters generated during clot formation were analyzed. For the comparison of CWA parameters between patients with prolonged immobilization and healthy controls, the Mann-Whitney test was used. A paired t-test was used for the comparison of clot wave parameters between day one and after day three of immobilization. This study was approved by the Universiti Sains Malaysia Research Ethics Committee. Result The mean values of PT and aPTT in healthy controls were 11.66 seconds and 33.98 seconds, respectively. There was no statistically significant difference between the patients and the healthy controls in the median values of aPTT (P=0.935). However, patients with prolonged immobilization exhibited significantly higher median PT CWA parameter values than controls (P=0.007). These parameters included the delta change (P<0.001), peak time velocity (P=0.008), and height velocity (P<0.001). On the other hand, the delta change (P<0.001) and height velocity (P<0.001) of the aPTT CWA parameters were significantly higher in patients with prolonged immobilization than in controls. In patients with prolonged immobilization, there was no significant difference in PT CWA parameters between day one and after day three of immobilization, while for aPTT CWA, all parameters were higher on day three, except for the endpoint time. Conclusion Patients with prolonged immobilization exhibit increased PT and aPTT CWA parameters compared to normal controls. CWA parameters could aid in identifying patients at risk of developing thrombosis through changes in the clot waveform. However, further study is needed to fully utilize additional information from routine coagulation testing.

Exploring Extended White Blood Cell Parameters for the Evaluation of Sepsis among Patients Admitted to Intensive Care Units.

Sepsis is a major cause of mortality and morbidity in intensive care units. This case-control study aimed to investigate the haematology cell population data and extended inflammatory parameters for sepsis management. The study included three groups of patients: sepsis, non-sepsis, and healthy controls. Patients suspected of having sepsis underwent a Sequential Organ Failure Assessment (SOFA) evaluation and had blood drawn for blood cultures, complete peripheral blood counts (CBC), and measurements of various markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). We observed significant changes in numerous CBC parameters and extended inflammation parameters (EIPs), in addition to significant biochemical analysis markers CRP and IL-6 in sepsis cohorts. Multiple logistic regression analyses showed that combining different CBC parameters and EIPs were effective to profile these patients. Two different models have been developed using white blood cell counts and their extended parameters. Our findings indicate that the absolute counts of white blood cells, and the EIPs which reflect their activation states, are important for the prediction and assessment of sepsis, as the body responds to an insult that triggers an immune response. In an emergency situation, having timely updates on patient conditions becomes crucial for guiding the management process. Identifying trends in these specific patient groups will aid early diagnosis, complementing clinical signs and symptoms, especially as CBC is the most commonly ordered test in a diagnostic workup.

Significance of Zone 2 Peak on Capillary Electrophoresis in the Detection of Hemoglobin Constant Spring.

Objectives: Hemoglobin constant spring (Hb CS) is a point mutational defect associated with α thalassemia. The aims of this study were to compare the hematological profiles between different Hb CS genotypes and to estimate the range for Zone 2 peak using capillary electrophoresis (CE) with different Hb CS genotypes. Methods: For this cross-sectional study, patient blood samples that showed a positive peak in zone 2 of CE were selected. Hemoglobin and DNA of the samples were investigated to ascertain the presence and levels of non-deletional and deletional α thalassemia. The results were statistically analyzed. Results: Of the 137 samples investigated, 118 (86.1%) were positive for termination codon Hb CS mutation. Heterozygous Hb CS was found in 92 (67.2%), compound heterozygous Hb CS in 22 (16.1%), and homozygous Hb CS in four (2.9%) samples. The ranges of Hb CS level for heterozygous Hb CS, compound heterozygous Hb CS, and homozygous Hb CS were within 0.2-2.7%, 0.3-2.2%, and 4.5-5.5%, respectively. Significant hematological differences in the Hb level, mean cell volume, mean cell hemoglobin, red cell distribution width, red blood cell count, and Hb CS level were observed between heterozygous, homozygous, and compound heterozygous Hb CS. Conclusions: In view of the overlapping prevalence range of Hb CS level for heterozygous and compound heterozygous Hb CS, only Hb CS level within the range 4.5-5.5% was helpful in the diagnosis of homozygous Hb CS.

Plasma-derived exosomal miRNA as potential biomarker for diagnosis and prognosis of vector-borne diseases: A review.

Early disease diagnosis is critical for better management and treatment outcome of patients. Therefore, diagnostic methods should ideally be accurate, consistent, easy to perform at low cost and preferably non-invasive. In recent years, various biomarkers have been studied for the detection of cardiovascular diseases, cerebrovascular diseases, infectious diseases, diabetes mellitus and malignancies. Exosomal microRNA (miRNA) are small non-coding RNA molecules that influence gene expression after transcription. Previous studies have shown that these types of miRNAs can potentially be used as biomarkers for cancers of the breast and colon, as well as diffuse large B-cell lymphoma. It may also be used to indicate viral and bacterial infections, such as the human immunodeficiency virus (HIV), tuberculosis and hepatitis. However, its use in the diagnosis of vector-borne diseases is rather limited. Therefore, this review aims to introduce several miRNAs derived from exosomal plasma that may potentially serve as a disease biomarker due to the body's immune response, with special focus on the early detection of vector-borne diseases.

Incidence of anemia and red blood cell (RBC) transfusion requirement in breast cancer.

Background: Cancer-related anaemia is one of the main burdens in oncology, although the available data on its prevalence and treatment options such as blood transfusion are often contradictory. This study aimed to evaluate the prevalence of anaemia and the requirement for packed red blood cell (PRBC) transfusion among women with breast cancer (BC) and to determine the associated factors for chemotherapy-induced anaemia (CIA). Methods: This cross-sectional retrospective study conducted in Kelantan involved 104 newly diagnosed female BC patients from 2015 to 2016 who underwent chemotherapy. For statistical analysis, chi-square was used to compare between CIA and non-CIA groups. In addition, simple and multiple logistic regression were used to determine the association of the CIA. Results: Our study revealed that 34.6% (n=36) of patients had mild anaemia, and 59.6% (n=62) had normal haemoglobin at pre-chemotherapy. The prevalence of anaemia increased from 40.4% to 77% at the end of our study. About 30.8% of patients received PRBC transfusion during chemotherapy with mean haemoglobin before the first transfusion of 7.9 g/dl. CIA was observed in 54.8% of cases. There was no significant association between CIA concerning the patient characteristic, cancer characteristic, or cancer treatment. Conclusion: We concluded that a significant proportion (40.4%) of BC patients was anaemic even before chemotherapy, with the red blood cell requirements up to 30.8% throughout chemotherapy. A larger prospective study is needed to determine the predictors for the CIA and subsequently improve patient management.

Acute hemolytic transfusion reaction following ABO-mismatched platelet transfusion: Two case reports.

Acute hemolytic transfusion reaction following ABO-incompatible platelet transfusion: two case reports An ideal platelet transfusion should provide ABO identical platelet concentrate, and cross match compatibility is not routinely performed in the standard practices. However, ABO non identical platelet transfusions are not uncommon with the limited resources and short shelf life of platelet concentrate. Though rare, acute hemolytic transfusion reaction (AHTR) may occur following minor ABO-incompatible platelet transfusion. Here, we report two cases of thrombocytopenic patients (one child and one adult) type as Group B RhD positive and received Group O RhD positive platelet transfusions. Both patients experienced an AHTR evidenced by a drop in hemoglobin level, spherocytosis and small agglutinations on the blood film, and positive direct Coombs test. They were treated symptomatically, recovered and discharged well post-event without any morbidity. No anti-B isohemagglutinins titer were done to confirm the high titer of the antibody in the platelet donors. Our cases highlighted the importance of ABO-compatible platelet transfusion, especially to children and those vigilant groups of patients.

Haemostasis and Inflammatory Parameters as Potential Diagnostic Biomarkers for VTE in Trauma-Immobilized Patients.

Venous thromboembolism (VTE), which encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major public health concern due to its high incidences of morbidity and mortality. Patients who have experienced trauma with prolonged immobilization are at an increased risk of developing VTE. Plasma D-dimer levels have been known to be elevated in trauma patients, and they were closely correlated with the number of fractures. In other words, plasma D-dimer levels cannot be used as the only indicator of VTE in trauma cases. Given the limitations, further study is needed to explore other potential biomarkers for diagnosing VTE. To date, various established and novel VTE biomarkers have been studied in terms of their potential for predicting VTE, diagnostic performance, and improving clinical therapy for VTE. Therefore, this review aims to provide information regarding classic and essential haemostasis (including prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, thrombin generation, protein C, protein S, antithrombin, tissue factor pathway inhibitor, and platelet count) and inflammatory biomarkers (C-reactive protein, erythrocyte sedimentation rate, and soluble P-selectin) as potential diagnostic biomarkers that can predict the risk of VTE development among trauma patients with prolonged immobilization. Thus, further advancement in risk stratification using these biomarkers would allow for a better diagnosis of patients with VTE, especially in areas with limited resources.

Hereditary Protein S Deficiency With an Extensive Femoral Artery Thrombosis.

Protein S (PS) deficiency is widely recognized for its connection to venous thromboembolism risk. However, the relation between PS deficiency and arterial thrombotic events (ATEs) remains uncertain. Here, we report a patient who experienced an ATE with a family history of PS deficiency. We highlight an attention to the issues related to the management of arterial thrombotic events and discuss the potential use of antiplatelet therapy as a treatment option for a specific group of patients diagnosed with PS deficiency.

The Role of Epigenetics in the Development and Progression of Multiple Myeloma.

Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.

Single Nucleotide Polymorphisms in XMN1-HBG2, HBS1L-MYB, and BCL11A and Their Relation to High Fetal Hemoglobin Levels That Alleviate Anemia.

Anemia is a condition in which red blood cells and/or hemoglobin (Hb) concentrations are decreased below the normal range, resulting in a lack of oxygen being transported to tissues and organs. Those afflicted with this condition may feel lethargic and weak, which reduces their quality of life. The condition may be manifested in inherited blood disorders, such as thalassemia and sickle cell disease, whereas acquired disorders include aplastic anemia, chronic disease, drug toxicity, pregnancy, and nutritional deficiency. The augmentation of fetal hemoglobin (HbF) results in the reduction in clinical symptoms in beta-hemoglobinopathies. Several transcription factors as well as medications such as hydroxyurea may help red blood cells produce more HbF. HbF expression increases with the downregulation of three main quantitative trait loci, namely, the XMN1-HBG2, HBS1L-MYB, and BCL11A genes. These genes contain single nucleotide polymorphisms (SNPs) that modulate the expression of HbF differently in various populations. Allele discrimination is important in SNP genotyping and is widely applied in many assays. In conclusion, the expression of HbF with a genetic modifier is crucial in determining the severity of anemic diseases, and genetic modification of HbF expression may offer clinical benefits in diagnosis and disease management.

A case of naturally occurring anti-Dia antibody in a young man.

The Diego (Di) blood group system comprises 22 antigens located on the band 3 protein, most of which are low-prevalence antigens. The majority of antibodies to Diego system antigens were of clinically insignificant; however anti-Dia, -Dib, -Wra, -ELO and-DISK may cause hemolytic disease of the fetus and newborn (HDFN) and transfusion reaction. We reported a case of naturally occurring of anti-Dia in a young man who presented to our hospital for wound debridement of fingers injury. His serological results were suggestive of anti-Dia antibody, and his molecular blood group showed he has Di (a-b+) antigen. Anti-Dia may be clinically significant. It can cause mild-to-severe HDFN, but there are only infrequent reports of it being clearly implicated in a hemolytic transfusion reaction. We suggest the need for reagent red blood cell panels to include Dia antigen-positive cells in antibody identification tests for our populations.

Blood Transfusion Knowledge among Nurses in Malaysia: A University Hospital Experience.

Blood transfusion is a fundamental and life-saving procedure where the consequence of errors can be fatal. Nurses' knowledge plays an essential role in ensuring quality and safety in blood transfusion. The objective of this study was to assess blood transfusion-associated knowledge of tertiary hospital nurses on the east coast of Malaysia. This was a cross-sectional study with 200 registered nurses involved in blood transfusion procedures at Hospital Universiti Sains Malaysia. The knowledge of the nurses was evaluated by using the routine blood transfusion knowledge questionnaire based on five parts, and <50%, 50-74%, or ≥75% of the knowledge was considered as poor, moderate, or high, respectively. Based on the scoring system, the overall knowledge of blood transfusion among Malaysian nurses (33.2 ± 8.4 years) was estimated to be 54.9 ± 7.6%. In individual items, the scoring was 81.0%, 45.4%, 49.2%, 63.0%, and 90.0% in knowledge prior to blood transfusion, on pre-transfusion, on post-transfusion, on complications, and on transfusion policy, respectively. The findings of this study indicated that most of the nurses' overall knowledge of blood transfusion was at a moderate level; therefore, training courses and continuous medical education are warranted to improve knowledge and skills of the nurses to ensure good practices of blood transfusion.

Hemolytic Disease of Fetus and Newborn in a Primigravida with Multiple Alloantibodies Involving Anti-Jka and Anti-E: A Case Report.

The majority of hemolytic disease of the fetus and newborn (HDFN) reported in the literature is due to ABO and rhesus incompatibility. However, there are also other minor blood groups that have been identified as a cause of HDFN, although the occurrence is much rarer. The antibody screening program for D negative mother and the anti-D immunoglobulin treatment showed a significant reduction of the occurrence of HDFN secondary to anti-D. In a developed country, the screening for red blood cell antibody in the pregnant mother other than anti-D reduced the possibility of HDFN occurrence hence reduced the fetal morbidity and subsequently increased the fetal well being during pregnancy and after the postnatal period. In this case report, we discuss HDFN in a primigravida patient secondary to multiple alloantibodies (anti-Jka and anti-E). The baby developed jaundice with bilirubin levels approaching the exchange transfusion level. However, with extensive phototherapy and immunoglobulin treatment, the child did not require exchange transfusion. We also included the importance of the routine antenatal antibody screening program. This practice will help the transfusion center to find the antigen negative blood in a timely manner and reduce the morbidities and mortalities of HDFN among the newborns.