DVT/PE
hey, to keep things in order, pls "comment" on this post rather than "new post"
CBL – Deep Venous Thrombosis/Pulmonary Embolus
Differential Diagnoses for presentation with symptoms discussed in case:
- AMI: Tightness, central crushing squeeziness. Radiating pain, dyspnoea, sweating, quick onset.
- Pulmonary oedema: Usually due to left ventricular failure or ischemic heart disease. May present with Dyspnoea, orthopnoea, pink frothy sputum, pale & sweaty, pulse and JVP, Tachypnoea, lung crackles.
- Pneumonia: This is an acute lower respiratory tract illness involving infection of the lung parenchyma. Main clinical symptoms include dyspnoea, pleuritic chest pain, haemoptysis, cough, purulent sputum, malaise, fever.
- Cellulitis: (Differential for DVT): Cellulitis is an acute inflammation of the connective tissue of the skin, caused by infection with staphylococcus, streptococcus or other bacteria Localized skin inflammation with pain or tenderness in the area, warmth over area of redness. May present with fever, chills, sweating, fatigue, and ache.
- Hyperventilation: Main symptom is dyspnoea, dizziness with tingling of and numbness of limbs, ¯PaCO2 and normal or PaO2.
- Oesophageal spasm: Heartburn and worse with straining. Most common cause of chest pain
- Pulmonary embolism: Dyspnoea, Tachypnoea, Hypoxemia, Hypocarbia with clinical presentation resembling hyperventilation. ¯PaO2 and decrease in partial pressure of PaCO2. Results in a positive D-dimer assay
- Pericarditis: Sudden onset pleuritic pain. Change of posture can influence pain and a friction sound can be heard.
- Costochondral pain: Palpation tenderness and movements of chest influence pain.
References:- http://www.guideline.gov/summary/summary.aspx?doc_id=6534
- Oxford Handbook
Differential Diagnoses for presentation with symptoms discussed in case:
- AMI: Tightness, central crushing squeeziness. Radiating pain, dyspnoea, sweating, quick onset.
- Pulmonary oedema: Usually due to left ventricular failure or ischemic heart disease. May present with Dyspnoea, orthopnoea, pink frothy sputum, pale & sweaty, pulse and JVP, Tachypnoea, lung crackles.
- Pneumonia: This is an acute lower respiratory tract illness involving infection of the lung parenchyma. Main clinical symptoms include dyspnoea, pleuritic chest pain, haemoptysis, cough, purulent sputum, malaise, fever.
- Cellulitis: (Differential for DVT): Cellulitis is an acute inflammation of the connective tissue of the skin, caused by infection with staphylococcus, streptococcus or other bacteria Localized skin inflammation with pain or tenderness in the area, warmth over area of redness. May present with fever, chills, sweating, fatigue, and ache.
- Hyperventilation: Main symptom is dyspnoea, dizziness with tingling of and numbness of limbs, ¯PaCO2 and normal or PaO2.
- Oesophageal spasm: Heartburn and worse with straining. Most common cause of chest pain
- Pulmonary embolism: Dyspnoea, Tachypnoea, Hypoxemia, Hypocarbia with clinical presentation resembling hyperventilation. ¯PaO2 and decrease in partial pressure of PaCO2. Results in a positive D-dimer assay
- Pericarditis: Sudden onset pleuritic pain. Change of posture can influence pain and a friction sound can be heard.
- Costochondral pain: Palpation tenderness and movements of chest influence pain.
References:- http://www.guideline.gov/summary/summary.aspx?doc_id=6534
- Oxford Handbook
posted by third year at
6:45 PM
2 Comments:
Pharmocological Management of DVT/PE - Warfarin
MECHANISM OF ACTION OF WARFARIN
Vitamin K is a cofactor in the conversion of glutamic acid (“protein”) to -carboxyglutamic acid. Warfarin inhibits this process by inhibiting the reduction of Vitamin K into its active form.
Warfarin is absorbed fast, as it’s bound to albumin, so its levels in the blood are high after an hour or so. However it takes a few days to have an effect due to the turnover rates of the respective clotting factors. VII, IX, X and II have half lives of around 6, 24, 40, 60 hours respectively. So we don’t measure warfarin levels not only because it’d be harder, but also because it’s clinically silly.
Get an INR done every 24 hours until you’re happy (i.e., 2-3) These long half lives have two implications 1) you need bridging therapy, as they warfarin won’t have it’s peak effect until 2-3 days later. PEs often hurt. 2) longer onset means longer offset, so if INR is too high,
Vitamin K reverses the effect of warfarin over 6-12 hours. FFP (plasma and colloid) works right away.
It takes 2-3 half-lives for warfarin to reach full therapeutic effect, which can be up to 5 days. In the mean time, bridging therapy with heparin (LMWH) is required, as it has the much shorter activation and deactivation time. Therapeutic Guidelines recommend starting DVT / PE patients on anticoagulation stat, with both heparin and warfarin. Heparin because it acts sooner, warfarin because you can take a tablet.
Refs:
Rang & Dale
TGs
Baker et al. Warfarin Reversal: consensus guidelines MJA 181:9;492-497
Tharmarajah et al. Efficacy of warfarin reversal in orthopedic trauma surgery patients. [Clinical Trial. Journal Article] Journal of Orthopaedic Trauma. 21(1):26-30, 2007 Jan.
- pat
By
Patoriku, At
February 21, 2008 at 6:46 PM
HEPARIN
What is heparin?
• Made of a family of sulfated glycosaminoglycans – not a single substance
• Present (along with histamine) in the granules of mast cells
• Doses are specified in units of activity, rather than mass as preparations differ in potency thus must be assayed against an international standard
• Heparin fragments or a synthetic pentasaccharide (referred to as low-molecular-weight heparin – LMWH) are increasingly used in favour of unfractionated heparin
Mechanism of action
• Inhibits coagulation, both in vivo and in vitro, by activating antithrombin III (AT III):
– AT III inhibits thrombin and other serine proteases by binding to their active serine site
• Heparin modifies this AT III interaction:
– Binds to AT III, changing its conformation and accelerating its rate of action
○ this binding occurs via a unique pentasaccharide sequence
• Thrombin (IIa) is considerably more sensitive to the heparin-antithrombin III complex than is factor X:
– To inhibit thrombin, it is necessary for heparin to bind to both the enzyme and AT III
– To inhibit factor Xa, it is necessary only for heparin to bind to AT III
• The LMWHs increase the action of AT III on factor Xa but not on thrombin
– The molecules are too small to bind to both enzyme and inhibitor, essential for inhibition of thrombin (but not of factor Xa)
Administration and pharmacokinetic aspects
• Heparin is not absorbed from the gut because of its charge and molecular size
– Therefore administered either subcutaneously or intravenously (intramuscularly would cause a haematoma)
○ acts immediately following intravenous administration
○ onset delayed up to 60 minutes when given subcutaneously
• Elimination half-life approximately 40 – 90 minutes
• In urgent situations usual to give the first treatment as a bolus intravenous dose
– This would be then followed by a constant-rate infusion
• Activated partial thromboblastin time (APTT):
– An in vitro clotting test
– Measured, and the dose of unfractionated heparin adjusted to achieve a value within a target range
• LMWHs are given subcutaneously
• LMWHs have a longer elimination half-life than unfractionated heparin:
– This is independent of dose (first order kinetics)
○ therefore the effects are more predictable and the dosing less frequent
• LMWHs do not prolong the APTT
• LMWHs are eliminated by renal excretion
– Therefore unfractionated heparins are preferred in renal failure
Unwanted effects
• Haemorrhage:
– Treated by ceasing therapy and if necessary administering protamine sulfate (a heparin antagonist, given intravenously):
○ dose is estimated from the dose of heparin that is administered currently
○ NB: it is important not to give too much as it can itself cause bleeding
• Thrombosis:
– An uncommon but serious effect of heparin therapy
○ may be misattributed to the natural history of the disease that resulted in heparin administration
– Paradoxically, associated with heparin-induced thrombocytopaenia (HIT):
○ a transitory early decrease in platelet numbers is not uncommon, and is not clinically significant
○ more serious thrombocytopaenia occurring 2 – 4 days following the administration of heparin is uncommon:
caused by IgG antibodies against complexes of heparin and platelet factor 4 (PF4)
because of opposite charges, heparin binds to the PF4 molecules. This complex forms an antigen.
an IgG antibody against this antigen is produced
this antibody binds to the heparin-PF4 complex via the Fab region on the platelet surface
this new immunocomplex can bind to the platelet’s Fc receptor:
◊ triggers activation and aggregation of platelets
▫ activated platelets release PF4, thus perpetuating the cycle of heparin-induced platelet activation
▫ platelet activation leads to the production of prothrombotic platelet microparticles that promote coagulation
antibody binds to PF4 complexed with glycosaminoglycans on the surface of endothelial cells
◊ leads to immune injury of the vessel wall, thrombosis, and disseminated intravascular coagulation
1. LMWHs are more likely to cause thrombocytopaenia and thrombocytosis than unfractionated heparin
2. Management of patients with HIT:
○ danaparoid
○ a direct thrombin inhibitor
• Osteoporosis:
3. Has been reported with long term (>6 months) heparin use
• Hypoaldosteronism
• Hypersensitivity reactions:
4. Rare with heparin occur more commonly with protamine
Sources
Rang pp. 336-37
Yeager BF, Matheny SC. Low-molecular-weight heparin in outpatient treatment of DVT. Am Fam Physician. 1999 Feb 15;59(4):945-52.
http://www.thrombosisjournal.com/content/3/1/14, accessed 20/2/08
Baglin TP. Heparin induced thrombocytopenia thrombosis (HIT/T) syndrome: diagnosis and treatment. J Clin Pathol. 2001;54:272–274.
By
third year, At
February 22, 2008 at 10:18 PM
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