Transcription
Let's continue our series in hematology and discuss drug-induced immune-mediated hemolysis. Wow, that was a mouthful. Coming up, médicos is perfection. Alice here, Amy on hemolytic anemia. As you know from previous videos, we have three different causes. Autoimmune hemolytic anemia is by far the most common. We have the warm subtype and the cold subtype. Of the warm subtype, please don't forget lupus; pretty important. The second most common is drug-induced hemolytic anemia, also known as drug-induced immune hemolytic anemia. Please don't say DIHA.
So what's the story? You take a drug, and this drug will fool your immune system. Now the immune system is confused, so it develops antibodies against their red blood cells—your own red blood cells—against the self, and hemolysis will occur, which is never a good idea. So the drugs that cause drug-induced immune hemolytic anemia include, but are not limited to: cephalosporins, especially cefotetan and ceftriaxone (cefotetan is second generation, ceftriaxone is third generation); cephalosporins; penicillin family; and one of the members of the glorious penicillin family is piperacillin; methyl dopa; quinidine; methyldopa; nitrofurantoin; and rifampin. Drug-induced immune hemolytic anemia most commonly will be drug-dependent antibodies. What does this mean? These antibodies are only detected in the presence of the drug; no drug, no antibodies. Also, less commonly, drug-independent antibodies. Such antibodies do not need the drug to be present to obtain in vitro reactions. One of the examples here will be for Europe. One of the examples here will be penicillin. Cephalosporins. We will elaborate on four of these: cephalosporins, penicillins, methyl dopa, and quinidine. Cephalosporins and penicillin are quite similar, so we have three different stories: the penicillin story, the methyl dopa story, and the quinidine story.
Story number one: the great penicillin. Penicillin has a group called BPO, or benzylpenicilloyl. It acts like a hapten or a baby antigen. This BPO group attaches to the red blood cell surface, forming a covalent bond. This is called membrane adsorption. "Ad" means attached to or pretty close, as in adrenal, which is the gland attached to the kidney. This will lead to an IgG formation because this doesn't seem familiar to your body; it seems like an enemy or a foreigner, which will lead to IgG attached to the BPO and the red blood cell. They go nicely to the spleen and get phagocytosis by the macrophage thanks to the Fc receptor in the macrophage recognizing the Fc portion of the IgG antibody. What type of hemolysis is there? Extravascular hemolysis. What type of hypersensitivity reaction is there? Type 2 hypersensitivity reaction, which is also known as cytotoxic. As you know, cyto means cell, and I do need the cell, or the red blood cell, for this process to occur. To be a great student, there are three different scenarios for penicillin. First, the patient takes penicillin and immediately develops a rash and hypotension. What's that? This is a type 1 hypersensitivity reaction: IgE, mast cell, or basophil activation, release of histamine, etc. Second scenario: the patient takes penicillin, develops hemolysis, and jaundice. What's the diagnosis? This is drug-induced immune hemolytic anemia, type 2 hypersensitivity reaction, cytotoxic. Third and last scenario: the patient takes penicillin one to two weeks later and develops fever, urticaria, or rash, or throat or joint pain. What's the diagnosis? This is a serum sickness-like reaction, kind of similar to serum sickness reaction in the symptoms, but quite different. And there are two differences between serum sickness and serum sickness-like reaction. First, serum sickness reaction is a type 3 hypersensitivity reaction, but serum sickness-like reaction has an unknown mechanism till this moment. Also, serum sickness reaction: there are immune complexes there, but in serum sickness-like reaction, no immune complexes are found. All of this is pretty high-yield for your exam. Many students don't get there because they see it's kind of difficult, but now you want.
Story number two: the glorious methyl dopa. Methyl dopa is an antihypertensive drug used especially in pregnancy. What are the other antihypertensive medications that can be given to a pregnant woman? Hydralazine, methyldopa, labetalol. Can we use diuretics in pregnancy? We shouldn't. Why? They can cause volume depletion and compromise the uteroplacental blood supply. Can we use ACE inhibitors in pregnancy? No, they can damage the kidney of the baby. Wow, that was a cool pharmacology review there, Bank 2. Methyl dopa. Methyl dopa, the drug, will change or alter the Rh antigen on the surface of your red blood cell. Now it has a different shape. IgG will recognize that because it's not familiar; this sounds non-self. Attached to it, they go nicely to the spleen. Macrophages will attack them. What's the type of the hemolytic anemia? Extravascular. What's the type of hypersensitivity reaction? Type 2, or cytotoxic. A great mnemonic to remember that type 2 hypersensitivity is cytotoxic. Okay.
Number three: the quinidine. It's a class 1A antiarrhythmic. It increases the action potential duration and prolongs the QT interval. Let's review the antiarrhythmic classes. We have class 1, which is sodium channel blocker; class 2, which is beta blocker; class 3, potassium channel blocker; class 4, calcium channel blocker. And here's a cute little mnemonic to remember the four classes of antiarrhythmics: sodium, beta blocker, potassium, and calcium channel blocker. You're welcome. Please don't do that; it's just a joke. Okay. Quinidine acts like a hapten. IgM recognizes that. IgM and the drug, without the red blood cell yet, will flow nicely inside your blood vessel. This is intravascular. Now the complement will get activated because IgM can fix the complement avidly, leading to a complement activation. Now, for the complement to activate, it needs a cell surface. Here comes the red blood cell. Complement will get activated, C5 through C9, the MAC pore in the red blood cell, disrupting the osmotic environment, which will lead to hemolysis. What kind of hemolysis is that? Intravascular hemolysis. You can regard this process as a type 3 hypersensitivity reaction, since, still this step, we didn't need a cell surface, so it's not type 2; it's kind of type 3, but that's okay. Here is the story of extravascular hemolysis: these are the causes; this is the mechanism. We have discussed this before in my video, extravascular vs. intravascular hemolysis, so please go back and watch that video. Also, here is intravascular hemolysis: causes, mechanism (again, discussed before), or symptoms of anemia: the same—tired, pale, short of breath, hyperdynamic circulation, heart murmur, angina, plus jaundice and urine discoloration, huge spleen, skeletal changes (maybe not). How to diagnose it? Ask the patient about the history. There is a history of drug intake such as penicillin, cephalosporin, methyl dopa, quinidine, etc., plus some investigation. You know, CBC will give you low hemoglobin, low hematocrit. Reticulocytes will be high because this is hemolysis. MCV could be normal, but the reticulocytes could raise the MCV because reticulocytes are bigger than the red blood cell. LDH high, unconjugated bilirubin high, haptoglobin low. How to diagnose it? Direct Coombs test. Direct Coombs test, as you know, detects antibodies on the surface of the red blood cell. In the urine: hemoglobinuria, hemosiderinuria, especially in cases of intravascular hemolysis. As you know, drug-induced immune hemolytic anemia could be either extravascular or intravascular. How to treat drug-induced immune hemolytic anemia? Maybe, like, look at the name: drug-induced hemolysis, so maybe, I don't know, stop the drug. Okay, of course, this is the first step. Don't forget that the drug is causing the problem. You take out this drug. Also, you can give prednisone. Prednisone, anti-inflammatory steroids, of course, will prevent this process. Severe cases will need blood transfusions. Thank you so much for watching this video. Please consider subscribing, and I'm posting questions and answers on Facebook, so please like me on Facebook. I'll see you in the next video. Be safe, stay happy, study hard. Médicos is perfection!