1. INR, risk of ischemic stroke vs risk of hemorrhagic stroke in people with a-fib on coumadin {source: hospital data-bases of patients diagnosed between 1996-1997, total n>13,000, published 2013 in the NEJM} 

2. Predictors of mortality at 30 days of patients hospitalized with ischemic stroke 

- From the same study {source: hospital data-bases, total n>13,000, NEJM}. People with a-fib who are correctly anticoagulated on warfarin who get ischemic strokes are less likely to die than those who are not correctly anticoagulated. 

3. Anticoagulation in patients with A-Fib: ARISTOTLE trial -- Apixaban vs Warfarin. 

- NEJM, 2011, n=18,000

- Median follow up: 1.8 years. 

Outcome (% per year)	Apixaban	Warfarin	P
Ischemic or hemorrhagic stroke or systemic embolism (primary outcome)	1.27	1.6	P<0.001 noninferiority P=0.01 superiority
Major bleed	2.13	3.09	P<0.001
Death from any cause	3.52	3.94	P=0.047
Hemorrhagic Stroke	0.24	0.47	P<0.001
Ischemic/Uncertain stroke	0.97	1.05	P=0.42

4. Anticoagulation in patients with A-Fib: RE-LY trial -- Dabigatran vs Warfarin. 

- NEJM, 2009, n=18,000

- Median follow up : 2 years 

5. Anticoagulation in patients with A-Fib: ROCKET-AF trial -- Rivaroxaban vs Warfarin 

- NEJM, 2011, n=14,000

Outcome (% per year)	Rivaroxaban	Warfarin	P
Stroke or systemic embolism (primary outcome)	1.7	2.2	P<0.001 noninferior
Stroke or systemic embolism (intention to treat)	2.1	2.4	P<0.001 noninferior P=0.12 superiority
Major and nonmajor clinically relevant bleed	14.9	14.5	P=0.44
Intracranial hemorrhage	0.5	0.7	P=0.02
Fatal bleed	0.2	0.5	P=0.003

6. Comparative study of all 3 above trials examining QALY published in clinical pharmacology & therapeutics (Nature group journal)

J Pink et al Comparative Effectiveness of Dabigatran, Rivaroxaban, Apixaban, and Warfarin in the Management of Patients With Nonvalvular Atrial Fibrillation Clinical Pharmacology & Therapeutics (2013); 94 2, 269–276.

- Abstract: "..Using a discrete event simulation method adopting a lifetime horizon of analysis, we made an indirect comparison of the RE-LY, ROCKET-AF, and ARISTOTLE trial results for AF patients in the US population. Over a lifetime, apixaban, dabigatran, and rivaroxaban accrued 0.130 (95% central range (CR) −0.030 to 0.264), 0.106 (95% CR −0.048 to 0.248), and 0.095 (95% CR −0.052 to 0.242) more quality-adjusted life-years (QALYs), respectively, than warfarin, with apixaban having a 55% probability of accruing the highest total QALYs. In the absence of a definitive trial, and acknowledging the limitations of an indirect comparison, the available evidence suggests apixaban to be the most effective anticoagulant."

- TL; DR: APIXABAN IS THE BEST 

7. Pharmacokinetics/pharmacogenomics of warfarin:

- Racemic mixture of the R and S enantiomer, S enantiomer is more potent
- Half life of the racemic warfarin is 36 to 42 hours. R warfarin: 45 hours. S warfarin: 29 hours
- 9% bound to plasma proteins and mostly to albumin.
- Metabolism: hepatic. S enantiomer: CYP2C9, R enantiomer: CYP1A2 and CYP3A4
- Summertime - more leafy green vegetables, more vitamin K, dip in INR
- People with CYP2C9 mutations need to have reductions in warfarin dose
- People with VKORC1 mutations can be either resistant to warfarin or hypersensitive to warfarin depending on the mutation.
- www.warfarindosing.org to determine dose.
8. Half life of coag factors: 
- Factor VII: 4-6 hours
- Factor IX: 24-36 hours
- Factor X: 36-48 hours
- Factor II: 60 hours
- Protein C: 8 hours
- Protein S: 30 hours
9. Microangiopathic hemolytic anemia with thrombocytopenia
- TTP (ADAMTS13 functional <5%, increased ADAMTS13 inhibitor. Classically look for neuro symptoms but they are not always present). Of note, sepsis and malignant HTN can cause TTP like picture of MAHA + thrombocytopenia
- HUS (kids age 4-5, Shiga toxin Ecoli O157:H7, binds platelet glycoproteins, classically look for renal sx)
- DIC (decrease in factors I, II, V, VIII)
- HELLP (no renal, no neuro, pregnant women)
- Drugs (clopidogrel/ticlopigrel, quinine, mitomycin, penicillin, OCP)
10. Microangiopathic hemolytic anemia without thrombocytopenia
- Mechanical valves (2/2 jets of turbulent blood)
- Vasculitis
- Malignant HTN
- Repeative stress injury (bongo drumming, marching across a bridge)