3 Conditions to Form Thrombus

Thrombus are the pathological formation of intravascular blood clots that are attached to the vessel wall (If it’s not attached, it could be an embolus!). This can either be in an artery or a vein, each leading to different complications. The most common type of thrombus is a Deep Vein Thrombus (DVT) in the leg below the knee.

Cause of a thrombus:

The causes closely relate to Virchow’s triad

  1. Disruption of normal blood flow:

Normal blood flow is expected to be linear and non-turbulent. When blood stops flowing (stasis) or becomes turbulent, clots start to form.

For example:

  • Stasis:
    • Due to immobilisation / prolonged bedrest
    • Left atrial dilatation due to mitral stenosis
  • Turbulent flow:
    • Arterial stenosis (narrowing of the vessels)
    • Cardiac wall dysfunction
    • Atrial fibrillation
  1. Endothelial damage:

Damage to the vessel walls expose the subendothelial collagen fibres and trigger platelet adhesion, aggregation and the clotting cascade to occur (listen to our haemostasis podcast).

Diseases that precipitate thrombi formation from vessel damage include:

  • Atherosclerosis
  • Vasculitis
  • High levels of homocysteine (from B12 and Folate deficiency)
    • can lead to atherosclerosis
  • Cigarette smoking
  1. Where the blood is in a hypercoagulable state

A disease causes a hypercoagulable state in the blood by having either too much pro-coagulation factors or too little anti-coagulant proteins. Patients with these diseases will present with recurrent DVTs or at a very young age.

Disease include:

  • Activation of coagulation system
    • Disseminated Intravascular Coagulation (DIC)
  • Hereditary or acquired factor deficiencies
    • Hereditary antithrobin III deficiency
    • Oral Contraceptives (Estrogen)
  • Antiphospholipid syndrome
    • Due to lupus anticoagulant
  • Thrombocytosis: (Too many platelets)
    • Malignancy

References:

  • Pathoma 2011
  • Goljan Rapid Review of pathology 4th ed.

Tests and markers in hemolysis

Direct and Indirect Coombs test:

Their use is to detect antibodies that BIND to the surface of red blood cells (RBC).
Basic principle:
     Anti-Human Globulins (AHG) are mixed with the patient’s RBCs. If the RBC has the antibodies attached, the AHG will bind to those antibodies and bind RBCs together. This will lead to agglutination – a visible clumping of red blood cells.

Direct Coombs’ test:

Is used to detect antibodies already attached onto the red blood cell. This could be for cases such as immune mediated haemolytic anaemias.

Steps:

  1. Add AHG to washed red cell
    • Washed = removing the patient’s own plasma
  2. Wait and see if there is agglutination.

Indirect Coombs’ test:

This test is used to determine antibodies in patient’s serum that is unbound to their red blood cells. This is useful in cases such as crossmatching prior to transfusion, and also in pre-natal screening of pregnant women.

Steps:

  1. Serum from the patient is cultured with RBCs of a known antigenicity from another patient.
  2. This process allows binding of antibodies to RBCs in vitro
  3. AHG then added to RBC
  4. Wait and see if there is agglutination
          Still unclear? Watch a youtube video

Serum Haptoglobin:

An indication of serum haptoglobin is to determine if hemolysis is present.
Haptoglobin is a protein produced by the liver and is found in the blood. Haptoglobin binds to free hemoglobin released from red blood cells. The Haptoglobin-hemoglobin complex will then be removed by the reticulo-endothelial system.
Hemoglobin is released in large quantities into the blood during hemolysis. This will cause lots of serum haptoglobin to bind to hemoglobin and consequently be removed.
Thus, during hemolysis, it is reasonable to expect haptoglobin levels to decrease.

Lactate Dehydrogenase (LDH) levels

Is an enzyme found in almost all cells. There are many indications to test for LDH levels. During haemolytic anaemias, the lysis of red blood cells causes a release of LDH into the blood. Thus it is reasonable to expect LDH levels as a marker of hemolysis.

Another indication for observing LDH levels is when the patient experiences muscle trauma or injury as it can also indicate tissue damage.

References:

  1. Kumar P, Clark M. Kumar & Clark Clinical Medicine. 5th ed. London: Elsevier limited; 2002.
  2. Hoffbrand A, Moss P. Essential Haematology. 6th ed. Oxford: Wiley-Blackwell; 2011.

Episode 13: Hemochromatosis – A few reasons iron supplements are not candy

“Feeling tired? You might have anaemia! Try our iron supplements to make you feel better.” Says an ad campaign.

Well, too much iron can be detrimental too! The Common Rounds presents  Hemochromatosis — that disease when you have too much iron deposited.

So think twice if you are going to overload yourself with iron tablets, you could give yourself secondary hemochromatosis. (That being said, it’ll take you quite a few decades for the side effects to show…)

Join the Common Rounds as they talk through the normal physiology of iron absorption, pathology of Primary Hemochromatosis and many more!

Listen to the podcast

Read the notes

Supplementary resource:

Episode 11: How much do you know about Inflammatory Bowel Disease?

Join the Common Rounds as we talk you through the key distinguishing characteristics of Inflammatory Bowel Disease.

As you may know, IBD is broken down into two disease subsets: Crohns and Ulcerative Collitis.

Do you think you can distinguish between these two diseases? Join Hamed and Andy as they talk you though the differences in just 20 mins.

Listen to the podcast

Download the notes

Episode 8 and 9: Alcoholic Liver disease and NAFLD – Why your liver gets fat

A fatty liver is when there is excess fat droplets being deposited in hepatocytes. Usually this occurs from damages done to the liver. Alcohol is one of such factors to cause damage, but is it the only one? What other disease processes will alcohol lead to in the liver?

Stay tuned and learn about alcoholic liver disease, and non-alcoholic fatty liver disease (NAFLD)

Episode 8: Alcoholic liver diseases

Episode 9: NAFLD

Download the notes here