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  1. ARISTOTLE trial (apixaban vs warfarin)
    Friday, February 10, 2012
  2. What causes BUN and Creatinine abnormalities?
    Monday, January 30, 2012
  3. Causes of low platelet count ( pseudothrombocytopenia/ pathologic causes)
    Monday, January 30, 2012
  4. What causes platelet count variation among hema analyzers??
    Monday, January 30, 2012
  5. Limitations of calculated LDL-C (Friedewald method)
    Monday, January 02, 2012
  6. Which is more accurate direct LDL or calculated LDL?
    Monday, January 02, 2012
  7. Pre-analytical variables which can affect PT-INR results?
    Saturday, September 10, 2011
  8. What is the difference between calculated LDL & measured/direct LDL?
    Wednesday, August 31, 2011
  9. Causes of low voltage QRS?
    Friday, July 22, 2011
  10. Differential diagnosis for prominent T wave inversion
    Friday, July 22, 2011

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ARISTOTLE trial (apixaban vs warfarin)

ARISTOTLE  2011 (Bristol-Myer-Squibb)

Population - 18,201 patients with atrial fibrillation with at least one risk factor

Intervention - apixaban 5 mg/tab BID vs warfarin (target INR 2-3), ff up 1.8 years

Outcome - Apixaban was associated with 21% risk reduction in stroke or systemic embolism, 31 % reduction in bleeding, 11% reduction in all-cause mortality

Method: randomized controlled trial  (RCT)

Posted by Dr. Ted Alviar at 2/10/2012 5:08 AM | Add Comment

What causes BUN and Creatinine abnormalities?

Elevated BUN

An increase in the BUN level is known as azotemia. An elevated BUN may be caused by:

  1.         Impaired renal function 
  2.         Congestive heart failure as a result of poor renal perfusion
  3.         Dehydration
  4.         Shock
  5.          Hemorrhage into the gastrointestinal tract
  6.          Acute myocardial infarction
  7.           Stress
  8.          Excessive protein intake or protein catabolism

 Low BUN

A decreased BUN may be seen in:

  1.           Liver failure
  2.           Malnutrition
  3.           Anabolic steroid use
  4.           Overhydration, Which can result from prolonged intravenous fluids
  5.          Pregnancy (due to increased plasma volume)
  6.           Impaired nutrient absorption
  7.          Syndrome of inappropriate anti-diuretic secretion (SIADH)

Elevated creatinine

1. Creatine use as a supplement

2. Dehydration
Diabetes
Drugs particularly chemotherapy medicines such as cisplatin

3. Kidney disease

4. Diabetic Nephropathy
Creatinine levels are elevated in patients who have diabetic nephropathy. Management of hypertension is the mainstay of prevention and treatment of diabetic renal disease. Tight blood pressure control slows renal disease progression in established diabetic nephropathy.

Contrast agent ( those undergoing CT scan)

Posted by Dr. Ted Alviar at 1/30/2012 11:06 AM | Add Comment

Causes of low platelet count ( pseudothrombocytopenia/ pathologic causes)

Pseudothrombocytopenia can complicate an accurate determination of a platelet count in a patient with an underlying thrombocytopenic disorder. Platelet clumping may be a result of poor mixing - too little and/or too late, and/or a small, whole blood clot or very small fibrin clots in the EDTA-anticoagulated specimen. 

Additionally, the improper collection of the blood sample may cause thrombin release and a falsely low platelet count due to platelet aggregation.Clotting can also be the result of insufficient EDTA, usually caused by overfilling the vacuum tube, or poor solubility of EDTA (most commonly disodium EDTA).

Pathologic causes of low platelet count

  1. Viruses – lparvo virus, rubella, mumps, varicella, hepa C, EBV, HIV 
  2. Aplastic anemia
  3. Medications – gold, chloramphenicol, Dilantin, Valproate (Depacon) or Radiation, Fanconi anemia
  4. Chemotherapy
  5. Cancers – leukemia, lymphoma
  6. Long term alcohol can cause direct toxicity of none marrow
  7. Heparin induced thrombocytopenia
  8. Idiopathic thrombocytopenia purpura
  9. Inflammation of the blood vessels (vasculitis)
  10. Artificial heart valves
  11. False thrombocytopenia – due to clumping. If this is suspected the blood should be re drawn and re checked

Posted by Dr. Ted Alviar at 1/30/2012 9:30 AM | Add Comment

What causes platelet count variation among hema analyzers??

Factors causing platelet count variation among hema analyzers - patient population ( Cancer vs non cancer patients), sample selection ( EDTA use - platelet clumps),reference method (flow cytometry vs impedance, light scatter method).

Remember different laboratories uses different hema analyzers and even if they're using the same machine platelet clumping differs per specimen collection

Platelet clumping is usually flagged by hema analyzers:

Platelet flags occurs when the analyzer detects the ff :1) RBC 2)Leukocyte fragments. It selects samples with platelet counts between 75 to 150 x 10 9. 

Regarding platelet flags the best way to confirm them is using manual method (draw back: inter observer variability) or do a repeat extraction.

Here is a study done by Dr Sandhaus ( Cleveland University Hospital) published at the American Society of Clinical Pathology 2002. It compared platelet flags reported by 3 Hema analyzers (Sysmex, Coulter and Advivia) and it was rechecked manually to confirm  their sensitivity and specificity.

Low platelet count sensitivity and specificity in 3 different hema analyzers

1) Sysmex -Platelet clumps flag – 20 samples

True positive (with real platelet clumping when inspected manually) 4/20

False positive ( w/o any platelet clumping) 16/20

 2) Coulter LH750 - Platelet clumps flag – 3 samples

True positive (with real platelet clumping when inspected manually) 2/3

False positive ( w/o any platelet clumping) 1/3

 3) Advia 120 - Platelet clumps flag – 4 samples

True positive (with real platelet clumping when inspected manually) 3/4

False positive ( w/o any platelet clumping) 1/4

HENCE , OUT OF 27 REPORTED " LOW PLATELET COUNT " RESULTS - 18 TURNED OUT TO BE NORMAL (66% ERROR).

TAKE HOME MESSAGE: ALWAYS DOUBLE CHECK PLATELET CLUMPS IT OCCURS 10% OF THE TIME WHETHER BLOOD IS DRAWN  VIA VENOUS OR CAPILLARY ROUTE.



Posted by Dr. Ted Alviar at 1/30/2012 9:15 AM | Add Comment

Limitations of calculated LDL-C (Friedewald method)

One of the limitations of using the the Friedewald-calculated LDL method is that when the trigly is greater than 400 mg/dl the LDL-C is FALSELY LOW

e.g. Patient X: Total cholesterol = 250 mg/dl , HDL = 40 mg/dl, Trigly = 400 mg/dl
 Friedewal LDL-C = 250 - (40 - 450/5)
 Friedewald LDL-C = 250 - (40 - (-90)) 
 Friedewald LDL -C = 250 - 130
 Friedewald LDL-C = 120 mg/dl ( falsely low because of a high denominator)

Which comes to our question - "will direct LDL solve the problem of not being able to report LDL-C values when trigly exceeds 400 mg/dl?"

Sad to say NCEP concluded, in ATP III, that current direct methods  ( Genzyme N-Genous LDL, Reference Diagnostic LDL, Roche LDL-C-Plus, Sigma EZ-LDL) also suffer from various inaccuracies when triglycerides is greater than 400 mg/dl.

Source:

1. Nauck M, Warnick GR, Rifai N. Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by 

homogeneous assays versus calculation. Clin Chem 2002; 48:236-54. 

2. Miller WG, Waymack PP, Anderson FP, Ethridge SF, Jayne EC. Performance of four homogeneous direct methods for LDL- 

cholesterol. Clin Chem 2002; 48:489-98. 




Posted by Dr. Ted Alviar at 1/2/2012 7:41 PM | Add Comment

Which is more accurate direct LDL or calculated LDL?

Calculated LDL uses the Friedwald formula (LDL-C = total chole - HDL - (Trigly/5)
Direct LDL - direct homogenous method in measuring LDL

Direct LDL method are no better than the Friedwald-calculated value when the triglycerides is < 400 mg/dl ( >90% of the population)

The following comparison shows that the Fridewald-LDL-C results were as good if not better than direct LDL ( calculated for specimens with trigly concentration < 400 mg/dl)

Sigma EZ -LDL direct method vs Friedwald LDL C
LDL < 130 mg/dl population - 76% correlation (direct LDL) vs 96% (calculated LDL)
LDL 130-160 mg/dl population - 75% correlation (direct LDL) vs 75% (calculated LDL)
LDL >160 mg/dl population - 100% correlation (direct LDL) vs 100% (calculated LDL)

Roche LDL - C plus direct method vs Friedwald LDL C
LDL < 130 mg/dl population - 92% correlation (direct LDL) vs 96% (calculated LDL)
LDL 130-160 mg/dl population - 75% correlation (direct LDL) vs 75% (calculated LDL)
LDL >160 mg/dl population - 94% correlation (direct LDL) vs 100% (calculated LDL)

Source:

Miller WG, Waymack PP, Anderson FP, Ethridge SF, Jayne EC. Performance of four homogeneous direct methods for LDL- 

cholesterol. Clin Chem 2002; 48:489-98. 




Posted by Dr. Ted Alviar at 1/2/2012 7:13 PM | Add Comment

Pre-analytical variables which can affect PT-INR results?

A patient of mine once tested his protime INR results (Yes, he is a warfarin user) sending blood samples to 2 tertiary hospitals and 2 secondary laboratories. Upon receiving his results he was dumbfounded to get different results (ranging from 1.5 up to 3.0). So i  decided to research on the conditions affecting PT-INR results. So here's what i got:

Pre-analytical variables (accounts to 64% of all errors in PT/INR testing)
1. Anticoagulant used - WHO guidelines recommends 3.2% buffered citrate.
2. The test tube must be completely filled up with blood (at least 90% full) for proper anticoagulant to blood ratio.
3. The specimen should be centrifuged for at least 10 minutes to create a platelet poor plasma (platelets tends to normalize INR in patients taking warfarin)
4. For delayed testing (> 24 hours) the platelet poor plasma should be frozen.

Analytical variables - The American Association of Clinical Chemistry revealed that there is a poor agreement among PT INR results depending on the method used by the laboratory ( Juha et al Poor aAgreement among PT INR: comparison of Seven Commercial Reagents Clin Chem 51: 533-560,2005).  Hence, the take home message for med tech is to know the pre analytical variables and to MDs know the method of your hospital. Recently the AHA advocates the use of self test meters for INR monitoring (Coaguchek by Roche) for patients taking warfarin, its accurate, its reliable and above all it provides instant result to avoid over dosage of warfarin.


Posted by Dr. Ted Alviar at 9/10/2011 5:56 PM | Add Comment

What is the difference between calculated LDL & measured/direct LDL?

LDL cholesterol (LDL-C) results have been determined for many years by calculation using the Friedewald formula. These results have been used in the epidemiologic studies and therapeutic trials that form the backbone of hyperlipidemia management today.

Friedewald formula: LDL-C = TC – HDL – (TG/5),

LDL = Low Density Lipoprotein
TC = Total Cholesterol
HDL = High Density Lipoprotein
TG = triglycerides

Currently there is a newer method in calculating LDL, this is by the direct method  and with the emergence of this new modality in determining LDL will the use of the Friedewald formula be obsolete?
Posted by Dr. Ted Alviar at 8/31/2011 9:26 AM | Add Comment

Causes of low voltage QRS?

  1. Artifactual
  2. Adrenal Insufficiency
  3. Anasarca
  4. Cardiac Infiltration or replacement ( amyloidosis, sarcoid, tumors)
  5. Cardiac transplantation
  6. Cardiomyopathies
  7. COPD
  8. Constrictive pericarditis
  9. Hypothyroidism
  10. left pneumothorax
  11. Myocardial Infarction - extensive
  12. Myocarditis
  13. Normal variant
  14. Obesity
  15. Pericardial effusion/tamponade
  16. Pectus carinatum
Posted by Dr. Ted Alviar at 7/22/2011 8:19 PM | Add Comment

Differential diagnosis for prominent T wave inversion

  1. Normal variants - juvenile T waves, early rep + ST depression
  2. Ischemia
  3. Cardiomyopathies - HOCM
  4. Intracranial bleeding
  5. LV overload
  6. post MI T wave pattern
  7. Idiopathic global T wave inversion
  8. T wave inversion due to BBB
  9. Wolff parkinson White pattern
  10. Ventricular pacing - memory T waves
Braunwald's Heart Disease p 183
Posted by Dr. Ted Alviar at 7/22/2011 8:14 PM | Add Comment
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