Only a few patients with heparin‐induced antibodies develop heparin‐induced thrombocytopenia (HIT). In this study, we investigated whether different immunglobulin classes can be used to differentiate between antibody‐positive patients with and without HIT. Four different patient populations were investigated: 32 patients with the immune type of HIT with thromboembolic complications, 13 patients with HIT without thromboembolism, 24 patients with heparin–platelet factor 4 (PF4) antibodies without clinical symptoms of HIT, and 20 heparin‐treated patients with thrombocytopenia caused by other reasons. In all patients the immunglobulin mixture of IgG, IgM and IgA, and the single immunglobulin classes of heparin–PF4 antibodies, were investigated. No significant differences between HIT patients with thromboembolic complications and patients with isolated HIT were found concerning the different immunglobulin classes. Antibody‐positive patients with HIT had significantly higher levels of IgG antibodies than those without HIT (P < 0·05), while they did not differ concerning IgM and IgA antibodies. By determining IgG antibodies, the specificity of the enzyme‐linked immunosorbent assay (ELISA) system was increased without loss of sensitivity. Heparin–PF4–IgG antibodies can identify patients at risk of developing life‐threatening HIT. Future ELISAs should only include this immunglobulin class, as the determination of the antibody mixture may lead to overestimation of HIT.

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Dispositional risk factors for developing the immune-type of heparin-induced thrombocytopenia (HIT) are yet unclear. This article presents a long-term follow-up of patients with HIT to define possible risk factors that may increase the risk of HIT. The clinical course of acute HIT was analyzed retrospectively in 52 patients with HIT. Thirteen patients died; 8 due to HIT. A follow-up investigation was performed in 28 of the remaining 39 patients 29 +/- 12 months after the onset of HIT, including genotyping for the factor V G1691A- and the prothrombin G20210A-mutation, measurement of antithrombin, protein C, protein S, factor VIII, and factor XII activity as well as the concentration of antiphospholipid antibodies. The results were compared to an age- and sex-matched control group. New thromboembolic events and re-exposure to heparin were also documented. No difference between patients and controls was observed concerning the factor V Leiden mutation, the prothrombin mutation, factor XII, antithrombin, protein S, or protein C deficiency and antiphospholipid antibodies. Increased factor VIII activity was found in 16 of 21 HIT patients compared to 4 of 21 controls (p=0.0005). New thromboembolic events developed in 5 patients within 9 months after HIT. One patient had been re-exposed to heparin 9 months after acute HIT without any complications. Increased factor VIII activity was frequently observed in patients in whom HIT developed. Thromboembolic complications within the first months after onset of HIT occurred often.

A constant in vitro hypersensitivity of platelets (adenosine diphosphate) has been suggested as a risk factor for arterial and even venous thrombosis. Our aim was to determine phenotypic and functional alterations of platelets by flow cytometry as potential prothrombotic risk factors in patients with a history of unexplained spontaneous venous thrombosis. Forty-nine patients with a history of spontaneous venous thrombosis and no inherited or acquired thrombophilic risk factors were compared with a reference group of 39 healthy volunteers. Flow cytometry (FACS) was used to analyze the surface expression of CD62 (P-selectin) and CD63 in nonactivated platelets and after in vitro stimulation with adenosine diphosphate and thrombin receptor activator peptide 6. Mean fluorescence intensity of CD62 and CD63 surface expression as well as percentage of CD62 and CD63 positive cells and binding index differed in patients with a history of thrombosis compared with the reference group, but failed to reach statistical significance. Similar results were observed after in vitrostimulation with adenosine diphosphate and thrombin receptor activator peptide 6. In conclusion, the expression of CD62 and CD63 of resting and in vitro activated platelets could not be established as a risk factor for spontaneous venous thromboembolism.

Indications for heparin during pregnancy are expanding. Heparin-induced thrombocytopenia caused by heparin-platelet factor 4 antibodies (HPF4-As), however, remains a serious concern. While up to 50% of cardiovascular surgical patients develop HPF4-As while receiving heparin, the rate of seroconversion is lower in medical patients, suggesting an impact of the patient population on the underlying immune response. We therefore prospectively analyzed HPF4-As development in 31 pregnant women (32 +/- 5 years) receiving thromboprophylaxis with dalteparin for more than 4 weeks. According to their individual risk, study individuals were stratified to receive subcutaneous dosages of 2500-10 000 IU/day. The median treatment duration was 33 weeks (6-45 weeks). HPF4-As isotypes (IgG, IgM, IgA) were measured at baseline, on days 6-9, days 19-21 and subsequently every month until the end of therapy. Platelet counts and clinical examinations were carried out routinely or earlier if indicated. Throughout the study no thromboembolic event occurred, and in none of the patients was HPF4-As seroconversion noted. A prolonged drop in platelets to less than 50% from baseline was observed in one case (3%) after 35 weeks of treatment, which spontaneously resolved after child delivery. These findings suggest that long-term thromboprophylaxis with low-molecular-weight heparin is associated with a low rate of HPF4-As seroconversion in pregnancy.

We found a low adherence with our protocol and substantial over- and undertreatment in VTE prophylaxis. Besides, we identified disregarding of renal function and safety laboratory examinations as additional safety concerns. To identify safety problems associated with medical VTE prophylaxis and "hot spots" quality management-audits proved to be valuable instruments.