He read and gave useful suggestions and corrections for the manuscript.

Individuals with diabetes mellitus (DM) are at high risk of thrombosis in which hyperactive platelets are implicated. The platelet hyperactivity has been linked to hyperglycemia. This hypothesis is supported by studies in type II diabetes mellitus showing increased sensitivity of platelets to stimulating agonists in the context of tissue resistance to high-circulating insulin. However, controversy still exists regarding the altered platelet functions in type 1 diabetes mellitus (T1DM) and the link to modifying factors such as blood glucose, hyperlipidemia, metabolic acidosis and insulin treatment. Moreover, increased insulin dosage or treatment appears to have antagonistic actions: diminished functions at low doses and enhanced activation at high doses, the switch being attributable to insulin-like growth factor. The physiological role of insulin in suppressing platelet activation is lost in T1DM, a scenario that favors increased platelet sensitivity to stimulating agonists. Furthermore, the response to antiplatelet agents and statins is sub-optimal in diabetics presenting clinical and research knowledge gap regarding the ideal antiplatelet treatment in DM in general and T1DM in particular. This chapter reviews the unique characteristics of platelet functions in T1DM highlighting the controversial areas linking unique behavior of platelets and the abnormal response to therapeutic interventions.

The interest in platelet functions in HIV/AIDS is due to the high incidence of microvascular thrombosis in these individuals. A lot of laboratory data have been generated regarding platelet functions in this population. The tests demonstrate platelet hyperactivity but decreased aggregation, though results are inconsistent depending on the study design. Antiretroviral treatments currently in use display complex interactions. Many studies on platelet functions in these patients have been for research purposes, but none have found utility in guiding drug treatment of thrombosis.

Traumatic tissue injury triggers blood coagulation to stanch bleeding and concomitant blood clot lysis to restore vascular patency. Approximately, 40% of trauma cases potentially present with trauma-induced coagulopathy that may coexist with clot dissolution or fibrinolysis. Laboratory test results of fibrinolysis biomarkers stratify fibrinolytic phenotypes into hyperfibrinolysis, physiological, hypofibrinolysis, and fibrinolytic shutdown. However, often, there is incongruence between laboratory findings and clinical presentation of bleeding or vascular thrombosis. Increasingly, it is becoming clear that laboratory findings transiently depend on the timing of blood sampling. The spectrum of evolving fibrinolysis phenotypes, a component of nature’s adaptation to wound healing that ranges from initial promotion of blood fluidity to subsequent thrombosis, presents a clinical diagnostic dilemma with regard to the timing of antifibrinolytics or anticoagulants intervention. This chapter will review the available literature on post-traumatic fibrinolytic phenotypes, diagnostic challenges, evolution over time, clinical outcomes following therapeutic interventions, and association with vascular thrombosis.

Platelets halt bleeding accompanying traumatic injury by performing primary hemostasis to repair vascular leakage at injury sites. In trauma individuals, ex vivo platelet function tests often indicate impairment despite normal count. Moreover, incubation of platelets from normal non-traumatized individuals with plasma from trauma victims demonstrates impairment suggesting association with factors in circulation. Notably, not all trauma victims die from hemorrhage. Despite laboratory evidence of dysfunction, thrombotic vascular occlusions are persistent in trauma survivors as corroborated by postmortem findings from victims who die. The time course of platelet reactions post-traumatic injury, that is, the transition from states favoring bleeding to those that facilitate thrombosis is still unclear. Of the several terminologies describing platelet behavior with regards to injury, including hyporeactivity, anergy, exhaustion, and maladaptive states, few have focused on platelet-platelet interactions. It is increasingly becoming clear that platelet interaction with injured endothelium is a probable missing link in the mechanistic explanation of vascular thrombosis post-traumatic injury. This postulate is supported by evidence of increased adhesive protein, von Willebrand factor, and released from injured endothelium. In all, this potentially explains the suboptimal response to anticoagulants or antiplatelets post-trauma. This chapter will review current knowledge on platelet functions in relation to vascular thrombosis post-trauma, the time course, mechanistic hypothesis, and response to therapeutic interventions and clinical outcomes.