The clinical significance of differences between point-of-care and laboratory INR methods in over-anticoagulated patients.

INTRODUCTION: Patients receiving warfarin are at increased risk of bleeding when their International Normalised Ratio (INR) >4.5. Although not standardised above 4.5 the INR is measured in over-anticoagulated patients, consequently we have examined the reliability of INR results ≥4.5. We assessed: the relationship between different prothrombin time systems for INRs >4.5; the relationships between the INR and levels of vitamin K-dependent coagulation factors (VKD-CF) and thrombin generation test (TGT) parameters; and the impact that variation in results would have on warfarin dosing. METHODS: INRs were performed using a CoaguChek XS Plus point-of-care (POC) device (measuring range 0.6-8.0). For POC INRs ≥4.5, laboratory INRs were also measured using a recombinant tissue factor (rTF) and a rabbit brain (RBT) thromboplastin. RESULTS: There was good correlation between POC (INR ≥4.5, <8.0) and Lab INRs (rTF n=154, rs=0.87, p<0.0001; RBT n=102, rs=0.76, p<0.0001); and significant correlations between each of the VKD-CF and the INR, the strongest being with FVII (POC INR rs=-0.53 p<0.0001; Lab rTF-INR rs=-0.70 p<0.0001). TGT peak thrombin and ETP also showed good correlations with INR values (R(2)>0.71). Using POC and Lab rTF-INR, 109/154 (71%), or POC and Lab RBT-INR 75/102 (74%) results exhibited dosage concordance and/or were within 0.5 INR units. In the remaining patients variation in warfarin dosing was generally slight. CONCLUSIONS: Our data suggest that CoaguChek XS Plus INRs >4.5 and <8.0 are comparable to laboratory INRs (both methods) and it is probably unnecessary to perform laboratory INRs for clinical management of patients with INRs >4.5 including those >8.0.

Performance evaluation of the Celltac F haematology analyser.

INTRODUCTION: Performance of the Celltac F haematology analyser (MEK-8222) which provides 22 parameters, including a 5-part differential, was compared with the Sysmex XE-2100. METHODS: 242 EDTA samples were investigated. Differential results from both instruments were compared with the reference microscopic count. Flagging performance was compared with cell morphology seen in the blood films. RESULTS: Precision met or exceeded manufacturer's specifications, carryover was minimal (≤1.37%) and linearity was excellent (R ≥ 0.99). Results were stable for at least 8 h at room temperature and for 24 h at 4 °C. Comparisons were excellent for white blood cells, red cell count, Hb, HCT and platelets (R ≥ 0.98). All other red cell and platelet parameters showed good correlation with the XE-2100 (R ≥ 0.93) except for mean cell haemoglobin concentration. The differential was comparable to the XE-2100 for neutrophils, lymphocytes and eosinophils and acceptable for monocytes. Correlation of automated differentials with manual reference counts and the efficiency of flagging of blasts, immature granulocytes and platelet clumps were similar for both instruments. Celltac F demonstrated better efficiency for atypical lymphocyte and platelet clumps. CONCLUSION: The Celltac F shows broadly comparable analytical performance to the XE-2100 for the parameters assessed. The Celltac F is recommendable for medium-sized laboratories or as a back-up instrument in larger laboratories.

Self-monitoring of oral anticoagulation: does it work outside trial conditions?

BACKGROUND: Patient self-monitoring (PSM) of oral anticoagulation therapy (OAT) can improve anticoagulant control, but poor uptake and high dropout rates have prompted suggestions that PSM is suitable for only a minority of patients in the UK. AIMS: To determine whether PSM could be a viable alternative to regular hospital anticoagulant clinic attendance, if offered from the start of treatment. METHODS: 318 consecutive patients referred, for the first time, to an anticoagulation clinic were assessed for eligibility using established criteria. Patients electing for PSM attended training and, following successful assessment, performed a capillary blood INR every two weeks or more frequently if directed to do so by the anticoagulation clinic. Primary outcome measures were uptake of PSM and the percentage time in target therapeutic INR range (TIR) compared to patients electing for routine clinic care. RESULTS: Of 318 patients referred for OAT, 188 were eligible for PSM. 84 (26%) elected to self-monitor, of whom 72 (23%) remained self-monitoring or had completed their course of treatment at the end of the audit. Self-monitoring patients had significantly better anticoagulant control than those receiving routine hospital anticoagulation clinic care (TIR 71% vs 60%, p = 0.003) and significantly less time outside critical limits, ie, INR <1.5 or >5.0 (0.45% vs 2.04%, p = 0.008). CONCLUSIONS: Patients offered PSM from the start of treatment show increased uptake compared to previous UK studies and a level of oral anticoagulation control comparable to that reported in previous clinical trials.

Cardiac involvement in acute thrombotic thrombocytopenic purpura: association with troponin T and IgG antibodies to ADAMTS 13.

INTRODUCTION: Evidence for cardiac involvement in thrombotic thrombocytopenic purpura (TTP) is uncommonly described. METHODOLOGY: We retrospectively reviewed 41 patients assessing troponin T as a marker for cardiac involvement in acute TTP with clinical symptoms, electrocardiograms (ECG) and echocardiograms. A histopathological review of five patients who died of acute TTP was also undertaken. RESULTS: In 54% (22/41) of patients, troponin T was >or=0.05microg L(-1) (normal range 0-0.01 microg L(-1)). Half (12/22) had cardiac symptoms and 8/22 with a raised troponin T reported chest pain. ECG changes were present in 62% of patients with a raised troponin T. Median anti-ADAMTS 13 IgG antibody was significantly higher (P=0.018) in patients with troponin T>or=0.05 microg L(-1) (58.5% (range 17-162%), compared with patients with troponin T<0.05 microg L(-1) (35%, range 9-134%). Patients who died had higher troponin T levels (median 0.305 microg L(-1)) and raised anti-ADAMTS 13 IgG (median 66.5%). On admission, there were no deaths in those with troponin Tor=0.05 microg L(-1)) signify myocardial necrosis associated with microvascular thrombi. Mortality and acute morbidity was associated with higher admission troponin T and raised IgG antibody (>67%) to ADAMTS 13.

Can automated blood film analysis replace the manual differential? An evaluation of the CellaVision DM96 automated image analysis system.

Automation of differentials is desirable for economic and time-saving reasons. Over the last 20 years, automated imaging processes have started to be introduced where stained blood films are scanned by a computer-driven microscope and leucocytes classified; however, early methods were slow and had difficulty in classifying abnormal cells. More recently the CellaVision DM96 (CellaVision AB, Lund, Sweden) has been introduced with added features such as continuous loading of slides and a faster throughput than previous instruments. The accuracy of CellaVision DM96 has been evaluated by comparing results to reference manual differentials. Results from different operators using the DM96 were compared with their own manual differential and to a 400-cell reference manual differential. Precision of the instrument was compared to the manual differential. The preclassification accuracy of the DM96 was 89.2%. Precision was similar to that of the 100-cell manual differential. The DM96 was faster than the manual method, even after reclassification by a laboratory scientist of any cells wrongly categorized by the instrument. The DM96 accuracy in morphological classification of leucocytes and red blood cells; depends upon both blood pathology and experience of the laboratory scientist using the instrument. For some cell types and operators, DM96 accuracy was better than the individual's 100 cell manual differential.

Cryosupernatant and solvent detergent fresh-frozen plasma (Octaplas) usage at a single centre in acute thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is an acute, life-threatening disorder and plasma exchange (PEX) remains the mainstay of treatment. METHODS: We reviewed 50 acute TTP episodes to establish the efficacy and safety of cryosupernatant (CPP) and Octaplas. RESULTS: Twelve episodes used CPP only and 15 episodes started with CPP and changed to Octaplas. Once Octaplas had been used, it was continued on further admissions. Cryosupernatant was used exclusively in 24% and Octaplas exclusively in 42% of all episodes. The number of citrate reactions and allergic (plasma) reactions were halved in those receiving only Octaplas compared with cryosupernatant. There were 22 line infections and in approximately 70% of cases the infection was associated with a reduction in platelet count. In all 50 episodes, the only documented thrombosis was a superficial non-central vein. In episodes receiving only cryosupernatant or Octaplas, there was no significant difference in the median number of PEX to remission, 7.0 (interquartile range, IQR 5-8.8) and 8.0 (IQR 6.5-22), respectively. Baseline viral screen in all episodes was negative after discharge following an acute episode. CONCLUSION: There was no difference in number of PEX to remission with cryosupernatant and solvent/detergent fresh-frozen plasma (Octaplas). However, allergic/urticarial and citrate reactions were more common with cryosupernatant. There was no documented viral transmission with either product.