Boring Question | Do patients with liver disease need FFP before procedures?

I was recently asked to give fresh frozen plasma to a patient with liver disease and an elevated INR before a therapeutic thoracentesis. He was otherwise healthy and had no history of bleeding diathesis. While I was asking for consent and explaining the risks and benefits of blood product transfusion, I began to wonder about the true benefits in his case. Knowing that liver failure leads to both pro and anti-coagulant deficiencies, I wondered: Is an elevated INR in an individual with hepatic disease really a good indicator of their coagulability?

Do patients with liver disease need FFP before procedures?

The coagulation cascade can be simplified into two competing forces: clot formation and clot breakdown. Within the micro-environment of a vessel wall tear, whichever force is largest will govern whether, and how quickly, a thrombus is generated. So, how does liver disease modify these forces? During my literature search I found a very good review article entitled “The prothrombin time test as a measure of bleeding risk and prognosis in liver disease” [1]. The following discussion owes much to this article.

The “INR” test is a measure, in vitro, of the time to coagulate (formation of a fibrin clot as detected optically) in a patient’s isolated sera that has been seeded with tissue factor. This mimics the process that happens in vivo when a vessel wall is damaged, exposing this factor and setting off the coagulation cascade. However, time to coagulation calculated by an INR only reflects how long it takes for the clot to reach a certain size, and not the speed of its subsequent growth (which is also physiologically important for coagulation). This is where anticoagulant factors (which may also be absent in a patient with liver failure), such as protein C, play a role. They put the ‘breaks’ on clot enlargement after it is formed so their deficiency will not necessarily be reflected with an elevated aPTT or INR.

This problem does not influence the measurement of coagulability in otherwise healthy patients on warfarin (e.g. those with atrial fibrillation). In this setting, coagulability is dependent specifically on the vitamin-K dependant proteins and INR does a good job of indicating the extent of anticoagulation. While vitamin-K factors may also be low in a patient with liver failure, so are other proteins (e.g. protein C) which makes INR a poor reflection of in vivo coagulation. Effectively, both coagulation and anticoagulation can be impaired in liver failure.

Effect of thrombomodulin

Effect of thrombomodulin on clotting in liver cirrhosis [2]

An article entitled “Evidence of Normal Thrombin Generation in Cirrhosis Despite Abnormal Conventional Coagulation Tests” [2] addresses the question of how to measure coagulability in these individuals. It found that thrombin generation was not statistically different between those with cirrhosis and healthy controls once thrombomodulin, a factor essential for protein C function, was added to the assay. Thrombomodulin is found in vivo attached to the endothelium so it is not present in vitro unless added. As you can see from the figure, without thrombomoduliun, cirrhotics (the circles) had much less thrombin generation (ie. clotting activity), whereas when it was added, there was no difference between those with liver disease and healthy controls.

That being the case, coagulability (as measured by thrombin generation) in an in vitro setting that more resembles the in vivo environment (by taking into account protein C) is no different in those with cirrhosis than those without, despite elevated INRs in the former. In addition, numerous observation studies exist that show little relation between INR and bleeding risk in those with liver disease. For example, one study [3] found no relation between INR and severity of bleeding post liver biopsy, a review article [4] of the surgical management of cirrhotic patients found that fresh frozen plasma has not yet been shown to be effective, and another study [5] showed that the addition of fresh frozen plasma to the sera of cirrhotic patients decreased the INR but did not change thrombin generation.

Conclusion

In a patient with cirrhosis, INR is a poor predictor of bleeding risk and the common practice of transfusing fresh frozen plasma before surgery or procedures in otherwise stable patients with liver disease and an elevated INR is questionable.

References

  1. Tripodi, A., et al. Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease” Alimentary pharmacology & therapeutics. 2007: 2, 141-148.
  2. Tripodi, A, et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology, 2005: 3. 553-558.
  3. Ewe, K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Digestive diseases and sciences, 1981: 5. 388-393.
  4. Westerkamp AC, Lisman T, & Porte RJ. How to minimize blood loss during liver surgery in patients with cirrhosis. HPB, 2009: 6, 453-458.
  5. Tripodi, A, et al. Thrombin generation in plasma from patients with cirrhosis supplemented with normal plasma: considerations on the efficacy of treatment with fresh-frozen plasma.” Internal and emergency medicine, 2012: 2, 139-144.

Reviewing with the Staff | Dr. Kerstin de Wit

Dr. de Wit (@kerstinhogg) is an Assistant Professor in the Department of Medicine at McMaster University.  She is cross-appointed between the divisions of Emergency Medicine and Thrombosis. She has reviewed the above piece, and has also written the following.

Bleeding can occur in patients with liver disease for a variety of reasons. The liver synthesis of Factors factors II, V, VI, IX, X, XI, XIII, Protein S, Protein C and fibrinogen can be reduced. Malnutrition is common and vitamin K deficiency results in a further reduction of factors II, VII, IX, X, Protein C and Protein S. Cirrhosis is commonly associated with thrombocytopenia. Furthermore, cirrhotic patients are at risk of bleeding secondary to portal hypertension, in places such as the esophagus where tamponade is challenging to achieve. Falls are common in alcoholic patients and the relative fragility of their tissues is seen in the high prevalence of subdural hematoma in those with minor head injury.

Clotting is not infrequent in cirrhotic patients, with many patients diagnosed with portal vein thrombosis. This venous thrombosis is likely to result from venous stasis in the portal vein, accompanied by reduced presence of our natural anticoagulants Protein C and Protein S.

It is difficult to know whether the bleeding propensity is ‘measureable’, for the reasons stated in this article. However, we should be aware that regardless of coagulation test results, all cirrhotic patients have a high risk of bleeding.

What can we do to mitigate risk of bleeding and improve outcomes in those who present with bleeding?

  • Limiting exposure to anticoagulants and antiplatelet agents (particularly aspirin). Weight appropriate dosing of prophylactic heparin is important. (Patients weighing <50kg should have reduce dose low molecular weight heparin).
  • For bleeding cirrhotic patients we should give IV vitamin K in the emergency department.
  • It is unlikely that fresh frozen plasma is harmful and should be administered in major bleeds.
  • Treatment will also include transfusion of packed red blood cells to a targeted hemoglobin and platelet transfusion to maintain a platelet count >50.

Of course, the ultimate treatment is hemostasis.

This post was peer-reviewed by Dr. Brent Thoma (@Brent_Thoma)

Author information

Michael Garfinkle
Internal Medicine Resident at the University of Saskatchewan and Creator of the LR Database website and Dx Logic app.

The post Boring Question | Do patients with liver disease need FFP before procedures? appeared first on BoringEM and was written by Michael Garfinkle.

Life Beyond Medicine | Humanities and Visual Arts

Do What You Love

Obviously, med school is stressful. It’s especially stressful in third year, when students are starting to reflect on their extra-curricular involvements in the past two years for CaRMs applications and residency. For those who have managed to push out 5 publications, sit in student council, and still managed to go out on a Tuesday night and stumble into a physiology class at 830 on a Wed morning: kudos to them because I don’t know how they did it. For me, one of the most important things I’ve learned in medical school has been this: do what you love, and everything else will fall into place. I hope in sharing my experience, it helps junior medical students and pre-medical students pursue and get involved in their passions, rather than do activities simply to boost their resumes.

Getting involved with med school was a bit different for me. I was never interested in running for student reps, or taking on administrative roles as the class’s treasurer, or even joining intramurals (mostly because I have two left feet, zero hand-eye coordination and my body is built like a brick).

image 1 However, I found my niche in my school’s humanities program. I was lucky enough to attend a school at which humanities were actively encouraged and woven into our curriculum. We had the opportunity to get involved in varied interests ranging from visual arts to theatre to creative writing, and the program hosted frequent events such as art shows and history of medicine lectures to engage students in the humanities.

My partner has a degree in the arts. With my history of being a science nerd, he jokingly mocks the idea of a medical humanities program and specifically my involvement in it. Much to his surprise, I loved the humanities program. My involvement in art shows, presenting at conferences on various humanities projects, putting up my photography for display, and painting pieces representing the medical school experience did not feel like work. I did not feel as though I was just going through the motions of “padding up” my CaRMS application. I enjoyed photography, painting, and writing in humanities and I would’ve enjoyed them in my spare time as hobbies even if it wasn’t for credit. It made me happier. My art pieces became conversation starters for my peers. We bonded over the work I created. I took pride in sharing my passion with others and was encouraged when they decided to get involved too.
I’ve always felt in the past that the visual arts were rarely showcased in school but in medicine (of all places!) I was lucky to be able to incorporate what I love- photography, painting and writing- into my academic experience. For me, combining my hobbies with medicine was a break from endless lectures and classroom work. It was a significant outlet for my stress. I met some wonderful, like-minded people who appreciated the more “artsy” side of medicine as I did, and they, like me, understood how the arts could be used as a medium to portray the unique experiences we have. More importantly, the peers that I worked with understood how important the arts are in my efforts to stay well in medical school.

 

My passion for the humanities and the arts created new opportunities and opened new doors. I had the chance to present at confernces and visited new cities. My artwork was picked to be on the cover of a humanities magazine and was shared nationally. It was also selected to be on the cover of Academic Medicine, as well as the Dalhousie Medical Journal. I then went on to be a humanities editor for our school journal, and combined my loimage 2ve for the humanities and writing. I had incorporated my love of photography into a mandatory classroom project. As a part of this project, I had the privilege to photograph palliative care patients and share their stories with a visual narrative. The project, titled “When Words Are Not Enough: The Role of Visual Narratives in Palliative Care” was presented at a national humanities conference in Calgary. The aim of the project was to use visual narratives to portray the difficulty of the experiences and complex emotions of a patient nearing the end of his/her life. This work was eventually presented to the Provincial Health Minister on behalf of the palliative care team at the hospital, which helped shape funding and policies in palliative care. More importantly, the photographs were gifted to the families of the palliative care patients after they had passed. I had the chance to develop a special relationship with those patients and their families, and learned another significant lesson in medicine: that often, death is not the end. Their stories will carry on through their loved ones and the lives they have touched.

All that time dedicated to humanities- spending hours on a painting or editing photos, preparing presentations and writing reflective pieces- none of it felt like work. It gave me energy, and it was something I looked forward to doing at the end of the day. Sure, I was a little bit bleary eyed getting up early on a Sunday morning post ER-shift, but once I was photographing my classmates swimming with developmentally challenged children at a local swimming pool as part of our Making Waves Program- I did not mind in the least having to get only 3 hours of sleep the night prior. I wanted to do the things I enjoyed, and I was happy to do them. How simple is that?
One of my friends is in first year medical school, and she asked me for advice on surviving medical school at the start of the year. The only advice I could give her with absolute certainty was to get involved with something she was passionate about. I was lucky enough to find my niche in the humanities, and I don’t think my medical school experience would have been the same without it. Do what you love, and everything will fall into place.

image 3

Author information

Jessie Kang
Jessie Kang
Jessie Kang is a medical student at Dalhousie University.

The post Life Beyond Medicine | Humanities and Visual Arts appeared first on BoringEM and was written by Jessie Kang.