INR reduction with FFP – How low can you go?

Background

Bleeding patients or those undergoing procedures that are at high risk of bleeding may require correction of their INR. Multiple products can be used to achieve this, including fresh frozen plasma (FFP). FFP contains many substances, including clotting factors, fibrinogen, plasma proteins, electrolytes, and anticoagulant factors. It is sometimes said that the intrinsic INR of FFP is approximately 1.6-1.7 and that it’s not possible to achieve a lower INR. This pearl will further explore these concerns.

Evidence

  • What is the INR of FFP?
    • The mean INR of FFP appears to be ~1.1 (0.9-1.3) [1,2].
    • Reports that the intrinsic INR of FFP is 1.6-1.7 may be based on the clinical experience of not being able to achieve an INR <1.6-1.7 with FFP.
  • Is it possible to “normalize” the INR with FFP alone?
    • Several studies have found that it’s difficult to achieve an INR <1.7 with only FFP [3,4]. However, other studies were able to achieve lower average INR values [2,5,6]. 
    • Overall, these studies found that there was a significantly greater decrease in INR when the pre-FFP INR was higher, but there was a much smaller decrease when the INR was closer to the normal range.
  • Why does FFP appear to have diminishing returns when the pre-FFP INR is lower?
    • The relationship between the INR and percentage of clotting factors present in the blood is not linear (see figure) [7].
    • For example: An increase of ~5% in clotting factors may decrease the INR from 3 to 2.5 but the same amount of FFP may only reduce an INR of 1.7 to 1.6.

Figure 1: Adapted from Dzik  2012 [7].

    • Additionally, the table below also demonstrates that small volumes of FFP result in large changes when the initial INR is elevated, but very large amounts of FFP are required to achieve an INR of 1.3 no matter the initial INR (see table).
Amount of FFP to Achieve a Target INR Based on Pre-FFP INR
Target INR
1.31.73.0
Initial INRVolume (L)Dose (mL/kg)Factor (%)Volume (L)Dose (mL/kg)Factor (%)Volume (L)Dose (mL/kg)Factor (%)
6.04.564452.536251.52115
5.04.361432.332231.01410
4.04.057402.029200.575
3.03.550351.52115
2.02.536250.575

Table 1: Adapted from Holland 2006 [3]. Note: 1 unit of FFP is ~200-250 mL

    • Given the above data, the issue preventing the achievement of an INR <1.7 appears to be the dose/volume of FFP required and not the intrinsic INR of FFP.
  • Does the INR need to be <1.7 to achieve hemostasis?
    • Since the INR only provides limited information regarding a single aspect of anticoagulation status, complete normalization for the INR to control bleeding is usually not necessary [6].
    • An INR elevation alone does not indicate a patient is coagulopathic or at an increased risk of bleeding [7]. Additionally, an INR elevation in patients with liver dysfunction likely reflects an overall state of decreased factor production, both procoagulant and anticoagulant factors [8].
    • The target INR varies depending on multiple patient factors and planned interventions, but an INR of 1.0 is likely not necessary to prevent bleeding or achieve hemostasis.

Bottom Line

  • A unit of FFP has an INR of ~1.1, but this doesn’t mean it can easily normalize the INR.
  • There is a non-linear relationship between percentage of clotting factors and the INR, resulting in diminishing returns from each unit of FFP as the INR decreases.
  • Very large doses of FFP may be required to fully correct an elevated INR, which frequently precludes its use.
  • Complete normalization of the INR is not required to achieve hemostasis or prevent bleeding from a procedure.

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Holland LL, Foster TM, Marlar RA, Brooks JP. Fresh frozen plasma is ineffective for correcting minimally elevated international normalized ratios. Transfusion. 2005;45(7):1234-1235. doi: 10.1111/j.1537-2995.2005.00184.x. PMID: 15987373.
  2. Only AJ, DeChristopher PJ, Iqal O, Fareed J. Restoration of normal prothrombin time/international normalized ratio with fresh frozen plasma in hypocoagulable patients. Clin Appl Thromb Hemost. 2016;22(1):85-91. doi: 10.1177/1076029614550819. PMID: 25294634.
  3. Holland LL, Brooks JP. Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results. Am J Clin Pathol. 2006;126(1):133-139. doi: 10.1309/NQXH-UG7H-ND78-LFFK. PMID: 16753596.
  4. Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion. 2006;46(8):1279-1285. doi: 10.1111/j.1537-2995.2006.00891.x. PMID: 16934060.
  5. Müller MCA, Straat M, Meijers JCM, et al. Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy. J Thromb Haemost. 2015;13(6):989-997. doi: 10.1111/jth.12908. PMID: 25809519.
  6. McCully SP, Fabricant LJ, Kunio NR, et al. The International Normalized Ratio overestimates coagulopathy in stable trauma and surgical patients. J Trauma Acute Care Surg. 2013;75(6):947-953. doi: 10.1097/TA.0b013e3182a9676c. PMID: 24256665.
  7. Dzik W “Sunny.” Reversal of drug-induced anticoagulation: old solutions and new problems. Transfusion. 2012;52(s1):45S-55S. doi: 10.1111/j.1537-2995.2012.03690.x. PMID: 22578371.
  8. Harrison MF. The misunderstood coagulopathy of liver disease: a review for the acute setting. West J Emerg Med. 2018;19(5):863-871. doi: 10.5811/westjem.2018.7.37893. PMID: 30202500.
By |2021-08-28T10:03:39-07:00Aug 21, 2021|EM Pharmacy Pearls, Heme-Oncology|

Diagnosis on Sight: Neck Bruising Leads to a Surprise Diagnosis

A 76-year-old female with a history of HTN, TIA, CAD, left CEA, and CKD presented to the emergency department for evaluation of neck bruising and swelling. The patient stated that the night before, she was eating popcorn and choked on a kernel. She states that she coughed to clear her throat and shortly after she developed swelling and bruising to the left side of her neck, which has progressively gotten worse. The patient has a remote history of left carotid endarterectomy and was concerned that her symptoms could be related to the prior surgery. On examination, she had ecchymosis and a hematoma/mass to the left side of her neck without palpable thrill or bruit. A well-healed CEA scar was noted. A CTA of the neck was obtained to determine the source of the ecchymosis/hematoma. What is the diagnosis?

A large neck mass with venous bleeding causing cervical hematoma and ecchymosis.

Explanation:

Neck Mass

Image 2. This axial CT angiogram image shows the large left-sided mass with vessels and hemorrhage, which appears to originate from the inferior parotid.

Spontaneous cervical hematoma is an uncommon condition, which can be life-threatening [1]. This first case of spontaneous neck hematoma was described by Capps who observed this condition in a patient with a parathyroid adenoma [2]. Symptoms of neck hematoma include the classic triad named for Capps, which consists of:

  •       tracheal and esophageal compression
  •       neck edema and ecchymosis
  •       tracheal displacement

The condition can be caused by a variety of etiologies including bleeding from masses, underlying coagulopathies, rupture of aneurysms, and infections [1]. CT angiography is typically the test of choice to evaluate the source and extent of bleeding [3]. Large hematomas can lead to airway compromise and require airway and surgical/IR intervention. Smaller, stable hematomas may be observed and can be self-limited. The underlying etiology of the hematoma should be sought and treated.

Case Conclusion:

The hematoma and ecchymosis resolved over time without intervention. The patient underwent ultrasound-guided lymph node biopsy by interventional radiology. Pathology revealed an aggressive double expressor diffuse large B-Cell lymphoma. A pet scan revealed lymphatic involvement on both sides of the diaphragm. The patient was counseled on treatment options including chemotherapy and after discussion palliative radiation was pursued.  Ultimately, the patient transitioned to hospice care.

Want more visual stimulation? Check out the Diagnose on Sight archives!

References:

  1. Cohen O, Yehuda M, Adi M, Lahav Y, Halperin D. Spontaneous neck hematoma in a patient with fibromuscular dysplasia: a case report and a review of the literature. Case Rep Otolaryngol. 2013;2013:352830. PMID: 24191215.
  2. Zammit M, Siau R, Panarese A. Importance of serum calcium in spontaneous neck haematoma. BMJ Case Rep. 2020 Sep 6;13(9):e237267. PMID: 32895253.
  3. Haynes J, Arnold KR, Aguirre-Oskins C, Chandra S. Evaluation of neck masses in adults. Am Fam Physician. 2015 May 15;91(10):698-706. PMID: 25978199.
By |2021-05-24T08:27:03-07:00Jun 4, 2021|Diagnose on Sight, Heme-Oncology|

SAEM Clinical Image Series: Sun-burnt Hands and Lips

blistering

A 44-year-old Caucasian male with a past medical history of hepatitis C presents with a complaint of pain, swelling, and skin blistering of his hands. He also notes skin sores on his nose, lower lip, and the tops of his ears. The patient claims that these have become progressively worse since starting work a month ago in outdoor construction. The patient denies the use of medications or illicit drugs and denies any medical allergies. He admits to tobacco use and daily alcohol use. The patient denies any other symptoms.

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SAEM Clinical Image Series: The Insidious Rash

rash

A 60-year-old African American female with a history of hypertension presents to the emergency department for an itchy, diffuse rash. She first noticed the lesions a few years prior, and they have progressively become larger and more inflamed. The lesions have become severely pruritic over the last couple of months. Steroid creams did not appear to improve symptoms. Currently, the lesions on her arm have become painful with yellow drainage. The patient denies nausea, vomiting, and fever.

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SAEM Clinical Image Series: Rash with Blood Pressure Cuff Inflation

Rash with blood pressure cuff inflation - petechiae

[Click for larger view]

Chief Complaint: Possible seizure, Left arm rash

History of Present Illness: A 29-year-old with a history of migraine headaches, thalassemia of unknown phenotype, and no history of hypertension or epilepsy arrived to the emergency department via ambulance after possible seizure. The patient had nausea and vomiting the morning after a night of heavy drinking. After several rounds of vomiting, she felt shaky, lightheaded and experienced paresthesia in both of her hands and feet. There was no loss of consciousness, confusion or incontinence. EMS reported hypertension and tremors with upper extremity spasms. The patient developed a left upper extremity rash distal to the blood pressure cuff after paramedics did the first blood pressure measurement.

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Traumatic Bleeding in Anticoagulated Patients: 5 Other Sources Beyond the Brain

anticoagulated patientsWhen a patient is started on anticoagulant therapy, the purpose is to prevent clot formation or propagation. Anticoagulants can improve morbidity and mortality by maintaining cardiac stent patency, reducing the propagation of pulmonary emboli, or preventing formation of intra-cardiac thrombi.1,2 Unfortunately even after minor trauma, these medications can cause major problems. When a patient on clopidogrel is in a motor vehicle collision (MVC) or an elderly patient on warfarin falls out of their bed, the once life-improving therapy becomes potentially life-threatening. It is important for emergency care providers to maintain a high index of suspicion for life-threatening bleeds in all patients on anticoagulation following even minor injuries. The purpose of this discussion is to look beyond the intracranial hemorrhages (ICH) and to consider 5 other sources of bleeding that can occur in anticoagulated patients.

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By |2017-06-04T15:51:12-07:00May 29, 2017|Heme-Oncology, Trauma|

Lumbar Puncture on an Anticoagulated Patient in the Emergency Department: Is it safe?

lumbar punctureThe lumbar puncture (LP) procedure is commonly performed in the Emergency Department (ED). While minor complications of LP such as post-procedure headache or back pain occur somewhat regularly, significant complications such as post-procedural spinal hematomas, are rare.1 Despite their low incidence, these spinal hematomas are associated with a significant amount of morbidity for the patient and increased medicolegal risk for the provider.

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By |2016-11-11T19:47:00-08:00Jun 27, 2016|Heme-Oncology, Medicolegal, Neurology|
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