The Novel Coronavirus and Haemostatic Abnormalities: Pathophysiology, Clinical Manifestations, and Treatment Recommendations.

The COVID-19 pandemic, caused by the SARS-C0V-2 virus, was initially considered and managed in a similar manner to the previous SARS epidemic as they are both caused by coronaviruses. What has now become apparent is that a major cause of morbidity and mortality in COVID-19 is abnormal thrombosis. This thrombosis occurs on a macro- and microvascular level and is unique to this disease. The virus has been demonstrated in the endothelium of the pulmonary alveoli and as such is thought to contribute to the devastating respiratory complications encountered. D-dimer concentrations are frequently raised in COVID to levels not frequently seen previously. The optimal anticoagulation treatment in COVID remains to be determined, and the myriad of pathophysiologic effects caused by this virus in the human host have also yet to be fully elucidated.

Overview of the Haematological Effects of COVID-19 Infection.

From its early origins, COVID-19 has spread extensively and was declared a global pandemic by the World Health Organization in March of 2020. Although initially thought to be predominantly a respiratory infection, more recent evidence points to a multisystem systemic disease which is associated with numerous haematological and immunological disturbances in addition to its other effects. Here we review the current knowledge on the haematological effects of COVID-19.

Plasmablastic lymphoma in Johannesburg, South Africa, in the era of widescale antiretroviral therapy use.

OBJECTIVES: Plasmablastic lymphoma (PBL) is a clinically aggressive lymphoma which has a predilection for extranodal sites and is frequently HIV-associated. The incidence of non-Hodgkin lymphoma is thought to be reduced by widescale antiretroviral therapy (ART) coverage, but the literature is sparse as regards the impact of ART on the incidence of PBL and its outcomes in South Africa (SA). This study aimed to compare factors of interest in cases of PBL diagnosed before and after the widespread availability of ART in Johannesburg, SA. METHODS: All cases of PBL diagnosed in the state sector hospitals of Johannesburg in 2007 and 2017 (before and after the widespread availability of ART, respectively) were extracted from the laboratory information system, and factors of interest compared. RESULTS: The majority (> 95%) of cases of PBL were seen among people with HIV infection (PWH) at both time-points, and the proportion of patients on ART and with virological suppression (VS) increased significantly in 2017. However, the number of cases of PBL did not differ significantly between the two years assessed, comprising 46/397 (11.6%) and 53/582 (9.6%) of all lymphomas in 2007 and 2017, respectively (P = 0.23). Ongoing risk for PBL among PWH with virological control and immunological recovery was evident in 2017, as 18.9% of the patients had both VS and CD4 counts > 200 cells/µL at diagnosis. Inferior survival times were associated with elevated lactate dehydrogenase (LDH) levels and Epstein Barr virus (EBV) negativity, but were not influenced by the presence of AIDS, ART or VS. EBV negativity was significantly associated with VS, and appeared to flag a particularly aggressive form of the disease. CONCLUSIONS: Widescale ART coverage has not reduced the incidence of PBL in Johannesburg, and an ongoing risk for this disease among PWH with adequate virological control and immunological recovery persists.

The prevalence of HIV seropositivity and associated cytopenias in full blood counts processed at an academic laboratory in Soweto, South Africa.

BACKGROUND: The HIV epidemic in South Africa (SA) has had a substantial impact on laboratory services, at least partially owing to the well-described propensity to cytopenias in HIV-positive patients. OBJECTIVES: (i) To formally gauge the impact of HIV infection on the state sector haematology services in SA by determining the HIV seropositivity rate among full blood counts (FBCs) performed at a large academic state sector laboratory; and (ii) to document the prevalence of cytopenias among HIV-positive patients in this setting. METHODS: Randomly selected FBCs submitted to the National Health Laboratory Service laboratory at Chris Hani Baragwanath Academic Hospital, Johannesburg, were extracted from the laboratory information system (LIS) and retrospectively reviewed. HIV test results and other pertinent information in the LIS were documented, as was the presence of any cytopenias. RESULTS: HIV status was documented in 561 of 1 006 samples (55.8%), with 307 (54.7%) of these being HIV-positive. Of the HIV-positive patients, 63.2% had one or more cytopenia/s. Anaemia was present in 183/307 (59.6%) of the HIV-positive patients, and was severe (haemoglobin <8 g/dL) in 32/307 (10.4%). Multivariate linear regression analysis showed significant independent associations between the presence of anaemia and both immunological AIDS (iAIDS) (p<0.0001) and male sex (p<0.025), but not HIV viral load (VL) (p=0.33) or antiretroviral therapy (ART) exposure (p=0.70). Thrombocytopenia and neutropenia were present in 37/307 (12.1%) and 11/51 (21.6%) of the HIV-positive patients, respectively, with no statistically significant association between either of these cytopenias and iAIDS, exposure to ART or VL. CONCLUSIONS: The findings reflect the substantial impact of the HIV epidemic on state sector laboratory resources, particularly the haematology service.

The prevalence of HIV seropositivity and associated cytopenias in full blood counts processed at an academic laboratory in Soweto, South Africa

Background. The HIV epidemic in South Africa (SA) has had a substantial impact on laboratory services, at least partially owing to the well-described propensity to cytopenias in HIV-positive patients.Objectives. (i) To formally gauge the impact of HIV infection on the state sector haematology services in SA by determining the HIV seropositivity rate among full blood counts (FBCs) performed at a large academic state sector laboratory; and (ii) to document the prevalence of cytopenias among HIV-positive patients in this setting.Methods. Randomly selected FBCs submitted to the National Health Laboratory Service laboratory at Chris Hani Baragwanath Academic Hospital, Johannesburg, were extracted from the laboratory information system (LIS) and retrospectively reviewed. HIV test results and other pertinent information in the LIS were documented, as was the presence of any cytopenias.Results. HIV status was documented in 561 of 1 006 samples (55.8%), with 307 (54.7%) of these being HIV-positive. Of the HIV-positive patients, 63.2% had one or more cytopenia/s. Anaemia was present in 183/307 (59.6%) of the HIV-positive patients, and was severe (haemoglobin <8 g/dL) in 32/307 (10.4%). Multivariate linear regression analysis showed significant independent associations between the presence of anaemia and both immunological AIDS (iAIDS) (p<0.0001) and male sex (p<0.025), but not HIV viral load (VL) (p=0.33) or antiretroviral therapy (ART) exposure (p=0.70). Thrombocytopenia and neutropenia were present in 37/307 (12.1%) and 11/51 (21.6%) of the HIV-positive patients, respectively, with no statistically significant association between either of these cytopenias and iAIDS, exposure to ART or VL.Conclusions. The findings reflect the substantial impact of the HIV epidemic on state sector laboratory resources, particularly the haematology service

Prevalence and causes of thrombocytopenia in an academic state-sector laboratory in Soweto, Johannesburg, South Africa.

BACKGROUND: Causes of thrombocytopenia range from laboratory errors to life-threatening pathological conditions. To establish the cause, appropriate laboratory investigation is required. OBJECTIVES: To determine the prevalence and causes of platelet counts <100 × 10(9)/L in state health facilities in Johannesburg, South Africa, as well as the quality of the subsequent laboratory work-up in this setting. METHODS: Full blood counts (FBCs) performed on 7 randomly selected days at the National Health Laboratory Service laboratory at Chris Hani Baragwanath Academic Hospital were retrospectively reviewed. Samples with platelet counts <100 × 109/L were identified, and pertinent information was extracted from the laboratory database. RESULTS: Of 4 456 FBCs included, 381 (8.6%) had a platelet count of <100 × 10(9)/L. Thrombocytopenia prevalence rates were high in haematology/oncology wards (34.4%), intensive care units (20.5%) and medical wards (18.7%) and among neonatal inpatients (16.5%), and were lowest in outpatient clinics (1-2%). A cause was apparent in ~60% of patients, the commonest causes being chemotherapy and sepsis (each comprising >20% of the recognised causes). Spurious thrombocytopenia, disseminated tuberculosis, aplastic anaemia, immune thrombocytopenia and malignant marrow infiltration each accounted for 5 - 10% of the causes, while malaria, thrombotic thrombocytopenic purpura, HIV effect and liver disease were each identified in <5% of cases. HIV status was documented in ~70% of the patients, of whom ~50% tested positive. The quality of the laboratory work-up showed differences between specialties within the hospital setting, and was poorest in the primary healthcare clinic sector. CONCLUSION: Thrombocytopenia is common in hospitalised patients in the Johannesburg academic state sector. Differences in the quality of the laboratory work-up emphasise the need for a standardised approach to thrombocytopenia investigation and increased awareness among clinicians.

Lower frequency of NPM1 and FLT3-ITD mutations in a South African adult de novo AML cohort.

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hemopoietic progenitor cells diagnosed in individuals of any age, but with a median age of 67 years at presentation in adults. Assessment of the mutation status of nucleophosmin protein-1 (NPM1) and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is essential for the prognosis, and treatment of AML. METHODS: A total of 160 de novo AML cases, both cytogenetically normal and abnormal, were analyzed for the presence of NPM1 and FLT3-ITD mutations, and the results assessed in conjunction with epidemiological, clinical, and laboratory findings. RESULTS: Nucleophosmin protein-1 mutations were found in 7.5%, while FLT3-ITD was present in 12% of these cases. Both of these were lower than expected. The median age at diagnosis of AML was 41 years, and for the FLT3-ITD only cases, median age was 33 years; these ages were younger than expected. CONCLUSION: The lower reported frequencies and younger median age at diagnosis of AML and these specific mutations may be contributed to by a number of factors including effects of race on age of presentation, inclusion of patients diagnosed with de novo AML only, and a generally younger median age of the South African population.

Challenges in lymphoma diagnosis in HIV positive patients in the South African setting.

An increase in high grade B-cell lymphomas has been noted in HIV infection. Sub-Saharan Africa is the epicentre of the epidemic and in Gauteng, South Africa >90% of patients with high grade lymphoma tested positive for HIV infection. The diagnosis of lymphoma may be challenging in HIV because of reactive conditions which mimic lymphomas, the atypical clinical presentation and the atypical histological findings. The WHO classification divides lymphomas into discrete categories. Despite this, tumours in HIV positive patients commonly show atypical morphological, immunophenotypic, molecular and cytogenetic features, making exact classification difficult. This has lead to an increase in the diagnosis of the highly aggressive B-cell lymphoma, unclassifiable with features intermediate between DLBCL and BL. It appears likely that HIV-associated lymphomas represent a continuum of disease.

Evaluation of the NucliSens EasyQ assay in HIV-1-infected individuals in South Africa.

We compared the performance of the NucliSens EasyQ assay (bioMerieux) combined with the manual NucliSens miniMag extraction methodology to the Roche Cobas Ampliprep/Standard Amplicor Monitor methodology (Roche Diagnostics) for HIV-1 RNA quantitation in HIV-1-infected individuals in South Africa. Plasma samples (284) from HIV sero-positive patients at different stages of infection were analyzed. The distribution of results was typical of the clinical samples received at the laboratory where 20% have viral load results <400 copies/ml (2.6 log) and 18% have viral load results >750000 copies/ml (5.8 log) using the Roche Amplicor Monitor standard assay. All statistical analyses were performed using log10-transformed values for all the variables in the analyses, i.e. log10EasyQIU/ml, and log10RNA (log10 copies/ml, Amplicor). Roche values were converted from RNA copies per ml to IU/ml by multiplying the Roche value by 0.51. HIV RNA levels quantitated by the NucliSens EasyQ assay correlated significantly with those of the Roche Cobas Amplicor Monitor assay (r=0.874, p<0.0001). Reproducibility of the NucliSens EasyQ assay in the log6IU range yielded CV variance of 1.3-2.84% for two well-trained technologists. In addition, a retrospective evaluation of the performance of the NucliSens EasyQ assay in 102 runs (2448) samples was conducted in the laboratory over a 4-month interval. Factors considered during this evaluation included time taken to perform the assay, volume requirements, number of required repeats, potential for contamination.