Hypercoagulability: Primary Causes

by Brian Alverson, MD

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    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.

    00:14 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 Protein C and S are responsible for breaking down clotting factors, specifically VA and VIIIA.

    02:07 Patients who are heterozygous for this condition may present with mild increased risk for clots generally in their second decade of life.

    02:16 However, homozygous patients will present in infancy, specifically in the neonatal period with an entity called neonatal purpura fulminans.

    02:26 This is obviously an incredibly rare condition, but these patients have clots all over through their body and mortality is quite high.

    02:34 Let’s talk about prothrombin mutations.

    02:37 That’s another primary cause of hypercoagulability.

    02:41 In patients with prothrombin mutation, this can result in excess thrombin and formation of clots.

    02:49 There is an increased risk in adulthood, it’s less commonly found in children.

    02:55 Lastly, the MTHFR mutation.

    03:01 The MTHFR mutation is a genetic cause of increased homocysteine in the blood.

    03:08 Basically, it’s a mutation in methylenetetrahydrofolate reductase.

    03:14 This enzyme is responsible for turning homocysteine into methionine.

    03:19 And because it’s not working so well, these patients have a higher level of homocysteine.

    03:25 This results in a blood vessel wall damage and resultingly, a hypercoagulable state.

    About the Lecture

    The lecture Hypercoagulability: Primary Causes by Brian Alverson, MD is from the course Pediatric Hematology.

    Included Quiz Questions

    1. Factor VIII deficiency
    2. Homocysteinemia
    3. Protein C deficiency
    4. Prothrombin mutation
    5. MTHFR mutation
    1. Hemophilia
    2. Factor V leiden mutation
    3. Antithrombin III deficiency
    4. Protein C and S deficiency
    5. MTHFR mutation
    1. It is an inherited cause of hypercoagulability presenting in adulthood
    2. It presents in early childhood
    3. It is not a disease of adulthood
    4. Only venous clots are seen
    5. Only arterial clots are seen
    1. Presents in the 2ⁿᵈ decade of life
    2. Protein C and S caused the breakdown of factor VII and VIII
    3. Heterozygous patients have neonatal purpura
    4. Homozygous patients present in 3ʳᵈ decade of life
    5. Homozygous patients die in-utero
    1. Prothrombinmutation
    2. Factor V leiden mutation
    3. Antithrombin III deficiency
    4. Protein C and S deficiency
    5. MTHFR mutation

    Author of lecture Hypercoagulability: Primary Causes

     Brian Alverson, MD

    Brian Alverson, MD

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