Tag Archives: Blood work

Clotting Cascade – NOW WITH NOACs

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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.

Iron Metabolism

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When we eat iron, we generally get it in one of two forms: elemental iron or heme (from meat). In the intestine (proximal duodenum to be precise) the iron is either absorbed or actively transferred in. Iron is transported in the blood bound to transferrin and is stored in the liver bound to ferritin. This is why ferritin is measured when assessing iron stores.

Though most of the time you can make the diagnosis of iron deficiency anemia by assessing the patient’s history and CBC (microcytic anemia), you can also do an “iron study” that looks at the following:

  • Ferritin: indicator of iron stores, will be reduced in iron deficiency anemia
  • Serum iron (SI): decreased in iron deficiency anemia
  • Total iron binding capacity (TIBC): measures transferrin, this is elevated when iron is low
  • % saturation = SI/TIBC x 100, reduced in iron deficiency anemia

It’s good to keep the other causes of microcytic anemia in mind. To remember you can use the mnemonic TAILS

  • Thalassemia
  • Anemia of chronic disease
  • Iron deficiency
  • Lead poisoning
  • Sideroblastic anemia

*I realize that using “anemia” as the A is a little bit of a cop out in a mnemonic devoted to anemia, but I wasn’t the one who came up with it and TCILS just isn’t as easy to remember.

Hemostasis & How to Recognize Bleeding Disorders

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Hemostasis – What stops us from bleeding out.

Three main steps:

  1. Vasoconstriction
  2. Primary hemostasis (platelet plug) – the temporary way to stop bleeding
  3. Secondary hemostasis (clotting cascade) – the more permanent way

Bleeding disorders can be broadly divided into whether they affect platelet plug formation or the clotting cascade (if you need a refresher, click here)

 Platelet Disorder Clotting Cascade Disorders
Immediate bleeding
Muscosal and cutaneous
Bruises and petechiae
Nose bleeds (epistaxis)
Menorrhagia (heavy periods)
von Willebrand
Thrombocytopenia
DIC 		 Delayed Bleeding
Deep (muscles and joints)
Palpable bruises, large spreading hematomas
Hemarthrosis
Post-surgical bleeding
Hemophilia A (factor VIII)
Hemophilia B (factor IX)
Warfarin

Acid/Base (alkalosis vs acidosis, metabolic vs respiratory)

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This is the general way to approach an acid-base disturbance. They’re not really as bad as they seem at first. You just need to remember that CO2 is acidic and HCO3- is basic. So an increase in CO2 makes the body acidotic and an increase in HCO3- makes the body alkalotic.

It’s also good to remember to calculate the anion gap when doing these calculations.

AG = Na – (Cl- + HCO3-) it’s just the cations minus the anions. If this gap between the cations and anions is large, it means that the anions are stacking their team and have an extra anion helping out.

The classic mnemonic is MUDPILES

  • Methanol
  • Uremia
  • Diabetic ketoacidosis
  • Paraldehyde
  • Isopropyl alcohol
  • Lactic acidosis
  • Ethylene glycol
  • Salicylates

If the anion gap is big, it’s good to look at the ratio between the change in the gap and the change in the HCO3-.

  • Increase in AG < decrease in HCO3- = coexisting non-anion gap metabolic acidosis
  • Increase in AG > decrease in HCO3- = coexisting metabolic alkalosis

Erythrocyte growth and regulation

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Red blood cells (fancily known a erythrocytes) are the simple, non-nucleated cells that transport oxygen in the body. This just outlines their development in the bone marrow (hint, they start off with a nucleus) and the major growth factor erythropoietin that stimulates their production.

By looking at the peripheral blood and bone marrow, you can work on sorting out where and what kind of disease process is going on. For example, if there are too many reticulocytes in the peripheral blood.

Direct and indirect antibody tests

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direct antibody Test

Looks for the presence of IgG and/or complement on the RBCs. This causes hemolysis and can be due to an autoimmune disease, transfusion reaction, etc.

Indirect antibody Test

This is used when cross-matching people for a blood transfusion. It tests patients for the presence of unexpected alloantibodies (anti-D, anti-E, anti-C, anti-Kell, anti-Duffy). This is just a screen, if it is positive, you can then test for specific antibodies and then only transfuse blood that is negative for those specific antigens.

* 19/06/2013 Please excuse the doodle for saying “agglutination” though it is testing by agglutinating, the “A” in DAT stands for antibody. Thanks Robina for pointing this out!

Calcium homeostasis, parathyroid and vitamin D

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Calcium homeostasis is largely controlled by the parathyroid glands (tucked away underneath the thyroid). I’ve included a little bit of the vitamin D synthesis pathway as well, though D3 (the form that is absorbed in the intestines) is also synthesized in the skin as long as you’re getting a little bit of sunlight.

Hypercalcemia

  1. Hyperparathyroidism: usually an adenoma
  2. Malignancy: PTH-related peptide released by tumor (squamous cell, renal, breast, bladder)
  3. Vitamin D excess: granulomas (sarcoidosis, TB, Wegener’s)
  4. Increased bone turnover: hyperthyroidism, Paget’s
  5. Familial hypocalcuric hypercalcemia: mutation in the calcium-sensing receptor in parathyroid and kidney

Hypocalcemia

  1. Hypoparathyroidism: sporadic, caused by thyroid surgery, Wilson’s, hypomagnesemia
  2. Pseudo-Hypoparathyroidism: PTH end-organ resistance
  3. Vitamin D deficiency: no sunlight, GI disease
  4. Chronic renal failure: decreased 1,25(OH)D production, increased phosphate
  5. Calcium sequestration: acute phosphate increase

Liver Enzymes (hepatic vs cholestatic patterns)

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Liver enzymes can be elevated for a number of reasons, but the first step in an approach is to determine if the enzymes are in a hepatic pattern or cholestatic pattern. It is also very important to realize that Alk phos, GGT, ALP, and AST are liver enzymes, but they don’t give an indication of function; for that you need to look at INR and bilirubin.

Insulin Regimens and Dosing

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Insulin dosing has to be one of the most (seemingly) unnecessarily complicated dosings in medicine. Not only are there 4 ways to dose it (BID, QID with rapid, QID with fast, QID with extended-release) there are three different companies, all naming their insulins slightly differently. But how can you remember whether to give Humalog, Humulin N, Humulin R, NovoRapid, Novolin Toronto, NPH, Lantus, or some combination of the above?

This is a master illustration to help organize insulin dosing and amounts.

Total Daily Dose

0.3 – 0.6 units/kg
Start low, titrate up

BID (conventional therapy)

2/3 : 1/3 rule
2/3 breakfast : 1/3 supper
2/3 long : 1/3 fast

QID (with either Rapid or Fast-acting and either long or extended)

Breakfast: 20-25% long, 15-20% rapid
Lunch: 15-20% rapid
Supper: 15-20% rapid
Bedtime: 25-30% long

Causes of Acute Kidney Injury (AKI)

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Acute kidney injury can be caused by problems directly in the kidney, before the kidney or after the kidney. If you think about it that way, it’s much easier to develop a differentiate and establish a treatment.

The RIFLE criteria define the relative damage to the kidney and the outcome.
RIF = Severity in terms of serum creatinine (sCr), glomerular filtration rate (GFR) and urine production. Though for simplicity I only included serum creatinine since that is most likely what you’ll be looking at on initial blood work.
LE = Outcome variables (temporary or permanent)