A b s t r a c tHeparin-induced thrombocytopenia is a side effect of heparin therapy. In contrast to other drug-associated thrombocytopenias, however, the most frequently observed complication is not hemorrhage but thrombosis.

Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP). This multicentre study of the French-speaking CAT Club aimed at providing further evidence for the usefulness of such a normalisation

Summary. Heparin-induced thrombocytopenia (HIT) is frequently associated with antibodies (Abs) to heparin-PF4 complexes (H-PF4). In order to investigate whether there are variations in specificity of Abs, we studied 63 samples from patients with suspected HIT. Two groups of samples were separated after comparing their reactivity against H-PF4 or recombinant PF4 (r-PF4) using ELISA. In group Ab1 (n ¼ 46), Abs only or mainly bound to H-PF4 complexes and thus most of the epitopes recognized probably involved both heparin and PF4. In group Ab2 (n ¼ 17), Abs exhibited similar reactivity to r-PF4 and H-PF4, and the antigens recognized were possibly neoepitopes mainly expressed by modified PF4 and by H-PF4 complexes. Platelet activation tests were positive with 56 samples containing high titres of Abs to H-PF4. Most samples (n ¼ 59) contained IgG antibodies, often associated with IgA antibodies which were more frequently found in group Ab2, and/or IgM. With unfractionated heparin treatment, HIT was associated with Ab1 or Ab2 antibodies, whereas only Ab1 antibodies were detected after low-molecular-weight heparin (LMWH). Furthermore, cross-reactivity with danaparoid sodium was present only in group Ab1 and mainly involved LMWHtreated patients.

This report concerns 34 cases of heparin-associated thrombocytopenia in which standard heparin has been systematically replaced by LMW heparin CY 216 Choay. There were 21 women and 13 men, mean age, 69 years. Twenty-six of the 34 cases had thrombotic complications. All of the patients were treated by standard heparin of porcine mucosal origin, in most cases for prevention of deep vein thrombosis and pulmonary embolism. Twenty-six cases occurred along with orthopedic and traumatologic surgery (especially for total hip replacement, 15 cases). Four cases involved vascular surgery and three involved medical thrombotic disease. Standard heparin treatment was always replaced by LMW heparin CY 216. Initial doses were 0.30 ml three times daily, later increased to obtain global hypocoagulability. Surgical procedures (embolectomy and vena cava filter) were carried out when necessary. Five patients had thrombolytic treatment (urokinase) in conjunction with LMW heparin. The overall results were 31 recoveries, but with seven severe sequelae (three amputations and four hemiplegias) most often attributable to the first ischemic attack, and three deaths. For the last 16 patients, indirect platelet aggregation tests were performed (control platelet-rich plasma plus patient platelet-poor plasma plus LMW heparin): nine cases had negative tests, with nine recoveries and seven cases had positive tests, with five recoveries and two deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Several reagents are available to perform activated partial thromboplastin time (APTT) that is a key test in routine haemostasis laboratories. However, the ability of APTT reagents to detect specific coagulation factor deficiencies may be affected by several variables, including the origin (human, animal or vegetable), composition, configuration of phospholipids and the type of surface activator. These variations in sensitivity explain why specialized haemostasis laboratories often use several different APTT reagents for specific and variable applications, i.e. control of heparin therapy, screening for lupus anticoagulant, evaluation of coagulation status before surgery and one-stage APTT-based assays for measurement of factor VIII (FVIII), factor IX (FIX), factor XI (FXI) and factor XII (FXII) plasma levels.We have recently tested the Actin FS Ò reagent (Dade Behring, Marburg, Germany) in our laboratory and recorded higher FIX activity levels (FIX:C) in several haemophilia B (HB) patients than those previously assayed with our usual reagent. We therefore initiated a multicentre study in a larger sample of patients to confirm these results and to identify the reasons explaining such discrepancies in the results obtained.Three hospital haematology laboratories participated in this study: Tours (central laboratory), Caen and Nantes. Blood samples were obtained from 40 patients previously diagnosed as having HB and not regularly treated with plasma-derived or recombinant factor IX (rFIX) concentrates. The basal FIX:C level in these patients was £1 IU dL )1 (n = 6), between 1 and 5 IU dL )1 (n = 10), or between 5 and 40 IU dL )1 (n = 24). FIX antigen levels (FIX:Ag) were also measured in these 40 untreated HB patients using Asserachrom Ò IX:Ag (Stago, Asnières, France), and the values obtained were compared with FIX:C levels. In 13 patients FIX:Ag levels were comparable with those of procoagulant activity (FIX:C/FIX:Ag >0.7), and these patients were defined as having a Ôtype 1Õ FIX deficiency. In contrast, the amount of FIX measured by immunological assay in the plasma from 27 HB patients was markedly higher than functional level. These patients therefore exhibited a FIX:C/FIX:Ag ratio lower than 0.7 and were defined as having a Ôtype 2Õ FIX deficiency.Factor IX:C level was measured by one-stage assay carried out on a STAR Analyzer (Stago) which is used in the majority of reference laboratories in France. All analyses were performed in duplicate on plasma aliquots which had been stored at )80°C after double centrifugation to ensure efficient platelet depletion and the same reagent batches were used in all three centres.Three APTT reagents were used: CKPrest Ò from Stago (rabbit brain thromboplastin + Kaolin), PTTA Ò from Stago (rabbit brain thromboplastin + silica) and Actin FS Ò from Dade Behring (soy phospholipids + ellagic acid). For each APTT reagent, calibration curves from 100 to 12.5 IU dL )1 were obtained by diluting standard human plasma (RKL) from 1/5 to 1/80 in FIX-deficient plasma (both reagents from Dade...