Anti-Xa Monitoring of Apixaban (ZyQuis) in Venous Thrombo-Embolism and Atrial Fibrillation.

Apixaban is a direct oral Xa inhibitor and is indicated for the treatment of venous thrombo-embolism (VTE) and prevention of stroke in atrial fibrillation (AF). Recently, a generic (ZyQuis, Zydus Lifesciences Limited, India) has received Food and Drug Administration approval. While bioequivalence has been demonstrated with Eliquis (Bristol-Myers Squibb/Pfizer, UK), it is necessary to monitor its effectiveness prior to acceptance in medical practice. This prospective study independently evaluated Apixaban (ZyQuis) at two accredited laboratories. Participants were converted from Warfarin or Rivaroxaban to Apixaban 5 mg bd for a duration of one month. Peak anti-Xa levels were measured 3-4 h post the morning dose. The samples were processed on the Atellica COAG 360 (Siemens Healthineers, Marburg, Germany) analyzers with a chromogenic anti-Xa assay (Innovance, reference interval 69-321 ng/mL). There were 26 participants; 5 men, 21 women; mean ± standard deviation age of 46 ± 12 years. Indications for anticoagulation included: VTE (88.5%) and AF (11.5%). 69.2% of the participants had at least one comorbidity. 96.2% of the anti-Xa levels were within the laboratory's 95% reference interval. Mean anti-Xa activity was 191 ± 69 ng/mL and 186 ± 68 ng/mL measured at respective laboratories. Mean differences in anti-Xa measurements represented by Bland-Altman statistics were small (bias of -2.6%, 95% confidence interval -1.11 to -4.09) and a strong correlation was observed on Deming regression analysis (0.995). Apixaban (ZyQuis) was effective for the management of VTE and AF as evidenced by anti-Xa activity.

Performance Evaluation of the Atellica Hema 580 Automated Slidemaker and Stainer for Morphology Review.

BACKGROUND: Improved measurement technologies for automated peripheral blood smear (PBS) preparation have led to a more efficient workflow. In this report, we evaluated the Atellica Hema 580 automated slidemaker/stainer (Siemens Healthineers, Tarrytown, NY, USA). METHODS: The quality of PBS prepared and stained on the Atellica Hema 580 slidemaker/stainer were compared with manual films stained on the Hematek 3000. A 200-cell differential and morphology assessment were performed by two competent morphologists. RESULTS: Macroscopically, the automated PBS were of excellent quality, with a gradual transition in thickness, smooth edges, and sufficient length. The morphology was comparable between manual and automated PBS. Correlations between the manual and automated PBS were 0.95 (95% confidence interval: 0.92 to 0.96) for neutrophils, 0.63 (95% CI: 0.50 to 0.74) for monocytes and 0.90 (95% CI: 0.85 to 0.93) for lymphocytes. CONCLUSIONS: The performance of Atellica Hema 580 automated slidemaker/stainer was comparable to the manual method and represents a reliable automated solution for medium to large sized laboratories.

Verification of a Benchtop Hematology Analyzer with a 5-Part Differential Count: There is Nothing Wrong with Being Small.

BACKGROUND: The benchtop ADVIA 560 AL hematology analyzer (Siemens Healthineers Tarrytown, NY, USA) offers a small footprint and ease of operation making it suitable for satellite laboratories and intensive care units. A verification study of this analyzer was performed. METHODS: Between- and intra-run precision, carry-over, linearity, and throughput were evaluated on the ADVIA 560 AL. Accuracy was assessed on 94 patient samples by comparing the results obtained on the ADVIA 560 AL to the results on the reference Sysmex XN1000 analyzer (Sysmex Corporation, Kobe, Japan). RESULTS: The ADVIA 560 AL showed acceptable imprecision on control material and minimal bias in comparison to the XN 1000 on patient samples with a throughput of 60 samples per hour. The percentage carryover was not significant and the linearity was within acceptable limits. CONCLUSIONS: The ADVIA 560 AL bench-top analyzer is suitable for acute care centers and satellite laboratories owing to its small footprint, ease of use, and reproducible and accurate results.

Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study).

Objective: To 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. Design: Open label, single arm, phase 3B study. Setting: Sisonke study, South Africa, 17 February to 15 June 2021. Participants: The Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine. Main outcome measures: Observed 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). Results: Most 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. Conclusions: Vaccine 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 registration: ClinicalTrials.gov NCT04838795.

Pregnancy Related Venous Thromboembolism-Associated with HIV Infection and Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection in pregnancy is associated with substantial morbidity and mortality. Improved access to effective antiretroviral therapy (ART) has shifted the spectrum of pregnancy-related complications among HIV-infected pregnant women. In addition to placental vascular complications and preterm delivery, increased rates of venous thromboembolism (VTE) have been described. HIV infection is characterized by immune activation, inflammation, and endothelial dysfunction, which contribute to the activation of coagulation and its prothrombotic consequences. Indeed, activated coagulation factors have been reported to be increased and natural anticoagulants reduced in HIV. Several mechanisms for this persistent prothrombotic balance on ART have been identified. These may include: co-infections, immune recovery, and loss of the gastrointestinal mucosal integrity with microbial translocation. In addition to the direct effects of HIV and ART, traditional venous and obstetric risk factors also contribute to the risk of VTE. A research priority has been to understand the mechanisms of VTE in HIV-infected pregnant women receiving suppressive ART and to translate this into HIV-specific thromboprophylaxis recommendations. Management requires a multidisciplinary approach and further studies are indicated to guide the prevention and management of pregnancy-associated VTE in this population. The current review describes the epidemiology, mechanisms, and management of VTE in HIV-infected women in pregnancy and the postpartum period.

A genome-wide association study of plasma concentrations of warfarin enantiomers and metabolites in sub-Saharan black-African patients.

Diversity in pharmacogenomic studies is poor, especially in relation to the inclusion of black African patients. Lack of funding and difficulties in recruitment, together with the requirement for large sample sizes because of the extensive genetic diversity in Africa, are amongst the factors which have hampered pharmacogenomic studies in Africa. Warfarin is widely used in sub-Saharan Africa, but as in other populations, dosing is highly variable due to genetic and non-genetic factors. In order to identify genetic factors determining warfarin response variability, we have conducted a genome-wide association study (GWAS) of plasma concentrations of warfarin enantiomers/metabolites in sub-Saharan black-Africans. This overcomes the issue of non-adherence and may have greater sensitivity at genome-wide level, to identify pharmacokinetic gene variants than focusing on mean weekly dose, the usual end-point used in previous studies. Participants recruited at 12 outpatient sites in Uganda and South Africa on stable warfarin dose were genotyped using the Illumina Infinium H3Africa Consortium Array v2. Imputation was conducted using the 1,000 Genomes Project phase III reference panel. Warfarin/metabolite plasma concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Multivariable linear regression was undertaken, with adjustment made for five non-genetic covariates and ten principal components of genetic ancestry. After quality control procedures, 548 participants and 17,268,054 SNPs were retained. CYP2C9*8, CYP2C9*9, CYP2C9*11, and the CYP2C cluster SNP rs12777823 passed the Bonferroni-adjusted replication significance threshold (p < 3.21E-04) for warfarin/metabolite ratios. In an exploratory GWAS analysis, 373 unique SNPs in 13 genes, including CYP2C9*8, passed the Bonferroni-adjusted genome-wide significance threshold (p < 3.846E-9), with 325 (87%, all located on chromosome 10) SNPs being associated with the S-warfarin/R-warfarin outcome (top SNP rs11188082, CYP2C19 intron variant, p = 1.55E-17). Approximately 69% of these SNPs were in linkage disequilibrium (r 2 > 0.8) with CYP2C9*8 (n = 216) and rs12777823 (n = 8). Using a pharmacokinetic approach, we have shown that variants other than CYP2C9*2 and CYP2C9*3 are more important in sub-Saharan black-Africans, mainly due to the allele frequencies. In exploratory work, we conducted the first warfarin pharmacokinetics-related GWAS in sub-Saharan Africans and identified novel SNPs that will require external replication and functional characterization before they can be considered for inclusion in warfarin dosing algorithms.

Evaluation of markers of fibrinolysis and coagulation in pregnant women with human immunodeficiency virus.

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.

Profile of antiphospholipid antibodies in HIV-infected and HIV-uninfected women with a history of thrombosis.

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 (aß2GP1) 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 aß2GP1 IgG in 1.8%. In contrast, the HIV-infected controls (n = 4), included aCL IgM in 1.8% and aß2GP1 IgM in 5.3%. Only LAC was significantly associated with thrombosis (p < 0.003). On repeat testing, in a HIV-infected sub-population, 2/7 with thrombosis were positive, while 3/3 controls tested negative. CONCLUSION: In contrast to earlier reports, the prevalence and expression of aPL in HIV-infected women with a history of thrombosis in the present study, in the era of antiretroviral therapy, were similar to HIV-uninfected women. Baseline LAC positivity was associated with a significantly increased risk for thrombosis in HIV. Future studies are recommended to explore additional coagulation abnormalities in HIV.

Stable warfarin dose prediction in sub-Saharan African patients: A machine-learning approach and external validation of a clinical dose-initiation algorithm.

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.

von Willebrand factor propeptide-to-antigen ratio in HIV-infected pregnancy: Evidence of endothelial activation.

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 < .05). Increased high molecular weight multimers were observed in the HIV-infected groups, despite only a mild reduction in ADAMTS-13 activity compared to the HIV-negative group (P < .001). No correlation was observed between VWF antigen or VWF propeptide and ADAMTS-13 activity. CONCLUSION: HIV-infected virologically suppressed pregnant participants showed persistent endothelial activation. Future research should focus on whether endothelial activation contributes to the excess risk of pregnancy-related VTE.

Warfarin Anticoagulation and Fetal Central Nervous System Abnormalities: a Case Report.

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.

The Relationship between Serological Testing, Demographics, Clinical Presentation and RT-PCR Testing for COVID-19.

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.

Pregnancy in women with cardiac disease: a one-year retrospective review of management and maternal and neonatal outcomes in a tertiary hospital in Johannesburg, South Africa.

INTRODUCTION: In South Africa, cardiac disease continues to be the most important non-obstetric cause of maternal death. METHODS: A record review of 74 pregnant women with cardiac disease was performed to determine the prevalence and outcomes of cardiac disease at Charlotte Maxeke Johannesburg Academic Hospital between January and December 2017. RESULTS: Rheumatic heart disease was the most common cardiac diagnosis (n = 21, 28.4%), followed by pulmonary hypertension (n = 13, 17.6%) and congenital heart disease (n = 12, 16.2%). There were one (1.4%) maternal and two (2.7%) perinatal deaths. Neonatal complications included pre-term delivery (n = 20, 32.3%) and small-for-gestational-age infants (n = 10, 16.1%). Cardiac complications (n = 30, 40.5%) included heart failure (n = 15, 20.3%), pulmonary hypertension (n = 11, 14.9%) and blood transfusions (n = 8, 10.8%). CONCLUSIONS: Cardiac disease in pregnancy was associated with a high risk of maternal and neonatal complications. Pre-conceptual counselling and managing pregnant women at a dedicated centre by a multidisciplinary team could, however, improve outcomes.

Pregnancy-related venous thromboembolism and HIV infection.

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.

Asymptomatic catheter-related venous thrombosis in a child with cystic fibrosis: When to treat?

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.

Differences in erythrocyte sedimentation rates using a modified Westergren method and an alternate method.

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 K2 EDTA samples at three ESR measurement ranges (<20, 20-80 and >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 < 0.001). iSED ESR measurements were stable up to 24 hours when stored at room temperature or at 4-8°C. CONCLUSION: This study demonstrated differences in ESR results, predominantly at extremes of the analytical range, using an alternate method. Careful consideration and performance monitoring of these novel methods are advised.

Thrombotic thrombocytopenic purpura: A 5-year tertiary care centre experience.

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 < .05). The relapse rate was 9.8% and the mortality rate was 29.3%. CONCLUSION: The high mortality rate emphasises the importance of early diagnosis, referral, and appropriate management of TTP. Anti-retroviral therapy and adherence monitoring are essential to TTP management associated with HIV. Future studies to identify patients at risk for refractory disease are indicated.

A case of a drug reaction to sulfasalazine in a patient infected with HIV.

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.