Drugs That Cause Autoimmune Hemolytic Anemia

00:01 So now, what we’ll do is we’ll walk through some of these important drugs that you want to know that bring about either cold or warm type of autoimmune hemolytic anemia.

00:10 Let’s begin with penicillin.

00:12 In pharmacology, you’ve heard of penicillin-binding proteins.

00:16 When the penicillin binding proteins are in the membrane and at some point, in certain populations, this penicillin might then alter, what that green circle is? It’s the RBC.

00:26 What that P stands for is the penicillin-binding protein in which in the membrane it gets altered.

00:32 So therefore now, the RBCs looked at as being an antigen.

00:37 Guess what it’s going to do? It’s going to attract IgG, okay? What does IgG mean to you? Warm or cold? Warm.

00:46 What does IgG mean to you in terms of hypersensitivity? It is a type II hypersensitivity.

00:51 Once again, what does IgG do to that RBC? It coats it.

00:56 What is that RBC going to look like and where is it going to go? It will go to the spleen, undergo extravascular hemolysis.

01:04 On your peripheral blood smear, that RBC will look like a spherocyte, won't it? And what about your Coombs test, which you are going to use? Direct or indirect? You’re looking for an RBC bound to an IgG.

01:16 I’m hoping now at this point you can correctly answer and say and tell me that it’s direct.

01:23 Good.

01:24 So take a look at the description here, type II hypersensitivity, antibody dependent cellular cytotoxicity, extravascular hemolysis.

01:32 Therefore, tell me about the symptoms.

01:34 Significant jaundice and pigment stones.

01:36 Let us now move on to quinidine.

01:38 Now, quinidine is going to be one of your prototypes of what’s known as your class I antiarrhythmic, isn’t it? So you have quinidine here that the patient is taking because of arrhythmia and wants to block off the sodium channel.

01:52 Unfortunately, the quinidine has an interesting effect in which it then brings about what’s known as an immune complex deposition versus a type II hypersensitivity IgG, IgM you’re going to form an immune complex.

02:08 And that will then deposit on RBC due to quinidine.

02:11 Amazing.

02:11 So what kind of hypersensitivity is this? This will be a type III hypersensitivity.

02:16 And the big change of understanding now is the fact that if you have a type of cold IgM, then that IgM will trigger your complement.

02:27 And that complement pathway leads to C3b production and hence extravascular hemolysis, opsonization.

02:34 Those of you that have learned it being intravascular and such, well, be very careful because this is really not the case anymore clinically.

02:44 Methyldopa is what we’re looking at next.

02:45 Please pay attention here.

02:46 This is an important clinical scenario.

02:49 With methyldopa, who is your patient? Well, my patient is pregnant and she has blood pressure of 160/90, first trimester, okay? So you want to try to tackle this hypertension, obviously.

03:05 I gave you first trimester because I don’t want there to be any confusion with preeclampsia here, okay? So anyhow, you’re trying to treat the hypertension in a pregnant lady.

03:12 She had predisposing hypertension already.

03:17 She was already taking ACE inhibitor for hypertension.

03:20 She became pregnant.

03:20 Oh my goodness, please remove her off of the ACE inhibitor or otherwise, the ACE inhibitor will kill the fetal kidneys as you know, it's a teratogen.

03:32 But you still have to absolutely take care of that hypertension, because if you don’t, then increase risk of something like placental abruption/abruption placentae, right? Later on down the road.

03:39 So here, you give something called an alpha-2 agonist centrally acting.

03:44 So this is alpha methyldopa.

03:47 So by stimulating your alpha 2 receptors up in the brain, what have you done? Alpha-2 receptors are located where? On the presynaptic terminal, isn’t it? On the presynaptic terminal, you inhibit the release of your norepinephrine and therefore, you try to control that hypertension and safe from pregnancy, know that.

04:07 In certain populations, this methyldopa is -- what does Rh mean again? It’s a D antigen.

04:14 This methyldopa in certain population is going to configure or shall really disfigure the Rh antigen in the membrane to the point where the RBC becomes absolutely unrecognizable or recognized as an antigen.

04:29 Guess who’s going to come in? IgG.

04:33 So what’s IgG? A warm.

04:35 What is IgG? An opsonin.

04:36 Where does it go? To the spleen.

04:38 Extravascular hemolysis, type II hypersensitivity.

04:41 Do you see as to how the drugs bring about interesting autoimmune hemolytic anemias? I have given you three big ones: Penicillin, methyldopa - IgG warm, type II hypersensitivity.

04:53 Quinidine - IgM, immune complex.

04:57 We have all of these really having extravascular type of picture.