Uses and abuses of fresh frozen plasma for the treatment of bleeding

Major bleeding associated with trauma

In the past, ‘reactive’ infusions of FFP were typically prescribed only after abnormalities of PT were documented, but there is now a move towards the pro-active administration of FFP, aimed at preventing deterioration in coagulopathy. An empirical formula-driven approach is often used, defined by a high ratio of FFP transfusions to PRBC approaching 1:1. Although the results appear promising, the limited evidence to support improved patient outcomes and reduced mortality when this near 1:1 approach has been used should be recognised. The observational studies that have been carried out suffer from survivorship bias (only those that survived long enough were likely to have received FFP).⁶ When this was taken into account, Snyder et al⁷ found no significant reduction in mortality for patients who received high ratios of FFP. It is possible that concentrated sources of fibrinogen, such as cryoprecipitate, might prove superior to FFP in this setting, but their role remains to be determined.³

Major bleeding in settings outside trauma

At present, there is a tendency to apply trauma major haemorrhage protocols to other patient groups with bleeding. Therefore, FFP might commonly be given in combination with PRBC as part of a general massive-haemorrhage protocol. But many patients, such as those with gastrointestinal bleeding, are often older than the typical trauma patient and have very different comorbidities.

Patients with gastrointestinal bleeding might have underlying liver disease, which is characterised by complex changes in haemostasis (Table 1). A prolonged PT in a patient with liver disease is often assumed to represent ‘auto-anticoagulation’, but frequently this is not the case as many of these patients have a propensity towards thrombosis or have balanced haemostasis.⁸ Patients with liver disease often have other reasons to bleed, which can be more important than coagulopathy, such as increased portal venous pressure. If extrapolated from trauma practice, early or excessive use of plasma could lead to excessive volume replacement and exacerbate portal hypertension.

Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is predominantly a prothrombotic condition in which clotting factors, platelets and fibrinogen are rapidly consumed. The most important part of managing DIC is identifying and treating the underlying cause. A bleeding patient with DIC and a PT or activated partial thromboplastin time (APTT) greater than 1.5 times the upper limit of normal should be transfused with FFP, although there is no randomised controlled trial evidence to support this. FFP is not recommended for patients who are not bleeding.⁹ An exception to this rule is in the treatment of DIC in patients with acute promyelocytic leukaemia. These patients are at very high risk of bleeding and aggressive treatment of clotting abnormalities until PT or activated partial thromboplastin are normalised is indicated.¹⁰

Warfarin reversal

Major bleeding in a patient taking warfarin (defined as life- or limb-threatening bleeding that requires reversal in less than 6–8 hours) should, in preference, be treated with a combination of intravenous vitamin K and prothrombin complex concentrate (PCC).¹¹ FFP is considerably less effective at reversing warfarin over-anticoagulation than PCC. A commonly referenced study of reversal of warfarin over-anticoagulation recruited and compared 12 patients who received vitamin K and FFP to 29 patients who received vitamin K and PCC. None of the patients who received FFP completely corrected their coagulopathy, whereas all the patients in the PCC group achieved this rapidly.¹² There is, however, much less information on whether more rapid changes in laboratory-defined coagulopathy translate into improved clinical outcomes. FFP is only recommended for the reversal of warfarin over-anticoagulation if PCC is not readily available.