Early changes in coagulation following a paracetamol overdose and a controlled trial of fresh frozen plasma therapy.

Abstract

SUMMARY Early changes in coagulation were found in patients following a paracetamol overdose. Low levels of clotting factors II, V and VII were present within 24 hours of the overdose. As the levels of factor II correlated with plasma fibrinogen values at this time, it is possible that they were consumed in the process of intravascular coagulation, although this was not supported by the presence of raised titres of fibrin degradation products. The prothrombin time ratio was greater than 2-2 within 30 hours of ingestion of the overdose in all patients who eventually died, whereas it was less than this in those developing only moderate liver damage. The administration of fresh frozen plasma to patients did appear to reduce the maximum abnormality of the prothrombin time ratio, which was significantly less three days after the overdose in the group receiving fresh frozen plasma. However, the coagulation disturbance was of short duration, and the prothrombin time ratio had also returned to normal within one week of the overdose in the control patients, and the administration of fresh frozen plasma did not appear to reduce the morbidity or mortality in the treated patients.Paracetamol is frequently taken as an overdose in suicidal attempts, and hepatic damage of all grades of severity, from minor to fulminant hepatic failure, may result (Prescott, Wright, Roscoe, and Brown, 1971). In the latter group bleeding is often a major problem and is not infrequently the direct cause of death. It is thought to be due in part to low levels of clotting factors resulting both from impaired hepatic synthesis and increased consumption from intravascular coagulation (Rake, Flute, Shilkin, Lewis, Winch, and Williams, 1971). To replace this synthetic deficiency we have advocated the regular use offresh frozen plasma (FFP), although controlled evidence of its value was lacking.In this paper we describe detailed studies, including individual clotting factor assays, in 66 patients seen shortly after a paracetamol overdose, together with the results of a controlled trial of FFP in those patients in whom a severe coagulation disturbance subsequently developed.

Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury

“…5,7,28 In particular, continued improvement in serial determinations of prothrombin is strongly indicative of recovery. 6,29 This result was confirmed in the present study, in which a rapid decrease in INR was seen in virtually all (99%) of the survivors but virtually none (3%) of the nonsurvivors.…”

MELD score as a predictor of liver failure and death in patients with acetaminophen-induced liver injury

“…Coagulation factors are among the most important prognostic indicators in acetaminophen-induced FHF. 3,27,28 In particular, a continued improvement in serial determinations of prothrombin (corresponding with a negative ⌬INR) is strongly indicative of recovery. 29,30 In reality, the clinical implications of our findings on ⌬MELD are that patients who continually deteriorate after the onset of HE are likely to die, whereas patients who improve are likely to survive.…”

Outcome of Acute Liver Failure Due to Hepatitis a Treated With Medical Management

“…[7,15,16] Theoretically, prophylactic treatment with FFP in the absence of bleeding is not advised for two reasons; first, the decrease in prothrombin time after FFP administration decreases the accuracy with which prognosis can be judged and second, it results in volume overload and increased ICP. [17,18] In clinical practice, FFP may be beneficial, especially when options for liver transplantation are not available due to various reasons. In our study, 95% of patients received prophylactic FFP.…”