Medical devices such as mechanical heart valves, left-ventricular assistance devices, and aortic balloon pumps may be responsible for the destruction of platelets. In a study on 1,302 patients who underwent percutaneous coronary intervention (PCI) with baseline normal platelet counts (≥150*10⁹/L), 3.1 % developed post-PCI thrombocytopenia. Multivariate analysis showed that the use of intra-aortic balloon pump was an independent predictor of thrombocytopenia, with an odds ratio of 2.8, confidence intervals 1.1–6.8, p = 0.024. Post-PCI thrombocytopenia was significantly associated with major adverse cardiovascular events at 6 months (hazard ratio 2.7, CI 1.3–5.5, p = 0.0069) [13].

Microangiopathic processes such as thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and disseminated intravascular coagulation (DIC) may be responsible for thrombocytopenia due to enhanced platelet destruction.

TTP is characterized by microvascular platelet clumping, which leads to thrombocytopenia and microangiopathic hemolytic anemia. Common findings are “broken” erythrocytes or schistocytes (see algorithm reported in Fig. 6.1), neurological disorders, renal failure, and fever [14]. The disease is due to a congenital or acquired deficiency in ADAMTS13, a metalloprotease which cleaves von Willebrand factor. ADAMTS13 deficiency is responsible for microvascular thrombosis and thrombocytopenia. Plasma exchange is the optimal therapy, and its effectiveness is probably due to the removal of anti-ADAMTS13 autoantibodies and large von Willebrand factor multimers.

HUS is similar to TTP in that microvascular thrombosis, thrombocytopenia, microangiopathic hemolytic anemia, renal insufficiency, and altered mental status are common features. However, ADAMTS13 is normal and the disease is generally due to endothelial cell damage caused by a toxin produced by pathogenic strains of Escherichia or Shigella. In HUS, thrombocytopenia is usually not severe but dialysis may be required to treat renal insufficiency [23].

DIC does not occur as an isolated event but is practically always associated with an underlying condition such as tissue damage (trauma, burns, hemolytic transfusion reaction, acute transplant rejection), neoplasia, systemic infection, obstetric conditions (abruption placentae, placenta previa, amniotic fluid embolism), and other clinical conditions such as shock, cardiac arrest, and aortic aneurysm. DIC is the result of an overstimulation of the coagulation system and its clinical presentation varies from severe hemorrhage to thrombosis (or both simultaneously). Thrombocytopenia, abnormal prothrombin time and activated partial thromboplastin time (PT and aPTT), decreased fibrinogen and elevated fibrinogen degradation products are common laboratory features of DIC. DIC-associated mortality is mostly due to the original disease, which is complicated by hemorrhage or thrombosis. Multiorgan dysfunction syndrome is a frequent consequence of DIC and is due to hemorrhagic or thrombotic events in liver, heart, kidneys, central nervous system, and lungs [15].

The main therapeutic goal in DIC is that of treating the underlying condition. As far as transfusion of blood products is concerned, there has been a lot of debate on its benefit and potential harm; generally, platelet counts should be kept more than 20*10⁹/L in presence of mild bleeding and more than 50*10⁹/L when there is active bleeding. Plasma or cryoprecipitate should be considered when bleeding is associated with low fibrinogen levels. The aim of fibrinogen replacement is to maintain levels more than 100 mg/dl to prevent or treat bleeding [24].

In addition to Heparin-Induced Thrombocytopenia (HIT) which will be discussed in the following section, primary Immune Thrombocytopenia (ITP), post-transfusion purpura (PTP), and drugs may lead to immune platelet destruction.

ITP is an acquired disorder mediated by immunological mechanism, characterized by low platelet counts in the absence of any possible known cause of thrombocytopenia. It affects children and adults (with a slight prevalence in women) and symptoms range from massive bleeding (gastrointestinal, skin–mucosal, and intracranial) to minimal bruising or only alterations in whole blood count. Evaluation of the blood smear is important in the diagnosis of ITP (Fig. 6.1) and antiplatelet antibody assays are not routinely performed due to the low specificity of this test. Adult ITP is treated with corticosteroids or IVIg and platelet transfusions are recommended only for emergency cases in presence of active bleeding [16].

PTP is a rare complication of transfusion occurring 7–10 days after a red blood cell or platelet transfusion and is characterized by a dramatic fall in platelet count reaching a nadir less than 10*10⁹/L. Thrombocytopenia is caused by platelet alloantibodies in the recipient which at first destroy the transfused platelets, but successively also react with self-platelets. PTP is managed by administering IVIg or if available, compatible platelets (usually HPA-1a negative) [19].

Drug-induced thrombocytopenia (DITP) may either be caused by drugs suppressing bone marrow (see previous section) or by drugs eliciting diverse types of antibodies. Table 6.2 summarizes the main types of antibodies implicated in DITP [11]. DITP may be hard to diagnose in critically ill patients, since thrombocytopenia may become evident several days after the beginning of therapy, and has to be distinguished from other causes of thrombocytopenia.