How I evaluate and treat thrombocytopenia in the intensive care unit patient

Abstract

Multiple causes (pseudothrombocytopenia, hemodilution, increased consumption, decreased production, increased sequestration, and immune-mediated destruction of platelets) alone or in combination make thrombocytopenia very common in intensive care unit (ICU) patients. Persisting thrombocytopenia in critically ill patients is associated with, but not causative of, increased mortality. Identification of the underlying cause is key for management decisions in individual patients. While platelet transfusion might be indicated in patients with impaired platelet production or increased platelet destruction, it could be deleterious in patients with increased intravascular platelet activation. Sepsis and trauma are the most common causes of thrombocytopenia in the ICU. In these patients, treatment of the underlying disease will also increase platelet counts. Heparin-induced thrombocytopenia requires alternative anticoagulation at a therapeutic dose and immune thrombocytopenia immunomodulatory treatment. Thrombocytopenia with symptomatic bleeding at or above World Health Organization grade 2 or planned invasive procedures are established indications for platelet transfusions, while the evidence for a benefit of prophylactic platelet transfusions is weak and controversial. If the platelet count does not increase after transfusion of 2 fresh ABO blood group–identical platelet concentrates (therapeutic units), ongoing platelet consumption and high-titer anti-HLA class I antibodies should be considered. The latter requires transfusion of HLA-compatible platelet concentrates.

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

“…Platelet Numbers Are Altered in Critical Illness, Influence the Outcome of ARDS, and Are Regulated by Genetic Determinants in Clinical ALI Thrombocytopenia is common in critically ill patients at risk for, or with, ARDS and is associated with negative outcomes, including death (4,14,(85)(86)(87)(88)(89)(90). In clinical observations and a model of gram-negative pneumonia with sepsis, thrombocytopenia was associated with dysregulated inflammation and impaired host defense (76,91).…”

“…In clinical observations and a model of gram-negative pneumonia with sepsis, thrombocytopenia was associated with dysregulated inflammation and impaired host defense (76,91). Complex mechanisms contribute to thrombocytopenia in ICU patients, including altered thrombopoiesis and platelet consumption and sequestration (4,5), each of which may occur in ARDS. The inflamed lung is a significant site of platelet sequestration (14).…”

“…Circulating platelets are chief effector cells in physiologic hemostasis and pathologic thrombosis (2,3), and these are their best-known biologic functions. Management of bleeding, or its risk, owing to thrombocytopenia or platelet dysfunction remains an important clinical issue for pulmonary and critical care physicians (4,5). Nevertheless, platelets are versatile and intricate, and they have multiple additional activities in host response to injury and in tissue repair besides hemostasis (6,7).…”

The clinical development of obinutuzumab for the treatment of follicular lymphoma

“…As a single agent in a relapsed/refractory Phase I study, venetoclax produced an ORR of 38% and median PFS of 11 months 58. It was subsequently combined with R-CHOP and O-CHOP in a Phase IB study in 56 patients with B-cell NHL, primarily as a frontline regimen 59. Of those enrolled, 43% had FL, 30% had DLBCL, and 9% had marginal-zone lymphoma.…”

Thrombocytopenia in critically ill patients due to vascular microthrombotic disease: pathogenesis based on “two activation theory of the endothelium”

“…The known mechanisms producing thrombocytopenia in critically ill patients include: 1) decreased production of the platelet due to transient bone marrow suppression or myelodysplasia (e.g., infection-associated), 2) increased destruction due to immune or nonimmune response (e.g., drug or transfusion-induced), 3) increased utilization (e.g., disseminated intravascular coagulation -DIC), 4) increased consumption (e.g., heparin-induced thrombocytopenia, and thrombotic thrombocytopenic purpura -TTP), and 5) sequestration secondary to hypersplenism [5,6]. To date, TCIP is the term to use after the exclusion of known mechanisms.…”