Bleeding and Coagulopathies in Critical Care

Posted by • February 28th, 2014

In the latest article in our Critical Care series, “Bleeding and Coagulopathies in Critical Care,” common abnormalities of blood coagulation leading to thrombosis or bleeding in the intensive care unit are reviewed.

The definition of a coagulopathy is “a condition in which the blood’s ability to clot is impaired.”

Clinical Pearls

• What are possible adverse events associated with the use of fresh frozen plasma?

Retrospective studies of military and civilian casualties showing improved survival with transfusion of 1 U of fresh-frozen plasma for each unit of red cells have resulted in earlier administration of an increased number of units of fresh-frozen plasma. However, these studies have been criticized, particularly for methodologic flaws that include survival bias and heterogeneity between studies. Despite the lack of evidence that bleeding after surgery and gastrointestinal or obstetric hemorrhage are associated with hemostatic changes similar to those in acute traumatic coagulopathy, the early use of a transfusion ratio of fresh-frozen plasma to red cells of 1:1 or 1:2 has become widespread. This increased use of plasma is not risk-free, since the incidence of transfusion-related acute lung injury is increased, as may be the risk of the acute respiratory distress syndrome (ARDS). In one study involving trauma patients requiring a nonmassive transfusion (<10 U of packed red cells within 12 hours after admission), the administration of more than 6 units of fresh-frozen plasma, as compared with no transfusion, was associated with an increase by a factor of 12 in the rate of ARDS and an increase by a factor of 6 in the multiple organ dysfunction syndrome.

• What is the utility of tranexamic acid in the setting of acute bleeding?

Tranexamic acid is a synthetic lysine amino acid derivative that functions to diminish the breakdown of fibrin by plasmin (i.e., a fibrinolytic agent). Tranexamic acid should be administered to all patients with major bleeding after trauma. This recommendation is supported by a large, randomized, controlled trial, the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH-2) study, in which 20,000 trauma patients with bleeding or at risk for major bleeding were randomly assigned to receive either tranexamic acid or placebo. Patients received tranexamic acid within 3 hours after injury had a one-third reduction in deaths from bleeding. The drug ceased to confer benefit and appeared to be associated with increased mortality if it was administered more than 3 hours after injury. The incidence of thrombosis after trauma was not increased in the study patients. Strong evidence that tranexamic acid reduced the need for blood transfusion in surgery has been available for years, although the effect of tranexamic acid on thromboembolic events and mortality in such patients remains uncertain.

Morning Report Questions

Q: What is the pathogenesis, presentation, and appropriate treatment for disseminated intravascular coagulation (DIC)?

A: DIC typically originates in the microvasculature and can cause damage of such severity that it leads to organ dysfunction. DIC usually presents as hemorrhage, with only 5 to 10% of cases presenting with microthrombi (e.g., digital ischemia) alone. Sepsis is the most common cause of DIC in critical care. The consumption of the coagulation proteins and platelets produces a bleeding tendency, with thrombocytopenia, a prolonged prothrombin time and activated partial-thromboplastin time, hypofibrinogenemia, and elevated levels of fibrin degradation products, such as d-dimers. The physiologic anticoagulants are also consumed in the process of inhibiting the many activated coagulation factors. In fulminant DIC, the consumption and exhaustion of platelets and coagulation proteins usually results in oozing at vascular access sites and wounds but occasionally causes profuse hemorrhage. The cornerstone for managing this condition remains the management of the underlying cause (e.g., sepsis). Guidelines for management are based mainly on expert opinion, which suggests replacement of coagulation proteins and platelets in patients who are bleeding. The use of antifibrinolytic agents is contraindicated in the management of DIC, since the fibrinolytic system is required in recovery to ensure the dissolution of the widespread fibrin.

Figure 2.Pathogenesis of Disseminated Intravascular Coagulation in Sepsis.

Table 2. Diagnostic Scoring System for Disseminated Intravascular Coagulation (DIC).

Q: What is the pathogenesis, presentation and appropriate treatment for thrombotic thrombocytopenic purpura (TTP)?

A: TTP is a microangiopathic hemolytic anemia causing red-cell fragmentation. The majority of cases of TTP are due to a deficiency of a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13), a disorder that may be hereditary or caused by autoimmune destruction. The rate of death in untreated cases is nearly 95%, but with early plasmapheresis, the survival rate is 80 to 90%. The use of rituximab, a chimeric monoclonal antibody against the surface B-cell protein CD20, which leads to destruction of those cells, has been shown to reduce the rate of recurrence of the acquired form of this disorder from 57% to 10%. Thrombotic thrombocytopenic purpura is a medical emergency and in untreated cases is associated with a rate of death of 90%, usually from myocardial infarction due to platelet thrombi in the coronary arteries. An active diagnosis of this disorder or failure to rule it out should lead to urgent plasmapheresis.

3 Responses to “Bleeding and Coagulopathies in Critical Care”

  1. Nahla Anber says:

    l have a great owner to be a reviewer in your journal. I would like to be a member in the journal and to reseave the full text of publishing research.

    with my best regards

    Nahla Anber

    Licture of Biochemistry
    Emergency Hospital, Faculty of Medicine
    Mansoura University, Egypt

  2. Andrea Parent says:

    Hi Nahla,

    You can subscribe to the Journal here!

  3. eman says:

    very nice yopic but need to be more concerned about obst and gyn