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Warfarin remains the most widely prescribed oral anticoagulant in sub‐Saharan Africa. However, because of its narrow therapeutic index, dosing can be challenging. We have therefore (a) evaluated and compared the performance of 21 machine‐learning techniques in predicting stable warfarin dose in sub‐Saharan Black‐African patients and (b) externally validated a previously developed Warfarin Anticoagulation in Patients in Sub‐Saharan Africa (War‐PATH) clinical dose–initiation algorithm. The development cohort included 364 patients recruited from eight outpatient clinics and hospital departments in Uganda and South Africa (June 2018–July 2019). Validation was conducted using an external validation cohort (270 patients recruited from August 2019 to March 2020 in 12 outpatient clinics and hospital departments). Based on the mean absolute error (MAE; mean of absolute differences between the actual and predicted doses), random forest regression (12.07 mg/week; 95% confidence interval [CI], 10.39–13.76) was the best performing machine‐learning technique in the external validation cohort, whereas the worst performing technique was model trees (17.59 mg/week; 95% CI, 15.75–19.43). By comparison, the simple, commonly used regression technique (ordinary least squares) performed similarly to more complex supervised machine‐learning techniques and achieved an MAE of 13.01 mg/week (95% CI, 11.45–14.58). In summary, we have demonstrated that simpler regression techniques perform similarly to more complex supervised machine‐learning techniques. We have also externally validated our previously developed clinical dose–initiation algorithm, which is being prospectively tested for clinical utility.

Background: Endothelial activation has been proposed as a potential mechanism for the increased risk of venous thromboembolism (VTE) in human immunodeficiency virus (HIV)–infected pregnancy. Objectives: To assess the state of endothelial activation in HIV-infected pregnancy by measuring the von Willebrand factor (VWF) propeptide-to-antigen ratio, as an index of acute endothelial activation. Methods: VWF antigen and VWF propeptide were measured in HIV-negative participants (n = 85), HIV-infected virologically suppressed participants, (n = 89) and HIV-infected participants with HIV viral load (VL) of >50 copies/ml (n = 63) in each trimester. Results were correlated with multimer patterns and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) antigen, activity, and antibody levels. Results: VWF propeptide-to-antigen ratio was increased, in the first, second, and third trimester, in the HIV-infected virologically suppressed group (1.7 ± 0.7, 1.7 ± 0.4, 1.6 ± 0.5) and the HIV-infected group with VL > 50 copies/ml (1.9 ± 0.9, 1.7 ± 0.9, 1.6 ± 1.1) compared to the HIV-negative group (1.4 ± 0.6, 1.3 ± 0.4, 1.2 ± 0.3, P

Introduction: Human immunodeficiency virus (HIV) in pregnant women is characterized by immune activation and inflammation despite suppressive antiretroviral therapy (ART). The extent to which ongoing inflammation contributes to activation of coagulation and fibrinolysis is unknown. Materials and methods: This cross-sectional study included pregnant women in the following three groups: HIV negative (n = 109), HIV infected virologically suppressed (n = 109) and HIV infected with HIV viral load (VL) of >50 copies/mL (n = 80). Fibrinolytic activity was evaluated by measuring d-dimer and plasminogen activator inhibitor-1 (PAI-1) as well as thrombin-antithrombin (TAT) complex concentrations, as an index of coagulation, in the first, second and third trimesters. Results: In this population, with a mean age of 33 ± 6 years, pregnancy outcomes were recorded for 277 (93.0 %) participants with live births. HIV infected participants with virological suppression and VL of >50 copies/mL showed significantly increasing levels of d-dimer and PAI-1 in the first, second and third trimesters, as compared to HIV negative participants. No significant differences were observed between HIV infected participants with virological suppression and HIV infected participants with VL > 50 copies/mL for levels of first and third trimester d-dimer and PAI-1 in each trimester. In addition, TAT complex levels in the first trimester were significantly increased in HIV infected virologically suppressed participants as compared to HIV negative participants. Conclusion: HIV infected virologically suppressed pregnant women show evidence of persistently impaired markers of fibrinolysis. Future research should explore the risk of adverse pregnancy complications among HIV infected pregnant women in the modern era of ART.

Objective: To assess risk factors for venous thromboembolism (VTE) in African women in order to guide thromboprophylaxis. Methods: A case-control study was performed at a specialist obstetric unit in South Africa from July 1, 2017 to June 30, 2020. We identified 128 cases with VTE and 640 controls, matched for gestation. Results: Prepartum risk factors associated with VTE included; medical comorbidities (odds ratios [OR] 5.32, 95% confidence intervals [CI] 1.82–15.56), human immunodeficiency virus (HIV) (OR 2.84, 95% CI 1.50–5.41), and hospital admission or immobility (OR 5.33, 95% CI 1.17–24.22). Postpartum, the following were identified as significant risk factors; medical comorbidities (OR 23.72, 95% CI 8.75–64.27), hospital admission or immobility (OR 13.18, 95% CI 5.04–34.49), systemic infection (OR 4.48, 95% CI 1.28–15.68), HIV (OR 3.20, 95% CI 1.49–6.87), pre-eclampsia and fetal growth restriction (OR 2.74, 95% CI 1.18–6.36), and postpartum hemorrhage (OR 4.38, 95% CI 1.75–10.97). Antiretroviral therapy, opportunistic infections, and viral load >50 copies/ml, however, were not associated with VTE risk among HIV-infected participants. Conclusion: HIV was a significant risk factor for pregnancy-related thrombosis. This was independent of traditional HIV risk factors. As such, future studies are recommended to explore the mechanisms of thrombosis associated with HIV infection.

ObjectiveTo assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population.DesignOpen label, single arm, phase 3B study.SettingSisonke study, South Africa, 17 February to 15 June 2021.ParticipantsThe Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine.Main outcome measuresObserved rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software).ResultsMost of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population.ConclusionsVaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates.Trial registrationClinicalTrials.govNCT04838795.

Introduction: Increased antiphospholipid antibodies (aPL) have been described in human immunodeficiency virus (HIV) infection. However, the association between aPL and the increased risk of thrombosis in HIV requires further clarification. Methods: We reviewed the medical records of 215 consecutive women with a history of thrombosis and/or obstetric complications (158 HIV-uninfected and 57 HIV-infected) between July 2017 and March 2021. Participants (n = 215) without clinical criteria manifestations for antiphospholipid syndrome were included as matched controls. Testing for lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-beta2-glycoprotein1 (aβ2GP1) IgM and IgG was performed. Results: Thirty-two (10.1%) HIV-uninfected and 15 (13.2%) HIV-infected participants were positive at baseline for one of the five criteria aPL, with no statistically significant difference. The profile of the HIV-infected participants with thrombosis (n = 11) included LAC in 15.8%, aCL IgG in 3.5% and aβ2GP1 IgG in 1.8%. In contrast, the HIV-infected controls (n = 4), included aCL IgM in 1.8% and aβ2GP1 IgM in 5.3%. Only LAC was significantly associated with thrombosis (p

Background Anticoagulation of pregnant woman with mechanical prosthetic heart valves is associated with significant maternal and fetal risks. Methods We describe a case of dorsal midline dysplasia in a fetus at 11 weeks' gestation. The mother was receiving warfarin therapy at a dose of 7.5 mg daily following a mechanical mitral valve replacement for rheumatic heart disease. Results Histological assessment revealed a meningocele with hemorrhage. No cerebellar or cerebral tissue was present in the skull confirming anencephaly. Conclusions A multidisciplinary approach in pregnant women with mechanical prosthetic heart valves is essential in order to improve fetal outcomes.

BACKGROUND: Serological tests provide an important tool to diagnose previous exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein we describe the relationship between the demographics, clinical characteristics, and molecular investigations and the presence of coronavirus disease 2019 (COVID-19) antibodies. METHODS: Three hundred and four participants, living in Gauteng, South Africa, were screened for COVID-19 antibodies between September 12, and December 12, 2020. Indications for serological testing included previous infection (n = 45, 14.80%), World Health Organization (WHO) symptoms (n = 122, 40.13%), positive household contact (n = 40, 13.16%), and/or positive close non-household contact (n = 80, 26.32%). RESULTS: There were 58 (19.08%) positive rapid antibody tests. Risk factors associated with a positive rapid antibody test included WHO symptoms, namely fever/chills (odds ratio [OR] 3.50, 95% confidence interval [CI] 1.50 to 8.19), loss of taste or smell (OR 8.66, 95% CI 3.27 to 22.94), and the presence of a household contact (OR 3.66, 95% CI 1.59 to 8.40). CONCLUSIONS: The findings support the measures implemented to reduce the spread of infection.

Despite long-standing experience with warfarin, anticoagulation clinic services are often confronted with the challenging clinical situation of patients with overanticoagulation. This requires repeat international normalized ratio (INR) monitoring and in some cases administration of vitamin K to minimize the risk of bleeding. A study was performed to determine the safety and efficacy of outpatient management in order to provide guidance on the management of patients with prolonged INRs. Patients on stable warfarin therapy for more than 1 month attending a dedicated academic hospital anticoagulation clinic who had an INR ≥5 were identified over a 1-year period. Follow-up INR results and outcomes were recorded for 30 days. One hundred and ninety-five episodes of overanticoagulation in 148 patients were identified. Patients were classified as low risk (n = 85, 57.4%) and moderate risk of bleeding (n = 63, 42.6%). The mean index INR was 7.22 (1.88). Management with low-dose oral vitamin K (n = 32, 16.4%) did not significantly result in a more rapid correction of the INR when compared to conservative management (n = 163, 83.6%; P = .103). Follow-up INR testing was performed at a mean of 11.1 (8.9) days from the index measurement. A mean of 1.6 (0.9) follow-up INR tests were performed per episode. During the 30-day follow-up, there was 1 (0.5%) episode of major bleeding and 1 (0.5%) death. The management of asymptomatic outpatients with overanticoagulation is associated with a low risk of major bleeding within 30 days. Conservative management of overanticoagulation is as effective as utilizing low-dose oral vitamin K.

INTRODUCTION In the developing world, point-of-care (POC) testing for international normalized ratio (INR) plays an important role in the monitoring of patients on long-term warfarin therapy with limited access to healthcare ensuring safe and effective anticoagulation. A newly developed POC device for INR measurement by healthcare workers is the handheld qLabs POC device® (Micropoint Biotechnologies Incorporated, Guangdong, China). METHODS The qLabs POC device® was evaluated in 262 patients attending an anticoagulation clinic with regards to accuracy and precision of the INR results. The results were compared to the results obtained on the Stago STA R Max® coagulation analyzer (Stago Diagnostica, Paris, France) on a wide range of normal and abnormal results of clinical relevance. RESULTS The mean laboratory INR (2.50 ± 1.08) was significantly higher than the qLabs POC device® INR (2.38 ± 1.07) (P 3.5). The imprecision was within acceptable limits (

Background. Venous thromboembolism (VTE) is associated with considerable morbidity and mortality in the absence of thromboprophylaxis. Method. The Southern African Society of Thrombosis and Haemostasis reviewed the available literature and comprehensive evidencebased guidelines on the prevention of VTE in obstetrics and gynaecology. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by an independent international expert to avoid local bias. Results and conclusion. We present concise, practical thromboprophylaxis guidelines for the clinical management of patients in obstetrics and gynaecology. Recommendations reflect current best practice, which it is hoped will lead to improved anticoagulation practice in this group of patients

Background The automated Sysmex XN-9000 hematology system has been designed to meet the throughput and efficiency requirements of high volume laboratories with predominantly abnormal samples. New measurement channels have been introduced namely the white cell nucleated (WNR), white cell differential (WDF), white cell precursor (WPC) and fluorescent platelet (PLT-F) channels. Methods The performance of the new measurement channels was evaluated with regards to precision, accuracy, linearity, carryover, throughput and stability. 275 slides were assessed for morphology flagging. Adult and pediatric samples with normal and abnormal hematology profiles were included. Results The XN-9000 demonstrated acceptable imprecision, good linearity for high and low ranges and no carryover. The full blood count and reticulocyte on the XN-9000 correlated well with the reference ADVIA(2)120. The PLT-F (127 ± 84 × 109/l) compared with the optical platelet count (131 ± 76 × 109/l) (r = 0.97) and the imprecision was Conclusion The XN-9000 showed enhanced analytical performance and workflow efficiency for a wide range of patient samples which can be attributed to the incorporation of new measurement channels.

The use of central venous catheters (CVCs) in patients with cystic fibrosis is associated with an increased incidence of right atrial thrombosis. Practically, the management of CVC-related right atrial thrombosis presents a challenge as there are no clinical trials or systematic reviews in pediatric patients with cystic fibrosis. We describe a case of a 5-year-old child who presented with a CVC-related infection due to Candida parapsilosis. Echocardiogram revealed the presence of an incidental thrombus, measuring 1.4 cm × 0.4 cm, at the tip of the catheter, adherent to the right atrial wall and discrete from the tricuspid valve leaflets. Imaging was performed at monthly intervals and showed spontaneous resolution of the thrombus after six months. Follow-up blood cultures were negative, and the course of the patient was uneventful.

Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors.This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital.The most common indication for anticoagulation was atrial fibrillation (n = 55, 37.4%). The mean warfarin dose was significantly higher in black patients as compared to white patients (5.4 ± 2.9 mg/day and 3.8 ± 2.1 mg/day, respectively; P 0.001). Older age was significantly associated with a lower maintenance warfarin dose (P 0.001). Drugs which decreased the international normalized ratio (INR) were significantly associated with a higher maintenance warfarin dose of 6.4 ± 3.4 mg/day (P 0.034). In contrast, there was no significant difference in warfarin dosage requirements in the presence of CYP2C9 and VKORC1 variant alleles (P 0.05). Patients, however, homozygous for CYP2C9 *1,*3, and VKORC1 required less than 5 mg/day of warfarin to maintain the INR within the therapeutic range.In conclusion, this study indicates that clinical characteristics including; age, ethnic group, and drugs which decrease the INR might help to predict better dose requirements in this population group and thereby reduce the risk of bleeding and thrombotic complications.

Introduction: The diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) in human immunodeficiency virus (HIV) patients on multiple drugs with concomitant disorders presents a diagnostic challenge.Patient presentation: We describe a case of a drug reaction to sulfasalazine in a 46 year old HIV-infected female with concurrent rheumatoid arthritis which presented atypically with a marked peripheral blood plasmacytosis mimicking a lymphoproliferative neoplasm.Management and outcome: A diagnosis of DRESS was made in conjunction with the laboratory and clinical presenting findings. Sulfasalazine was immediately discontinued. The mucocutaneous rash and systemic symptoms (which included fever, lymphadenopathy and multi-organ dysfunction) resolved with supportive treatment. This included topical and systemic corticosteroids.Conclusion: In conclusion, it is important to consider drug reactions when evaluating patients infected with HIV.

INTRODUCTION Thrombotic thrombocytopenic purpura (TTP) is associated with high mortality if not managed timeously with therapeutic plasma exchange (TPE). TTP secondary to human immunodeficiency virus (HIV) infection is unique to sub-Saharan Africa. The management and outcome of TTP in the era of improved access to therapy has not been described. METHODS The present study describes the clinical presentation, treatment, therapeutic endpoints, and outcome of TTP patients at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa. The inpatient and outpatient records of 41 consecutive adults with TTP were reviewed between 2012 and 2016. Patients were classified according to aetiology and treatment response. RESULTS TTP was the initial presenting feature of HIV infection in 78.0%, and 12.5% were noncompliant with antiretroviral therapy (ART). Most study patients were of black ethnicity (95%) and female gender (78.1%). Treatment included initial TPE (87.8%), plasma infusion (78.1%), antiretroviral therapy (78.3%), corticosteroids (61.0%) intensive care admission (41.5%), renal dialysis (12.2%), and other immunosuppressive agents (4.9%). The median (range) number of TPEs was 10.0 (7.0-15.0). A high rate of refractory disease (63.4%) was reported. Haemoglobin, platelet count, lactate dehydrogenase, red cell distribution width, and creatinine were reliable therapeutic end-points (P

Thromboembolic conditions are a leading cause of mortality, estimated to account for 1 in 4 deaths worldwide in 2010. Over time, the incidence and mortality rates of these conditions have declined in developed countries, but are increasing in developing countries. A delicate balance exists between procoagulant and anticoagulant factors within the vascular system. Numerous acquired or inherited conditions may tip the balance either way, i.e. towards a prothrombotic or prohaemorrhagic state. Acquired thrombotic disorders are the subject of discussion in this issue, the second of a 2-part series on thrombophilia.

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare disease in children. Despite advances in diagnosis and treatment, acquired TTP remains a challenging disease due to the lack of a simple diagnostic test and the variable response to plasma exchange. Herein, we describe a case of a 5-year-old of black ethnicity boy who presented with a sudden onset of fatigue and body aches. Laboratory investigations revealed a thrombotic microangiopathic manifestation. TTP was diagnosed, and plasma exchange and corticosteroids were initiated, with an excellent response. Subsequently, reduced disintegrin and metalloprotease with thrombospodin-2-like repeats (ADAMTS-13) activity and human immunodeficiency virus (HIV) were confirmed. Antiretroviral treatment was started as long-term management. At last follow-up, he continues in stable remission.

INTRODUCTION Iron deficiency (ID) is a major cause of morbidity in pregnancy. Antenatal clinics use a hemoglobin to screen for ID, which delays the diagnosis of subclinical ID. The aim of this study was to investigate the clinical utility of the percentage of microcytic red cells (%Micro-R), percentage of hypochromic red cells (%Hypo-He), and reticulocyte hemoglobin content (Ret-He) on the Sysmex hematology analyzer in pregnant patients. METHODS For this study, 102 nonanemic patients in the first trimester of pregnancy presenting for the first time to antenatal clinic were screened for ID. There were 50 (49.02%) patients with ID as defined according to iron studies. The independent t test and receiver operating characteristic (ROC) analysis were applied. RESULTS There was a significant difference in the Ret-He, %Micro-R, and %Hypo-He between the ID and non-ID groups (P

Abnormal bleeding is a common clinical presentation in general practice, and a rational approach to this problem is therefore required. Investigation of a suspected bleeding disorder necessitates a comprehensive history, thorough physical examination and systematic laboratory work-up. Inherited bleeding disorders (IBDs) typically manifest in childhood, but may present later in life after a haemostatic challenge (such as trauma, surgery, tooth extraction). This two-part CME series is intended to provide insight to the medical practitioner on the clinical spectrum, diagnosis and management of bleeding disorders. Bleeding due to inherited disorders is the subject of discussion in part 1 (current issue), and in part 2 (forthcoming issue) the focus is on bleeding from acquired causes. Patients diagnosed with an IBD should ideally be referred to a dedicated tertiary healthcare facility, e.g. haemophilia centre, for management and follow-up.

Background New erythrocyte and reticulocyte parameters provide improved classification of anemia and monitoring of erythropoeitic activity. Parameters available on the Sysmex XN analyzers include the percentage of microcytic red blood cells (%Micro-R), percentage of macrocytic red blood cells (%Macro-R), percentage of hypochromic red blood cells (%Hypo-He), percentage of hyperchromic red blood cells (%Hyper-He), reticulocyte hemoglobin content (Ret-He), and immature reticulocyte fraction (IRF). However, use of these parameters is limited by specimen stability. Methods To verify the stability of the new erythrocyte and reticulocyte parameters during prolonged storage, 20 blood specimens were analyzed on the Sysmex XN-9000 hematology analyzer. The specimens included healthy patients (60%) and patients with anemia (40%). The specimens were stored at room temperature (RT) and at 4° to 8°C. Analysis was performed after 12, 24, 48, and 72 hours of storage. Results Reticulocyte parameters IRF and Ret-He were precise and stable for at least 72 hours after collection when stored at RT and 4° to 8°C. The volume-dependent parameters, %Macro-R and %Micro-R, were stable for less than 12 hours after collection at RT (mean [SD%], 6.55 [3.19%] and -20.70 [10.37%], respectively). Storage at 4° to 8°C showed a reduction in osmotic swelling. However, %Macro-R and %Micro-R were stable for less than 12 hours after collection (mean [SD%], 4.89 [2.02%] and -17.17 [8.38%], respectively). Similarly, %Hypo-He showed a mean (SD%) increase of 0.73 (4.05%) and %Hyper-He showed a decrease of -0.70 (9.72%) at less than 12 hours after storage at 4° to 8°C. Conclusion New reticulocyte parameters stored at RT and 4° to 8°C are suitable for testing on the Sysmex XN analyzer.

Summary Background Critical value policies are used by clinical laboratories to decide when to notify caregivers of life-threatening results. There, however, remains much debate regarding which tests should be included in critical value lists and clinically relevant limits. Method An electronic survey was designed to determine the critical value policies of specialists for haematology tests in South African intensive care units. Data collected included a demographic component, critical value policies and critical value reporting. Results There were 68 respondents who represented a range of specialists from different disciplines. Four key critical values were identified, namely white cell count (WCC), haemoglobin, platelet count and international normalised ratio (INR). Median low and high adult and paediatric critical limits for the most frequently listed tests were as follows: haemoglobin 20 g/dL, platelet count 1000 × 109/L, WCC 20 × 109/L and INR > 4. Specific critical limits for neonates were reported by 20 of the respondents. Of the respondents, 95.92% indicated that it was important to be contacted with first-time critical results and approximately half for repeat critical values. The majority preferred that the person notified of the critical value be the caregiver directly involved with the patient's care. Conclusion It is important for critical value policies to be reviewed by each discipline to ensure cut-offs are clinically relevant.

The diagnosis of iron deficiency anaemia in hospital patients with chronic infections and inflammation presents a challenge. Recently laboratory tests such as the reticulocyte haemoglobin content, which are independent of infection and inflammation, have become available for routine diagnostic use.

Background: The measurement of haemoglobin (Hb) concentration provides a reliable, primary screening test for the presence and severity of anaemia. The HemoCue® is a point-of-care test for Hb measurement. The introduction of point-of-care testing in hospitals and general practice has improved patient care and accessibility. This study was performed to evaluate the utility of point-of-care Hb measurement with the HemoCue® device for the diagnosis of anaemia. Method: In this prospective study, we compared the analytical performance of the HemoCue® to the Coulter® LH 750 automated haematology analyser with regard to accuracy, precision and linearity in the measurement of Hb in adult and paediatric patient samples, referred for routine laboratory testing. Results: Samples from 100 patients were analysed with both instruments, and the results were compared using standard scatter and difference plots. The mean Hb value of the HemoCue® (11.3 g/dl; range 4.6-16.7) was comparable to the Coulter® LH 750 (11.3 g/dl; range 4.7-17.2). The Bland-Altman difference plot revealed good correlation. Bias between the two methods was small, and the imprecision was within acceptable limits. Hb measurement was linear in the range of 4.8-20 g/dl. Conclusion: In all age groups, the HemoCue® point-of-care device can be used to provide accurate and reliable Hb measurements with a smaller sample volume, improved turnaround time, and long-term cost saving.Keywords: haemoglobin, HemoCue®, point-of-care testing, anaemia screening

INTRODUCTION: Worldwide laboratories have adopted the use of modified or alternate methods for measurement of the erythrocyte sedimentation rate (ESR). The iSED from Alcor Scientific is a novel, alternate ESR method based on photometric aggregometry which offers improved operator safety and reduced analysis time. This study evaluated the diagnostic utility of the iSED in a South African patient population with a range of inflammatory disorders. METHODS: We compared the iSED with the predicate modified Westergren method (StaRRsed, Mechatronics, Zwaag, the Netherlands) measured at 60 minutes. Analysis was performed on K(2) EDTA samples at three ESR measurement ranges (80 mm/h) in 120 pediatric and adult inpatients and outpatients over a 2‐week period. Precision, stability, and carryover were performed in accordance with the revised International Council for Standardisation in Haematology guidelines. RESULTS: The iSED demonstrated acceptable imprecision with minimal carryover (2.86%). The correlation coefficients at the 3 ESR measurement ranges were r = 0.58, r = 0.71, and r = 0.56, respectively. The y‐intercepts were −10.74 (CI −29.17 to 7.69), −5.95 (CI −18.60 to 6.69) and 246.05 (CI 591.42‐99.31). This indicated a difference of a constant nature with an overall mean difference of 7.99 mm/h (CI 5.87‐10.13) (P

In neonates presenting with a non-immune haemolytic anaemia, a high index of suspicion is raised for hereditary red cell membrane disorders. The distinction between red cell membrane disorders, however, is often difficult in neonates in the absence of a complete family history. We describe a case of a 26-day-old female twin who presented with jaundice and severe haemolysis, which required multiple red cell transfusions. Laboratory investigations revealed a non-immune haemolysis. Red cell membrane extraction and sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis, including spectrin analysis, revealed the presence of mutant spectrin αI/74. A diagnosis of hereditary elliptocytosis with transient infantile poikilocytosis was favoured. On follow-up at 4 months, a decline in haemolysis was observed.

Background: Referral of samples for the work-up of haematological disorders from remote laboratories can result in a delay in analysis. Objective: The stability of the full blood count (FBC), differential count (DIFF), reticulocyte and peripheral blood smear (PBS) morphology during extended storage was evaluated. Methods: Forty blood samples stored in ethylenediaminetetraacetic acid (EDTA) were analysed on an ADVIA® 120 haematology analyser. The samples (25% abnormal; 75% normal) were stored at room temperature (RT) and at 4 °C – 8 °C. Analysis of samples stored at RT was performed every 12 hours for two days. Analysis of samples stored at 4 °C – 8 °C was performed at 12 hours and subsequently every 24 hours for seven days. Results: FBC parameters (red cell count, haemoglobin) and DIFF parameters (percentages of basophils, lymphocytes and monocytes) were stable for at least 48 hours when stored at RT. Platelets were only stable for 12 hours and the white cell count was stable for 36 hours when stored at RT. Storing samples at 4 °C – 8 °C significantly increased the stability of most parameters, in particular, mean cell volume and percentage of reticulocytes. However, DIFF parameters were associated with lower stability at 4 °C – 8 °C. PBS morphology was compromised prior to 12 hours whether stored at RT or at 4 °C – 8 °C. Conclusion : This study provides evidence that blood samples stored in EDTA at 4 °C – 8 °C for seven days are suitable for testing on the ADVIA® 120 analyser for the FBC and percentage of reticulocyte parameters. However, storage at 4 °C – 8 °C is not a solution for samples referred for DIFF and PBS morphology review.

Introduction: Primary plasma cell leukaemia is a rare and highly aggressive disease that is commonly diagnosed a decade earlier than multiple myeloma, at a median age of 55 years. However, it has also been described in younger patients, as documented in this case report. It often presents with hepatosplenomegaly and lymphadenopathy, whilst the presence of bony lesions are less-commonly seen when compared to multiple myeloma. Case presentation: This report describes the case of a young woman who presented with symptoms of anaemia and a history of menorrhagia. On further careful examination, she was found to have additional signs and symptoms and was later diagnosed with primary plasma cell leukaemia. Management and outcome: On admission, the patient received supportive care measures, including blood products. At diagnosis, a specific chemotherapy regimen was commenced; however, this failed to induce remission. The decision to continue with supportive care only was made and the patient died seven months later. Discussion: This case study is presented because of its rarity, the young age of the patient at presentation and the unusual clinical and laboratory findings. Persistent anaemia unresponsive to standard treatment should raise the index of suspicion and further investigations directed to exclude malignancies should be considered. (Full article to follow)

Background. The management of pregnant patients with mechanical heart valves remains challenging because there are no large randomised studies to provide guidelines for effective anticoagulant therapy. Both vitamin K antagonists and heparins may be associated with maternal and foetal adverse events. Method. The Southern African Society of Thrombosis and Haemostasis reviewed available literature and comprehensive evidence-based guidelines for the anticoagulation of pregnant patients with mechanical heart valves. A draft document was produced and revised by consensus agreement. The guidelines were adjudicated by independent international experts to avoid local bias. Results and conclusion. We present concise, practical guidelines for the clinical management of pregnant patients with mechanical heart valves. Recommendations reflect current best practice which will hopefully lead to improved anticoagulation practice in this select group of high risk patients.

Background Automated hematology analyzers generate white blood cell (WBC) suspect flags to indicate smears requiring manual review. In a human immunodeficiency virus (HIV) patient population with a high frequency of abnormal specimens, the usefulness of these flags depends on their sensitivity and specificity. The white cell precursor (WPC) channel on the Sysmex XN-9000 analyzer (Sysmex Corporation, Kobe, Japan) has recently been introduced in order to distinguish immature cells such as blasts and abnormal lymphocytes. Methods The efficiency of the flags generated by WPC reflex testing was compared to the white cell differential (WDF) on the Sysmex XN-9000 in 400 routine HIV samples. Results A flag was generated by the WDF channel in 346 (86.50%) samples. Addition of the WPC to the WDF resulted in a 20.99% reduction in the smear review rate. WPC analysis correctly identified the initial WDF flag in 59 (60.82%) samples with ‘blasts?’ or ‘abnormal lympho?’ flags. WPC showed an excellent sensitivity of 100%. However, the specificity remained poor. On investigation, samples with chronic infection/inflammation (35.00%) and lymphopenia (63.25%) were associated with a high false positive rate of 76.32% and 55.56%, respectively. WPC analysis removed 45 (51.72%) coexisting ‘atypical lympho?’ false positive WDF flags. The ‘atypical lympho?’ flag showed an increased sensitivity and specificity of 88.46% and 74.67%, respectively. Conclusion White cell precursor reflex testing showed improved flagging efficiency for the ‘atypical lympho?’ flag, which was a good indicator of reactive lymphocytes during chronic infection/inflammation. Nevertheless, the false positive rate for ‘abnormal lympho/blasts?’ was high in the presence of lymphopenia and infection.

Objective. Critical value policies are used by clinical laboratories to decide when to notify caregivers of life-threatening results. Despite their widespread use, critical value policies have not been published locally. A survey was designed to determine critical value policies for haematology tests in South Africa.Methods. A survey was carried out on 136 identified laboratories across South Africa in January 2013. Of these, 36 responded. Data collected included critical value policies, critical values for haematology parameters, and critical value reporting.Results. Of the 36 laboratories surveyed, 11.1% (n=4) were private, 33.3% (n=12) were affiliated to academic institutions and 55.6% (n=20) were peripheral or regional National Health Laboratory Service laboratories. All the laboratories confirmed that they had a critical value policy, and 83.3% of such policies were derived from local clinical opinion. Mean low and high critical limits for the most frequently listed tests were as follows: haemoglobin 20 g/dl, platelet count 1 000 ×109/l, white cell count 46×109/l, activated partial thromboplastin time >101 seconds, and international normalised ratio >6. In almost all cases critical value reporting was performed by the technologist on duty (97.2%). The majority of laboratories required that the person notified of the critical value be the doctor who ordered the test or the caregiver directly involved in the patient’s care (83.3%); 73.3% of laboratories indicated that they followed an algorithm if the doctor/caregiver could not be reached.Conclusion. Each laboratory is responsible for establishing clinically relevant critical limits. Clinicians should be involved in developing the laboratory’s critical value policy. The findings of this survey may be of value to local laboratories that are in the process of establishing or reviewing critical value policies.

BACKGROUND: Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed. This has resulted in unacceptable rates of morbidity and mortality. METHOD: The Southern African Society of Thrombosis and Haemostasis held a meeting to update the previous guideline and review new literature including guidelines from other societies. The following specialties were represented on the committees: anaesthetics, cardiology, clinical haematology, critical care, obstetrics and gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery and pulmonology. A draft document was presented at the meeting, which was then revised by consensus agreement. To avoid local bias, the guideline was adjudicated by recognised international external experts. RESULTS AND CONCLUSION: A concise, practical updated guideline for thromboprophylaxis and treatment in medical and surgical patients has been produced for South African conditions. It is hoped that this guideline will continue to improve anticoagulation practice in this country, which we believe will directly benefit patient outcomes.

Background. Measurement of the international normalised ratio (INR) is essential in the management of patients on long-term warfarin therapy. The CoaguChek XS portable coagulometer is a point-of-care test for INR measurement. It offers the advantage of improved patient accessibility, particularly in peripheral clinics. Objectives. To evaluate the clinical utility of the CoaguChek XS for monitoring of patients on standard warfarin therapy (INR 2 - 3) as well as those with mechanical heart valve replacements (INR 2.5 - 3.5). Methods. We compared the performance of the CoaguChek XS device with that of the STAGO laboratory analyser with regard to accuracy and precision in 304 patients referred for routine testing. Results. The mean INR value of the CoaguChek XS of 2.75 (standard deviation (SD) 1.18) was comparable to that of the STAGO (2.65 (SD 1.04)). The Bland Altman difference plot revealed good agreement. Bias between the two methods was small, and the imprecision was within acceptable limits. Within the target range (2.0 - 3.5), 93.9% of the CoaguChek XS INR readings were within 0.5 units of the standard laboratory method result. There was, however, an increase in the variability of the differences between the two test methods when the INR was >3.6. Conclusion. The CoaguChek XS point-of-care device can be used to provide accurate and precise INR measurements over a wide range for monitoring of valvular and non-valvular patients on long-term warfarin therapy.

Objective. The HemoCue is a point-of-care analytical system for haemoglobin concentration (Hb) measurement. Point-of-care testing hasbeen validated in hospitals and outpatient departments to assist with urgent patient management by providing rapid laboratory test results.Method. In this prospective study we compared the analytical performance of the HemoCue with that of the Advia 120 haematology analyser with regard to accuracy, precision and linearity in the measurement of Hb in neonates and infants.Results. Samples from 44 patients were analysed by both instruments and the results compared using difference plots. The mean Hb value for the HemoCue (11.8 g/dl; range 4.8 - 18.7) was comparable to that for the Advia (11.8 g/dl; range 5.2 - 19.2). The Bland-Altman difference plot revealed good agreement. Bias between the two methods was small and the imprecision was within acceptable limits. Hb measurement was linear in the range 4.8 - 20 g/dl.Conclusion. In neonates and infants, the diagnostic accuracy of the HemoCue point-of-care device is comparable with that of the Advia 120 analyser. In neonatal and paediatric units, where the volume of blood available is limited and turnaround time critical, an appropriately quality-assured HemoCue can replace standard haematology analysers in the measurement of Hb.

BACKGROUND: Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed, which unfortunately results in unacceptable morbidity and mortality in a substantial number of patients. METHOD: The Southern African Society of Thrombosis and Haemostasis reviewed the available literature as well as guidelines from other societies. Specialties represented on the committees included anaesthetics, cardiology, clinical haematology, critical care, gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery, pulmonology and vascular surgery. A draft document was produced, which was revised by consensus agreement. To avoid local bias, the guidelines were adjudicated by recognised independent international external experts. RESULTS AND CONCLUSION: A concise, practical guideline for thrombo-prophylaxis and treatment in medical and surgical patients has been produced for South African conditions. These guidelines will hopefully lead to improved anticoagulation practice in this country, which we believe will directly benefit patient outcomes.

Prepared on behalf of the South African Society of Thombosis and Haemostasis. Background. Recent progress has been made in the understanding of venous thrombo-embolism (VTE) in children and neonates; however, indications for laboratory investigations and therapeutic interventions are not well defined. Method. The Southern African Society of Thrombosis and Haemostasis reviewed available literature and comprehensive evidence-based guidelines for paediatric antithrombotic therapy. A draft document was produced and revised by consensus agreement. The guidelines were adjudicated by independent international experts to avoid local bias. Results and conclusion. We present concise, practical guidelines for the clinical management and laboratory investigation of VTE in children and neonates. Recommendations reflect current best practice which will hopefully lead to improved anticoagulation practice in this age group.