Page 1242 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 90: Bleeding Disorders 849

activators and inhibitors. Each of these different assay variations results to 68%. Following admission, the incidence of new thrombocytope-
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in different thromboelastographs and permits isolation and examina- nia ranges from 13% to 44% of patients. 45,46 Severe thrombocytopenia
tion of different aspects of coagulation function, including separation of (<50 × 10 /L) is significantly less common and is described in 1.6% to
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coagulation factor–based clotting behavior from platelet-based clotting. 15% patients. 44,47
Thromboelastography has been increasingly used in critically ill Thrombocytopenia is associated with multiple adverse outcomes and
patients to guide blood product administration and as an indicator functions as an indicator of disease severity. Adjusted mortality rates and
of severity of illness. The potential advantages of thrombelastography severity of illness scores are generally higher in patients with worsening
include point-of-care testing, ability to assess the combined result of severity of thrombocytopenia, lower nadir platelet counts, or a relative
platelet and coagulation factor activation, as well as rapid access to drop in platelet count of 30% or more. 44-48 Thrombocytopenia has been
results. Particularly in surgeries that have typically had high utilization associated with use of inotropes and vasopressors, renal replacement
of blood products such as cardiac surgery, thromboelastography has therapy, and liver dysfunction. Thrombocytopenia has also been
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been examined as a determinant of transfusion need. A randomized trial associated with increased rates and duration of mechanical ventilation
comparing intraoperative and perioperative protocols with and without and blood product utilization. 46,47 While disease-specific cohort studies
thromboelastography for cardiac surgery patients showed significantly have shown a relationship of bleeding and hemorrhage to severe throm-
decreased blood product utilization compared to traditional coagulation bocytopenia, this generalization has not been consistently observed
times alone. As a prognostic indicator in general medical and surgical in unselected ICU patients. A systematic review found little evidence
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ICU admissions, patients with hypocoagulability on TEG assessment linking generally defined thrombocytopenia with hemorrhage. This
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had higher sequential organ failure assessment (SOFA) scores, higher suggests that additional factors including the etiology of thrombocy-
rate of ventilator and renal replacement therapy, and higher 30-day topenia, degree of thrombocytopenia, comorbid conditions, and other
mortality. In the specific subset of medical ICU patients with sepsis concurrent coagulation defects contribute to bleeding risk. Patients with
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and severe sepsis, thromboelastography measurements also provide severe thrombocytopenia (platelet count <20 × 10 /L) have the highest
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prognostic information. In three separate studies involving single risk and incidence of bleeding. 49
cohorts of sepsis patients, abnormal coagulation profiles were associated The majority of patients who develop thrombocytopenia in the ICU
with worse SOFA scores. Patients who progressed to hypocoagulable develop this by day 3 to 5. Those who recover and survive demonstrate a
status had significantly lower 28- or 30-day survival. 38-40 more rapid and complete recovery of platelet count compared to nonsur-
vivors who have a delayed recovery in platelet counts or no recovery. 50,51
PLATELET DISORDERS Persistent absolute thrombocytopenia in patients on ICU day 7 or a
relative decrease in platelet counts of 30% from baseline independently
Coagulopathy in critically ill patients may result from disorders of predicts higher risk of death. These findings of delayed recovery of
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platelet number as well as platelet function. Abnormal circulating platelet counts even in patients without absolute thrombocytopenia
platelet number results from increased destruction, decreased synthesis, suggest that changes over time are particularly important and may be
sequestration from the circulation, and combinations of these prob- more helpful indicators of patient status than any single measurement
lems. Disorders of platelet function arise from impaired or inhibited of platelet concentration.
platelet adhesion, activation, and degranulation. Common findings in
patients with clinically significant thrombocytopenia include petechial ■ ETIOLOGY OF THROMBOCYTOPENIA IN ICU PATIENTS
hemorrhages and ecchymoses when thrombocytopenia is mild to mod-
erate. When more severe, florid purpura and bleeding from the nose Identification of the causes of thrombocytopenia requires a system-
gums, gut, urinary tract, intravenous access sites, and surgical wounds atic search for disorders of platelet production, destruction, dilution,
are seen. Independent of etiology, worsening thrombocytopenia and and sequestration. Particularly for critically ill patients, the greatest
inhibition of normal platelet function are associated with increased ICU likelihood is that multiple, simultaneous factors contribute to
morbidity and mortality as well as increased utilization of resources. thrombocytopenia. Severe thrombocytopenia should be investigated
While some defects in platelet number and function may improve with by review of nutritional factors, medications, autoimmunity diseases,
platelet transfusion, specific platelet transfusion guidelines limit the use infection, coagulation, and bone marrow function. Important coexist-
of this treatment to actively bleeding patients and to those who have ing defects in soluble coagulation factors as well as comorbid conditions
extreme thrombocytopenia plus risk factors for hemorrhage. should be used to determine both the risk associated with thrombocyto-
penia and appropriate therapy. The approach to determining the cause
■ THROMBOCYTOPENIA of thrombocytopenia should include assessment of the patient’s history,

The life span of platelets in the circulation is limited to 9 to 10 days. In exposures, and medications, as well as consideration of risk for malig-
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nancy and disseminated infection. Laboratory testing should include
the absence of disease, platelet life span is likely related to the attenuation review of the complete blood count, prothrombin time, nutritional
of proteasome function in the platelets themselves which then triggers markers, and hepatic function. While routine bone marrow biopsy has
conformational changes in surface protein expression and clearance been shown to add important new information to the understanding of
from the circulation through phagocytosis by macrophages. Given this thrombocytopenia, this should be reserved for patients with refractory,
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rapid turnover, any disorder which has a negative effect on platelet pro- unexplained disease.
duction, circulation, or clearance can quickly lead to a cumulative result A highly detailed evaluation of 301 mixed adult ICU patients which
of clinically significant thrombocytopenia. included bone marrow biopsy, demonstrated that the majority of
Thrombocytopenia is one of the most common coagulation abnor- patients had at least two, but commonly three or four, potential etiolo-
malities critically ill patients. The reported incidence and prevalence gies for thrombocytopenia. In this cohort, the most important causes of
of thrombocytopenia varies by the clinical definition applied and with thrombocytopenia were sepsis, disseminated intravascular coagulation,
subgroups of ICU patients. Applied general definitions of thrombocyto- dilutional thrombocytopenia, massive transfusion, drug-induced, folate
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penia are platelet concentrations below 150 × 10 /L or below 100 × 10 /L. deficiency, and malignancy. Table 90-4 lists the most common etiolo-
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A small number of reports use cut-offs of 50 × 10 /L to specifically gies and clinical characteristics of thrombocytopenia in ICU patients.
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designate severe thrombocytopenia. Typical definitions are mild
thrombocytopenia—concentrations of 100 to 149 × 10 /L; moderate—50 Spurious Thrombocytopenia and Pseudothrombocytopenia: The first
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to 99 × 10 /L; and severe—<50 × 10 /L. Using a cut-off of 150 × 10 /L assessment in any patient with thrombocytopenia is to confirm
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or lower, the prevalence of thrombocytopenia in medical, surgical, and that the result is consistent with the clinical scenario and that there
trauma patients on admission to the ICU shows a wide range from 8.3% were no errors in measurement. Routine platelet concentration
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