An K. Stroobants

Measuring direct thrombin inhibitors with routine and dedicated coagulation assays: which assay is helpful?

The use of direct thrombin inhibitors (DTIs) for prophylactic or therapeutic anticoagulation is increasing because of the predictable bioavailability and short half-life of these DTIs. However, in certain situations, indication of the concentration is warranted. We investigated the effects of 3 DTIs (lepirudin, argatroban, and bivalirudin) in 6 pooled plasma specimens on routine coagulation assays (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]) and dedicated DTI assays (Hemoclot, HemosIL, the ecarin clotting time, and a chromogenic ecarin clotting time) on 2 coagulation analyzers. We found routine tests to be nondiscriminative between concentrations of different DTIs in the aPTT. Moreover, for PT and TT, the responses for different DTIs differed. This was similar for ecarin clotting assays. The Hemoclot and HemosIL assays showed identical linear increases for all 3 DTIs. We conclude that dedicated calibrated assays based on a diluted TT (Hemoclot and HemosIL) appear to be the most suitable for monitoring purposes.

Multicentre evaluation of the Tosoh HbA1c G8 analyser

Abstract Background: We report a Dutch–Belgian multicentre evaluation of the Tosoh HLC-723G8 glycohaemoglobin analyser, an ion-exchange HPLC instrument for the separation and quantification of haemoglobin A1c (HbA1c) in whole blood. Methods: We evaluated the analytical performances of the Tosoh G8 analyser and compared the results for blood samples with its predecessor, the Tosoh G7, and with two other widely used analysers, the Bio-Rad Variant II and Adams Arkray HA-8160. Results: Within- and between-batch imprecision [coefficient of variation (CVs)] was <0.5% and 2%, respectively, and compared favourably with the G7. The excellent performances in terms of speed (1.6 min/analysis) did not result in increased variability of the results or carry-over between samples. The method shows no interference from carbamylated haemoglobin, and recognises the presence of haemoglobinopathies, which triggers the correction of the HbA1c result. Comparison with established methods showed good correlation, not only with the G7 but also with the Variant II and HA-8160 systems. Conclusions: With respect to reproducibility, chromatographic resolution, speed of analysis and identification of Hb variants, the Tosoh G8 analyser can be considered to be state of the art. Clin Chem Lab Med 2010;48:365–71.

Participation, yield, and interval carcinomas in three rounds of biennial FIT-based colorectal cancer screening

BACKGROUND The effectiveness of colorectal cancer screening programs based on the fecal immunochemical test (FIT) is influenced by program adherence during consecutive screening rounds. We aimed to evaluate the participation rate, yield, and interval cancers in a third round of biennial CRC screening using FIT and to compare those with the first and the second screening round. METHODS A total of 3566 average-risk individuals aged 50-75 years were invited to participate in a third round of biennial FIT-based CRC screening. All FIT positives were recommended to undergo colonoscopy. We merged our data with the national cancer registry in the Netherlands to identify all non-screen-detected cancers in our cohort. RESULTS Of the invitees, 2142 (60%) returned the FIT in this third screening round, compared to 56% in the second round and 57% in the first round. Overall, 153 of the third-round participants (7.1%) had a positive FIT result, versus 7.9% in the second round and 8.1% in the first round (P=0.05). Of all FIT positives, 123 (80%) underwent colonoscopy. Within this group, 33 persons had advanced neoplasia. The predictive value of FIT positivity for advanced neoplasia was 27% (33/123), compared to 42% in the second round and 54% in the first round - a significant decline (P<0.01). CONCLUSION In an FIT-based screening program, participation rates remained stable over consecutive biennial screening rounds, while the FIT positivity rate and positive predictive value for advanced neoplasia gradually declined. Cancers in non-participants are significantly more advanced in staging than cancers in participants in the first round of screening.

Catastrophic antiphospholipid syndrome mimicking a malignant pancreatic tumour – a case report

Abstract The catastrophic antiphospholipid syndrome is characterised by rapid onset thromboses, often resistant to conventional anticoagulant treatment, and resulting in life threatening multiple organ dysfunction. The diagnosis of catastrophic antiphospholipid syndrome may be difficult, predominantly due to its frequently atypical presentation. We report a case of a 35-year-old female who presented with a pancreatic tumour and extensive thromboses. Following a storm of ischemic events due to thrombotic occlusions in spite of therapeutic heparin dose, the suspicion of catastrophic antiphospholipid syndrome emerged. The patient was successfully treated with anticoagulants, immunuglobulins, plasmapheresis and rituximab. The present report shows that the use of the diluted Russell’s viper venom time can be helpful in providing additional information on the lupus anticoagulans antibody status, allowing careful monitoring of lupus anticoagulans conversion and hence response to therapy.

The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus

Summary.  Background:  Low‐dose aspirin seems to offer no benefit in the primary prevention of cardiovascular disease in type 2 diabetes mellitus (DM2). The anti‐platelet effect may be diminished by poor glycemic control or inadequate dosing of aspirin.

Hemoglobin Analyses in The Netherlands Reveal More Than 80 Different Variants Including Six Novel Ones

Abstract More than 20 000 blood samples of individuals living in The Netherlands and suspected of hemolytic anemia or diabetes were analyzed by high resolution cation exchange high performance liquid chromatography (HPLC). Besides common disease-related hemoglobins (Hbs), rare variants were also detected. The variant Hbs were retrospectively analyzed by capillary zone electrophoresis (CZE) and by isoelectric focusing (IEF). For unambiguous identification, the globin genes were sequenced. Most of the 80 Hb variants detected by initial screening on HPLC were also separated by capillary electrophoresis (CE), but a few variants were only detectable with one of these methods. Some variants were unstable, had thalassemic properties or increased oxygen affinity, and some interfered with Hb A2 measurement, detection of sickle cell Hb or Hb A1c quantification. Two of the six novel variants, Hb Enschede (HBA2: c.308G > A, p.Ser103Asn) and Hb Weesp (HBA1: c.301C > T, p.Leu101Phe), had no clinical consequences. In contrast, two others appeared clinically significant: Hb Ede (HBB: c.53A > T, p.Lys18Met) caused thalassemia and Hb Waterland (HBB: c.428C > T, pAla143Val) was related to mild polycytemia. Hb A2-Venlo (HBD: c.193G > A, p.Gly65Ser) and Hb A2-Rotterdam (HBD: c.38A > C, p.Asn13Thr) interfered with Hb A2 quantification. This survey shows that HPLC analysis followed by globin gene sequencing of rare variants is an effective method to reveal Hb variants.

Fecal immunochemical testing results and characteristics of colonic lesions

BACKGROUND AND STUDY AIMS Fecal immunochemical tests (FIT) are used to detect blood in feces, which might indicate the presence of colorectal neoplasia. The aim of this study was to investigate whether FIT results vary depending on the characteristics of colonic lesions. PATIENTS AND METHODS This was a retrospective analysis of lesions detected in a cohort of asymptomatic individuals (aged 50 - 75 years) who were invited to participate in a FIT-based screening pilot in The Netherlands. The mean FIT result was compared across subgroups of individuals defined by histopathology of the most advanced lesion detected. In addition, the results were compared with data from a primary colonoscopy screening trial, in which participants also completed a FIT. RESULTS In three rounds of FIT-based screening, a total of 877 FIT-positive individuals underwent colonoscopy. Higher mean FIT results (hemoglobin [Hb]/g feces) were observed in individuals with carcinomas (199 μg Hb/g) and advanced adenomas (87 μg Hb/g) compared with participants with nonadvanced adenomas (50 μg Hb/g) or those with serrated lesions (46 μg Hb/g) (P < 0.001). In the primary colonoscopy trial, 1256 participants completed a FIT test and underwent colonoscopy. The number of participants with nonadvanced adenomas as the most advanced lesion was comparable between this group and the FIT-based screening group (20 % vs. 22 %). CONCLUSION In FIT-based screening, the mean FIT results varied depending on the characteristics of the most advanced colonic lesion. The proportion of participants with a nonadvanced adenoma as the most advanced lesion was similar in the FIT-based screening group and in the primary colonoscopy screening group, suggesting that these lesions are coincidental findings rather than FIT-detected findings. CLINICAL TRIAL REGISTRATION www.trialregister.nl number NTR2755.

Inappropriate use of the faecal occult blood test in a university hospital in the Netherlands.

Objectives Although all international guidelines state that there is no indication to perform a faecal occult blood test (FOBT) in symptomatic patients, we believe the test is frequently used as a diagnostic test. The objective of this study was to investigate whether the current guidelines for FOBT use are being followed in the Netherlands. Methods The frequency of reasons for ordering a FOBT in 15 hospitals over a time period of 1 year was determined and the consequences of the test result on the diagnostic workup were determined by a retrospective search of electronic hospital charts. Results In 14 of the 15 hospitals a FOBT was available and totally 2993 FOBTs were performed in 1 year. A total of 201 electronic charts were retrieved. The FOBTs were ordered because of anaemia (41%), suspicion of rectal bleeding (17%), abdominal pain (14%), changed bowel habits (10%) or others (18%). A positive test result was found in 66 (33%) patients and a negative in 133 (66%). Respectively, 38% (25/66) of the patients with a positive and 41% (55/133) of the patients with a negative test result received a gastrointestinal follow-up investigation. In 25/80 investigations, a possible cause of rectal blood loss was detected, of which 13 had a positive FOBT result. Conclusion This study demonstrates that current guidelines on FOBT use are not followed in the Netherlands and that a FOBT is often used as a diagnostic tool instead of a screening tool, thereby causing confusion and unnecessary delays in the diagnostic workup of patients.

Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography.

Abstract Background: Haemoglobin (Hb) variants are well-known factors interfering with accurate HbA1c testing. This report describes two novel Hb variants leading to inappropriate quantification of HbA1c by ion-exchange chromatography. Methods: Glycated forms of novel Hb variants were recognised in the blood of two patients with diabetes mellitus screened by HbA1c ion-exchange chromatography. Dedicated high-resolution cation-exchange chromatography and subsequent DNA sequencing revealed the exact nature of the variants. Other common techniques for quantifying HbA1c were applied on both samples and haematological parameters were determined to judge possible pathology associated with the novel Hb variants. Results: A fraction of 15% of abnormal Hb was observed in a 37-year-old female. DNA sequencing revealed a heterozygous mutation in the α1-globin gene, resulting in a leucine-to-phenylalanine amino-acid substitution (HBA1: c.301C>T, p.Leu101Phe). We named this variant Hb Weesp. The other novel variant, Hb Haelen, presented as a 40% fraction in a 63-year-old male and resulted from a heterozygous amino acid substitution in the β-globin gene (HBB: c.335T>C, p.Val112Gly). The presence of both Hb variants resulted in aberrant separation of the Hb components, leading to an inadequate quantification of HbA1c. Conclusions: Close examination of HbA1c chromatograms revealed two novel, clinically silent Hb variants that interfere with HbA1c quantification. Healthcare providers need to be aware of the potential of such Hb variants when interpreting HbA1c results.

Successful co-administration of dabigatran etexilate and protease inhibitors ritonavir/lopinavir in a patient with atrial fibrillation

Successful co-administration of dabigatran etexilate and protease inhibitors ritonavir/lopinavir in a patient with atrial fibrillation -