Lara Fenu

Point-of-care (POCT) prothrombin time monitors: is a periodical control of their performance useful?

INTRODUCTION Point-of-care testing (POCT) prothrombin time monitors are now widely used to monitor oral anticoagulant treatment. Although portable coagulometers are extremely easy to use, checking the quality of their performance presents some difficulties. MATERIALS AND METHODS The aims of this study were to investigate on a quarterly basis the performance of 95 Coagucheck S assigned to 99 anticoagulated patients at home. This was done checking the monitors versus a reference coagulometer in the laboratory at our Thrombosis Centre (TC). The other aims were to carry out an external quality assessment employing different sets of INR certified plasmas with 5 different ranges of anticoagulation and to assess the performance of the different lots of strips employed by the patients during the study. RESULTS No difference between the PT INR obtained with both the systems at the first quarterly check was noted but a significant difference was found when the two systems were compared at the second and third quarterly checks. The Bland-Altman test showed increased disagreement between the first and the third controls. The percentage of INR values that showed a difference of more or less than 0.5 INR units in the PT values performed with both the systems was: 1.0% (first control), 7.5% (second control) and 11.5% (third control) (Chi-Square: 8.315, p=0.0156). Lots with differences higher than 10% in terms of +/- 0.5 INR Units at the first, second and third controls were 16%, 20.8% and 61%, respectively. Seven monitors (7.3%) failed to test one or two of the INR certified plasmas of one set but performed well using a second set of plasmas. Three monitors (3.1%) failed to test two sets of plasmas but performed well using a different lot of strips (from 279A to 483A). One monitor (1%) gave unsatisfactory results with different sets of plasmas and strips. All the other PT INR obtained with the monitors fell well within the different ranges of the INR certified plasmas. CONCLUSIONS Anticoagulated patient in self-testing or self-management should periodically bring their portable coagulometer to a reference Thrombosis Centre especially when the lot of strips have to be changed. The role of Thrombosis Centre appears therefore crucial in this regard.

Allele 4G of gene PAI-1 associated with prothrombin mutation G20210A increases the risk for venous thrombosis

Several studies have tried to clarify the role of polymorphism 4G/5G of the PAI-1 gene in venous thromboembolism without reaching any final conclusion. It has been demonstrated that this polymorphism may induce an increased risk for venous thromboembolism (VTE) in patients with thrombophilic defects. We studied the association of prothrombin mutation G20210A with 4G/5G polymorphism in 402 VTE patients and 466 healthy controls. Patients affected by prothrombin mutation G20210A, with or without the concomitant presence of allele 4G, had a 3.7 thrombotic risk (C.I. 95% 2.3-6.0; p<0.0001). Moreover, genotype 4G/4G is a mild risk factor for VTE, irrespectively of whether the prothrombin mutation was present. Logistic regression analysis showed that patients carrying the G20210A prothrombin mutation with allele 4G gave an odds ratio for VTE of 6.1 (C.I. 95% 3.2-11.4; p<0.001). The risk increased up to 13.0 (C.I. 95% 3.0-60.4; p<0.001) when we considered the association of the prothrombin mutation with genotype 4G/4G. The G20210A mutation without allele 4G (5G/5G) was not a risk factor for VTE. In conclusion, we believe that patients affected by VTE with concomitant presence of the G20210A prothrombin mutation could be tested for genotype 4G/4G to better define their thrombotic risk.

Bleeding diathesis and gastro-duodenal ulcers in inherited cytosolic phospholipase-A2 alpha deficiency

Arachidonic acid (AA), when cleaved from phospholipids by cytosolic phospholipase A2 alpha (cPLA2a), generates eicosanoids, with pro-hemostatic, pro-inflammatory, vasoactive and gastro-protective functions. We describe a patient (27-year-old man) and his twin-sister with early-onset bleeding diathesis and recurrent gastro-intestinal (GI) ulcers. Platelet aggregation/δ-granules secretion by collagen was impaired, but normal by AA; serum levels of thromboxane (Tx) B2 and 12-hydroxyeicosatetraenoic acid, and urinary levels of 11-dehydro-TxB2 were extremely low. Patients were homozygous for 1723G>C transition in PLA2G4A gene, which changed the codon for Asp575 to His. GI ulcers affected 5/14 heterozygous (< 40 years) and 1/16 wild-type homozygous (> 60 years) family members; none had bleeding diathesis. The proband, his sister and mother also had mildly reduced factor XI levels. Platelet messenger RNA expression did not differ among subjects with different PLA2G4A genotypes. Conversely, platelet cPLA2a was undetectable by Western Blotting in the proband and his sister, and decreased in 1723G>C heterozygous subjects, suggesting that the variant is transcribed, but not translated or translated into an unstable protein. We described a syndromic form of deficiency of cPLA2a , characterised by recurrent GI ulcers and bleeding diathesis, associated with mild inherited deficiency of factor XI. Unlike other reported patients with cPLA2a deficiency, these patients had extremely low levels of platelet TxA2 biosynthesis.

Telemedicine can improve the quality of oral anticoagulation using portable devices and self-testing at home

Point-of-care testing (POCT) devices can be used to monitor anticoagulant therapy. We compared patients being monitored at home by self-testing using a POCT device and telemedicine support with a previous period of conventional monitoring at a Thrombosis Centre. A total of 114 anticoagulated patients participated. The number of blood checks (INR) was significantly higher in the home monitoring group and the interval between checks was significantly shorter. The percentage of missed INR checks was significantly higher during the conventional monitoring period compared with home monitoring. Patients were divided into two groups on the basis of the time spent within the therapeutic range (TTR) during conventional monitoring: the unstable group had TTR<70% and the stable group had TTR ≥70%. In the unstable group there was a significant increase in TTR with home monitoring: 63% to 68% (P < 0.001) while in the stable group there was no significant change (77% to 75%). The study showed that oral anticoagulation management by means of self-testing is suitable and safe.

Point-of-care testing INR: an overview

Abstract Oral anticoagulant therapies with the anti-vitamin K drugs (AVK), warfarin, acenocoumarol and phenprocoumon, are employed in primary and secondary anti-thrombotic prophylaxis in patients with venous thromboembolism, atrial fibrillation and cardiac mechanical valves. However, a monitoring test such as the International Normalized Ratio (INR) is required. The periodic monitoring of this therapy entails discomfort for the patients. Telemedicine and telecare can provide significant aid in the management of this therapy allowing patients to perform the test at home or anywhere else with a portable device, i.e. point-of-care testing (POCT), and to send the result to a thrombosis (TC) via web. Patients can receive dose adjustment sent back by the TC. The effectiveness of this type of management is equal or superior to the traditional AVK monitoring in terms of hemorrhagic and thrombotic events. Analysis of the costs with a horizon of 10 years reveals that both self-testing and self-management are cost-effective. The aim of this overview is to describe the pros and cons of the use of POCT as an alternative in the monitoring of AVK. In particular, description of the POCT, decentralization, quality of the therapy, safety and costs will be examined.

Oral anticoagulant therapy and telemedicine.

We read the interesting paper by Testa et al.1 and the editorial comment by Pengo2 about the devolution of oral anticoagulant therapy (OAT) by using a telemedicine system that involves rest houses, peripheral hospitals and general practitioners. The architecture of the system, which improves quality of therapy and patient satisfaction, as those preliminary findings report, seems to be a valid future alternative in the monitoring of OAT. A few months ago, the Anticoagulation Clinic (AC) of Cagliari (Italy), which operates in the frame of the Italian Federation of Anticoagulation Clinics (FCSA), has started a similar project, by involving about 150 patients in selftesting and a control group matched for sex, age and diagnosis, followed by the AC and monitored by TAONET (EDP-Progetti, Bolzano, Italy). Patients were all on chronic OAT and criteria for enrollment in the study were the following: patients on OAT since at least 3 months; patients who cannot leave home because of serious physical illness, advanced age; patients who live far from the AC, lack of time due to hard work. The main outcomes of the study were the following: a) overdosage states, b) thrombotic and haemorrhagic events, c) time spent in the therapeutic range, and d) quality of life assessed by means of a questionnaire. After a training course, every patient received a portable coagulometer3 (Coagucheck S, Roche Diagnostics, Basel, Switzerland), which was submitted to a 3-monthly quality control by comparing the prothrombin time-INR measurement with that of the AC. We also asked the software house to create a personal and safe account to connect the patient to the referring AC through a web site. This procedure allows patients to interact with the AC where we use a system (TAONET), firstly designed by MM in 1999, to devolve OAT monitoring on territorial settings. We report here a brief description of the system: TAONET allows patient management in the territorial settings coordinated and assisted by the referring AC, the application to the involved territorial seats of the same quality standards as those of the AC, the extension of the procedure to all the remaining territory, with differentiated supports, according to the dedicated caregiver or to the patient himself. The system is developed on an Oracle standard procedure and is organised as a centralised netsupported program. The hardware is composed of a modular system, using a server and PC stations in the AC and workstations in the peripheral districts, and utilised by family doctors, nurses, pharmacies, and rest houses. Patients in self-testing can rely on a bidirectional connection with the AC; they can send their clinical data (e.g. pharmacological variations, intervening diseases, complications, etc.) and the INR value (obtained by portable monitor) by compiling a pre-set electronic datasheet and by receiving the schedule with the adjusted dose regimen at home in no more than 10 min. The questionnaire is relevant to dose assumption, pharmacological variations, possible haemorrhagic events, surgery, diet behaviour, and gives the patients the possibility of sending to doctors at the AC personal comments about the reported events. Every modification in therapy or in the clinical status will be simultaneously registered by the central data-base and will remain under control of the dedicated staff of the AC. The system allows a manual dose adjustment or an electronic proposal by the dose calculation algorithm of the program. Monitoring patients in self-testing could lead to an improvement in quality of life of the single patient even greater than that of patients monitored by the family doctors or by the nursing centres since it can be considered an “at home OAT monitoring”, under the direct control of the AC. Moreover, these patients have the possibility of interacting with the AC via this system, even when they are outside home or abroad, by simply finding an Internet point and using their personal connection to the web site. In conclusion, we think that in the near future this system could significantly improve the management of patients treated with coumarins. Even if this system will not be immediately available to all patients, a considerable proportion will save time and money, by simultaneously reducing the huge overcrowding in the AC. Coumarins could therefore be more resistant to the entry of new anticoagulants and to be still the drugs of choice in particular settings. Finally, a system like the TAONET could be helpful in the clinical monitoring of patients treated with new anticoagulants, which do not need a laboratory control as recently suggested4. A progressive lack in time of adherence to therapy may occur. Patients could periodically interact with the AC by answering a simple questionnaire on drug assumption, their general