Page 1243 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

850 PART 7: Hematologic and Oncologic Disorders

history (eg, cancer, alcohol ingestion, medications, dietary habits,
TABLE 90-4 Etiologies of Thrombocytopenia
chemotherapy, or radiation), and concurrent red blood cell and white
Spurious blood cell abnormalities (eg, leukopenia, microcytic, or macrocytic
Decreased platelet production anemia). If suspected, specific viral infections including HIV, Epstein-
Infection Barr virus, parvovirus, and varicella may be diagnosed by history and
• Epstein Barr virus serologic testing.
• HIV Dilution and Distributional Thrombocytopenia: Dilutional thrombocyto-
• Parvovirus penia reflects inadequate preservation of platelet concentration when
• Varicella intravascular volume is rapidly replaced with platelet-poor solutions
Drugs and toxins and crystalloid. For practical purposes, this only occurs in settings
• Alcohol of massive blood loss and massive transfusion (see massive transfu-
• Cancer chemotherapy sion below). Distributional thrombocytopenia occurs in patients with
• Heparin-Induced thrombocytopenia splenomegaly from portal hypertension and reflects removal and
• Antiepileptics and sedatives sequestration of platelets from the circulation. However, patients with
• Antibiotics advanced portal hypertension and splenomegaly are also likely to have
• Salicylates and glycoprotein IIb/IIIa inhibitors decreased thrombopoietin production associated with cirrhotic liver
• Histamine 2 receptor blockers disease and may have alcohol-related bone marrow suppression. 54,55
Nutritional deficiency
• Vitamin B 12 Drug and Medication-Induced Thrombocytopenia: Hundreds of drugs,
• Folate supplements, and foods have been causally associated with thrombo-
• Iron cytopenia. While specialized laboratory testing may be available to
Myelodysplastic syndromes confirm the diagnosis of drug and medication-induced thrombocyto-
Increased platelet destruction penia (DITP), the clinical diagnosis is often established only by clinical
Sepsis consideration of the time course, response to removing the drug, and
Disseminated intravascular coagulation (DIC) exclusion of alternative causes. These factors require a high index of
Thrombotic thrombocytopenic purpura (TTP) suspicion and a systematic review of potential drug-related etiology in
Immune thrombocytopenic purpura (ITP) any patient with thrombocytopenia. The most typical clinical feature
Posttransfusion purpura of DITP is clinical presentation 5 to 10 days after exposure to the drug
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9
Antiphospholipid antibody syndrome with platelet counts usually less than 20 × 10 /L. Clinical criteria
HELLP syndrome (hemolytic anemia, elevated liver function tests, low platelet) and a scoring scale for the likelihood of DITP have been proposed.
One commonly applied scale assigns probability based only on clini-
Abnormal distribution and dilution cal information of exposure and response to removal of exposure and
Hypersplenism secondary to portal hypertension does not require specialized laboratory testing evidence (Table 90-5). 57
Massive blood transfusion
The most common specific classes of drugs associated with idio-
syncratic or unpredictable thrombocytopenia include the cinchona
alkaloids, platelet inhibitors, heparins, antibiotics, anticonvulsants, and
analgesics. Thrombocytopenia is anticipated and predictable with cyto-
measurement is performed by an automated analyzer that is triggered toxic chemotherapeutic and immunosuppressive medications. Common
by the relative size of the particles and cells in the sample. Errors in medications associated with DITP are shown in Table 90-6. Specific
sample collection including incorrectly labeled specimens, delays medications strongly associated with DITP and consistently detected
in processing, and inadequate anticoagulant in the collection tubes antiplatelet antibodies include quinine, quinidine, trimethoprim/
may allow platelets to clump and cause the automated counter to sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine,
generate incorrect or falsely low results. Ethylenediaminetetraacetic ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin, abciximab,
acid (EDTA) anticoagulant used in peripheral blood collection tubes tirofiban, eptifibatide, and heparin. Importantly, antibody-mediated
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may also trigger antibody-dependent clumping or agglutination of platelet destruction may result not only in removal of circulating platelets
platelets leading to low measured platelets in patients with severe ill-
ness, autoimmune, liver, and neoplastic diseases. In these instances
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of pseudothrombocytopenia, examination of the peripheral blood by TABLE 90-5 Criteria and Clinical Likelihood for Drug-Induced Thrombocytopenia
microscopy quickly reveals the actual platelet density as well as other
features of the problem such as giant or clumped platelets. While Criterion
manual recounting of platelets on peripheral blood smear may be 1 Therapy with the candidate drug preceded thrombocytopenia and recov-
performed, it is recommended that patients with clumped platelets ery from thrombocytopenia was complete and sustained after therapy
have repeat testing using citrate anticoagulant or heparin anticoagu- with the drug was discontinued
lant specimen tubes as this will facilitate continued monitoring and 2 The candidate drug was the only drug used before the onset of thrombocy-
assessment of actual platelet count over time. topenia or other drugs were continued or reintroduced after discontinuation
Decreased Platelet Production and Disorders of Bone Marrow: The short, of therapy with the candidate drug with sustained normal platelet count
limited life span of platelets creates a physiologic requirement for 3 Other causes for thrombocytopenia were excluded
rapid platelet production to maintain steady-state circulating levels. 4 Reexposure to the candidate drug resulted in recurrent thrombocytopenia
Nutritional deficiencies, toxins, and infectious diseases which affect
bone marrow stem cells, specifically megakaryocytes, can cause Clinical Likelihood
thrombocytopenia. The most common causes of decreased platelet Definite Criteria 1, 2, 3, and 4 met
production in ICU patients include hematologic malignancies, non- Probable Criteria 1, 2, and 3 met
hematologic malignancies, aplasia after chemotherapy, vitamin B
12
and folate deficiencies, and bacterial and viral infections. While Possible Criterion 1 met
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iron deficiency is typically associated with thrombocytosis, it may Unlikely Criterion 1 not met
also be associated with thrombocytopenia. Clinical features that Adapted with permission from George JN, Raskob GE, Shah SR, et al. Drug-induced thrombocytopenia: a
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suggest impaired bone marrow production include specific medical systematic review of published case reports. Ann Intern Med. 1998 Dec 1;129(11):886-890.

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