Thrombocytopenic Disorders in Critically Ill Patients (2000)

Thrombocytopenia, often defined as a platelet count below 100,000/ m l, is a relatively common hematologic problem seen in a wide variety of critically ill patients. Studies conducted in medical and surgical intensive care units (ICUs) have found platelet counts less than 100,000/ m l in 20 to 40% of patients at some point during their stay in the unit, whereas severe thrombocytopenia (platelet counts , 50,000/ m l) occurred in 10 to 20% of patients (1, 2). Although the cause was often not identified (1), thrombocytopenia was commonly associated with sepsis, disseminated intravascular coagulation (DIC), massive blood transfusion (dilutional thrombocytopenia), and chemotherapy (1, 2). Intensivists caring for patients with thrombocytopenia must establish the cause of the thrombocytopenia, monitor and manage the clinical consequences of thrombocytopenia and/or its underlying cause, and decide whether or not to support the platelet count by platelet transfusion. An abnormally low platelet count arises from one or more of four general mechanisms ( see Table 1): ( 1 ) decreased platelet production, ( 2 ) increased platelet destruction, ( 3 ) dilutional or distributional causes, and ( 4 ) spurious thrombocytopenia. Dilutional thrombocytopenia may arise during transfusion for massive blood loss. In one study, 75% of patients transfused with 20 or more red blood cell units in 24 h developed platelet counts less than 50,000/ m l, while no patients receiving fewer than 20 red blood cell units developed platelet counts below this level (3). “Distributional” thrombocytopenia is commonly attributed to increased splenic sequestration in patients with splenomegaly. However, in patients with hepatic cirrhosis and splenomegaly from portal venous hypertension, thrombocytopenia may derive less from splenic sequestration than from reduced levels of thrombopoietin, which is produced by the liver (4). Spurious thrombocytopenia, diagnosed by examining the peripheral blood smear, arises from platelet clumping in vitro due to either insufficient anticoagulation of the collected blood sample or EDTA-dependent agglutinins. Besides a careful history, physical examination, and review of all medications, initial evaluation of the patient with thrombocytopenia should include review of other blood cell counts and examination of the peripheral blood smear. The presence of schistocytes (red blood cell fragments) is diagnostic of a microangiopathy. The presence of tear drops, nucleated red cells, and immature granulocyte precursors suggests replacement of hematopoietic tissue in the bone marrow by abnormal tissue (myelophthisis) from fibrosis, granulomatous inflammation, infection, cancer metastatic to the marrow, or primary hematopoietic disorders such as leukemia. A myelodysplastic syndrome is suggested by dyspoiesis including coarse basophilic stippling of red cells, pelgeroid cells, Dohle bodies, hypogranulation of neutrophils, and giant platelets. Drug-induced thrombocytopenias can be challenging to diagnose, since many medicines may be associated with thrombocytopenia and patients, particularly when critically ill, are often receiving more than one medicine. Heparin (in particular unfractionated heparin), quinine, quinidine, trimethoprim-sulfamethoxazole, gold, and valproic acid are commonly implicated drugs (5). If heparin-induced thrombocytopenia (HIT) is suspected, all heparin sources, including low molecular weight heparins (LMWHs), must be discontinued promptly. Isolated megakaryocytic hypoplasia or aplasia is rare, but should be considered in patients using thiazide diuretics, alcohol, or estrogens. Unless specific drug–platelet-associated antibodies are suspected, anti-platelet antibody testing is not recommended since it lacks sufficient sensitivity and specificity to be useful (6). Blood chemistries are useful for evidence of hemolysis, including increased serum lactate dehydrogenase (LDH) and indirect bilirubin accompanied by decreased haptoglobin levels. The presence of a consumptive coagulopathy, which supports a diagnosis of DIC (and is not a component of thrombotic thrombocytopenic purpura–hemolytic uremic syndrome [TTP–HUS]), is demonstrated by decreasing serum fibrinogen levels; increasing thrombin, prothrombin, and activated partial thromboplastin times (TT, PT, and aPTT, respectively); and increasing fibrin degradation products. Increasing D-dimer levels are the most specific DIC parameter, reflecting fibrinolysis of cross-linked fibrin, while increasing PTs and decreasing levels of fibrinogen and platelet counts are most sensitive in detecting early DIC development. While measuring levels of factor V (a vitamin K-independent clotting factor produced by liver) and factor VIII (a clotting factor not produced by liver) may help to distinguish a role for DIC (which consumes both factors) in bleeding associated with liver disease, this is generally not necessary.