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2072 Part XII Hemostasis and Thrombosis

TABLE Differential Diagnosis of Thrombocytopenia in TABLE Differential Diagnosis of Prolonged aPTT and/or PT in
139.1 Suspected Disseminated Intravascular Coagulation 139.2 Suspected Disseminated Intravascular Coagulation
Differential Diagnosis Additional Diagnostic Clues Test Result Cause
DIC Prolonged aPTT and PT, increased PT prolonged, aPTT Factor VII deficiency
FDP, low levels of antithrombin or normal Mild vitamin K deficiency
protein C Mild liver insufficiency
Sepsis without DIC Positive (blood) cultures, positive Low doses of vitamin K antagonists
sepsis criteria, hematophagocytosis PT normal, aPTT Factor VIII, IX, or XI deficiency
in bone marrow prolonged Unfractionated heparin
Massive blood loss Major bleeding, low hemoglobin, Inhibitory antibody and/or antiphospholipid
prolonged aPTT and PT antibody
Factor XII or prekallikrein deficiency
Thrombotic microangiopathy Schistocytes evident on blood smear,
Coombs-negative hemolysis, fever, Both PT and aPTT Factor X, V, II, or fibrinogen deficiency
neurologic symptoms, renal prolonged Severe vitamin K deficiency
insufficiency, coagulation tests Vitamin K antagonists
usually normal, ADAMTS13 levels Global clotting factor deficiency
decreased • Decreased synthesis: liver failure
• Increased loss: massive bleeding, DIC
Heparin-induced Use of heparin, venous or arterial
thrombocytopenia thrombosis, positive HIT test aPTT, Activated partial thromboplastin time; PT, prothrombin time.
(usually immunoassay for
heparin-platelet factor 4
antibodies), increase in platelet by cytostatic agents), or by immune-mediated mechanisms. Drug-
count after cessation of heparin; induced thrombocytopenia is a difficult diagnosis in patients suspected
coagulation tests usually normal
of DIC because these patients are often receiving multiple drugs and
Immune thrombocytopenia Antiplatelet antibodies, normal or have several other potential reasons for the thrombocytopenia. Drug-
increased number of induced thrombocytopenia is often diagnosed based upon the timing
megakaryocytes in bone marrow of initiation of a new agent in relationship to the development of
aspirate, normal levels of TPO thrombocytopenia, after exclusion of other causes of thrombocyto-
(TPO levels are usually normal or penia. The observation of rapid restoration of the platelet count after
slightly increased in ITP); discontinuation of the suspected agent is highly suggestive of drug-
coagulation tests usually normal induced thrombocytopenia.
Drug-induced Decreased number of megakaryocytes A prolongation of global coagulation tests may be due to a defi-
thrombocytopenia in bone marrow aspirate or ciency of one or more coagulation factors (Table 139.2). In addition,
detection of drug-induced but more rarely, the prolonged tests may be due to an inhibitory
antiplatelet antibodies, increase in antibody. Some of these antibodies may be clinically important, such
platelet count after cessation of as antibodies to factor VIII that lead to acquired hemophilia (see
drug; coagulation tests usually Chapter 136), whereas others may be less important, such as
normal antiphospholipid antibodies (see Chapter 141). However, patients
ADAMTS13, A disintegrin and metalloproteinase with thrombospondin 13; with antiphospholipid antibodies may have thrombocytopenia and
aPTT, activated partial thromboplastin time; DIC, disseminated intravascular may be at increased risk of thrombosis particularly if they also have
coagulation; FDP, fibrin degradation products; HIT, heparin-induced a lupus anticoagulant. Inhibitory antibodies and lupus anticoagulants
thrombocytopenia; PT, prothrombin time; ITP, immune thrombocytopenia; can be identified and distinguished with mixing studies (see Chapters
TPO, thrombopoietin.
136 and 141).
In general, acquired deficiencies of coagulation factors can be due
to impaired synthesis, massive loss, or increased turnover (consump-
tion). Impaired synthesis is often due to hepatic insufficiency or
value (100%) but a low positive predictive value (10%). Although vitamin K deficiency. Vitamin K deficiency may be caused by poor
the gold standard for the diagnosis of HIT is a sensitive platelet nutrition in combination with the use of antibiotics that impair
activation assay, this test is not routinely available in most hospitals. bacterial vitamin K production in the intestine. The PT is sensitive to
Normalization of the platelet count 1–3 days after discontinuation both conditions because this test is highly dependent on the plasma
of heparin may further support the diagnosis of HIT. levels of factor VII, the vitamin K–dependent coagulation factor with
The group of thrombotic microangiopathies includes thrombotic the shortest half-life. Liver failure may be differentiated from vitamin
thrombocytopenic purpura (see Chapter 134), hemolytic–uremic K deficiency by measuring the levels of factor V, which is not vitamin
syndrome (see Chapter 134), malignant hypertension, chemotherapy- K dependent. In fact, the factor V level is included in several scoring
induced microangiopathic hemolytic anemia, and the HELLP syn- systems for acute liver failure. Uncompensated loss of coagulation
drome. A common pathogenic feature of these disorders is endothelial factors may occur after massive bleeding, which can occur in trauma
damage, which triggers platelet adhesion and aggregation, thrombin patients or those undergoing major surgical procedures. This is
generation, and an impaired fibrinolysis. The clinical consequences common in patients with major bleeding who receive intravascular
of extensive endothelial dysfunction include thrombocytopenia, volume replacement with crystalloids, colloids, and red cells without
mechanical fragmentation of red cells with hemolytic anemia, and simultaneous administration of coagulation factors. This results in
microvasular occlusion, which leads to multiorgan dysfunction, a dilutional coagulopathy, which can exacerbate the bleeding. In
including renal insufficiency and neurologic symptoms. Despite this addition, transfusion in these patients may lead to systemic activation
common final pathway, the various thrombotic microangiopathies of inflammatory processes and may contribute to further coagula-
have different underlying etiologies (see Chapter 134). tion derangements. In hypothermic patients (e.g., trauma patients)
Drug-induced thrombocytopenia is another frequent cause of measurement of the global coagulation tests may underestimate the
thrombocytopenia in critically ill patients (see Chapter 131). Throm- extent of the coagulopathy because these assays are performed at 37°C
bocytopenia may be caused by drug-induced myelosuppression, (e.g., to mimic normal body temperature.