Hemophilia: Etiology and Pathology (Pediatric Nursing)

00:01 Now we'll cover hemophilia.

00:03 Hemophilia is a rare disorder in which blood doesn't clot normally because it lacks sufficient blood clotting proteins.

00:09 These are your clotting factors.

00:11 This results in longer bleeding times, puts patients at risk for internal bleeding, can be life-threatening and it can be treated with the replacement of the missing clotting factors.

00:23 Let's talk about hemophilia.

00:25 Typically it's a factor VIII deficiency but there can be other factors involved and we'll talk about that.

00:30 These patients could be missing a defective gene on their factor VIII clotting protein.

00:36 There can be one in 5000 births this can present and all races and ethnic groups can be affected.

00:42 So genetics cause two-thirds of the cases.

00:45 And there's another option, a third of the cases are acquired and this is a spontaneous genetic mutation.

00:51 This happens at some point in the patient's life and this will cause them to have hemophilia.

00:56 These patients are not born with the gene mutation that causes hemophilia.

01:01 There are different types: Hemophilia A - this is the most common and this is classic, these patients have a factor VIII deficiency.

01:09 The next type is hemophilia B, also known as Christmas disease and this is less common.

01:14 This is a factor IX deficiency.

01:16 And finally hemophilia C, this is a mild form.

01:19 This is a factor XI deficiency and this can be passed to male and female children.

01:26 First we'll discuss acquired hemophilia which is approximately a third of the hemophilia cases.

01:31 This is a rare form of hemophilia and it's different than the genetic forms.

01:35 It's going to affect men and women equally.

01:38 The acquired form is not caused by an inherited genetic mutation instead it's a spontaneous mutation that usually happens in adulthood where the body starts making, mistaking antibodies that attack and disable the clotting factor VIII.

01:53 This can be life-threatening as the bleeding can be severe and unexpected and healthcare professionals may not recognise that this is happening and this can cause a delay in the diagnosis and the interventions.

02:04 In addition, in contrast to patients who were born with hemophilia, these patients likely do not know they've even acquired this condition and that puts them at a huge risk for bleeding.

02:14 It's not clear how many patients with acquired hemophilia die as a consequence of their bleeding but the estimates are between VIII and 22%.

02:23 So what are the causes of acquired hemophilia? Well pregnancy, certain autoimmune disorders, cancer or reaction to certain medications, other - the general category, and unknown etiology which is about 50% of the cases, we just don't know.

02:41 As you can see here, there a lot of possible causes of acquired hemophilia here in the green you're going to see that the unknown causes account for about half of the cases.

02:51 Now that we've talked about the third of hemophilia cases that are acquired in adulthood and develop spontaneously, now we'll talk about the genetic forms of hemophilia Hemophilia A and B are inherited in an X-linked recessive pattern.

03:05 The genes associated with hemophilia are found on the X chromosome.

03:09 Chromosomes come in pairs.

03:11 We know females have two X chromosomes while males have one X and one Y chromosome.

03:16 Only the X chromosome carries the genes related to clotting factors.

03:21 A male who has hemophilia gene on his only X chromosome will have hemophilia since he only has one copy of the gene and that is sufficient to cause the condition.

03:31 Females however, have two X chromosomes so a mutation would have to occur on both copies of the gene in order to cause the disorder.

03:39 Because this is unlikely that the female's gonna have two altered copies of this gene, it is very rare for females to have the genetic form of hemophilia.

03:49 This pedigree shows one example of how hemophilia can be inherited.

03:53 In this example, the father does not have hemophilia, he has two normal chromosomes - an X and a Y and the mother is a carrier of hemophilia which means she only has one gene that's diseased and one normal X chromosome.

04:06 Remember, this is a disorder linked to the sex chromosomes so the gender of the child will change the odds of them inheriting this disorder.

04:14 Each daughter has a 50% chance of inheriting the hemophilia gene from her mother and being a carrier.

04:19 And each son has a 50% chance of inheriting the hemophilia gene from his mother and having hemophilia because remember, he only needs the one mutated gene.

04:30 The mother who was a carrier of the hemophilia gene may not even know that she has this mutation because she's likely asymptomatic.

04:37 This pedigree shows another example of a way for hemophilia to be inherited.

04:41 In this example, the father has hemophilia, he has the hemophilia gene on his only X chromosome.

04:47 The mother isn't a hemophilia carrier because she has two normal X chromosomes.

04:53 Each daughter will inherit the hemophilia gene from her father and be a carrier.

04:57 None of the sons will inherit hemophilia from their father because they will get the Y chromosome from their dad, thus they'll be alright.

05:05 Hemophilia A, remember this is a change in the gene that makes factor VIII and hemophilia B is a change in the gene that makes Factor IX.

05:14 Here we see a blood vessel up top, it's broken, there is an injury.

05:18 On the left, usually these clotting factors are gonna start working to begin the clotting process.

05:23 A clot will form including fibrin and other substances.

05:26 But on the right, you see these patients have an altered or missing protein that can't participate effectively in the clotting process so their bleeding is hard to control.

05:35 Now let's compare normal clotting with patients who have hemophilia.

05:39 So let's say they get an injury, maybe they're cooking something in the kitchen and they cut the hand with a knife.

05:44 That's a vascular injury, initially they're gonna bleed the same amount.

05:48 Their body's gonna respond immediately by trying to vasoconstrict to slow the bleeding to this wound, and that step is the same.

05:56 This is when things start to change - the patient who has normal clotting is going to develop a platelet plug.

06:01 The patient with hemophilia is gonna have dysfunctional clotting cascades and incomplete platelet plugs and they are going to keep bleeding.

06:09 Finally the patient without hemophilia is gonna form their fibrin clot while the patient with hemophilia is gonna have incomplete or delayed formation of the fibrin clot and they are gonna keep bleeding.