Page 2518 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 153 Hematologic Manifestations of Liver Disease 2241

If no improvement is seen after 10 to 20 mg of vitamin K, additional Management of Coagulopathy in Liver Disease
vitamin K is unlikely beneficial. Although it may be reasonable to use
vitamin K replacement alone in asymptomatic patients, it should be • Actively bleeding patients should be adequately resuscitated.
considered as an adjunct to other therapy in actively bleeding patients. Admission to the intensive care setting may be appropriate.
Frozen plasma (FP) has traditionally been used to correct liver- • Basic coagulation tests should be ordered to identify the cause
related coagulopathy because it replaces all the coagulation and of bleeding; these include CBC, PT (INR), PTT, thrombin clotting
fibrinolytic factors. Despite its widespread use, its clinical effective- time, fibrinogen, D-Dimer, FDP, and mixing studies. The need
ness in reducing bleeding has not been supported by data from for more specialized tests will be dictated by the clinical situation
randomized controlled trials. Guidelines variably support the use of and response to therapy.
10 to 20 mL/kg of FP for major hemorrhage or prevention of bleed- • It is important to identify any localized source of bleeding
ing before major invasive procedures. Evidence-based guidelines (e.g., varices) amenable to procedural intervention to achieve
hemostasis.
recommend against the use of platelets or plasma as prophylaxis • A trial of 5 to 10 mg of vitamin K is reasonable in asymptomatic
against bleeding in liver disease laboratory parameters, including a patients with prolonged PT and PTT but should be used with
complete blood count (CBC), PT, PTT, fibrinogen, and D-dimer, other therapies in actively bleeding patients.
should be followed to assess therapeutic effect. In general, moderate • In patients with thrombocytopenia platelet transfusions can be
correction of the PT and PTT is achieved after FP transfusion but is used, targeting platelet counts greater than 50 × 10 /L.
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transient, and repeat doses may have to be administered every 6 to • In patients who can tolerate volume, FP 4 to 6 units
12 hours to maintain the effect. Patients should be monitored for (1000–1500 mL) given over 1 to 2 hours can be used to replace
complications of FP, including transfusion reactions and volume coagulation factors. Coagulation parameters should be monitored
overload. Plasma infusion may not be well tolerated in patients with to document effect and determine the timing and need for
additional units.
liver disease who already have expanded intravascular plasma volume. • Dysfibrinogenemia or hypofibrinogenemia should be suspected if
Plasma exchange in addition to FP has been described primarily in coagulation assays do not correct with FP or fibrinogen levels are
the setting of acute liver failure and in preparation for liver transplan- low, respectively. Replacement can be attempted with 10 to 20
tation. However, the efficacy of this approach has not been thoroughly units of cryoprecipitate while following laboratory results.
studied in controlled trials. • Patients who are intravascularly overloaded or who do not
The presence of hyperfibrinolysis, DIC, and dysfibrinogenemia respond to FP should be considered for rFVIIa. Low doses of
may exacerbate bleeding and are inadequately treated with FP alone. rFVIIa (25–50 µg/kg) are generally used, and repeated doses may
These disorders should be suspected if coagulation parameters fail to be required because of the short rfVIIa half-life of 2 to 3 hours.
correct with FP or there is persistent bleeding. Administration of rFVIIa may be most suitable as a temporizing measure to enable
invasive procedures or hemostasis to be achieved by other
cryoprecipitate, rich in fibrinogen, vWF, factor VIII, and factor XIII, means. Avoid use in the setting of DIC.
may help control bleeding. One unit of cryoprecipitate for every
10 kg of body weight increases plasma fibrinogen by approximately CBC, Complete blood count; DIC, disseminated intravascular coagulation; FDP,
50 mg/dL. Cryoprecipitate carries similar risks to FP. Although FP, frozen plasma; INR, international normalized ratio; PT, prothrombin time;
antifibrinolytic agents could be considered in the setting of hyperfi- PTT, partial thromboplastin time; rFVIIa, recombinant factor VIIa.
brinolysis, no randomized trials have demonstrated efficacy or safety
outside the setting of liver transplantation. Tranexamic acid has been HYPERCOAGULABILITY AND THROMBOSIS
shown to reduce blood loss and the need for transfusion in liver
resection, transplantation and variceal bleeding. Thrombotic risks IN PATIENTS WITH LIVER DISEASE
must be weighed and DIC must be excluded before usage.
Three- and four-factor prothrombin complex concentrates (PCCs) Although retrospective studies have reported variable rates of venous
contain the vitamin K–dependent factors II, IX, and X and may or thromboembolism (VTE) in patients with cirrhosis, it is clear that
may not contain variable amounts of factor VII. They are effective these patients are not “autoanticoagulated” and thus not immune to
in reversing anticoagulation with vitamin K antagonists (VKAs), but thrombotic events as once believed. The risk of VTE may actually be
have not been widely studied in liver disease. Data are limited to case higher in patients with liver disease than those without. Reported
reports and small, uncontrolled studies describing improvement in incidences of deep venous thrombosis (DVT) or pulmonary embo-
coagulation parameters, subjective clinical improvement, and safe lism (PE) have ranged from 0.5% to 6.3%. Thrombotic complica-
administration in patients with liver disease. The use of PCCs in liver tions can also involve portal, mesenteric, and hepatic veins. PVT
disease should be undertaken cautiously because of the risk of DIC, occurs in approximately 8% to 15% of patients with cirrhosis and is
thrombotic complications, and anaphylaxis; its use should be associated with both severity of disease and inferior prognosis in liver
restricted to emergency situations such as refractory bleeding or if FP transplantation.
administration is limited by risk of circulatory overload. Despite the increased bleeding risks in liver disease, patients may
Recombinant factor VIIa (rFVIIa) is formally approved for the benefit from prophylactic or therapeutic anticoagulation. Hepatic
treatment and prevention of bleeding episodes in patients with thrombosis or PVT may result in worsening liver function, ascites,
hemophilia and inhibitors, acquired hemophilia, and congenital varices, and hemorrhage. Furthermore, microvascular thrombosis has
factor VII deficiency. Because of proven efficacy in these other disor- been proposed to promote hepatic fibrosis and progression of cir-
ders, rFVIIa has been investigated for GI or variceal bleeding in liver rhosis. Clinical decisions are limited by a paucity of studies establish-
disease, liver resection or biopsy, and liver transplantation. Studies ing the optimal dose, duration, monitoring, or choice of anticoagulant
have demonstrated transient normalization of the PT after rFVIIa, and importantly, clear clinical benefit and safety.
yet correlation with improved clinical outcomes has been inconsis- There are currently no standard means of identifying patients with
tent. The only two randomized trials examining rFVIIa in active GI liver disease requiring thromboprophylaxis nor means to reconcile the
and variceal bleeding did not show any benefit over placebo. rFVIIa perceived increased risk of bleeding in these patients. Standard
appears to reduce blood loss and blood product requirements when pharmacologic thromboprophylaxis may be safe and should not be
used prophylactically in invasive procedures or surgery; however, withheld in patients with abnormal coagulation studies in the absence
there is no clear mortality benefit. These potential benefits may be of bleeding. Guidelines on thromboprophylaxis do not address cir-
offset by an observed increase in arterial thromboembolic events, rhosis, so decisions remain individualized. Patients who may particu-
particularly in elderly adults. Compared with FP, rFVIIa can be given larly benefit from primary prophylaxis are those awaiting liver
in small volumes and has no infectious risk. Additional research is transplantation because PVT worsens the long-term posttransplant
required to establish the overall benefit and risk of rFVIIa, and clini- prognosis. Small trials have recently suggested that low-molecular-
cians should proceed with the use of rFVIIa judiciously in the weight heparins (LMWHs) may be safe for thromboprophylaxis in
interim. cirrhosis. Use of VKAs for thromboprophylaxis in patients with liver