Systematic evaluations of
anemia,
thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder.
Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes.
Drug-induced
thrombocytopenias present diagnostic challenges, because many medicines can cause
thrombocytopenia and
critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all
heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because
warfarin anticoagulation induces
acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT,
warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of
thrombocytopenia supports a diagnosis of
DIC, not
TTP-HUS, and is demonstrated by decreasing serum
fibrinogen levels, and increasing TTs, PTs, aPTTs, and
fibrin degradation products. Increasing
D-dimer, levels are the most specific
DIC parameter and reflect fibrinolysis of cross-linked
fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors,
antiphospholipid antibodies (e.g.,
lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess
phospholipid or platelets. Paradoxically, a tendency to
thrombosis, not
bleeding, accompanies lupus
anticoagulants and the
antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In
critically ill patients, administering RBCs can enhance
oxygen delivery to tissues. Among euvolemic patients who do not have
ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from
blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate
iron,
folate, and
cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in
critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis,
platelet transfusions are often important in managing patients who are
bleeding or at risk of
bleeding with
thrombocytopenia or impaired platelet function.
Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important,
platelet transfusions are generally contraindicated if the underlying disorder is
TTP or type II HIT, because
platelet transfusion in these settings may fuel
thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when
bleeding arises from malfunction, consumption, or underproduction of plasma coagulation
proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct
clotting factor deficiencies, particularly coagulopathies that are attributable to multiple
clotting factor deficiency states as in
liver disease,
DIC, or
warfarin anticoagulation. PCC or
rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies.
Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of
rFVIIa in managing
hemostatic abnormalities from severe
liver dysfunction; extensive surgery,
trauma, or
bleeding; excessive
warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated
protein C reduces mortality from
severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In
severe sepsis, levels of
protein C decrease, as do
fibrinogen and platelet levels. Because of its
anticoagulant effect, however, drotrecogin alfa may induce
bleeding. Guidelines for drotrecogin alfa use must take into account
bleeding risks.