Arterial vs venous clots

Arterial clots

Arteries are thick blood vessels with fast flowing blood. Blood clots in arteries are typically triggered by underlying arteriosclerosis (roughening of the artery wall). Blood platelets get stuck to the roughened blood vessel wall and form a clot. Thus, the medication of choice in trying to prevent thrombosis in arteries are medications that act against platelets. The following medications are anti-platelet drugs:

• Aspirin (= ASA)
• Plavix (= Clopidogrel)
• Ticlid (= Ticlopidine)
• Aggrenox (= aspirin plus dipyridamole)

By interfering with platelet function, these drugs increase the patient's risk of bleeding, even though to a lesser degree than coumadin. The INR is not influenced by these drugs and vitamin K intake does not influence their effect.

Venous clots

Veins are thin blood vessels with slow flowing blood. Blood clots that form in veins (DVT, pulmonary embolism) are mainly made up of clotting proteins; platelets do not play a big role in venous clots. Warfarin is an effective anticoagulant by preventing the production of clotting factors in the liver, increasing the INR. It is therefore the drug of choice in venous thrombosis. Anti-platelet drugs do not play much of a role in preventing venous clots.

Occasionally, clots in arteries originate from one of the two left heart chambers and travel from there with the blood stream to the brain, the retina, or the extremities. This typically happens in atrial fibrillation. Such a clot is an arterial embolism that resembles the type of clots seen in veins i.e. they have little platelet participation. They are therefore best treated with warfarin, not with anti-platelet drugs, even though they are clots in arteries.

References:

• Thrombophilia Support page
  

INR & warfarin

If a patient's INR is > 3 (normal 0.8-1.2) then stop warfarin for a few days rather than reversing it with Vit K/FFPs.

Aneurysms

An aneurysm is a localized abnormal dilation of a blood vessel or the wall of the heart.

Classification of aortic aneurysms

Aneurysms can be classified by macroscopic shape and size.

• Saccular aneurysms are essentially spherical (involving only a portion of the vessel wall) and vary in size from 5 to 20 cm in diameter, often partially or completely filled by thrombus.
  
• Fusiform aneurysms involve a long segment and vary in diameter (up to 20 cm) and length; many involve the entire ascending and transverse portions of the aortic arch, whereas others may involve large segments of the abdominal aorta or even the iliacs.
  

The shape of an aneurysm is not specific for any disease or clinical manifestations.

Causes of aortic aneurysms

• atherosclerosis - causes arterial wall thinning through medial destruction secondary to plaque that originates in the intima.
• cystic degeneration of the arterial media
  
• trauma (traumatic aneurysms or arteriovenous aneurysms)
• congenital defects such as those causing berry aneurysms (in the brain)
  
• infection resulting in mycotic aneurysms,
• systemic diseases e.g. vasculitides

Abdominal aortic aneurysms

• Usually positioned below the renal arteries and above the bifurcation of the aorta.
• Saccular or fusiform, sometimes up to 15 cm in greatest diameter and of variable length (up to 25 cm).
  
• The aneurysm and the nearby aorta often contain atheromatous ulcers covered by granular mural thrombi, prime sites for the formation of atheroemboli that may lodge in the vessels of the kidneys or lower extremities.
• AAAs rarely develop before age 50 and are more common in men.
  
• There is a genetic susceptibility to AAA beyond the genetic predisposition to atherosclerosis or HT.
  

Aneurysm growth

Most aneurysms expand at a rate of 0.2 to 0.3 cm/year, but 20% expand more rapidly. The most important clinical factor affecting aneurysm growth is blood pressure.

Clinical consequences of AAAs

• Rupture into the peritoneal cavity or retroperitoneal tissues with massive, potentially fatal, hemorrhage.
• The risk of rupture is directly related to the size of the aneurysm.
• Risk varies from zero for a small AAA (less than approximately 4 cm in diameter), to 1% per year for aneurysms measuring 4.0 to 4.9 cm indiameter, 11% per year for aneurysms between 5.0 and 5.9 cm in diameter, and 25% per year for those larger than 6.0 cm.

• Obstruction of a vessel, particularly of the iliac, renal, mesenteric, or vertebral branches that supply the spinal cord leading to ischemic tissue injury
• Embolism from atheroma or mural thrombus
• Impingement on an adjacent structure, such as compression of a ureter or erosion of vertebrae
• Presentation as an abdominal mass (often palpably pulsating) that simulates a tumo

Management Large aneurysms are managed aggressively; operative mortality for unruptured aneurysms is approximately 5%, whereas emergency surgery after rupture carries a mortality rate of more than 50%.

The treatment of abdominal and thoracic aortic aneurysms is evolving toward endoluminal approaches using stent grafts (expandable wire frames covered by a cloth sleeve) rather than surgery for some patients.

Divarication

The rectus abdominis muscles should meet in the midline at the linea alba. Superior to the umbilicus, some people have a congenital defect that results in a widened linea alba. As a result, when a patient flexes the abdominal muscles the rectus muscles spread apart (divaricate).

Divarication and abdominal hernias appear very similiar. To differentiate between a divarication and a hernia clinically:

• get the patient to do a sit-up - rectus muscles spread apart in both a hernia and a divarication
• get the patient to cough - rectus muscles will only split apart if its a hernia. When coughing all abdominal muscles are used (not just the rectus), so a divarication will show a diffuse bulging, rather than locally down the midline.
  

Divarication is common in obese men. It can be surgically corrected, although such an operation would be almost entirely for cosmetic purposes and not of any functional value (unlike a hernia).

Blood flow patterns

Peripheral muscular arteries always show a triphasic pattern (forward-reverse-forward flow):

• forward - steep rise during ventricular systole
  
• reverse - brusque return to baseline with a small negative wave in early diastole caused by the high resistance of small peripheral arteries and capillaries
• forward - slow late diastolic rise due to the compliance of the peripheral arterial walls.
  

A monophasic waveform without the reverse component occurs when the volume in the artery is insufficient and extra flow is required during diastole. This is usually because stenosis or occlusion reduces the blood available to fill the reservoir during systole, but may also occur when there is a large flow to the limb caused by exercise or gross infection.

Neostigmine methylsulfate

Actions

• An anticholinesterase agent which reversibly inhibits the hydrolysis of acetylcholine by competing with acetylcholine for attachment to acetylcholinesterase. As a result, acetylcholine accumulates at cholinergic synapses and its effects are prolonged and exaggerated.
  
• Produces a generalised cholinergic response, including miosis, increased tonus of intestinal and skeletal musculature, constriction of bronchi and ureters, bradycardia and stimulation of salivary and sweat glands.
  
• Used mainly for its direct cholinomimetic effect on skeletal muscle and to a lesser extent to increase the activity of smooth muscle.
• Because of its quaternary ammonium structure, neostigmine in moderate doses, does not cross the BBB to produce CNS effects. Extremely high doses, however, produce CNS stimulation followed by CNS depression.

Indications

• Reversal of the effects of neuromuscular blocking agents (e.g. tubocurarine, pancuronium).
  
• Prophylaxis and treatment of postoperative intestinal atony and urinary retention.
  
• Treatment of myasthenia gravis during acute exacerbations, when the condition is severe, or in neonates.

Pharmacokinetics

• For IV administration the elimination half-life is 47-60 minutes.
• For IM administration the elimination half-life is 50-91 minutes.
  
• Approximately 80% of a single IM dose of neostigmine is excreted in the urine in 24 hours, about 50% as unchanged drug and the remainder as metabolites.
  
• The major site of uptake is in the liver. It is metabolised partly by the hydrolysis of the ester linkage and partly by microsomal enzymes in the liver.