4.1 levine vitamin k - acmt · 2012. 3. 16. · a) 4 units ffp b) 10 mg sq vitamin k c) 10 mg iv...
TRANSCRIPT
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• Discuss pathophysiology of vitamin K antagonists with regards to coagulation.
• Review pharmacology of vitamin K.
• Review several guidelines for warfarin reversal.
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• There are no conflicts of interest to disclose.
• 79 year old female presents with headache, confusion for 2 hours.
• PMH: A-Fib, HTN, CAD.
• Meds: Metoprolol, warfarin, HCTZ.
• INR: 2.2.
• Head CT with intraparenchymal hemorrhage.
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• Which of the following represents the best treatment strategy? a) 4 units FFP b) 10 mg SQ vitamin K c) 10 mg IV vitamin K d) 4 units FFP and 2 mg SQ vitamin K e) 4 units FFP and 10 mg IV vitamin K
• 50 year old female with history of DVT, on warfarin, presents to the ED for high INR.
• Routine check by PCP revealed INR of 8. She was referred to the ED.
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• Which of the following represents the best treatment strategy? a) 2.5 mg PO vitamin K b) 10 mg PO vitamin K c) 5 mg SQ vitamin K d) 4 units FFP and 2 mg SQ vitamin K e) 4 units FFP and 10 mg IV vitamin K
• A 2 year old male presents to the emergency department after ingestion of 5 pellets of D-con.
• The patient is asymptomatic, and not normally on any medication.
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• Which represents the best treatment option for this patient? a) No therapy required; if there is concern the
patient ate many pellets, the patient can be referred for labs in 24-36 hours
b) 10 mg oral vitamin K c) 10 mg IV vitamin K d) 2 Units FFP, 5 mg IV vitamin K e) 4 Units FFP, 10 mg IV vitamin K
• 1920’s: Chicken fed a poor diet bleed.
• 1935: Administration of a fat-soluble substance in the diet reduces bleeding “Koagulation factor.”
• 1948: warfarin used as rodenticide.
• 2004: 31 million Americans on warfarin.
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• Current uses of vitamin K antagonists include: – Medicinal (warfarin) – Rodenticides (bordifacoum)
CLOTTING FACTOR HALF-LIFE (H)
II 50
VII 6
IX 24
X 36
Protein C 8
Protein S 30
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• 2-3 half-lives needed before significant change in INR noted.
• Full effect may not be apparent for several days.
• Term “vitamin K” actually encompasses: – Vitamin K1 (phytonadione, phylloquinone)
– Vitamin K2 (menaquinones)
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• Vitamin K1 (phytonadione, phylloquinone) – Synthesized from plants and algae – Primary form in diet
• Vitamin K2 (menaquinones) – Synthesized by bacteria; destruction of bacteria
partly explains interaction between warfarin and many antibiotics
• Relatively little required in diet.
• Adult RDA 1 mcg/kg/d.
• 10 mcg/kg/d needed in infants to maintain normal homeostasis.
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• Bile salts and fatty acids are required for vitamin K absorption.
• After absorption, vitamin K moved to liver via lymphatic system.
• Travels bound to chylomicrons.
• Once in liver, it helps with production of clotting factors.
• Several different forms of vitamin K are available: – K1 (phylloquinone, phytonadione) – K3 (menadione) – K4 (menadiol sodium diphosphate)
• K3, K4 associated with several adverse effects: – Neonates: Hemolysis, hyperbilirubinemia, and
kernicterus – G6PD deficient: Hemolysis
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De Zee KJ, Shimeall WT, Douglas KM. Treatmetn of excessive anticoagulation with phytonadione (vitamin K): A meta-analysis. Arch Intern Med. 2006; 166:391-7.
Percentage of patients having an INR in the therapeutic range (1.8-4.0) 24 hours after vitamin K vs. placebo.
Percentage of patients having an INR remain > 4.0 24 hours after vitamin K vs. placebo.
• Vitamin K cycles between inactive and active forms.
• Only the reduced (quinol) form has biologic activity.
• The active quinol form can be formed via vitamin K dependent pathway or via NADPH-dependent pathway.
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OH O
CO2 + O2
Vitamin K epoxide reductase
Vitamin K quinone reductase
Inactive factors II, VII, IX, X, Protein C and S
Active factors II, VII, IX, X, Protein C and S
Vitamin K Quinol
Vitamin K Quinone
Vitamin K 2, 3 epoxide
NADPH dependent quinone reductase
(Active)
• The NADPH-dependent pathway is insensitive to warfarin.
• The epoxide reducatase and the quinone reductase are dithiol-dependent vitamin K reductases.
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• Deficiency can result from inadequate intake, malabsorption, or interference with vitamin K cycle.
• Deficiency can also be acquired from xenobiotics.
• Warfarin interferes with vitamin K cycle, resulting in accumulation of the inactive 2,3 epoxide.
• Super-warfarins even more potent vitamin K reductase inhibitors.
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• PO: no significant adverse effects.
• IM/SQ: hematoma. No role in routine management.
• IV: Potential for anaphylactoid reaction.
• In general, IV route very safe if administered slowly.
• IV vitamin K available as colloidal suspension of polyoxythylated castor oil, dextrose, and benzyl alcohol.
• Previously with higher rates of anaphylactoid reaction because of different components of suspension.
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• Doses of up to 250 mg daily for several weeks to months may be required for massive bordifacoum ingestions.
• Published guidelines are for reversal of warfarin and do not apply to bordifacoum ingestions.
INR CHEST Guidelines
Australasian Society of Thrombosis and Haemostasis
2-5; no bleeding
Lower or omit dose Lower or omit dose
5-9; no bleeding
Hold 1-2 doses. OR 1-2.5 mg PO vitamin K*
Hold warfarin. If bleeding risk high, 1-2 mg PO or 0.5-1 mg IV vitamin K
> 9; no bleeding
Hold warfarin; give 5 mg PO vitamin K
Hold warfarin. If bleeding risk low, give 2.5-5 mg PO vitamin K or 1 mg IV vitamin K. If high risk, give 1 mg IV vitamin K, consider PCC, FFP
Serious bleeding
Hold warfarin. Give 10 mg IV vitamin K, supplemented by FFP, PCC, or rVIIa
Hold warfarin. Give 5-10 mg IV vitamin K, PCC and FFP
Life threatening bleeding
Hold warfarin. Give FFP, PCC, or rVIIa, supplemented by 10 mg IV vitamin K
* 5 mg can be given if more rapid reduction in INR needed (e.g. patient going to surgery)
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• Correct coagulopathy in liver failure patients; can give dose to correct any nutritional component of the coagulopathy.
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• 79 year old female presents with headache, confusion for 2 hours.
• PMH: A-Fib, HTN, CAD.
• Meds: Metoprolol, warfarin, HCTZ.
• INR: 2.2.
• Head CT with intraparenchymal hemorrhage.
• Which of the following represents the best treatment strategy? a) 4 units FFP b) 10 mg SQ vitamin K c) 10 mg IV vitamin K d) 4 units FFP and 2 mg SQ vitamin K e) 4 units FFP and 10 mg IV vitamin K
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3/10/11
17
• Which of the following represents the best treatment strategy? a) 4 units FFP b) 10 mg SQ vitamin K c) 10 mg IV vitamin K d) 4 units FFP and 2 mg SQ vitamin K e) 4 units FFP and 10 mg IV vitamin K
• 50 year old female with history of DVT, on warfarin, presents to the ED for high INR.
• Routine check by PCP revealed INR of 8. She was referred to the ED.
-
3/10/11
18
• Which of the following represents the best treatment strategy? a) 2.5 mg PO vitamin K b) 10 mg PO vitamin K c) 5 mg SQ vitamin K b) 4 units FFP and 2 mg SQ vitamin K c) 4 units FFP and 10 mg IV vitamin K
• Which of the following represents the best treatment strategy? a) 2.5 mg PO vitamin K b) 10 mg PO vitamin K c) 5 mg SQ vitamin K d) 4 units FFP and 2 mg SQ vitamin K e) 4 units FFP and 10 mg IV vitamin K
-
3/10/11
19
• A 2 year old male presents to the emergency department after ingestion of 5 pellets of D-con.
• The patient is asymptomatic, and not normally on any medication.
• Which represents the best treatment option for this patient? a) No therapy required; if there is concern the
patient ate many pellets, the patient can be referred for labs in 24-36 hours
b) 10 mg oral vitamin K c) 10 mg IV vitamin K d) 2 Units FFP, 5 mg IV vitamin K e) 4 Units FFP, 10 mg IV vitamin K
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3/10/11
20
• Which represents the best treatment option for this patient? a) No therapy required; if there is concern the
patient ate many pellets, the patient can be referred for labs in 24-36 hours
b) 10 mg oral vitamin K c) 10 mg IV vitamin K d) 2 Units FFP, 5 mg IV vitamin K e) 4 Units FFP, 10 mg IV vitamin K
• Vitamin K antagonists block vitamin K cycle resulting in accumulation of inactive precursors.
• IV route rarely associated with anaphylactoid reactions.
• IM/SQ routes should not be used.
• Guidelines available for reversal of warfarin-induced supratherapeutic INRs.
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THANK YOU