Hypercoagulability: Primary Causes

00:01 In this lecture, we’re going to discuss clotting disorders in children.

00:05 Let’s pause for a moment and re-remember Virchow’s triad.

00:09 This is the setting in which clots can form inside blood vessels.

00:13 This happens as a result of blood stasis, through endothelial damage and because of hypercoagulable state.

00:21 And in this lecture, we’re going to focus a little bit on the hypercoagulable state of children.

00:26 In general, clots in children are far rarer than in adults.

00:31 Their endothelial lining is in perfect condition, but they may have a hypercoagulable state that can lead them to form blood clots.

00:40 So let’s talk about the primary causes of hypercoagulability and the first one I want to talk about is factor V Leiden mutation.

00:48 Okay.

00:49 Factor V Leiden mutation is a mutation that causes resistance in the breakdown of factors by protein C.

00:59 So this is the most common inheritable cause of hypercoagulability and it presents typically in adulthood, not in childhood, but rarely can.

01:09 This is usually presenting with arterial and venous clots in patients.

01:16 So another one is antithrombin III deficiency.

01:22 This is a problem where antithrombin III forms a complex with activated thrombin, factors 10A, 9A, and 11A.

01:32 Antithrombin III neutralizes these clotting factors and homozygous patients die in utero, but heterozygous patients often have venous thrombosis.

01:44 And they usually present in the teen years.

01:46 Another type of hypercoagulability is protein C and S deficiency.

01:52 If you recall, protein C and S are necessary for breaking down clotting factors VA and VIIIA.

01:59 Patients who are heterozygous for this condition may present with mild increased risk for clots generally in their second decade of life.

02:07 However, homozygous patients will present in infancy, specifically in the neonatal period with an entity called neonatal purpura fulminans.

02:17 This is obviously an incredibly rare condition, but these patients have clots all over through their body and mortality is quite high.

02:26 Let’s talk about prothrombin mutations.

02:29 That’s another primary cause of hypercoagulability.

02:33 In patients with prothrombin mutation, this can result in excess thrombin and formation of clots.

02:40 There is an increased risk in adulthood, it’s less commonly found in children.

02:46 Lastly, the MTHFR mutation.

02:52 The MTHFR mutation is a genetic cause of increased homocysteine in the blood.

03:00 Basically, it’s a mutation in methylenetetrahydrofolate reductase.

03:06 This enzyme is responsible for turning homocysteine into methionine.

03:11 And because it’s not working so well, these patients have a higher level of homocysteine.

03:16 This results in a blood vessel wall damage and resultingly, a hypercoagulable state.