Heparin-Induced Thrombocytopenia, Paradoxical Thromboembolism, and Other Side Effects of Heparin Therapy

Walenga, Jeanine M.; Bick, Rodger L.

doi:10.1016/s0025-7125(05)70015-8

Cited by 90 publications

(93 citation statements)

References 53 publications

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“…Heparin is widely used as an anti-coagulant for the treatment of thrombosis (28). Parenteral administration of heparin can result in severe side effects such as heparin-induced thrombocytopenia, elevation of serum aminotransferase levels, hyperkalemia, alopecia, and osteoporosis (29). The sRBCs showed high amounts of heparin loading (70 g heparin per mg particles) and continuous release over a period of several days in vitro (Fig.…”

Section: Resultsmentioning

confidence: 99%

Red blood cell-mimicking synthetic biomaterial particles

Doshi

Zahr

Bhaskar³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

328

270

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Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.biomimetic ͉ drug delivery ͉ erythrocyte ͉ imaging ͉ nanotechnology

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Section: Resultsmentioning

confidence: 99%

Red blood cell-mimicking synthetic biomaterial particles

Doshi

Zahr

Bhaskar³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

328

270

View full text Add to dashboard Cite

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“…Finally, increasing levels of heparin increased the number and occlusiveness of aggregates in the blood of High Responders. Thus, either the formation of the thrombinÀantithrombin complex does not play a key role in the HIPA mechanism, or heparin may also activate other pathways such as with heparin-induced thrombocytopenia and thrombosis syndrome (HIT-TS) [51].…”

Section: Discussionmentioning

confidence: 99%

Hypothermia‐induced platelet aggregation in heparinized flowing human blood: Identification of a high responder subpopulation

Hall¹,

Goodman²,

Alston³

et al. 2001

American J Hematol

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Cold-induced platelet aggregation (CIPA) in PRP has previously been documented in connection with platelet preservation (4±15°C). This report describes hypothermia-induced platelet aggregation (HIPA) in whole blood and at temperatures used in open-heart surgery (24±32°C). HIPA (speci®cally, the formation of occlusive aggregates) was studied in human whole blood. Fresh heparinized (1.5 U/ml) human blood was cooled and maintained at target temperatures (15, 20, 24, 28, 32, or 37°C) as it¯owed (1 ml/min) through 75-cm long 1/32" internal diameter polymer conduit. The formation of aggregates in the tubing was veri®ed using optical video microscopy and was quanti®ed by a lightscattering method and a constant-pressure ®ltration method. Donors were tested at least twice at each target temperature and were classi®ed into three separate response regimes (Low, Medium, and High) on the basis of the number of aggregates and the duration of their appearance. The screening of 121 donors (average age 22.3 4.3 years) for HIPA at 24°C (the temperature of maximum response) indicated 14% High Responders, 18% Medium Responders, and 68% Low Responders. HIPA was inhibited by EDTA, citrate, PGE 1 , and Tiro®ban, but not by aspirin, and it was enhanced by elevated heparin levels. HIPA was consistently noted in the blood of a subpopulation of donors, and the associated platelet aggregates in the blood of High Responders were rigid and occlusive. It is postulated that such aggregates may contribute to cognitive dysfunction noted in patients undergoing hypothermic open-heart surgery, and that postulus is being investigated. Am.

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“…Although the use of UFH and LMWH are associated with bleeding, anaphylaxis, and osteoporosis, HIT is generally the most serious adverse effect of these drugs. [1][2][3] A potential advantage of LMWH from clinical and cost perspectives is a lower risk for HIT. HIT can be categorized as the immunemediated form, or HIT type 2, and as the nonimmunogenic form, or HIT type 1.…”

Section: Introductionmentioning

confidence: 99%