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Summary. Background: Recent studies have shown that a low clinical pretest probability may be adequate for excluding heparin-induced thrombocytopenia. However, for patients with intermediate or high pretest probability, laboratory testing is essential for confirming or refuting the diagnosis. Rapid assessment of anti-PF4/heparin-antibodies may assist clinical decision-making. Objectives: To evaluate the performance of rapid ID-H/PF4-PaGIA. In particular, we verified reproducibility of results between plasma and serum specimens, between fresh and frozen samples, and between different ID-H/PF4-polymer lots (polystyrene beads coated with heparin/PF4-complexes). Patients/Methods: The samples studied were 1376 plasma and 914 corresponding serum samples from patients investigated for suspected heparin-induced thrombocytopenia between January 2000 and October 2008. Anti-PF4/heparin-antibodies were assessed by ID-H/PF4-PaGIA, commercially available ELISAs and heparin-induced platelet aggregation test. Results: Among 914 paired plasma/serum samples we noted discordant results (negative vs. low-titre positive) in nine instances (1%; 95%CI, 0.4–1.6%). Overall, agreement between titres assessed in plasma vs. serum was highly significant (Spearman correlation coefficient, 0.975; P

Hereditary plasma prekallikrein (PK) deficiency was diagnosed in a 71-year-old man with an 8-year history of osteomyelofibrosis. PK deficiency was suspected in view of a severely prolonged activated partial thromboplastin time (aPTT) that nearly normalized following prolonged preincubation (10 min) of patient plasma with kaolin-inosithin reagent. Hereditary PK deficiency was demonstrated by very low PK values in the propositus (PK clotting activity 5%, PK amidolytic activity 5%, PK antigen 2% of normal plasma, respectively) and half normal PK values in his children. Normalization of a severely increased aPTT (>120 s) after prolonged preincubation with aPTT reagent occurred in plasma deficient in PK but not in plasma deficient in factor XII (FXII), high-molecular-weight kininogen (HK), factor XI (FXI), factor IX, factor VIII, Passovoy trait plasma or plasma containing lupus anticoagulant. Autoactivation of FXII in PK-deficient plasma in the presence of kaolin paralleled the normalization of aPTT. Addition of OT-2, a monoclonal antibody inhibiting activated FXII, prevented the normalization of aPTT. We conclude that the normalization of a severely prolonged aPTT upon increased preincubation time (PIT), characteristic of PK deficiency, is due to FXII autoactivation.

H eparin-induced skin necrosis, first described by O'Toole [1] in 1973 has since been recognized as a rare side effect of heparin therapy. This phenomenon may accompany the more frequently occurring heparin-associated thrombocytopenia and thrombosis syndrome (HATT) [2] and seems to be independent from dose [3,4]. In most reported cases, heparin-induced skin necrosis occurred after subcutaneous heparin administration, but in a few instances it has also been observed with intravenous use of the drug [5]. Bovine heparin was found to bear a greater potential of causing H A T T than do porcine mucosal dr low-molecularweight heparins [3,6,7]. Heparin-associated thrombocytopenia presents in two distinct forms [8]: the first is a mild, transient thrombocytopenia beginning within two to five days after starting heparinization; the pat ient remains asymptomatic. The second, severe form occurs after an interval of at least six days from initiating heparin administration and is accompanied in more than half of the cases by thromboembolic complications. Unlike the former, this late-onset heparinassociated thrombocytopenia does not resolve unless the drug is discontinued. Pathogenetically, an IgG antibody causing heparin-dependent platelet aggregation has been found in plasma from patients with lateonset thrombocytopenia [8]. Intravascular platelet aggregation in the presence of therapeut ic heparin concentrations may be responsible for the frequently fatal thromboembolic complications seen with continued heparinization [4]. We describe a patient with heparin-associated skin necrosis, thrombocytopenia, and deep vein thrombosis. The patient's plasma consistently induced fast and pronounced heparin-dependent aggregation of normal platelets from several donors. In order to assess the specificity of this in vitro test, 159 control plasma samples were examined.