Platelet Response / ARU / PRU

VerifyNow for Clopidogrel:

  • Values less than 194 PRU are specific evidence of a P2Y12 inhibitor effect

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VerifyNow for Aspirin:

  • ≤ 549: Evidence of platelet dysfunction due to aspirin
  • > 550: No evidence of aspirin-induced platelet dysfunction

 

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ASA-specific VerifyNow uses arachidonic acid as an agonist for platelet aggregation onto fibrinogen-coated beads.

VerifyNow (P2Y12) uses adenosine diphosphate and is more commonly utilized to detect platelet dysfunction due to clopidogrel.

Degree of platelet aggregation is recorded as aspirin reaction units (ARUs) or P2Y12 reaction units (PRUs).

Abnormally functiong platelets are defined as ARU <550 or PRU 208 (U of Cincinnati lab normal value, cutoff not universally defined).

 

VerifyNow Reference Guide

Clinical Value of the VerifyNow System

 

REFERENCES:

Click to access mvn0005_-_verifynow_pocket_guide_1.pdf

Click to access CLMA_Educ_Day_Presentation_-VerifyNow_2-18-14.pdf

Martin, G., Shah, D., Elson, N., Boudreau, R., Hanseman, D., Pritts, T., Makley, A., Foreman, B. and Goodman, M. (2018). Relationship of Coagulopathy and Platelet Dysfunction to Transfusion Needs After Traumatic Brain Injury. Neurocritical Care.

 

Interpreting Procalcitonin Values

Units:  ng/mL (normal <0.10)

Interpretation:

1. predicting progression to severe sepsis / septic shock (taken on D1 ICU admission)

  • >2 = high risk
  • <0.5 = low risk

2. As guide to Abx therapy in respiratory infections

  • <0.1 = ABx not needed
  • >0.5 = ABx needed

PCT-Algorithms-1 PCT-Algorithms-2 PCT-Algorithms-3 PCT-Algorithms-4bild_15_pct_04_06 procalcitonin-img Procalcitonin for diagnosis Figure 2

Basics:

  • precursor of calcitonin
  • produced by parafollicular cells of thyroid gland and neuroendocrine cells of lung / intestine / other tissues in response to inflammation, esp bacterial.
  • serum values correlate with severity of sepsis, recede with improvement, worsen with exacerbation.

Test performance:

  • Bacteremia (Sn 76%, Sp 70%)
  • systemic inflammatory response syndrome (SIRS)
  • sepsis
  • septic shock.

A/G Ratio

Total Protein Levels

  • Low = liver disorder, kidney disorder, malabsorption of kidney; malnutrition
  • High = chronic inflammation, infections (viral hepatitis or HIV), bone marrow diseases, multiple myeloma

A/G Ratio (normally, there is a little more albumin than globulins, so slightly >1)

  • Low = decreased albumin (cirrhosis, nephrotis syndrome) or increased globulins (MM, autoimmune diseases)
  • High = increased albumin <?> or decreased globulin (leukemias, genetic deficiencies)

Next tests: liver enzyme tests, SPEP

NOTE:  plasma expansion decreases total protein but A/G ratio will be normal because both albumin and globulin will be diluted to the same extent


Vitamin K Cycle and Coumadin

Explanation of Vitamin K Cycle from NEJM  (N Engl J Med 2013; 369:2345-2346December 12, 2013DOI: 10.1056/NEJMe1313682)

Vitamin K plays a single role in human biology — as a cofactor for the synthesis of γ-carboxyglutamic acid. 


Importance of γ-carboxyglutamic acid?

1.  component of at least 14 proteins (factor IX, factor VII, factor X, and prothrombin, protein C and protein S)

2. critical for the physiologic function of these proteins


We do not synthesize vitamin K, we ingest it in our diet. 


Vit K Cycle:

1. vitamin K quinone reduced to the semiquinone –> cofactor required for conversion of glutamic-acid residues on the vitamin K–dependent proteins to γ-carboxyglutamic acid by vitamin K–dependent carboxylase

2.  reaction produces Vitamin K epoxide –>  converted back to vitamin K quinone by VKOR (vitamin K epoxide reductase)


Warfarin inhibits VKOR –> post-translational modification of the vitamin K–dependent blood-coagulation proteins is impaired –>  reduced function of factors 10, 9, 7, 2 leads to delayed coagulation


Simplified Diagram:


Where the Protein products come in the cycle:

A more complicated diagram to illustrate the Vit K cycle:

Illustration showing where warfarin works in the Vit K cycle: