Skin Necrosis at the Injection Site Induced by Low-Molecular-Weight Heparin: Case Report and Review

Abstract

Heparin-induced skin necrosis at the injection site is a rare adverse effect, more commonly associated with standard heparins than with low-molecular-weight heparins (LMWH) and its mechanism remains unclear. We report a case of LMWH-induced skin necrosis in a female during prophylactic treatment with LMWH after a surgical procedure. Determination of heparin-platelet-factor-4(PF4)-induced antibodies was positive. This case describes the occurrence of LMWH-induced skin necrosis and antibodies to heparin-PF4 complex, suggesting that this effect is more frequent than previously suspected.

Low molecular weight heparin-induced skin necrosis—a systematic review

“…Of these, we identified 20 reported cases of LMWH-induced skin necrosis (Table 1) [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Thus, a total of 21 cases was reviewed, including the case from our clinic.…”

“…The size of the necrotic areas varied, but generally appeared small and circumscribed, with a maximum diameter of a few centimetres. Occasionally, the skin necrosis enlarged to more than 10 cm [11,13,14,19,23], in one case involving 6% of the body surface area [24].…”

“…Platelet count was within the normal range in ten cases, while severe thrombocytopenia occurred in four of 19 patients (thrombocyte concentration <100,000 cells/ml) [13,18,20,21] and mild thrombocytopenia (thrombocyte concentration 100,000 cells/ml-150,000 cells/ml) in five of 19 patients [19,[23][24][25]28]. Two articles did not report on platelet concentrations [16,26].…”

“…After diagnosis of LMWH-induced skin necrosis, antithrombotic therapy was switched to coumarin (n=5) [12,15,18,20,27], unfractionated heparin (n=5, subcutaneous UFH n=2, intravenous UFH n=3) [10, 11, 14, 21, present case], aspirin (n=3) [13,19,23], and hirudin (n=2) [25,28]. In two cases, anti-thrombotic therapy was stopped [22,24], and in four cases data on anticoagulant switch were not reported [16,17,26].…”

Akral betonte Hautnekrosen

“…[12].Sie werden jedoch auch -wenngleich seltener -nach Applikation niedermolekularer Heparine beobachtet; hierüber existieren etwa 40 Fallberichte sowohl nach subkutaner als auch nach intravenöser Applikation [5,13].Heparininduzierte Hautnekrosen treten meist an der Injektionsstelle auf, seltener wurde ein disseminiertes Auftreten beschrieben [2,4,6,14].Der zugrunde liegende Pathomechanismus ist bisher unklar; am wahrscheinlichsten ist eine Typ-III-Allergie mit Ausbildung von Antikör-pern gegen Komplexe aus Heparin und Thrombozyten [15].Passend zu dieser Hypothese können heparininduzierte Hautnekrosen mit einer heparininduzierten Thrombozytopenie (HIT) Typ II einhergehen [1,16], die über eine Thrombozytenaggregation und -aktivierung zu thromboembolischen Komplikationen führen kann.…”