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CHAPTER 90: Bleeding Disorders 855

INR, as well as age. Other factors predictive of bleeding during war- As the direct result of the association of DIC with major systemic
131
farin therapy include history of stroke, prior bleeding, age >75 years, disease, it is associated with particularly high mortality. For ICU patients
hepatic or renal disease, malignancy, thrombocytopenia, uncontrolled with overt clinical and laboratory evidence of DIC, mortality ranges
hypertension, ethanol abuse, anemia, and excessive risk of falls. 132 from 45% to 78%. 142-144
There are two main considerations in managing patients receiving Clinical and laboratory features of DIC include abnormalities in all
warfarin with supratherapeutic INR or bleeding complications: the aspects of blood and coagulation including coagulation times, red blood
degree of INR elevation and the presence or absence of bleeding. cell morphology, and thrombocytopenia. Bedside findings include pete-
Serious bleeding in patients with any degree of elevated INR requires chiae, ecchymosis, and bleeding from venipuncture sites. Bleeding from
simultaneous reversal of vitamin K antagonism as well as immediate surgical wounds and noninjured mucosal surfaces may develop.
replacement of deficient vitamin K–dependent factors. Intravenous DIC is a clinical diagnosis established by the presence of severe
vitamin K (phytonadione) in doses of 5 to 10 mg has an effect within clinical disease, exclusion of other similar conditions, and consistent
hours, but does not correct INR until 24 hours. 133,134 Urgent correction laboratory findings. Peripheral blood smear demonstrates few platelets
of coagulopathy also requires exogenous factor replacement. Fresh and hemolysis with schistocytes. The majority of patients have platelet
frozen plasma restores coagulation protein concentrations but, at rec- count <50 × 10 /L. Both the aPTT and INR are prolonged and reflect
9
ommended doses of 15 to 30 mL/kg, risks volume overload, acute lung consumption of clotting factors in the common, intrinsic, and extrinsic
injury, and infection. Prothrombin complex concentrates (PCC) are coagulation cascades. DIC is also a fibrinolytic state characterized by
135
mixtures of highly concentrated factors II, IX, X (three-factor PCC) or the presence of fibrin degradation products and elevated D-dimer levels.
II, VII, IC, X, protein C, and protein S (four-factor PCC) that permit Other markers of DIC include detectable plasma fibrin monomers,
rapid, low-volume infusion of essential coagulation factors. PCCs are decreased plasma antithrombin activity, and decreased levels of indi-
effective in promoting hemostasis in urgent, life-threatening bleeding in vidual clotting factors, particularly factor VIII.
patients receiving warfarin and have been recommended as a first-line Given the complexity of the clinical conditions that cause DIC as
treatment. 136,137 Known complications of PCCs include thrombosis and well as the nonspecific individual laboratory findings, diagnostic scor-
fatal thromboembolism. 138 ing systems for DIC have been proposed. The International Society for
Patients receiving warfarin with supratherapeutic INR but without Thrombosis and Haemostasis scoring system has been shown to have a
bleeding should be treated based on risk for hemorrhage and anticipated sensitivity of 91% and specificity of 97% compared to expert opinion in a
need for invasive procedures. Patients with elevated risk for bleeding prospective group of patients admitted to a single tertiary medical center
(discussed above), having highly elevated INR (>9), or who require ICU (Table 90-9). 142,145
urgent invasive procedures should have warfarin discontinued and Treatment for patients with DIC is focused on the underlying disorder.
receive oral vitamin K in doses of 2.5 to 5 mg. Patients with INR <9 and The benefit of prophylactic transfusion of blood products for patients in
low risk for bleeding may be treated with temporary discontinuation DIC without active bleeding or with low risk for bleeding has not been
of warfarin and restarting at lower dose when the INR returns to the established. High-risk patients and actively bleeding patients should receive
therapeutic range. Low-dose oral vitamin K (1 mg) may also be used platelets to maintain at least 50 × 10 /L, while in nonbleeding patients lower
9
in patients with lower risk for bleeding and moderate to significantly values are accepted (above 10-20 × 10 /L). Fresh frozen plasma and cryo-
9
elevated INR. 136,139,140 precipitate should be used in bleeding and high-risk patients to maintain an
INR ≤2.0 and fibrinogen concentration >50 mg/dL. Heparin treatment is
Oral Direct Thrombin and Factor Xa Inhibitors: The oral direct thrombin indicated for patients with DIC who develop clinically apparent thrombosis.
inhibitor dabigatran and the oral direct factor Xa inhibitors rivaroxa-
ban and apixaban have demonstrated efficacy in thromboprophylaxis
in atrial fibrillation and for venous thromboembolism prophylaxis. TABLE 90-9 International Society of Thrombosis and Hemostasis Disseminated
These medications have relatively short half-lives (5-15 hours) and have
been associated with relatively low rates of major bleeding compared Intravascular Coagulation Scoring System
to low-molecular-weight heparin and warfarin. None of these agents 1. Risk assessment: Does the patient have an underlying disorder known to be associated
has specific antidotes. Management of serious life-threatening bleeding with overt DIC? If yes, proceed; if no, do not use this algorithm
should focus on discontinuation of the medication and other antiplatelet 2. Score coagulation test results Level Score
medications, local source control, and transfusion support. Prothrombin Platelet count (×10 /L) >100 0
9
complex concentrates, antifibrinolytics, and activated recombinant
factor VII are therapeutic options, but there are limited results in 50-99 1
humans demonstrating beneficial effect. 141 <50 2
Fibrin-related marker No increase 0
COMBINED PLATELET AND COAGULATION (D-dimer or fibrin degradation products) Moderate 1
FACTOR DISORDERS (SEE Table 90-10) High 2
■ DISSEMINATED INTRAVASCULAR COAGULATION Prothrombin time <3 s 0

Unlike single disorders of soluble clotting factors or platelets, dis- 3-6 1
seminated intravascular coagulation (DIC) is characterized by systemic >6 s 2
activation of the clotting cascade, fibrin deposition throughout the Fibrinogen concentration >1.0 g/L 0
microvasculature, fibrinolysis, hemolysis, thrombocytopenia, and con-
sumption of clotting factors. DIC occurs as the result of exposure of the <1.0 g/L 1
blood to inflammatory cytokines and procoagulants such as tissue factor
and tissue thromboplastins. Risk factors for DIC include massive tissue 3. Cumulative score:
injury, extensive vascular endothelial injury, shock of any cause, ABO
transfusion incompatibility, amniotic or fat embolism, burns, traumatic 5 or more—compatible with overt DIC
brain injury, malignancy, and severe or systemic infection. Systemic less than 5: suggestive but not affirmative for DIC
activation of thrombosis leads directly to a state of fibrinolysis character- Adapted with permission from Taylor FB Jr, Toh CH, Hoots WK, et al. Towards definition, clinical and
ized by rapid lysis of fibrin, accumulation of plasma fibrin degradation laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost.
products, and thrombocytopenia. November 2001;86(5):1327-1330.

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