Case Report: Maggots' Infestation As a Predisposing Condition for Heparin-Induced Thrombocytopenia, a Newest Entity

Introduction

Thromobocytopenia is a well-recognized complication of heparin with risk of venous or arterial thrombosis. Heparin induced thrombocytopenia, Type I (HIT-I) is a self-limiting, nonautoimmune, and most common form of thrombocytopenia. Heparin induced thrombocytopenia, Type - II (HIT-II) is an immune mediated and serious adverse drug reaction caused by formation of heparin-platelet factor 4 (PF4) complex antibodies. Its incidence ranges from 0.2% – 5.0% in patients exposed to heparin for more than 4 days and 0.2% for those treated with unfractionated heparin (UFH) for less than 4 days. HIT-II is referred as HIT in this abstract. Maggots' therapy is used in clinical centers all over the world for the treatment of chronic wounds, such as leg ulcers, pressure sores, diabetic and necrotic ulcers, as well as infected surgical wounds, burns and trauma injuries. Maggots' therapy has core beneficial effects on a non-healing wound by mechanisms of debridement, disinfection and enhanced healing. In the last decade, maggots have been used to treat wounds of thousands of patients worldwide, so clinicans have recognized maggots' therapy as an important adjunct to conventional medicine. Despite its widespread usage, the relationship between maggots and heparin-induced thrombocytopenia is undiscovered and unexplored. We are reporting a first ever case of heparin-induced thrombocytopenia where maggots predisposed to this medical condition.

Case

Patient is a 50-year-old morbidly obese (body mass index 68) male with medical history significant for diabetes mellitus-2 and hypertension presented in the hospital with left lower leg pain, which was sharp, 6/10, non-radiating, with no aggravating, and relieving factors. On presentation, he was hemodynamically stable. Physical examination revealed bilateral lower extremity hyper-pigmentation, chronic stasis changes and a superficial posterior malodorous ulcer of the left leg infested with 5-6 maggots. Rest of the examination was unremarkable. Maggots were removed, started antibiotics and he received subcutaneous heparin as thromboprophylaxis. His platelets dropped from 108X10⁹/L to 66X10⁹/L after a single dose of subcutaneous unfractionated heparin. 4 T score revealed high pre-test probability. Laboratory results showed positive heparin-PF4 antibody. Imaging studies were negative for any venous or arterial thrombi/emboli. Heparin was discontinued immediately and argatroban was begun. There was noticeable rise in his platelet count. He was discharged upon symptomatic improvement of his leg pain along with normalization of his platelet counts.

Discussion

Heparin-induced thrombocytopenia is a clotting disorder where antibodies like IgG, IgM, and IgA are provoked by heparin, and highly immunogenic complex of heparin-PF4. Then, heparin-PF4-antibody complex binds to an activated platelet surface, binding of this immune complex to endothelial cell surfaces and tissue factor leads to thrombosis. Genetic and patient-specific interactions may also have an impact on HIT. Maggots have been extensively studied in the wound healing process and various mechanisms of actions have been described in the literature. Maggots combat clinical infection by exudate production, ingestion of wound bacteria and secreting potent bactericidal agents. Maggots form granulation tissue by complex interactive healing process. Upon maggots’ exposure, growth factors, such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) and transforming growth factor (TGF), are produced and released from the wound site to rapidly recruit inflammatory cells via cytokines and chemokines to an injured area. These factors increase the capillary permeability to the wound site. Also, these growth factors are formed, stored and released from platelets, as is platelet factor 4 complex. Hence, maggots activate platelets, release immunogenic PF-4 complex and initiate the whole cascade of heparin-induced thrombocytopenia. We need further studies to validate the interrelation of maggots’ therapy or infestation and heparin-induced thrombocytopenia.