Clotting Cascade – NOW WITH NOACs

clotting_cascade_NOAC

The clotting cascade was one of the first doodles posted on Sketchy Medicine, I’ve now updated it to include some of the Novel Oral Anticoagulants (NOACs): Dabigatran, Rivaroxaban and Apixiban.

Dabigatran (Pradaxa)

  • Selective, reversible direct thrombin inhibitor
  • Is actually a prodrug that reaches peak concentration 2-3 h post ingestion
  • Approved (in Canada) for:  Thromboprophylaxis in atrial fib, post-op, and treatment of VTE and VTE recurrence
  • T1/2: 7-17 h
  • CYP independent (not as many drug-drug interactions)
  • Excreted in urine 95% / Feces 5%
  • Reversal: hemodialysis?
  • Big trial = RELY, REMEDY

Rivaroxaban (Xarelto)

  • Selective, reversible direct factor Xa inhibitor
  • Approved (in Canada) for:  Thromboprophylaxis in atrial fib, post-op, and treatment of VTE and VTE recurrence
  • T1/2: 3-9 h (relatively speedy!)
  • CYP3A4
  • Very good oral bioavailability
  • Almost all of it is protein-bound in the serum
  • Urine 70% / Feces 30%
  • Reversal: ???? (not hemodialysis)

Apixaban (Eliquis)

  • Selective, reversible direct factor Xa inhibitor
  • Approved (in Canada) for:  Thromboprophylaxis in atrial fib, post-op, and treatment of VTE and VTE recurrence (only atrial fib in the USA)
  • T1/2: 8-15
  • CYP3A4
  • Almost all (95%) protein-bound in the serum
  • Urine 30% / Feces 70%
  • Reversal: ???? (not hemodialysis)

Reversal agents:

  • Hemodialysis
    • Only good for agents that aren’t highly protein bound (i.e. dabigatran).
    • Warfarin, rivaroxaban and apixaban are all mostly bound to protein in the serum, so dialysis won’t get rid of them
  • PCC
    • Plasma-derived product containing factors II, IX and X (3-factor PCC) or II, VII, IX and X (4-factor PCC) in addition to variable amounts of proteins C and S, and heparin
  • aPCC
    • Plasma-derived product containing activated factors II, VII, IX and X
  • Recombinant factor VIIa
    • Looks good in test tubes, clinical evidence lacking
  • Idarucizumab
    • Humanized monoclonal antibody against dabigatran
  • Andxanet alfa
    • Recombinant factor Xa derivative
    • Could theoretically be used for rivaroxaban and apixaban

Anticoagulation Assays

Effect of oral anticoagulants on coagulation assays (Jackson II & Becker, 2014)

(Adapted from Jackson II & Becker, 2014)

Approach to bleeding

Managing target-specific oral anticoagulant (Siegal, 2015)

(From Siegal, 2015)

References

  • Jackson II LR & Becker RC. (2014). Novel oral anticoagulants: pharmacology, coagulation measures, and considerations for reversal. Journal of Thrombosis and Thrombolysis, 37(3), 380-391.
  • Ufer M. (2010). Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thrombosis and Haemostasis. 103: 572-585.
  • Siegal DM. (2015). Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents. Journal of Thrombosis and Thrombolysis, 1-8.

Treatment of scaphoid fractures

scaphoid-flow-chart

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Scaphoid fractures are very common but due to its weird blood supply, the scaphoid is prone to not healing well (review the anatomy of the scaphoid in this doodle). This is why fractures of the scaphoid and even SUSPECTED fractures of the scaphoid are treated very conservatively.

Even if you’re suspicious of a fracture but don’t see one on x-ray, that’s enough to subject someone to a cast for 2 weeks and then bring them back to re-x-ray.

This doodle goes through the basic algorithm for treating scaphoid fractures centred around a timeline to show how long the treatment course can be. There are of course nuances to the management, so take a person’s work and hobbies and handedness into consideration. Also, don’t be afraid to consult your friendly hand/wrist specialist.

Scaphoid bone anatomy and fractures

scaphoid_fracturesThe scaphoid bone is one of the eight carpal bones of the wrist (you can check out this doodle for a refresher).

The scaphoid is the most commonly fractured carpal bone, accounting for almost 70% of fractures. It tends to be young males who break their scaphoid this is both an anatomical thing: younger kids get ligament injuries and older folks break their distal radius and a lifestyle thing: falling on outstretched hands (skateboarding, snowboarding) or throwing a punch both place a lot of force across the scaphoid leading to fractures.

The bad thing about scaphoid fractures is that the blood supply (from a branch of the radial artery) comes from distal to proximal. Since most fractures happen at the waist of the scaphoid the likelihood of having poor blood supply to the fracture site is quite high. It doesn’t help matters that around 80% of the scaphoid is articular surface (joint surface), so if it doesn’t heel well, it can lead to problems with arthritis of the wrist later on.

 

Presentation

Scaphoid fractures present with a pretty classic story and the person is usually swollen and bruised and will have tenderness in their “snuffbox.” So even if the x-ray doesn’t show a fracture, it’s best to treat with a cast for comfort and safety and then recheck them in 2 week’s time (this will be discussed in a separate post).

Intracranial Hemorrhages

For the most part, bleeding in the brain (intracranial hemorrhage) is a pretty bad thing. Though like most things in medicine, there are varying degrees of badness, all with different mechanisms that help us sort of why we really wouldn’t want something to happen.

Intracranial hemorrhages are categorized into 5 subtypes, and are given obvious sounding names depending on where the bleed is in the brain and in relation to the layers of the meninges.

  1. Epidural (above the dura, right under the skull)
  2. Subdural (below the dura, above the arachnoid)
  3. Subarachnoid (below the arachnoid, above the brain)
  4. Intraventricular (in the ventricles)
  5. Intraparenchymal (in the meat* of brain)

* The brain is not meaty, “parenchyma” means the functional part of the organ

The poor pia mater did not get any hemorrhage named after it, but if you want you can think of intraparenchymal as “subpial” just so it doesn’t feel left out.

Telling them apart

The most confusing thing, and thing that likes to get asked the most on exams, is the difference between epidural and subdural hematomas.

Epidural Subdural Subarachnoid
Above the dura Below the dura Below the arachnoid
Respects suture lines Doesn’t respect suture lines No respect for anything
High force trauma Low force trauma Aneurysm rupture or high force trauma
Arterial blood (commonly the middle meningeal artery) Venous (from venous plexus) Arterial from the circle of Willis
Lentiform (lens-shaped) or biconcave on CT Cresent (banana-shaped) on CT Lining surface, going into fissures and sulci and sella (death-star)
Acute presentation May be insidious (worsening headache over days) Acute presentation (thunderclap headache)

The reason intraventricular and intraparenchymal aren’t included in the table as they each have a bunch of causes, but for both of them trauma is a potential cause as well as hypertension and stroke. It’s good to remember that premature infants are at a much higher risk of intraventricular hemorrhages.

Blood on CTs

  • New blood: bright white
  • 1-2 weeks: isodense
  • Old blood (2-3 weeks): dark grey

Shock

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Shock is “a syndrome resulting from failure of the cardiovascular system to maintain adequate tissue perfusion.”

Weil-Shubin Classification of Shock

  1. Cardiogenic –  Poor cardiac function reduces forward blood flow.
  2. Hypovolemic – Loss of intravascular volume caused by: hemorrhage, dehydration, third space loss, vomiting, diarrhea.
  3. Obstructive – Impair cardiac filling due to external restriction. Caused by cardiac tamponade, tension pneumothorax, pulmonary embolus.
  4. Distributive – Primarily characterized by loss of peripheral vascular tone. Caused by septic, anaphylactic, adrenal insufficiency, neurogenic, liver failure.

Adrenergic Receptors

  • α1: Vasoconstriction
  • α2: Inhibits norepinephrine release, decreases BP, sedative effects
  • β1: Positive inoptrope (increases cardiac contractility and stroke volume)
  • β2: Vasodilation, broncodilation

Vasoactive Drugs

Epinephrine

  • Effects: Causes vasoconstriction and increases cardiac output. Inotrope effect predominates at low doses (< 4.0 mcg/min).
  • Disadvantages: Associated with lactic acidosis, hyperglycemia, pulmonary hypertension, tachyarrythmias, and compromised hepatosplanchnic perfusion.
  • Use: First-line agent for cardiac arrest and anaphylaxis. Second-line agent for vasopressor and inotrope effects, when other agents have failed.

Norepinephrine

  • Effects: Potent vasoconstrictor. Causes a minor increase in stroke volume and cardiac output.
  • Disadvantages: May decrease renal blood flow and increase myocardial oxygen demand. Extravasation at site of intravenous administration may lead to tissue necrosis.
  • Use: First line therapy for maintenance of blood pressure.

Ephedrine

  • Effects: Increases heart rate, cardiac output. Bronchodilator. Some anti-emetic effects. Longer duration than epinephrine. Has indirect actions on adrenergic system.
  • Disadvantages: Epedrine losses effect with subsequent doses since part of its effect is indirect, by icreasing NE release, which becomes depleted
  • Use: Common vasopressor during anesthesia, but only a temporizing agent in acute shock.

Dopamine

  • Effects are dose-dependent:
    • < 5 mcg/kg/min – Acts at dopamine receptors only, with mild inotrope effect. Vasodilatory effects purported to improve perfusion through renal and mesenteric vessels; however, there is no clear clinical benefit of dopamine on organ function.
    • 5-10 mcg/kg/min – Predominantly β1 adrenergic effects. Increases cardiac contractility and heart rate.
    • >10 mcg/kg/min – Predominately α1 effects, causing arterial vasoconstriction and increased blood pressure. Overall decrease in renal and splanchnic blood flow at this dose.
  • Disadvantages: Has a high propensity for tachycardia and dysrythmias. Potential for prolactin suppression and immunosuppression.
  • Use: First line vasopressor for shock, but may be associated with more adverse outcomes than norepinephrine.

Dobutamine

  • Effects: Racemic mixture. where the L-isomer acts at α1/β1 receptors and D-isomer acts at β1/β2 receptors. Increases cardiac output and decreases systemic/pulmonary cascular resistance. Can increase splanchnic blood flow and decrease endogenous glucose production.
  • Disadvantages: May cause mismatch in myocardial oxygen delivery and requirement. Vasodilation undesirable in septic patients.
  • Use: A ‘gold standard‘ inotropic agent in cardiogenic shock with low output and increased afterload. In sepsis, vasodilatory effects should be counteracted by co-administration with norepinephrine.

Dopexamine

  • Effects: Acts at β2 and dopamine receptors. Causes vasodilation and decreased afterload. Has some positive inotrope effect. Bronchodilatory. Unlike dopamine, dopexamine is not associated with pituitary suppression.
  • Disadvantages: Not widely accepted in practice.
  • Use: Like dobutamine, useful for cardiogenic shock with decreased output and high afterload.

Phenylephrine

  • Effects: Classic selective α1 agonist, causing vasoconstriction. Rapid onset and short duration.
  • Disadvantages: Can reduce hepatosplanchnic perfusion. May cause significant reflex bradycardia.
  • Use: Generally considered a temporary vasopressor until more definitive therapy is begun. Useful for vasdilated patients with adequate cardiac output, for whom other vasopressors present risk of tachyarrhythmias.

Dexmedetomidine/Clonidine

  • Effects: Arousable sedation with preserved respiratory drive. Improved tissue perfusion and renal function. General sympathetic inhibition.
  • Disadvantages: Bradycardia and hypotension.
  • Use: Not used in acute shock setting, but may be useful in later critical care setting.

Vasopressin (not actually an adrenergic drug)

  • Effects: Acts on V1 receptors to cause vasoconstriction. Increases vasculature response to catecholamines.
  • Disadvantages: May cause tachycardia and tachyarrythmias. Excessive vasoconstriction can impair oxygen delivery and and cause limb ischemia.
  • Use: May be used to augment norepinephrine or other agents. Not typically used alone.

Glasgow Coma Scale (GCS)

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The Glasgow Coma Scale is a scoring system used to evaluate someone’s level of consciousness. It is scored out of 15 with 15 being totally awake and alert and 3 being totally not.

The important thing to remember is that the lowest score possible is 3.

Absolutely anything can score a 3, however if you are a living, breathing human being, hopefully you are scoring well up into the 10s.

Generally the GSC is applied in trauma situations and can be used as part of the decision making process of such thing things like should this patient be intubated?

  • ≥13 correlates with mild brain injury (or being ok)
  • 9-12 correlates with moderate injury
  • ≤8 represents severe brain injury – you should probably consider intubating them as they most likely cannot protect their airway
Thanks to Mike for the guest doodle!

Lung surface anatomy and chest tubes vs needle decompression

Surface anatomy of the lungs

  • Lungs extend from about 2 cm above the clavicle down to the 6th rib in the midclavicular line and 8th rib in the midaxillary line
  • The oblique fissure goes from the 6th rib midclavicular line to T3 in the back
  • The horizontal fissure (only on the right) starts at the 4th rib at the sternum and then meets the oblique fissure at the 5th rib in the midaxillary line.
  • The pleura generally is 2 ribs below

Chest Tube

Insert a chest tube in the 4th or 5th intercostal space in the anterior axillary line. When making the incision, make it one rib below the intercostal space you want to insert the tube into. Also, remember to go above the rib, as the neurovascular bundles travel along the underside of the ribs.

These can be done to relieve a pneumothorax, drain a malignant pleural effusion, drain a empyema, or drain a hemopneumothorax. They can also be placed post-operatively following a thoracotomy, esophagectomy or cardiac surgery.

Needle Decompression

These are used in a pinch when a patient is suspected to have a tension pneumothorax and needs immediate decompression. A 14 or 16 gauge needle is inserted above the 2nd or 3rd rib in the midclavicular line.

A tension pneumothorax is recognized by:

  • Dyspnea
  • Hypotension
  • Decreased breath sounds on the affected side
  • Distended neck veins
  • Trachea deviating away from affected side

 

Coupe and contre-coupe traumatic brain injury

When you hit your head on something (or something hits your head) there are two typical patterns of injury. The first is the coupe where the brain injury is directly under the spot that was hit. This usually happens when your head is stationary and something moving hits it (such as someone’s fist).

The second is the contre-coupe, which happens when your head is moving and hits something stationary (such as if you fall and hit your head on the wall or the floor.

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