Biological and clinical features of low‐molecular‐weight heparin‐induced thrombocytopenia

Abstract

Summary. Heparin‐induced thrombocytopenia (HIT) is a common adverse effect of unfractionated heparin (UFH) therapy. In contrast, only a few patients have been reported with HIT following low‐molecular‐weight heparin (LMWH) therapy (LMW‐HIT). To define the clinical and biological characteristics of LMW‐HIT, 180 patients treated for suspected HIT at 15 French centres were investigated. Clinical history was recorded and HIT was confirmed in 59 patients with positive serotonin release assay results: 57 of them had high levels of antibodies (Abs) to heparin–platelet factor 4 complexes (H/PF4) and two had Abs to interleukin 8. Eleven patients were treated exclusively with LMWH (LMW‐HIT) and 48 with UFH either alone (UF‐HIT, n = 34) or combined with LMWH (UF/LMW‐HIT, n = 14). The LMW‐HIT and UF‐HIT groups were similar with respect to sex, age, platelet count before heparin therapy, frequency of bleeding and occurrence of disseminated intravascular coagulation. The interval to onset of HIT was longer in LMW‐HIT patients compared with UF‐HIT patients (P = 0·03). Severe thrombocytopenia (platelets < 15 × 109/l) was more frequent in the LMW‐HIT group (P = 0·04). Thrombosis occurred in three of 11 LMW‐HIT patients, i.e. as frequently as in UF‐HIT patients. LMW‐HIT is potentially severe and may be observed after longer heparin treatment compared with UF‐HIT. It is highly recommended, therefore, that platelet counts be monitored carefully whenever LMWH is administered.

The temporal profile of the anti-PF4/heparin immune response

“…However, there is increasing evidence that patients who have a history of clinical HIT do not show a typical anamnestic immune response when reexposed to heparin. 8,11,33 On the contrary, other reports 34,35 suggested that there might sometimes be a more rapid formation of heparin antibodies in the case of reexposure. But neither of these studies 34,35 established that their patients had had 2 distinct episodes of HIT.…”

“…8,11,33 On the contrary, other reports 34,35 suggested that there might sometimes be a more rapid formation of heparin antibodies in the case of reexposure. But neither of these studies 34,35 established that their patients had had 2 distinct episodes of HIT. Moreover, 2 reports in which patients did clearly have 2 distinct episodes of serologically confirmed HIT several years apart found that the onset of thrombocytopenia during the second episode of HIT appeared to be no sooner than that observed during the first episode of HIT.…”

Anti‐PF4/heparin antibody formation postorthopedic surgery thromboprophylaxis: the role of non‐drug risk factors and evidence for a stoichiometry‐based model of immunization

“…Indeed, enoxaparin and fondaparinux were administered in these four clinical trials for a mean of only approximately 7 days [19], likely contributing to the low frequency of clinical HIT observed, and rendering clinical HIT unsuitable as an end point for these analyses, especially given that HIT as a result of LMWH administration may take longer Risk factors for anti-PF4/heparin antibodies 511 to develop than HIT triggered by UFH [20]. Of interest, the single case of HIT identified (Fig.…”

Case studies in anticoagulation management

“…The risk of thrombosis without further treatment is 10-15% in 2 days, 40% in 1 week and 53% in 1 month [28][29][30][31][32][33][34][35][36]. The type of thromboembolic events is 50% DVT, 25% PE, 5-10% acute limb ischemia, 20% amputation and 3-5% acute myocardial infarction (AMI) [28][29][30][31][32][33][34][35][36]. HIT mortality may be as high as 30-50% [28][29][30][31][32][33][34][35][36].…”