Effect of prothrombin complex concentrate on INR and blood coagulation system in emergency patients treated with warfarin overdose

Abstract

We investigated the effect of prothrombin complex concentrate (PCC) on the international normalized ratio (INR) and blood coagulation system in two emergent patients treated with warfarin for secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation. An 80-year-old woman developed massive subcutaneous hemorrhage and swelling on her right upper extremity with weak pulsation of the right radial artery and had an INR above 10. An 83-year-old man had pleural effusion with an INR value of 6.69 and pleural puncture was immediately required. We administered 500 IU of PCC to the two patients (17.2 IU/kg and 12.5 IU/kg) with 10 mg of vitamin K. The INR decreased to 1.12 and 1.85, respectively, with an increase of plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa 10 min after administration. The plasma levels of the thrombin-antithrombin III complex increased (from 4.0 to 12.0 micro g/l and from 0.5 to 28.9 micro g/l, respectively, normal value <3.0), but prothrombin fragment 1+2 increased minimally 10 min after administration (from 0.4 to 1.1 nmol/ml and from 0.4 to 0.7 nmol/ml, respectively, normal value 0.4-1.4 nmol/ml). Plasma levels of D-dimer remained unchanged. The massive subcutaneous hemorrhage in the former patient improved in 14 days. Anticoagulation was restarted in the latter patient after 14 days of PCC administration. There were no embolic episodes during the month after PCC administration. In conclusion, a small amount of PCC may be effective in immediately correcting increased INR levels with increased plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa and may partially activate the coagulation system without any effects on plasma levels of D-dimer.

Prothrombin Complex Concentrates for Oral Anticoagulant Therapy-Related Intracranial Hemorrhage: A Review of the Literature

“…It is essential to include vitamin K in the regimen to reverse the INR, since the effects of PCC may be transient [44]. In contrast, vitamin K produces a delayed (6-8 h), but sustained rise in PCC factors assuming intact hepatic function [51].…”

“…For factors VII and IX, it is estimated that the ''in vivo recoveries'' are about 1, meaning that for each 1 IU/kg injection of a given factor, the plasma concentration of that factor will increase by about 1% [49]. The maximum infusion rate of PCC has been studied; however the safe upper limit for rate of infusion is not well- [34][35][36][37][38][39][40][41][42][43][44][45] established. Some suggest not exceeding 75-100 IU/min [34,50]; however, an infusion rate up to 210 IU/min of PCC was well-tolerated in a study of healthy volunteers [36].…”

“…Preparations of PCC that contain higher concentrations of factors II, X, or contain the activated form of factor VII may increase thrombogenicity [59,60]. Some PCC formulations contain protein C and S, with the aim of Data derived from references: [34][35][36][37][38][39][40][41][42][43][44][45]47] shifting the balance of coagulation factors to a more physiological state, and thus preventing excessive coagulation [58]; however, no large scale randomized trials exist to compare the different formulations. The presence of activated clotting factors in some PCC may favor coagulation.…”

“…Multiple studies have evaluated the effects of PCC on the coagulation system [34][35][36][37][38][39][40][41][42][43][44][45]. Given the heterogeneity among various PCC formulations, and different methods of measuring coagulation parameters, it is difficult to generalize their hematological effects.…”

The role of anticoagulants, antiplatelet agents, and their reversal strategies in the management of intracerebral hemorrhage

“…39,78 Prothrombin complex concentrate is increasing in popularity as a low-volume, rapidreversal agent, and has been reported as superior to FFP in several studies. 49,68,72,76 Individualized dosing of PCC may be the most effective method of reversal. In 1 study, individualized dosing of PCC based on the patient's body weight and initial INR was superior at reaching the target INR 15 minutes after dosing compared with the standard dosage of PCC.…”