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The aim of this study was to identify clinical and laboratory phenotype distribution patterns and their usefulness as prognostic markers in COVID-19 patients admitted to the intensive care unit (ICU) at Tygerberg Hospital, Cape Town.A latent class analysis (LCA) model was applied in a prospective, observational cohort study. Data from 343 COVID-19 patients were analysed. Two distinct phenotypes (1 and 2) were identified, comprising 68.46% and 31.54% of patients, respectively. The phenotype 2 patients were characterized by increased coagulopathy markers (D-dimer, median value 1.73 ng/L vs 0.94 ng/L;The identification of COVID-19 phenotypes and sub-phenotypes in ICU patients could help as a prognostic marker in the day-to-day management of COVID-19 patients admitted to the ICU.

AimTo compare the frequently used CD138 immunohistochemistry-based method of plasma cell quantitation, to a proposed new method, using interobserver and intraobserver concordance parameters.MethodsArchival CD138 immunohistochemically stained slides made from paraffin-embedded bone marrow biopsies of 33 patients with a confirmed diagnosis of multiple myeloma were used. Light microscopic examination was performed using low magnification lenses (10×) for both the overview estimation method (method A) and the new method (method B), and high magnification lenses (50×), for method B only. For method B, reviewers selected three areas with low, intermediate and high plasma cell densities using 10× lenses. Using a well-defined technique, the 50× lens was then used to count plasma cells as a percentage of all nucleated cells. After blinded relabelling of all the slides, the nine reviewers repeated the plasma cell quantitation using both methods. The plasma cell counts were obtained, and the review times were recorded.ResultsOverall intraobserver concordance was comparable for method A (concordance correlation coefficient (CCC)=0.840) and method B (CCC=0.733). Interobserver concordance for method A (intraclass correlation coefficient (ICC)=0.793 and 0.713) and method B (ICC=0.657 and 0.658) indicated high similarity between reviewers. Method A showed poor interobserver concordance (ICC=0.105) at low plasma cell densities.ConclusionsThe new method is comparable to the frequently used overview estimation method in terms of intraobserver and interobserver concordance, and cost. The new method has superior interobserver concordance at low plasma cell densities. The new method appears more amenable to digital scanning and analysis.

Objective The aim of this study was to identify arterial blood gas (ABG) abnormalities, with a focus on a high anion gap (AG) metabolic acidosis and evaluate outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU. Methods A retrospective, observational study was conducted in a tertiary hospital in Cape Town during the first and second COVID-19 waves. Age, gender, sodium (Na), potassium (K), chloride (Cl), bicarbonate (HCO3std), pH, partial pressure of carbon dioxide (pCO2), creatinine, estimated glomerular filtration rate (eGFR), lactate levels and ABG results were obtained. The Pearson χ2 test or Fisher exact test and the Wilcoxon rank-sum test were used to compare mortality and survival. To identify factors associated with non-survival, a multivariable model was developed. Results This study included 465 patients, 226 (48%) of whom were female. The sample population’s median (IQR) age was 54.2 (46.1–61.3) years, and 63% of the patients died. ABG analyses found that 283 (61%) of the 465 patients had alkalosis (pH ≥ 7.45), 65 (14%) had acidosis (pH ≤ 7.35) and 117 (25%) had normal pH (7.35–7.45). In the group with alkalosis, 199 (70.3%) had a metabolic alkalosis and in the group with acidosis, 42 (64%) had a metabolic acidosis with an increased AG of more than 17. Non-survivors were older than survivors (56.4 years versus 50.3 years, p < .001). Conclusion Most of the COVID-19 patients admitted to the ICU had an alkalosis, and those with acidosis had a much worse prognosis. Higher AG metabolic acidosis was not associated with patients’ characteristics.

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to evolve. Globally, COVID-19 continues to strain even the most resilient healthcare systems, with Omicron being the latest variant. We made a thorough search for literature describing the effects of the COVID-19 in a high human immunodeficiency virus (HIV)/tuberculosis (TB) burden district-level hospital setting. We found scanty literature. Methods: A retrospective observational study was conducted at Khayelitsha District Hospital in Cape Town, South Africa (SA) over the period March 2020 – December 2021. We included confirmed COVID-19 cases with HIV infection aged from 18 years and above. Analysis was performed to identify predictors of mortality or hospital discharge among people living with HIV (PLWH). Predictors investigated include CD4 count, antiretroviral therapy (ART), TB, non-communicable diseases, haematological, and biochemical parameters. Findings: This cohort of PLWH with SARS-CoV-2 infection had a median (IQR) age of 46 (37–54) years, male sex distribution of 29.1%, and a median (IQR) CD4 count of 267 (141–457) cells/mm3. Of 255 patients, 195 (76%) patients were discharged, 60 (24%) patients died. One hundred and sixty-nine patients (88%) were on ART with 73(28%) patients having acquired immunodeficiency syndrome (AIDS). After multivariate analysis, smoking (risk ratio [RR]: 2.86 (1.75–4.69)), neutrophilia [RR]: 1.024 (1.01–1.03), and glycated haemoglobin A1 (HbA1c) [RR]: 1.01 (1.007–1.01) were associated with mortality. Conclusion: The district hospital had a high COVID-19 mortality rate among PLWH. Easy-to-access biomarkers such as CRP, neutrophilia, and HbA1c may play a significant role in informing clinical management to prevent high mortality due to COVID-19 in PLWH at the district-level hospitals.

Inborn errors of immunity (IEI) are inherited monogenic disorders resulting in defective immune response. Non-infectious presentations are increasingly more apparent. Widely available, cost-effective early indicators are needed. Peripheral-blood cytopenia may be a presenting laboratory feature or an observed secondary phenomenon. This retrospective review of the South African Primary Immunodeficiency Registry (SAPIDR) aimed to assess the haematological indices at presentation and their association with the International Union of Immunological Societies (IUIS) 2019 IEI classification and mortality. Of 396 patients on the SAPIDR, 66% (n = 257) had available haematological results. Sixty percent were males and 85% under 18 years. A majority (53%) had predominantly antibody deficiency. At presentation, infection was prominent (86%) followed by cytopenia (62%). Neutropenia was associated with IUIS III [odds ratio (OR) 3.65, confidence interval (CI) 1.44-9.25], thrombocytopenia with IUIS II (OR 14.39, CI 2.89-71.57), lymphopenia with IUIS I (OR 12.16, CI 2.75-53.73) and pancytopenia with IUSI I (OR 12.24, CI 3.82-39.05) and IUIS II (OR 5.99, CI 2.80-12.76). Cytopenia showed shorter overall survival (OR 2.81, CI 1.288-4.16). Cytopenias that are severe, persistent, unusual and/or recurrent should prompt further investigation for IEI. The full blood count and leucocyte differential may facilitate earlier identification and serve as an adjunct to definitive molecular classification.

Background: More than 90% of the global 400 000 annual malaria deaths occur in Africa. The current SARS-CoV-2 pandemic has resulted in more than 830 000 deaths in its first 10 months. Case presentation: This case describes a patient who had travelled from Mozambique to Cape Town, presented with a mild febrile illness, and was diagnosed with both COVID-19 and uncomplicated Plasmodium falciparum malaria infection. She responded well to malaria treatment and had an uneventful COVID-19 admission. Her blood smear showed a low malaria parasitaemia and a relatively high gametocyte load. Conclusion: We postulate that her clinical course and abnormal smear could well be due to reciprocal disease-modifying effects of the infections. The presenting symptoms of COVID-19 may mimic endemic infectious diseases including malaria, tuberculosis, pneumocystis pneumonia and influenza thus there is a need for clinical vigilance to identify and treat such co-infections. The full article is available at https://doi.org/10.36303/JMLSTSA.2020.2.2.57

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the coronavirus disease 2019 (COVID-19) it causes, are associated with several haematological abnormalities which manifest as some of the clinical syndromes seen in COVID-19. The main organ affected by COVID-19 is the lung, where an intense inflammatory response occurs in the alveoli and the lung vasculature. This may result in severely compromised gaseous exchange consistent with acute respiratory disease syndrome (ARDS). Multiple organ failure and death may ensue. The extent to which SARS-CoV-2 directly affects erythroid, granulocytic and monocytic progenitors is unknown, however related Coronaviridae have previously been shown to infect megakaryocytes and their progenitors. Furthermore, SARS-CoV-2 may directly infect lymphocytes or monocytes causing the production of cytokines and chemokines, which then cause lymphocyte death and lymphopenia. The quantitative changes seen in monocytes and granulocytes are at least partly due to the marked increase in various cytokines also called the “cytokine storm” and the downstream effects of these cytokines. A COVID-19-associated coagulopathy (CAC) may occur, which ranges from a mild derangement of laboratory haemostatic tests, through to sepsis-induced coagulopathy (SIC), and later, frank disseminated intravascular coagulation (DIC). The most common and devastating haemostatic abnormality is widespread thrombosis, which is associated with severe lung inflammation, hypoxia and death. COVID-19 is associated with immune perturbation states namely, immune thrombocytopenia (ITP), Guillain-Barre syndrome, the anti-phospholipid syndrome and a Kawasaki-like syndrome in children. The pathophysiology of the haematological abnormalities seen in COVID-19 is briefly reviewed in this article. The full article is available at https://doi.org/10.36303/JMLSTSA.2020.2.2.48

The antiphospholipid syndrome (APS) is a thrombophilic condition characterised by thromboses and/or adverse pregnancy outcomes. International criteria for the diagnosis of APS require that certain laboratory and clinical criteria are met. Lupus anticoagulant (LA) testing using coagulation tests is an essential component. This review aims to provide a national guideline for LA testing in the South African context and intends to standardise testing, interpretation and reporting of results. Key aspects of the pre-analytical, analytical and post-analytical phases of testing are considered and highlighted. The full articles is available at https://doi.org/10.36303/JMLSTSA.2020.2.1.39

The second wave of coronavirus disease 2019 (COVID-19) in South Africa was caused by the Beta variant of severe acute respiratory syndrome coronavirurus-2. This study aimed to explore clinical and biochemical parameters that could predict outcome in patients with COVID-19.A prospective study was conducted between 5 November 2020 and 30 April 2021 among patients with confirmed COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital. The Cox proportional hazards model in Stata 16 was used to assess risk factors associated with survival or death. Factors withPatients who died were found to have significantly lower median pH (The mortality of patients with COVID-19 admitted to the ICU was associated with elevated D-dimer and a low HCO3std level. Large studies are warranted to increase the identification of patients at risk of poor prognosis, and to improve the clinical approach.

Background Data on biochemical markers and their association with mortality rates observed in patients with severe COVID-19 disease admitted to Intensive Care Units (ICUs) in sub-Saharan Africa are scanty. We performed an evaluation of baseline routine biochemical parameters as prognostic biomarkers in COVID-19 patients admitted to ICU. Methods Demographic, clinical, and laboratory data were collected prospectively on patients with PCR-confirmed COVID-19 admitted to the adult ICU in a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results A total of 82 patients [(median age 53.8 years (IQR: 46.4-59.7)] were enrolled, of whom 27 (33%) were male. The median duration of ICU stay was 10 days (IQR: 5-14); 54/82 (66% CFR) patients died. Baseline lactate dehydrogenase (LDH) (aRR: 1.002, 95%CI: 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NTProBNP) (aRR: 1.0004, 95%CI: 1.0001-1.0007; P = 0.014) were both independent risk factors of a poor prognosis with optimal cut-off values of 449.5 U/L (sensitivity: 1; specificity: 0.43) and 551 pg/mL (sensitivity: 0.49; specificity: 0.86), respectively. Conclusion LDH and NTProBNP appear to be promising predictors of COVID-19 poor prognosis in the ICU. Larger sample size studies are required to confirm the validity of this combination of biomarkers.

BackgroundData on biochemical markers and their association with mortality rates observed in patients with severe COVID-19 disease admitted to Intensive Care Units (ICUs) in sub-Saharan Africa are scanty. We performed an evaluation of baseline routine biochemical parameters as prognostic biomarkers in COVID-19 patients admitted to ICU. MethodsDemographic, clinical and laboratory data were collected prospectively on patients with PCR-confirmed COVID-19 admitted to the adult ICU in a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. ResultsA total of 82 patients [(median age 53.8 years (IQR: 46.4-59.7)] were enrolled, of whom 27 (33%) were male. The median duration of ICU stay was 10 days (IQR: 5-14); 54/82 (66% CFR) patients died. Baseline lactate dehydrogenase (LDH) (aRR: 1.002, 95%CI: 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NTProBNP) (aRR: 1.0004, 95%CI: 1.0001-1.0007; P = 0.014) were both independent risk factors of a poor prognosis with optimal cut-off values of 449.5 U/L (sensitivity: 1; specificity: 0.43) and 551 pg/mL (sensitivity: 0.49; specificity: 0.86), respectively.ConclusionLDH and NTProBNP appear to be promising predictors of COVID-19 poor prognosis in the ICU. Larger sample size studies are required to confirm the validity of this combination of biomarkers.

Background: The performance of laboratories can be objectively assessed using the overall turn-around time (TAT). However, TAT is defined differently by the laboratory and clinicians; therefore, it is important to determine the contribution of all the different components making up the laboratory test cycle. Objective: We carried out a retrospective analysis of the TAT of full blood count tests requested from the haematology outpatient department at Tygerberg Academic Hospital in Cape Town, South Africa, with an aim to assess laboratory performance and to identify critical steps influencing TAT. Methods: A retrospective audit was carried out, focused on the full blood count tests from the haematology outpatient department within a period of 3 months between 01 February and 30 April 2018. Data was extracted from the National Health Laboratory Service laboratory information system. The time intervals of all the phases of the test cycle were determined and total TAT and within-laboratory (intra-lab) TAT were calculated. Results: A total of 1176 tests were analysed. The total TAT median was 275 (interquartile range [IQR] 200.0–1537.7) min with the most prolonged phase being from authorisation to review by clinicians (median 114 min; IQR: 37.0–1338.5 min). The median intra-lab TAT was 55 (IQR 40–81) min and 90% of the samples were processed in the laboratory within 134 min of registration. Conclusion: Our findings showed that the intra-lab TAT was within the set internal benchmark of 3 h. Operational phases that were independent of the laboratory processes contributed the most to total TAT.

Background Pre-analytical variables can have a significant adverse impact on the quality and credibility of coagulation test results. Therefore, correct and consistent identification of pre-analytical variables that compromise coagulation specimen quality is of paramount importance. Lack of standardization and heterogeneity among laboratory staff when assessing coagulation specimens can lead to inconsistent identification of these variables. Failure to recognize such pre-analytical variables results in the analysis of poor quality specimens and the authorization of spurious test results. Objectives To determine the impact of a laboratory staff training workshop on coagulation specimen rejection rates and to ascertain the level of knowledge of laboratory personnel concerning coagulation specimen rejection criteria before and after the workshop. Methods A retrospective three-month audit was performed with rejection data of incorrect blood to additive ratio, clotted, aged and haemolysed specimens collected. Training workshops and evaluation sessions were subsequently presented. A revised standard operating procedure delineating coagulation specimen rejection criteria was implemented and a repeat three-month audit was conducted. Results In total, 13 162 coagulation specimens were received during the initial audit with 1 104 specimens (8.39%) rejected. Following the workshops, the rejection rate increased by 3.49% to 11.88% with 12 743 coagulation specimens received and 1 514 specimens rejected. Evaluation sessions performed before and after the workshops revealed that 95.2% of attendees attained improved knowledge. Conclusion This study demonstrated the pivotal importance of regular laboratory staff training. The increase in specimen rejection following the workshops signifies their success in educating laboratory personnel regarding the correct identification of pre-analytical variables. Since most pre-analytical variables occur outside the laboratory, educational workshops need to be extended to non-laboratory personnel responsible for specimen collection and transport.

Background: Bone marrow examination is a useful diagnostic tool in human immunodeficiency virus (HIV)-positive patients presenting with cytopenias and fever. However, its role in the afebrile and asymptomatic patient presenting with an isolated cytopenia is not well established. This study was conducted to determine the indications for bone marrow examination and its diagnostic yield, in HIV-positive patients at Tygerberg Hospital.Methods: A retrospective, cross-sectional descriptive study was performed over a 3-year period from 01 September 2015 to 31 August 2018. The bone marrow examination reports for the HIV-positive patients who had a bone marrow examination during the study period were retrieved. Clinical and laboratory information was captured.Results: Altogether 374 bone marrow reports for HIV-positive patients were found. The indication of the bone marrow examination included investigation of unexplained cytopenias, suspected haematological malignancies, follow-up examination for patients with known haematological diseases, staging of haematological or non-haematological malignancies and investigation of suspected disseminated infection. The patients’ median age was 43 years and the interquartile range was 27–60 years. There was a slight female predominance with females 51% and males 49%. The diagnostic yield was 33.7%. Acute leukaemia and lymphoma were the most common diagnoses. Haematinic deficiency and pure red cell aplasia were found in the majority of cases with isolated anaemia. All cases with isolated thrombocytopenia were due to immune thrombocytopenia.Conclusion: Bone marrow examination is a useful investigation for HIV-positive patients with cytopenias, suspected haematological malignancy and lymphoma staging. However, its early use in patients with isolated anaemia and isolated thrombocytopenia is questionable.

This case study explores a clinicopathological presentation of Adult T-cell leukaemia/lymphoma (ATLL) at Tygerberg Hospital; a disease associated with adulthood noted in an adolescent patient. Adult T-cell leukaemia–lymphoma oncogenesis develops through a multistep process with an accumulation of mutations. Infection through human T-lymphotropic virus type 1 (HTLV-1) is the first step of a multistep process resulting in eventual clonal proliferation of mature T-cells. There is a long latency period of 20–50 years from the time of infection with HTLV-1 to the development of symptoms of ATLL; thus, ATLL is a malignancy associated with adulthood. The median age of diagnosis is 58, ranging from the third to ninth decade of life. This is an ideal learning case as it highlights the importance of recognising ATLL in children and young adults in our population.

Background: Burkitt lymphoma(BL) is a high grade non-Hodgkin lymphoma, which may be underdiagnosed in South Africa, due to a high burden of infectious diseases such as HIV and TB which may present with similar clinical features. Aim: To describe demographics and clinico-pathological characteristics of patients diagnosed with BL. Setting: Tygerberg Hospital (TBH), South Africa between 2007-2014. Methods: We performed a retrospective descriptive and survival analysis of patients diagnosed with BL at TBH between 01 January 2007 and 31 December 2014 with at least 24-month follow-up. Data was collected from the Tygerberg Lymphoma Study Group database and the South African Children Cancer Study Group Tumour Registry. Results: There were 73 patients with BL, of whom 68 were admitted to TBH and whose data was further analysed. The majority of patients were adults (74%). There was a female predominance in adults and a male predominance in children ( p = 0.002). Various regimens were used in adults while a single treatment protocol was used in children. The proportion of patients with HIV and advanced BL was higher in adults than in children. The 2-year overall survival of the treatment group was 45%. The outcome of patients with BL in adults (34%) was poorer than that of children (69%) ( p = 0.022). HIV negative patients had a non-significant survival advantage (57%) over HIV positive patients with 41% 2-year overall survival ( p = 0.2876). Conclusion: This study demonstrates a better cure rate in children treated for BL compared to adults, with HIV-infection being a risk factor for poor outcome.

BackgroundThrombophilia-screen tests are specialised haemostasis tests that are affected by numerous unique patient variables including the presence of acute thrombosis, the concomitant use of medication and patient demographics. Complete information on the request form is therefore crucial for the haematological pathologist to make patient-specific interpretation of patients' results.ObjectivesTo assess the completeness of thrombophilia-screen test request forms and determine the impact of provision of incomplete information, on the interpretive comments generated by reporting haematological pathologists. To assess the impact of an educational session given to clinicians on the importance of providing all the relevant information on the request forms.MethodTwo retrospective audits, each covering 3 months, were performed to evaluate the completeness of demographic and clinical information on thrombophilia-screen request forms and its impact on the quality of the interpretive comments before and after an educational intervention.ResultsOne hundred and seventy-one request forms were included in the first audit and 146 in the second audit. The first audit revealed that all 171 thrombophilia-screen request forms had complete patient demographic information but none had clinical information. Haematological pathologists only made generic comments which could not be applied to a specific patient. The second audit, conducted after a physician educational session, did not reveal any improvement in the clinical information provision by the test-ordering physicians. This was reportedly due to the lack of space on the request form. The interpretive comments therefore remained generic and not patient-specific.ConclusionPhysicians' failure to provide relevant clinical information made it impossible for pathologists to make patient-specific interpretation of the results. A single physician education session did not change the practice, reportedly due to the inappropriate design of the test request form. Further studies are required to investigate the impact of an improved request form and the planned electronic test requesting.

Aims Certain systems for self-monitoring of blood glucose (SMBG) demonstrate inaccuracy at low and high hematocrit (HCT). Manufacturers define HCT ranges for accurate performance. Our objective was to assess the frequency of HCT values that can lead to clinically relevant errors. Methods In this cross-sectional study, we collected real-world data representing over 360,000 outpatients from the Netherlands (NL), the Czech Republic (CZ), and South Africa (ZA). These were subsequently stratified by sex and age and compared to commonly specified HCT range limits, reference intervals, and data from 1780 healthy Czech subjects. Results HCT values were comparably distributed in NL and CZ. Outpatients had a higher dispersion of values than healthy subjects. Low HCT values in Europe were common in age groups with a high prevalence of diabetes. All ZA age groups showed a higher prevalence of low HCT than in Europe. Conclusions Real-world data indicate that SMBG systems specified to perform only within the frequently used 30–55% HCT range would leave 3% of outpatients in Europe and 18% in South Africa at risk of false SMBG results, with individual age strata being substantially higher. This could affect their diabetes management. Adequate SMBG systems should thus be chosen.