Grand Rounds Recap 1.12.22
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R1 Clinical diagnostics: ITP, TTP, and dic WITH dr. moulds
Normal Platelet Physiology
Primary hemostasis is platelet driven; secondary hemostasis is driven by the coagulation cascade. When clots are no longer needed, they undergo fibrinolysis.
Causes of thrombocytopenia include:
Decreased platelet production - seen with bone marrow disease or liver disease (decreased thrombopoietin production)
Increased platelet consumption - due to antibody mediated destruction or massive thrombosis (consumption)
Redistribution - due to dilution (unbalanced product resuscitation) or hypersplenism (splenic sequestration)
When do we worry about thrombocytopenia?
We should worry when there is severe thrombocytopenia plus bleeding, the need for an urgent procedure, pregnancy, suspected thrombotic microangiopathy, or suspected marrow failure.
Idiopathic Thrombocytopenic Purpura (ITP)
This is a disorder of platelet quantity. The platelets present function normally, but there aren’t enough platelets around.
This disease is typically due to autoantibodies against platelets which lead to platelet destruction. There may also be some component of impaired megakaryocyte production.
80% of the time this occurs without a clear precipitant, 20% of the time it is secondary to an underlying illness which triggers the disorder.
Clinical presentation can vary widely:
Asymptomatic
Mucocutaneous bleeding or heavy menstrual bleeding
Severe bleeding such as intracranial hemorrhage
Diagnosis:
This is a diagnosis of exclusion. Essentially, we identify thrombocytopenia and then exclude other causes.
Obtain a CBC and peripheral smear (schistocytes and rouleaux formation)
Obtain HIV and HCV testing as these can be precipitants for ITP
Treatment
Critical Bleeding - any bleeding that is a threat to life, limb, or sight
Platelet transfusions - as often as q1hr
IVIG (1g/kg)
Steroids (40mg IV decadron, or 1g IV of methylprednisolone) to suppress the immune system
Severe Bleeding - bleeding that results in a hemoglobin drop by 2+ g/dL or requires transfusion of 2 or more units of pRBCs, but does not meet the criteria for critical bleeding.
Treat with glucocorticoids or IVIG as you would in critical bleeding
Minor Bleeding - mucocutaneous bleeding or petechiae
Decadron 40mg PO or IV qd x 4d or Prednisone 1mg/kg daily x 1-2 weeks with a taper.
Asymptomatic patients
If the platelet count is > 20k and they have no symptoms, no treatment is needed
Patients with platelets < 20K with minor bleeding are treated with oral steroids
Special considerations: any patients requiring an invasive procedure, elderly patients at high risk of falls, or patients who otherwise have an increased risk of bleeding (liver disease or anticoagulated) warrant treatment.
Disposition
Patients with ITP and critical or severe bleeding, or any patients with < 10K platelets should be admitted for treatment and close monitoring.
Thrombotic Thrombocytopenic Purpura (TTP)
Due to deficiency of the ADAMTS-13 enzyme
ADAMTS-13 is a von-Willebrand factor cleaving protease. Without ADAMTS-13 present to regulate von-Willebrand factor, widespread microthrombi form resulting in a consumptive thrombocytopenia.
95% of the time this is related to acquired auto-antibodies. About 5% of the time this is due to a genetic mutation in ADAMTS-13.
The classic presentation is a pentad of fever, anemia, thrombocytopenia, renal failure, neuro symptoms. However, we would ideally catch this disorder and begin treatment before the patient develops the entirety of the pentad.
Diagnosis
CBC with a peripheral smear will demonstrate hemolysis
Hemolysis labs will be elevated
End organ dysfunction will be noted (elevated creatinine and troponin)
You can send an ADAMTS-13 level although this will not result in the ED course
PLASMIC score for TTP
A score that predicts ADAMTS13 deficiency in suspected thrombotic thrombocytopenic purpura (TTP) , but has not been validated for use in the emergency department. Includes INR MCV, hemolysis, thrombocytopenia, history of cancer, and history of transplant as categories for scoring.
Treatment
Plasma exchange therapy - Reduces all-cause mortality compared to plasma infusion alone.
Replaces the deficient ADAMTS-13 with plasma transfusions
Removes the causative auto-antibodies
Plasma transfusion alone can assist in replacing deficient ADAMTS-13 but does not remove causative autoantibodies and can predispose to volume overload
Do not transfuse platelets, as this can worsen the pathophysiology of the disease by feeding it with platelets.
Disseminated Intravascular Coagulation (DIC)
A self-perpetuating cycle of consumptive coagulopathy.
Blood is exposed to large amounts of procoagulants → this leads to widespread massive activation of the coagulation cascade → thrombi form from platelets and fibrin → platelets and coagulation factors are consumed faster than they can be produced → fibrinolysis is activated at sites of thrombus →clots are degraded resulting in elevated fibrin degradation products and widespread bleeding → lack of available platelets and coagulation factors leads to further bleeding → bleeding triggers platelet plug formation and the coagulation cascade with what little components remain and the cycle continues.
Presentation
Presents with widespread bleeding, may see gum bleeding or oozing from IV sites. Chronic DIC may present with thrombosis. Evidence of end organ damage will be present.
Diagnosis
CBC and peripheral smear which will show hemolysis
PTT and INR will be elevated
Markers of end-organ damage will be elevated
Treatment
DIC is typically triggered by an underlying disease or disorder (such as sepsis or trauma). Treat the underlying cause and counter bleeding with transfusions as needed.
Diversity, equity, and inclusion grand rounds WITH visiting lecturer dr. landry
“Of all the forms of inequality, injustice in healthcare is the most shocking and inhumane” - Dr. Martin Luther King Jr.
One of the key moments for Dr. Landry occurred while he was on a routine shift as a resident during which he was taking care of a patient with symptoms of diverticulitis. Due to ED crowding and hospital boarding, the patient , who was Black, was placed in a hallway bed throughout the entirety of their encounter. Dr. Landry had a good shift, built a relationship with this patient, and diagnosed and treated him. However, at the end of the shift the patient asked him, “Why are all the black patients in hallway beds?”. As a trainee, Dr. Landry tried to explain the decision based on a given patient’s acuity, need for monitoring, availability of beds at the time of check-in, and so on. But as he looked around the department, he noticed the pattern as well. He was bothered that this was happening, that he was relatively blind to it previously, and that he was part of the system creating space for such a disparity to occur.
Equality vs Equity
Equality is giving each individual the same resources, regardless of their needs. This leads to unequal outcomes despite equal resources. Equity is providing resources and opportunities based on individual needs in order for each person to reach the same outcome.
A study published by Schulman et al in the NEJM in the late 90s looked at the effect of race and sex on physicians' recommendations for cardiac catheterizations. In this study, 720 physicians viewed recorded interviews of patients presenting with typical chest pain, with the patients varying in age and race. They found that the elderly black female was less likely to be referred for cardiac catheterization when compared to the younger Caucasian male patient.
What was also interesting were the responses from the medical community at this time, which frequently included attempts to discredit various aspects of the study.
This study triggered many early discussions about health disparities in various spaces, how we as a body of providers can highlight awareness of these disparities, and how we can begin to address them.
Following this article was a book entitled “Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care” by the Institute of Medicine, which brought attention to further disparities in healthcare.
How do we move from recognition to change?
We need to intentionally utilize culturally and linguistically appropriate care.
We need to dashboard disparities to further our awareness and understanding.
We should address bias, microaggressions, and racism towards both patients and staff members.
We need to include health equity and medical disparities in undergraduate and graduate medical education as a longitudinal curriculum.
We need to diversify faculty and trainees.
URiM faculty need to be involved in research and offer scholarly opportunities for advancement within academic medicine.
r4 capstone: the science of laughter WITH dr. urbanowicz
Gelotology - The study of humor and laughter
As we get older, we laugh less
Laughter is both a physical response and also a form of communication.
The social benefit of laughter - you are statistically more likely to laugh when you are with other people vs when you are alone, and your likelihood of laughter increases with increasing familiarity with your cohort.
Laughter can highlight dissonance between expectation and reality - frequently when a situation does not go as planned, we respond with laughter, which further highlights the unexpected and draws our attention to it.
Your overall disposition and perception of the world improves when there is more laughter among your immediate social group - similar to how smiling even when you aren’t happy can trick your brain into thinking you are actually happy.
Laughter has been shown to have numerous physiologic benefits including:
Decreasing markers of stress
Increasing immune system activity
Stimulating the dopamine reward pathway
Improving sleep quality
Increasing laughter in day-to-day life:
Ask what made people laugh that day
Laugh together over shared experiences
Plant funny stimuli
Practice laughter yoga and forced laughter
iron toxicity WITH cchcm pem
Pathophysiology of iron toxicity
Ingestion of iron results in free radical production leading to peroxidation.
Iron is also a direct vasodilator and is caustic to the GI mucosa.
The toxicity of iron depends on the dose of elemental iron, which varies depending on the iron formulation of the product ingested.
20 mg/kg ingestion: patients will develop symptoms of toxicity
40 mg/kg ingestion: requires medical evaluation
60 mg/kg ingestion: results in severe toxicity
Clinical Presentation
Phase I (Gastrointestinal)
Occurs 30 min to 6 hours post-ingestion.
Typically presents with abdominal pain, vomiting, diarrhea, +/- GI bleeding.
Mild to moderate ingestions typically do not progress past this phase. If children have not developed symptoms within 6 hours of ingestion, they are likely to remain asymptomatic.
Phase II (Latent)
Occurs 6 to 24 hours post ingestion
GI symptoms typically improve and may or may not resolve entirely.
Cellular toxicity from free radicals persists despite symptomatic improvement.
This phase can be difficult to distinguish from symptom resolution due to a less severe ingestion, similarly to the lucid interval in epidural hematomas.
Phase III (Shock and Metabolic Acidosis)
Occurs 12 to 24 hours post-ingestion.
Patients present in profound shock with metabolic acidosis. The shock may have cardiogenic, hypovolemic, and distributive components.
This can progress to multi-system organ failure due to widespread free radical cellular damage.
Once a critical amount of iron has become intracellular and reached the mitochondria, treatment is ineffective and the patient outcome is poor.
Phase IV (Hepatotoxicity)
Occurs within 2 days post-ingestion.
The liver is exposed to iron through the portal system as well as passive absorption and is more susceptible to oxidative stress than other organs.
Hepatotoxicity is the second leading cause of death from iron ingestion.
Phase V (GI Scarring)
Occurs 2 to 8 weeks post-ingestion.
Scarring and strictures which can result in gastric outlet obstructions and other blockages.
Management
Supportive Care
Always start with assessment and support of the ABCs.
Chelation with Deferoxamine
Deferoxamine binds with ferric iron in the blood to form a water-soluble compound which can be excreted by the kidneys.
Indications include:
A serum iron level > 500 nanograms/dL
Severe symptoms
Metabolic acidosis
An estimated ingestion > 60 mg/kg of elemental iron
Once iron has moved intracellularly, chelation is no longer effective. Therefore, you should start chelation therapy ASAP.
GI Decontamination
Performed simultaneously with chelation therapy. Used in patients with moderate to severe ingestion and/or large amounts of radio-opaque material in the GI tract
If there is a large number of pills, they may have coalesced into a large boulder and may need to be removed by endoscopy
Pitfalls
Miscalculation of the elemental iron dose and misclassification of ingestion quantity can lead to false reassurance and undertreatment.
Failure to recognize the latent phase of iron toxicity can lead to untreated progression and severe outcomes.
Do not solely rely on serum iron levels to determine severity of the ingestion as they may not accurately reflect the quantity ingested.
Remember that deferoxamine can cause acute lung injury if administered for more than 24 hours.
